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Sample records for blocks lung vascular

  1. Substance P antagonist CP-96345 blocks lung vascular leakage and inflammation more effectively than its stereoisomer CP-96344 in a mouse model of smoke inhalation and burn injury.

    Science.gov (United States)

    Jacob, Sam; Deyo, Donald J; Cox, Robert A; Jacob, Reuben K; Herndon, David N; Traber, Daniel L; Hawkins, Hal K

    2010-05-01

    The recently developed murine model of smoke inhalation and burn (SB) injury was used to study the effect of the substance-P antagonist CP96345. C57BL/6 mice were pre-treated with an i.v. dose of a specific NK-1 receptor antagonist, CP9635, or its inactive enantiomer, CP96344, (10 mg/Kg) 1 h prior to SB injury per protocol (n = 5). Mice were anesthetized and exposed to cooled cotton smoke, 2X 30 s, followed by a 40% total body surface area flame burn per protocol. At 48 h after SB injury Evans Blue (EB) dye and myeloperoxidase (MPO) were measured in lung after vascular perfusion. Lungs were also analyzed for hemoglobin (Hb) and wet/dry weight ratio. In the current study, CP96345 pre-treatment caused a significant decrease in wet/dry weight ratio (23%, p = 0.048), EB (31%, p = 0.047), Hb (46%, p = 0.002), and MPO (54%, p = 0.037) levels following SB injury compared to animals with SB injury alone. CP-96344 pre-treatment caused an insignificant decrease in wet/dry weight ratio (14%, p = 0.18), EB (16%, p = 0.134), Hb (9%, p = 0.39), and an insignificant increase in MPO (4%, p = 0.79) as compared to mice that received SB injury alone. As expected, levels of EB, Hb, MPO, and wet/dry weight ratios were all significantly (p CP-96345 attenuates the lung injury and inflammation induced by SB injury in mice.

  2. Vascular injury in lung disease

    International Nuclear Information System (INIS)

    Tucker, A.D.; Wyatt, J.H.; Barry, J.M.; Undery, Dawn.

    1975-10-01

    Inhaled particulates which stimulate a 'delayed', cellular mode of alveolar clearance are excreted to the airways through lymphoid foci in the bronchial bifurcations. The anatomic relations and developing pathology of the tissues adjacent to these foci, including the divisions of accompanying arteries, were studied by serial sectioning and photomicrographic modelling of rat lungs. The changes are typical of classic 'delayed' inflammatory reactions and, in the rat, the fully developed stage is characterised by fibrinoid necrosis involving all three layers of the arterial wall in a linear lesion across the leading edge of the flow divider. An hypothesis was developed to relate the injury to pulsatile forces. Recent published findings indicate that similarly placed lesions, with species-specific changes in development, are universal in both cerebral and extra-cranial arterial forks of man and animals. Possible associations of the microvascular changes with human atherosclerosis and their further significance in pulmonary and systemic effects arising from industrial and environmental contaminants are explored. (author)

  3. Alteration of rat lung vascular response to radiation with drugs

    International Nuclear Information System (INIS)

    Evans, M.L.; Graham, M.M.; Mahler, A.; Rasey, J.S.

    1987-01-01

    Vascular permeability to albumin increases in the lung at one day after radiation to the thorax, returns to normal, and increases again at three weeks after exposure. To block different proposed pathways of permeability increase, several drugs were given to irradiated rats. Each drug was selected for its ability to act at a different point in the hypothesized pathway leading to elevated vascular permeability and subsequent pulmonary fibrosis. To obtain maximum effect, each was delivered continuously in drinking water from two days before 18 Gy whole thorax radiation to measurement of response at 1 or 21 days. Dexamethasone (a glucocorticoid) was most effective at 21 days, reducing vascular permeability to below control levels. Epsilonamino caproic acid (a protease inhibitor) and diethylcarbamazine (an anti-leukotriene) were also somewhat effective, reducing permeability by 26% and 37% respectively. Dapsone (a neutrophil migration inhibitor) and indomethacin (an anti-prostaglandin) had no effect. Suppression of vascular permeability with drugs, and observation of the effects of suppression on subsequent development of fibrosis should help clarify the role of vascular permeability in the development of radiation induced fibrosis

  4. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension.

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    Ghobadi, G; Bartelds, B; van der Veen, S J; Dickinson, M G; Brandenburg, S; Berger, R M F; Langendijk, J A; Coppes, R P; van Luijk, P

    2012-04-01

    Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension. Different sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage. Early loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction. The findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.

  5. Identification of novel vascular targets in lung cancer.

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    Zhuang, X; Herbert, J M J; Lodhia, P; Bradford, J; Turner, A M; Newby, P M; Thickett, D; Naidu, U; Blakey, D; Barry, S; Cross, D A E; Bicknell, R

    2015-02-03

    Lung cancer remains the leading cause of cancer-related death, largely owing to the lack of effective treatments. A tumour vascular targeting strategy presents an attractive alternative; however, the molecular signature of the vasculature in lung cancer is poorly explored. This work aimed to identify novel tumour vascular targets in lung cancer. Enzymatic digestion of fresh tissue followed by endothelial capture with Ulex lectin-coated magnetic beads was used to isolate the endothelium from fresh tumour specimens of lung cancer patients. Endothelial isolates from the healthy and tumour lung tissue were subjected to whole human genome expression profiling using microarray technology. Bioinformatics analysis identified tumour endothelial expression of angiogenic factors, matrix metalloproteases and cell-surface transmembrane proteins. Predicted novel tumour vascular targets were verified by RNA-seq, quantitative real-time PCR analysis and immunohistochemistry. Further detailed expression profiling of STEAP1 on 82 lung cancer patients confirmed STEAP1 as a novel target in the tumour vasculature. Functional analysis of STEAP1 using siRNA silencing implicates a role in endothelial cell migration and tube formation. The identification of cell-surface tumour endothelial markers in lung is of interest in therapeutic antibody and vaccine development.

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

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

    2012-01-01

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

  7. Mast cells promote lung vascular remodelling in pulmonary hypertension.

    Science.gov (United States)

    Hoffmann, J; Yin, J; Kukucka, M; Yin, N; Saarikko, I; Sterner-Kock, A; Fujii, H; Leong-Poi, H; Kuppe, H; Schermuly, R T; Kuebler, W M

    2011-06-01

    Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential. In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was tested in vivo by genetic and pharmacological strategies. In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficient Ws/Ws rats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to non-cardiogenic PH. In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH.

  8. Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury

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    Duan Yingli

    2012-01-01

    Full Text Available Abstract Background Proline-rich tyrosine kinase 2 (Pyk2 is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1 myeloperoxidase content in lung tissues, 2 vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3 the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and

  9. Gap junction protein connexin43 exacerbates lung vascular permeability.

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    James J O'Donnell

    Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

  10. IKKβ Activation in the Fetal Lung Mesenchyme Alters Lung Vascular Development but Not Airway Morphogenesis.

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    McCoy, Alyssa M; Herington, Jennifer L; Stouch, Ashley N; Mukherjee, Anamika B; Lakhdari, Omar; Blackwell, Timothy S; Prince, Lawrence S

    2017-12-01

    In the immature lung, inflammation and injury disrupt the epithelial-mesenchymal interactions required for normal development. Innate immune signaling and NF-κB activation disrupt the normal expression of multiple mesenchymal genes that play a key role in airway branching and alveolar formation. To test the role of the NF-κB pathway specifically in lung mesenchyme, we utilized the mesenchymal Twist2-Cre to drive expression of a constitutively active inhibitor of NF-κB kinase subunit β (IKKβca) mutant in developing mice. Embryonic Twist2-IKKβca mice were generated in expected numbers and appeared grossly normal. Airway branching also appeared normal in Twist2-IKKβca embryos, with airway morphometry, elastin staining, and saccular branching similar to those in control littermates. While Twist2-IKKβca lungs did not contain increased levels of Il1b, we did measure an increased expression of the chemokine-encoding gene Ccl2. Twist2-IKKβca lungs had increased staining for the vascular marker platelet endothelial cell adhesion molecule 1. In addition, type I alveolar epithelial differentiation appeared to be diminished in Twist2-IKKβca lungs. The normal airway branching and lack of Il1b expression may have been due to the inability of the Twist2-IKKβca transgene to induce inflammasome activity. While Twist2-IKKβca lungs had an increased number of macrophages, inflammasome expression remained restricted to macrophages without evidence of spontaneous inflammasome activity. These results emphasize the importance of cellular niche in considering how inflammatory signaling influences fetal lung development. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Parameters Derived from Integrated Nuclear Fluorescence, Syntactic Structure Analysis, and Vascularization in Human Lung Carcinomas

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    Klaus Kayser

    1997-01-01

    Full Text Available Combined measurements of integrated nuclear fluorescence (INF and vascularization were performed on surgical specimens of human lung carcinomas. Histological slides of formalin‐fixed, paraffin‐embedded tissue samples were treated with Texas Red‐labeled antibody to factor VIII and the fluorochrome DAPI. The resulting images were analyzed with an epi‐illumination fluorescence microscope and two different filter blocks. The first image displayed the vessels, and the second the DAPI‐stained nuclei of surrounding cells. The extent of vascularization was assessed by calculating the volume fraction (Vv, the surface fraction (Sv, the area, and the minimum diameter of the vessels. The INF was measured in tumour cells and lymphocytes, and was grouped according to the distance from the nearest vascular boundary into the intervals of 0–20, 21–40, 41–60, 61–80, and >80 μ. The numerical densities (Nv as well as the percentages of S‐phase‐related tumour cell fraction (SPRF and of tumour cells with an INF > 5C were computed. A minimum of 50 vessels and 300 tumour cells were examined. The material included 100 cases with primary lung carcinoma (39 epidermoid carcinomas, 39 adenocarcinomas, 13 large cell carcinomas, three small cell anaplastic carcinomas, and 6 carcinoid tumours. On the average, the volume density of the stroma amounts to 16.7%, and that of the vessels (Vv to 12.8%. The minimum diameter of the intratumoral vessels is 13 μ and the measured circumference 138 μ. The numerical densities of tumour cells (lymphocytes decrease with increasing distance from the vascular boundary from 6.3 (1.7 to 1.0 (0.1. A reduction is also seen in the percentage of the SPRF from 10.7 to 8.1%. The percentage of tumour cells with an INF > 5C, however, is positively correlated to the distance from the vascular surfaces from 34.2 to 38.2%. The measurements reveal that tumour cells are densely positioned and have an increased proportion of

  12. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an

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

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    Mansoor A Syed

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

  14. The mast cell-B cell axis in lung vascular remodeling and pulmonary hypertension.

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    Breitling, Siegfried; Hui, Zhang; Zabini, Diana; Hu, Yijie; Hoffmann, Julia; Goldenberg, Neil M; Tabuchi, Arata; Buelow, Roland; Dos Santos, Claudia; Kuebler, Wolfgang M

    2017-05-01

    Over past years, a critical role for the immune system and, in particular, for mast cells in the pathogenesis of pulmonary hypertension (PH) has emerged. However, the way in which mast cells promote PH is still poorly understood. Here, we investigated the mechanisms by which mast cells may contribute to PH, specifically focusing on the interaction between the innate and adaptive immune response and the role of B cells and autoimmunity. Experiments were performed in Sprague-Dawley rats and B cell-deficient JH-KO rats in the monocrotaline, Sugen/hypoxia, and the aortic banding model of PH. Hemodynamics, cell infiltration, IL-6 expression, and vascular remodeling were analyzed. Gene array analyses revealed constituents of immunoglobulins as most prominently regulated mast cell-dependent genes in the lung in experimental PH. IL-6 was shown to link mast cells to B cells, as 1 ) IL-6 was upregulated and colocalized with mast cells and was reduced by mast-cell stabilizers and 2 ) IL-6 or mast cell blockade reduced B cells in lungs of monocrotaline-treated rats. A functional role for B cells in PH was demonstrated in that either blocking B cells by an anti-CD20 antibody or B-cell deficiency in JH-KO rats attenuated right ventricular systolic pressure and vascular remodeling in experimental PH. We here identify a mast cell-B cell axis driven by IL-6 as a critical immune pathway in the pathophysiology of PH. Our results provide novel insights into the role of the immune system in PH, which may be therapeutically exploited by targeted immunotherapy. Copyright © 2017 the American Physiological Society.

  15. From here to there, progenitor cells and stem cells are everywhere in lung vascular remodeling

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    Rebecca L. Heise

    2016-08-01

    Full Text Available The field of stem cell biology, cell therapy and regenerative medicine has expanded almost exponentially in the last decade. Clinical trials are evaluating the potential therapeutic use of stem cells in many adult and pediatric lung diseases with vascular component, such as bronchopulmonary dysplasia (BPD, chronic obstructive pulmonary disease (COPD, idiopathic pulmonary fibrosis (IPF or pulmonary arterial hypertension (PAH. Extensive research activity is exploring lung resident and circulating progenitor cells and their contribution to vascular complications of chronic lung diseases, and researchers hope to use resident or circulating stem/progenitor cells to treat chronic lung diseases and their vascular complications. It is becoming more and more clear that progress in mechanobiology will help to understand the various influences of physical forces and extracellular matrix composition on the phenotype and features of the progenitor cells and stem cells. The current review provides an overview of current concepts in the field.

  16. MiR-221 and miR-130a regulate lung airway and vascular development.

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    Sana Mujahid

    Full Text Available Epithelial-mesenchymal interactions play a crucial role in branching morphogenesis, but very little is known about how endothelial cells contribute to this process. Here, we examined how anti-angiogenic miR-221 and pro-angiogenic miR-130a affect airway and vascular development in the fetal lungs. Lung-specific effects of miR-130a and miR-221 were studied in mouse E14 whole lungs cultured for 48 hours with anti-miRs or mimics to miR-130a and miR-221. Anti-miR 221 treated lungs had more distal branch generations with increased Hoxb5 and VEGFR2 around airways. Conversely, mimic 221 treated lungs had reduced airway branching, dilated airway tips and decreased Hoxb5 and VEGFR2 in mesenchyme. Anti-miR 130a treatment led to reduced airway branching with increased Hoxa5 and decreased VEGFR2 in the mesenchyme. Conversely, mimic 130a treated lungs had numerous finely arborized branches extending into central lung regions with diffusely localized Hoxa5 and increased VEGFR2 in the mesenchyme. Vascular morphology was analyzed by GSL-B4 (endothelial cell-specific lectin immunofluorescence. Observed changes in airway morphology following miR-221 inhibition and miR-130a enhancement were mirrored by changes in vascular plexus formation around the terminal airways. Mouse fetal lung endothelial cells (MFLM-91U were used to study microvascular cell behavior. Mimic 221 treatment resulted in reduced tube formation and cell migration, where as the reverse was observed with mimic 130a treatment. From these data, we conclude that miR-221 and miR-130a have opposing effects on airway and vascular morphogenesis of the developing lung.

  17. Ambrisentan reduces pulmonary arterial hypertension but does not stimulate alveolar and vascular development in neonatal rats with hyperoxic lung injury.

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    Wagenaar, Gerry T M; Laghmani, El Houari; de Visser, Yvonne P; Sengers, Rozemarijn M A; Steendijk, Paul; Baelde, Hans J; Walther, Frans J

    2013-02-15

    Ambrisentan, an endothelin receptor type A antagonist, may be a novel therapeutic agent in neonatal chronic lung disease (CLD) by blocking the adverse effects of the vasoconstrictor endothelin-1, especially pulmonary arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We determined the cardiopulmonary effects of ambrisentan treatment (1-20 mg·kg(-1)·day(-1)) in neonatal rats with CLD in 2 models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included survival, lung and heart histopathology, right ventricular function, fibrin deposition, and differential mRNA expression in the lungs. In the early treatment model, we investigated the role of nitric oxide synthase (NOS) inhibition with N(ω)-nitro-L-arginine methyl ester (L-NAME; 25 mg·kg(-1)·day(-1)) during ambrisentan treatment. In the early treatment model, ambrisentan improved survival with reduced lung fibrin and collagen III deposition, arterial medial wall thickness, and RVH. These changes were not affected by L-NAME administration. Ambrisentan did not reduce the influx of macrophages and neutrophils or prevent reduced irregular elastin expression. In the late treatment model, ambrisentan diminished PAH, RVH, and right ventricular peak pressure, demonstrating that RVH is reversible in the neonatal period. Alveolarization and vascularization were not affected by ambrisentan. In conclusion, ambrisentan prolongs survival and reduces lung injury, PAH, and RVH via a NOS-independent mechanism but does not affect inflammation and alveolar and vascular development in neonatal rats with CLD.

  18. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis.

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    Cao, Zhongwei; Lis, Raphael; Ginsberg, Michael; Chavez, Deebly; Shido, Koji; Rabbany, Sina Y; Fong, Guo-Hua; Sakmar, Thomas P; Rafii, Shahin; Ding, Bi-Sen

    2016-02-01

    Although the lung can undergo self-repair after injury, fibrosis in chronically injured or diseased lungs can occur at the expense of regeneration. Here we study how a hematopoietic-vascular niche regulates alveolar repair and lung fibrosis. Using intratracheal injection of bleomycin or hydrochloric acid in mice, we show that repetitive lung injury activates pulmonary capillary endothelial cells (PCECs) and perivascular macrophages, impeding alveolar repair and promoting fibrosis. Whereas the chemokine receptor CXCR7, expressed on PCECs, acts to prevent epithelial damage and ameliorate fibrosis after a single round of treatment with bleomycin or hydrochloric acid, repeated injury leads to suppression of CXCR7 expression and recruitment of vascular endothelial growth factor receptor 1 (VEGFR1)-expressing perivascular macrophages. This recruitment stimulates Wnt/β-catenin-dependent persistent upregulation of the Notch ligand Jagged1 (encoded by Jag1) in PCECs, which in turn stimulates exuberant Notch signaling in perivascular fibroblasts and enhances fibrosis. Administration of a CXCR7 agonist or PCEC-targeted Jag1 shRNA after lung injury promotes alveolar repair and reduces fibrosis. Thus, targeting of a maladapted hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis.

  19. Pulmonary vascular abnormalities in chronic obstructive pulmonary disease undergoing lung transplant.

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    Peinado, Victor I; Gómez, Federico P; Barberà, Joan Albert; Roman, Antonio; Angels Montero, M; Ramírez, Josep; Roca, Josep; Rodriguez-Roisin, Roberto

    2013-12-01

    Little is known about the structure and function relationships of pulmonary vessels in the most severe chronic obstructive pulmonary disease (COPD) spectrum. We investigated morphometric, cellular, and physiologic characteristics of pulmonary arteries from COPD patients undergoing bilateral lung transplant. Seventeen patients with very severe COPD (forced expiratory volume in 1 second, 24% ± 7%) were assessed using inert gas exchange and pulmonary hemodynamics while breathing ambient air and 100% oxygen. Morphometry, in vitro reactivity to hypoxia, and inflammatory cell counts of pulmonary arteries were measured in explanted lungs. Patients had moderate ventilation-perfusion imbalance along with mild release of hypoxic pulmonary vasoconstriction. Mild pulmonary hypertension was observed in 7 patients. Explanted lungs had predominant emphysema with mild small airway involvement. In vitro reactivity was modestly altered, with relatively preserved endothelium-dependent relaxation, and vascular remodelling was discrete, with intense CD8+ T lymphocytes infiltrate. In vitro reactivity correlated with pulmonary vascular resistance (on ambient air) and oxygen-induced pulmonary artery pressure changes. Patients with pulmonary hypertension had more severe morphologic and physiologic emphysema. In end-stage COPD patients undergoing lung transplant, pulmonary vascular involvement is unexpectedly modest, with low-grade endothelial dysfunction. In this sub-set of COPD patients, pulmonary emphysema may constitute the major determinant of the presence of pulmonary hypertension. © 2013 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.

  20. The major thoracic vascular invasion of lung cancer

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    Soichi Oka

    2017-08-01

    Conclusion: The positive predictive value of the preoperative CT findings for tumor invasion of the thoracic vessels was low. Therefore, surgical opportunities that offer the chance of a cure shouldn't be missed in advanced lung cancer patients because the tumor is located near the major thoracic vessels on preoperative CT.

  1. HRCT of the lung in collagen vascular diseases

    International Nuclear Information System (INIS)

    Diederich, S.; Roos, N.; Schmitz-Linneweber, B.; Gaubitz, M.; Peters, P.E.

    1996-01-01

    Collagen vascular diseases, representing systemic soft tissue disorders, may cause a broad spectrum of pathologic changes of the respiratory tract. The type and extent of manifestations can vary considerably among individuals and entities. This survey describes the chest radiographic and, in particular, high-resolution computed tomographic and, in particular, high-resolution computed tomographic (HRCT) findings of individual lesions of the respiratory tract. It includes fibrosing alveolitis (alveolitis, interstitial pneumonia, pulmonary fibrosis) and bronchial (bronchitis/bronchiolitis, bronchiectasis), pleural and vascular manifestations, as well as lymphadenopathy and abnormalities related to therapy. We present typical patterns of changes in progressive systemic sclerosis (PSS, scleroderma), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD, Sharp syndrome), Sjoegren syndrome, overlap syndrome and rheumatoid arthritis (RA). Furthermore, we describe findings which are specific for individual entities such as esophageal involvement in PSS, acute pneumonitis and pulmonary hemorrhage in SLE, lymphoproliferative disease in Sjoegren syndrome and necrobiotic nodules in RA. (orig.) [de

  2. Pressure- and flow-controlled media perfusion differently modify vascular mechanics in lung decellularization.

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    da Palma, Renata K; Campillo, Noelia; Uriarte, Juan J; Oliveira, Luis V F; Navajas, Daniel; Farré, Ramon

    2015-09-01

    Organ biofabrication is a potential future alternative for obtaining viable organs for transplantation. Achieving intact scaffolds to be recellularized is a key step in lung bioengineering. Perfusion of decellularizing media through the pulmonary artery has shown to be effective. How vascular perfusion pressure and flow vary throughout lung decellularization, which is not well known, is important for optimizing the process (minimizing time) while ensuring scaffold integrity (no barotrauma). This work was aimed at characterizing the pressure/flow relationship at the pulmonary vasculature and at how effective vascular resistance depends on pressure- and flow-controlled variables when applying different methods of media perfusion for lung decellularization. Lungs from 43 healthy mice (C57BL/6; 7-8 weeks old) were investigated. After excision and tracheal cannulation, lungs were inflated at 10 cmH2O airway pressure and subjected to conventional decellularization with a solution of 1% sodium dodecyl sulfate (SDS). Pressure (PPA) and flow (V'PA) at the pulmonary artery were continuously measured. Decellularization media was perfused through the pulmonary artery: (a) at constant PPA=20 cmH2O or (b) at constant V'PA=0.5 and 0.2 ml/min. Effective vascular resistance was computed as Rv=PPA/V'PA. Rv (in cmH2O/(ml/min)); mean±SE) considerably varied throughout lung decellularization, particularly for pressure-controlled perfusion (from 29.1±3.0 in baseline to a maximum of 664.1±164.3 (pmechanics throughout decellularization provides information relevant for optimizing the process time while ensuring that vascular pressure is kept within a safety range to preserve the organ scaffold integrity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Protective role of vascular endothelial growth factor in endotoxin-induced acute lung injury in mice

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    Adachi Yoshiyuki

    2007-08-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF, a substance that stimulates new blood vessel formation, is an important survival factor for endothelial cells. Although overexpressed VEGF in the lung induces pulmonary edema with increased lung vascular permeability, the role of VEGF in the development of acute lung injury remains to be determined. Methods To evaluate the role of VEGF in the pathogenesis of acute lung injury, we first evaluated the effects of exogenous VEGF and VEGF blockade using monoclonal antibody on LPS-induced lung injury in mice. Using the lung specimens, we performed TUNEL staining to detect apoptotic cells and immunostaining to evaluate the expression of apoptosis-associated molecules, including caspase-3, Bax, apoptosis inducing factor (AIF, and cytochrome C. As a parameter of endothelial permeability, we measured the albumin transferred across human pulmonary artery endothelial cell (HPAEC monolayers cultured on porous filters with various concentrations of VEGF. The effect of VEGF on apoptosis HPAECs was also examined by TUNEL staining and active caspase-3 immunoassay. Results Exogenous VEGF significantly decreased LPS-induced extravascular albumin leakage and edema formation. Treatment with anti-VEGF antibody significantly enhanced lung edema formation and neutrophil emigration after intratracheal LPS administration, whereas extravascular albumin leakage was not significantly changed by VEGF blockade. In lung pathology, pretreatment with VEGF significantly decreased the numbers of TUNEL positive cells and those with positive immunostaining of the pro-apoptotic molecules examined. VEGF attenuated the increases in the permeability of the HPAEC monolayer and the apoptosis of HPAECs induced by TNF-α and LPS. In addition, VEGF significantly reduced the levels of TNF-α- and LPS-induced active caspase-3 in HPAEC lysates. Conclusion These results suggest that VEGF suppresses the apoptosis induced by

  4. Diabetes mellitus vs. Raynaud disease: different lung vascular bed disorders.

    Science.gov (United States)

    Boulbou, Mary S; Gourgoulianis, Konstantinos I; Krommydas, George C; Klisiaris, Vasilios K; Arseniou, Aggelos A; Dafopoulos, Konstantinos C; Molyvdas, Paschalis A

    2002-01-01

    In type II diabetes mellitus there are few data concerning pulmonary function abnormalities. In normal subjects and in patients with primary Raynaud phenomenon, cold pressor test induces a decrease in carbon monoxide single-breath diffusing capacity (DL,co) but not in secondary Raynaud phenomenon. Our objective was to assess evaluation of lung diffusion capacity postural changes in diabetes mellitus and in secondary Raynaud phenomenon, two diseases with different pulmonary capillaries functional disorders. Twenty-five patients with type II diabetes mellitus (mean age 52.24 years), 17 patients with secondary Raynaud phenomenon (mean age 47.06 years), non-smokers without pulmonary or heart disease, and 26 healthy matched subjects (mean age 47.50 years) underwent lung diffusion capacity measurements by single-breath method also corrected by alveolar volume (DL,co) in sitting and supine positions. Patients with diabetes mellitus exhibited lower values of DL,co and DL,co/VA measurements in comparison with subjects with Raynaud phenomenon and control group (p Raynaud phenomenon and in control group after cold pressor test showed a significant increase in DL,co/VA (120.93 vs. 109.78 in Raynaud and 114.36 vs. 99.47 in control group, p disease resulting from different pathophysiologic mechanisms such as diabetes mellitus and Raynaud phenomenon.

  5. A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro

    Directory of Open Access Journals (Sweden)

    Mi Ra Kim

    2017-03-01

    Full Text Available Vascular cell adhesion molecule-1 (VCAM-1 is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival in lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells into Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6 demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549 cell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab, which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung cancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain for regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

  6. Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion.

    Directory of Open Access Journals (Sweden)

    Erin J Debruin

    Full Text Available 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(ΔEC mice to study the homeostatic role of podocalyxin in adult mouse vessels. Although Podxl(ΔEC 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(ΔEC endothelial cells display mildly enhanced static adhesion to fibronectin but spread normally when plated on fibronectin-coated transwells. In contrast, Podxl(ΔEC 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.

  7. [Deep versus moderate neuromuscular block during one-lung ventilation in lung resection surgery].

    Science.gov (United States)

    Casanova, Javier; Piñeiro, Patricia; De La Gala, Francisco; Olmedilla, Luis; Cruz, Patricia; Duque, Patricia; Garutti, Ignacio

    Neuromuscular relaxants are essential during general anesthesia for several procedures. Classical anesthesiology literature indicates that the use of neuromuscular blockade in thoracic surgery may be deleterious in patients in lateral decubitus position in one-lung ventilation. The primary objective of our study was to compare respiratory function according to the degree of patient neuromuscular relaxation. Secondary, we wanted to check that neuromuscular blockade during one-lung ventilation is not deleterious. A prospective, longitudinal observational study was made in which each patient served as both treated subject and control. 76 consecutive patients programmed for lung resection surgery in Gregorio Marañon Hospital along the year of 2013 who required one-lung ventilation in lateral decubitus were included. Ventilator data, hemodynamic parameters were registered in different moments according to train-of-four response (intense, deep and moderate blockade) during one-lung ventilation. Peak, plateau and mean pressures were significantly lower during the intense and deep blockade. Besides, compliance and peripheral oxygen saturation were significantly higher in those moments. Heart rate was significantly higher during deep blockade. No mechanical ventilation parameters were modified during measurements. Deep neuromuscular blockade attenuates the poor lung mechanics observed during one-lung ventilation. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  8. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    LENUS (Irish Health Repository)

    Sands, Michelle

    2011-01-25

    Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2) or hypoxia (10% O2) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or potentiate the

  9. Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung

    Directory of Open Access Journals (Sweden)

    McLoughlin Paul

    2011-01-01

    Full Text Available Abstract Background Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium. Methods Male Sprague Dawley rats were exposed to conditions of normoxia (21% O2 or hypoxia (10% O2 for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA, VEGFB, placenta growth factor (PlGF, VEGF receptor 1 (VEGFR1 and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay. Results Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. In vitro PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic. Conclusions VEGFB and PlGF can either inhibit or

  10. Prenatal retinoic acid improves lung vascularization and VEGF expression in CDH rat.

    Science.gov (United States)

    Schmidt, Augusto F; Gonçalves, Frances L L; Regis, Aline C; Gallindo, Rodrigo M; Sbragia, Lourenço

    2012-07-01

    We sought to investigate the effects of antenatal retinoic acid on the pulmonary vasculature and vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) expression in a nitrofen-induced congenital diaphragmatic hernia (CDH) model. Rat fetuses were exposed to nitrofen at gestational day 9.5 and/or all-trans retinoic acid (ATRA) at gestational days 18.5-20.5. We assessed lung growth, airway, and vascular morphometry. VEGF, VEGFR1, and VEGFR2 expression was analyzed by Western blotting and immunohistochemistry. Continuous data were analyzed by analysis of variance and Kruskal-Wallis test. CDH decreased lung to body weight ratio, increased mean linear intercept and mean transection length/airspace, and decreased mean airspace cord length. ATRA did not affect lung growth or morphometry. CDH increased proportional medial wall thickness of arterioles while ATRA reduced it. ATRA recovered expression of VEGF and receptors, which were reduced in CDH. Retinoic acid and VEGF may provide pathways for preventing pulmonary hypertension in CDH. Copyright © 2012 Mosby, Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  12. Use of spiral CT angiography to judge central pulmonary vascular involvement from lung cancer

    International Nuclear Information System (INIS)

    Tan Qunyou; Zhao Shaohong; Wang Fangze; Cai Zulong

    2000-01-01

    Objective: To evaluate the accuracy of spiral CT angiography (SCTA) in judging central pulmonary vascular involvement from lung cancer located in the hilum and correlate the resultant images with pathologic and surgical findings. Methods: SCTA was done in 33 patients who were preoperatively diagnosed as having lung carcinoma located in the hilum. Contrast medium was injected at a rate of 3 ml/sec with a power injector. The delay time was from 20 to 25 seconds. The pitch was 1 with 3 mm-collimation. Images of central pulmonary arteries and veins were reconstructed with shaded surface display (SSD), maximum intensity projection (MIP), curved planar reformation (CPR), and multi-planar reformation (MPR). Then the relation between tumor and vessels was assessed prospectively on both 3 mm interval axial CT and SCTA images with comparison to subsequent pathologic or surgical findings. Results: (1) In showing the integrity of central pulmonary arteries and veins, images reconstructed by different ways of SCTA had different strong and weak points. (2) The grading standard in this study, with which the relation between vessels and tumor was judged, reflected the basic and common characters of central pulmonary vascular involvement by tumor located in the hilum. compared with axial CT images, SCTA was more accurate in judging the relation between central pulmonary vessels and tumor, and the correlation of SCTA imaging features with pathological patterns and surgical findings was better than that of axial CT images, P < 0.05 and P < 0.0001, respectively. Conclusion: It was feasible to show the relation between central pulmonary vessel and lung cancer located in the hilum with SCTA. And the accuracy of judging the vascular involvement with SCTA was higher than that with axial CT

  13. The suppression of bromodomain and extra-terminal domain inhibits vascular inflammation by blocking NF-κB and MAPK activation.

    Science.gov (United States)

    Huang, Mingcheng; Zeng, Shan; Zou, Yaoyao; Shi, Maohua; Qiu, Qian; Xiao, Youjun; Chen, Guoqiang; Yang, Xiuyan; Liang, Liuqin; Xu, Hanshi

    2017-01-01

    There is increasing evidence indicating that bromodomain and extra-terminal domain (BET) proteins play a critical role in the regulation of immune and inflammatory responses; however, their contribution to vascular inflammation has not yet been elucidated. In this study, we investigated the effect of inhibiting BET bromodomain on vascular inflammation and the underlying mechanisms. HUVECs were isolated from fresh umbilical cords. JQ1, a specific BET bromodomain inhibitor, and Brd shRNA were used to evaluate the regulation of the BET proteins in vascular inflammation. Leukocyte adhesion to HUVECs was measure by an adhesion assay. Western blot or immunohistochemical analysis was used to detect the protein expression. Real-time PCR was used to evaluate mRNA expression. Leukocyte accumulation in vivo was determined by an acute lung inflammation model. BET bromodomain inhibition suppressed the expression of adhesion molecules induced by TNF-α- or LPS, including ICAM-1, VCAM-1 and E-selectin, and inhibited leukocyte adhesion to activated HUVEC monolayers. Treatment with JQ1 also attenuated the LPS-induced accumulation of leukocytes and expression of endothelial adhesion molecules in the acute lung inflammation model in vivo. Furthermore, BET bromodomain inhibition reduced the activity of p38 and JNK MAPKs and NF-κB in TNF-α-stimulated HUVECs. TNF-α-induced NF-κB activation was also blocked by inhibitors of p38 (SB203580) or JNK (SP600125). BET bromodomain is important for regulating endothelial inflammation. Strategies targeting endothelial BET bromodomain may provide a new therapeutic approach for controlling inflammatory-related diseases. © 2016 The British Pharmacological Society.

  14. FDG uptake in the fatty tissues of supraclavicular and the vascular structure of the lung hilum

    International Nuclear Information System (INIS)

    Dang Yaping; Liu Gang; Li Miao

    2004-01-01

    Objectives: To investigate FDG uptake on the sites of supraclavicular region (SR) and the lung hilum (LH) and find out the exact tissues of the uptake. Methods: Supraclavicular region (SR) and lung hilum (LH) are common sites for lymph node metastases. A commonly reported site of non-malignant FDG uptake on PET imaging in the SR is muscular uptake. PET/CT offers a unique technique to correlate PET findings with CT anatomy in the SR and EH. From September 2002 to March 2003, 147 consecutive clinical patients imaged by FDG PET/CT whole-body scan (GE Discovery LS, CT attenuation correction, OSEM reconstruction) were retrospectively reviewed. The presence of abnormal FDG uptake on PET images in the sites of SR and LH regions was evaluated and the corresponding CT findings on the same regions were also assessed. Results: Of 147 patients, 8 cases (2M, 6F and mean age 44 years) were found with increased symmetrical FDG uptake in the regions of the lower neck and shoulder as well as costo-vertebral articulations, the positive rates were 2.1% and 11.3 % for men and women respectively, and the average rate was 5.4%. However, no FDG uptake was seen in the greater muscular structures of the cervical or thoracic spine. FDG uptake was seen in the fatty tissue between the shoulder muscle and the dorsal thoracic wall, but not within the muscles itself. Five patients (3M, 2F, age 56-74 years,3.4%) showed abnormal LH FDG uptake, which were definitely localized in the vascular structure of the lung hilum by CT Conclusion: Co-registered PET/CT imaging shows that the FDG uptake been well known in the SR and LH regions are not fully located in greater muscular structures and lymph nodes, but in the costo-vertebral articulation complex of the thoracic spine and fatty tissue of the shoulders as well as in the vascular structure of both lung hilum. The FDG uptake in the fatty tissue of the shoulders was mostly seen in women, while the uptake in vascular structure of the lung hilum were

  15. Dysregulation of Vascular Endothelial Progenitor Cells Lung-Homing in Subjects with COPD

    Directory of Open Access Journals (Sweden)

    Brittany M. Salter

    2016-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterized by fixed airflow limitation and progressive decline of lung function and punctuated by occasional exacerbations. The disease pathogenesis may involve activation of the bone marrow stimulating mobilization and lung-homing of progenitor cells. We investigated the hypothesis that lower circulating numbers of vascular endothelial progenitor cells (VEPCs are a consequence of increased lung-sequestration in COPD. Nonatopic, current or ex-smokers with diagnosed COPD and nonatopic, nonsmoking normal controls were enrolled. Blood and induced sputum extracted primitive hemopoietic progenitors (HPCs and VEPC were enumerated by flow cytometry. Migration and adhesive responses to fibronectin were assessed. In sputum, VEPC numbers were significantly greater in COPD compared to normal controls. In blood, VEPCs were significantly lower in COPD versus normal controls. There were no differences in HPC levels between the two groups in either compartment. Functionally, there was a greater migrational responsiveness of progenitors from COPD subjects to stromal cell-derived factor-1alpha (SDF-1α compared to normal controls. This was associated with greater numbers of CXCR4+ progenitors in sputum from COPD. Increased migrational responsiveness of progenitor cells may promote lung-homing of VEPC in COPD which may disrupt maintenance and repair of the airways and contribute to COPD disease pathogenesis.

  16. Correlation between matrix metalloproteinase-9 and vascular endothelial growth factor expression in lung adenocarcinoma.

    Science.gov (United States)

    Wen, Y L; Li, L

    2015-12-29

    The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) and clinicopathological features of lung adenocarcinoma. The expression of MMP-9 and VEGF was evaluated by immunohistochemistry of 30 samples from lung adenocarcinoma patients and 12 paratumoral (normal) tissue samples. In addition, the change in VEGF or MMP-9 expression after MMP-9 or VEGF blockade, respectively, was measured using western blot in lung adenocarcinoma A549 cells. High expression of MMP-9 was found in 63.3% of adenocarcinoma tissues versus 16.7% in normal tissues (P correlation was identified between MMP-9 and VEGF expression (correlation coefficient = 0.7094, P < 0.001), and their mutual overexpression was associated with clinical staging and lymph node status (P < 0.05). In addition, an decrease in VEGF protein expression was observed after MMP-9 blockade by an MMP-9-specific monoclonal antibody. Similarly, a decrease in MMP-9 protein expression was found after VEGF blockade by a VEGF-specific monoclonal antibody. In conclusion, VEGF and MMP-9 are overexpressed in lung adenocarcinoma tissues, and they have a synergistic effect on the invasion and metastasis of adenocarcinoma.

  17. A block matching-based registration algorithm for localization of locally advanced lung tumors.

    Science.gov (United States)

    Robertson, Scott P; Weiss, Elisabeth; Hugo, Geoffrey D

    2014-04-01

    To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Small (1 cm(3)), nonoverlapping image subvolumes ("blocks") were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4-7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%-100%) in the initial bony alignment to 91% ± 8% (range: 56%-100%;p < 0.001). Left-right, anterior-posterior, and

  18. Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury.

    Science.gov (United States)

    Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L; Connelly, Rhykka; Nakano, Yoshimitsu; Traber, Lillian D; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-11-01

    Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Sheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 h. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P<0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P<0.05 each). This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  19. Pulmonary Vascular Congestion: A Mechanism for Distal Lung Unit Dysfunction in Obesity.

    Directory of Open Access Journals (Sweden)

    Beno W Oppenheimer

    Full Text Available Obesity is characterized by increased systemic and pulmonary blood volumes (pulmonary vascular congestion. Concomitant abnormal alveolar membrane diffusion suggests subclinical interstitial edema. In this setting, functional abnormalities should encompass the entire distal lung including the airways.We hypothesize that in obesity: 1 pulmonary vascular congestion will affect the distal lung unit with concordant alveolar membrane and distal airway abnormalities; and 2 the degree of pulmonary congestion and membrane dysfunction will relate to the cardiac response.54 non-smoking obese subjects underwent spirometry, impulse oscillometry (IOS, diffusion capacity (DLCO with partition into membrane diffusion (DM and capillary blood volume (VC, and cardiac MRI (n = 24. Alveolar-capillary membrane efficiency was assessed by calculation of DM/VC.Mean age was 45±12 years; mean BMI was 44.8±7 kg/m2. Vital capacity was 88±13% predicted with reduction in functional residual capacity (58±12% predicted. Despite normal DLCO (98±18% predicted, VC was elevated (135±31% predicted while DM averaged 94±22% predicted. DM/VC varied from 0.4 to 1.4 with high values reflecting recruitment of alveolar membrane and low values indicating alveolar membrane dysfunction. The most abnormal IOS (R5 and X5 occurred in subjects with lowest DM/VC (r2 = 0.31, p<0.001; r2 = 0.34, p<0.001. Cardiac output and index (cardiac output / body surface area were directly related to DM/VC (r2 = 0.41, p<0.001; r2 = 0.19, p = 0.03. Subjects with lower DM/VC demonstrated a cardiac output that remained in the normal range despite presence of obesity.Global dysfunction of the distal lung (alveolar membrane and distal airway is associated with pulmonary vascular congestion and failure to achieve the high output state of obesity. Pulmonary vascular congestion and consequent fluid transudation and/or alterations in the structure of the alveolar capillary membrane may be considered often

  20. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei, E-mail: chtw@sina.com

    2015-03-06

    Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and poor prognosis; however, the molecular basis of this process is still unknown. This study investigated the role of extracellular matrix metalloproteinase inducer (also known as cluster of differentiation (CD)147) in osteoclastogenesis resulting from bone metastasis, based on the enrichment of this glycoprotein on the surface of many malignant bone tumors. RNA interference was used to silence CD147 expression in A549 human lung cancer cells. Compared with conditioned medium (CM) from control cells (A549-CM), CM from CD147-deficient cells (A549-si-CM) suppressed receptor activator of nuclear factor κB ligand-stimulated osteoclastogenesis in RAW 264.7 cells and bone marrow-derived macrophages. The mRNA levels of osteoclast-specific genes such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K were also reduced in the presence of A549-si-CM. CD147 knockdown in A549 cells decreased interleukin (IL)-8mRNA and protein expression. IL-8 is present in large amounts in A549-CM and mimicked its inductive effect on osteoclastogenesis; this was reversed by depletion of IL-8 from the medium. Taken together, these results indicate that CD147 promotes lung cancer-induced osteoclastogenesis by modulating IL-8 secretion, and suggest that CD147 is a potential therapeutic target for cancer-associated bone resorption in lung cancer patients. - Highlights: • Bone loss frequently results from lung cancer metastasis. • Cluster of differentiation (CD)147 was depleted in A549 lung adenocarcinoma cells. • RAW 264.7 cell osteoclastogenesis was blocked by medium from CD147-deficient cells. • Interleukin (IL)-8 level was reduced in the conditioned medium. • Osteoclastogenesis induced by lung tumor cells requires CD147-mediated IL-8 release.

  1. A block matching-based registration algorithm for localization of locally advanced lung tumors

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, 23298 (United States)

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  2. A block matching-based registration algorithm for localization of locally advanced lung tumors

    International Nuclear Information System (INIS)

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm 3 ), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0.001). Left

  3. Antiangiogenic therapy in lung cancer: focus on vascular endothelial growth factor pathway.

    LENUS (Irish Health Repository)

    Korpanty, Grzegorz

    2010-01-01

    Lung cancer (LC) is a leading cause of death worldwide. Recent advances in chemotherapeutic agents have not yielded any significant improvement in the prognosis of patients with LC. The five-year survival rate for all combined disease stages remains about 15%. For this reason, new therapies such as those that inhibit tumor angiogenesis or block activity of growth factor receptors are of special interest in this group of patients. In this review we will summarize the most recent clinical data on biologic therapies that inhibit tumor angiogenesis in LC, focusing on those that are most clinically relevant.

  4. Vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 expression in non-small cell lung cancer patients: relation to prognosis

    DEFF Research Database (Denmark)

    Bonnesen, Barbara; Pappot, Helle; Holmstav, Julie

    2009-01-01

    elements in neoplastic cells and their microenvironment have recently been and are continuously developed including drugs inhibiting the angiogenic system. Angiogenic factor vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) seem to play key......BACKGROUND: The majority of patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced inoperable disease. While treatment with conventional chemotherapy has improved during the last decade the 5 years survival is still modest. Novel drugs, which selectively target aberrant...

  5. Efficacy of stellate ganglion block with an adjuvant ketamine for peripheral vascular disease of the upper limbs

    Directory of Open Access Journals (Sweden)

    Kalpana R Kulkarni

    2010-01-01

    Full Text Available Stellate ganglion block (STGB is commonly indicated in painful conditions like reflex sympathetic dystrophy, malignancies of head and neck, Reynaud′s disease and vascular insufficiency of the upper limbs. The sympathetic blockade helps to relieve pain and ischaemia. Diagnostic STGB is usually performed with local anaesthetics followed by therapeutic blockade with steroids, neurolytic agents or radiofrequency ablation of ganglion. There is increasing popularity and evidence for the use of adjuvants like opioid, clonidine and N Methyl d Aspartate (NMDA receptor antagonist - ketamine - for the regional and neuroaxial blocks. The action of ketamine with sympatholytic block is through blockade of peripherally located NMDA receptors that are the target in the management of neuropathic pain, with the added benefit of counteracting the "wind-up" phenomena of chronic pain. We studied ketamine as an adjuvant to the local anaesthetic for STGB in 20 cases of peripheral vascular disease of upper limbs during the last 5 years at our institution. STGB was given for 2 days with 2 ml of 2% lignocaine + 8 ml of 0.25% bupivacaine, followed by block with the addition of 0.5 mg/kg of ketamine for three consecutive days. There was significant pain relief of longer duration with significant rise in hand temperature. We also observed complete healing of the gangrenous fingers in 17/19 patients.

  6. GPU-accelerated Block Matching Algorithm for Deformable Registration of Lung CT Images.

    Science.gov (United States)

    Li, Min; Xiang, Zhikang; Xiao, Liang; Castillo, Edward; Castillo, Richard; Guerrero, Thomas

    2015-12-01

    Deformable registration (DR) is a key technology in the medical field. However, many of the existing DR methods are time-consuming and the registration accuracy needs to be improved, which prevents their clinical applications. In this study, we propose a parallel block matching algorithm for lung CT image registration, in which the sum of squared difference metric is modified as the cost function and the moving least squares approach is used to generate the full displacement field. The algorithm is implemented on Graphic Processing Unit (GPU) with the Compute Unified Device Architecture (CUDA). Results show that the proposed parallel block matching method achieves a fast runtime while maintaining an average registration error (standard deviation) of 1.08 (0.69) mm.

  7. Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

    Science.gov (United States)

    Robertson, Scott Patrick

    To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

  8. Occlusive vascular Ehlers-Danlos syndrome accompanying a congenital cystic adenomatoid malformation of the lung: report of a case.

    Science.gov (United States)

    Sa, Young Jo; Kim, Young Du; Moon, Seok-Whan; Kim, Chi-Kyung; Ki, Chang Seok

    2013-12-01

    An 8-year-old male presented with a cystic lung lesion in the left lower lobe, which was initially detected during surgery for a spontaneous rupture of the sigmoid colon at the age of 6 years. Tissue fragility and a tendency to bleed easily were noted during the surgery, which strongly suggested vascular Ehlers-Danlos syndrome. Although there was no abnormality in the hemostasis screening test, or any suspicious hereditary problem in his pedigree, genetic gene testing for vascular Ehlers-Danlos syndrome was recommended, and showed a de novo mutation in the COL3A1 gene. This report presents the case of patient with occlusive vascular Ehlers-Danlos syndrome accompanying a congenital cystic adenomatoid malformation of lung, in addition to a duplicated infrarenal vena cava.

  9. In vivo immunotherapy of lung cancer using cross-species reactive vascular endothelial growth factor nanobodies

    Directory of Open Access Journals (Sweden)

    vFatemeh Kazemi-Lomedasht v

    2017-05-01

    Full Text Available Objective(s: Lung cancer is the main leading cause of cancer death worldwide. Angiogenesis is the main step in proliferation and spreading of tumor cells. Targeting vascular endothelial growth factor (VEGF is an effective approach for inhibition of cancer angiogenesis. Nanobodies (NBs are a novel class of antibodies derived from the camel. Unique characteristics of Nbs like their small size and good penetration to tumor tissues makes them promising tools in drug development.  Development of NBs targeting both human and mouse VEGF is required for understanding their in vivo functions.  Therefore, development of cross-species reactive anti-VEGF Nbs for immunotherapy of lung cancer was the main aim of the current study. Materials and Methods: Here we developed NBs from Camelus dromedarius library with high specificity and binding affinity to both human and mouse VEGF. In vitro and In vivo function of developed NB was evaluated on human endothelial cells and lung epithelial tumor cells (TC-1. Results: A nanobody showed the highest affinity to human and mouse VEGF and potently inhibited VEGF in the ELISA experiment. Anti-VEGF NBs significantly inhibited in vitro human endothelial cell migration through blockade of VEGF (P=0.045. Anti-VEGF NBs also significantly inhibited in vivo TC-1 growth in a dose-dependent manner (P=0.001 and resulted in higher survival rate in the nanobody treated group Conclusion: These findings demonstrate the potential of anti-VEGF NBsin tumor growth inhibition and are promising as novel cancer therapeutic candidate.

  10. Pulmonary vascular volume ratio measured by cardiac computed tomography in children and young adults with congenital heart disease: comparison with lung perfusion scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo; Park, Sang Hyub [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    Lung perfusion scintigraphy is regarded as the gold standard for evaluating differential lung perfusion ratio in congenital heart disease. To compare cardiac CT with lung perfusion scintigraphy for estimated pulmonary vascular volume ratio in patients with congenital heart disease. We included 52 children and young adults (median age 4 years, range 2 months to 28 years; 31 males) with congenital heart disease who underwent cardiac CT and lung perfusion scintigraphy without an interim surgical or transcatheter intervention and within 1 year. We calculated the right and left pulmonary vascular volumes using threshold-based CT volumetry. Then we compared right pulmonary vascular volume percentages at cardiac CT with right lung perfusion percentages at lung perfusion scintigraphy by using paired t-test and Bland-Altman analysis. The right pulmonary vascular volume percentages at cardiac CT (66.3 ± 14.0%) were significantly smaller than the right lung perfusion percentages at lung perfusion scintigraphy (69.1 ± 15.0%; P=0.001). Bland-Altman analysis showed a mean difference of -2.8 ± 5.8% and 95% limits of agreement (-14.1%, 8.5%) between these two variables. Cardiac CT, in a single examination, can offer pulmonary vascular volume ratio in addition to pulmonary artery anatomy essential for evaluating peripheral pulmonary artery stenosis in patients with congenital heart disease. However there is a wide range of agreement between cardiac CT and lung perfusion scintigraphy. (orig.)

  11. Correlation between PaO2/FiO2and airway and vascular parameters in the assessment of cellular ex vivo lung perfusion system.

    Science.gov (United States)

    Okamoto, Toshihiro; Wheeler, David; Liu, Qiang; Quintini, Cristiano; Hata, J Steven; McCurry, Kenneth R

    2016-11-01

    Ex vivo lung perfusion (EVLP) may be an essential process for the pre-transplant evaluation of the donor lungs. Currently, the partial pressure of oxygen/fraction of inspired oxygen (PaO 2 /FiO 2 , or PF) ratio is the standard in the assessment of lung function in cellular EVLP, whereas other parameters, including airway and vascular parameters, have only been partially utilized. The primary purpose of this study is to assess the potential utility of other parameters as a surrogate of lung function in EVLP. Yorkshire swine lungs (n = 12) and rejected human donor lungs (n = 12) were perfused in cellular-based EVLP for 2 hours. PF ratio, airway parameters (peak airway pressure, plateau pressure, dynamic compliance and static compliance) and vascular parameters (pulmonary vascular resistance and pulmonary artery pressure) were measured. The correlations between PF ratio and one of these parameters were analyzed. Correlations were identified in the following combinations: PF ratio and airway parameters (p swine lungs (p = 0.0001); and PF ratio and airway parameters in rejected human lungs (p swine lungs (p lung function in cellular EVLP, based on the correlations with PF ratio in both swine lungs and human lungs. Copyright © 2016. Published by Elsevier Inc.

  12. Extravascular lung water and pulmonary vascular permeability index as markers predictive of postoperative acute respiratory distress syndrome: a prospective cohort investigation.

    Science.gov (United States)

    Kor, Daryl J; Warner, David O; Carter, Rickey E; Meade, Laurie A; Wilson, Greg A; Li, Man; Hamersma, Marvin J; Hubmayr, Rolf D; Mauermann, William J; Gajic, Ognjen

    2015-03-01

    Robust markers of subclinical perioperative lung injury are lacking. Extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index are two promising early markers of lung edema. We aimed to evaluate whether extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index would identify patients at risk for clinically significant postoperative pulmonary edema, particularly resulting from the acute respiratory distress syndrome. Prospective cohort study. Tertiary care academic medical center. Adults undergoing high-risk cardiac or aortic vascular surgery (or both) with risk of acute respiratory distress syndrome. None. Extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index measurements were obtained intraoperatively and in the early postoperative period. We assessed the accuracy of peak extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index as predictive markers of clinically significant pulmonary edema (defined as acute respiratory distress syndrome or cardiogenic pulmonary edema) using area under the receiver-operating characteristic curves. Associations between extravascular lung water indexed to predicted body weight and pulmonary vascular permeability patient-important with important outcomes were assessed. Of 150 eligible patients, 132 patients (88%) had extravascular lung water indexed to predicted body weight and pulmonary vascular permeability index measurements. Of these, 13 patients (9.8%) had postoperative acute respiratory distress syndrome and 15 patients (11.4%) had cardiogenic pulmonary edema. Extravascular lung water indexed to predicted body weight effectively predicted development of clinically significant pulmonary edema (area under the receiver-operating characteristic curve, 0.79; 95% CI, 0.70-0.89). Pulmonary vascular permeability index discriminated acute respiratory distress

  13. Airway tree segmentation in serial block-face cryomicrotome images of rat lungs.

    Science.gov (United States)

    Bauer, Christian; Krueger, Melissa A; Lamm, Wayne J; Smith, Brian J; Glenny, Robb W; Beichel, Reinhard R

    2014-01-01

    A highly automated method for the segmentation of airways in the serial block-face cryomicrotome images of rat lungs is presented. First, a point inside of the trachea is manually specified. Then, a set of candidate airway centerline points is automatically identified. By utilizing a novel path extraction method, a centerline path between the root of the airway tree and each point in the set of candidate centerline points is obtained. Local disturbances are robustly handled by a novel path extraction approach, which avoids the shortcut problem of standard minimum cost path algorithms. The union of all centerline paths is utilized to generate an initial airway tree structure, and a pruning algorithm is applied to automatically remove erroneous subtrees or branches. Finally, a surface segmentation method is used to obtain the airway lumen. The method was validated on five image volumes of Sprague-Dawley rats. Based on an expert-generated independent standard, an assessment of airway identification and lumen segmentation performance was conducted. The average of airway detection sensitivity was 87.4% with a 95% confidence interval (CI) of (84.9, 88.6)%. A plot of sensitivity as a function of airway radius is provided. The combined estimate of airway detection specificity was 100% with a 95% CI of (99.4, 100)%. The average number and diameter of terminal airway branches was 1179 and 159 μm, respectively. Segmentation results include airways up to 31 generations. The regression intercept and slope of airway radius measurements derived from final segmentations were estimated to be 7.22 μm and 1.005, respectively. The developed approach enables the quantitative studies of physiology and lung diseases in rats, requiring detailed geometric airway models.

  14. Vascular Endothelial Growth Factor in Bronchoalveolar Lavage Fluid in SulfurMustard Exposed Lung Patients

    Directory of Open Access Journals (Sweden)

    Mobin Yassini

    2011-03-01

    Full Text Available Objectives: To determine the levels of vascular endothelial growth factor isoform consisting of 165 amino acids (VEGF165 in Bronchoalveolar Lavage Fluid from Mustard Exposed Patients.Methods: Bronchoscopy with Bronchoalveolar Lavage was performed on sulphur mustard exposed patients. A total of 39 patients with documented exposure to Sulfur Mustard during the Iran-Iraq war participated in this study, of which 38 patients were males and one patient was female.Results: The mean±SD age of patients was 41 ± 6.6 years. The mean time after exposure to sulfur mustard was 19 ±1.7 years. Eighteen patients had concomitant war injuries but they were not related to the respiratory system. While Twenty-two patients had a history of submassive persistent hemoptysis. There was no case with massive hemoptysis. Most of the patients had small airway obstruction (FEV1/FVC�0= 78.14 ± 9.76 and FEV1�0=82.79±18.23. Twenty-three patients had significant air trapping in the chest. High Resolution Computed Tomography was compatible with BOS. VEGF165 concentrations in BALF were 36.87 ± 34.68 pg/ml. When corrected to total protein of Bronchoalveolar Lavage Fluid (BALF it was 0.76 ± 0.70 pg/mg. BALF of VEGF did not correlate with hemoptysis or air trapping in chest HRCT. Thus, there was also no correlation between level of VEGF165 in BALF and any of PFT indexes (FVC, FEV1, MMEF or PEF.Conclusions: Although VEGF is one of the cytokines which has an important role in chronic pulmonary disorders, it seems that it has no essential role in the severity of Mustard Lung Disease.

  15. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism.

    Directory of Open Access Journals (Sweden)

    Sarah Garrido-Urbani

    Full Text Available Reactive oxygen species, ROS, are regulators of endothelial cell migration, proliferation and survival, events critically involved in angiogenesis. Different isoforms of ROS-generating NOX enzymes are expressed in the vasculature and provide distinct signaling cues through differential localization and activation. We show that mice deficient in NOX1, but not NOX2 or NOX4, have impaired angiogenesis. NOX1 expression and activity is increased in primary mouse and human endothelial cells upon angiogenic stimulation. NOX1 silencing decreases endothelial cell migration and tube-like structure formation, through the inhibition of PPARα, a regulator of NF-κB. Administration of a novel NOX-specific inhibitor reduced angiogenesis and tumor growth in vivo in a PPARα dependent manner. In conclusion, vascular NOX1 is a critical mediator of angiogenesis and an attractive target for anti-angiogenic therapies.

  16. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs.

    Science.gov (United States)

    Grasemann, Hartmut; Dhaliwal, Rupinder; Ivanovska, Julijana; Kantores, Crystal; McNamara, Patrick J; Scott, Jeremy A; Belik, Jaques; Jankov, Robert P

    2015-03-15

    Arginase is an enzyme that limits substrate L-arginine bioavailability for the production of nitric oxide by the nitric oxide synthases and produces L-ornithine, which is a precursor for collagen formation and tissue remodeling. We studied the pulmonary vascular effects of arginase inhibition in an established model of repeated systemic bleomycin sulfate administration in neonatal rats that results in pulmonary hypertension and lung injury mimicking the characteristics typical of bronchopulmonary dysplasia. We report that arginase expression is increased in the lungs of bleomycin-exposed neonatal rats and that treatment with the arginase inhibitor amino-2-borono-6-hexanoic acid prevented the bleomycin-induced development of pulmonary hypertension and deposition of collagen. Arginase inhibition resulted in increased L-arginine and L-arginine bioavailability and increased pulmonary nitric oxide production. Arginase inhibition also normalized the expression of inducible nitric oxide synthase, and reduced bleomycin-induced nitrative stress while having no effect on bleomycin-induced inflammation. Our data suggest that arginase is a promising target for therapeutic interventions in neonates aimed at preventing lung vascular remodeling and pulmonary hypertension. Copyright © 2015 the American Physiological Society.

  17. Function-blocking antibodies to human vascular adhesion protein-1: a potential anti-inflammatory therapy.

    Science.gov (United States)

    Kirton, Christopher M; Laukkanen, Marja-Leena; Nieminen, Antti; Merinen, Marika; Stolen, Craig M; Armour, Kathryn; Smith, David J; Salmi, Marko; Jalkanen, Sirpa; Clark, Michael R

    2005-11-01

    Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazide-sensitive amine oxidase and as an adhesion molecule. Blockade of VAP-1 has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.

  18. The Stumbling Block in Lung Repair of Emphysema: Elastic Fiber Assembly

    OpenAIRE

    Shifren, Adrian; Mecham, Robert P.

    2006-01-01

    The mechanical properties of the lung are largely determined by the connective tissue networks laid down during development. The macromolecules most important for lung mechanics and structural integrity are collagen, elastin, and proteoglycans. Members of the fibrillar collagen gene family provide the structural framework of the various lung compartments and elastic fibers provide elastic recoil. Elastin is also an important architectural component that influences lung development, predominan...

  19. An Isolated Pulmonary Hematoma Mimicking a Lung Tumor as the Initial Finding of Vascular Ehlers-Danlos Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eun Ju; Lee, Ki Nam; Choi, Pil Jo [Dept. of Radiology, Dong-A University Medicine Center, Dong-A University College of Medicine, Busan (Korea, Republic of); Ki, Chang Seok [Dept. of Radiology, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-09-15

    The vascular type of Ehlers-Danlos syndrome (vEDS) is an uncommon inherited disorder characterized by abnormalities in type III collagen, presenting itself as arterial dissection or rupture. We report a case of an isolated pulmonary hematoma mimicking a lung tumor in an 18-year-old man which turned out to be the initial finding of vEDS. Pneumothorax and hemothorax occurred repeatedly for 15 months following the surgical removal of the mass, and were treated by repeated left upper and lower lobectomy and thoracotomy. The diagnosis of vEDS was confirmed by pathologic and genetic studies.

  20. Bone marrow derived mesenchymal stem cells inhibit inflammation and preserve vascular endothelial integrity in the lungs after hemorrhagic shock.

    Directory of Open Access Journals (Sweden)

    Shibani Pati

    Full Text Available Hemorrhagic shock (HS and trauma is currently the leading cause of death in young adults worldwide. Morbidity and mortality after HS and trauma is often the result of multi-organ failure such as acute lung injury (ALI and acute respiratory distress syndrome (ARDS, conditions with few therapeutic options. Bone marrow derived mesenchymal stem cells (MSCs are a multipotent stem cell population that has shown therapeutic promise in numerous pre-clinical and clinical models of disease. In this paper, in vitro studies with pulmonary endothelial cells (PECs reveal that conditioned media (CM from MSCs and MSC-PEC co-cultures inhibits PEC permeability by preserving adherens junctions (VE-cadherin and β-catenin. Leukocyte adhesion and adhesion molecule expression (VCAM-1 and ICAM-1 are inhibited in PECs treated with CM from MSC-PEC co-cultures. Further support for the modulatory effects of MSCs on pulmonary endothelial function and inflammation is demonstrated in our in vivo studies on HS in the rat. In a rat "fixed volume" model of mild HS, we show that MSCs administered IV potently inhibit systemic levels of inflammatory cytokines and chemokines in the serum of treated animals. In vivo MSCs also inhibit pulmonary endothelial permeability and lung edema with concurrent preservation of the vascular endothelial barrier proteins: VE-cadherin, Claudin-1, and Occludin-1. Leukocyte infiltrates (CD68 and MPO positive cells are also decreased in lungs with MSC treatment. Taken together, these data suggest that MSCs, acting directly and through soluble factors, are potent stabilizers of the vascular endothelium and inflammation. These data are the first to demonstrate the therapeutic potential of MSCs in HS and have implications for the potential use of MSCs as a cellular therapy in HS-induced lung injury.

  1. Immunohistochemical examination of plexiform-like complex vascular lesions in the lungs of broiler chickens selected for susceptibility to idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Hamal, Krishna R; Erf, Gisela F; Anthony, Nicholas B; Wideman, Robert F

    2012-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a disease of unknown cause that is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance, and by extensive vascular remodelling. In human IPAH patients, remodelling of the pulmonary vasculature results in the formation of plexiform lesions in the terminal pulmonary arterioles. Various molecules are expressed in the human plexiform lesions, including alpha smooth muscle actin, von Willebrand factor, vascular endothelial growth factor, vascular endothelial growth factor receptor type 2, hypoxia inducible factor-1α, survivin, tenascin, collagen, fibronectin, and various immune/inflammatory cells such as, cytotoxic lymphocytes, B lymphocytes, MHC class II cells, and monocytes/macrophages are also present. Plexiform lesions rarely develop in the lungs of laboratory animals, but plexiform-like complex vascular lesions (CVL) do develop spontaneously in the lungs of broiler chickens from an IPAH-susceptible line. To examine angioproliferative and immune-system-related activities associated with CVL in broiler lungs, paraformaldehyde-fixed, paraffin-embedded lung sections from 8-week-old to 24-week-old broiler chickens were stained immunohistochemically using monoclonal or polyclonal antibodies specific for angioproliferative molecules and immune/inflammatory cells. The CVL in the lungs of broiler chickens exhibited positive staining for both angioproliferative molecules and immune/inflammatory cells. These observations combined with the close histological resemblance of broiler CVL to the plexiform lesions of human IPAH patients further validates chickens from our IPAH-susceptible line as an excellent animal model of spontaneous plexogenic arteriopathy.

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

    International Nuclear Information System (INIS)

    Ng, Q.-S.; Goh, Vicky; Milner, Jessica; Padhani, Anwar R.; Saunders, Michele I.; Hoskin, Peter J.

    2007-01-01

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

  3. Suppression of lymphangiogenesis by soluble vascular endothelial growth factor receptor-2 in a mouse lung cancer model.

    Science.gov (United States)

    Maehana, Shotaro; Nakamura, Masaki; Ogawa, Fumihiro; Imai, Rimika; Murakami, Rei; Kojima, Fumiaki; Majima, Masataka; Kitasato, Hidero

    2016-12-01

    The vascular endothelial growth factor (VEGF) family has a key role in the formation of blood vessels and lymphatics. Among the members of this family, VEGF-C is one of the most important factors involved in lymphangiogenesis via binding with two receptors (vascular endothelial growth factor receptor-2 and -3: VEGFR-2 and VEGFR-3). Soluble VEGFR-2 (sVEGFR-2) has a role in maintaining the alymphatic state of the cornea associated with binding to VEGF-C, and selectively inhibits lymphangiogenesis but not angiogenesis. In this study, we introduced sVEGFR-2 into lung cancer cells and evaluated the influence on tumor progression and on genes regulating lymphatic formation and metastasis in vivo. A retroviral vector was used to introduce the sVEGFR-2 gene into Lewis lung carcinoma cells (LLC), which were designated as LLC-sVEGFR-2 cells. Proteins secreted into the culture supernatant by these cells were detected by western blotting using specific antibodies. To examine lymphangiogenesis by primary lung cancer in vivo, LLC-sVEGFR-2 cells were subcutaneously injected into C57BL/6 mice. At 14days after injection, immunohistochemistry was performed using an antibody directed against lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), a marker of lymphatics. Expression of mRNA for VEGFR-2, VEGFR-3 and matrix metalloproteinases (MMPs) was also determined by real-time PCR. Furthermore, LLC-sVEGFR-2 cells were directly inoculated into the left lung in C57BL/6 mice and the number of micro-metastases in pulmonary lymph nodes was determined. Introduction of sVEGFR-2 into LLC cells resulted in secretion of sVEGFR-2 protein into the culture supernatant. There were fewer LYVE-1 positive lymphatics after inoculation of LLC-sVEGFR-2 into mice compared with the control group. In addition, VEGFR-2, VEGFR-3, and MMPs gene expression was suppressed in the primary tumors of the LLC-sVEGFR-2 group compared with the control group. Furthermore, there were fewer micro-metastases in the

  4. MEK inhibitors block growth of lung tumours with mutations in ataxia–telangiectasia mutated

    Science.gov (United States)

    Smida, Michal; Fece de la Cruz, Ferran; Kerzendorfer, Claudia; Uras, Iris Z.; Mair, Barbara; Mazouzi, Abdelghani; Suchankova, Tereza; Konopka, Tomasz; Katz, Amanda M.; Paz, Keren; Nagy-Bojarszky, Katalin; Muellner, Markus K.; Bago-Horvath, Zsuzsanna; Haura, Eric B.; Loizou, Joanna I.; Nijman, Sebastian M. B.

    2016-01-01

    Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo. Mechanistically, ATM mediates crosstalk between the prosurvival MEK/ERK and AKT/mTOR pathways. ATM loss also enhances the sensitivity of KRAS- or BRAF-mutant lung cancer cells to MEK inhibition. Thus, ATM mutational status in lung cancer is a mechanistic biomarker for MEK inhibitor response, which may improve patient stratification and extend the applicability of these drugs beyond RAS and BRAF mutant tumours. PMID:27922010

  5. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang, E-mail: zgliu@helix.nih.gov [Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-04

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80{sup +} macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206{sup +} TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  6. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2013-12-01

    Full Text Available Tumor-associated macrophages (TAMs promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA blocks occurrence of tumor associated macrophages (TAMs in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA, a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80+ macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206+ TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  7. Expression of lung vascular and airway ICAM-1 after exposure to bacterial lipopolysaccharide

    DEFF Research Database (Denmark)

    Beck-Schimmer, B; Schimmer, R C; Warner, R L

    1997-01-01

    lavage fluids (BALFs) of animals after intratracheal instillation of LPS. Retrieved alveolar macrophages showed a small, significant, and transient increase in surface expression of ICAM-1. These data indicate, at the very least, a dual compartmentalized (vascular and airway) upregulation of ICAM-1 after...

  8. The stumbling block in lung repair of emphysema: elastic fiber assembly.

    Science.gov (United States)

    Shifren, Adrian; Mecham, Robert P

    2006-07-01

    The mechanical properties of the lung are largely determined by the connective tissue networks laid down during development. The macromolecules most important for lung mechanics and structural integrity are collagen, elastin, and proteoglycans. Members of the fibrillar collagen gene family provide the structural framework of the various lung compartments and elastic fibers provide elastic recoil. Elastin is also an important architectural component that influences lung development, predominantly during the alveolar stage. Previous studies have conclusively shown that elastin degradation is a key step in the pathogenesis of chronic obstructive pulmonary disease. Exacerbating the disease process is the inability of lung cells to repair damaged elastic fibers, which leads to permanently compromised lung function and ongoing degenerative disease. Elastic fibers are among the most difficult matrix structures to repair because of their size, molecular complexity, and the requirement for numerous helper proteins to facilitate fiber assembly. Recent studies of elastin assembly combined with new insight into the functional role of elastic fiber proteins obtained from gene inactivation studies and linkage of human disease to elastin mutations provide new insight into the molecular and cellular complexities of elastin homeostasis.

  9. Supplemental single shot femoral nerve block for total hip arthroplasty: impact on early postoperative care, pain management and lung function.

    Science.gov (United States)

    Wiesmann, T; Steinfeldt, T; Wagner, G; Wulf, H; Schmitt, J; Zoremba, M

    2014-01-01

    Peripheral regional anesthesia is beneficial in the management of postoperative pain in hip surgery, and can also reduce post-operative care unit (PACU) stay. Its opioid-sparing actions may also be beneficial for respiratory mechanics and pulmonary function. The aim of our pilot study was to evaluate the effect of a supplemental single shot femoral block for elective total hip arthroplasty on early respiratory function and postoperative management within the first 24 postoperative hours. We prospectively studied 80 patients undergoing total hip arthroplasty. Written informed consent was obtained after ethics committee approval. Forty patients were randomLy assigned to receive single shot femoral nerve block (FNB) using 15mL bupivacaine 0.25% and 20 mg clonidine while the remainder received standard treatment without nerve block (STN). Premedication and general anesthesia were standardized. Pulse oximetry saturation and spirometric lung function were measured preoperatively (baseline) and at 0.5 h, 2 h, 6 h and 24 h, after extubation breathing room air. PACU surveillance and postoperative pain therapy was standardized. Oxygen saturation and spirometry results were significantly better within the FNB group during the first six postoperative hours. Although VAS scores during the PACU stay did not significantly differ between the study groups, PACU discharge criteria were met earlier in the FNB group (116±40 min [mean±SD] vs. 152±47 min in the STN group). The FNB group exhibited significantly lower VAS scores at 6 and 24 hours. Supplemental single shot femoral nerve block for total hip arthroplasty resulted in earlier PACU discharge capability, improved lung function during the first six hours and better pain control within the first 24 postoperative hours.

  10. Interstitial lung disease associated with collagen vascular disorders: disease quantification using a computer-aided diagnosis tool

    International Nuclear Information System (INIS)

    Marten, K.; Engelke, C.; Dicken, V.; Kneitz, C.; Hoehmann, M.; Kenn, W.; Hahn, D.

    2009-01-01

    The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool compared to human observers in quantification of interstitial lung disease (ILD) in patients with collagen-vascular disorders. A total of 52 patients with rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus (n=14) underwent thin-section CT. Two independent observers assessed the extent of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD assessed EoILD twice. Pulmonary function tests were obtained. Statistical evaluation used 95% limits of agreement and linear regression analysis. CAD correlated well with diffusing capacity (DL CO ) (R=-0.531, P CO (R=-0.705, P CO and moderately with FVC (DL CO : R=-0.663; FVC: R=-0.436; P≤0.005). The CAD system is a promising tool for ILD quantification, showing close correlation with human observers and physiologic impairment. (orig.)

  11. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Ishii, Sachiko; Koto, Masashi; Imai, Reiko; Saegusa, Kimiko; Michikawa, Yuichi; Imai, Takashi

    2003-01-01

    We cloned H2 cell line from IA cell line (human large cell lung cancer) in anoxic cell culture. AH2 nude tumor develops a poor vascular system with rich fibrous component and shows low radiosensitivity compared with IA tumor. In relation to radiosensitivity, we studied the gene expression of the both cell lines grown in culture under an oxic or anoxic condition, and in a nude tumor with a microarray method using 22K custom oligoallele. As a result, we found that the both cells depressed CXCL1 and CXCL gene in anoxic culture condition and depressed or expressed IF127, EBI3, and cytokine like protein C17 gene in a nude tumor. (author)

  12. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Ishii, Sachiko; Baba, Masayuki; Sugawara, Toshiyuki; Furuno, Aki; Saegusa, Kimiko; Michikawa, Y.; Imai, Takashi

    2004-01-01

    We cloned H2 cell line from IA cell line (human large cell lung cancer) in anoxic cell culture. AH2 nude tumor develops a poor vascular system with rich fibrous component and shows low radiosensitivity compared with IA tumor. In relation to radiosensitivity, we studied the gene expression of the both cell lines grown in culture under an oxic or anoxic condition, and in a nude tumor with a microarray method using 22K custom oligoallele. As a result, we found that the both cells depressed CXCL1 and CXCL gene in anoxic culture condition and depressed or expressed IFI27, EBI3, and cytokine like protein C17 gene in a nude tumor. (author)

  13. The relationship between the percentage of lung shunting on Tc-99m macroaggregated albumin (Tc-99m MAA scan and the grade of hepatocellular carcinoma vascularity

    Directory of Open Access Journals (Sweden)

    Rania Refaat

    2014-06-01

    Conclusion: Tc-99m MAA scan is fundamental prior to Y-90 microsphere SIRT as it minimizes the risk of post-radioembolization complications, hence, enhancing the safety of Y-90 microsphere subsequent administration. Moreover, the percentage of lung shunting varies considerably among patients with HCC relying on the grade of tumor vascularity.

  14. Ultrasound guidance for brachial plexus block decreases the incidence of complete hemi-diaphragmatic paresis or vascular punctures and improves success rate of brachial plexus nerve block compared with peripheral nerve stimulator in adults.

    Science.gov (United States)

    Yuan, Jia-Min; Yang, Xiao-Hu; Fu, Shu-Kun; Yuan, Chao-Qun; Chen, Kai; Li, Jia-Yi; Li, Quan

    2012-05-01

    The use of traditional techniques (such as landmark techniques, paresthesia and peripheral nerve stimulator) for upper-limb anesthesia has often been restricted to the expert or enthusiast, which was blind. Recently, ultrasound (US) has been applied to differ blood vessel, pleura and nerve, thus may reduce the risk of complications while have a high rate of success. The aim of this study was to determine if the use of ultrasound guidance (vs. peripheral nerve stimulator, (PNS)) decreases risk of vascular puncture, risk of hemi-diaphragmatic paresis and risk of Horner syndrome and improves the success rate of nerve block. A search strategy was developed to identify randomized control trials (RCTs) reporting on complications of US and PNS guidance for upper-extremity peripheral nerve blocks (brachial plexus) in adults available through PubMed databases, the Cochrane Central Register of Controlled Trials, Embase databases, SinoMed databases and Wanfang data (date up to 2011-12-20). Two independent reviewers appraised eligible studies and extracted data. Risk ratios (OR) were calculated for each outcome and presented with 95% confidence intervals (CI) with the software of Review Manager 5.1.0 System (Cochrane Library). Sixteen trials involving 1321 adults met our criteria were included for analysis. Blocks performed using US guidance were more likely to be successful (risk ratio (RR) for block success 0.36, 95%CI 0.23 - 0.56, P block performance (RR 0.13, 95%CI 0.06 - 0.27, P complete hemi-diaphragmatic paresis (RR 0.09, 95%CI 0.03 - 0.52, P = 0.0001). US decreases risks of complete hemi-diaphragmatic paresis or vascular puncture and improves success rate of brachial plexus nerve block compared with techniques that utilize PNS for nerve localization. Larger studies are needed to determine whether or not the use of US can decrease risk of neurologic complications.

  15. Improving Intensity-Based Lung CT Registration Accuracy Utilizing Vascular Information

    Directory of Open Access Journals (Sweden)

    Kunlin Cao

    2012-01-01

    Full Text Available Accurate pulmonary image registration is a challenging problem when the lungs have a deformation with large distance. In this work, we present a nonrigid volumetric registration algorithm to track lung motion between a pair of intrasubject CT images acquired at different inflation levels and introduce a new vesselness similarity cost that improves intensity-only registration. Volumetric CT datasets from six human subjects were used in this study. The performance of four intensity-only registration algorithms was compared with and without adding the vesselness similarity cost function. Matching accuracy was evaluated using landmarks, vessel tree, and fissure planes. The Jacobian determinant of the transformation was used to reveal the deformation pattern of local parenchymal tissue. The average matching error for intensity-only registration methods was on the order of 1 mm at landmarks and 1.5 mm on fissure planes. After adding the vesselness preserving cost function, the landmark and fissure positioning errors decreased approximately by 25% and 30%, respectively. The vesselness cost function effectively helped improve the registration accuracy in regions near thoracic cage and near the diaphragm for all the intensity-only registration algorithms tested and also helped produce more consistent and more reliable patterns of regional tissue deformation.

  16. Clinical Observation of Recombinant Human Vascular Endostatin Durative Transfusion Combined with Window Period Arterial Infusion Chemotherapy in the Treatment of 
Advanced Lung Squamous Carcinoma

    Directory of Open Access Journals (Sweden)

    Yuan LV

    2015-08-01

    Full Text Available Background and objective Lung cancer is one of the most common malignant tumors in China. The aim of this study is to observe the efficacy and safety of recombinant human vascular endostatin (endostar durative transfusion combined with window period arterial infusion chemotherapy in the treatment of advanced lung squamous carcinoma. Methods From February 2014 to January 2015, 10 cases of the cytological or histological pathology diagnosed stage IIIb - stage IV lung squamous carcinoma were treated with recombinant human vascular endostatin (30 mg/d durative transfusion combined with window period arterial infusion chemotherapy. Over the same period of 10 cases stage IIIb - stage IV lung squamous carcinoma patients for pure arterial perfusion chemotherapy were compared. Recombinant human vascular endostatin was durative transfused every 24 hours for 7 days in combination group, and in the 4th day of window period, the 10 patients were received artery infusion chemotherapy, using docetaxel combined with cisplatin. Pure treatment group received the same arterial perfusion chemotherapy regimen. 4 weeks was a cycle. 4 weeks after 2 cycles, to evaluate the short-term effects and the adverse drug reactions. Results 2 groups of patients were received 2 cycles treatments. The response rate (RR was 70.0%, and the disease control rate (DCR was 90.0% in the combination group; In the pure treatment group were 50.0%, 70.0% respectively, there were no statistically significant difference (P=0.650, 0.582. The adverse reactions of the treatment were mild, including level 1-2 of gastrointestinal reaction and blood toxicity, there were no statistically significant difference (P=0.999, P=0.628. In the combination group, 1 patient occurred level 1 of cardiac toxicity. Conclusion Recombinant human vascular endostatin durative transfusion combined with window period arterial infusion chemotherapy in the treatment of advanced lung squamous carcinoma could take a

  17. Anti-Vascular Endothelial Growth Factor Antibody Suppresses ERK and NF-κB Activation in Ischemia-Reperfusion Lung Injury.

    Directory of Open Access Journals (Sweden)

    Chou-Chin Lan

    Full Text Available Ischemia-reperfusion (IR-induced acute lung injury (ALI is implicated in several clinical conditions like lung transplantation, acute pulmonary embolism after thrombolytic therapy, re-expansion of collapsed lung from pneumothorax or pleural effusion, cardiopulmonary bypass and etc. Because mortality remains high despite advanced medical care, prevention and treatment are important clinical issues for IR-induced ALI. Vascular endothelial growth factor (VEGF has a controversial role in ALI. We therefore conducted this study to determine the effects of anti-VEGF antibody in IR-induced ALI. In the current study, the IR-induced ALI was conducted in a rat model of isolated-perfused lung in situ in the chest. The animals were divided into the control, control + preconditioning anti-VEGF antibody (bevacizumab, 5mg/kg, IR, IR + preconditioning anti-VEGF antibody (1mg/kg, IR+ preconditioning anti-VEGF antibody (5mg/kg and IR+ post-IR anti-VEGF antibody (5mg/kg group. There were eight adult male Sprague-Dawley rats in each group. The IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, neutrophilic infiltration in lung tissues, increased tumor necrosis factor-α, and total protein concentrations in bronchoalveolar lavage fluid. VEGF and extracellular signal-regulated kinase (ERK were increased in IR-induced ALI. Administration of preconditioning anti-VEGF antibody significantly suppressed the VEGF and ERK expressions and attenuated the IR-induced lung injury. This study demonstrates the important role of VEGF in early IR-induced ALI. The beneficial effects of preconditioning anti-VEGF antibody in IR-induced ALI include the attenuation of lung injury, pro-inflammatory cytokines, and neutrophilic infiltration into the lung tissues.

  18. Activation of Epac alleviates inflammation and vascular leakage in LPS-induced acute murine lung injury.

    Science.gov (United States)

    Wang, Xuefeng; Song, Shunde; Hu, Zhengqiang; Zhang, Zhewen; Li, Yajun; Yan, Chunguang; Li, Zigang; Tang, Huifang

    2017-12-01

    Exchange protein directly activated by cAMP (Epac) is an important molecule in cAMP signal transduction, but the effect of Epac on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unclear. In this study, we treated in vitro and in vivo models with the Epac activator 8CPT to determine the effect and related mechanisms of Epac. The in vitro results indicate that 8CPT inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) release from mouse macrophages (MH-S), whereas the protein kinase A (PKA) activator 6BnZ has no effect. Furthermore, Epac over-expression can significantly suppress TNF-α release from LPS induced MH-S cell, while Epac siRNA can slightly increase TNF-α release. Moreover, 8CPT reduces LPS-induced microvascular permeability in human pulmonary microvascular endothelial cells (HPMVECs), whereas the PKA activator 6BnZ has no effect. In mice with LPS-induced ALI, 8CPT significantly reduces LPS-induced inflammatory cytokine release, neutrophil recruitment, and albumin leakage. LPS simultaneously decreases the Epac but not the PKA levels. However, 8CPT reverses the decreased Epac levels. Furthermore, the mechanism involves the small GTPase Rac1/2 but not the mitogen-activated protein kinase (MAPK) pathway. Thus, Epac activation reduces inflammation and microvascular permeability in LPS-induced lung injury and an Epac activator represents a novel choice for the early therapy of ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Santos, Arnoldo; Gomez-Peñalver, Eva; Monge-Garcia, M Ignacio; Retamal, Jaime; Borges, João Batista; Tusman, Gerardo; Hedenstierna, Goran; Larsson, Anders; Suarez-Sipmann, Fernando

    2017-11-01

    To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome. Experimental study. University animal research laboratory. Twelve pigs (30.8 ± 2.5 kg). Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected. Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

  20. Niclosamide enhances the antitumor effects of radiation by inhibiting the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in human lung cancer cells.

    Science.gov (United States)

    Xiang, Mei; Chen, Zihong; Yang, Donghong; Li, Haiwen; Zuo, Yufang; Li, Jingjing; Zhang, Wendian; Zhou, Hechao; Jiang, Danxian; Xu, Zumin; Yu, Zhonghua

    2017-08-01

    Lung cancer is one of the leading causes of cancer-associated mortality, worldwide. The overall survival rate remains low, but progress has been made in improving the diagnosis and treatment of lung cancer over the past decades. Niclosamide, a salicylanilide derivative used for the treatment of tapeworm infections, is safe, well tolerated, inexpensive and readily available. Previous studies have identified niclosamide as a potential anticancer agent. The present study demonstrated that niclosamide enhanced the effect of irradiation by inhibiting the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway. These findings suggest that niclosamide may be a promising candidate for clinical evaluation as part of a combined regimen for the treatment of non-small cell lung cancer.

  1. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    . Blocking of IL-10 by Ab resulted in a 52% increase in lung vascular permeability, a 56% increase in TNF-alpha activity in bronchoalveolar lavage fluids, and a 47 to 48% increase in bronchoalveolar lavage neutrophils and lung myeloperoxidase content. These findings suggest that IL-10 is an important natural...

  2. Functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks CLEC-2/podoplanin-dependent platelet aggregation and lung metastasis.

    Science.gov (United States)

    Sasaki, T; Shirai, T; Tsukiji, N; Otake, S; Tamura, S; Ichikawa, J; Osada, M; Satoh, K; Ozaki, Y; Suzuki-Inoue, K

    2018-02-28

    Essentials We generated recombinant rhodocytin that could aggregate platelets via CLEC-2. Recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. Asp 4 in α-subunit of rhodocytin was required for binding to CLEC-2. Inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis. Background Rhodocytin, a disulfide-linked heterodimeric C-type lectin from Calloselasma rhodostoma consisting of α-subunits and β-subunits, induces platelet aggregation through C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a physiological binding partner of podoplanin (PDPN), which is expressed on some tumor cell types, and is involved in tumor cell-induced platelet aggregation and tumor metastasis. Thus, modified rhodocytin may be a possible source of anti-CLEC-2 drugs for both antiplatelet and antimetastasis therapy. However, its molecular function has not been well characterized, because of the lack of recombinant rhodocytin that induces platelet aggregation. Objective To produce recombinant rhodocytin, in order to verify its function with mutagenesis, and to develop an anti-CLEC-2 drug based on the findings. Methods We used Chinese hamster ovary cells to express recombinant rhodocytin (wild-type [WT] and mutant), which was analyzed for induction/inhibition of platelet aggregation with light transmission aggregometry, the formation of multimers with blue native PAGE, and binding to CLEC-2 with flow cytometry. Finally, we investigated whether mutant rhodocytin could suppress PDPN-induced metastasis in an experimental lung metastasis mouse model. Results Functional WT] rhodocytin (αWTβWT) was obtained by coexpression of both subunits. Asp4 in α-subunits of rhodocytin was required for CLEC-2 binding. αWTβWT formed a heterooctamer similarly to native rhodocytin. Moreover, an inhibitory mutant of rhodocytin (αWTβK53A/R56A), forming a heterotetramer, bound to CLEC-2 without inducing platelet aggregation, and blocked CLEC-2-PDPN

  3. Bioinformatics Analyses of the Role of Vascular Endothelial Growth Factor in Patients with Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available This study was aimed to identify the expression pattern of vascular endothelial growth factor (VEGF in non-small cell lung cancer (NSCLC and to explore its potential correlation with the progression of NSCLC.Gene expression profile GSE39345 was downloaded from the Gene Expression Omnibus database. Twenty healthy controls and 32 NSCLC samples before chemotherapy were analyzed to identify the differentially expressed genes (DEGs. Then pathway enrichment analysis of the DEGs was performed and protein-protein interaction networks were constructed. Particularly, VEGF genes and the VEGF signaling pathway were analyzed. The sub-network was constructed followed by functional enrichment analysis.Total 1666 up-regulated and 1542 down-regulated DEGs were identified. The down-regulated DEGs were mainly enriched in the pathways associated with cancer. VEGFA and VEGFB were found to be the initiating factor of VEGF signaling pathway. In addition, in the epidermal growth factor receptor (EGFR, VEGFA and VEGFB associated sub-network, kinase insert domain receptor (KDR, fibronectin 1 (FN1, transforming growth factor beta induced (TGFBI and proliferating cell nuclear antigen (PCNA were found to interact with at least two of the three hub genes. The DEGs in this sub-network were mainly enriched in Gene Ontology terms related to cell proliferation.EGFR, KDR, FN1, TGFBI and PCNA may interact with VEGFA to play important roles in NSCLC tumorigenesis. These genes and corresponding proteins may have the potential to be used as the targets for either diagnosis or treatment of patients with NSCLC.

  4. Interstitial lung disease associated with collagen vascular disorders: disease quantification using a computer-aided diagnosis tool

    Energy Technology Data Exchange (ETDEWEB)

    Marten, K.; Engelke, C. [University Hospital of Goettingen, Department of Radiology, Goettingen (Germany); Dicken, V. [MeVis Research GmbH, Bremen (Germany); Kneitz, C. [University Hospital of Wuerzburg, Dept. of Rheumatology and Clinical Immunology, Medizinische Klinik and Poliklinik, Wuerzburg (Germany); Hoehmann, M.; Kenn, W.; Hahn, D. [University Hospital of Wuerzburg, Department of Radiology, Wuerzburg (Germany)

    2009-02-15

    The purpose of this study was to evaluate a computer-aided diagnosis (CAD) tool compared to human observers in quantification of interstitial lung disease (ILD) in patients with collagen-vascular disorders. A total of 52 patients with rheumatoid arthritis (n=24), scleroderma (n=14) and systemic lupus erythematosus (n=14) underwent thin-section CT. Two independent observers assessed the extent of ILD (EoILD), reticulation (EoRet) and ground-glass opacity (EoGGO). CAD assessed EoILD twice. Pulmonary function tests were obtained. Statistical evaluation used 95% limits of agreement and linear regression analysis. CAD correlated well with diffusing capacity (DL{sub CO}) (R=-0.531, P<0.0001) and moderately with forced vital capacity (FVC) (R=-0.483, P=0.0008). There was close correlation between CAD and the readers (EoILD vs. CAD: R=0.716, P<0.0001; EoRet vs. CAD: R=0.69, P<0.0001). Subgroup analysis including patients with minimal EoGGO (<15%) strengthened the correlations between CAD and the readers, readers and PFT, and CAD and PFT. EoILD by readers correlated strongly with DL{sub CO} (R=-0.705, P<0.0001) and moderately with FVC (R=-0.559, P=0.0002). EoRet correlated closely with DL{sub CO} and moderately with FVC (DL{sub CO}: R=-0.663; FVC: R=-0.436; P{<=}0.005). The CAD system is a promising tool for ILD quantification, showing close correlation with human observers and physiologic impairment. (orig.)

  5. Enhanced Pulmonary Vascular and Alveolar Development via Prenatal Administration of a Slow-Release Synthetic Prostacyclin Agonist in Rat Fetal Lung Hypoplasia

    Science.gov (United States)

    Umeda, Satoshi; Miyagawa, Shigeru; Fukushima, Satsuki; Oda, Noriko; Saito, Atsuhiro; Sakai, Yoshiki; Sawa, Yoshiki; Okuyama, Hiroomi

    2016-01-01

    Lung hypoplasia and pulmonary hypertension are the major causes of mortality in neonates with congenital diaphragmatic hernia (CDH). Although the prostaglandin pathway plays a pivotal role in lung development, the reported efficacy of postnatal prostaglandin agonist treatment is suboptimal. We hypothesized that prenatal treatment with ONO-1301SR, a slow-release form of a novel synthetic prostacyclin agonist with thromboxane inhibitory activity, might enhance the development of lungs exhibiting hypoplasia in the fetal period. On embryonic day (E) 9.5, nitrofen was given to pregnant Sprague-Dawley rats to establish a CDH-related lung hypoplasia model, whereas normal rats received the vehicle only. The same day, either ONO-1301SR or a placebo was also randomly administered. On E21.5, the fetuses of the normal group and those exhibiting CDH were analyzed. Prenatal ONO-1301SR administration had no influence on the incidence of nitrofen-induced CDH. The lung-to-body weight ratio in the CDH+ONO group was greater than that in the CDH group. Histologically, the medial wall in the CDH+ONO group was two-thirds thinner than that in the CDH group. In addition, the number of Ttf-1-positive cells and the capillary density were ≥1.5 times greater in the CDH+ONO group than in the CDH group, and this increase was associated with higher expression of vascular endothelial growth factor and stromal cell-derived factor in the CDH+ONO group, suggesting enhanced development of the alveolar and capillary networks. Thus, prenatal ONO-1301SR was protective against the progression of lung hypoplasia associated with CDH in a nitrofen-induced rat model, indicating the potential of this treatment for pathologies exhibiting lung hypoplasia. PMID:27529478

  6. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats.

    Science.gov (United States)

    Machnik, Agnes; Dahlmann, Anke; Kopp, Christoph; Goss, Jennifer; Wagner, Hubertus; van Rooijen, Nico; Eckardt, Kai-Uwe; Müller, Dominik N; Park, Joon-Keun; Luft, Friedrich C; Kerjaschki, Dontscho; Titze, Jens

    2010-03-01

    We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain

  7. Rat monoclonal antibody distribution in mice: an epitope inside the lung vascular space mediates very efficient localization

    Energy Technology Data Exchange (ETDEWEB)

    Kennel, S.J. (Oak Ridge National Lab., TN (USA)); Lee, Ray (Washington Univ., St. Louis, MO (USA)); Bultman, Scott (Tennessee Univ., Oak Ridge, TN (USA). Graduate School of Biomedical Sciences); Kabalka, George (Tennessee Univ., Knoxville, TN (USA). Biomedical Imaging Center)

    1990-01-01

    MoAb to an epitope on lung endothelial cells accumulates rapidly in the lung resulting in localization ratios of over 100. MoAb to a macrophage antigen found in spleen and lung has maximum localization ratios of 24 and 5, respectively, while MoAb specific for a human tumor grown in nude mice has a maximum ratio of about 4. Epitope concentrations in target organs (300-600 ng/mg protein) are comparable in all three systems, indicating that the MoAb to endothelium is efficient in localization to the lung. (author).

  8. Cell block samples from endobronchial ultrasound transbronchial needle aspiration provide sufficient material for ancillary testing in lung cancer-a quaternary referral centre experience.

    Science.gov (United States)

    Hopkins, Emily; Moffat, David; Parkinson, Ian; Robinson, Peter; Jersmann, Hubertus; Dougherty, Brendan; Birader, Mohammed I; Francis, Kate; Nguyen, Phan

    2016-09-01

    Rapid on site examination (ROSE) is encouraged at endobronchial ultrasound transbronchial needles aspiration (EBUS-TBNA) to improve diagnostic yield. Due to new therapeutic options in lung cancer, it is not sufficient to merely distinguish between non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Immunohistochemistry (IHC) distinction is now standard practice, as well as additional molecular testing where clinically indicated. We investigated the diagnostic yield of on-site smears vs . cell block and the provision of cellular material for ancillary testing at our centre. A retrospective audit of all EBUS-TBNA procedures performed until July 2012 was undertaken. Diagnostic yield on smears versus cell block was recorded. Cell blocks were reviewed by an experienced pathologist to determine diagnostic accuracy and whether IHC and molecular testing were possible. In total, 234 procedures were recorded with 101 (43.2%) malignant cases, 107 (45.7%) benign cases and an initial 26/234 (11.1%) insufficient for diagnosis of which 11/234 (4.7%) were false negatives for malignancy after further follow up. The average number of passes was 4.5. For malignancies, smear diagnosis was possible in 95% (96/101) of cases and cell block diagnosis in 93.5% (87/93) of cases. There was sufficient material for IHC in 97.7% (85/87) of malignant cases. In 79.3% (69/87) of NSCLCs molecular testing for epidermal growth factor receptor (EGFR) mutation analysis was theoretically possible on samples obtained. Cell blocks are not inferior to smears for diagnostic accuracy and provide sufficient samples for histology. However, ROSE assists the physician on how best to manage samples for ancillary testing.

  9. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

    Directory of Open Access Journals (Sweden)

    Terrenato Irene

    2010-09-01

    Full Text Available Abstract Background Several studies demonstrated that epidermal growth factor receptor (EGFR gene copy number (GCN correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC and to anti-EGFR monoclonal antibodies (MoAbs in metastatic colorectal cancer (CRC. In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH is an alternative technique to fluorescence in situ hybridization (FISH, but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82% presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30% showed a low polysomy, 15 (45% a high polysomy and 2 (6% NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.

  10. CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks lung inflammation in swine barn dust-instilled mice.

    Science.gov (United States)

    Schneberger, D; Gordon, J R; DeVasure, J M; Boten, J A; Heires, A J; Romberger, D J; Wyatt, T A

    2015-04-01

    Inhalation of agricultural occupational dusts from swine confinement facilities can result in lung inflammation. The innate immune response to organic barn dusts results in production of a number of pro-inflammatory factors in the lungs of barn workers such as cytokines, chemokines, and an influx of neutrophils. Many of these inflammatory factors are influenced by the chemokine CXCL8/IL-8 (KC or MIP-2 in mice). Previously, we have demonstrated that an endotoxin-independent component of swine barn dust extract (SBE) elevates lung chemokines in a protein kinase C (PKC)-dependent manner resulting in the significant formation of lung inflammatory cell infiltrates in a mouse model of SBE injury. In this study we test the ability of a CXCR1/CXCR2 antagonist, CXCL8(3-74)K11R/G31P (G31P) to block many of the features of lung-inflammation in response to challenge with SBE in an established mouse exposure system. Injection of G31P concurrent with SBE nasal instillation over a course of 3 weeks significantly reduced neutrophil accumulation in the lungs of barn dust exposed animals compared to those given SBE alone. There was a similar reduction in pro-inflammatory cytokines and chemokines IL-6, KC, and MIP-2 in SBE plus G31P-treated mice. In addition to excreted products, the receptors ICAM-1, CXCR1, and CXCR2, which all were elevated with SBE exposure, were also decreased with G31P treatment. SBE activation of PKCα and PKCε was reduced as well with G31P treatment. Thus, G31P was found to be highly effective at reducing several features of lung inflammation in mice exposed to barn dust extracts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration.

    Science.gov (United States)

    Irwin, David C; Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva; Buehler, Paul W

    2015-05-01

    Haptoglobin (Hp) is an approved treatment in Japan for trauma, burns, and massive transfusion-related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia-mediated PH. Rats were simultaneously exposed to chronic Hb infusion (35 mg per day) and hypobaric hypoxia for 5 weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated nonheme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right-ventricular hypertrophy, which suggests a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia and (2) suggest a novel therapy for chronic hemolysis-associated PH. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Enhanced expression of vascular endothelial growth factor in lungs of newborn infants with congenital diaphragmatic hernia and pulmonary hypertension

    NARCIS (Netherlands)

    S.M.K. Shehata; W.J. Mooi (Wolter); T. Okazaki (Tadaharu); I. El-Banna; H.S. Sharma (Hari); D. Tibboel (Dick)

    1999-01-01

    textabstractBACKGROUND: Pulmonary hypoplasia accompanied by pulmonary hypertension resistant to treatment is an important feature of congenital diaphragmatic hernia (CDH). The pathogenesis of the pulmonary vascular abnormalities in CDH remains to be elucidated at the

  13. Lung tumorigenesis induced by human vascular endothelial growth factor (hVEGF)-A165 overexpression in transgenic mice and amelioration of tumor formation by miR-16.

    Science.gov (United States)

    Tung, Yu-Tang; Huang, Pin-Wu; Chou, Yu-Ching; Lai, Cheng-Wei; Wang, Hsiu-Po; Ho, Heng-Chien; Yen, Chih-Ching; Tu, Chih-Yen; Tsai, Tung-Chou; Yeh, Dah-Cherng; Wang, Jiun-Long; Chong, Kowit-Yu; Chen, Chuan-Mu

    2015-04-30

    Many studies have shown that vascular endothelial growth factor (VEGF), especially the human VEGF-A165 (hVEGF-A165) isoform, is a key proangiogenic factor that is overexpressed in lung cancer. We generated transgenic mice that overexpresses hVEGF-A165 in lung-specific Clara cells to investigate the development of pulmonary adenocarcinoma. In this study, three transgenic mouse strains were produced by pronuclear microinjection, and Southern blot analysis indicated similar patterns of the foreign gene within the genomes of the transgenic founder mice and their offspring. Accordingly, hVegf-A165 mRNA was expressed specifically in the lung tissue of the transgenic mice. Histopathological examination of the lung tissues of the transgenic mice showed that hVEGF-A165 overexpression induced bronchial inflammation, fibrosis, cysts, and adenoma. Pathological section and magnetic resonance imaging (MRI) analyses demonstrated a positive correlation between the development of pulmonary cancer and hVEGF expression levels, which were determined by immunohistochemistry, qRT-PCR, and western blot analyses. Gene expression profiling by cDNA microarray revealed a set of up-regulated genes (hvegf-A165, cyclin b1, cdc2, egfr, mmp9, nrp-1, and kdr) in VEGF tumors compared with wild-type lung tissues. In addition, overexpressing hVEGF-A165 in Clara cells increases CD105, fibrogenic genes (collagen α1, α-SMA, TGF-β1, and TIMP1), and inflammatory cytokines (IL-1, IL-6, and TNF-α) in the lungs of hVEGF-A165-overexpressing transgenic mice as compared to wild-type mice. We further demonstrated that the intranasal administration of microRNA-16 (miR-16) inhibited lung tumor growth by suppressing VEGF expression via the intrinsic and extrinsic apoptotic pathways. In conclusion, hVEGF-A165 transgenic mice exhibited complex alterations in gene expression and tumorigenesis and may be a relevant model for studying VEGF-targeted therapies in lung adenocarcinoma.

  14. Effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD.

    Science.gov (United States)

    Key, Angela; Parry, Matthew; West, Malcolm A; Asher, Rebecca; Jack, Sandy; Duffy, Nick; Torella, Francesco; Walker, Paul P

    2017-01-01

    β Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic worsening of breathlessness. Despite growing evidence of safety and efficacy, they remain underused. We examined the effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in a group of vascular surgical patients, a high proportion of who were expected to have COPD. People undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially recruited from vascular surgery clinic. They completed plethysmographically measured lung function and incremental cardiopulmonary exercise testing with dynamic measurement of inspiratory capacity while taking and not taking β blocker. 48 participants completed tests while taking and not taking β blockers with 38 completing all assessments successfully. 15 participants (39%) were found to have, predominantly mild and undiagnosed, COPD. People with COPD had airflow obstruction, increased airway resistance (Raw) and specific conductance (sGaw), static hyperinflation and dynamically hyperinflated during exercise. In the whole group, β-blockade led to a small fall in FEV1 (0.1 L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation. No difference in response to β-blockade was seen in those with and without COPD. In people with AAA, β-blockade has little effect on lung function and dynamic hyperinflation in those with and without COPD. In this population, the prevalence of COPD is high and consideration should be given to case finding with spirometry. NCT02106286.

  15. 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.

    Science.gov (United States)

    Kushimoto, Shigeki; Taira, Yasuhiko; Kitazawa, Yasuhide; Okuchi, Kazuo; Sakamoto, Teruo; Ishikura, Hiroyasu; Endo, Tomoyuki; Yamanouchi, Satoshi; Tagami, Takashi; Yamaguchi, Junko; Yoshikawa, Kazuhide; Sugita, Manabu; Kase, Yoichi; Kanemura, Takashi; Takahashi, Hiroyuki; Kuroki, Yuichi; Izumino, Hiroo; Rinka, Hiroshi; Seo, Ryutarou; Takatori, Makoto; Kaneko, Tadashi; Nakamura, Toshiaki; Irahara, Takayuki; Saito, Nobuyuki; Watanabe, Akihiro

    2012-12-11

    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. 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. 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 edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P pulmonary vascular permeability (r = 0.729, P 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

  16. Blocking the Wnt/β-Catenin Pathway by Lentivirus-Mediated Short Hairpin RNA Targeting β-Catenin Gene Suppresses Silica-Induced Lung Fibrosis in Mice

    Science.gov (United States)

    Wang, Xin; Dai, Wujing; Wang, Yanrang; Gu, Qing; Yang, Deyi; Zhang, Ming

    2015-01-01

    Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/β-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/β-catenin pathway in silicosis, we blocked Wnt/β-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epithelial cell line) and in a mouse silicosis model by using a lentiviral vector expressing a short hairpin RNA silencing β-catenin (Lv-shβ-catenin). In vitro, Lv-shβ-catenin significantly decreased the expression of β-catenin, MMP2 and MMP9, and secretion of TGF-β1. In vivo, intratracheal treatment with Lv-shβ-catenin significantly reduced expression of β-catenin in the lung and levels of TGF-β1 in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content and collagen I\\III synthesis in silica-administered mice. These results indicate that blockade of the Wnt/β-catenin pathway can prevent the development of silica-induced lung fibrosis. Thus Wnt/β-catenin pathway may be a target in prevention and treatment of silicosis. PMID:26340635

  17. Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro

    DEFF Research Database (Denmark)

    Pedersen, M W; Holm, S; Lund, E L

    2001-01-01

    We examined the relationship between (18)F- labeled 2-fluro-2-deoxy-d-glucose (FDG) uptake, and expression of glucose transporters (GLUTs) in two human small-cell lung cancer (SCLC) lines CPH 54A and CPH 54B. Changes in the expression of GLUTs and vascular endothelial growth factor (VEGF) during 12......-, 18-, and 24 hours of severe hypoxia in vivo (xenografts) and in vitro (cell cultures) were recorded for both tumor lines. The two SCLC lines are subpopulations of the same patient tumor. In spite of their common genomic origin they represent consistently different metabolic and microenvironmental...... phenotypes as well as treatment sensitivities. There were higher levels of Glut-1 protein in 54B and a correspondingly higher FDG uptake in this tumor line (P

  18. Molecular testing guidelines for lung adenocarcinoma: Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples

    Science.gov (United States)

    Heymann, Jonas J.; Bulman, William A.; Maxfield, Roger A.; Powell, Charles A.; Halmos, Balazs; Sonett, Joshua; Beaubier, Nike T.; Crapanzano, John P.; Mansukhani, Mahesh M.; Saqi, Anjali

    2014-01-01

    Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs) are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA) CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) virus homolog testing between FNA CBs and histology samples from the same patients. Materials and Methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22) and KRAS (17/17) mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology. PMID:24987443

  19. Measurement of the vascular pedicle width predicts fluid repletion: a cross-sectional comparison with inferior vena cava ultrasound and lung comets.

    Science.gov (United States)

    Salahuddin, Nawal; Hussain, Iqbal; Alsaidi, Hakam; Shaikh, Quratulain; Joseph, Mini; Hawa, Hassan; Maghrabi, Khalid

    2015-01-01

    Determination of a patient's volume status remains challenging. Ultrasound assessments of the inferior vena cava and lung parenchyma have been shown to reflect fluid status when compared to the more traditional static and dynamic methods. Yet, resource-limited intensive care units (ICUs) may still not have access to bedside ultrasound. The vascular pedicle width (VPW) measured on chest radiographs remains underutilized for fluid assessment. In this study, we aimed to determine the correlation between ultrasound assessment and vascular pedicle width and to identify a discriminant value that predicted a fluid replete state. Eighty-four data points of simultaneous VPW and inferior vena cava measurements were collected on mechanically ventilated patients. VPW measurements were compared with lung comet scores, fluid balance, and a composite variable of inferior vena cava diameter greater than or equal to 2 cm and variability less than 15 %. A VPW of 64 mm accurately predicted fluid repletion with a positive predictive value equal to 88.5 % and an area under the curve (AUC) of 0.843, 95 % CI 0.75-0.93, p comet score, Pearson's r = 0.12, p = 0.26, fluid balance, Pearson's r = 0.3, p = 0.058, and beta natriuretic peptide, Pearson's r = 0.12, p = 0.26. This study shows a high predictive ability of the VPW for fluid repletion, as compared to an accepted method of volume assessment. Given the relationship of fluid overload and mortality, these results may assist fluid resuscitation in resource-limited intensive care units.

  20. Prostacyclin Inhibits Non-Small Cell Lung Cancer Growth by a Frizzled 9-Dependent Pathway That Is Blocked by Secreted Frizzled-Related Protein 1

    Directory of Open Access Journals (Sweden)

    Meredith A. Tennis

    2010-03-01

    Full Text Available The goal of this study was to assess the ability of iloprost, an orally active prostacyclin analog, to inhibit transformed growth of human non-small cell lung cancer (NSCLC and to define the mechanism of iloprost's tumor suppressive effects. In a panel of NSCLC cell lines, the ability of iloprost to inhibit transformed cell growth was not correlated with the expression of the cell surface receptor for prostacyclin, but instead was correlated with the presence of Frizzled 9 (Fzd 9 and the activation of peroxisome proliferator-activated receptor-γ (PPARγ. Silencing of Fzd 9 blocked PPARγ activation by iloprost, and expression of Fzd 9 in cells lacking the protein resulted in iloprost's activation of PPARγ and inhibition of transformed growth. Interestingly, soluble Frizzled-related protein-1, a well-known inhibitor of Wnt/Fzd signaling, also blocked the effects of iloprost and Fzd 9. Moreover, mice treated with iloprost had reduced lung tumors and increased Fzd 9 expression. These studies define a novel paradigm, linking the eicosanoid pathway and Wnt signaling. In addition, these data also suggest that prostacyclin analogs may represent a new class of therapeutic agents in the treatment of NSCLC where the restoration of noncanonical Wnt signaling maybe important for the inhibition of transformed cell growth.

  1. 3′-epi-12β-hydroxyfroside, a new cardenolide, induces cytoprotective autophagy via blocking the Hsp90/Akt/mTOR axis in lung cancer cells

    Science.gov (United States)

    Sun, Yan; Huang, Yong-Hao; Huang, Feng-Ying; Mei, Wen-Li; Liu, Quan; Wang, Cai-Chun; Lin, Ying-Ying; Huang, Canhua; Li, Yue-Nan; Dai, Hao-Fu; Tan, Guang-Hong

    2018-01-01

    Rationale: Cardenolides have potential as anticancer drugs. 3′-epi-12β-hydroxyfroside (HyFS) is a new cardenolide structure isolated by our research group, but its molecular mechanisms remain poorly understood. This study investigates the relationship between its antitumor activities and autophagy in lung cancer cells. Methods: Cell growth and proliferation were detected by MTT, lactate dehydrogenase (LDH) release, 5-ethynyl-20-deoxyuridine (EDU) and colony formation assays. Cell apoptosis was detected by flow cytometry. Autophagic and signal proteins were detected by Western blotting. Markers of autophagy and autophagy flux were also detected by immunofluorescence, transmission electron microscopy and acridine orange staining. Real time RT-PCR was used to analyze the gene expression of Hsp90. Hsp90 ubiquitination was detected by coimmunoprecipitation. The antitumore activities of HyFS were observed in nude mice. Results: HyFS treatment inhibited cell proliferation and induced autophagy in A549 and H460 lung cancer cells, but stronger inhibition of cell proliferation and induction of cell apoptosis were shown when HyFS-mediated autophagy was blocked. The Hsp90/Akt/mTOR axis was found to be involved in the activation of HyFS-mediated autophagy. Evidence of direct interaction between Hsp90 and Akt was observed. HyFS treatment resulted in decreased levels of heat shock protein 90 (Hsp90) and phosphorylated Akt, overexpression of Hsp90 increased activation of autophagy, and inhibition of Hsp90 expression decreased autophagy. In addition, ubiquitin-mediated degradation of Hsp90 and subsequent dephosphorylation of its client protein Akt were also found in HyFS-treated lung cancer cells. Moreover, combination treatment with HyFS and chloroquine showed remarkably increased tumor inhibition in both A549- and H460-bearing mice. Conclusion: Our results demonstrate that HyFS induced cytoprotective autophagy through ubiquitin-mediated degradation of Hsp90, which further

  2. The vascular surgeon-scientist: a 15-year report of the Society for Vascular Surgery Foundation/National Heart, Lung, and Blood Institute-mentored Career Development Award Program.

    Science.gov (United States)

    Kibbe, Melina R; Dardik, Alan; Velazquez, Omaida C; Conte, Michael S

    2015-04-01

    The Society for Vascular Surgery (SVS) Foundation partnered with the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) in 1999 to initiate a competitive career development program that provides a financial supplement to surgeon-scientists receiving NIH K08 or K23 career development awards. Because the program has been in existence for 15 years, a review of the program's success has been performed. Between 1999 and 2013, 41 faculty members applied to the SVS Foundation program, and 29 from 21 different institutions were selected as awardees, resulting in a 71% success rate. Three women (10%) were among the 29 awardees. Nine awardees (31%) were supported by prior NIH F32 or T32 training grants. Awardees received their K award at an average of 3.5 years from the start of their faculty position, at the average age of 39.8 years. Thirteen awardees (45%) have subsequently received NIH R01 awards and five (17%) have received Veterans Affairs Merit Awards. Awardees received their first R01 at an average of 5.8 years after the start of their K award at the average age of 45.2 years. The SVS Foundation committed $9,350,000 to the Career Development Award Program. Awardees subsequently secured $45,108,174 in NIH and Veterans Affairs funds, resulting in a 4.8-fold financial return on investment for the SVS Foundation program. Overall, 23 awardees (79%) were promoted from assistant to associate professor in an average of 5.9 years, and 10 (34%) were promoted from associate professor to professor in an average of 5.2 years. Six awardees (21%) hold endowed professorships and four (14%) have secured tenure. Many of the awardees hold positions of leadership, including 12 (41%) as division chief and two (7%) as vice chair within a department of surgery. Eight (28%) awardees have served as president of a regional or national society. Lastly, 47 postdoctoral trainees have been mentored by recipients of the SVS Foundation Career Development

  3. Heat Shock Protein A12B Protects Vascular Endothelial Cells Against Sepsis-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yi Chen

    2017-05-01

    Full Text Available Background: Pulmonary endothelial injury is a critical process in the pathogenesis of acute lung injury (ALI during sepsis. Heat shock protein A12B (HSPA12B is mainly expressed in endothelial cells and protects against several harmful factors. However, the effects of HSPA12B in sepsis-induced ALI and its potential mechanisms of action remain unclear. Methods: For in vivo experiments, C57BL/6 mice were randomly divided into four groups (n=15: a sham operation group, a cecal ligation and puncture (CLP group, a HSPA12B siRNA-CLP group and a negative control (NC siRNA-CLP group. The mice were treated by nasal inhalation of 2-OMe-modified HSPA12B siRNA or NC siRNA. Sepsis was induced by CLP. Samples were harvested 24 and 48 hours post-CLP surgery. Pathological changes and scoring of lung tissue samples were monitored using hematoxylin and eosin staining. Levels of pro-inflammatory cytokines (e.g., interleukin (IL-1β, tumor necrosis factor (TNF-α, and IL-6 and myeloperoxidase activity in bronchoalveolar lavage fluid were analyzed by ELISA. Pulmonary edema was assessed using a wet-to-dry weight ratio. Neutrophils and alveolar macrophages were counted using flow cytometry. Pulmonary endothelial cell apoptosis was detected by TUNEL staining. Expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blot analysis. In addition, 7-day survival was recorded. For in vitro experiments, human umbilical vein endothelial cells were pre-transfected with HSPA12B siRNA or pIRES2-EGFP-HSPA12B-Flag plasmid and treated with lipopolysaccharide; subsequently, the expression levels of MAPK family signaling molecules and caspase-3 were measured by Western blotting. Results: Nasal inhalation of nano-polymer-encapsulated HSPA12B siRNA specifically downregulated mRNA and protein expression levels of HSPA12B in lung tissues. The administration of HSPA12B siRNA aggravated lung pathological injury, upregulated pro-inflammatory cytokine (e

  4. Radiosensitivity and gene expression of human lung cancer cells dividing in nude tumor before (anoxic) and after vascular induction

    International Nuclear Information System (INIS)

    Miyamoto, Tadaaki; Baba, Masayuki; Sugawara, Toshiyuki; Yashiro, Tomoyasu; Saegusa, Kumiko; Furuno, Aki; Michikawa, Yuichi; Imai, Takashi

    2005-01-01

    Using cultured and nude mouse tumor cell (IA) derived frome a human lung cancer, we studied their radiosensitivity by focusing attention on the dynamics of tumor clonogens. The movement of clonogens in the regrowing IA tumor after X rays irradiation can be divided into three phases: first,: the early and rapid survival recovery (PLD repair) phase, second, the delay phase involving a certain lag in survival change, and third, the repopulation phase consisting of two stagea. Now we compare with the dynamics of tumor clonogens before or after exposure to X rays and carbon-ion beams. PLD repair was not observed in a carbon-ion beam. In relation to radiosensitivity and repair mechanism, we studied the gene expression of the cultured cell and nude tumor with a microarray method using 22K custom oligoallele. (author)

  5. Utility of bronchial lavage fluids for epithelial growth factor receptor mutation assay in lung cancer patients: Comparison between cell pellets, cell blocks and matching tissue specimens.

    Science.gov (United States)

    Asaka, Shiho; Yoshizawa, Akihiko; Nakata, Rie; Negishi, Tatsuya; Yamamoto, Hiroshi; Shiina, Takayuki; Shigeto, Shohei; Matsuda, Kazuyuki; Kobayashi, Yukihiro; Honda, Takayuki

    2018-02-01

    The detection of epidermal growth factor receptor ( EGFR ) mutations is necessary for the selection of suitable patients with non-small cell lung cancer (NSCLC) for treatment with EGFR tyrosine kinase inhibitors. Cytology specimens are known to be suitable for EGFR mutation detection, although tissue specimens should be prioritized; however, there are limited studies that examine the utility of bronchial lavage fluid (BLF) in mutation detection. The purpose of the present study was to investigate the utility of BLF specimens for the detection of EGFR mutations using a conventional quantitative EGFR polymerase chain reaction (PCR) assay. Initially, quantification cycle (Cq) values of cell pellets, cell-free supernatants and cell blocks obtained from three series of 1% EGFR mutation-positive lung cancer cell line samples were compared for mutation detection. In addition, PCR analysis of BLF specimens obtained from 77 consecutive NSCLC patients, detecting EGFR mutations was validated, and these results were compared with those for the corresponding formalin-fixed paraffin-embedded (FFPE) tissue specimens obtained by surgical resection or biopsy of 49 of these patients. The Cq values for mutation detection were significantly lower in the cell pellet group (average, 29.58) compared with the other groups, followed by those in cell-free supernatants (average, 34.15) and in cell blocks (average, 37.12) for all three series (Pmatching FFPE tissue specimens. Notably, EGFR mutations were even detected in 10 cytological specimens that contained insufficient tumor cells. EGFR mutation testing with BLF specimens is therefore a useful and reliable method, particularly when sufficient cancer cells are not obtained.

  6. Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case-control study.

    Science.gov (United States)

    Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

    2014-09-29

    We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Urban tertiary care centre and occupational healthcare centre. Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1)≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/AWTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of vascular disease found in serum drawn within 6 months of WTC exposure. Increased PA/A is a potentially useful non-invasive biomarker of WTC-LI and warrants further study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

  7. Enlarged pulmonary artery is predicted by vascular injury biomarkers and is associated with WTC-Lung Injury in exposed fire fighters: a case–control study

    Science.gov (United States)

    Schenck, Edward J; Echevarria, Ghislaine C; Girvin, Francis G; Kwon, Sophia; Comfort, Ashley L; Rom, William N; Prezant, David J; Weiden, Michael D; Nolan, Anna

    2014-01-01

    Objectives We hypothesise that there is an association between an elevated pulmonary artery/aorta (PA/A) and World Trade Center-Lung Injury (WTC-LI). We assessed if serum vascular disease biomarkers were predictive of an elevated PA/A. Design Retrospective case-cohort analysis of thoracic CT scans of WTC-exposed firefighters who were symptomatic between 9/12/2001 and 3/10/2008. Quantification of vascular-associated biomarkers from serum collected within 200 days of exposure. Setting Urban tertiary care centre and occupational healthcare centre. Participants Male never-smoking firefighters with accurate pre-9/11 forced expiratory volume in 1 s (FEV1) ≥75%, serum sampled ≤200 days of exposure was the baseline cohort (n=801). A subcohort (n=97) with available CT scans and serum biomarkers was identified. WTC-LI was defined as FEV1≤77% at the subspecialty pulmonary evaluation (n=34) and compared with controls (n=63) to determine the associated PA/A ratio. The subcohort was restratified based on PA/A≥0.92 (n=38) and PA/AWTC dust that was associated with WTC-LI. The secondary outcome was to identify serum biomarkers predictive of the PA/A ratio using logistic regression. Results PA/A≥0.92 was associated with WTC-LI, OR of 4.02 (95% CI 1.21 to 13.41; p=0.023) when adjusted for exposure, body mass index and age at CT. Elevated macrophage derived chemokine and soluble endothelial selectin were predictive of PA/A≥0.92, (OR, 95% CI 2.08, 1.05 to 4.11, p=0.036; 1.33, 1.06 to 1.68, p=0.016, respectively), while the increased total plasminogen activator inhibitor 1 was predictive of not having PA/A≥0.92 (OR 0.88, 0.79 to 0.98; p=0.024). Conclusions Elevated PA/A was associated with WTC-LI. Development of an elevated PA/A was predicted by biomarkers of vascular disease found in serum drawn within 6 months of WTC exposure. Increased PA/A is a potentially useful non-invasive biomarker of WTC-LI and warrants further study. PMID:25270856

  8. Paravertebral Block Does Not Reduce Cancer Recurrence, but Is Related to Higher Overall Survival in Lung Cancer Surgery: A Retrospective Cohort Study.

    Science.gov (United States)

    Lee, Eun Kyung; Ahn, Hyun Joo; Zo, Jae Ill; Kim, Kyunga; Jung, Dae Myung; Park, Joo Hyun

    2017-10-01

    Postoperative analgesic methods are suggested to have an impact on long-term prognosis after cancer surgery through opioid-induced immune suppression. We hypothesized that regional analgesia that reduces the systemic opioid requirement would be related to lower cancer recurrence and higher overall survival compared to intravenous patient-controlled analgesia (PCA) for lung cancer surgery. Records for all patients who underwent open thoracotomy for curative resection of primary lung cancer between 2009 and 2013 in a tertiary care hospital were retrospectively analyzed. Patients were divided by postoperative analgesic methods: PCA (n = 574), thoracic epidural analgesia (TEA, n = 619), or paravertebral block (PVB, n = 536). Overall and recurrence-free survivals were compared among 3 analgesic methods via a multivariable Cox proportional hazard model and a log-rank test after adjusting confounding factors using propensity score matching (PSM). Analgesic method was associated with overall survival (P= .0015; hazard ratio against TEA [95% confidence intervals]: 0.58 [0.39-0.87] for PCA, 0.60 [0.45-0.79] for PVB). After confounder adjustment using PSM, PVB showed higher overall survival than PCA (log-rank P= .0229) and TEA (log-rank P= .0063) while PCA and TEA showed no difference (log-rank P= .6). Hazard ratio for PVB was 0.66 [0.46-0.94] against PCA and 0.65 [0.48-0.89] against TEA after PSM. However, there was no significant association between the analgesic methods and recurrence-free survival (P= .5; log-rank P with PSM = .5 between PCA and TEA, .5 between PCA and PVB, .1 between TEA and PVB). Pain-control methods are not related to cancer recurrence. However, PVB may have a beneficial effect on overall survival of patients with lung cancer.

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

    Science.gov (United States)

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

    2015-06-01

    To appraise the significance of extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), and intrathoracic blood volume index (ITBVI) in the differential diagnosis of the type of burn-induced pulmonary edema. The clinical data of 38 patients, with severe burn hospitalized in our burn ICU from December 2011 to September 2014 suffering from the complication of pulmonary edema within one week post burn and treated with mechanical ventilation accompanied by pulse contour cardiac output monitoring, were retrospectively analyzed. The patients were divided into lung injury group ( L, n = 17) and hydrostatic group (H, n = 21) according to the diagnosis of pulmonary edema. EVLWI, PVPI, ITBVI, oxygenation index, and lung injury score ( LIS) were compared between two groups, and the correlations among the former four indexes and the correlations between each of the former three indexes and types of pulmonary edema were analyzed. Data were processed with t test, chi-square test, Mann-Whitney U test, Pearson correlation test, and accuracy test [receiver operating characteristic (ROC) curve]. There was no statistically significant difference in EVLWI between group L and group H, respectively (12.9 ± 3.1) and (12.1 ± 2.1) mL/kg, U = 159.5, P > 0.05. The PVPI and LIS of patients in group L were respectively 2.6 ± 0.5 and (2.1 ± 0.6) points, and they were significantly higher than those in group H [1.4 ± 0.3 and (1.0 ± 0.6) points, with U values respectively 4.5 and 36.5, P values below 0.01]. The ITBVI and oxygenation index of patients in group L were respectively (911 197) mL/m2 and (136 ± 69) mmHg (1 mmHg = 0.133 kPa), which were significantly lower than those in group H [(1,305 ± 168) mL/m2 and (212 ± 60) mmHg, with U values respectively 21.5 and 70.5, P values below 0.01]. In group L, there was obviously positive correlation between EVLWI and PVPI, or EVLWI and ITBVI (with r values respectively 0.553 and 0.807, P pulmonary edema was 0

  10. Nuclear factor κB inhibition reduces lung vascular lumen obliteration in severe pulmonary hypertension in rats.

    Science.gov (United States)

    Farkas, Daniela; Alhussaini, Aysar A; Kraskauskas, Donatas; Kraskauskiene, Vita; Cool, Carlyne D; Nicolls, Mark R; Natarajan, Ramesh; Farkas, Laszlo

    2014-09-01

    NF-κB and IL-6, a NF-κB downstream mediator, play a central role in the inflammatory response of tissues. We aimed to determine the role of the classical NF-κB pathway in severe pulmonary arterial hypertension (PAH) induced by SU5416 and chronic hypoxia (SuHx) in rats. Tissue samples from patients with idiopathic PAH (iPAH) and control subjects were investigated. SuHx rats were treated from Days 1 to 3, 1 to 21, and 29 to 42 with the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and/or from Days 1 to 21 with anti-IL-6 antibody. Nuclear staining for NF-κB, an indicator of the activation of the classical NF-κB pathway, was detected in pulmonary arterial lesions of patients with iPAH and SuHx rats. NF-κB inhibition with PDTC prevented and reduced pulmonary arterial obliteration without reducing muscularization. However, the elevated lung levels of IL-6 were not reduced in PDTC-treated SuHx animals. PDTC treatment prevented or reduced apoptosis of pulmonary artery wall cells and pulmonary arterial obliteration. IL-6 inhibition had only a partial effect on apoptosis and obliteration. Pulmonary arterial media wall thickness was not affected by any of these treatments. Preventive and therapeutic PDTC treatment promoted immune regulation by increasing the number of perivascular CD4(+) T cells, in particular regulatory T cells (early treatment), and by reducing the number of perivascular CD8(+) T lymphocytes and CD45RA(+) B lymphocytes. Therapeutic PDTC treatment further preserved right ventricular function in SuHx animals. Inhibition of NF-κB may represent a therapeutic option for pulmonary arterial obliteration via reduced vessel wall cell apoptosis and improved regulation of the immune system.

  11. Podophyllotoxin acetate blocks IR-induced invasion of non-small cell lung cancer cell, A549

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jeong Hyun; Choi, Jae Yeon; Hwang, Sang-Gu; Um, Hong-Duck; Park, Jong Kuk [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2015-05-15

    Some research result presented that local radiotherapy administered to primary tumors speeds their metastatic growth in vivo (4-6), thereby suggesting that besides its therapeutic effects, IR promotes the malignant behaviors of surviving cancer cells. Our findings demonstrate podophyllotoxin acetate (PA), one of new natural products, prevented side effects of IR such as invasion or metastasis promotion for improve the efficacy of radiotherapy. In this study, we demonstrated that PA inhibits IR-induced invasion and migration of A549 cells. We also observed that IR stimulates several intracellular pathway involving EMT and MAPKinses; EMT-associated events including an increase of vimentin levels and increased phosphorylation of p38 ERK, JNK in A549 cells. PA could decrease these activations of several intracellular signaling molecules. Therefore, PA might inhibit IRinduced invasion and migration via blocking EMT and MAPKiase pathway of A549 cells.

  12. Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zang JL

    2017-01-01

    Full Text Available Jialan Zang,1–3,* Yong Hu,1,2,* Xiaoyue Xu,1,2 Jie Ni,1,2 Dali Yan,1,2 Siwen Liu,4 Jieyu He,5 Jing Xue,4 Jianzhong Wu,4 Jifeng Feng2 1The Fourth Clinical School of Nanjing Medical University, 2Department of Chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 3Department of Oncology, The First Hospital of Harbin City, Harbin, 4Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, 5Department of Public Health, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Aim: This study was designed to investigate the predictive and prognostic values of serum vascular endothelial growth factor (VEGF level in non-small cell lung cancer (NSCLC patients treated with platinum-based chemotherapy. Methods: Patients’ peripheral blood samples were collected prior to chemotherapy and after 1 week of the third cycle of combination chemotherapy. Serum VEGF levels were evaluated through Luminex multiplex technique. Between September 2011 and August 2015, a total of 135 consecutive advanced or recurrent histologically verified NSCLC patients were enrolled in the study. Moreover, all the patients received platinum-based combination chemotherapy as a first-line treatment. Results: No significant associations were found between pretreatment serum VEGF levels and clinical characteristics, such as sex (P=0.0975, age (P=0.2522, stage (P=0.1407, lymph node metastasis (P=0.6409, tumor location (P=0.3520, differentiated degree (P=0.5608, pathological (histological type (P=0.4885, and response to treatment (P=0.9859. The VEGF load per platelet (VEGFPLT levels were not correlated with sex, age, primary tumor site, and pathological type in NSCLC patients (all P>0.05. The median survival time of progression-free survival (PFS was 6.407 and 5.29 months in the low and high groups, respectively, when using 280 pg/mL VEGF level as the cutoff point (P=0.024. Conclusion

  13. Blocking NF-κB sensitizes non-small cell lung cancer cells to histone deacetylase inhibitor induced extrinsic apoptosis through generation of reactive oxygen species.

    Science.gov (United States)

    Karthik, Selvaraju; Sankar, Renu; Varunkumar, Krishnamoorthy; Anusha, Chidambaram; Ravikumar, Vilwanathan

    2015-02-01

    NF-κB signalling is one of the main cell survival pathways that attenuate the anticancer efficacy of therapeutic drugs. Previous studies demonstrated that the histone deacetylase (HDAC) inhibitor induces apoptosis in some malignancies through multiple mechanisms including up-regulation of death receptors, disruption of Hsp90 function and generation of reactive oxygen species (ROS). However, HDAC inhibitor also induces a cell survival signal through NF-κB activation. In this report, we found that romidepsin, a class I HDAC inhibitor, induces NF-κB activation in A549 non-small-cell lung cancer (NSCLC) cells. We also found that inhibition of A549 cells with bortezomib (proteasome inhibitor) has blocked IκB degradation that leads to the loss of NF-κB activation and translocation which enhanced the romidepsin induced mitochondrial injury and sensitizes NSCLC cells to apoptosis. Romidepsin significantly enhances NF-κB reporter gene transcription and these effects were inhibited by bortezomib as determined by reporter gene assay. Consistently, the combined exposure of romidepsin and bortezomib reversed the effects on IκB degradation as evident with IL-8, p50 and p65 (NF-κB) expression. Apoptosis was markedly sensitized with greater ROS generation and more cell death in A549 cell lines. These events are most closely related in that bortezomib prevents the romidepsin mediated RelA acetylation and NF-κB activation, resulting in caspase activation. A strategy of blocking NF-κB activation to enhance HDAC inhibitor activity warrants further attention in NSCLC cells. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    Science.gov (United States)

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-08-01

    Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese

  15. Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between classical thiol-protectant, N-acetyl-l-cysteine, and novel thiol antioxidant, N,N′-bis-2-mercaptoethyl isophthalamide

    Science.gov (United States)

    Patel, Rishi B.; Kotha, Sainath R.; Sauers, Lynn A.; Malireddy, Smitha; Gurney, Travis O.; Gupta, Niladri N.; Elton, Terry S.; Magalang, Ulysses J.; Marsh, Clay B.; Haley, Boyd E.; Parinandi, Narasimham L.

    2012-01-01

    Lung vascular alterations and pulmonary hypertension associated with oxidative stress have been reported to be involved in idiopathic lung fibrosis (ILF). Therefore, here, we hypothesize that the widely used lung fibrosis inducer, bleomycin, would cause cytoskeletal rearrangement through thiol-redox alterations in the cultured lung vascular endothelial cell (EC) monolayers. We exposed the monolayers of primary bovine pulmonary artery ECs to bleomycin (10 µg) and studied the cytotoxicity, cytoskeletal rearrangements, and the macromolecule (fluorescein isothiocyanate-dextran, 70,000 mol. wt.) paracellular transport in the absence and presence of two thiol-redox protectants, the classic water-soluble N-acetyl-l-cysteine (NAC) and the novel hydrophobic N,N′-bis-2-mercaptoethyl isophthalamide (NBMI). Our results revealed that bleomycin induced cytotoxicity (lactate dehydrogenase leak), morphological alterations (rounding of cells and filipodia formation), and cytoskeletal rearrangement (actin stress fiber formation and alterations of tight junction proteins, ZO-1 and occludin) in a dose-dependent fashion. Furthermore, our study demonstrated the formation of reactive oxygen species, loss of thiols (glutathione, GSH), EC barrier dysfunction (decrease of transendothelial electrical resistance), and enhanced paracellular transport (leak) of macromolecules. The observed bleomycin-induced EC alterations were attenuated by both NAC and NBMI, revealing that the novel hydrophobic thiol-protectant, NBMI, was more effective at µM concentrations as compared to the water-soluble NAC that was effective at mM concentrations in offering protection against the bleomycin-induced EC alterations. Overall, the results of the current study suggested the central role of thiol-redox in vascular EC dysfunction associated with ILF. PMID:22409285

  16. Structural failures of the blood–gas barrier and the epithelial–epithelial cell connections in the different vascular regions of the lung of the domestic fowl, Gallus gallus variant domesticus, at rest and during exercise

    Science.gov (United States)

    Maina, John N.; Jimoh, Sikiru A.

    2013-01-01

    Summary Structural failure of blood–gas barrier (BGB) and epithelial–epithelial cell connections (EECCs) in different vascular regions of the exchange tissue of the lung was studied in rested and exercised chickens. The number of red blood cells (nRBCs) was counted and protein concentration (PC) measured after lavaging the respiratory system, and blood was sampled to determine the blood lactate levels (BLLs). The numbers of complete BGB breaks (nBGBBs) and those of the EECCs (nEECCBs) were counted in the different vascular territories of the lung. The nRBCs and the PCs increased with increasing exercise intensities but the rate of increase decreased at higher workloads. From rest to the fastest experimental treadmill speed of 2.95 m.sec−1, BLLs increased 4-fold. In all cases, the nEECCBs exceeded those of the BGB, showing that structurally the BGB is relatively weaker than the EECC. The increase in the number of breaks with increasing exercise can be attributed to increase in the pulmonary capillary blood pressure (PCBP) from faster heart rates and higher cardiac outputs, while the leveling out of the measurements made at higher workloads may have arisen from hemodynamic changes that initially ensued from exudation of blood plasma and then flow of blood into the air capillaries on failure of the BGB. The relative differences in the nBGBBs and the nEECCBs in the different vascular regions of the lung were ascribed to diameters of the branches and their points of origin and angles of bifurcation from the pulmonary artery. Presence of RBCs in the air capillaries of the lungs of rested chickens showed that failure of the BGB commonly occurs even in healthy and unstressed birds. Rapid repair and/or defense responses, which were observed, may explain how birds cope with mechanical injuries of the BGB. PMID:23519074

  17. Structural failures of the blood-gas barrier and the epithelial-epithelial cell connections in the different vascular regions of the lung of the domestic fowl, Gallus gallus variant domesticus, at rest and during exercise.

    Science.gov (United States)

    Maina, John N; Jimoh, Sikiru A

    2013-03-15

    Structural failure of blood-gas barrier (BGB) and epithelial-epithelial cell connections (EECCs) in different vascular regions of the exchange tissue of the lung was studied in rested and exercised chickens. The number of red blood cells (nRBCs) was counted and protein concentration (PC) measured after lavaging the respiratory system, and blood was sampled to determine the blood lactate levels (BLLs). The numbers of complete BGB breaks (nBGBBs) and those of the EECCs (nEECCBs) were counted in the different vascular territories of the lung. The nRBCs and the PCs increased with increasing exercise intensities but the rate of increase decreased at higher workloads. From rest to the fastest experimental treadmill speed of 2.95 m.sec(-1), BLLs increased 4-fold. In all cases, the nEECCBs exceeded those of the BGB, showing that structurally the BGB is relatively weaker than the EECC. The increase in the number of breaks with increasing exercise can be attributed to increase in the pulmonary capillary blood pressure (PCBP) from faster heart rates and higher cardiac outputs, while the leveling out of the measurements made at higher workloads may have arisen from hemodynamic changes that initially ensued from exudation of blood plasma and then flow of blood into the air capillaries on failure of the BGB. The relative differences in the nBGBBs and the nEECCBs in the different vascular regions of the lung were ascribed to diameters of the branches and their points of origin and angles of bifurcation from the pulmonary artery. Presence of RBCs in the air capillaries of the lungs of rested chickens showed that failure of the BGB commonly occurs even in healthy and unstressed birds. Rapid repair and/or defense responses, which were observed, may explain how birds cope with mechanical injuries of the BGB.

  18. Structural failures of the blood–gas barrier and the epithelial–epithelial cell connections in the different vascular regions of the lung of the domestic fowl, Gallus gallus variant domesticus, at rest and during exercise

    Directory of Open Access Journals (Sweden)

    John N. Maina

    2013-01-01

    Structural failure of blood–gas barrier (BGB and epithelial–epithelial cell connections (EECCs in different vascular regions of the exchange tissue of the lung was studied in rested and exercised chickens. The number of red blood cells (nRBCs was counted and protein concentration (PC measured after lavaging the respiratory system, and blood was sampled to determine the blood lactate levels (BLLs. The numbers of complete BGB breaks (nBGBBs and those of the EECCs (nEECCBs were counted in the different vascular territories of the lung. The nRBCs and the PCs increased with increasing exercise intensities but the rate of increase decreased at higher workloads. From rest to the fastest experimental treadmill speed of 2.95 m.sec−1, BLLs increased 4-fold. In all cases, the nEECCBs exceeded those of the BGB, showing that structurally the BGB is relatively weaker than the EECC. The increase in the number of breaks with increasing exercise can be attributed to increase in the pulmonary capillary blood pressure (PCBP from faster heart rates and higher cardiac outputs, while the leveling out of the measurements made at higher workloads may have arisen from hemodynamic changes that initially ensued from exudation of blood plasma and then flow of blood into the air capillaries on failure of the BGB. The relative differences in the nBGBBs and the nEECCBs in the different vascular regions of the lung were ascribed to diameters of the branches and their points of origin and angles of bifurcation from the pulmonary artery. Presence of RBCs in the air capillaries of the lungs of rested chickens showed that failure of the BGB commonly occurs even in healthy and unstressed birds. Rapid repair and/or defense responses, which were observed, may explain how birds cope with mechanical injuries of the BGB.

  19. A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer. Osteopontin, carbonic anhydrase IX and vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Ostheimer, C.; Bache, M.; Guettler, A.; Vordermark, D. [Martin-Luther-University Halle-Wittenberg, Department of Radiation Oncology, Halle (Saale) (Germany); Kotzsch, M. [Technical University Dresden, Department of Pathology, Dresden (Germany)

    2014-03-15

    Hypoxic radioresistance plays a critical role in the radiotherapy of cancer and adversely impacts prognosis and treatment response. This prospective study investigated the interrelationship and the prognostic significance of several hypoxia-related proteins in non-small cell lung cancer (NSCLC) patients treated by radiotherapy ± chemotherapy. Pretreatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase IX (CA IX) plasma levels were determined by ELISA in 55 NSCLC (M0) patients receiving 66 Gy curative-intent radiotherapy or chemoradiation. Marker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was evaluated. All biomarkers were linearly correlated and linked to different clinical parameters including lung function, weight loss (OPN), gross tumor volume (VEGF) and T stage (CA IX). High OPN (p = 0.03), VEGF (p = 0.02) and CA IX (p = 0.04) values were significantly associated with poor survival. Double marker combination additively increased the risk of death by a factor of 2 and high plasma levels of the triple combination OPN/VEGF/CA IX yielded a 5.9-fold risk of death (p = 0.009). The combined assessment of OPN/VEGF/CA IX correlated independently with prognosis (p = 0.03) in a multivariate Cox regression model including N stage, T stage and GTV. This pilot study suggests that a co-detection augments the prognostic value of single markers and that the integration of OPN, VEGF and CA IX into a hypoxic biomarker profile for the identification of patients with largely hypoxic and radioresistant tumors should be further evaluated. (orig.) [German] Hypoxische Radioresistenz spielt eine kritische Rolle in der Radiotherapie maligner Tumoren und beeinflusst Prognose und Therapieansprechen negativ. Diese prospektive Studie untersuchte den Zusammenhang und die prognostische Bedeutung einiger hypoxieassoziierter Proteine bei Patienten mit nicht-kleinzelligem Bronchialkarzinom

  20. Pulmonary artery reconstruction with a tailor-made bovine pericardial conduit following sleeve resection of a long segmental pulmonary artery for the treatment of lung cancer: technical details of the dog-ear method for adjusting diameter during vascular anastomosis.

    Science.gov (United States)

    Shimizu, Kimihiro; Nagashima, Toshiteru; Ohtaki, Yoichi; Takahashi, Toru; Mogi, Akira; Kuwano, Hiroyuki

    2017-05-01

    Sleeve resection of the pulmonary artery (PA) is always required for lung-sparing operations in which half or more of the vessel circumference is infiltrated by the primary tumor or metastatic hilar nodes. Following sleeve resection, conduit reconstruction may be indicated if there is excessive distance between the two vascular stumps, because there is a high degree of tension when repaired by direct anastomosis. We herein present a case of PA reconstruction using a tailor-made bovine pericardial conduit after sleeve resection of PA during lung cancer surgery. The length of resection was longer than 3 cm, and the difference in diameter between the conduit and peripheral PA stump was larger than 0.5 cm. We describe the surgical and oncological merits of a bovine pericardial conduit, and provide details of our reconstruction technique, focusing on adjustment of diameter between the conduit and peripheral PA (dog-ear method).

  1. Blocking of α1β1 and α2β1 adhesion molecules inhibits eosinophil migration through human lung microvascular endothelial cell monolayer

    Directory of Open Access Journals (Sweden)

    Stanisława Bazan-Socha

    2014-12-01

    Full Text Available In cell trafficking to the airways in asthma, among integrins the most important are those containing α4 and β2 subunits. We have previously shown that also blocking of collagen receptors, α1β1 and α2β1 integrins, inhibits transmigration of eosinophils of asthmatic subjects through a monolayer of skin microvascular endothelial cells seeded on collagen IV coated inserts. However, it was not clear whether this observation was limited to asthma or depended on the type of microvascular cell and collagen IV used as a base. In the current study we performed a transmigration assay using human lung microvascular endothelial cells seeded directly on a plastic surface as a base and blood cells isolated from 12 representatives of each of two groups, asthmatics and healthy donors, by gradient centrifugation, followed by immunomagnetic negative separation of eosinophils. Isolated eosinophils and peripheral blood mononuclear cells (PBMC were inhibited by snake venom-derived integrin antagonists including viperistatin and VP12, as inhibitors of α1β1 and α2β1 integrin, respectively, and VLO5 and VLO4, as inhibitors of α4β1 and α5β1 integrin, respectively. All snake venom-derived anti-adhesive proteins were effective in inhibiting eosinophil transmigration, whilst only VLO5 and VLO4 reduced PBMC mobility in this assay. This observation was similar in both groups of subjects studied. α1β1 and α2β1 integrins could be involved in transmigration of eosinophil to the inflammatory site. Migratory inhibition was observed in asthma subjects as well as in healthy donors, and did not depend on origin of endothelial cells or the extracellular matrix component used as a base.

  2. Upregulation of Klotho potentially inhibits pulmonary vascular remodeling by blocking the activation of the Wnt signaling pathway in rats with PM2.5-induced pulmonary arterial hypertension.

    Science.gov (United States)

    Cong, Lu-Hong; Du, Shi-Yu; Wu, Yi-Na; Liu, Ying; Li, Tao; Wang, Hui; Li, Gang; Duan, Jun

    2018-01-30

    We evaluated the effects of Klotho on pulmonary vascular remodeling and cell proliferation and apoptosis in rat models with PM2.5-induced pulmonary arterial hypertension (PAH) via the Wnt signaling pathway. After establishing rat models of PM2.5-induced PAH, these Sprague-Dawley male rats were randomized into control and model groups. Cells extracted from the model rats were sub-categorized into different groups. Activation of Wnt/β-catenin signaling transcription factor was detected by a TOPFlash/FOPFlash assay. A serial of experiment was conducted to identify the mechanism of Klotho on PHA via the Wnt signaling pathway. VEGF levels and PaCO 2 content were higher in the model group, while PaO 2, NO 2 - /NO 3 - content and Klotho level was lower compared to the control group. In comparison to the control group, the model group had decreased Klotho and Bax levels, and elevated Wnt-1, β-catenin, bcl-2, survivin, and PCNA expression, VEGF, IL-6, TNF-α, TNF-β1, and bFGF levels, as well as the percentage of pulmonary artery ring contraction. The Klotho vector, DKK-1 and DKK-1 + Klotho vector groups exhibited reduced cell proliferation, luciferase activity, and the expression of Wnt-1, β-catenin, bcl-2, survivin, and PCNA, as well as shortened S phase compared with the blank and NC groups. Compared with the Klotho vector and DKK-1 groups, the DKK-1 + Klotho vector groups had reduced cell proliferation, luciferase activity, and the expression of Wnt-1, β-catenin, bcl-2, survivin, and PCNA, as well as a shortened S phase. Conclusively, Klotho inhibits pulmonary vascular remodeling by inactivation of Wnt signaling pathway. © 2018 Wiley Periodicals, Inc.

  3. Blocking TGFβ via Inhibition of the αvβ6 Integrin: A Possible Therapy for Systemic Sclerosis Interstitial Lung Disease

    Directory of Open Access Journals (Sweden)

    Tamiko R. Katsumoto

    2011-01-01

    Full Text Available Interstitial lung disease (ILD is a commonly encountered complication of systemic sclerosis (SSc and accounts for a significant proportion of SSc-associated morbidity and mortality. Its pathogenesis remains poorly understood, and therapies that treat SSc ILD are suboptimal, at best. SSc ILD pathogenesis may share some common mechanisms with other fibrotic lung diseases, in which dysregulation of lung epithelium can contribute to pathologic fibrosis via recruitment or in situ generation and activation of fibroblasts. TGFβ, a master regulator of fibrosis, is tightly regulated in the lung by the integrin αvβ6, which is expressed at low levels on healthy alveolar epithelial cells but is highly induced in the setting of lung injury or fibrosis. Here we discuss the biology of αvβ6 and present this integrin as a potentially attractive target for inhibition in the setting of SSc ILD.

  4. Vascular L-type Ca²⁺ channel blocking activity of sulfur-containing indole alkaloids from Glycosmis petelotii.

    Science.gov (United States)

    Cuong, Nguyen Manh; Khanh, Pham Ngoc; Huyen, Pham Thu; Duc, Ho Viet; Huong, Tran Thu; Ha, Vu Thi; Durante, Miriam; Sgaragli, Giampietro; Fusi, Fabio

    2014-07-25

    In the search for novel natural compounds endowed with potential antihypertensive activity, a new sulfur-containing indole alkaloid, N-demethylglypetelotine (2), and its known analogue glypetelotine (1), were isolated from the leaves of Glycosmis petelotii. Their structures were established on the basis of spectroscopic evidence. The two alkaloids were assessed for vasorelaxing activity on rat aorta rings and for L-type Ba(2+) current [I(Ba(L))] blocking activity on single myocytes isolated from rat tail artery. Both glypetelotine and N-demethylglypetelotine inhibited phenylephrine-induced contraction with IC50 values of 20 and 50 μM, respectively. The presence of endothelium did not modify their spasmolytic effect. Neither glypetelotine nor N-demethylglypetelotine affected Ca(2+) release from the sarcoplasmic reticulum induced by phenylephrine. The spasmolytic effect of glypetelotine increased with membrane depolarization. In the presence of 60 mM K(+), both compounds inhibited, in a concentration-dependent manner, the contraction induced by cumulative addition of Ca(2+), this inhibition being inversely related to Ca(2+) concentration. Glypetelotine and, less efficiently N-demethylglypetelotine, inhibited I(Ba(L)), the former compound also affecting I(Ba(L)) kinetics. In conclusion, glypetelotine is a novel vasorelaxing agent which antagonizes L-type Ca(2+) channels.

  5. Analgesia and pulmonary function after lung surgery: is a single intercostal nerve block plus patient-controlled intravenous morphine as effective as patient-controlled epidural anaesthesia? A randomized non-inferiority clinical trial.

    Science.gov (United States)

    Meierhenrich, R; Hock, D; Kühn, S; Baltes, E; Muehling, B; Muche, R; Georgieff, M; Gorsewski, G

    2011-04-01

    Thoracic epidural anaesthesia (EDA) is regarded as the 'gold standard' for postoperative pain control and restoration of pulmonary function after lung surgery. Easier, less time-consuming, and, perhaps, safer is intercostal nerve block performed under direct vision by the surgeon before closure of the thoracotomy combined with postoperative i.v. patient-controlled analgesia with morphine. We hypothesized that this technique is as effective as thoracic EDA. The study was designed as a single-centre, open labelled, randomized non-inferiority trial. A total of 92 patients undergoing elective lung surgery were randomly assigned to the epidural (n=47) or intercostal group (n=45), and 83 patients completed the study. Pain scores, inspiratory vital capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR) were assessed during the first four postoperative days. Median treatment differences regarding pain scores at rest failed to demonstrate non-inferiority of the intercostal nerve block at the first postoperative day. Patients of the intercostal group reported significantly higher pain scores on coughing during the first and second postoperative days. The epidural group had a significantly higher median FVC, FEV1, and PEFR values on the second postoperative day. No difference was found in pulmonary complications, length of hospital stay, or in-hospital deaths. In patients undergoing lung surgery, single intercostal nerve block plus i.v. patient-controlled analgesia with morphine is not as effective as patient-controlled EDA with respect to pain control and restoration of pulmonary function.

  6. Vascular Cures

    Science.gov (United States)

    ... vascular disease, such as stroke, aneurysm and pulmonary artery disease. Each one has their own unique story about their battle with vascular disease and their road to recovery. SEE PATIENT STORIES Our Supporters Caring ...

  7. Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function After Hemorrhagic Shock.

    Science.gov (United States)

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

    2016-01-01

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

  8. CCR researchers show that blocking the estrogen receptor restores the sensitivity of lung cancer cells to therapy | Center for Cancer Research

    Science.gov (United States)

    Claudia Palena, Ph.D., of CCR’s Laboratory of Tumor Immunology and Biology, and her colleagues wondered if it would be possible to identify compounds that could reverse the therapy resistance imparted by the process called epithelial-mesenchymal transition (EMT) in lung cancer.

  9. Morphological appearance, content of extracellular matrix and vascular density of lung metastases predicts permissiveness to infiltration by adoptively transferred natural killer and T cells

    DEFF Research Database (Denmark)

    Yang, Q.; Goding, S.; Hagenaars, M.

    2006-01-01

    . Analyses of tumors for extracellular matrix (ECM) components and PECAM-1(+) vasculature, revealed that the I-R lesions are hypovascularized and contain very little laminin, collagen and fibronectin. In contrast, the I-P loose tumors are well-vascularized and they contain high amounts of ECM components...... infiltration by activated NK and T cells correlates with the presence of ECM components and PECAM-1(+) vasculature in the malignant tissue. Thus, analysis of the distribution of ECM and vasculature in tumor biopsies may help select patients most likely to benefit from cellular adoptive immunotherapy....

  10. Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

    Directory of Open Access Journals (Sweden)

    Cyril Francioli

    Full Text Available Damaged lung grafts obtained after circulatory death (DCD lungs and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP. Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6 or in presence of PDTC (2.5g/L, PDTC group, N = 6. Static pulmonary compliance (SPC, peak airway pressure (PAWP, pulmonary vascular resistance (PVR, and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema, and the concentration of LDH (cell damage, proteins (permeability edema and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL, and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

  11. Vascular and lung function related to ultrafine and fine particles exposure assessed by personal and indoor monitoring: a cross-sectional study

    DEFF Research Database (Denmark)

    Olsen, Yulia; Karottki, Dorina Gabriela; Jensen, Ditte Marie

    2014-01-01

    and PM2.5 were monitored in living rooms of 60 homes with 81 non-smoking subjects (30-75 years old), 59 of whom carried personal monitors both when at home and away from home. We measured lung function in terms of the FEV1/FVC ratio, microvascular function (MVF) and pulse amplitude by digital artery...... negatively associated with total personal PNC. Indoor PNC and PM2.5 showed positive association with blood pressure and inverse association with eosinophil counts. Conclusions: The inverse association between personal exposure away from home and MVF is consistent with adverse health effects of UFP from...

  12. Caffeine's Vascular Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Darío Echeverri

    2010-01-01

    Full Text Available 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.

  13. The new InsP3Kinase inhibitor BIP-4 is competitive to InsP3 and blocks proliferation and adhesion of lung cancer cells.

    Science.gov (United States)

    Schröder, Dominik; Tödter, Klaus; Gonzalez, Beatriz; Franco-Echevarría, Elsa; Rohaly, Gabor; Blecher, Christine; Lin, Hong-Ying; Mayr, Georg W; Windhorst, Sabine

    2015-07-15

    As ectopic expression of the neuronal inositol-1,4,5-trisphosphate-3-kinase A (InsP3Kinase) in tumor cells increases the metastatic potential, InsP3Kinase is an interesting target for tumor therapy. Recently, we have identified a membrane-permeable InsP3Kinase inhibitor (BAMB-4) exhibiting an IC50-value of 20 μM. Here we characterized a new InsP3Kinase inhibitor which shows a 130-fold lower IC50 value (157 ± 57 nM) as compared to BAMB-4. We demonstrate that this nitrophenolic compound, BIP-4, is non-competitive to ATP but competitive to InsP3, thus exhibits a high selectivity for inhibition of InsP3Kinase activity. Docking analysis suggested a putative binding mode of this molecule into the InsP3Kinase active site. Determination of cellular uptake in lung cancer cells (H1299) revealed that 6% of extracellular BIP-4 is internalized by non-endosomal uptake, showing that BIP-4 is not trapped inside endo/lysosomes but is available to inhibit cellular InsP3Kinase activity. Interestingly, we found that BIP-4 mediated inhibition of InsP3Kinase activity in the two lung cancer cell lines H1299 and LN4323 inhibited proliferation and adhesion at IC50 values of 3 μM or 2 μM, respectively. InsP3Kinase inhibition did not alter ATP-induced calcium signals but significantly reduced the level of Ins(1,3,4,5,6)P5. From these data we conclude that the inhibitory effect of BIP-4 on proliferation and adhesion of lung cancer cells does not result from alterations of calcium but from alterations of inositol phosphate signals. In summary, we reveal that inhibition of cellular InsP3Kinase by BIP-4 impairs proliferation and adhesion and therefore BIP-4 might be a promising compound to reduce the metastatic potential of lung carcinoma cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Efficacy of plasma vascular endothelial growth factor in monitoring first-line chemotherapy in patients with advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Mohan Anant

    2009-12-01

    Full Text Available Abstract Background Along with the development of new cancer therapeutics, more effective tools for the estimation of response to therapy and prediction of disease progression are required for the better management of inoperable cancer patients. Methods We studied 134 newly diagnosed and primarily untreated advanced non-small cell lung cancer patients and 100 controls. Forty two patients received platinum-based chemotherapy. Plasma VEGF levels were quantified in all samples at baseline and also before second and third chemotherapy cycle in 42 patients and correlated with response to therapy as assessed by computed tomography after the third chemotherapy cycle. Results We observed that, patients who went into remission had significantly lower baseline VEGF levels before second and third cycles of chemotherapy when compared with patients with no change and progression. Plasma VEGF levels showed a greater decrease from cycle 1 to 2 and from cycle 1 to 3 in patients who showed remission in comparison to those with no change or progression. Plasma VEGF levels before the second cycle detected poor response to therapy with a sensitivity and specificity of 76.9% and 75.0%, respectively (area under the ROC curve = 0.724. Early prediction of disease progression was achieved with a sensitivity and specificity of 71.4% for plasma VEGF before cycle 2 (area under the ROC curve = 0.805. The kinetics of VEGF form cycle 1 to 2 and cycle 1 to 3 also gave significant information for predicting disease progression as well as insufficient therapy response. Conclusion Monitoring of plasma VEGF levels during the course of first-line chemotherapy could identify patients who are likely to have insufficient response to therapy and disease progression at an early stage. This may help in individualizing treatment and could lead to better management of the advanced stage lung cancer.

  15. Bigelovii A Protects against Lipopolysaccharide-Induced Acute Lung Injury by Blocking NF-κB and CCAAT/Enhancer-Binding Protein δ Pathways

    Directory of Open Access Journals (Sweden)

    Chunguang Yan

    2016-01-01

    Full Text Available Optimal methods are applied to acute lung injury (ALI and the acute respiratory distress syndrome (ARDS, but the mortality rate is still high. Accordingly, further studies dedicated to identify novel therapeutic approaches to ALI are urgently needed. Bigelovii A is a new natural product and may exhibit anti-inflammatory activity. Therefore, we sought to investigate its effect on lipopolysaccharide- (LPS- induced ALI and the underlying mechanisms. We found that LPS-induced ALI was significantly alleviated by Bigelovii A treatment, characterized by reduction of proinflammatory mediator production, neutrophil infiltration, and lung permeability. Furthermore, Bigelovii A also downregulated LPS-stimulated inflammatory mediator expressions in vitro. Moreover, both NF-κB and CCAAT/enhancer-binding protein δ (C/EBPδ activation were obviously attenuated by Bigelovii A treatment. Additionally, phosphorylation of both p38 MAPK and ERK1/2 (upstream signals of C/EBPδ activation in response to LPS challenge was also inhibited by Bigelovii A. Therefore, Bigelovii A could attenuate LPS-induced inflammation by suppression of NF-κB, inflammatory mediators, and p38 MAPK/ERK1/2—C/EBPδ, inflammatory mediators signaling pathways, which provide a novel theoretical basis for the possible application of Bigelovii A in clinic.

  16. Vascular Vertigo

    Directory of Open Access Journals (Sweden)

    Mazyar Hashemilar

    2017-02-01

    Full Text Available Vertigo is a common complaint in neurology and medicine. The most common causes of vertigo are benign paroxysmal positional vertigo, vestibular neuritis, Meniere’s disease, and vascular disorders. Vertigo of vascular origin is usually limited to migraine, transient ischemic attacks, and ischemic or hemorrhagic stroke. Vascular causes lead to various central or peripheral vestibular syndromes with vertigo. This review provides an overview of epidemiology and clinical syndromes of vascular vertigo. Vertigo is an illusion of movement caused by asymmetrical involvement of the vestibular system by various causes. Migraine is the most frequent vascular disorder that causes vertigo in all age groups. Vertigo may occur in up to 25% of patients with migraine. The lifetime prevalence of migrainous vertigo is almost 1%. Cerebrovascular disorders are estimated to account for 3% to 7% of patients with vertigo. Vestibular paroxysmia has been diagnosed in 1.8% to 4% of cases in various dizziness units. Vasculitic disorders are rare in the general population, but vertigo may be seen in almost up to 50% of patients with different vasculitic syndromes. Conclusions: Migraine, cerebrovascular disorders especially involving the vertebrobasilar territory, cardiocirculatory diseases, neurovascular compression of the eighth nerve, and vasculitis are vascular causes of vertigo syndromes.

  17. Population Blocks.

    Science.gov (United States)

    Smith, Martin H.

    1992-01-01

    Describes an educational game called "Population Blocks" that is designed to illustrate the concept of exponential growth of the human population and some potential effects of overpopulation. The game material consists of wooden blocks; 18 blocks are painted green (representing land), 7 are painted blue (representing water); and the remaining…

  18. Decursin was Accelerated Human Lung Cancer Cell Death Caused by Proton Beam Irradiation via Blocking the p42/44 MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Hwan; Ra, Se Jin; Kim, Kye Ryung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    Decursin, which is one of the extract of Angelica gigas Nakai root, has been traditionally used in Korean folk medicine as a tonic and for treatment of anemia and other common diseases. There are some reports about the pharmacological properties of decursin showing anti-bacterial and anti-amnestic effect, depression of cardiac contraction, antitumor and anti-angiogenic activity. Cell death induced by proton beam is identified as apoptosis. The study investigated that genes involved in apoptosis are checked by RT-PCR and used LET instead of SPBP of proton beam. Apoptosis is the tight regulated by multi-protein action in physiological cell death program. Proton therapy is an attractive approach for the treatment of deep-seated tumor. Recently, many researchers tried to new therapeutic strategy, combination of proton therapy and chemotherapy, in order to increase therapeutic effect. In this study, we investigate whether decursin can accelerate effect of human lung cell apoptosis in proton irradiated cancer cells

  19. Decursin was Accelerated Human Lung Cancer Cell Death Caused by Proton Beam Irradiation via Blocking the p42/44 MAPK pathway

    International Nuclear Information System (INIS)

    Jung, Myung Hwan; Ra, Se Jin; Kim, Kye Ryung

    2011-01-01

    Decursin, which is one of the extract of Angelica gigas Nakai root, has been traditionally used in Korean folk medicine as a tonic and for treatment of anemia and other common diseases. There are some reports about the pharmacological properties of decursin showing anti-bacterial and anti-amnestic effect, depression of cardiac contraction, antitumor and anti-angiogenic activity. Cell death induced by proton beam is identified as apoptosis. The study investigated that genes involved in apoptosis are checked by RT-PCR and used LET instead of SPBP of proton beam. Apoptosis is the tight regulated by multi-protein action in physiological cell death program. Proton therapy is an attractive approach for the treatment of deep-seated tumor. Recently, many researchers tried to new therapeutic strategy, combination of proton therapy and chemotherapy, in order to increase therapeutic effect. In this study, we investigate whether decursin can accelerate effect of human lung cell apoptosis in proton irradiated cancer cells

  20. Novel agents in the management of lung cancer.

    LENUS (Irish Health Repository)

    Kennedy, B

    2012-01-31

    Lung cancer is the leading cause of cancer death worldwide. Survival remains poor as approximately 80% of cases present with advanced stage disease. However, new treatments are emerging which offer hope to patients with advanced disease. Insights into cell biology have identified numerous intracellular and extracellular peptides that are pivotal in cancer cell signalling. Disrupting the function of these peptides inhibits intracellular signal transduction and diminishes uncontrolled proliferation, resistance to apoptosis and tumour angiogenesis. The most widely studied signalling pathway is the Epidermal Growth Factor (EGF) pathway. EGF signalling can be disrupted at numerous points. Blockade of the cell surface receptor is achieved by the monoclonal antibody cetuximab; intracellular tyrosine kinase activity is inhibited by erlotinib. Vascular Endothelial Growth Factor (VEGF) regulates another pathway important for tumour growth. Inhibition of VEGF impairs angiogenesis and disrupts metastatic spread. Bevacizumab is a monoclonal antibody that binds to VEGF and blocks interaction with its cell surface receptor. Clinical trials have demonstrated that disruption of these signalling pathways can improve survival in advanced lung cancer. New compounds including folate antimetabolites such as pemetrexed, proteasome inhibitors such as bortezomib, modified glutathione analogues such as TLK286, and other agents such as epothilones and other small molecules are currently being evaluated in patients with lung cancer. As more and more signalling peptides are targeted for manipulation, it is hoped that a new era is dawning in the treatment of advanced stage lung cancer. This review will focus on emerging new therapies in the management of lung cancer.

  1. Vascular dementia

    African Journals Online (AJOL)

    Adele

    2003-12-10

    Dec 10, 2003 ... ischaemic VaD includes multiple lacunes and subcortical arteriosclerotic encephalopathy (Binswanger's disease) and imaging shows multiple deep ... culitis, multiple sclerosis, acute demyelinating encephalomy- ... Table I. The NINDS-AIREN criteria for the diagnosis of Vascular Dementia. 12. Require both ...

  2. VASCULAR SURGERY

    African Journals Online (AJOL)

    2016-06-02

    Jun 2, 2016 ... with the literature from South Africa over the last four decades, and reflects the high rate of interpersonal violence in the country.14,15 As expected, cervical ... via the intact circle of Willis in young patients is the most likely explanation for the lack of strokes. Five patients were referred to the Durban vascular ...

  3. Ultrasound -- Vascular

    Science.gov (United States)

    ... waves from passing into your body. The sonographer (ultrasound technologist) or radiologist then places the transducer on the ... is specialized and is best performed by a technologist and physician with experience in vascular ultrasound imaging. top of page Additional Information and Resources ...

  4. Quinacrine Inhibits ICAM-1 Transcription by Blocking DNA Binding of the NF-κB Subunit p65 and Sensitizes Human Lung Adenocarcinoma A549 Cells to TNF-α and the Fas Ligand.

    Science.gov (United States)

    Harada, Misuzu; Morimoto, Kyoko; Kondo, Tetsuya; Hiramatsu, Reiko; Okina, Yuji; Muko, Ryo; Matsuda, Iyo; Kataoka, Takao

    2017-12-02

    Quinacrine has been used for therapeutic drugs in some clinical settings. In the present study, we demonstrated that quinacrine decreased the expression of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor (TNF)-α and interleukin-1 (IL-1) α in human lung adenocarcinoma A549 cells. Quinacrine inhibited ICAM-1 mRNA expression and nuclear factor κB (NF-κB)-responsive luciferase reporter activity following a treatment with TNF-α and IL-1α. In the NF-κB signaling pathway, quinacrine did not markedly affect the TNF-α-induced degradation of the inhibitor of NF-κB or the TNF-α-induced phosphorylation of the NF-κB subunit, p65, at Ser-536 and its subsequent translocation to the nucleus. In contrast, a chromatin immunoprecipitation assay showed that quinacrine prevented the binding of p65 to the ICAM-1 promoter following TNF-α stimulation. Moreover, TNF-α and the Fas ligand effectively reduced the viability of A549 cells in the presence of quinacrine only. Quinacrine down-regulated the constitutive and TNF-α-induced expression of c-FLIP and Mcl-1 in A549 cells. These results revealed that quinacrine inhibits ICAM-1 transcription by blocking the DNA binding of p65 and sensitizes A549 cells to TNF-α and the Fas ligand.

  5. Syndrome of pathologically changed lung image

    International Nuclear Information System (INIS)

    Ginzburg, M.A.; Kinoshenko, Yu.T.

    1987-01-01

    Syndrome of pathologically changed lung image unites radiological signs arising on the basis of vascular, stromal and bronchial lung structures. Intrasyndrome differential diagnosis of pathologically changed lung image is presented. Elements of the lung image are characterized from the view point of their localization and extension of changes, quantity, size and form of shadows, their intensity and configuration (contours). Dynamics of syndrome changes in different variants is taken account of. Methods of roentgenological study in case of different syndromes are discussed

  6. Vascular neoplasms.

    Science.gov (United States)

    Williams, H B

    1980-07-01

    Vascular neoplasms in the broad sense represent a very common group of tumors or hamartomas that show great variability in gross appearance, microscopic appearance, and clinical course. Generally, neoplasms are composed of one cell type, but vascular neoplasms are collections of endothelial-lined tubes or tubules with connective tissue walls that may contain smooth muscle cells, pericytes, and nerve elements according to the specific tissues of origin. The classification of vascular neoplasms as outlined in this article attempts to delineate each tumor or hamartoma according to its histologic appearance and clinical behavior. The clinical course ranges from completely benign, self-involuting malformations such as the strawberry hemangioma to highly malignant angiosarcomas with their rapid growth and frequent metastases. Defects in the lymphatic system show gradations from simple lymphangiomas through lymphedema and lymphangiectasia, which can probably be explained by faulty embryologic development. Management of these lesions has been discussed, including brief descriptions of most of the currently accepted treatment methods for these frequently encountered clinical problems.

  7. A segmentation method for lung nodule image sequences based on superpixels and density-based spatial clustering of applications with noise.

    Science.gov (United States)

    Zhang, Wei; Zhang, Xiaolong; Zhao, Juanjuan; Qiang, Yan; Tian, Qi; Tang, Xiaoxian

    2017-01-01

    The fast and accurate segmentation of lung nodule image sequences is the basis of subsequent processing and diagnostic analyses. However, previous research investigating nodule segmentation algorithms cannot entirely segment cavitary nodules, and the segmentation of juxta-vascular nodules is inaccurate and inefficient. To solve these problems, we propose a new method for the segmentation of lung nodule image sequences based on superpixels and density-based spatial clustering of applications with noise (DBSCAN). First, our method uses three-dimensional computed tomography image features of the average intensity projection combined with multi-scale dot enhancement for preprocessing. Hexagonal clustering and morphological optimized sequential linear iterative clustering (HMSLIC) for sequence image oversegmentation is then proposed to obtain superpixel blocks. The adaptive weight coefficient is then constructed to calculate the distance required between superpixels to achieve precise lung nodules positioning and to obtain the subsequent clustering starting block. Moreover, by fitting the distance and detecting the change in slope, an accurate clustering threshold is obtained. Thereafter, a fast DBSCAN superpixel sequence clustering algorithm, which is optimized by the strategy of only clustering the lung nodules and adaptive threshold, is then used to obtain lung nodule mask sequences. Finally, the lung nodule image sequences are obtained. The experimental results show that our method rapidly, completely and accurately segments various types of lung nodule image sequences.

  8. Vascular ultrasound.

    Science.gov (United States)

    Pilcher, D B; Ricci, M A

    1998-04-01

    Surgeon-interpreted diagnostic ultrasound has become the preferred screening test and often the definitive test for the diagnosis of arterial stenosis, aneurysm, and venous thrombosis. As a modality for surveillance, its noninvasive quality makes it particularly appealing as the test of choice to screen patients for abdominal aortic aneurysms or to perform follow-up examinations on those patients with a carotid endartectomy or in situ bypass grafts. The increasing reliance on intraoperative duplex imaging of vascular procedures demands that the surgeon learn the skills to perform the studies without a technologist or radiologist to interpret the examination.

  9. Overexpression of both platelet-derived growth factor-BB and vascular endothelial growth factor-C and its association with lymphangiogenesis in primary human non-small cell lung cancer.

    Science.gov (United States)

    Liu, Jiannan; Liu, Chuanyong; Qiu, Liyun; Li, Juan; Zhang, Pei; Sun, Yuping

    2014-06-27

    Metastatic spread of tumor through lymphatic vasculature is an important adverse prognostic factor in a variety of human cancer and tumor lymphangiogenesis requires the interplay of several growth factors. Platelet-derived growth factor (PDGF)-BB and vascular endothelial growth factor (VEGF)-C are two important molecules involving in tumor metastasis and lymphangiogenesis. Therefore, the aim of this study was to investigate the coexpression of PDGF-BB and VEGF-C in primary human non-small cell lung cancer (NSCLC) and its association with lymphangiogenesis. Using immunohistochemical staining, PDGF-BB and VEGF-C expression were detected in 109 primary NSCLC tissues, while the lymphatic micro-vessel density (LMVD) was counted. Of 109 cases, PDGF-BB and VEGF-C overexpression was 66.97% (73/109) and 65.14% (71/109), respectively. 52 (47.7%) had overexpression of both PDGF-BB and VEGF-C (P+V+), 21 (19.3%) overexpression of PDGF-BB but low expression of VEGF-C (P+V-), 19(17.4%) overexpression of VEGF-C but low expression of PDGF-BB (P-V+) and 17(15.6%) low expression of both PDGF-BB and VEGF-C (P-V-). PDGF-BB expression was positively related to that of VEGF-C (r=0.451, p=0.034). LMVD in cases with P+V+was much higher than those with P-V- (p=0.004). In addition, the patients with P+V+were younger and also had larger tumor size, more likely lymph node metastasis and worse histological differentiation than those with P-V-. Moreover, the overall survival (OS) of patients with P+V+was shorter than those with P-V- (p=0.015). Coexpression of both PDGF-BB and VEGF-C was associated with lymphangiogenesis and poor prognosis in NSCLC, and might play a critical role in NSCLC progression. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2261801312571320.

  10. Testicular orphan nuclear receptor 4-associated protein 16 promotes non-small cell lung carcinoma by activating estrogen receptor β and blocking testicular orphan nuclear receptor 2.

    Science.gov (United States)

    Fang, Fang; Zheng, Qingfeng; Zhang, Jianzhi; Dong, Bin; Zhu, Sainan; Huang, Xiaoyun; Wang, Yang; Zhao, Bingtian; Li, Shaolei; Xiong, Hongchao; Chen, Jinfeng; Wu, Nan; Song, Sonya Wei; Chang, Chawnshang; Yang, Yue

    2013-01-01

    The possible involvement of estrogen receptors (ERs) and testicular orphan nuclear receptors (TRs) in human non-small cell lung carcinoma (NSCLC) has been suggested, but their precise roles and their relationship remain largely unknown. This study aimed to investigate whether TR4-associated protein 16 (TRA16) regulates the ERβ and TR2 pathways and could be a potential target in NSCLC. We used tissue microarrays including NSCLC tissues (n=154) and negative controls (n=14) to examine the expression of TRA16 and ERβ, and in vitro reporter gene assays, the mammalian two-hybrid method and immunoprecipitation in Cos-1 cells to investigate the relationships among TRA16, ERβ and TR2. We found that TRA16 was highly expressed in approximately 90% of the NSCLC tissues examined. TRA16 overexpression was significantly associated with TNM stage, tumor size, lymph node metastasis, tumor thrombus in vein, tumor differentiation and prognosis of NSCLC patients, in which TRA16 was shown to be an independent prognostic factor. Introduction of TRA16 into Cos-1 cells enhanced cell proliferation. Co-expression of TRA16 and ERβ in Cos-1 cells using different reporter gene systems and mammalian two-hybrid approaches revealed that TRA16 enhanced ERβ-mediated transcriptional activity. By adopting similar approaches, and immunoprecipitation and immunocytofluorescence assays, we found that TRA16 also interacted with TR2, and blocked the TR2 inhibitory effect on ERβ. Our findings demonstrate that TRA16 could be a promising diagnostic and prognostic biomarker in NSCLC, and promotes cancer cell growth through activation of the ERβ pathway by interacting with ERβ and TR2.

  11. Ultrasound-guided peripheral nerve blocks: what are the benefits?

    DEFF Research Database (Denmark)

    Nielsen, Zbigniew Jerzy Koscielniak

    2008-01-01

    comparative studies. The occurrence of paraesthesia during block performance was also reduced, but not the incidence of short-lasting post-operative neuropraxia. The frequency of accidental vascular punctures may be lower, but the data are contradictory. Block onset time was significantly shortened. Block...

  12. Angiosarcoma of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Grafino, Monica; Alves, Paula; Almeida, Margarida Mendes de; Garrido, Patricia; Hasmucrai, Direndra; Teixeira, Encarnacao; Sotto-Mayor, Renato, E-mail: mgrafino@gmail.com [Centro Hospitalar Lisboa Norte, EPE, Lisboa (Portugal)

    2016-06-01

    Angiosarcoma is a rare malignant vascular tumor. Pulmonary involvement is usually attributable to metastasis from other primary sites, primary pulmonary angiosarcoma therefore being quite uncommon. We report a case of angiosarcoma with pulmonary involvement, probably primary to the lung, which had gone untreated for more than two years. We describe this rare neoplasm and its growth, as well as the extensive local invasion and hematogenous metastasis at presentation. We also discuss its poor prognosis. (author)

  13. Lung Emergencies

    Science.gov (United States)

    ... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at increased risk of sudden lung ...

  14. Pathophysiological consequences of VEGF-induced vascular permeability

    Science.gov (United States)

    Weis, Sara M.; Cheresh, David A.

    2005-09-01

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

  15. MR evaluation of right pulmonary agenesis and vascular airway compression in pediatric patients.

    Science.gov (United States)

    Newman, B; Gondor, M

    1997-01-01

    The purpose of this study was to evaluate the spectrum of airway and vascular anomalies in agenesis of the right lung and to assess the role of imaging in defining the anatomy. Symptomatic children with right lung agenesis often have anatomic distortion of the airway with vascular compression, and occasionally they have intrinsic airway stenosis. MR imaging most accurately defines the entire spectrum of airway and vascular anatomic abnormalities. Precise delineation of the anatomy is essential in patient management and surgical planning.

  16. Lung density

    DEFF Research Database (Denmark)

    Garnett, E S; Webber, C E; Coates, G

    1977-01-01

    The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...

  17. Rapamycin nanoparticles localize in diseased lung vasculature and prevent pulmonary arterial hypertension.

    Science.gov (United States)

    Segura-Ibarra, Victor; Amione-Guerra, Javier; Cruz-Solbes, Ana S; Cara, Francisca E; Iruegas-Nunez, David A; Wu, Suhong; Youker, Keith A; Bhimaraj, Arvind; Torre-Amione, Guillermo; Ferrari, Mauro; Karmouty-Quintana, Harry; Guha, Ashrith; Blanco, Elvin

    2017-05-30

    Vascular remodeling resulting from pulmonary arterial hypertension (PAH) leads to endothelial fenestrations. This feature can be exploited by nanoparticles (NP), allowing them to extravasate from circulation and accumulate in remodeled pulmonary vessels. Hyperactivation of the mTOR pathway in PAH drives pulmonary arterial smooth muscle cell proliferation. We hypothesized that rapamycin (RAP)-loaded NPs, an mTOR inhibitor, would accumulate in diseased lungs, selectively targeting vascular mTOR and preventing PAH progression. RAP poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL) NPs were fabricated. NP accumulation and efficacy were examined in a rat monocrotaline model of PAH. Following intravenous (IV) administration, NP accumulation in diseased lungs was verified via LC/MS analysis and confocal imaging. Pulmonary arteriole thickness, right ventricular systolic pressures, and ventricular remodeling were determined to assess the therapeutic potential of RAP NPs. Monocrotaline-exposed rats showed increased NP accumulation within lungs compared to healthy controls, with NPs present to a high extent within pulmonary perivascular regions. RAP, in both free and NP form, attenuated PAH development, with histological analysis revealing minimal changes in pulmonary arteriole thickness and no ventricular remodeling. Importantly, NP-treated rats showed reduced systemic side effects compared to free RAP. This study demonstrates the potential for nanoparticles to significantly impact PAH through site-specific delivery of therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema.

    Science.gov (United States)

    Yu, Jinyan; Ma, Zhongsen; Shetty, Sreerama; Ma, Mengshi; Fu, Jian

    2016-07-01

    Lung endothelial damage contributes to the pathogenesis of acute lung injury. New strategies against lung endothelial barrier dysfunction may provide therapeutic benefits against lung vascular injury. Cell-cell junctions and microtubule cytoskeleton are basic components in maintaining endothelial barrier integrity. HDAC6, a deacetylase primarily localized in the cytoplasm, has been reported to modulate nonnuclear protein function through deacetylation. Both α-tubulin and β-catenin are substrates for HDAC6. Here, we examined the effects of tubastatin A, a highly selective HDAC6 inhibitor, on TNF-α induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. Selective HDAC6 inhibition by tubastatin A blocked TNF-α-induced lung endothelial cell hyperpermeability, which was associated with increased α-tubulin acetylation and microtubule stability. Tubastatin A pretreatment inhibited TNF-α-induced endothelial cell contraction and actin stress fiber formation with reduced myosin light chain phosphorylation. Selective HDAC6 inhibition by tubastatin A also induced β-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of β-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-α-induced barrier dysfunction and increased α-tubulin and β-catenin acetylation in endothelial cells. Furthermore, in a mouse model of endotoxemia, tubastatin A was able to prevent endotoxin-induced deacetylation of α-tubulin and β-catenin in lung tissues, which was associated with reduced pulmonary edema. Collectively, our data indicate that selective HDAC6 inhibition by tubastatin A is a potent approach against lung endothelial barrier dysfunction. Copyright © 2016 the American Physiological Society.

  19. Image diagnostic evaluation of pulmonary vascular permeability

    International Nuclear Information System (INIS)

    Kato, Shiro; Asai, Sumihiko; Shimada, Yuji; Ogawa, Kenichi; Nakamoto, Ryumei; Yoshimura, Masaharu; Nomura, Sumi.

    1990-01-01

    To determine the validity of computed tomography (CT) in evaluating pulmonary vascular permeability, dynamic CT scans were consequently obtained from 23 dogs with oleic acid-induced pulmonary edema (the edema group) and 12 normal dogs (the control group). The findings of CT were compared with the wet/dry lung weight ratio and the iodine concentration in the lung tissue. The time-density curve of ROI created over the left ventricular cavity reached the maximum density value at 2 minutes after the injection of contrast medium, and it returned to the pre-injection level 5 to 10 minutes later. Similar tendency was observed for the right and left lung fields in the control group; however, in the edema group, the maximum CT numbers attained at 2 minutes were only slightly reduced later on. The ratio of CT numbers at 5 and 10 minutes after the injection to that at 2 minutes was defined as the residual CT number ratio. The residual CT number ratios for both the left ventricular cavity and the right and left lung fields were significantly higher in the edema group than the normal group. The lung/heart CT number ratio at 5 and 10 minutes was also significantly higher in the edema group than the control group. In addition, both the wet/dry weight ratio of the right and left lungs and iodine concentration in the lung tissue were significantly higher in the edema group than the control group. There was a significant linear correlation between the wet/dry lung weight ratio and the iodine concentration for both the right lung (r=0.819) and for the left lung (r=0.871). (N.K.)

  20. Collagen vascular disease

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001223.htm Collagen vascular disease To use the sharing features on ... were previously said to have "connective tissue" or "collagen vascular" disease. We now have names for many ...

  1. Vascular Anomalies in Pediatrics.

    Science.gov (United States)

    Foley, Lisa S; Kulungowski, Ann M

    2015-08-01

    A standardized classification system allows improvements in diagnostic accuracy. Multidisciplinary vascular anomaly centers combine medical, surgical, radiologic, and pathologic expertise. This collaborative approach tailors treatment and management of vascular anomalies for affected individuals.

  2. Peripheral Vascular Disease

    Science.gov (United States)

    ... Topics FAQs Peripheral Vascular Disease Peripheral vascular disease (PVD) involves damage to or blockage in the blood ... the organs in and below your stomach area. PVD may also affect the arteries leading to your ...

  3. Lung scintigraphy

    International Nuclear Information System (INIS)

    Dalenz, Roberto.

    1994-01-01

    A review of lung scintigraphy, perfusion scintigraphy with SPECT, lung ventilation SPECT, blood pool SPECT. The procedure of lung perfusion studies, radiopharmaceutical, administration and clinical applications, imaging processing .Results encountered and evaluation criteria after Biello and Pioped. Recommendations and general considerations have been studied about relation of this radiopharmaceutical with other pathologies

  4. Lung transplant

    Science.gov (United States)

    ... transplant surgery include: You are placed on the heart-lung machine. One or both of your lungs are removed. For people who are having a double lung transplant, most or all of the steps from the first side are completed before the second side is ...

  5. Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary growth phase killing of P. aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr -/--mice

    DEFF Research Database (Denmark)

    Hoffmann, N.; Lee, Bao le ri; Hentzer, Morten

    2007-01-01

    The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM...

  6. Epithelioid lung haenangioendiothelioma

    International Nuclear Information System (INIS)

    Finozzi, V.; Andrade, E.; Campos, N.; Pizarrosa, C.

    2000-01-01

    The first national case of epithelioid lung haenangioendiothelioma concerned a 60 years old woman. Clinical picture and TC diagnosis showed a vascularized tumor producing persistent haenoptoic expectoration.It is necessary to be acquainted with it for the purpose of a differentiated diagnosis. It is a tumor with specific immunohistochemical markers against factor V III.Treatment consisted of surgical resection. Concerning its classification it is situated at the limit between benign and malignant, prognosis is usually good, but evolution is slow, extending for over 20 years

  7. Intraoperative lung ultrasound: A clinicodynamic perspective

    Directory of Open Access Journals (Sweden)

    Amit Kumar Mittal

    2016-01-01

    Full Text Available In the era of evidence-based medicine, ultrasonography has emerged as an important and indispensable tool in clinical practice in various specialties including critical care. Lung ultrasound (LUS has a wide potential in various surgical and clinical situations for timely and easy detection of an impending crisis such as pulmonary edema, endobronchial tube migration, pneumothorax, atelectasis, pleural effusion, and various other causes of desaturation before it clinically ensues to critical level. Although ultrasonography is frequently used in nerve blocks, airway handling, and vascular access, LUS for routine intraoperative monitoring and in crisis management still necessitates recognition. After reviewing the various articles regarding the use of LUS in critical care, we found, that LUS can be used in various intraoperative circumstances similar to Intensive Care Unit with some limitations. Except for few attempts in the intraoperative detection of pneumothorax, LUS is hardly used but has wider perspective for routine and crisis management in real-time. If anesthesiologists add LUS in their routine monitoring armamentarium, it can assist to move a step ahead in the dynamic management of critically ill and high-risk patients.

  8. Vascular anatomy of strictured small bowel.

    Science.gov (United States)

    Mansard, Magnus Jayaraj; Rao, Upender; Pradeep, R; Sekaran, Anuradha; Rao, G V; Reddy, D N

    2011-01-01

    To investigate the role of ischemia in the pathogenesis of small bowel strictures. Vascular anatomy of 39 small bowel strictures was studied using modified Spalteholtz method. Ten normal small bowel segments were studied as controls. 71.8% of small bowel strictures showed block in the mesenteric vessels (p=0.008). Subset analysis of tuberculous strictures showed block in the mesenteric vessels in 70.8% of strictures (p=0.0098). Ischemia plays a significant role in the pathogenesis of small bowel strictures. Mesenteric vasculopathy has a significant association with tuberculous strictures of the intestine.

  9. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak

    2013-09-01

    Ultrasound guided regional anaesthesia is becoming increasingly popular. The supraclavicular block has been transformed by ultrasound guidance into a potentially safe superficial block. We reviewed the techniques of performing supraclavicular block with special focus on ultrasound guidance.

  10. Cellular senescence in normal and premature lung aging.

    Science.gov (United States)

    Bartling, B

    2013-10-01

    The incidence of chronic respiratory diseases (e.g., chronic obstructive pulmonary disease, COPD) and interstitial lung diseases (e.g., pneumonia and lung fibrosis) increases with age. In addition to immune senescence, the accumulation of senescent cells directly in lung tissue might play a critical role in the increased prevalence of these pulmonary diseases. In the last couple of years, detailed studies have identified the presence of senescent cells in the aging lung and in diseased lungs of patients with COPD and lung fibrosis. Cellular senescence has been shown for epithelial cells of bronchi and alveoli as well as mesenchymal and vascular cells. Known risk factors for pulmonary diseases (cigarette smoke, air pollutions, bacterial infections, etc.) were identified in experimental studies as being possible mediators in the development of cellular senescence. The present findings indicate the importance of cellular senescence in normal lung aging and in premature aging of the lung in patients with COPD, lung fibrosis, and probably other respiratory diseases.

  11. Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells

    OpenAIRE

    Ogawa, Hiroyuki; Koyanagi-Aoi, Michiyo; Otani, Kyoko; Zen, Yoh; Maniwa, Yoshimasa; Aoi, Takashi

    2017-01-01

    In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named ...

  12. Vascularity in thyroid neoplasms

    DEFF Research Database (Denmark)

    Larsen, Karen Kjaer; Andersen, Niels Frost; Melsen, Flemming

    2006-01-01

    The aim of the present study was to evaluate the reliability of four different methods (vascular grading, Chalkley count, microvessel density (MVD) and stereological estimation) for quantifying intratumoral microvascularity in thyroid neoplasms, by comparing the variability within and between...... count should be the preferred method for assessing microvascularity in thyroid neoplasms. The diagnostic evaluation revealed a tendency towards higher degree of vascularity in FA compared to both FC and PC for all methods. No statistically significant association was seen between vascular density...

  13. Ghrelin improves vascular autophagy in rats with vascular calcification.

    Science.gov (United States)

    Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan

    2017-06-15

    This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Douglas class were classified in [3]; they are unilateral block shifts of arbitrary block size (i.e. dim H(n) can be anything). However, no examples of irreducible homogeneous bilateral block shifts of block size larger than 1 were known until now.

  15. Lung Cancer

    Science.gov (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  16. Systemic vasculitis and the lung.

    Science.gov (United States)

    Talarico, Rosaria; Barsotti, Simone; Elefante, Elena; Baldini, Chiara; Tani, Chiara; Mosca, Marta

    2017-01-01

    The purpose of this review is to provide a critical analysis of the recent literature on this topic, with particular focus on the most relevant studies published over the last year. Many studies are published every year on the diagnosis, pathogenesis and treatment of pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). The main subjects covered by this article are the pathogenesis, diagnosis and clinical aspects of lung involvement in ANCA-associated vasculitis and non-ANCA-associated vasculitis. Lung involvement is a common feature in systemic vasculitis. The lungs are one of the most frequently involved organs in systemic vasculitis. In order to provide an update on the recent advances in the pathogenesis, clinical features and novel treatments of lung involvement in systemic vasculitis, a systematic MedLine search has been performed.Most of the data analyzed have confirmed that lung involvement seems to develop more frequently in patients with myeloperoxidase-ANCA-positive AAV, mainly in those with a diagnosis of microscopic polyangiitis (MPA), compared with patients with proteinase 3 ANCA-positive AAV. Moreover, among non-ANCA-associated vasculitis lung involvement may represent a worrying complication of the disease, mainly when associated with vascular involvement.

  17. Vascular disease: Hemorrhage

    International Nuclear Information System (INIS)

    Norman, D.

    1987-01-01

    An understanding of the role of magnetic resonance (MR) in detection and characterization of vascular lesions is evolving. Improvements in spatial detail suggest great promise in delineation of structural vascular lesions, and insights into the appearance of evolving intraparenchymal hematoma have broadened the applications

  18. RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

    Science.gov (United States)

    Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

    2017-10-15

    Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Lung Cancer Screening

    Science.gov (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? Go ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  20. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... was moderately reproduced (kappa = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all...... impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  1. Early detection of acute lung injury uncoupled to hypoxemia in pigs using ultrasound lung comets.

    Science.gov (United States)

    Gargani, Luna; Lionetti, Vincenzo; Di Cristofano, Claudio; Bevilacqua, Generoso; Recchia, Fabio A; Picano, Eugenio

    2007-12-01

    Oleic acid-induced lung injury is an established experimental model of acute lung injury in pigs and is considered to reproduce the early exudative phase of acute respiratory distress syndrome. Ultrasound lung comets are an echographic sign of extravascular lung water, originating from thickened interlobular septa. The objective of this study was to evaluate the timing and relationship between the number of ultrasound lung comets, the Pao2/Fio2 ratio, and the static respiratory compliance in an experimental model of oleic acid-induced lung injury in pigs. Laboratory experiment. Research institute. Ten anesthetized pigs. Acute lung injury was induced by injection of oleic acid (0.1 mL/kg, intravenously). Ultrasound lung comets, Pao2/Fio2, and static respiratory compliance were measured at baseline and at 15, 30, 60, and 90 mins after the injection of oleic acid. We evaluated ultrasound lung comets by transthoracic echography (7.5-MHz vascular probe), scanning on right and left hemithoraxes at 12 predefined scanning sites. Acute lung injury/acute respiratory distress syndrome was present in all pigs at 90 mins. The number of ultrasound lung comets increased over time and was consistently earlier than the decrease in Pao2/Fio2. At 15 mins, ultrasound lung comets were markedly increased, but no significant changes in Pao2/Fio2 were observed. Accordingly, static respiratory compliance was dramatically reduced at 15 mins compared with baseline (17.04 +/- 1.82 vs. 34.84 +/- 2.62 mL/cm H2O, p comets, assessed by transthoracic echography, detected extravascular lung water accumulation very early in the course of the oleic acid lung injury in pigs, in the presence of a normal Pao2/Fio2. These results suggest that ultrasound lung comets could be a very early, noninvasive, and simple method to detect and quantify pulmonary edema in acute lung injury.

  2. Life-supporting function of genetically modified swine lungs in baboons.

    Science.gov (United States)

    Nguyen, Bao-Ngoc H; Azimzadeh, Agnes M; Zhang, Tianshu; Wu, Guosheng; Schuurman, Henk-Jan; Shuurman, Henk-Jan; Sachs, David H; Ayares, David; Allan, James S; Pierson, Richard N

    2007-05-01

    During ex vivo perfusion with human blood, homozygous galactosyl transferase knockout swine lungs exhibit prolonged survival (approximately 2 hours) relative to wild-type (swine lungs expressing human decay accelerating factor (lungs was evaluated. Three galactosyl transferase knockout swine left lungs were transplanted into baboons in a life-supporting model. One baboon lung allograft and two swine lung xenografts transgenic for human membrane cofactor protein (CD46) served as controls. Whereas two membrane cofactor protein lungs exhibited high pulmonary vascular resistance (>500 mm Hg x min/L) and failed to support life within 21 minutes, two of three galactosyl transferase knockout lungs supported life, for 90 and 215 minutes, and displayed low peripheral vascular resistance (48 +/- 12 mm Hg x min/L at 60 minutes), similar to the allogeneic control. Complement activation (delta C3a lungs. Neutrophils, monocytes, and platelets were rapidly sequestered in galactosyl transferase knockout and human membrane cofactor protein lung recipients, unlike the allogeneic control ( 0.5 nmol/L) was seen in the galactosyl transferase knockout recipients. Platelet activation (beta-thromboglobulin rise > 200) and appearance of capillary congestion and vessel thrombosis confirmed coagulation activation associated with galactosyl transferase knockout lung failure. Galactosyl transferase knockout swine lungs are significantly protected in vivo from the physiologic consequences (increased pulmonary vascular resistance, capillary leak) associated with hyperacute lung rejection. As during ex vivo perfusion, dysregulated coagulation-thrombin elaboration, platelet activation, and intravascular thrombosis-mediates galactosyl transferase knockout lung xenograft injury.

  3. Atypical arteriole anastomoses for fingertip replantations under digital block.

    Science.gov (United States)

    Koshima, Isao

    2008-01-01

    Reconstructive microsurgery is now in a new stage of supermicrosurgery. With this technique, very tiny (0.3mm) vascular anastomoses are possible. In this paper, we describe two cases of successful fingertip replantations employing arteriole (terminal branch of digital artery) anastomoses, the arteriole graft being obtained from the same fingertip defect, reverse arteriole flow to subdermal venule, and delayed venular drainage for venous congestion. These atypical tiny vascular anastomoses were successfully carried out under digital block.

  4. Pediatric vascular access

    International Nuclear Information System (INIS)

    Donaldson, James S.

    2006-01-01

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

  5. Vascular Access in Children

    International Nuclear Information System (INIS)

    Krishnamurthy, Ganesh; Keller, Marc S.

    2011-01-01

    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.

  6. Vascular endothelium receptors and transduction mechanisms

    CERN Document Server

    Gillis, C; Ryan, Una; Proceedings of the Advanced Studies Institute on "Vascular Endothelium: Receptors and Transduction Mechanisms"

    1989-01-01

    Beyond their obvious role of a barrier between blood and tissue, vascular endothelial cells are now firmly established as active and essential participants in a host of crucial physiological and pathophysiological functions. Probably the two most important factors responsible for promoting the current knowledge of endothelial functions are 1) observations in the late sixties-early seventies that many non-ventilatory properties of the lung could be attributed to the pulmonary endothelium and 2) the establishment, in the early and mid-seventies of procedures for routine culture of vascular endothelial cells. Many of these endothelial functions require the presence of receptors on the surface of the plasma membrane. There is now evidence for the existence among others of muscarinic, a-and /3-adrenergic, purine, insulin, histamine, bradykinin, lipoprotein, thrombin, paf, fibronectin, vitronectin, interleukin and albumin receptors. For some of these ligands, there is evidence only for the existence of endothelial ...

  7. Vascular malformations in pediatrics

    International Nuclear Information System (INIS)

    Reith, W.; Shamdeen, M.G.

    2003-01-01

    Vascular malformations are the cause of nearly all non-traumatic intracranial hemorrhage in children beyond the neonatal stage. Therefore, any child presenting with spontaneous intracranial hemorrhage should be evaluated for child abuse and for vascular malformations. Intracerebral malformations of the cerebral vasculature include vein of Galen malformations, arteriovenous malformation (AVM), cavernomas, dural arteriovenous fistulas, venous anomalies (DVA), and capillary teleangiectasies. Although a few familial vascular malformation have been reported, the majority are sporadic. Clinical symptoms, diagnostic and therapeutic options are discussed. (orig.) [de

  8. Lung cancer

    Science.gov (United States)

    ... causing chemicals such as uranium, beryllium, vinyl chloride, nickel chromates, coal products, mustard gas, chloromethyl ethers, gasoline, and diesel exhaust Exposure to radon gas Family history of lung cancer ...

  9. Congenital Vascular Malformation

    Science.gov (United States)

    ... surgery or less invasive therapy of the enlarged superficial veins can also be helpful. T he V ascular D isease F oundation Established in 1998, t he Vascular Disease Foundation (VDF) develops educational information and initiatives for patients, ...

  10. Uterine Vascular Lesions

    Science.gov (United States)

    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

  11. Heart and vascular services

    Science.gov (United States)

    ... maintain body temperature, among other things. CARDIOVASCULAR MEDICINE Cardiovascular medicine refers to the branch of health care that specializes in the treatment of diseases or conditions dealing with the heart and vascular systems. Common ...

  12. Vascular Access Procedures

    Science.gov (United States)

    ... vascular access catheters: A peripherally inserted central catheter (PICC) is a long catheter that extends from an ... central catheter may be larger caliber than a PICC, and is designed to be placed via a ...

  13. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    A new 3-parameter family of homogeneous 2-by-2 block shifts is described. These are the first examples of irreducible homogeneous bilateral block shifts of block size larger than 1. Author Affiliations. Adam Korányi1. Department of Mathematics, The Graduate Center, City University of New York, New York, NY 10016, USA ...

  14. Ultrasound for vascular access in pediatric patients.

    Science.gov (United States)

    Schindler, Ehrenfried; Schears, Gregory J; Hall, Stuart R; Yamamoto, Tomohiro

    2012-10-01

    In pediatric patients vascular access is often more difficult than in adults because of the smaller size of the vessels and the inability of the patient to cooperate without deep sedation or general anesthesia. Therefore Ultrasound has already become an invaluable tool for vascular access, but the full potential of ultrasound has yet to be fully realized. Improvements in image quality and a better understanding of optimal insertion techniques continue to help clinicians safely and efficiently place catheters with fewer complications. The probes used for the vascular access are mainly linear and convex type. Higher- frequency ultrasound provides a vivid image; however, the signals are remarkably attenuated. Therefore, the choice of the probe with appropriate frequency is essential. As blood vessels are relatively easily identified with ultrasound, ultrasound-guided vascular access does not require as sharp images as ultrasound-guided nerve block. For pediatric vascular access, the linear probe with 5-15 MHz, 2-5 cm depth is ideal and adequate for almost all cases. Ultrasound-guided vascular access has two main approaches: 'long-axis' or 'in-plane approach' and 'short-axis' or 'transverse approach'. The long-axis approach visualizes the vessel along the insertion pathway and is commonly used to monitor the entire approach of the needle into the vessel. The short-axis approach is easier to show the positional relationship and depth of target vessels, but it is much harder to follow the needle tip within the tissues. The use of 'real-time' ultrasound has been shown to increase first insertion success, reduce access time, have a higher overall success, and reduce arterial puncture. As the technology continues to improve the use of ultrasound will become as ubiquitous as the lines themselves. © 2012 Blackwell Publishing Ltd.

  15. Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies.

    Science.gov (United States)

    Morin, Jean-Paul; Baste, Jean-Marc; Gay, Arnaud; Crochemore, Clément; Corbière, Cécile; Monteil, Christelle

    2013-01-01

    1.We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches. 2.Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology. 3.A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture. They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting. 4.Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.

  16. Lung function

    International Nuclear Information System (INIS)

    Sorichter, S.

    2009-01-01

    The term lung function is often restricted to the assessment of volume time curves measured at the mouth. Spirometry includes the assessment of lung volumes which can be mobilised with the corresponding flow-volume curves. In addition, lung volumes that can not be mobilised, such as the residual volume, or only partially as FRC and TLC can be measured by body plethysmography combined with the determination of the airway resistance. Body plethysmography allows the correct positioning of forced breathing manoeuvres on the volume-axis, e.g. before and after pharmacotherapy. Adding the CO single breath transfer factor (T LCO ), which includes the measurement of the ventilated lung volume using He, enables a clear diagnosis of different obstructive, restrictive or mixed ventilatory defects with and without trapped air. Tests of reversibility and provocation, as well as the assessment of inspiratory mouth pressures (PI max , P 0.1 ) help to classify the underlying disorder and to clarify treatment strategies. For further information and to complete the diagnostic of disturbances of the ventilation, diffusion and/or perfusion (capillar-)arterial bloodgases at rest and under physical strain sometimes amended by ergospirometry are recommended. Ideally, lung function measurements are amended by radiological and nuclear medicine techniques. (orig.) [de

  17. Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: A better model

    Energy Technology Data Exchange (ETDEWEB)

    Dong Qingshan [Department of Oral and Maxillofacial Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070 (China); Shang Hongtao; Wu Wei [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Chen Fulin [Lab of Tissue Engineering, Faculty of Life Science, Northwest University, Xi' an 710069 (China); Zhang Junrui [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China); Guo Jiaping [Department of Oral and Maxillofacial Surgery, Wuhan General Hospital of Guangzhou Military Command, Wuhan 430070 (China); Mao Tianqiu, E-mail: tianqiumao@126.com [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China)

    2012-08-01

    The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone. - Highlights: Black-Right-Pointing-Pointer A modified arteriovenous loop (AVL) model in rabbit was developed in this study. Black-Right-Pointing-Pointer Axial prevascularization was induced in a larger coral block by using the AVL. Black-Right-Pointing-Pointer The prefabrication of axial vascularized coral bone is superior as vascular carrier.

  18. Prefabrication of axial vascularized tissue engineering coral bone by an arteriovenous loop: A better model

    International Nuclear Information System (INIS)

    Dong Qingshan; Shang Hongtao; Wu Wei; Chen Fulin; Zhang Junrui; Guo Jiaping; Mao Tianqiu

    2012-01-01

    The most important problem for the survival of thick 3-dimensional tissues is the lack of vascularization in the context of bone tissue engineering. In this study, a modified arteriovenous loop (AVL) was developed to prefabricate an axial vascularized tissue engineering coral bone in rabbit, with comparison of the arteriovenous bundle (AVB) model. An arteriovenous fistula between rabbit femoral artery and vein was anastomosed to form an AVL. It was placed in a circular side groove of the coral block. The complex was wrapped with an expanded-polytetrafluoroethylene membrane and implanted beneath inguinal skin. After 2, 4, 6 and 8 weeks, the degree of vascularization was evaluated by India ink perfusion, histological examination, vascular casts, and scanning electron microscopy images of vascular endangium. Newly formed fibrous tissues and vasculature extended over the surfaces and invaded the interspaces of entire coral block. The new blood vessels robustly sprouted from the AVL. Those invaginated cavities in the vascular endangium from scanning electron microscopy indicated vessel's sprouted pores. Above indexes in AVL model are all superior to that in AVB model, indicating that the modified AVL model could more effectively develop vascularization in larger tissue engineering bone. - Highlights: ► A modified arteriovenous loop (AVL) model in rabbit was developed in this study. ► Axial prevascularization was induced in a larger coral block by using the AVL. ► The prefabrication of axial vascularized coral bone is superior as vascular carrier.

  19. Antioxidants and vascular health.

    Science.gov (United States)

    Bielli, Alessandra; Scioli, Maria Giovanna; Mazzaglia, Donatella; Doldo, Elena; Orlandi, Augusto

    2015-12-15

    Oxygen free radicals and other reactive oxygen species (ROS) are common products of normal aerobic cellular metabolism, but high levels of ROS lead to oxidative stress and cellular damage. Increased production of ROS favors vascular dysfunction, inducing altered vascular permeability and inflammation, accompanied by the loss of vascular modulatory function, the imbalance between vasorelaxation and vasoconstriction, and the aberrant expression of inflammatory adhesion molecules. Inflammatory stimuli promote oxidative stress generated from the increased activity of mitochondrial nicotinamide adenine dinucleotide phosphate oxidase, particularly of the Nox4 isoform, with the consequent impairment of mitochondrial β-oxidation. Vascular dysfunction due to the increase in Nox4 activity and ROS overproduction leads to the progression of cardiovascular diseases, diabetes, inflammatory bowel disease, and neurological disorders. Considerable research into the development of effective antioxidant therapies using natural derivatives or new synthetic molecules has been conducted. Antioxidants may prevent cellular damage by reducing ROS overproduction or interfering in reactions that involve ROS. Vitamin E and ascorbic acid are well known as natural antioxidants that counteract lipid peroxidative damage by scavenging oxygen-derived free radicals, thus restoring vascular function. Recently, preliminary studies on natural antioxidants such as goji berries, thymus, rosemary, green tea ginseng, and garlic have been conducted for their efficacy in preventing vascular damage. N-acetyl-cysteine and propionyl-L-carnitine are synthetic compounds that regulate ROS production by replacing endogenous antioxidants in both endothelial and smooth muscle cells. In this review, we consider the molecular mechanisms underlying the generation of oxidative stress-induced vascular dysfunction as well as the beneficial effects of antioxidant therapies.

  20. Lung cancer - small cell

    Science.gov (United States)

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  1. Interstitial Lung Diseases

    Science.gov (United States)

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

  2. Blocked Randomization with Randomly Selected Block Sizes

    Directory of Open Access Journals (Sweden)

    Jimmy Efird

    2010-12-01

    Full Text Available When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  3. Blocked randomization with randomly selected block sizes.

    Science.gov (United States)

    Efird, Jimmy

    2011-01-01

    When planning a randomized clinical trial, careful consideration must be given to how participants are selected for various arms of a study. Selection and accidental bias may occur when participants are not assigned to study groups with equal probability. A simple random allocation scheme is a process by which each participant has equal likelihood of being assigned to treatment versus referent groups. However, by chance an unequal number of individuals may be assigned to each arm of the study and thus decrease the power to detect statistically significant differences between groups. Block randomization is a commonly used technique in clinical trial design to reduce bias and achieve balance in the allocation of participants to treatment arms, especially when the sample size is small. This method increases the probability that each arm will contain an equal number of individuals by sequencing participant assignments by block. Yet still, the allocation process may be predictable, for example, when the investigator is not blind and the block size is fixed. This paper provides an overview of blocked randomization and illustrates how to avoid selection bias by using random block sizes.

  4. 31 CFR 595.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TERRORISM SANCTIONS REGULATIONS General Definitions § 595.301 Blocked account; blocked property. The terms blocked account and blocked...

  5. Lung radiopharmaceuticals

    International Nuclear Information System (INIS)

    Gonzalez, B.M.

    1994-01-01

    Indication or main clinical use of Lung radiopharmaceuticals is presented and clasification of radiopharmaceuticals as ventilation and perfusion studies. Perfusion radiopharmaceuticals, main controls for administration quality acceptance. Clearence after blood administration and main clinical applications. Ventilation radiopharmaceuticals, gases and aerosols, characteristics of a ideal radioaerosol, techniques of good inhalation procedure, clinical applications. Comparison of several radiopharmaceuticals reflering to retention time as 50% administered dose, percent administered dose at 6 hours post inhalation, blood activity at 30 and 60 minutes post inhalation, initial lung absorbed dose, cumulated activity.Kinetic description of two radiopharmaceuticals, 99mTcDTPA and 99mTc-PYP

  6. Welders’ lung

    Directory of Open Access Journals (Sweden)

    Izidor Kern

    2010-02-01

    Conclusions: h is study coni rms that longterm welders may have symptoms with no functional disorders, but with prominent morphological changes. h e key to correct diagnosis is an occupational history of the patient. Diagnostic work-up includes funda-mental procedures in suspected interstitial lung disease. h e best therapy is cessation of exposure.

  7. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M

    1999-01-01

    The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxins...

  8. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe

    2015-01-01

    Block tearing is considered in several codes as a pure block tension or a pure block shear failure mechanism. However in many situations the load acts eccentrically and involves the transfer of a substantial moment in combination with the shear force and perhaps a normal force. A literature study...... shows that no readily available tests with a well-defined substantial eccentricity have been performed. This paper presents theoretical and experimental work leading towards generalized block failure capacity methods. Simple combination of normal force, shear force and moment stress distributions along...

  9. Vascular tone and reactivity to serotonin in the internal and external carotid vascular beds of the dog.

    Science.gov (United States)

    Vidrio, H; Hong, E

    1976-04-01

    The effects of intra-arterial infusions of serotonin on internal and external carotid blood flow were determined in anesthetized dogs by electromagnetic flow measurements. Serotonin decreased flow in the internal carotid and increased it in the external carotid. Both responses were blocked by the serotonin antagonist methysergide. The alpha adrenergic antagonist zolertine, the ganglionic blocking agent chlorisondamine and the vasodilator diazoxide blocked external carotid dilator responses but did not modify constriction in the internal carotid. Blockade of external carotid responses by the three drugs was also demonstrated in experiments in which this bed was perfused at a constant rate. These results indicate that the internal and external carotid vascular beds of the dog react in opposite ways to serotonin, that both responses are mediated through the same type of serotonin receptors and that the dilator responses of the external carotid are dependent on vascular tone.

  10. tion of vascular malformations

    African Journals Online (AJOL)

    Imaging is only required in cases where there is diag- nostic uncertainty or where interven- tion is required. Ultrasound (with doppler) will rapidly distinguish solid haemangiomas from vascular malfor- mations. Computed tomography. (CT) and magnetic resonance imag- ing (MRI) will help to assess the depth and extent of ...

  11. Active Component of Danshen (Salvia miltiorrhiza Bunge, Tanshinone I, Attenuates Lung Tumorigenesis via Inhibitions of VEGF, Cyclin A, and Cyclin B Expressions

    Directory of Open Access Journals (Sweden)

    Yu-Tang Tung

    2013-01-01

    Full Text Available Tanshinone I (T1 and tanshinone II (T2 are the major diterpenes isolated from Danshen (Salvia miltiorrhiza Bunge. Three human lung adenocarcinoma cell lines, A549, CL1-0, and CL1-5, were treated with T1 and T2 for the in vitro antitumor test. Results showed that T1 was more effective than T2 in inhibiting the growth of lung cancer cells via suppressing the expression of VEGF, Cyclin A, and Cyclin B proteins in a dose-dependent manner. Moreover, a transgenic mice model of the human vascular endothelial growth factor-A165 (hVEGF-A165 gene-induced pulmonary tumor was further treated with T1 for the in vivo lung cancer therapy test. T1 significantly attenuated hVEGF-A165 overexpression to normal levels of the transgenic mice (Tg that were pretreated with human monocytic leukemia THP-1 cell-derived conditioned medium (CM. It also suppressed the formation of lung adenocarcinoma tumors (16.7% compared with two placebo groups (50% for Tg/Placebo and 83.3% for Tg/CM/Placebo; P<0.01. This antitumor effect is likely to slow the progression of cells through the S and G2/M phases of the cell cycle. Blocking of the tumor-activated cell cycle pathway may be a critical mechanism for the observed antitumorigenic effects of T1 treatment on vasculogenesis and angiogenesis.

  12. Acupuncture for vascular dementia.

    Science.gov (United States)

    Peng, W N; Zhao, H; Liu, Z S; Wang, S

    2007-04-18

    Dementia is a widespread condition characterized by acquired global impairment of intellect, memory and personality, but with no impairment of consciousness. There is no definitive medical or surgical treatment for vascular dementia. Acupuncture is an ancient Chinese method which has been used for both the prevention and treatment of diseases for over three thousand years. Preliminary searches revealed more than 105 studies of acupuncture for treating vascular dementia. Benefit was reported in up to 70-91% of the treatment group. Body acupuncture and electroacupuncture were the most commonly used techniques. A comparison of electroacupuncture and acupuncture therapy alone suggested that the former was more effective in promoting the recovery of cognitive function. The objective is to assess the efficacy and possible adverse effects of acupuncture therapy for treating vascular dementia. The trials were identified from a search of the Cochrane Dementia and Cognitive Improvement group's Specialized Register on 2 February 2007 which contains records from all major health care databases and many ongoing trials databases. In addition the Allied and Complementary Medicine Database was searched and the web was searched using the search engine Copernic. Randomized controlled trials testing acupuncture therapy in the treatment of vascular dementia were included regardless of language and publication types. The intervention and control group had to receive identical treatment apart from the acupuncture intervention. In view of possible confounding, studies in which acupuncture was combined with other treatments were subjected to subgroup analyses. Titles and abstracts identified from the searches were checked by two reviewers. If it was clear that the study did not refer to a randomized controlled trial in vascular dementia, it was excluded. If it was not clear from the abstract and title, then the full text of study was obtained for an independent assessment by two reviewers

  13. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav

    2003-01-01

    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  14. The extracellular matrix - the under-recognized element in lung disease?

    NARCIS (Netherlands)

    Burgess, Janette K.; Mauad, Thais; Tjin, Gavin; Karlsson, Jenny C.; Westergren-Thorsson, Gunilla

    2016-01-01

    The lung is composed of airways and lung parenchyma, and the extracellular matrix (ECM) contains the main building blocks of both components. The ECM provides physical support and stability to the lung, and as such it has in the past been regarded as an inert structure. More recent research has

  15. Homogeneous bilateral block shifts

    Indian Academy of Sciences (India)

    Homogeneous bilateral block shifts. ADAM KORÁNYI. Department of Mathematics, The Graduate Center, City University of New York,. New York, NY 10016, USA. E-mail: Adam.Koranyi@lehman.cuny.edu. MS received 18 January 2013. Abstract. A new 3-parameter family of homogeneous 2-by-2 block shifts is described.

  16. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim

    2010-01-01

    Related Drupal Nodes Block This module exposes a block that uses Latent Semantic Analysis (Lsa) internally to suggest three nodes that are relevant to the node a user is viewing. This module performs three tasks. 1) It periodically indexes a Drupal site and generates a Lsa Term Document Matrix.

  17. Control rod blocking monitor

    International Nuclear Information System (INIS)

    Suzuki, Shigeru.

    1993-01-01

    The number of times for setting up a control rod blocking monitor of a BWR type power plant is remarkably reduced to mitigate operator's burden. In the control rod blocking monitor, trip levels, as a judging standard upon outputting control rod blocking inhibition signals, are set up stepwise depending on the power level around control rods put to blocking control. The present invention comprises an allowance judging means capable of setting up trip levels for each of power levels corresponding to a plurality of control rods at once if the power levels are within the set up allowable range. With such a constitution, the set up allowable range is determined previously in the allowance judging means. Accordingly, when a gang blocking is conducted to control rods, if power levels around the control rods are increased at once into the set up allowable range, the trip levels for each of the control rods are set up at once. (I.S.)

  18. The pulmonary mesenchyme directs lung development.

    Science.gov (United States)

    McCulley, David; Wienhold, Mark; Sun, Xin

    2015-06-01

    Each of the steps of respiratory system development relies on intricate interactions and coordinated development of the lung epithelium and mesenchyme. In the past, more attention has been paid to the epithelium than the mesenchyme. The mesenchyme is a source of specification and morphogenetic signals as well as a host of surprisingly complex cell lineages that are crucial for normal lung development and function. This review highlights recent research focusing on the mesenchyme that has revealed genetic and epigenetic mechanisms of its development in the context of other cell layers during respiratory lineage specification, branching morphogenesis, epithelial differentiation, lineage distinction, vascular development, and alveolar maturation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M

    1999-01-01

    The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxi...... II trials, but results from large phase III trials are necessary in order to measure the impact of these new agents in the management of NSCLC. Major improvements of therapy for mesothelioma have not occurred within the last year....

  20. Hyperlucent lung

    International Nuclear Information System (INIS)

    Jimenez-Gutierrez, Florana; Soto-Quiros, Manuel E.

    2007-01-01

    Unilateral hyperlucent lung is also known as Swyer-James Syndrome, Macleod Syndrome or lobular or unilateral emphysema. It is an uncommon disease characterized by lung or unilateral lobe hiperlucency associated to an air trapping upon expiration. As regards to etiology, this syndrome is considered to be an acquired disease that appears secondary to respiratory infections during the early years of life, probably bronchiolitis and/ or viral pneumonia. The clinical presentation varies among patients. Some of them are asymptomatic, others present a history of recurrent episodes of pulmonary infections from early years of life or present effort dyspnea. The diagnosis is usually made accidentally by a chest radiograph in a child with history of respiratory infections or in an adult during a routine chest x- ray in an asymptomatic person. It is important to differentiate this syndrome from other causes of unilateral pulmonary hiperlucency on conventional chest x-rays. Few cases of Swyer-James Syndrome in children have been reported, it is presented the clinical case of a patient who had a parainfluenza 3 bronchopneumonia when he was a month and eighteen days of age. The differential diagnosis of this syndrome should be done with other thoracic entities that diminish the radiological pulmonary unilateral density. A case of a child who is the bearer of hyperlucent lung is described. (author) [es

  1. Lung function is associated with arterial stiffness in children.

    Directory of Open Access Journals (Sweden)

    Julian G Ayer

    Full Text Available BACKGROUND: In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life. OBJECTIVE: To determine the relationship between lung function and carotid augmentation index (AIx, a measure of vascular stiffness, in 8-year old children. METHODS: Data on brachial blood pressure, lung function (FEV(1, FVC, FEV(1/FVC, obtained by spirometry and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention as covariates. RESULTS: In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = -0.17,b = -6.72, partial R(2 = .02, p = 0.03, FVC (standardised β = -0.29, b = -9.31, partial R(2 = 0.04, p<0.001 and FEV1/FVC (standardised β = .13, b = 18.4, partial R(2 = 0.02, p = 0.04. CONCLUSION: Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.

  2. Monoacylglycerol lipase (MAGL inhibition attenuates acute lung injury in mice.

    Directory of Open Access Journals (Sweden)

    Carolina Costola-de-Souza

    Full Text Available Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that, for 2-Arachidonoylglycerol (2-AG, is mediated by monoacylglycerol lipase (MAGL. The piperidine carbamate, 4-nitrophenyl- 4-(dibenzo[d] [1,3]dioxol-5-yl (hydroxy methyl piperidine- 1-carboxylate (JZL184, is a drug that inhibits MAGL and presents high potency and selectivity. Thus, JZL184 increases the levels of 2-AG, an endocannabinoid that acts on the CB1 and CB2 cannabinoid receptors. Here, we investigated the effects of MAGL inhibition, with a single dose (16 mg/kg, intraperitoneally (i.p. of JZL184, in a murine model of lipopolysaccharide (LPS -induced acute lung injury (ALI 6, 24 and 48 hours after the inflammatory insult. Treatment with JZL184 decreased the leukocyte migration into the lungs as well as the vascular permeability measured through the bronchoalveolar lavage fluid (BAL and histological analysis. JZL184 also reduced the cytokine and chemokine levels in the BAL and adhesion molecule expression in the blood and BAL. The CB1 and CB2 receptors were considered involved in the anti-inflammatory effects of JZL184 because the AM281 selective CB1 receptor antagonist (1-(2,4-dichlorophenyl-5-(4-iodophenyl-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide and the AM630 selective CB2 receptor antagonist ([6-iodo-2-methyl-1-[2-(4-morpholinylethyl]-1H-indol-3-yl](4-methoxyphenyl-methanone blocked the anti-inflammatory effects previously described for JZL184. It was concluded that MAGL inhibition, and consequently the increase in 2-AG levels, produced anti-inflammatory effects in a murine model of LPS-induced ALI, a finding that was considered a consequence of the activation of the CB1 and CB2 receptors.

  3. Blockade of Vascular Endothelial Growth Factor Receptor 1 Prevents Inflammation and Vascular Leakage in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Jianbo He

    2015-01-01

    Full Text Available Diabetic retinopathy (DR is a leading cause of blindness in working age adults. The objective of this study is to investigate the effects of vascular endothelial growth factor receptor 1 (VEGFR1 blockade on the complications of DR. Experimental models of diabetes were induced with streptozotocin (STZ treatment or Insulin2 gene mutation (Akita in mice. Protein expression and localization were examined by western blots (WB and immunofluorescence (IF. mRNA expression was quantified by PCR array and real-time PCR. The activity of VEGFR1 signaling was blocked by a neutralizing antibody called MF1. Vascular leakage was evaluated by measuring the leakage of [3H]-mannitol tracer into the retina and the IF staining of albumin. VEGFR1 blockade significantly inhibited diabetes-related vascular leakage, leukocytes-endothelial cell (EC adhesion (or retinal leukostasis, expression of intercellular adhesion molecule- (ICAM- 1 protein, abnormal localization and degeneration of the tight junction protein zonula occludens- (ZO- 1, and the cell adhesion protein vascular endothelial (VE cadherin. In addition, VEGFR1 blockade interfered with the gene expression of 10 new cytokines and chemokines: cxcl10, il10, ccl8, il1f6, cxcl15, ccl4, il13, ccl6, casp1, and ccr5. These results suggest that VEGFR1 mediates complications of DR and targeting this signaling pathway represents a potential therapeutic strategy for the prevention and treatment of DR.

  4. Predictability of blocking

    International Nuclear Information System (INIS)

    Tosi, E.; Ruti, P.; Tibaldi, S.; D'Andrea, F.

    1994-01-01

    Tibaldi and Molteni (1990, hereafter referred to as TM) had previously investigated operational blocking predictability by the ECMWF model and the possible relationships between model systematic error and blocking in the winter season of the Northern Hemisphere, using seven years of ECMWF operational archives of analyses and day 1 to 10 forecasts. They showed that fewer blocking episodes than in the real atmosphere were generally simulated by the model, and that this deficiency increased with increasing forecast time. As a consequence of this, a major contribution to the systematic error in the winter season was shown to derive from the inability of the model to properly forecast blocking. In this study, the analysis performed in TM for the first seven winter seasons of the ECMWF operational model is extended to the subsequent five winters, during which model development, reflecting both resolution increases and parametrisation modifications, continued unabated. In addition the objective blocking index developed by TM has been applied to the observed data to study the natural low frequency variability of blocking. The ability to simulate blocking of some climate models has also been tested

  5. Inhibition ofαvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    McCurley, Amy; Alimperti, Stella; Campos-Bilderback, Silvia B; Sandoval, Ruben M; Calvino, Jenna E; Reynolds, Taylor L; Quigley, Catherine; Mugford, Joshua W; Polacheck, William J; Gomez, Ivan G; Dovey, Jennifer; Marsh, Graham; Huang, Angela; Qian, Fang; Weinreb, Paul H; Dolinski, Brian M; Moore, Shaun; Duffield, Jeremy S; Chen, Christopher S; Molitoris, Bruce A; Violette, Shelia M; Crackower, Michael A

    2017-06-01

    Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The α v β 5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit α v β 5 in a rat model of renal IRI. Pretreatment with this anti- α v β 5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the α v β 5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that α v β 5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with α v β 5 antibody treatment. Immunostaining for α v β 5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for α v β 5 in modulating vascular leak. Additional studies showed α v β 5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with α v β 5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for α v β 5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal α v β 5 inhibition as a promising therapeutic strategy for AKI. Copyright © 2017 by the American Society of Nephrology.

  6. Hypoxic vasoconstriction of partial muscular intra-acinar pulmonary arteries in murine precision cut lung slices

    Directory of Open Access Journals (Sweden)

    Goldenberg Anna

    2006-06-01

    Full Text Available Abstract Background Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV which serves to match lung perfusion to ventilation. The underlying mechanisms are not fully resolved yet. The major vascular segment contributing to HPV, the intra-acinar artery, is mostly located in that part of the lung that cannot be selectively reached by the presently available techniques, e.g. hemodynamic studies of isolated perfused lungs, recordings from dissected proximal arterial segments or analysis of subpleural vessels. The aim of the present study was to establish a model which allows the investigation of HPV and its underlying mechanisms in small intra-acinar arteries. Methods Intra-acinar arteries of the mouse lung were studied in 200 μm thick precision-cut lung slices (PCLS. The organisation of the muscle coat of these vessels was characterized by α-smooth muscle actin immunohistochemistry. Basic features of intra-acinar HPV were characterized, and then the impact of reactive oxygen species (ROS scavengers, inhibitors of the respiratory chain and Krebs cycle metabolites was analysed. Results Intra-acinar arteries are equipped with a discontinuous spiral of α-smooth muscle actin-immunoreactive cells. They exhibit a monophasic HPV (medium gassed with 1% O2 that started to fade after 40 min and was lost after 80 min. This HPV, but not vasoconstriction induced by the thromboxane analogue U46619, was effectively blocked by nitro blue tetrazolium and diphenyleniodonium, indicating the involvement of ROS and flavoproteins. Inhibition of mitochondrial complexes II (3-nitropropionic acid, thenoyltrifluoroacetone and III (antimycin A specifically interfered with HPV, whereas blockade of complex IV (sodium azide unspecifically inhibited both HPV and U46619-induced constriction. Succinate blocked HPV whereas fumarate had minor effects on vasoconstriction. Conclusion This study establishes the first model for investigation of basic characteristics of HPV

  7. Major Vascular Neurocognitive Disorder: A Reappraisal to Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Emre Kumral

    2017-03-01

    Full Text Available Major vascular neurocognitive disorder (NCD is the second leading form of dementia after Alzheimer’s disease, accounting for 17-20% of all dementias. Vascular NCD is a progressive disease caused by reduced cerebral blood flow related to multiple large volume or lacunar infarcts that induce a sudden onset and stepwise decline in cognitive abilities. Despite its prevalence and clinical importance, there is still controversy in the terminology of vascular NCD. Only after the release of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 (2013 did the American Psychiatric Association define vascular dementia as “major vascular NCD”. This review includes an overview of risk factors, pathophysiology, types, diagnostic and clinical features of major vascular NCD, and current treatment options of vascular NCD regarding to DSM-5 criteria

  8. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  9. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Vascular Thoracic Outlet Syndrome.

    Science.gov (United States)

    Hussain, Mohamad Anas; Aljabri, Badr; Al-Omran, Mohammed

    2016-01-01

    Two distinct terms are used to describe vascular thoracic outlet syndrome (TOS) depending on which structure is predominantly affected: venous TOS (due to subclavian vein compression) and arterial TOS (due to subclavian artery compression). Although the venous and arterial subtypes of TOS affect only 3% and <1% of all TOS patients respectively, the diagnostic and management approaches to venous and arterial TOS have undergone considerable evolution due to the recent emergence of minimally invasive endovascular techniques such as catheter-directed arterial and venous thrombolysis, and balloon angioplasty. In this review, we discuss the anatomical factors, etiology, pathogenesis and clinical presentation of vascular TOS patients. In addition, we use the most up to date observational evidence available to provide a contemporary approach to the diagnosis and management of venous TOS and arterial TOS patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Engineered vascularized bone grafts

    OpenAIRE

    Tsigkou, Olga; Pomerantseva, Irina; Spencer, Joel A.; Redondo, Patricia A.; Hart, Alison R.; O’Doherty, Elisabeth; Lin, Yunfeng; Friedrich, Claudia C.; Daheron, Laurence; Lin, Charles P.; Sundback, Cathryn A.; Vacanti, Joseph P.; Neville, Craig

    2010-01-01

    Clinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce host neovascularization at the graft surface, but hypoxic conditions cause cell death at the core. Addition of cellular components that generate an extensive primitive plexus-like vascular network that would perfuse the entire scaffold upon anastomosis could potentially yield significantly higher-quality grafts. W...

  12. Pulmonary vascular imaging

    Energy Technology Data Exchange (ETDEWEB)

    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.

  13. Vascular lesions following radiation

    International Nuclear Information System (INIS)

    Fajardo, L.F.; Berthrong, M.

    1988-01-01

    The special radiation sensitivity of the vascular system is mainly linked to that of endothelial cells, which are perhaps the most radiation-vulnerable elements of mesenchymal tissues. Within the vascular tree, radiation injures most often capillaries, sinusoids, and small arteries, in that order. Lesions of veins are observed less often, but in certain tissues the veins are regularly damaged (e.g., intestine) or are the most affected structures (i.e., liver). Large arteries do suffer the least; however, when significant damage does occur in an elastic artery (e.g., thrombosis or rupture), it tends to be clinically significant and even fatal. Although not always demonstrable in human tissues, radiation vasculopathy generally is dose and time dependent. Like other radiation-induced lesions, the morphology in the vessels is not specific, but it is characteristic enough to be often recognizable. Vascular injury, especially by therapeutic radiation is not just a morphologic marker. It is a mediator of tissue damage; perhaps the most consistent pathogenetic mechanism in delayed radiation injury

  14. Pulmonary vascular imaging

    International Nuclear Information System (INIS)

    Fedullo, P.F.; Shure, D.

    1987-01-01

    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

  15. 31 CFR 594.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY GLOBAL TERRORISM SANCTIONS REGULATIONS General Definitions § 594.301 Blocked account; blocked property. The terms blocked account and...

  16. Bundle Branch Block

    Science.gov (United States)

    ... 2015. Bundle branch block Symptoms & causes Diagnosis & treatment Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  17. Blocked Urethral Valves

    Science.gov (United States)

    ... the penis. Rarely, small membranes form across the urethra in boys early in pregnancy, and they can block the flow of urine out of the bladder. These membranes are called posterior urethral valves and can have life-threatening consequences ...

  18. Optoelectronics using block copolymers.

    Energy Technology Data Exchange (ETDEWEB)

    Botiz, I.; Darling, S. B.; Center for Nanoscale Materials

    2010-05-01

    Block copolymers, either as semiconductors themselves or as structure directors, are emerging as a promising class of materials for understanding and controlling processes associated with both photovoltaic energy conversion and light emitting devices.

  19. Mechanisms for suppressing NADPH oxidase in the vascular wall

    Directory of Open Access Journals (Sweden)

    Gregory J Dusting

    2005-03-01

    Full Text Available Oxidative stress underlies many forms of vascular disease as well as tissue injury following ischemia and reperfusion. The major source of oxidative stress in the artery wall is an NADPH oxidase. This enzyme complex as expressed in vascular cells differs from that in phagocytic leucocytes both in biochemical structure and functions. The crucial flavin-containing catalytic subunits, Nox1 and Nox4, are not found in leucocytes, but are highly expressed in vascular cells and upregulated with vascular remodeling, such as that found in hypertension and atherosclerosis. The difference in catalytic subunits offers the opportunity to develop "vascular specific" NADPH oxidase inhibitors that do not compromise the essential physiological signaling and phagocytic functions carried out by reactive oxygen and nitrogen species. Nitric oxide and targeted inhibitors of NADPH oxidase that block the source of oxidative stress in the vasculature are more likely to prevent the deterioration of vascular function that leads to stroke and heart attack, than are conventional antioxidants. The roles of Nox isoforms in other inflammatory conditions are yet to be explored.

  20. How Lungs Work

    Science.gov (United States)

    ... Health and Diseases > How Lungs Work How Lungs Work The Respiratory System Your lungs are part of ... Parts of the Respiratory System and How They Work Airways SINUSES are hollow spaces in the bones ...

  1. Lung diffusion testing

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003854.htm Lung diffusion testing To use the sharing features on this page, please enable JavaScript. Lung diffusion testing measures how well the lungs exchange gases. This ...

  2. Belatacept for Maintenance Immunosuppression in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Christine Hui PharmD

    2014-06-01

    Full Text Available Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS. In the third year posttransplant, he developed hemolytic uremic syndrome (HUS attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed.

  3. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    IL-10 has regulatory effects in vitro on cytokine production by activated macrophages. In the IgG immune complex model of lung injury, exogenously administered IL-10 has been shown to suppress in vivo formation of TNF-alpha, up-regulation of vascular ICAM-1, neutrophil recruitment, and ensuing lung...

  4. Physiological and biochemical aspects of the effect of ionizing radiations on the lung parenchyma

    International Nuclear Information System (INIS)

    Pasquier, Christian.

    1975-03-01

    Concerning the biochemical reactions of the lung parenchyma to irradiation the following points have been developed. Role of biochemically active substances (histamine, serotonin, kinins, catecholamines, prostaglandins) in the early reaction of the lung to irradiation, their common feature being their vascular impact point. Lung irradiation and lipids (fatty acids and lipid metabolism in general); irradiation, by raising the proportion of unsaturated at the expense of saturated fatty acids, may give rise to serious physiological respiratory disorders. Lung irradiation and blood fluidity (fibrinolytic activity, heparin, platelet factors). Pulmonary interstitium and irradiation (of the three interstitium components collagen plays a preferential part). Irradiation and immunological lung reaction (reasons behind the immunological theory, immunological assistance, immunological mechanism of pulmonary reactions towards pollutants). Enzymatic lung radiolesion indicators. Three kinds of physiological changes have been considered. Vascular physiology disturbances caused by the initial biochemical reactions; anomalies of physiological or functional trials, images of the lesion formed; disorders of the cell physiology of carcinogenesis [fr

  5. Extravascular Lung Water and Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Ritesh Maharaj

    2012-01-01

    Full Text Available Acute lung injury carries a high burden of morbidity and mortality and is characterised by nonhydrostatic pulmonary oedema. The aim of this paper is to highlight the role of accurate quantification of extravascular lung water in diagnosis, management, and prognosis in “acute lung injury” and “acute respiratory distress syndrome”. Several studies have verified the accuracy of both the single and the double transpulmonary thermal indicator techniques. Both experimental and clinical studies were searched in PUBMED using the term “extravascular lung water” and “acute lung injury”. Extravascular lung water measurement offers information not otherwise available by other methods such as chest radiography, arterial blood gas, and chest auscultation at the bedside. Recent data have highlighted the role of extravascular lung water in response to treatment to guide fluid therapy and ventilator strategies. The quantification of extravascular lung water may predict mortality and multiorgan dysfunction. The limitations of the dilution method are also discussed.

  6. Pathology of radiation induced lung damage

    International Nuclear Information System (INIS)

    Kawabata, Yoshinori; Murata, Yoshihiko; Ogata, Hideo; Katagiri, Shiro; Sugita, Hironobu; Iwai, Kazuo; Sakurai, Isamu.

    1985-01-01

    We examined pathological findings of radiation induced lung damage. Twenty-three cases are chosen from our hospital autopsy cases for 9 years, which fulfil strict criteria of radiation lung damage. Lung damage could be classified into 3 groups : 1) interstitial pneumonia type (9 cases), 2) intermediate pneumonia type (8 cases), and 3) alveolar pneumonia type (6 cases), according to the degree of intra-luminal exudation. These classification is well correlated with clinical findings. Pathological alveolar pneumonia type corresponds to symptomatic, radiologic ground glass pneumonic shadow. And pathologic interstitial type corresponds to clinical asymptomatic, radiologic reticulo-nodular shadow. From the clinico-pathological view point these classification is reasonable one. Radiation affects many lung structures and showed characteristic feature of repair. Elastofibrosis of the alveolar wall is observed in every cases, obstructive bronchiolitis are observed in 5 cases, and obstructive bronchiolitis in 9 cases. They are remarkable additional findings. Thickening of the interlobular septum, broncho-vascular connective tissue, and pleural layer are observed in every cases together with vascular lesions. (author)

  7. Vascular Targeting of a Gold Nanoparticle to Breast Cancer Metastasis.

    Science.gov (United States)

    Peiris, Pubudu M; Deb, Partha; Doolittle, Elizabeth; Doron, Gilad; Goldberg, Amy; Govender, Priya; Shah, Shruti; Rao, Swetha; Carbone, Sarah; Cotey, Thomas; Sylvestre, Meilyn; Singh, Sohaj; Schiemann, William P; Lee, Zhenghong; Karathanasis, Efstathios

    2015-08-01

    The vast majority of breast cancer deaths are due to metastatic disease. Although deep tissue targeting of nanoparticles is suitable for some primary tumors, vascular targeting may be a more attractive strategy for micrometastasis. This study combined a vascular targeting strategy with the enhanced targeting capabilities of a nanoparticle to evaluate the ability of a gold nanoparticle (AuNP) to specifically target the early spread of metastatic disease. As a ligand for the vascular targeting strategy, we utilized a peptide targeting alpha(v) beta(3) integrin, which is functionally linked to the development of micrometastases at a distal site. By employing a straightforward radiolabeling method to incorporate Technetium-99m into the AuNPs, we used the high sensitivity of radionuclide imaging to monitor the longitudinal accumulation of the nanoparticles in metastatic sites. Animal and histological studies showed that vascular targeting of the nanoparticle facilitated highly accurate targeting of micrometastasis in the 4T1 mouse model of breast cancer metastasis using radionuclide imaging and a low dose of the nanoparticle. Because of the efficient targeting scheme, 14% of the injected AuNP deposited at metastatic sites in the lungs within 60 min after injection, indicating that the vascular bed of metastasis is a viable target site for nanoparticles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

    Science.gov (United States)

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

    2018-01-01

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

  9. Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert

    2005-11-01

    muscularization. The upregulation of extracellular matrix regulation and adhesion genes was reduced by nearly 80% by inhalation of the tolafentrine. When assessed in vitro, tolafentrine blocked the enhanced PASMC migratory response. Conclusion In conclusion, we demonstrate for the first time that inhalation of combined PDE3/4 inhibitor reverses pulmonary hypertension fully developed in response to monocrotaline in rats. This "reverse-remodeling" effect includes structural changes in the lung vascular wall and key molecular pathways of matrix regulation, concomitant with 60% normalization of hemodynamics.

  10. Triple role of platelet-activating factor in eosinophil migration across monolayers of lung epithelial cells: eosinophil chemoattractant and priming agent and epithelial cell activator

    NARCIS (Netherlands)

    Liu, L.; Zuurbier, A. E.; Mul, F. P.; Verhoeven, A. J.; Lutter, R.; Knol, E. F.; Roos, D.

    1998-01-01

    Infiltration of eosinophils into the lung lumen is a hallmark of allergic asthmatic inflammation. To reach the lung lumen, eosinophils must migrate across the vascular endothelium, through the interstitial matrix, and across the lung epithelium. The regulation of this process is obscure. In this

  11. Intersections of lung progenitor cells, lung disease and lung cancer

    Directory of Open Access Journals (Sweden)

    Carla F. Kim

    2017-06-01

    Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

  12. Right bundle branch block

    DEFF Research Database (Denmark)

    Bussink, Barbara E; Holst, Anders Gaarsdal; Jespersen, Lasse

    2013-01-01

    AimsTo determine the prevalence, predictors of newly acquired, and the prognostic value of right bundle branch block (RBBB) and incomplete RBBB (IRBBB) on a resting 12-lead electrocardiogram in men and women from the general population.Methods and resultsWe followed 18 441 participants included.......5%/2.3% in women, P Right bundle branch block was associated with significantly...... increased all-cause and cardiovascular mortality in both genders with age-adjusted hazard ratios (HR) of 1.31 [95% confidence interval (CI), 1.11-1.54] and 1.87 (95% CI, 1.48-2.36) in the gender pooled analysis with little attenuation after multiple adjustment. Right bundle branch block was associated...

  13. Interventional vascular radiology

    International Nuclear Information System (INIS)

    Yune, H.Y.

    1984-01-01

    The papers published during this past year in the area of interventional vascular radiology presented some useful modifications and further experiences both in the area of thromboembolic therapy and in dilation and thrombolysis, but no new techniques. As an introductory subject, an excellent monograph reviewing the current spectrum of pharmacoangiography was presented in Radiographics. Although the presented material is primarily in diagnostic application of various pharmacologic agents used today to facilitate demonstration of certain diagnostic criteria of various disease processes, both vasodilatory and vasoconstrictive reaction to these agents are widely used in various therapeutic vascular procedures. This monograph should be reviewed by every angiographer whether or not he or she performs interventional procedures, and it would be very convenient to have this table available in the angiography suite. In a related subject, Bookstein and co-workers have written an excellent review concerning pharmacologic manipulations of various blood coagulative parameters during angiography. Understanding the proper method of manipulation of the bloodclotting factors during angiography, and especially during interventional angiography, is extremely important. Particularly, the method of manipulating the coagulation with the use of heparin and protamine and modification of the platelet activity by using aspirin and dipyridamole are succinctly reviewed. The systemic and selective thrombolytic activities of streptokianse are also discussed

  14. Spinal vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Krings, Timo [University Hospital Aachen, Department of Neuroradiology, Aachen (Germany); University Hospital Aachen, Department of Neurosurgery, Aachen (Germany); Mull, Michael; Thron, Armin [University Hospital Aachen, Department of Neuroradiology, Aachen (Germany); Gilsbach, Joachim M. [University Hospital Aachen, Department of Neurosurgery, Aachen (Germany)

    2005-02-01

    Spinal vascular malformations are rare diseases that consist of true inborn cavernomas and arteriovenous malformations (including perimedullary fistulae, glomerular and juvenile AVMs) and presumably acquired dural arteriovenous fistulae. This review article gives an overview of the imaging features both on MRI and angiography, the differential diagnoses, the clinical symptomatology and the potential therapeutic approaches to these diseases. It is concluded that MRI is the diagnostic modality of first choice in suspected spinal vascular malformation and should be complemented by selective spinal angiography. Treatment in symptomatic patients offers an improvement in the prognosis, but should be performed in specialized centers. Patients with spinal cord cavernomas and perimedullary fistulae type I are surgical candidates. Dural arteriovenous fistulae can either be operated upon or can be treated by an endovascular approach, the former being a simple, quick and secure approach to obliterate the fistula, while the latter is technically demanding. In spinal arteriovenous malformations, the endovascular approach is the method of first choice; in selected cases, a combined therapy might be sensible. (orig.)

  15. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  16. [The association of lung cancer and atheromatous arterial disease].

    Science.gov (United States)

    Lamour, A; Azorin, J; Tchandjou Ngoko, L E; Valeyre, D; Morère, F; Destable, M D; de Saint-Florent, G

    1989-01-01

    This work is based on the retrospective study of the case history of 26 patients who were treated between September 1979 and January 1987 in the department of thoracic and vascular surgery at the Avicenne Hospital--and who were all suffering from both lung cancer and atheromatous arterial disease. It is now well established by all the epidemiologic research that the link between lung cancer and atheromatous arterial disease is smoking tobacco. The risks involved in the misunderstanding of such an association are not without danger for the patient, particularly the risk of severe complication of possible coronary or carotid lesions, threatening survival; from this derives the necessity to decide automatically for a minimum of pre-surgery vascular investigations in the case of patients suffering from lung cancer. The therapeutic strategy in this association must be thorough, considering that there are three priorities in the vascular field which must absolutely be treated before the lung itself: --the coronary and carotid lesions which are likely to be complicated cancer after surgery and any state of emergency in the other vascular territories. The fight against tobacco smoking must also be considered as a priority aim.

  17. E-Block: A Tangible Programming Tool with Graphical Blocks

    OpenAIRE

    Danli Wang; Yang Zhang; Shengyong Chen

    2013-01-01

    This paper designs a tangible programming tool, E-Block, for children aged 5 to 9 to experience the preliminary understanding of programming by building blocks. With embedded artificial intelligence, the tool defines the programming blocks with the sensors as the input and enables children to write programs to complete the tasks in the computer. The symbol on the programming block's surface is used to help children understanding the function of each block. The sequence information is transfer...

  18. Genetic regulation of systemic angiogenesis in the mouse lung.

    Science.gov (United States)

    Mitzner, W; Srisuma, S; Wagner, E

    2003-10-01

    The work in this study takes advantage of a new experimental model in the mouse that completely isolates the angiogenic process from the direct effects of ischemia. The model also leads to lung angiogenesis that mimics the vascular source of many lung pathologies, and allows investigation of the temporal and spatial factors that can promote or inhibit angiogenesis. This work describes the expression patterns of genes relevant to pro-angiogenic signals and conditions in response to ischemia in the lung. The most notable changes were increases in the expression of genes involved in inflammation and tissue remodeling. In particular, the results confirm a important role of ELR+ CXC chemokines as proangiogenic signals. In addition, the experimental findings in this mouse lung model show that lung ischemia, rather than hypoxia, is the essential trigger for angiogenesis. Results from this model also suggest potential approaches for determining critical pathways and potential therapeutic strategies related to the control of angiogenesis.

  19. Increased isoprostane levels in oleic acid-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Koichi [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Koizumi, Tomonobu, E-mail: tomonobu@shinshu-u.ac.jp [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Nakagawa, Rikimaru [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Obata, Toru [Department of Molecular Cell Biology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo (Japan)

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  20. Lung needle biopsy

    Science.gov (United States)

    ... if you have certain lung diseases such as emphysema. Usually, a collapsed lung after a biopsy does not need treatment. But ... any type Bullae (enlarged alveoli that occur with emphysema) Cor pulmonale (condition ... of the lung High blood pressure in the lung arteries Severe ...

  1. Lung Cancer Screening

    Science.gov (United States)

    ... experience complications from follow-up tests. For this reason, lung cancer screening is offered to people who are in ... is more likely to be cancerous. For that reason, you might be referred to a lung ... problems. Your lung cancer screening test may detect other lung and heart ...

  2. Monitoring of celiac plexus block in chronic pancreatitis

    DEFF Research Database (Denmark)

    Myhre, John Gabriel; Hilsted, J; Tronier, B

    1989-01-01

    Pharmacological, percutaneous celiac plexus blockade is often inefficient in the treatment of pain in chronic pancreatitis. Lack of efficiency could be due to incomplete denervation of the plexus; however, a method for measuring the completeness of celiac plexus blockade is not yet available. We...... have, therefore, monitored the physiological completeness of pharmacological percutaneous celiac blockade with 40 ml 25% ethanol by measuring the effect of posture on heart rate, blood pressure, hepato-splanchnic vascular resistance, and pancreatic hormone concentrations before and after celiac plexus...... block in 6 patients with chronic pancreatitis. Blood pressure decreased and heart rate increased after the block (P less than 0.025), whereas no significant change was found in hepato-splanchnic vascular resistance nor in the change of these parameters during transition from the supine to standing...

  3. Temporary vascular shunting in vascular trauma: A 10-year review ...

    African Journals Online (AJOL)

    Five patients with non-viable limbs had the vessel ligated. Conclusions. A TIVS in the damage control setting is both life- and limb-saving. These shunts can be inserted safely in a facility without access to a surgeon with vascular surgery experience if there is uncontrollable bleeding or the delay to definitive vascular surgery ...

  4. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  5. Contaminated soil concrete blocks

    NARCIS (Netherlands)

    de Korte, A.C.J.; Brouwers, Jos; Limbachiya, Mukesh C.; Kew, Hsein Y.

    2009-01-01

    According to Dutch law the contaminated soil needs to be remediated or immobilised. The main focus in this article is the design of concrete blocks, containing contaminated soil, that are suitable for large production, financial feasible and meets all technical and environmental requirements. In

  6. Making Block Grants Accountable.

    Science.gov (United States)

    Chelimsky, Eleanor

    Methods of accountability are presented in considering the Reagan administration plan to consolidate 84 federal health, education and social service grants into six block grant areas and to cut overall funding. After matching aspects of public criticism with proposal objectives, a rationale is developed for building elements of accountability into…

  7. Linoleum Block Printing Revisited.

    Science.gov (United States)

    Chetelat, Frank J.

    1980-01-01

    The author discusses practical considerations of teaching linoleum block printing in the elementary grades (tool use, materials, motivation) and outlines a sequence of design concepts in this area for the primary, intermediate and junior high grades. A short list of books and audiovisual aids is appended. (SJL)

  8. Effects of Block Scheduling

    Directory of Open Access Journals (Sweden)

    William R. Veal

    1999-09-01

    Full Text Available This study examined the effects of a tri-schedule on the academic achievement of students in a high school. The tri-schedule consists of traditional, 4x4 block, and hybrid schedules running at the same time in the same high school. Effectiveness of the schedules was determined from the state mandated test of basic skills in reading, language, and mathematics. Students who were in a particular schedule their freshman year were tested at the beginning of their sophomore year. A statistical ANCOVA test was performed using the schedule types as independent variables and cognitive skill index and GPA as covariates. For reading and language, there was no statistically significant difference in test results. There was a statistical difference mathematics-computation. Block mathematics is an ideal format for obtaining more credits in mathematics, but the block format does little for mathematics achievement and conceptual understanding. The results have content specific implications for schools, administrations, and school boards who are considering block scheduling adoption.

  9. Coding with Blockly

    CERN Document Server

    Lovett, Amber

    2017-01-01

    "Blockly is a fun, graphical programming language designed to get kids interested in creating their own computer programs. Through simple text written to foster creativity and problem solving, students will the art of innovation. Large, colorful images show students how to complete activities. Additional tools, including a glossary and an index, help students learn new vocabulary and locate information."-- Provided by publisher.

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

    International Nuclear Information System (INIS)

    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 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

  11. [Masquerading bundle branch block].

    Science.gov (United States)

    Kukla, Piotr; Baranchuk, Adrian; Jastrzębski, Marek; Bryniarski, Leszek

    2014-01-01

    We here describe a surface 12-lead electrocardiogram (ECG) of a 72-year-old female with a prior history of breast cancer and chemotherapy-induced cardiomyopathy. An echocardiogram revealed left ventricular dysfunction, ejection fraction of 23%, with mild enlarged left ventricle. The 12-lead ECG showed atrial fibrillation with a mean heart rate of about 100 bpm, QRS duration 160 ms, QT interval 400 ms, right bundle branch block (RBBB) and left anterior fascicular block (LAFB). The combination of RBBB features in the precordial leads and LAFB features in the limb leads is known as ''masquerading bundle branch block''. In most cases of RBBB and LAFB, the QRS axis deviation is located between - 80 to -120 degrees. Rarely, when predominant left ventricular forces are present, the QRS axis deviation is near about -90 degrees, turning the pattern into an atypical form. In a situation of RBBB associated with LAFB, the S wave can be absent or very small in lead I. Such a situation is the result of not only purely LAFB but also with left ventricular hypertrophy and/or focal block due to scar (extensive anterior myocardial infarction) or fibrosis (cardiomyopathy). Sometimes, this specific ECG pattern is mistaken for LBBB. RBBB with LAFB may imitate LBBB either in the limb leads (known as 'standard masquerading' - absence of S wave in lead I), or in the precordial leads (called 'precordial masquerading' - absence of S wave in leads V₅ and V₆). Our ECG showed both these types of masquerading bundle branch block - absence of S wave in lead I and in leads V₅ and V₆.

  12. Peripheral vascular injuries

    Directory of Open Access Journals (Sweden)

    Celal Yavuz

    2009-01-01

    Full Text Available Aim: To determine etiology and management in patients with peripheral vascular trauma.Materials and Methods: From 2005 to 2006 with a diagnosis of peripheral artery injury, 69 cases admitted to Diyarbakır State Hospital Department of Cardiovascular surgery.Results: These cases have been respectively reviewed. The causes of injuries were; penetrating injuries in 60 cases (87%, blunt trauma in seven cases (10% and gunshot injuries in two cases (3%. In 53 cases (74% upper extremity, in 15 cases (21% lower extremity was involved. As a surgical procedure, in 34 cases (47% end-to-end anastomosis, in 28 cases (39% lateral suture, in five cases (7% venous graft interposition, in five cases (7% ligation was performed.Conclusion: Early intervention, transfusion of fluid and blood, systemic anticoagulation, preoperative and postoperative detailed debridement decreased the morbidity and mortality rates.

  13. Anatomic resection to manage donor partial anomalous pulmonary venous return during lung transplantation: a case report and review.

    Science.gov (United States)

    Melvan, J N; Force, S D; Sancheti, M S

    2015-04-01

    Rare vascular malformations are discovered infrequently in donor lungs before implantation into recipients. However, the proper handling of such malformations can influence ischemic time, implantation strategies, and subsequent patient outcomes. We report a simplified method for addressing the technical challenges of anomalous pulmonary venous return in a donor lung before implantation. We demonstrate that anatomic resection is a safe and efficient method for managing this rare congenital vascular malformation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Information supplied by lung perfusion scintiscan in children

    International Nuclear Information System (INIS)

    Grimfeld, A.; Gerbeaux, J.; Mensch, B.

    1975-01-01

    150 lung scans in children were studied: 80 case records were studied statistically. The information supplied was regrouped under two headings: diagnosis and course. Firstly, the benign character of this examination in children which is easy to carry out and reproductible when the operator is properly equipped was emphasized. Diagnostically, it permits to understand better the significance of hyperlucent lung and helps in the discovery of malformations. If offers the possibility of assessing the vascular consequences of certain chronic bronchial and lung diseases. As far as the course is concerned, it permits to follow up these same diseases, judge the efficacy of removal of an endo-bronchial foreign body, and sometimes control the results of certain pulmonary or vascular operations. Apart from right to left shunts, there are no contra-indications. In any case, youth is not a contra-indication [fr

  15. The vascular secret of Klotho

    DEFF Research Database (Denmark)

    Lewin, Ewa; Olgaard, Klaus

    2015-01-01

    Klotho is an evolutionarily highly conserved protein related to longevity. Increasing evidence of a vascular protecting effect of the Klotho protein has emerged and might be important for future treatments of uremic vascular calcification. It is still disputed whether Klotho is locally expressed ...

  16. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings

    2012-01-01

    The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here ...

  17. Diagnostic criteria for vascular dementia

    NARCIS (Netherlands)

    Scheltens, P.; Hijdra, A. H.

    1998-01-01

    The term vascular dementia implies the presence of a clinical syndrome (dementia) caused by, or at least assumed to be caused by, a specific disorder (cerebrovascular disease). In this review, the various sets of criteria used to define vascular dementia are outlined. The various sets of criteria

  18. Maternal vitamin A deficiency during pregnancy affects vascularized islet development.

    Science.gov (United States)

    Chien, Chiao-Yun; Lee, Hsuan-Shu; Cho, Candy Hsin-Hua; Lin, Kuo-I; Tosh, David; Wu, Ruei-Ren; Mao, Wan-Yu; Shen, Chia-Ning

    2016-10-01

    Vitamin A deficiency is known to affect 20 million pregnant women worldwide. However, the prenatal effects of maternal vitamin A deficiency on pancreas development have not been clearly determined. The present study examined how maternal vitamin A deficiency affects fetal islet development. Vitamin A-deficient mice were generated by feeding female mice with a chemically defined diet lacking vitamin A prior to mating as well as during pregnancy. We found that maternal vitamin A deficiency during pregnancy affected fetal pancreas development. Although the exocrine differentiation appeared normal, development of islet tissue was impaired. In the pancreas of neonatal mice, only a few endocrine cell clusters were formed, and these cell clusters lacked capillary endothelial cells. To further determine how vitamin A metabolites, such as retinoic acid, regulate vascularized islet development, ex vivo culture of embryonic pancreas either in the presence of 4-diethylaminobenzaldehyde (DEAB; an inhibitor of retinaldehyde dehydrogenase), all-trans retinoic acid (atRA) or retinoic acid receptor agonist (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl] benzoic acid (TTNPB) was carried out. We found that the addition of DEAB blocked vascularization and suppressed β-cell differentiation. Conversely, atRA or TTNPB promoted β-cell differentiation accompanied by enhanced expression of vascular basement component, laminin. We further demonstrated that atRA regulated vascularization via upregulating vascular endothelial growth factor-A (VEGF-A) secretion in embryonic pancreas and treatment with VEGF-A was able to partially rescue vascularization and β-cell differentiation in DEAB-treated embryonic pancreas cultures. The findings explain why maternal vitamin A deficiency affects fetal islet development and support an essential role of retinoid signaling in regulating vascularized islet development. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Revalidation of a modified and safe approach of stellate ganglion block

    Directory of Open Access Journals (Sweden)

    Ashok Jadon

    2011-01-01

    Full Text Available Stellate ganglion block (SGB is very effective in management of chronic regional pain syndrome (CRPS-1. However, serious complication may occur due to accidental intravascular (intra-arterial injection of local anaesthetic agents. Abdi and others, has suggested a modified technique in which fluoroscopy-guided block is given at the junction of uncinate process and body of vertebra at C7 level. In this approach vascular structures remain away from the trajectory of needle and thus avoid accidental vascular injection. We have used this technique of SGB in nine patients who were treated for CRPS-I. The blocks were effective in all the patients all the time without any vascular or other serious complication.

  20. Social media in vascular surgery.

    Science.gov (United States)

    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. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  1. Comparison of Celsior and Perfadex lung preservation solutions in rat lungs subjected to 6 and 12 hours of ischemia using an ex-vivo lung perfusion system

    Directory of Open Access Journals (Sweden)

    Arteiro Queiroz Menezes

    2012-11-01

    Full Text Available OBJECTIVE: This study evaluated the performance of lungs that were preserved with different solutions (Celsior, Perfadex or saline in an ex vivo rat lung perfusion system. METHODS: Sixty Wistar rats were anesthetized, anticoagulated and randomized into three groups (n = 20. The rats were subjected to antegrade perfusion via the pulmonary artery with Perfadex, Celsior, or saline, followed by 6 or 12 hours of ischemia (4ºC, n = 10 in each group. Respiratory mechanics, gas exchange and hemodynamics were measured at 10-minute intervals during the reperfusion of heart-lung blocks in an ex vivo system (IL2-Isolated Perfused Rat or Guinea Pig Lung System, Harvard Apparatus, Holliston, Massachusetts, USA; Hugo Sachs Elektronik, Germany for 60 minutes. The lungs were prepared for histopathology and evaluated for edema following reperfusion. Group comparisons were performed using ANOVA and the Kruskal-Wallis test with a 5% level of significance. RESULTS: Gas exchange was not significantly different between lungs perfused with either Perfadex or Celsior at the same ischemic times, but it was very low in lungs that were preserved with saline. Airway resistance was greater in the lungs that were preserved for 12 hours. Celsior lungs that were preserved for 6 and 12 hours exhibited lower airway resistance (p = 0.01 compared to Perfadex lungs. Pulmonary artery pressure was not different between the groups, and no significant differences in histopathology and apoptosis were observed between the groups. CONCLUSIONS: Lungs that were preserved with Celsior or Perfadex exhibited similar gas exchange and histopathological findings. Airway resistance was slightly lower in the Celsior-preserved lungs compared with the Perfadex-preserved lungs.

  2. Influence of soluble or matrix-bound isoforms of vascular endothelial growth factor-A on tumor response to vascular-targeted strategies.

    Science.gov (United States)

    Akerman, Simon; Fisher, Matthew; Daniel, Rachel A; Lefley, Diane; Reyes-Aldasoro, Constantino C; Lunt, Sarah Jane; Harris, Sheila; Bjorndahl, Meit; Williams, Leigh J; Evans, Helen; Barber, Paul R; Prise, Vivien E; Vojnovic, Borivoj; Kanthou, Chryso; Tozer, Gillian M

    2013-12-01

    Antiangiogenic therapy based on blocking the actions of vascular endothelial growth factor-A (VEGF) can lead to "normalization" of blood vessels in both animal and human tumors. Differential expression of VEGF isoforms affects tumor vascular maturity, which could influence the normalization process and response to subsequent treatment. Fibrosarcoma cells expressing only VEGF120 or VEGF188 isoforms were implanted either subcutaneously (s.c.) or in dorsal skin-fold "window" chambers in SCID mice. VEGF120 was associated with vascular fragility and hemorrhage. Tumor-bearing mice were treated with repeat doses of SU5416, an indolinone receptor tyrosine kinase inhibitor with activity against VEGFR-2 and proven preclinical ability to induce tumor vascular normalization. SU5416 reduced vascularization in s.c. implants of both VEGF120 and VEGF188 tumors. However, in the window chamber, SU5416 treatment increased red cell velocity in VEGF120 (representing vascular normalization) but not VEGF188 tumors. SU5416 treatment had no effect on growth or necrosis levels in either tumor type but tended to counteract the increase in interstitial fluid pressure seen with growth of VEGF120 tumors. SU5416 pretreatment resulted in the normally fragile blood vessels in VEGF120-expressing tumors becoming resistant to the vascular damaging effects of the tubulin-binding vascular disrupting agent (VDA), combretastatin A4 3-O-phosphate (CA4P). Thus, vascular normalization induced by antiangiogenic treatment can reduce the efficacy of subsequent VDA treatment. Expression of VEGF120 made tumors particularly susceptible to vascular normalization by SU5416, which in turn made them resistant to CA4P. Therefore, VEGF isoform expression may be useful for predicting response to both antiangiogenic and vascular-disrupting therapy. Copyright © 2013 UICC.

  3. Measurement of extravascular lung water using the single indicator method in patients: research and potential clinical value.

    Science.gov (United States)

    Brown, Lisa M; Liu, Kathleen D; Matthay, Michael A

    2009-10-01

    Extravascular lung water includes all of the fluid within the lung but outside of the vasculature. Lung water increases as a result of increased hydrostatic vascular pressure or from an increase in lung endothelial and epithelial permeability or both. Experimentally, extravascular lung water has been measured gravimetrically. Clinically, the chest radiograph is used to determine whether extravascular lung water is present but is an insensitive instrument for determining the quantity of lung water. Bedside measurement of extravascular lung water in patients is now possible using a single indicator thermodilution method. This review critically evaluates the experimental and clinical evidence supporting the potential value of measuring extravascular lung water in patients using the single indicator method.

  4. Study of lung perfusion in colagenosis

    International Nuclear Information System (INIS)

    Macedo de Carvalho, A.C.; Calegaro, J.U.M.

    1982-01-01

    The lung involvement in the various types of colagenosis has been widely described in the literature. However, the study of lung perfusion utilizing radionuclides has been only mentioned in a few papers. With the intention of ascertaining the importance of the lung perfusion scanning in colagenosis, ten cases were studied, seven of which were females and three males, with the following pathologies: 4 rheumatoid arthritis, 4 systemic lupus eritematosous, 1 scleroderma and 1 scleroderma plus dermatomyositis. The ages of the patients varied from 20 to 73 years, and the duration of the disease from 1 month to 39 years. The lung scanning showed perfusion defects in 100% of the cases, not related with the type of colagenosis, duration of the disease, sex or age. On the other hand, the X rays study showed alterations in only 2 patients (20% of the cases). The ventilatory and respiratory functions were tested on 7 patients showing alteration (mixed pattern with predominance of the restrictive factor) in only one (14.3%), while the other patients were normal (85.7%). The importance of the lung perfusion scanning study in all patients with collagen vascular diseases is emphasized. (author) [es

  5. Understanding the mechanisms of lung mechanical stress

    Directory of Open Access Journals (Sweden)

    C.S.N.B. Garcia

    2006-06-01

    Full Text Available Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area or strain (any forced change in length in relation to the initial length and shear stress (the stress component parallel to a given surface. The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

  6. Study of lung perfusion in colagenosis

    Energy Technology Data Exchange (ETDEWEB)

    Macedo de Carvalho, A.C.; Calegaro, J.U.M. (Fundacao Hospitalar do Distrito Federal, Distrito Federal (Brazil). Unidade de Medicina Nuclear)

    1982-07-01

    The lung involvement in the various types of colagenosis has been widely described in the literature. However, the study of lung perfusion utilizing radionuclides has been only mentioned in a few papers. With the intention of ascertaining the importance of the lung perfusion scanning in colagenosis, ten cases were studied, seven of which were females and three males, with the following pathologies: 4 rheumatoid arthritis, 4 systemic lupus eritematosous, 1 scleroderma and 1 scleroderma plus dermatomyositis. The ages of the patients varied from 20 to 73 years, and the duration of the disease from 1 month to 39 years. The lung scanning showed perfusion defects in 100% of the cases, not related with the type of colagenosis, duration of the disease, sex or age. On the other hand, the X rays study showed alterations in only 2 patients (20% of the cases). The ventilatory and respiratory functions were tested on 7 patients showing alteration (mixed pattern with predominance of the restrictive factor) in only one (14.3%), while the other patients were normal (85.7%). The importance of the lung perfusion scanning study in all patients with collagen vascular diseases is emphasized.

  7. Lung growth and development.

    Science.gov (United States)

    Joshi, Suchita; Kotecha, Sailesh

    2007-12-01

    Human lung growth starts as a primitive lung bud in early embryonic life and undergoes several morphological stages which continue into postnatal life. Each stage of lung growth is a result of complex and tightly regulated events governed by physical, environmental, hormonal and genetic factors. Fetal lung liquid and fetal breathing movements are by far the most important determinants of lung growth. Although timing of the stages of lung growth in animals do not mimic that of human, numerous animal studies, mainly on sheep and rat, have given us a better understanding of the regulators of lung growth. Insight into the genetic basis of lung growth has helped us understand and improve management of complex life threatening congenital abnormalities such as congenital diaphragmatic hernia and pulmonary hypoplasia. Although advances in perinatal medicine have improved survival of preterm infants, premature birth is perhaps still the most important factor for adverse lung growth.

  8. SUPERFICIAL CERVICAL PLEXUS BLOCK

    Directory of Open Access Journals (Sweden)

    Komang Mega Puspadisari

    2014-01-01

    Full Text Available Superficial cervical plexus block is one of the regional anesthesia in  neck were limited to thesuperficial fascia. Anesthesia is used to relieve pain caused either during or after the surgery iscompleted. This technique can be done by landmark or with ultrasound guiding. The midpointof posterior border of the Sternocleidomastoid was identified and the prosedure done on thatplace or on the level of cartilage cricoid.

  9. Change Around the Block?

    Science.gov (United States)

    Berlin, Joey

    2017-04-01

    Proponents of a block grant or per-capita cap trumpet them as vehicles for the federal government to give the states a capped amount of funding for Medicaid that legislatures would effectively distribute how they see fit. Questions abound as to what capped Medicaid funding would look like, and what effect it would have on the current Medicaid-eligible population, covered services, and physician payments.

  10. Epidemiology of Lung Cancer

    Science.gov (United States)

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

  11. Managing access block.

    Science.gov (United States)

    Cameron, Peter; Scown, Paul; Campbell, Donald

    2002-01-01

    There is pessimism regarding the ability of the Acute Health Sector to manage access block for emergency and elective patients. Melbourne Health suffered an acute bed crisis in 2001 resulting in record ambulance diversions and emergency department (ED) delays. We conducted an observational study to reduce access block for emergency patients whilst maintaining elective throughput at Melbourne Health. This involved a clinician-led taskforce using previously proven principles for organisational change to implement 51 actions to improve patient access over a three-month period. The primary outcome measures were ambulance diversion, emergency patients waiting more than 12 hours for an inpatient bed, elective throughput and theatre cancellations. Despite a reduction in multi-day bed numbers all primary objectives were met, ambulance diversion decreased to minimal levels, 12-hour waits decreased by 40% and elective throughput was maintained. Theatre cancellations were also minimised. We conclude that access block can be improved by clinician-led implementation of proven process improvements over a short time frame. The ability to sustain change over the longer term requires further study.

  12. Danshen improves survival of patients with advanced lung cancer and targeting the relationship between macrophages and lung cancer cells

    Science.gov (United States)

    Wu, Ching-Yuan; Cherng, Jong-Yuh; Yang, Yao-Hsu; Lin, Chun-Liang; Kuan, Feng-Che; Lin, Yin-Yin; Lin, Yu-Shih; Shu, Li-Hsin; Cheng, Yu-Ching; Liu, Hung Te; Lu, Ming-Chu; Lung, Jthau; Chen, Pau-Chung; Lin, Hui Kuan; Lee, Kuan-Der; Tsai, Ying-Huang

    2017-01-01

    In traditional Chinese medicine, Salvia miltiorrhiza Bunge (danshen) is widely used in the treatment of numerous cancers. However, its clinical effort and mechanism in the treatment of advanced lung cancer are unclear. In our study, the in vivo protective effort of danshen in patients with advanced lung cancer were validated using data from the National Health Insurance Research Database in Taiwan. We observed in vitro that dihydroisotanshinone I (DT), a bioactive compound in danshen, exerts anticancer effects through many pathways. First, 10 μM DT substantially inhibited the migration ability of lung cancer cells in both macrophage and macrophage/lung cancer direct mixed coculture media. Second, 10 μM DT repressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), the protein expression of S-phase kinase associated protein-2 (Skp2), and the mRNA levels of STAT3-related genes, including chemokine (C–C motif) ligand 2 (CCL2). In addition, 10 μM DT suppressed the macrophage recruitment ability of lung cancer cells by reducing CCL2 secretion from both macrophages and lung cancer cells. Third, 20 μM DT induced apoptosis in lung cancer cells. Furthermore, DT treatment significantly inhibited the final tumor volume in a xenograft nude mouse model. In conclusion, danshen exerts protective efforts in patients with advanced lung cancer. These effects can be attributed to DT-mediated interruption of the cross talk between lung cancer cells and macrophages and blocking of lung cancer cell proliferation. PMID:29207614

  13. Angiopoietins regulate vascular reactivity after haemorrhagic shock in rats through the Tie2-nitric oxide pathway.

    Science.gov (United States)

    Xu, Jing; Lan, Dan; Li, Tao; Yang, Guangming; Liu, Liangming

    2012-11-01

    Vascular reactivity shows biphasic changes after severe trauma or shock. Our aim was to elucidate the mechanisms of biphasic-changed vascular reactivity after haemorrhagic shock by observing the regulation of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) on it. Haemorrhagic-shock Sprague-Dawley rats, hypoxia-treated superior mesenteric arteries (SMAs) with intact endothelia, and a cell mixture of vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) were adopted to evaluate the regulatory effects of Ang-1 and Ang-2 on vascular reactivity and their relationship to Tie2 (receptor tyrosine kinase)-Akt-endothelial nitric oxide synthase (eNOS) and Tie2-extracellular signal-regulated kinase (Erk)-inducible nitric oxide synthase (iNOS) signal pathways. Ang-1 expression, Tie2 phosphorylation, and nitric oxide (NO) release were increased at early shock. Exogenous Ang-1 maintained the vascular reactivity of SMAs after early hypoxia. Tie2-blocking antibody and the antagonists of Akt and eNOS antagonized Ang-1-induced maintenance in vascular reactivity and a slight release in NO at the early stage of shock. Ang-2 expression, Tie2 phosphorylation, and NO release were greatly increased at late shock, but exogenous Ang-2 further decreased the vascular reactivity of SMAs after late hypoxia. Tie2-blocking antibody and the antagonists of Erk and iNOS andtagonized the Ang-2-induced decrease in vascular reactivity and a large release of NO at the late stage of shock. Ang-1 and Ang-2 participated in the regulation of vascular reactivity after haemorrhagic shock. Ang-1 was mainly responsible for the hyperreactivity at early shock through the Tie2-Akt-eNOS pathway and an appropriate amount of NO release. Ang-2 was mainly responsible for the hyporeactivity at late shock through the Tie2-Erk-iNOS pathway and the release of a large amount of NO.

  14. Mitigation of Radiation Induced Pulmonary Vascular Injury by Delayed Treatment with Captopril

    Science.gov (United States)

    MOLTHEN, Robert C.; WU, Qingping; FISH, Brian L.; MOULDER, John E.; JACOBS, Elizabeth R.; MEDHORA, Meetha M.

    2013-01-01

    Background and objective A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2-months post-exposure. In this study we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2-months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2-weeks after radiation exposure, with 2 doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary hemodynamics, lung ACE activity, pulmonary arterial distensibility, and peripheral vessel density. Results Captopril, given at a vasoactive but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly these beneficial effects were observed even if drug therapy was delayed for up to two weeks after exposure. Conclusions Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident. PMID:22882664

  15. Contemporary vascular smartphone medical applications.

    Science.gov (United States)

    Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W

    2013-08-01

    Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Vascular disease in cocaine addiction.

    Science.gov (United States)

    Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-07-01

    Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. [The future of vascular medicine].

    Science.gov (United States)

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step. Georg Thieme Verlag KG Stuttgart · New York.

  18. [Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

    Science.gov (United States)

    Nocke, H; Meyer, F; Lessmann, V

    2014-10-01

    To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting

  19. Microparticles and acute lung injury.

    Science.gov (United States)

    McVey, Mark; Tabuchi, Arata; Kuebler, Wolfgang M

    2012-09-01

    The pathophysiology of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), is characterized by increased vascular and epithelial permeability, hypercoagulation and hypofibrinolysis, inflammation, and immune modulation. These detrimental changes are orchestrated by cross talk between a complex network of cells, mediators, and signaling pathways. A rapidly growing number of studies have reported the appearance of distinct populations of microparticles (MPs) in both the vascular and alveolar compartments in animal models of ALI/ARDS or respective patient populations, where they may serve as diagnostic and prognostic biomarkers. MPs are small cytosolic vesicles with an intact lipid bilayer that can be released by a variety of vascular, parenchymal, or blood cells and that contain membrane and cytosolic proteins, organelles, lipids, and RNA supplied from and characteristic for their respective parental cells. Owing to this endowment, MPs can effectively interact with other cell types via fusion, receptor-mediated interaction, uptake, or mediator release, thereby acting as intrinsic stimulators, modulators, or even attenuators in a variety of disease processes. This review summarizes current knowledge on the formation and potential functional role of different MPs in inflammatory diseases with a specific focus on ALI/ARDS. ALI has been associated with the formation of MPs from such diverse cellular origins as platelets, neutrophils, monocytes, lymphocytes, red blood cells, and endothelial and epithelial cells. Because of their considerable heterogeneity in terms of origin and functional properties, MPs may contribute via both harmful and beneficial effects to the characteristic pathological features of ALI/ARDS. A better understanding of the formation, function, and relevance of MPs may give rise to new promising therapeutic strategies to modulate coagulation, inflammation, endothelial function, and permeability either through

  20. Role of preoperative vascular ultrasonography in hemodialysis vascular access operation.

    Science.gov (United States)

    Siribumrungwong, Boonying; Tomtitchong, Prakitpunthu; Kanpirom, Kitti

    2010-12-01

    Preoperative vascular mapping increase rate of successful hemodialysis vascular access operation. Several studies recommend using this procedure routinely. But some studies recommend using this procedure in selected patients. So this study aims to determine the impacts of preoperative vascular mapping in unfavorable-examined patients. 55 patients were studied retrospectively from August 2006 to October 2009. Before April 2008, the operative plans were based on physical examination (group 1). After April 2008, the surgeon did preoperative vascular mapping prior to the operation in unfavorable-examined patients (group 2). The results were compared. There were high maturation rates in favorable-examined patients. In unfavorable-examined patients, preoperative vascular mapping can identified nonpalpable favorable vein which successful maturation of 18.75%. Complementary duplex scan decrease rate of unsuccessful operation significantly (p = 0.037) but does not increase maturation rate. Careful physical examination is important part before operation. Preoperative vascular mapping has benefit only in patients with unfavorable-examined patients. It finds some nonpalpable favorable vein and decrease unsuccessful exploration.

  1. Trauma vascular, visión del cirujano vascular

    Directory of Open Access Journals (Sweden)

    Dr. D. Cristián Salas

    2011-09-01

    Full Text Available El 3% de todas las lesiones en trauma tiene un componente vascular. Con los conflictos armados del siglo pasado se lograron grandes avances en este campo. A partir de la Guerra de Vietnam gracias a las mejoras en el manejo prehospitalario, traslado de pacientes, y avances en técnica quirúrgica se lograron tasas de sobrevida y de amputaciones que se han mantenido estables hasta la fecha. El diagnóstico de lesiones vasculares en extremidades se realiza con el examen físico, sin embargo las lesiones de vasos torácicos y abdominales requieren de imágenes de apoyo, siempre que el paciente se encuentre estabilizado, generalmente tomografía axial computada. La mayoría de las lesiones vasculares son por trauma penetrante, comprometiendo principalmente las extremidades. Con el desarrollo de los procedimientos invasivos vasculares en los últimos años se ha observado un aumento de lesiones vasculares iatrogénicas. Hoy en día muchos pacientes con trauma vascular son manejados por vía endovascular.

  2. Vascular injuries during gynecological laparoscopy: the vascular surgeon's advice

    Directory of Open Access Journals (Sweden)

    Marcello Barbosa Barros

    Full Text Available CONTEXT: Iatrogenic vascular problems due to laparoscopy are a well recognized problem and lead to significant repercussions. In this context, a ten-year review of cases topic is presented, based on experience gained while heading two important vascular surgery services. CASES: Five patients with vascular injuries during elective laparoscopy are described. These patients presented with seven lesions of iliac vessels. All cases were evaluated immediately and required laparotomy, provisional hemostasis and urgent attendance by a vascular surgeon. Direct suturing was performed in three cases. One aortoiliac bypass and one ilioiliac reversed venous graft were made. Venous lesions were sutured. One case of a point-like perforation of the small bowel was found. There were no deaths and no complications during the postoperative period. DISCUSSION: Important points on this subject are made, and advice is given. There needs to be immediate recognition of the vascular injury, and expert repair by a vascular surgeon is recommended, in order to significantly reduce the degree of complications.

  3. Paving block study : final report.

    Science.gov (United States)

    1971-10-01

    The Louisiana Department of Highways has conducted field tests with an experimental revetment consisting of cellular concrete revetment blocks used in conjunction with plastic filter cloth and/or vegetation such as grass or vines. The precast blocks ...

  4. Habitat Blocks and Wildlife Corridors

    Data.gov (United States)

    Vermont Center for Geographic Information — Habitat blocks are areas of contiguous forest and other natural habitats that are unfragmented by roads, development, or agriculture. Vermonts habitat blocks are...

  5. Demographic Data - MDC_Block

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — A polygon feature class of Miami-Dade Census 2000 Blocks. Census blocks are areas bounded on all sides by visible and/or invisible features shown on a map prepared...

  6. Mouse Hepatic Tumor Vascular Imaging by Experimental Selective Angiography.

    Directory of Open Access Journals (Sweden)

    Sang Kyum Kim

    Full Text Available Human hepatocellular carcinoma (HCC has unique vascular features, which require selective imaging of hepatic arterial perfusion and portal venous perfusion with vascular catheterization for sufficient evaluation. Unlike in humans, vessels in mice are too small to catheterize, and the importance of separately imaging the feeding vessels of tumors is frequently overlooked in hepatic tumor models. The purpose of this study was to perform selective latex angiography in several mouse liver tumor models and assess their suitability.In several ectopic (Lewis lung carcinoma, B16/F10 melanoma cell lines and spontaneous liver tumor (Albumin-Cre/MST1fl/fl/MST2fl/fl, Albumin-Cre/WW45fl/fl, and H-ras12V genetically modified mouse models, the heart left ventricle and/or main portal vein of mice was punctured, and latex dye was infused to achieve selective latex arteriography and/or portography.H-ras12V transgenic mice (a HCC and hepatic adenoma model developed multiple liver nodules that displayed three different perfusion patterns (portal venous or hepatic artery perfusion predominant, mixed perfusion, indicating intra-tumoral vascular heterogeneity. Selective latex angiography revealed that the Lewis lung carcinoma implant model and the Albumin-Cre/WW45fl/fl model reproduced conventional angiography findings of human HCC. Specifically, these mice developed tumors with abundant feeding arteries but no portal venous perfusion.Different hepatic tumor models showed different tumor vessel characteristics that influence the suitability of the model and that should be considered when designing translational experiments. Selective latex angiography applied to certain mouse tumor models (both ectopic and spontaneous closely simulated typical characteristics of human HCC vascular imaging.

  7. Ultrasonography for clinical decision-making and intervention in airway management: From the mouth to the lungs and pleurae

    DEFF Research Database (Denmark)

    Kristensen, M. S.; Teoh, W. H.; Graumann, O.

    2014-01-01

    enables diagnosis and treatment of interstitial syndrome, lung consolidation, atelectasis, pleural effusion and differentiates causes of acute breathlessness during pregnancy. Patient safety can be enhanced by performing procedures under ultrasound guidance, e.g. thoracocentesis, vascular line access......-of-care ultrasonography of the airways has a steep learning curve. • Lung ultrasonography allows treatment of interstitial syndrome, consolidation, atelectasis and effusion....

  8. Uncommon vascular tumor of the ovary. Primary ovarian epithelioid hemangioendothelioma or vascular sarcomatous transformation in ovarian germ cell tumor?

    Science.gov (United States)

    Illueca, Carmen; Machado, Isidro; García, Ana; Covisa, Amparo; Morales, Javier; Cruz, Julia; Traves, Victor; Almenar, Sergio

    2011-12-01

    Epithelioid hemangioendothelioma (EHE) is an unusual vascular tumor, which usually occurs in the soft tissue, liver, breast, lung and bone. We submit a case of EHE, a tumor never before reported in the ovary. A 20-year-old woman was admitted with a medical history of unilateral ovarian tumor. The right ovary was totally removed and histologically, the tumor was composed of epithelioid cells with eosinophilic cytoplasm and prominent intracytoplasmic vacuoles associated with myxohyaline matrix. No morphologic evidence of germ cell tumor was observed. Immunohistochemically, the tumor cells were positive for CD31 and CD34. However, all germ cell tumor markers were negative. The final diagnosis was EHE of the ovarian gland and sarcomatous transformation in ovarian germ cell tumor was excluded after extensive histopathological and immunohistochemical study. EHE is an uncommon vascular tumor, which is rarely seen in female genital tract and this is the first report of EHE in ovarian gland. Final diagnosis depends on histopathological and immunohistochemical features.

  9. Lungs and Respiratory System

    Science.gov (United States)

    ... even smaller tubes called bronchioles. Bronchioles end in tiny air sacs called alveoli, where the exchange of oxygen and carbon dioxide actually takes place. Each lung houses about 300-400 million alveoli. The lungs also ...

  10. Nutrition for Lung Cancer

    Science.gov (United States)

    ... to help prepare meals or do the grocery shopping for you. Most people you know want to ... Better Breathers Clubs Asthma Basics LUNG FORCE Expos Online Support Communities FUNDRAISERS Fight For Air Climb LUNG ...

  11. Lung Cancer Trends

    Science.gov (United States)

    ... Cervical Colorectal (Colon) Ovarian Prostate Skin Cancer Home Lung Cancer Trends Language: English Español (Spanish) Recommend on Facebook ... in the United States, the incidence rate of lung cancer— Men Decreased significantly by 2.5% per year ...

  12. Blocking the Hawking radiation

    DEFF Research Database (Denmark)

    Autzen, M.; Kouvaris, C.

    2014-01-01

    grows after its formation (and eventually destroys the star) instead of evaporating. The fate of the black hole is dictated by the two opposite mechanics, i.e., accretion of nuclear matter from the center of the star and Hawking radiation that tends to decrease the mass of the black hole. We study how...... the assumptions for the accretion rate can in fact affect the critical mass beyond which a black hole always grows. We also study to what extent degenerate nuclear matter can impede Hawking radiation due to the fact that emitted particles can be Pauli blocked at the core of the star....

  13. How Artists Overcome Creative Blocks.

    Science.gov (United States)

    Hirst, Barbara

    1992-01-01

    Six practicing artists were interviewed about how they overcome creative blocks. Their responses indicated that feelings of self-doubt, fear, and depression accompany blocks but that relaxing and working on new directions and playing ideas off a supportive person helped to overcome such blocks. (DB)

  14. Block Scheduling in High Schools.

    Science.gov (United States)

    Irmsher, Karen

    1996-01-01

    Block Scheduling has been considered a cure for a lengthy list of educational problems. This report reviews the literature on block schedules and describes some Oregon high schools that have integrated block scheduling. Major disadvantages included resistance to change and requirements that teachers change their teaching strategies. There is…

  15. Abdominal wall blocks in adults

    DEFF Research Database (Denmark)

    Neimann, Jens Dupont Børglum; Gögenür, Ismail; Bendtsen, Thomas F.

    2016-01-01

    Purpose of review Abdominal wall blocks in adults have evolved much during the last decade; that is, particularly with the introduction of ultrasound-guided (USG) blocks. This review highlights recent advances of block techniques within this field and proposes directions for future research.  Rec...

  16. ( Elaeis guineensis Jacq ) vascular wilt

    African Journals Online (AJOL)

    Effet de la jachére sur l'expérimentation de la fusariose vasculaire du palmier à huile ( Elaeis guineensis Jacq ) : Effects of the fallow in the expression of oil-palm ( Elaeis guineensis Jacq ) vascular wilt.

  17. Endotoxin increases pulmonary vascular protein permeability in the dog

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  18. Vascular lesions of the hand

    Energy Technology Data Exchange (ETDEWEB)

    Drape, Jean-Luc [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France)]. E-mail: jean-luc.drape@cch.ap-hop-paris.fr; Feydy, Antoine [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Guerini, Henri [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Desmarais, Eric [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Godefroy, Didier [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France); Viet, Dominique Le [Institut de la main, Paris (France); Chevrot, Alain [Service de Radiologie B, Hopital Cochin, APHP, Universite Paris, 27 rue du Fbg Saint-Jacques, 75014 Paris (France)

    2005-12-15

    The vascular malformations are not uncommon on the hand and offer diagnostic and therapeutic challenges. Enjolras and Mulliken's classification is exposed. Their depiction and pretreatment assessment may benefit from non-invasive imaging as color-Doppler ultrasound and MRI combined with magnetic resonance angiography (MRA). Some chronic traumatic vascular injuries as the hypothenar hammer syndrome may also take advantage of these imaging modalities.

  19. Hemimegalencephaly, hemihypertrophy and vascular lesions.

    Science.gov (United States)

    Cristaldi, A; Vigevano, F; Antoniazzi, G; di Capua, M; Andreuzzi, A; Morselli, G; Iorio, F; Fariello, G; Trasimeni, G; Gualdi, G F

    1995-02-01

    We report on two children with hemihypertrophy and ipsilateral hemimegalencephaly. Vascular lesions in one were consistent with a diagnosis of the Klippel-Trénaunay-Weber Syndrome. MRI performed in the first days of life and at 1 month of age revealed the presence of the neuronal anomaly. The occurrence of hemimegalencephaly in our patients indicates that hemihypertrophy and vascular dysplasia are pathogenetically related phenomena of a continuous spectrum in which this brain disorder may appear.

  20. Facial vascular malformations in children

    International Nuclear Information System (INIS)

    Brunelle, F.O.; Lallemand, D.; Chaumont, P.; Teillac, D.; Manach, Y.

    1988-01-01

    The authors present their experience with conventional and digital angiography of vascular malformations of the head and neck in children. 22 hemangioendotheliomas, 8 venous angiomas, and 3 arteriovenous fistula were studied. 22 patients were embolised. DSA offers many advantages during the diagnostic as well as during the therapeutic phase of angiography. Embolization appears to have a major role in treatment of such vascular malformations. (orig.)

  1. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the reti...... vasculature may affect the retinal response to potential vascular disease in later life....

  2. Angiogenesis, Cancer, and Vascular Aging

    Directory of Open Access Journals (Sweden)

    Junji Moriya

    2017-10-01

    Full Text Available Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging or endothelial cell senescence. There is considerable evidence supporting the hypothesis that vascular cell senescence contributes to the pathogenesis of age-related CVD, suggesting that vascular aging could be an important therapeutic target. Since therapeutic angiogenesis is now regarded as a promising concept for patients with ischemic CVD, it has become even more important to understand the detailed molecular mechanisms underlying impairment of angiogenesis in older patients. To improve the usefulness of therapeutic angiogenesis, approaches are needed that can compensate for impaired angiogenic capacity in the elderly while not promoting the development or progression of malignancy. In this review, we briefly outline the mechanisms of angiogenesis and vascular aging, followed by a description of how vascular aging leads to impairment of angiogenesis. We also examine potential therapeutic approaches that could enhance angiogenesis and/or vascular function in the elderly, as well as discussing the possibility of anti-senescence therapy or reversal of endothelial cell senescence.

  3. Program structure-based blocking

    Science.gov (United States)

    Bertolli, Carlo; Eichenberger, Alexandre E.; O'Brien, John K.; Sura, Zehra N.

    2017-09-26

    Embodiments relate to program structure-based blocking. An aspect includes receiving source code corresponding to a computer program by a compiler of a computer system. Another aspect includes determining a prefetching section in the source code by a marking module of the compiler. Yet another aspect includes performing, by a blocking module of the compiler, blocking of instructions located in the prefetching section into instruction blocks, such that the instruction blocks of the prefetching section only contain instructions that are located in the prefetching section.

  4. CT findings of inoperable lung carcinoma

    International Nuclear Information System (INIS)

    Gay, S.B.; Black, W.C.

    1987-01-01

    CT is useful in the evaluation of patients with newly diagnosed or highly suspected lung cancer. The principal role of CT is to screen those patients with metastatic disease beyond the hili from an attempt at curative thoracotomy. While CT is regarded as very sensitive, it is not considered highly specific, and thus a surgical procedure is usually recommended for definitive diagnosis of most ''positive'' CT findings. However, the authors demonstrate a few characteristic CT findings that are highly predictive of unresectable metastatic disease. These CT findings include massive mediastinal lymphadenopathy, diffuse mediastinal infiltration, pericardial involvement, vascular encasement, and advanced chest wall invasion

  5. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects......Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...

  6. Horseshoe lung associated with left-lung hypoplasia, left pulmonary artery sling and bilateral agenesis of upper lobe bronchi

    International Nuclear Information System (INIS)

    Oguz, Berna; Haliloglu, Mithat; Alan, Serdar; Ozcelik, Ugur

    2009-01-01

    Horseshoe lung, a rare congenital anomaly, is almost always associated with unilateral (usually right-sided) lung hypoplasia, and, in most cases, in conjunction with the scimitar syndrome. We present an 8-month-old boy with horseshoe lung associated with left-lung hypoplasia, left pulmonary artery sling and bilateral agenesis of the upper lobe bronchi, diagnosed by multidetector CT (MDCT) imaging. The study also revealed an anomalous origin of the left vertebral artery as the last branch of the aortic arch, distal to the left subclavian artery, and an anomalous origin of the left common carotid artery from the brachiocephalic trunk. A hemivertebral anomaly of the seventh cervical vertebra was incidentally detected. MDCT with high-quality multiplanar and three-dimensional reconstructions is a noninvasive and rapid technique for detecting the complex combination of vascular, tracheobronchial and parenchymal anomalies, and any potential bone anomalies, in one imaging study. (orig.)

  7. Horseshoe lung associated with left-lung hypoplasia, left pulmonary artery sling and bilateral agenesis of upper lobe bronchi

    Energy Technology Data Exchange (ETDEWEB)

    Oguz, Berna; Haliloglu, Mithat [Hacettepe University Faculty of Medicine, Department of Radiology, Ankara (Turkey); Alan, Serdar; Ozcelik, Ugur [Hacettepe University Faculty of Medicine, Department of Pediatrics, Ankara (Turkey)

    2009-09-15

    Horseshoe lung, a rare congenital anomaly, is almost always associated with unilateral (usually right-sided) lung hypoplasia, and, in most cases, in conjunction with the scimitar syndrome. We present an 8-month-old boy with horseshoe lung associated with left-lung hypoplasia, left pulmonary artery sling and bilateral agenesis of the upper lobe bronchi, diagnosed by multidetector CT (MDCT) imaging. The study also revealed an anomalous origin of the left vertebral artery as the last branch of the aortic arch, distal to the left subclavian artery, and an anomalous origin of the left common carotid artery from the brachiocephalic trunk. A hemivertebral anomaly of the seventh cervical vertebra was incidentally detected. MDCT with high-quality multiplanar and three-dimensional reconstructions is a noninvasive and rapid technique for detecting the complex combination of vascular, tracheobronchial and parenchymal anomalies, and any potential bone anomalies, in one imaging study. (orig.)

  8. Block copolymer investigations

    Science.gov (United States)

    Yufa, Nataliya A.

    The research presented in this thesis deals with various aspects of block copolymers on the nanoscale: their behavior at a range of temperatures, their use as scaffolds, or for creation of chemically striped surfaces, as well as the behavior of metals on block copolymers under the influence of UV light, and the healing behavior of copolymers. Invented around the time of World War II, copolymers have been used for decades due to their macroscopic properties, such as their ability to be molded without vulcanization, and the fact that, unlike rubber, they can be recycled. In recent years, block copolymers (BCPs) have been used for lithography, as scaffolds for nano-objects, to create a magnetic hard drive, as well as in photonic and other applications. In this work we used primarily atomic force microscopy (AFM) and transmission electron microscopy (TEM), described in Chapter II, to conduct our studies. In Chapter III we demonstrate a new and general method for positioning nanoparticles within nanoscale grooves. This technique is suitable for nanodots, nanocrystals, as well as DNA. We use AFM and TEM to demonstrate selective decoration. In Chapters IV and V we use AFM and TEM to study the structure of polymer surfaces coated with metals and self-assembled monolayers. We describe how the surfaces were created, exhibit their structure on the nanoscale, and prove that their macroscopic wetting properties have been altered compared to the original polymer structures. Finally, Chapters VI and VII report out in-situ AFM studies of BCP at high temperatures, made possible only recently with the invention of air-tight high-temperature AFM imaging cells. We locate the transition between disordered films and cylinders during initial ordering. Fluctuations of existing domains leading to domain coarsening are also described, and are shown to be consistent with reptation and curvature minimization. Chapter VII deals with the healing of PS-b-PMMA following AFM-tip lithography or

  9. Role of lymphangiogenesis in lung cancer.

    Directory of Open Access Journals (Sweden)

    Renata Jankowska

    2010-02-01

    Full Text Available Lung cancer represents one of the most frequent causes of death due to neoplastic disease in Poland and around the world. The high mortality which accompany neoplastic diseases used to be ascribed mainly to dissemination of cancerous cells. Studies on animal models suggest that tumour lymphangiogenesis represents the principal factor in the process of metastases formation. Lymphangiogenesis involves a process of formation of new lymphatic vessels from already existing lymphatic capillaries. Lymphangiogenesis is stimulated by vascular endothelial growth factors (VEGF and other, recently reported factors, such as, e.g., cyclooxygenase 2, fibroblast growth factor 2, angiopoetin-1 and the insulin-resembling growth factor. In lymphangiogenesis a key role is played by neutropilin 2 or podoplanin and this promoted development of studies on lymphangiogenesis. Activation of VEGF-C/VEGF-D/VEGFR-3 axis increases motility and invasiveness of neoplastic cells, promotes development of metastases in several types of tumours such as, e.g., lung cancer, mammary carcinoma, cancers of the neck, prostate and large intestine. In recent years lymphangiogenesis provided topic of many studies. A positive correlation was detected between expressions of VEGF-C/D and VEGFR-3 in non-small cell lung cancer. In patients with lung cancer with high expression of VEGF-C a markedly abbreviated survival was noted. Positive correlation was detected between expression of VEGF-C and VEGF-D on one hand and expression of LYVE-1 on the other in sentinel lymph nodes with metastases of neoplastic cells in patients with non-small cell lung cancer. Also, high density of lymphatic vessels and high density of intraneoplastic microvessels proved to be independent poor prognostic indices in patients with non-small cell lung cancer. Extensive hope is linked to studies on inhibitors of lymphangiogenesis, which may improve results of treatment also in tumour patients.

  10. Breast Angiosarcoma: Case Series and Expression of Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Rondeep Brar

    2009-12-01

    Full Text Available Purpose: Angiosarcoma of the breast is a rare, malignant tumor for which little is known regarding prognostic indicators and optimal therapeutic regimens. To address this issue, we performed a retrospective analysis of breast angiosarcoma cases seen at Stanford University along with immunohistochemical analysis for markers of angiogenesis. Methods: Breast angiosarcoma cases seen between 1980 and 2008 were examined. Viable tissue blocks were analyzed for expression of vascular endothelial growth factor and its receptors. Results: A total of 16 cases were identified. Data was collected regarding epidemiology, treatment, response rates, disease-free survival, and the use of various imaging modalities. Five tissue blocks remained viable for immunohistochemical analysis. Vascular endothelial growth factor-A was positively expressed in 3 of these samples. Conclusion: Angiosarcoma of the breast is an aggressive malignancy with a propensity for both local recurrence and distant metastases. Angiogenesis inhibition may represent a novel therapeutic modality in this rare, vascular malignancy.

  11. Vascular endothelial growth factor receptor-3 directly interacts with phosphatidylinositol 3-kinase to regulate lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Sanja Coso

    Full Text Available BACKGROUND: Dysfunctional lymphatic vessel formation has been implicated in a number of pathological conditions including cancer metastasis, lymphedema, and impaired wound healing. The vascular endothelial growth factor (VEGF family is a major regulator of lymphatic endothelial cell (LEC function and lymphangiogenesis. Indeed, dissemination of malignant cells into the regional lymph nodes, a common occurrence in many cancers, is stimulated by VEGF family members. This effect is generally considered to be mediated via VEGFR-2 and VEGFR-3. However, the role of specific receptors and their downstream signaling pathways is not well understood. METHODS AND RESULTS: Here we delineate the VEGF-C/VEGF receptor (VEGFR-3 signaling pathway in LECs and show that VEGF-C induces activation of PI3K/Akt and MEK/Erk. Furthermore, activation of PI3K/Akt by VEGF-C/VEGFR-3 resulted in phosphorylation of P70S6K, eNOS, PLCγ1, and Erk1/2. Importantly, a direct interaction between PI3K and VEGFR-3 in LECs was demonstrated both in vitro and in clinical cancer specimens. This interaction was strongly associated with the presence of lymph node metastases in primary small cell carcinoma of the lung in clinical specimens. Blocking PI3K activity abolished VEGF-C-stimulated LEC tube formation and migration. CONCLUSIONS: Our findings demonstrate that specific VEGFR-3 signaling pathways are activated in LECs by VEGF-C. The importance of PI3K in VEGF-C/VEGFR-3-mediated lymphangiogenesis provides a potential therapeutic target for the inhibition of lymphatic metastasis.

  12. Lung cancer—a fractal viewpoint

    Science.gov (United States)

    Lennon, Frances E.; Cianci, Gianguido C.; Cipriani, Nicole A.; Hensing, Thomas A.; Zhang, Hannah J.; Chen, Chin-Tu; Murgu, Septimiu D.; Vokes, Everett E.; W. Vannier, Michael; Salgia, Ravi

    2016-01-01

    Fractals are mathematical constructs that show self-similarity over a range of scales and non-integer (fractal) dimensions. Owing to these properties, fractal geometry can be used to efficiently estimate the geometrical complexity, and the irregularity of shapes and patterns observed in lung tumour growth (over space or time), whereas the use of traditional Euclidean geometry in such calculations is more challenging. The application of fractal analysis in biomedical imaging and time series has shown considerable promise for measuring processes as varied as heart and respiratory rates, neuronal cell characterization, and vascular development. Despite the advantages of fractal mathematics and numerous studies demonstrating its applicability to lung cancer research, many researchers and clinicians remain unaware of its potential. Therefore, this Review aims to introduce the fundamental basis of fractals and to illustrate how analysis of fractal dimension (FD) and associated measurements, such as lacunarity (texture) can be performed. We describe the fractal nature of the lung and explain why this organ is particularly suited to fractal analysis. Studies that have used fractal analyses to quantify changes in nuclear and chromatin FD in primary and metastatic tumour cells, and clinical imaging studies that correlated changes in the FD of tumours on CT and/or PET images with tumour growth and treatment responses are reviewed. Moreover, the potential use of these techniques in the diagnosis and therapeutic management of lung cancer are discussed. PMID:26169924

  13. Lung cancer-a fractal viewpoint.

    Science.gov (United States)

    Lennon, Frances E; Cianci, Gianguido C; Cipriani, Nicole A; Hensing, Thomas A; Zhang, Hannah J; Chen, Chin-Tu; Murgu, Septimiu D; Vokes, Everett E; Vannier, Michael W; Salgia, Ravi

    2015-11-01

    Fractals are mathematical constructs that show self-similarity over a range of scales and non-integer (fractal) dimensions. Owing to these properties, fractal geometry can be used to efficiently estimate the geometrical complexity, and the irregularity of shapes and patterns observed in lung tumour growth (over space or time), whereas the use of traditional Euclidean geometry in such calculations is more challenging. The application of fractal analysis in biomedical imaging and time series has shown considerable promise for measuring processes as varied as heart and respiratory rates, neuronal cell characterization, and vascular development. Despite the advantages of fractal mathematics and numerous studies demonstrating its applicability to lung cancer research, many researchers and clinicians remain unaware of its potential. Therefore, this Review aims to introduce the fundamental basis of fractals and to illustrate how analysis of fractal dimension (FD) and associated measurements, such as lacunarity (texture) can be performed. We describe the fractal nature of the lung and explain why this organ is particularly suited to fractal analysis. Studies that have used fractal analyses to quantify changes in nuclear and chromatin FD in primary and metastatic tumour cells, and clinical imaging studies that correlated changes in the FD of tumours on CT and/or PET images with tumour growth and treatment responses are reviewed. Moreover, the potential use of these techniques in the diagnosis and therapeutic management of lung cancer are discussed.

  14. Peribronchial innervation of the rat lung.

    Science.gov (United States)

    Artico, Marco; Bosco, Sandro; Bronzetti, Elena; Felici, Laura M; Pelusi, Giuseppe; Lo Vasco, Vincenza Rita; Vitale, Marco

    2004-10-01

    Mammalian peribronchial tissue is supplied by several peptide-containing nerve fibers. Although it is well established that different neuropeptides exert significant effects on bronchial and vascular tone in the lungs, the role played by some neuromediators on the general regulation, differentiation and release of locally active substances is still controversial. We studied the innervation of rat peribronchial tissue by immunohistochemical techniques. The immunoperoxidase method with nickel amplification was applied to detect the distribution of nerve fibers using antibodies against the general neuronal marker PGP 9.5 (neuron-specific cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was studied by immunohistochemistry. A slight immunoreactivity for NT receptors is observed in lung bronchial epithelium. There is increasing evidence that NTs may act with a paracrine mechanism regulating functional activity of neuronal and non-neuronal structures. A specific immunoreactivity for NTs and NT receptors was also demonstrated within different layers of large, medium and small sized intrapulmonary arteries and veins, according to a recent study of our group. Moreover our data describe the expression of NTs and NT receptors in lymphoid aggregates of the lung (BALT) in which both lymphocytes and macrophages express TrkA receptor and synthesize NTs. Our results show the presence of an extensive network of innervation in the rat peribronchial tissue, confirming a morphological basis for a possible neural modulation of the respiratory mucosa and the physiological/pathophysiological mechanisms of the lung.

  15. Celiac ganglia block

    Energy Technology Data Exchange (ETDEWEB)

    Akinci, Devrim [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey); Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Sihhiye, 06100 Ankara (Turkey)]. E-mail: oakhan@hacettepe.edu.tr

    2005-09-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation.

  16. Photovoltaic building blocks

    DEFF Research Database (Denmark)

    Hanberg, Peter Jesper; Jørgensen, Anders Michael

    2014-01-01

    efficiency of about 15% for commercial Silicon solar cells there is still much to gain. DTU Danchip provides research facilities, equipment and expertise for the building blocks that comprises fabricating the efficient solar cell. In order to get more of the sun light into the device we provide thin film......Photovoltaics (PV), better known as solar cells, are now a common day sight on many rooftops in Denmark.The installed capacity of PV systems worldwide is growing exponentially1 and is the third most importantrenewable energy source today. The cost of PV is decreasing fast with ~10%/year but to make...... it directcompetitive with fossil energy sources a further reduction is needed. By increasing the efficiency of the solar cells one gain an advantage through the whole chain of cost. So that per produced Watt of power less material is spent, installation costs are lower, less area is used etc. With an average...

  17. Atomic Basic Blocks

    Science.gov (United States)

    Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang

    Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.

  18. Celiac ganglia block

    International Nuclear Information System (INIS)

    Akinci, Devrim; Akhan, Okan

    2005-01-01

    Pain occurs frequently in patients with advanced cancers. Tumors originating from upper abdominal viscera such as pancreas, stomach, duodenum, proximal small bowel, liver and biliary tract and from compressing enlarged lymph nodes can cause severe abdominal pain, which do not respond satisfactorily to medical treatment or radiotherapy. Percutaneous celiac ganglia block (CGB) can be performed with high success and low complication rates under imaging guidance to obtain pain relief in patients with upper abdominal malignancies. A significant relationship between pain relief and degree of tumoral celiac ganglia invasion according to CT features was described in the literature. Performing the procedure in the early grades of celiac ganglia invasion on CT can increase the effectiveness of the CGB, which is contrary to World Health Organization criteria stating that CGB must be performed in patients with advanced stage cancer. CGB may also be effectively performed in patients with chronic pancreatitis for pain palliation

  19. Editor's Highlight: Pulmonary Vascular Thrombosis in Rats Exposed to Inhaled Sulfur Mustard.

    Science.gov (United States)

    McGraw, Matthew D; Osborne, Christopher M; Mastej, Emily J; Di Paola, Jorge A; Anderson, Dana R; Holmes, Wesley W; Paradiso, Danielle C; Garlick, Rhonda B; Hendry-Hofer, Tara B; Rancourt, Raymond C; Smith, Russell W; Burns, Carol; Roe, Gates B; Rioux, Jacqueline S; White, Carl W; Veress, Livia A

    2017-10-01

    Sulfur mustard (SM) is a chemical warfare agent. When inhaled, SM causes significant injury to the respiratory tract. Although the mechanism involved in acute airway injury after SM inhalation has been well described previously, the mechanism of SM's contribution to distal lung vascular injury is not well understood. We hypothesized that acute inhalation of vaporized SM causes activated systemic coagulation with subsequent pulmonary vascular thrombi formation after SM inhalation exposure. Sprague Dawley rats inhaled SM ethanolic vapor (3.8 mg/kg). Barium/gelatin CT pulmonary angiograms were performed to assess for pulmonary vascular thrombi burden. Lung immunohistochemistry was performed for common procoagulant markers including fibrin(ogen), von Willebrand factor, and CD42d in control and SM-exposed lungs. Additionally, systemic levels of d-dimer and platelet aggregometry after adenosine diphosphate- and thrombin-stimulation were measured in plasma after SM exposure. In SM-exposed lungs, chest CT angiography demonstrated a significant decrease in the distal pulmonary vessel density assessed at 6 h postexposure. Immunohistochemistry also demonstrated increased intravascular fibrin(ogen), vascular von Willebrand factor, and platelet CD42d in the distal pulmonary vessels (<200 µm diameter). Circulating d-dimer levels were significantly increased (p < .001) at 6, 9, and 12 h after SM inhalation versus controls. Platelet aggregation was also increased in both adenosine diphosphate - (p < .01) and thrombin- (p < .001) stimulated platelet-rich plasma after SM inhalation. Significant pulmonary vascular thrombi formation was evident in distal pulmonary arterioles following SM inhalation in rats assessed by CT angiography and immunohistochemistry. Enhanced systemic platelet aggregation and activated systemic coagulation with subsequent thrombi formation likely contributed to pulmonary vessel occlusion. © The Author 2017. Published by Oxford University Press on

  20. Pulmonary hypertension and vascular remodeling in mice exposed to crystalline silica.

    Science.gov (United States)

    Zelko, Igor N; Zhu, Jianxin; Ritzenthaler, Jeffrey D; Roman, Jesse

    2016-11-28

    Occupational and environmental exposure to crystalline silica may lead to the development of silicosis, which is characterized by inflammation and progressive fibrosis. A substantial number of patients diagnosed with silicosis develop pulmonary hypertension. Pulmonary hypertension associated with silicosis and with related restrictive lung diseases significantly reduces survival in affected subjects. An animal model of silicosis has been described previously however, the magnitude of vascular remodeling and hemodynamic effects of inhaled silica are largely unknown. Considering the importance of such information, this study investigated whether mice exposed to silica develop pulmonary hypertension and vascular remodeling. C57BL6 mice were intratracheally injected with either saline or crystalline silica at doses 0.2 g/kg, 0.3 g/kg and 0.4 g/kg and then studied at day 28 post-exposure. Pulmonary hypertension was characterized by changes in right ventricular systolic pressure and lung histopathology. Mice exposed to saline showed normal lung histology and hemodynamic parameters while mice exposed to silica showed increased right ventricular systolic pressure and marked lung pathology characterized by a granulomatous inflammatory reaction and increased collagen deposition. Silica-exposed mice also showed signs of vascular remodeling with pulmonary artery muscularization, vascular occlusion, and medial thickening. The expression of pro-inflammatory genes such as TNF-α and MCP-1 was significantly upregulated as well as the expression of the pro-remodeling genes collagen type I, fibronectin and the metalloproteinases MMP-2 and TIMP-1. On the other hand, the expression of several vasculature specific genes involved in the regulation of endothelial function was significantly attenuated. We characterized a new animal model of pulmonary hypertension secondary to pulmonary fibrosis induced by crystalline silica. Our data suggest that silica promotes the damage of the

  1. Obesity in Indian subjects with Vascular Dementia

    OpenAIRE

    Chandra, Mina; Anand, Kuljeet Singh Anand

    2015-01-01

    ABSTRACT Background: Obesity is considered a public health challenge in South Asia. Obesity is an independent risk factor in vascular dementia. It also contributes to other risk factors of vascular dementia like hypertension, coronary artery disease, dyslipidaemia and diabetes. As the rate of obesity in Indian subjects with vascular dementia is not known, we decided to assess obesity in subjects with vascular dementia. Methods: Subjects with vascular dementia presenting to Mem...

  2. The α and Δ isoforms of CREB1 are required to maintain normal pulmonary vascular resistance.

    Directory of Open Access Journals (Sweden)

    Lili Li

    Full Text Available Chronic hypoxia causes pulmonary hypertension associated with structural alterations in pulmonary vessels and sustained vasoconstriction. The transcriptional mechanisms responsible for these distinctive changes are unclear. We have previously reported that CREB1 is activated in the lung in response to alveolar hypoxia but not in other organs. To directly investigate the role of α and Δ isoforms of CREB1 in the regulation of pulmonary vascular resistance we examined the responses of mice in which these isoforms of CREB1 had been inactivated by gene mutation, leaving only the β isoform intact (CREB(αΔ mice. Here we report that expression of CREB regulated genes was altered in the lungs of CREB(αΔ mice. CREB(αΔ mice had greater pulmonary vascular resistance than wild types, both basally in normoxia and following exposure to hypoxic conditions for three weeks. There was no difference in rho kinase mediated vasoconstriction between CREB(αΔ and wild type mice. Stereological analysis of pulmonary vascular structure showed characteristic wall thickening and lumen reduction in hypoxic wild-type mice, with similar changes observed in CREB(αΔ. CREB(αΔ mice had larger lungs with reduced epithelial surface density suggesting increased pulmonary compliance. These findings show that α and Δ isoforms of CREB1 regulate homeostatic gene expression in the lung and that normal activity of these isoforms is essential to maintain low pulmonary vascular resistance in both normoxic and hypoxic conditions and to maintain the normal alveolar structure. Interventions that enhance the actions of α and Δ isoforms of CREB1 warrant further investigation in hypoxic lung diseases.

  3. A Robust Method to Generate Mechanically Anisotropic Vascular Smooth Muscle Cell Sheets for Vascular Tissue Engineering.

    Science.gov (United States)

    Backman, Daniel E; LeSavage, Bauer L; Shah, Shivem B; Wong, Joyce Y

    2017-06-01

    In arterial tissue engineering, mimicking native structure and mechanical properties is essential because compliance mismatch can lead to graft failure and further disease. With bottom-up tissue engineering approaches, designing tissue components with proper microscale mechanical properties is crucial to achieve the necessary macroscale properties in the final implant. This study develops a thermoresponsive cell culture platform for growing aligned vascular smooth muscle cell (VSMC) sheets by photografting N-isopropylacrylamide (NIPAAm) onto micropatterned poly(dimethysiloxane) (PDMS). The grafting process is experimentally and computationally optimized to produce PNIPAAm-PDMS substrates optimal for VSMC attachment. To allow long-term VSMC sheet culture and increase the rate of VSMC sheet formation, PNIPAAm-PDMS surfaces were further modified with 3-aminopropyltriethoxysilane yielding a robust, thermoresponsive cell culture platform for culturing VSMC sheets. VSMC cell sheets cultured on patterned thermoresponsive substrates exhibit cellular and collagen alignment in the direction of the micropattern. Mechanical characterization of patterned, single-layer VSMC sheets reveals increased stiffness in the aligned direction compared to the perpendicular direction whereas nonpatterned cell sheets exhibit no directional dependence. Structural and mechanical anisotropy of aligned, single-layer VSMC sheets makes this platform an attractive microstructural building block for engineering a vascular graft to match the in vivo mechanical properties of native arterial tissue. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Trauma vascular, visión del cirujano vascular

    OpenAIRE

    Dr. D. Cristián Salas

    2011-01-01

    El 3% de todas las lesiones en trauma tiene un componente vascular. Con los conflictos armados del siglo pasado se lograron grandes avances en este campo. A partir de la Guerra de Vietnam gracias a las mejoras en el manejo prehospitalario, traslado de pacientes, y avances en técnica quirúrgica se lograron tasas de sobrevida y de amputaciones que se han mantenido estables hasta la fecha. El diagnóstico de lesiones vasculares en extremidades se realiza con el examen físico, sin embargo las lesi...

  5. Acidente vascular cerebral e demência vascular no idoso

    OpenAIRE

    Ionel, Cristina

    2015-01-01

    Trabalho final de mestrado integrado em Medicina, apresentado à Faculdade de Medicina da Universidade de Coimbra. Em consequência de um fenómeno global de envelhecimento populacional, é expectável um aumento na prevalência de demência. A demência vascular é a segunda causa mais comum de demência, depois da doença de Alzheimer. Trata-se de uma entidade clínica bastante heterogénea, sendo o acidente vascular cerebral (AVC) um dos seus mecanismos subjacentes. No entanto, nem todos os doentes ...

  6. The Role of Serotonin Transporter in Human Lung Development and in Neonatal Lung Disorders

    Directory of Open Access Journals (Sweden)

    E. C. C. Castro

    2017-01-01

    Full Text Available Introduction. Failure of the vascular pulmonary remodeling at birth often manifests as pulmonary hypertension (PHT and is associated with a variety of neonatal lung disorders including a uniformly fatal developmental disorder known as alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV. Serum serotonin regulation has been linked to pulmonary vascular function and disease, and serotonin transporter (SERT is thought to be one of the key regulators in these processes. We sought to find evidence of a role that SERT plays in the neonatal respiratory adaptation process and in the pathomechanism of ACD/MPV. Methods. We used histology and immunohistochemistry to determine the timetable of SERT protein expression in normal human fetal and postnatal lungs and in cases of newborn and childhood PHT of varied etiology. In addition, we tested for a SERT gene promoter defect in ACD/MPV patients. Results. We found that SERT protein expression begins at 30 weeks of gestation, increases to term, and stays high postnatally. ACD/MPV patients had diminished SERT expression without SERT promoter alteration. Conclusion. We concluded that SERT/serotonin pathway is crucial in the process of pulmonary vascular remodeling/adaptation at birth and plays a key role in the pathobiology of ACD/MPV.

  7. Imaging findings of pulmonary vascular disorders in portal hypertension

    International Nuclear Information System (INIS)

    Nagasawa, Kenichi; Takahashi, Koji; Furuse, Makoto

    2004-01-01

    The purpose of this study was to demonstrate and compare the imaging findings of hepatopulmonary syndrome and portopulmonary hypertension. We retrospectively reviewed the imaging findings of five patients with hepatopulmonary syndrome and four patients with portopulmonary hypertension. We evaluated chest radiographs, chest and abdominal computed tomography (CT) scans, 99m Tc-macroaggregated albumin (MAA) lung perfusion scans, and pulmonary angiograms. In patients with hepatopulmonary syndrome, the presence of peripheral pulmonary vascular dilatation was detected by chest radiograph, chest CT scan, and pulmonary angiogram, especially the basilar segment. 99m Tc-MAA lung perfusion scan showed extrapulmonary tracer distribution (brain, thyroid, and kidney), which revealed pulmonary right-left shunting. In patients with portopulmonary hypertension, chest radiographs and chest CT scans showed the classic findings of primary pulmonary hypertension. In patients with both disorders, extrahepatic features of portal hypertension including ascites, splenomegaly, and portosystemic collateral vessels were seen on abdominal CT. In conclusion, chest radiographs and CT in hepatopulmonary syndrome usually showed peripheral pulmonary vascular dilatation, whereas those in portopulmonary hypertension showed central pulmonary artery dilatation. The extrahepatic features of portal hypertension might be helpful for the diagnosis of both disorders. (author)

  8. Promoting Tropoelastin Expression in Arterial and Venous Vascular Smooth Muscle Cells and Fibroblasts for Vascular Tissue Engineering.

    Science.gov (United States)

    Rothuizen, Tonia C; Kemp, Raymond; Duijs, Jacques M G J; de Boer, Hetty C; Bijkerk, Roel; van der Veer, Eric P; Moroni, Lorenzo; van Zonneveld, Anton Jan; Weiss, Anthony S; Rabelink, Ton J; Rotmans, Joris I

    2016-10-01

    Elastin, critical for its structural and regulatory functions, is a missing link in vascular tissue engineering. Several elastin-inducting compounds have previously been reported, but their relative efficiency in promoting elastogenesis by adult arterial and venous vascular smooth muscle cells (VSMCs) and fibroblasts, four main vascular and elastogenic cells, has not been described. In addition to elasto-inductive substances, microRNA-29a was recently established as a potent post-transcriptional inhibitor of elastogenesis. Here, we explored if stimulating positive regulators or blocking inhibitors of elastogenesis could maximize elastin production. We tested whether the elasto-inducing compounds IGF-1, TGF-β1, and minoxidil could indeed augment elastin production, and whether microRNA-29a antagonism could block elastin production in adult arterial and venous fibroblasts and VSMCs. The effects on elastin, lysyl oxidase, and fibrillin-1 mRNA expression levels and tropoelastin protein were determined. IGF-1 and minoxidil exerted little effect on tropoelastin mRNA expression levels in all cell types, while TGF-β1 predominantly enhanced mRNA tropoelastin levels, but this mRNA increase did not impact tropoelastin protein abundance. In contrast, microRNA29a inhibition resulted in the upregulation of tropoelastin mRNA in all cell types, but most pronounced in venous VSMCs. Importantly, microRNA-29a-antagonism also enhanced lysyl oxidase and fibrillin-1 mRNA expression, and revealed a dose-dependent increase in tropoelastin protein expression in venous VSMCs. Our studies suggest that the elastogenic potential of microRNA-29a inhibition in vascular cells is superior to that of established elastin-stimulating compounds IGF-1, TGF-β1, and minoxidil. Thus, microRNA-29a antagonism could serve as an attractive means of enhancing elastin synthesis in tissue-engineered blood vessels.

  9. Imaging after vascular gene therapy

    International Nuclear Information System (INIS)

    Manninen, Hannu I.; Yang, Xiaoming

    2005-01-01

    Targets for cardiovascular gene therapy currently include limiting restenosis after balloon angioplasty and stent placement, inhibiting vein bypass graft intimal hyperplasia/stenosis, therapeutic angiogenesis for cardiac and lower-limb ischemia, and prevention of thrombus formation. While catheter angiography is still standard method to follow-up vascular gene transfer, other modern imaging techniques, especially intravascular ultrasound (IVUS), magnetic resonance (MR), and positron emission tomography (PET) imaging provide complementary information about the therapeutic effect of vascular gene transfer in humans. Although molecular imaging of therapeutic gene expression in the vasculatures is still in its technical development phase, it has already offered basic medical science an extremely useful in vivo evaluation tool for non- or minimally invasive imaging of vascular gene therapy

  10. Fetal origin of vascular aging

    Directory of Open Access Journals (Sweden)

    Shailesh Pitale

    2011-01-01

    Full Text Available Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke. It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD. These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ′Barker′s Hypothesis′. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

  11. Dimensional reduction for conformal blocks

    Science.gov (United States)

    Hogervorst, Matthijs

    2016-09-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO( d + 1 , 1) up into multiplets of SO( d, 1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d - 1 dimensions. In particular, we obtain a formula for 3 d conformal blocks as an infinite sum over 2 F 1 hypergeometric functions with closed-form coefficients.

  12. Ethyl Pyruvate Prevents Methyglyoxal-Induced Retinal Vascular Injury in Rats

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2013-01-01

    Full Text Available Pyruvate is an endogenous antioxidant substance. The aim of this study was to investigate the protective effects of ethyl pyruvate (EP on retinal vascular injury in diabetic retinopathy. To investigate the protective effect of EP on vascular cell apoptosis and blood-retinal barrier (BRB breakage, we have used intravitreally methylglyoxal-(MGO- injected rat eyes. Apoptosis of the retinal vascular cell that was stimulated by the intravitreal injection of MGO was evidently attenuated by the EP treatment. EP exerts inhibitory effect on MGO-induced vascular cell apoptosis by blocking oxidative injury. In addition, EP treatment prevented MGO-induced BRB breakage and the degradation of occludin, an important tight junction protein. These observations suggest that EP acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal vessels.

  13. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  14. Differential Effect of Soy Isoflavones in Enhancing High Intensity Radiotherapy and Protecting Lung Tissue in a Pre-Clinical Model of Lung Carcinoma

    Science.gov (United States)

    Hillman, Gilda G.; Singh-Gupta, Vinita; Hoogstra, David J.; Abernathy, Lisa; Rakowski, Joseph; Yunker, Christopher K.; Rothstein, Shoshana E.; Sarkar, Fazlul H.; Gadgeel, Shirish; Konski, Andre A.; Lonardo, Fulvio; Joiner, Michael C.

    2013-01-01

    Background Radiotherapy of locally-advanced non-small cell lung cancer is limited by radiation-induced pneumonitis and fibrosis. We have further investigated the role of soy isoflavones to improve the effect of a high intensity radiation and reduce lung damage in a pre-clinical lung tumor model. Methods Human A549 NSCLC cells were injected i.v. in nude mice to generate a large tumor burden in the lungs. Mice were treated with lung irradiation at 10 Gy and with oral soy. The therapy effect on the tumor cells and surrounding lung tissue was analyzed on lung sections stained with H&E, Ki-67 and Masson’s Trichrome. Pneumonitis and vascular damage were evaluated by measurements of alveolar septa and immunofluorescent staining of vessel walls. Results Combined soy and radiation caused a significantly stronger inhibition of tumor progression compared to each modality alone in contrast to large invasive tumor nodules seen in control mice. At the same time, soy reduced radiation injury in lung tissue by decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and vessels. Conclusions These studies demonstrate a differential effect of soy isoflavones on augmenting tumor destruction induced by radiation while radioprotecting normal lung tissue and support using soy to alleviate radiotoxicity in lung cancer. PMID:24021346

  15. Learning Potentials in Number Blocks

    DEFF Research Database (Denmark)

    Majgaard, Gunver; Misfeldt, Morten; Nielsen, Jacob

    2012-01-01

    . The tool is called Number Blocks and it combines physical interaction, learning, and immediate feedback. Number Blocks supports the children's understanding of place value in the sense that it allows them to experiment with creating large numbers. We found the blocks contributed to the learning process...... in several ways. The blocks combined mathematics and play, and they included and supported children at different academic levels. The auditory representation, especially the enhanced rhythmic effects due to using speech synthesis, and the rhythm helped the children to pronounce large numbers. This creates...

  16. Common blocks for ASQS(12

    Directory of Open Access Journals (Sweden)

    Lorenzo Milazzo

    1997-05-01

    Full Text Available An ASQS(v is a particular Steiner system featuring a set of v vertices and two separate families of blocks, B and G, whose elements have a respective cardinality of 4 and 6. It has the property that any three vertices of X belong either to a B-block or to a G-block. The parameter cb is the number of common blocks in two separate ASQSs, both defined on the same set of vertices X . In this paper it is shown that cb ≤ 29 for any pair of ASQSs(12.

  17. Antioxidant defenses in the preterm lung: role for hypoxia-inducible factors in BPD?

    International Nuclear Information System (INIS)

    Asikainen, Tiina M.; White, Carl W.

    2005-01-01

    Pulmonary antioxidants and their therapeutic implications have been extensively studied during past decades. The purpose of this review is to briefly summarize the key findings of these studies as well as to elaborate on some novel approaches with respect to potential preventive treatments for neonatal chronic lung disease bronchopulmonary dysplasia (BPD). Such new ideas include, for example, modification of transcription factors governing the hypoxic response pathways, important in angiogenesis, cell survival, and glycolytic responses. The fundamental strategy behind that approach is that fetal lung normally develops under hypoxic conditions and that this hypoxic, growth-favoring environment is interrupted by a premature birth. Importantly, during fetal lung development, alveolar development appears to be dependent on vascular development. Therefore, enhancement of signaling factors that occur during hypoxic fetal life ('continued fetal life ex utero'), including angiogenic responses, could potentially lead to improved lung growth and thereby alleviate the alveolar and vascular hypoplasia characteristic of BPD

  18. Vascular injuries caused by acupuncture.

    Science.gov (United States)

    Bergqvist, D

    2008-08-01

    To systematically review the literature on vascular injuries caused by acupuncture. Systematic literature search in Medline and PubMed. Twentyone cases were identified and the majority developed symptoms in direct connection with the acupuncture treatment. Three patients died, two from pericardial tamponade and one from an aortoduodenal fistula. There were five more tamponades, seven pseudoaneurysms, two with ischaemia, two with venous thrombosis, one with compartment syndrome and one with bleeding. The two patients with ischaemia had remaining sequeleae. Information on follow-up was suboptimal with no information in nine patients. Vascular injuries are rare, bleeding and pseudoaneurysm dominating. Follow-up is insufficient in the hitherto published papers.

  19. Vascular malforma- tions part 1 — normal and abnormal vascular ...

    African Journals Online (AJOL)

    Enrique

    Ang2 with VEGF produces loss of adhesion of endothelial cells allowing their migration to occur. 3. Fibroblast growth factor : (aFGF, bFGF). •. Are potent stimulators of endothelial cell migration, proliferation, sprouting and tube formation. •. Are mainly involved with vascular maintenance and repair. 4. Platelet derived factor ...

  20. 31 CFR 545.301 - Blocked account; blocked property.

    Science.gov (United States)

    2010-07-01

    ... (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TALIBAN (AFGHANISTAN) SANCTIONS... name of the Taliban or persons whose property or interests in property are blocked pursuant to § 545.201, or in which the Taliban or persons whose property or interests in property are blocked pursuant...

  1. Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells.

    Science.gov (United States)

    Ogawa, Hiroyuki; Koyanagi-Aoi, Michiyo; Otani, Kyoko; Zen, Yoh; Maniwa, Yoshimasa; Aoi, Takashi

    2017-09-26

    In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named them "lung cancer organoids". We found that interleukin-6 (IL-6), which was expressed in the lung induced CSCs, facilitates the formation of lung cancer organoids via the conversion of mesenchymal stem cells into alpha-smooth muscle actin (αSMA)-positive cells. Interestingly, the combination of anti-IL-6 antibody and cisplatin could destroy the lung cancer organoids, while cisplatin alone could not. Furthermore, IL-6 mRNA-positive cancer cells were found in clinical lung cancer samples. These results suggest that IL-6 could be a novel therapeutic target in lung cancer.

  2. Pathogenesis of vascular leak in dengue virus infection.

    Science.gov (United States)

    Malavige, Gathsaurie Neelika; Ogg, Graham S

    2017-07-01

    Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-α, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1β through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease. © 2017 John Wiley & Sons Ltd.

  3. Phosphodiesterase 1 regulation is a key mechanism in vascular aging

    DEFF Research Database (Denmark)

    Niño, Paula K Bautista; Durik, Matej; Danser, A H Jan

    2015-01-01

    Reduced nitric oxide (NO)/cGMP signalling is observed in age-related vascular disease. We hypothesize that this disturbed signalling involves effects of genomic instability, a primary causal factor in aging, on vascular smooth muscle cells (VSMCs) and that the underlying mechanism plays a role...... in human age-related vascular disease. To test our hypothesis, we combined experiments in mice with genomic instability resulting from the defective nucleotide excision repair gene ERCC1 (Ercc1(d/-) mice), human VSMC cultures and population genome-wide association studies (GWAS). Aortic rings of Ercc1(d...... in lungs was higher in Ercc1(d/-) mice. No differences in activity or levels of cGMP-dependent protein kinase 1 or sGC were observed in Ercc1(d/-) mice compared with WT. Senescent human VSMC showed elevated PDE1A and PDE1C and PDE5 mRNA levels (11.6-, 9- and 2.3-fold respectively), which associated...

  4. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

  5. Lung scintigraphy in children with pulmonary hypertension

    International Nuclear Information System (INIS)

    Fukushima, Hideki

    1992-01-01

    We evaluated 37 patients with pulmonary hypertension (PH) with Tc-99mMAA lung scintigraphy (LS) and compared findings of LS with those of cardiac catheterization (cath) and lung histology. Findings of LS were graded to 4 groups according to the degree of mottling of LS; M0: normal, M1: slight, M2: moderate, M3: severe. The patient group was divided to two groups according to the cath findings; R: reactive to oxygen and tolazoline, N: not reactive to them. Histological findings were evaluated according to Heath-Edwards classification. Most patients with LS findings of M0 and M1 belonged to R group. Their pulmonary arterial mean pressure and pulmonary vascular resistance increased consistent with mottling of LS. Ten out of 12 patients with LS findings of M2 and M3 had H-E III changes histologically. Thus pulmonary blood flow pattern in patients with PH was precisely evaluated by LS, and its findings correlated well to cath and histological findings. These findings suggested that LS can evaluate pulmonary vascular bed non invasively, and LS can be one of the useful diagnosis method of PH. (author)

  6. Local immune-complexes and inflammatory response in patients with chronic interstitial pulmonary disorders associated with collagen vascular diseases

    NARCIS (Netherlands)

    Jansen, H. M.; Schutte, A. J. H.; Elema, J. D.; van der Giessen, M.; Reig, R. P.; van Leeuwen, M. A.; Sluiter, H. J.; The, T. Hauw

    Evidence is accumulating that the lung injury in collagen vascular diseases (CVD) is triggered by immune complexes (IC). These reactions are neutrophil- and complement-dependent. The direct, in vivo phagocytosis of IC by bronchoalveolar lavage polymorphonuclear leucocytes (BAL-PMN), was studied in

  7. Nonrespiratory lung function

    International Nuclear Information System (INIS)

    Isawa, Toyoharu

    1994-01-01

    The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo

  8. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... are only ameliorated to a minor degree by a healthy diet....

  9. Lung disease - resources

    Science.gov (United States)

    ... Pulmonary Disease): COPD Foundation -- www.copdfoundation.org National Emphysema Foundation -- www.emphysemafoundation.org National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov/health/ ...

  10. Parasitic diseases of lungs

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.

    1987-01-01

    Roentgenologic semiotics of the main parasitic diseases of lungs is described: echinococcosis, paragonimiasis, cysticercosis, toxoplasmosis, ascariasis, amebiosis and some rarely met parasitic diseases

  11. Vascular cognitive impairment in dementia.

    Science.gov (United States)

    Etherton-Beer, Christopher D

    2014-10-01

    Vascular risk factors and cerebrovascular disease are common causes of dementia. Shared risk factors for vascular dementia and Alzheimer's disease, as well as frequent coexistence of these pathologies in cognitively impaired older people, suggests convergence of the aetiology, prevention and management of the commonest dementias affecting older people. In light of this understanding, the cognitive impairment associated with cerebrovascular disease is an increasingly important and recognised area of the medicine of older people. Although the incidence of cerebrovascular events is declining in many populations, the overall burden associated with brain vascular disease will continue to increase associated with population ageing. A spectrum of cognitive disorders related to cerebrovascular disease is now recognised. Cerebrovascular disease in older people is associated with specific clinical and imaging findings. Although prevention remains the cornerstone of management, the diagnosis of brain vascular disease is important because of the potential to improve clinical outcomes through clear diagnosis, enhanced control of risk factors, lifestyle interventions and secondary prevention. Specific pharmacological intervention may also be indicated for some patients with cognitive impairment and cerebrovascular disease. However the evidence base to guide intervention remains relatively sparse. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Vascular involvement in tuberous sclerosis.

    Science.gov (United States)

    Salerno, Ann E; Marsenic, Olivera; Meyers, Kevin E C; Kaplan, Bernard S; Hellinger, Jeffrey C

    2010-08-01

    Vascular involvement in tuberous sclerosis (TS) is rare. Central and peripheral aneurysms and large and medium size arterial stenotic-occlusive disease have been reported in patients with TS. We present here three pediatric patients with TS and severe vascular abnormalities, followed by a review of the literature. The three cases include a 14-month-old girl with polycystic kidneys and cerebral tubers who had a large asymptomatic abdominal aortic aneurysm, a 2-year-old boy with multiple features of TS who had hypertension and was found to have mid-aortic syndrome with bilateral renal artery stenosis, and an 18-year-old girl with abdominal pain and TS features who had greater than 70% celiac artery stenosis. In all cases, noninvasive vascular imaging modalities were utilized for either initial diagnosis, surveillance, or both. These cases highlight the collaborative roles of the pediatric nephrologist and cardiovascular imager in the diagnosis and management of the vascular complications in TS patients. Appropriate care can only be made through a high index of suspicion.

  13. Postprandial lipaemia and vascular disease.

    Science.gov (United States)

    Kolovou, Genovefa; Ooi, Teik Chye

    2013-07-01

    In this review we discuss the postprandial pathophysiological mechanisms that promote vascular disease, the evidence for a role of postprandial lipaemia (PPL) in vascular disease and the effect of modifiable and nonmodifiable factors in PPL. PPL refers to the dynamic changes in serum lipids and lipoproteins (mainly in serum triglycerides) that occur after a fat load or a meal. Recent data indicate that postprandial or nonfasting triglyceride levels are better predictors of cardiovascular risk, suggesting that efficiency of postprandial handling of triglyceride-rich lipoproteins plays a role in the causation of vascular disease. The recent finding that postprandial serum triglyceride levels are even better than fasting serum triglyceride levels as predictors of vascular disease indicate that it is better to measure an index of triglyceride-rich lipoproteins (in most cases serum triglyceride levels) in the postprandial period than in the postabsorptive fasting state. Moreover, by the time the postabsorptive state is reached, some of these proatherogenic triglyceride-rich lipoprotein changes may be missed in the measurement.

  14. Peripheral vascular imaging and intervention

    International Nuclear Information System (INIS)

    Kim, D.; Orron, D.E.

    1990-01-01

    This reference addresses the entire clinical approach to the vascular system from the diagnosis of pathology to surgery or interventional radiological management. All diagnostic imaging modalities currently available are included with specific information on how to interpret various results. It features discussions of the latest therapeutic techniques, including laser angioplasty, intravascular stents, and transluminal embolization

  15. Limb vascular function in women

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Gliemann, Lasse

    2018-01-01

    tone and oxidative stress and thereby functions such as oxygen delivery and blood pressure. The acute hormonal fluctuations do not substantially impact health, but their influence should be considered with regard to measurements of vascular function. The chronic hormonal change with menopause strongly...

  16. FOTOPROTECCION EN PLANTAS VASCULARES ANTARTICAS.

    OpenAIRE

    PEREZ TORRES, EDUARDO; PEREZ TORRES, EDUARDO

    2006-01-01

    Colobanthus quitensis y Deschampsia antarctica son las únicas plantas vasculares que han colonizado de manera natural la Antártida Marítima, donde resisten episodios de alta intensidad lumínica y baja temperatura, condiciones que combinadas suelen causar 83p.

  17. Image Quality in Vascular Radiology

    International Nuclear Information System (INIS)

    Vanhavere, F.; Struelens, L.

    2005-01-01

    In vascular radiology, the radiologists use the radiological image to diagnose or treat a specific vascular structure. From literature, we know that related doses are high and that large dose variability exists between different hospitals. The application of the optimization principle is therefore necessary and is obliged by the new legislation. So far, very little fieldwork has been performed and no practical instructions are available to do the necessary work. It's indisputable that obtaining quantitative data is of great interest for optimization purposes. In order to gain insight into these doses and the possible measures for dose reduction, we performed a comparative study in 7 hospitals. Patient doses will be measured and calculated for specific procedures in vascular radiology and evaluated against their most influencing parameters. In view of optimization purposes, a protocol for dose audit will be set-up. From the results and conclusions in this study, experimentally based guidelines will be proposed, in order to improve clinical practice in vascular radiology

  18. Classical Virasoro irregular conformal block

    Science.gov (United States)

    Rim, Chaiho; Zhang, Hong

    2015-07-01

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  19. Classical Virasoro irregular conformal block

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Chaiho; Zhang, Hong [Department of Physics and Center for Quantum Spacetime (CQUeST), Sogang University,Seoul 121-742 (Korea, Republic of)

    2015-07-30

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  20. Four-block beam collimator

    CERN Document Server

    CERN PhotoLab

    1977-01-01

    The photo shows a four-block collimator installed on a control table for positioning the alignment reference marks. Designed for use with the secondary beams, the collimators operated in vacuum conditions. The blocks were made of steel and had a standard length of 1 m. The maximum aperture had a square coss-section of 144 cm2. (See Annual Report 1976.)

  1. OPAL Various Lead Glass Blocks

    CERN Document Server

    These lead glass blocks were part of a CERN detector called OPAL (one of the four experiments at the LEP particle detector). OPAL uses some 12 000 blocks of glass like this to measure particle energies in the electromagnetic calorimeter. This detector measured the energy deposited when electrons and photons were slowed down and stopped.

  2. Writing Blocks and Tacit Knowledge.

    Science.gov (United States)

    Boice, Robert

    1993-01-01

    A review of the literature on writing block looks at two kinds: inability to write in a timely, fluent fashion, and reluctance by academicians to assist others in writing. Obstacles to fluent writing are outlined, four historical trends in treating blocks are discussed, and implications are examined. (MSE)

  3. Block storage subsystem performance analysis

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    You feel that your service is slow because of the storage subsystem? But there are too many abstraction layers between your software and the raw block device for you to debug all this pile... Let's dive on the platters and check out how the block storage sees your I/Os! We can even figure out what those patterns are meaning.

  4. Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection.

    Science.gov (United States)

    Nguyen, Bao-Ngoc H; Azimzadeh, Agnes M; Schroeder, Carsten; Buddensick, Thomas; Zhang, Tianshu; Laaris, Amal; Cochrane, Megan; Schuurman, Henk-Jan; Sachs, David H; Allan, James S; Pierson, Richard N

    2011-01-01

    Galactosyl transferase gene knock-out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection. We perfused GalTKO miniature swine lungs with human blood. Results were compared with those from previous studies using wild-type and human decay-accelerating factor-transgenic (hDAF(+/+) ) pig lungs. GalTKO lungs survived 132 ± 52 min compared to 10 ± 9 min for wild-type lungs (P = 0.001) and 45 ± 60 min for hDAF(+/+) lungs (P = 0.18). GalTKO lungs displayed stable physiologic flow and pulmonary vascular resistance (PVR) until shortly before graft demise, similar to autologous perfusion, and unlike wild-type or hDAF(+/+) lungs. Early (15 and 60 min) complement (C3a) and platelet activation and intrapulmonary platelet deposition were significantly diminished in GalTKO lungs relative to wild-type or hDAF(+/+) lungs. However, GalTKO lungs adsorbed cytotoxic anti-non-Gal antibody and elaborated high levels of thrombin; their demise was associated with increased PVR, capillary congestion, intravascular thrombi and strong CD41 deposition not seen at earlier time points. In summary, GalTKO lungs are substantially protected from injury but, in addition to anti-non-Gal antibody and complement, platelet adhesion and non-physiologic intravascular coagulation contribute to Gal-independent lung injury mechanisms. © 2011 John Wiley & Sons A/S.

  5. Ultrasound-guided greater auricular nerve block as sole anesthetic for ear surgery

    Directory of Open Access Journals (Sweden)

    Michael K. Ritchie

    2016-05-01

    Full Text Available A greater auricular nerve (GAN block was used as the sole anesthetic for facial surgery in an 80-year-old male patient with multiple comorbidities which would have made general anesthesia challenging. The GAN provides sensation to the ear, mastoid process, parotid gland, and angle of the mandible. In addition to anesthesia for operating room surgery, the GAN block can be used for outpatient or emergency department procedures without the need for a separate anesthesia team. Although this nerve block has been performed using landmark-based techniques, the ultrasoundguided version offers several potential advantages. These advantages include increased reliability of the nerve block, as well as prevention of inadvertent vascular puncture or blockade of the phrenic nerve, brachial plexus, or deep cervical plexus. The increasing access to ultrasound technology for medical care providers outside the operating room makes this ultrasound guided block an increasingly viable alternative.

  6. Congenital anomalous/aberrant systemic artery to pulmonary venous fistula: Closure with vascular plugs & coil embolization

    Directory of Open Access Journals (Sweden)

    Pankaj Jariwala

    2014-01-01

    Full Text Available A 7-month-old girl with failure to thrive, who, on clinical and diagnostic evaluation [echocardiography & CT angiography] to rule out congenital heart disease, revealed a rare vascular anomaly called systemic artery to pulmonary venous fistula. In our case, there was dual abnormal supply to the entire left lung as1 anomalous supply by normal systemic artery [internal mammary artery]2 and an aberrant feeder vessel from the abdominal aorta. Left Lung had normal bronchial connections and normal pulmonary vasculature. The fistula drained through the pulmonary veins to the left atrium leading to ‘left–left shunt’. Percutaneous intervention in two stages was performed using Amplatzer vascular plugs and coil embolization to close them successfully. The patient gained significant weight in follow up with other normal developmental and mental milestones.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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 125 I- and 131 I-labeled albumin tracers. Decreases in vascular Ca 2+ and Mg 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 2+ and Mg 2+ play a role in the maintenance of normal pulmonary vascular permeability to proteins

  8. Lung lobar volume in patients with chronic interstitial pneumonia

    International Nuclear Information System (INIS)

    Harada, Hisao; Koba, Hiroyuki; Saitoh, Tsukasa; Abe, Shosaku.

    1997-01-01

    We measured lung lobar volume by using helical computed tomography (HCT) in 23 patients with idiopathic interstitial pneumonia (IIP), 7 patients with chronic interstitial pneumonia associated with collagen vascular disease (CVD-IP), and 5 healthy volunteers HCT scanning was done at the maximal inspiratory level and the resting end-expiratory level. To measure lung lobar volume, we traced the lobar margin on HCT images with a digitizer and calculated the lobar volume with a personal computer. The lower lobar volume and several factors influencing it in chronic interstitial pneumonia were studied. At the maximal inspiratory level, the lower lobar volume as a percent of the whole lung volume was 46.8±4.13% (mean ± SD) in the volunteers, 39.5±6.19% in the patients with IIP, and 27.7±7. 86% in the patients with CVD-IP. The lower lobar volumes in the patients were significantly lower than in the volunteers. Patients with IIP in whom autoantibody tests were positive had lower lobar volumes that were very low and were similar to those of patients with CVD-IP. These data suggest that collagen vascular disease may develop in patients with interstitial pneumonia. The patients with IIP who had emphysematous changes on the CT scans had smaller decreases in total lung capacity and lower ratios of forced expiratory volume in one second to forced vital capacity than did those who had no emphysematous changes, those two groups did not differ in the ratio of lower lobar volume to whole lung volume. This suggests that emphysematous change is not factor influencing lower lobar volume in patients with chronic interstitial pneumonia. We conclude that chronic interstitial pneumonia together with very low values for lower lobar volume may be a pulmonary manifestation of collagen vascular disease. (author)

  9. Genetics Home Reference: lung cancer

    Science.gov (United States)

    ... and a history of lung disease such as tuberculosis, emphysema, or chronic bronchitis. A history of lung ... Cancer Society: Cancer Facts & Figures 2017 (PDF) Byers LA, Rudin CM. Small cell lung cancer: where do ...

  10. Pediatric central nervous system vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Burch, Ezra A. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Orbach, Darren B. [Boston Children' s Hospital, Neurointerventional Radiology, Boston, MA (United States)

    2015-09-15

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  11. Pediatric central nervous system vascular malformations

    International Nuclear Information System (INIS)

    Burch, Ezra A.; Orbach, Darren B.

    2015-01-01

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  12. ESRD QIP - Vascular Access - Payment Year 2018

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes facility details, performance rates, vascular access topic measure score, and the state and national average measure scores for the vascular...

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

    Science.gov (United States)

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

    2013-09-01

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

  14. Comparison of paravertebral and interpleural block in patients undergoing modified radical mastectomy

    Directory of Open Access Journals (Sweden)

    Pankaj Kundra

    2013-01-01

    Conclusion: To conclude, lung functions are well-preserved in patients undergoing modified radical mastectomy under general anesthesia supplemented with paravertebral or IPB. IPB is as effective as PVB for post-operative pain relief. PVB has the added advantage of achieving a more complete block.

  15. The role of fibrocytes in sickle cell lung disease.

    Directory of Open Access Journals (Sweden)

    Joshua J Field

    Full Text Available Interstitial lung disease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lung diseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lung disease.Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lung disease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology.These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease.

  16. Vascular smooth muscle function: defining the diabetic vascular phenotype.

    Science.gov (United States)

    Bruno, Rosa Maria; Ghiadoni, Lorenzo

    2013-10-01

    In this issue of Diabetologia, a meta-analysis performed by Montero and co-authors (Diabetologia doi 10.1007/s00125-013-2974-1 ) demonstrates a significant impairment of vascular smooth muscle (VSM) function in type 2 diabetic patients. Endothelial function and VSM function between type 2 diabetic and healthy individuals were associated, especially in the microcirculation, confirming the hypothesis that unresponsiveness of VSM cells to NO may amplify the consequences of reduced NO availability. This study suggests a novel interpretation for endothelial dysfunction in diabetic patients, indicating VSM cells as key players. Causative mechanisms of VSM dysfunction, which seems to be a feature of the vascular phenotype of type 2 diabetes mellitus, are largely unexplored in humans. Future studies should also address the crucial issue of the prognostic significance of VSM dysfunction in diabetic patients, and possibly in other conditions characterised by high cardiovascular risk.

  17. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Student Guide.

    Science.gov (United States)

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This student guide together with an instructor guide comprise a set of curriculum materials on the criminal justice system. The student guide contains self-contained instructional material that students can study at their own pace most of the time. Six major subject areas or blocks, which are further broken down into several units, with some units…

  18. Criminal Justice Systems. Block I: Law Enforcement. Block II: The Courts. Block III: Corrections. Block IV: Community Relations. Block V: Proficiency Skills. Block VI: Criminalistics. Instructor Guide.

    Science.gov (United States)

    Florida State Dept. of Education, Tallahassee. Div. of Vocational, Adult, and Community Education.

    This instructor guide together with a student guide comprise a set of curriculum materials on the criminal justice system. The instructor guide is a resource for planning and managing individualized, competency-based instruction in six major subject areas or blocks, which are further broken down into several units with some units having several…

  19. MRI of the lung

    Energy Technology Data Exchange (ETDEWEB)

    Kauczor, Hans-Ulrich (ed.) [University Clinic Heidelberg (Germany). Diagnostic and Interventional Radiology

    2009-07-01

    For a long time, only chest X-ray and CT were used to image lung structure, while nuclear medicine was employed to assess lung function. During the past decade significant developments have been achieved in the field of magnetic resonance imaging (MRI), enabling MRI to enter the clinical arena of chest imaging. Standard protocols can now be implemented on up-to-date scanners, allowing MRI to be used as a first-line imaging modality for various lung diseases, including cystic fibrosis, pulmonary hypertension and even lung cancer. The diagnostic benefits stem from the ability of MRI to visualize changes in lung structure while simultaneously imaging different aspects of lung function, such as perfusion, respiratory motion, ventilation and gas exchange. On this basis, novel quantitative surrogates for lung function can be obtained. This book provides a comprehensive overview of how to use MRI for imaging of lung disease. Special emphasis is placed on benign diseases requiring regular monitoring, given that it is patients with these diseases who derive the greatest benefit from the avoidance of ionizing radiation. (orig.)

  20. Lung Cancer Indicators Recurrence

    Science.gov (United States)

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  1. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H

    2010-01-01

    In lung cancer screening with low-dose spiral computed tomography (LDCT), the proportion of stage I disease is 50-85%, and the survival rate for resected stage I disease can exceed 90%, but proof of real benefit in terms of lung cancer mortality reduction must come from the several randomized...

  2. Regional assessment of treatment in lung cancer using lung perfusion and ventilation images

    Energy Technology Data Exchange (ETDEWEB)

    Horikoshi, Masaki; Teshima, Takeo; Yanagimachi, Tomohiro; Ogata, Yuuko [Sendai Kohsei Hospital (Japan); Nukiwa, Toshihiro

    2000-11-01

    In 30 patients with lung cancer undergoing non-surgical treatment, we performed perfusion lung imaging using {sup 99m}Tc-MAA and inhalation lung studies using Technegas before and after treatment and evaluated regional perfusion and ventilation status in the lung regions where bronchogenic carcinoma was located. Regional ventilation status was preserved rather than perfusion counterpart (V>P) in 18 patients (18/30=60.0%) before treatment, while the former was better than the latter in 27 patients (27/30=90.0%) after treatment, indicating that regional ventilation status improved more significantly than regional perfusion counterpart after treatment (P=0.005). We also classified the therapeutic effect for regional perfusion and ventilation status as improved, unchanged, or worsened, respectively; improvement in regional perfusion status was observed in 17 patients (56.7%) and that in regional ventilation status in 24 patients (80.0%). There was a statistically significant correlation between improved regional perfusion and ventilation status (P=0.0018) when therapeutic effect was recognized. The patients who showed improvement in regional perfusion status after treatment always showed improved regional ventilation status, but 7 patients showed either unchanged or worsened regional perfusion status after treatment, although regional ventilation status was improved. In conclusion the pulmonary vascular beds seem more vulnerable to bronchogenic carcinoma and improvement in regional perfusion status was revealed to be more difficult than that in regional ventilation status after treatment. (author)

  3. Regional assessment of treatment in lung cancer using lung perfusion and ventilation images

    International Nuclear Information System (INIS)

    Horikoshi, Masaki; Teshima, Takeo; Yanagimachi, Tomohiro; Ogata, Yuuko; Nukiwa, Toshihiro

    2000-01-01

    In 30 patients with lung cancer undergoing non-surgical treatment, we performed perfusion lung imaging using 99m Tc-MAA and inhalation lung studies using Technegas before and after treatment and evaluated regional perfusion and ventilation status in the lung regions where bronchogenic carcinoma was located. Regional ventilation status was preserved rather than perfusion counterpart (V>P) in 18 patients (18/30=60.0%) before treatment, while the former was better than the latter in 27 patients (27/30=90.0%) after treatment, indicating that regional ventilation status improved more significantly than regional perfusion counterpart after treatment (P=0.005). We also classified the therapeutic effect for regional perfusion and ventilation status as improved, unchanged, or worsened, respectively; improvement in regional perfusion status was observed in 17 patients (56.7%) and that in regional ventilation status in 24 patients (80.0%). There was a statistically significant correlation between improved regional perfusion and ventilation status (P=0.0018) when therapeutic effect was recognized. The patients who showed improvement in regional perfusion status after treatment always showed improved regional ventilation status, but 7 patients showed either unchanged or worsened regional perfusion status after treatment, although regional ventilation status was improved. In conclusion the pulmonary vascular beds seem more vulnerable to bronchogenic carcinoma and improvement in regional perfusion status was revealed to be more difficult than that in regional ventilation status after treatment. (author)

  4. 21 CFR 870.4450 - Vascular clamp.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vascular clamp. 870.4450 Section 870.4450 Food and... CARDIOVASCULAR DEVICES Cardiovascular Surgical Devices § 870.4450 Vascular clamp. (a) Identification. A vascular clamp is a surgical instrument used to occlude a blood vessel temporarily. (b) Classification. Class II...

  5. Block by Block: Civic Action in the Battle of Baghdad

    Science.gov (United States)

    2007-11-01

    bedding, and latrine facilities. Additionally, provide milk , baby formula, diapers, 7 Bogart: Block by Block and infant/family care items such as...viable agricultural businesses. The cattle are a cross breed of a “regular” Iraqi cow and a water buffalo. Chicken farms are mostly egg farms, and...a problem. Contractors did not want to work for fear of being shot or kid - napped. For example, four contractors were shot over the duration of

  6. Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis.

    Science.gov (United States)

    Peng, Huiming; Li, Cao; Kadow, Stephanie; Henry, Brian D; Steinmann, Jörg; Becker, Katrin Anne; Riehle, Andrea; Beckmann, Natalie; Wilker, Barbara; Li, Pin-Lan; Pritts, Timothy; Edwards, Michael J; Zhang, Yang; Gulbins, Erich; Grassmé, Heike

    2015-06-01

    Pulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus-induced sepsis and an important cause of human pathology and death. We investigated the role of the mammalian acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm reduced lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of superoxide, resulting in degradation of tight junction proteins followed by lung edema. Treatment of infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from lung edema caused by S. aureus, but did not reduce systemic bacterial numbers. In turn, treatment with antibiotics reduced bacterial numbers but did not protect mice from lung edema. In contrast, only the combination of antibiotics and amitriptyline inhibited both pulmonary edema and bacteremia protecting mice from lethal sepsis and lung dysfunction suggesting the combination of both drugs as novel treatment option for sepsis. Antibiotics are often insufficient to cure S. aureus-induced sepsis. S. aureus induces lung edema via the Asm/ceramide system. Genetic deficiency of Asm inhibits lung dysfunction upon infection with S. aureus. Pharmacologic inhibition of Asm reduces lung edema induced by S. aureus. Antibiotics plus amitriptyline protect mice from lung edema and lethal S. aureus sepsis.

  7. Electrical impedance tomography (EIT) for quantification of pulmonary edema in acute lung injury.

    Science.gov (United States)

    Trepte, Constantin J C; Phillips, Charles R; Solà, Josep; Adler, Andy; Haas, Sebastian A; Rapin, Michael; Böhm, Stephan H; Reuter, Daniel A

    2016-01-22

    Assessment of pulmonary edema is a key factor in monitoring and guidance of therapy in critically ill patients. To date, methods available at the bedside for estimating the physiologic correlate of pulmonary edema, extravascular lung water, often are unreliable or require invasive measurements. The aim of the present study was to develop a novel approach to reliably assess extravascular lung water by making use of the functional imaging capabilities of electrical impedance tomography. Thirty domestic pigs were anesthetized and randomized to three different groups. Group 1 was a sham group with no lung injury. Group 2 had acute lung injury induced by saline lavage. Group 3 had vascular lung injury induced by intravenous injection of oleic acid. A novel, noninvasive technique using changes in thoracic electrical impedance with lateral body rotation was used to measure a new metric, the lung water ratioEIT, which reflects total extravascular lung water. The lung water ratioEIT was compared with postmortem gravimetric lung water analysis and transcardiopulmonary thermodilution measurements. A significant correlation was found between extravascular lung water as measured by postmortem gravimetric analysis and electrical impedance tomography (r = 0.80; p pulmonary edema.

  8. Concise review: current status of stem cells and regenerative medicine in lung biology and diseases.

    Science.gov (United States)

    Weiss, Daniel J

    2014-01-01

    Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lung diseases. © AlphaMed Press.

  9. Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs

    Directory of Open Access Journals (Sweden)

    Stevenson Christopher S

    2010-02-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF and VEGF receptor 2 (VEGFR2-mediated survival signaling is critical to endothelial cell survival, maintenance of the vasculature and alveolar structure and regeneration of lung tissue. Reduced VEGF and VEGFR2 expression in emphysematous lungs has been linked to increased endothelial cell death and vascular regression. Previously, we have shown that CS down-regulated the VEGFR2 and its downstream signaling in mouse lungs. However, the VEGFR2-mediated survival signaling in response to oxidants/cigarette smoke (CS is not known. We hypothesized that CS exposure leads to disruption of VEGFR2-mediated endothelial survival signaling in rat lungs. Methods Adult male Sprague-Dawley rats were exposed CS for 3 days, 8 weeks and 6 months to investigate the effect of CS on VEGFR2-mediated survival signaling by measuring the Akt/PI3-kinase/eNOS downstream signaling in rat lungs. Results and Discussion We show that CS disrupts VEGFR2/PI3-kinase association leading to decreased Akt and eNOS phosphorylation. This may further alter the phosphorylation of the pro-apoptotic protein Bad and increase the Bad/Bcl-xl association. However, this was not associated with a significant lung cell death as evidenced by active caspase-3 levels. These data suggest that although CS altered the VEGFR2-mediated survival signaling in the rat lungs, but it was not sufficient to cause lung cell death. Conclusion The rat lungs exposed to CS in acute, sub-chronic and chronic levels may be representative of smokers where survival signaling is altered but was not associated with lung cell death whereas emphysema is known to be associated with lung cell apoptosis.

  10. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  11. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [DESY Hamburg, Theory Group,Notkestraße 85, 22607 Hamburg (Germany); Sobko, Evgeny [Nordita and Stockholm University,Roslagstullsbacken 23, SE-106 91 Stockholm (Sweden); Isachenkov, Mikhail [Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel)

    2017-03-15

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  12. Harmony of spinning conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Sobko, Evgeny [Stockholm Univ. (Sweden); Nordita, Stockholm (Sweden); Isachenkov, Mikhail [Weizmann Institute of Science, Rehovoth (Israel). Dept. of Particle Physics and Astrophysics

    2016-12-07

    Conformal blocks for correlation functions of tensor operators play an increasingly important role for the conformal bootstrap programme. We develop a universal approach to such spinning blocks through the harmonic analysis of certain bundles over a coset of the conformal group. The resulting Casimir equations are given by a matrix version of the Calogero-Sutherland Hamiltonian that describes the scattering of interacting spinning particles in a 1-dimensional external potential. The approach is illustrated in several examples including fermionic seed blocks in 3D CFT where they take a very simple form.

  13. Scanning electron microscopy of vascular corrosion casts--technique and applications: updated review.

    Science.gov (United States)

    Lametschwandtner, A; Lametschwandtner, U; Weiger, T

    1990-12-01

    The present paper states very briefly the main steps leading to the technique of scanning electron microscopy (SEM) of vascular corrosion casts. From the terms presently used (injection method, microcorrosion cast, injection replica, vascular corrosion cast, vascular cast) the use of "vascular corrosion cast" for lymphatic and blood vessels is recommended. Specification and pretreatment (kind, volume, dosage of anticoagulants, vasoactive substances and spasmolytica used) of the animals examined are referenced as they are available from the literature. The recommendation is given to pay more attention to these parameters than done so far. The steps necessary for producing reasonable and suitable vascular corrosion casts are critically described. Special attention is paid to the physical and chemical properties of the casting media and their significance for polymerization, shrinkage, casting quality, corrosion resistance, and thermal and spatial stability. Emphasis is also focused on the advantages of cutting the vascular corrosion casts embedded in an ice block by a band saw, a self constructed multi-blade cutting device or a mini wheel-saw placed in the chamber of a cryomicrotome. From the drying methods presently used freeze-drying is stressed because of minimal specimen damage. To render casts conductive in most cases sputter-coating is sufficient. It is recommended to run the SEM with 5-10 kV since the resolution received still reveals all details the casting media presently can replicate. Further the application of scanning electron microscopy of vascular corrosion casts in fully differentiated normal tissue, in pathologic tissue as well as in developing tissues and organs is stated. Lastly possibilities and conditions are discussed under which SEM of vascular corrosion casts can serve to quantify vascular structures in order to make the technique more than pure descriptive.

  14. Intrathoracic manifestations of collagen vascular diseases on high-resolution chest computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Silva, C. Isabela S. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital]. E-mail: isabela.silva@vch.ca; Mueller, Nestor L. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital. Dept. of Radiology

    2008-05-15

    Intrathoracic manifestations of collagen vascular diseases are very common. The frequency of intrathoracic manifestations and the patterns of abnormality are variable depending on the type of collagen vascular disease and may simultaneously involve one or more of the following: lung parenchyma, airways, pulmonary vessels, pericardium, and pleura. The most common pulmonary manifestations are diffuse interstitial pneumonia and pulmonary hypertension which together represent the main causes of morbidity and mortality of these patients. Pulmonary, airway and pleural involvement may also be secondary to the disease therapy, or result from bacterial pneumonia or opportunistic infection. In the present review, the authors summarize the main intrathoracic manifestations of collagen vascular diseases and the differential diagnosis on high-resolution chest computed tomography. (author)

  15. Complications from Stereotactic Body Radiotherapy for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Kylie H. [School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Okoye, Christian C.; Patel, Ravi B. [Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 (United States); Siva, Shankar [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002 (Australia); Biswas, Tithi; Ellis, Rodney J.; Yao, Min; Machtay, Mitchell; Lo, Simon S., E-mail: Simon.Lo@uhhospitals.org [Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2015-06-15

    Stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage, node negative non-small cell lung cancer (NSCLC) in patients who are either medically inoperable or refuse surgical resection. SBRT has high local control rates and a favorable toxicity profile relative to other surgical and non-surgical approaches. Given the excellent tumor control rates and increasing utilization of SBRT, recent efforts have focused on limiting toxicity while expanding treatment to increasingly complex patients. We review toxicities from SBRT for lung cancer, including central airway, esophageal, vascular (e.g., aorta), lung parenchyma (e.g., radiation pneumonitis), and chest wall toxicities, as well as radiation-induced neuropathies (e.g., brachial plexus, vagus nerve and recurrent laryngeal nerve). We summarize patient-related, tumor-related, dosimetric characteristics of these toxicities, review published dose constraints, and propose strategies to reduce such complications.

  16. Oxidative Stress and Lung Ischemia-Reperfusion Injury

    Science.gov (United States)

    Ferrari, Renata Salatti; Andrade, Cristiano Feijó

    2015-01-01

    Ischemia-reperfusion (IR) injury is directly related to the formation of reactive oxygen species (ROS), endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients. PMID:26161240

  17. Oxidative Stress and Lung Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Renata Salatti Ferrari

    2015-01-01

    Full Text Available Ischemia-reperfusion (IR injury is directly related to the formation of reactive oxygen species (ROS, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients.

  18. RAGE inhibition reduces acute lung injury in mice.

    Science.gov (United States)

    Blondonnet, Raiko; Audard, Jules; Belville, Corinne; Clairefond, Gael; Lutz, Jean; Bouvier, Damien; Roszyk, Laurence; Gross, Christelle; Lavergne, Marilyne; Fournet, Marianne; Blanchon, Loic; Vachias, Caroline; Damon-Soubeyrand, Christelle; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

    2017-08-03

    The receptor for advanced glycation end-products (RAGE) is involved in inflammatory response during acute respiratory distress syndrome (ARDS). Growing body of evidence support strategies of RAGE inhibition in experimental lung injury, but its modalities and effects remain underinvestigated. Anesthetised C57BL/6JRj mice were divided in four groups; three of them underwent orotracheal instillation of acid and were treated with anti-RAGE monoclonal antibody (mAb) or recombinant soluble RAGE (sRAGE), acting as a decoy receptor. The fourth group served as a control. Lung injury was assessed by the analysis of blood gases, alveolar permeability, histology, AFC, and cytokines. Lung expression and distribution epithelial channels ENaC, Na,K-ATPase, and aquaporin (AQP)-5 were assessed. Treatment with either anti-RAGE mAb or sRAGE improved lung injury, arterial oxygenation and decreased alveolar inflammation in acid-injured animals. Anti-RAGE therapies were associated with restored AFC and increased lung expression of AQP-5 in alveolar cell. Blocking RAGE had potential therapeutic effects in a translational mouse model of ARDS, possibly through a decrease in alveolar type 1 epithelial cell injury as shown by restored AFC and lung AQP-5 expression. Further mechanistic studies are warranted to describe intracellular pathways that may control such effects of RAGE on lung epithelial injury and repair.

  19. Your Lung Operation: After Your Operation

    Medline Plus

    Full Text Available ... Surgeons Education Patients and Family Skills Programs Your Lung Operation Your Lung Operation DVD After Your Operation Back to Your Lung Operation Your Lung Operation DVD Welcome Your Lung ...

  20. Lung cancer - non-small cell

    Science.gov (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  1. Vascularized osseous graft for scaphoid

    International Nuclear Information System (INIS)

    Mendez Daza, Carlos Hernan; Mathoulin, Cristophe

    2004-01-01

    The most commonly used technique for treatment of pseudo-arthrosis of the scaphoid is osteo-synthesis with Kirschnet wires and cortical sponge grafts. Results reported by different teams using this procedure show no more than 90% osseous consolidation, especially in cases where vascularisation of the proximal fragment of the scaphoid is compromised. Here we present a series of ten cases of pseudo-arthrosis of the scaphoid, treated using a new surgical technique involving a vascularized osseous graft of the distal radius. Using this procedure we obtained 100% consolidation, with no complications either during the procedure or immediately post-operatively. Patients returned to work in week 15 on average. In 4 cases we observed discomfort in the area of the scar, which was successfully treated using local cortisone injection. The results obtained are very similar to those seen in the literature on the different techniques for vascularized osseous grafts for pseudo-arthrosis of the scaphoid

  2. [Menopause: Hypertension and vascular disease].

    Science.gov (United States)

    Zilberman, J M

    Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Vascular diagnostics for Raynaud's phenomenon

    Directory of Open Access Journals (Sweden)

    Dinsdale G

    2014-10-01

    Full Text Available Graham Dinsdale, Ariane L Herrick Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Abstract: Raynaud's phenomenon (RP is common, and in most patients is primary (idiopathic when due to reversible vasospasm and does not progress to irreversible tissue injury. However, in those patients for whom RP is secondary to an underlying disease (eg, systemic sclerosis or atherosclerosis, progression to digital ulceration or critical ischemia can occur. Therefore, the key question for the clinician is “Why does this patient have RP?” Vascular diagnostics play a key role in answering this. In this review, we firstly discuss the different vascular investigations relevant to clinical practice: nail fold capillaroscopy (including the different methodologies for examining the nail fold capillaries, and the role of capillaroscopy in helping to differentiate between primary and systemic sclerosis-related RP, thermography (available in specialist centers, and evaluation of large vessel disease (for example, due to atherosclerosis. We then discuss research tools, mainly laser Doppler methods, including laser Doppler imaging and laser speckle contrast imaging. These are commercially available as complete imaging systems and are (relatively easy to use. The main current goal in vascular imaging research is to validate these novel state-of-the-art techniques as outcome measures of digital vascular disease, and then apply them in early and later phase studies of new treatment approaches, thus facilitating drug development programs. Keywords: Raynaud's phenomenon, systemic sclerosis, nail fold capillaroscopy, thermography, laser Doppler, angiography

  4. Circadian clock and vascular disease.

    OpenAIRE

    Takeda, Norihiko; Maemura, Koji

    2010-01-01

    Cardiovascular functions, including blood pressure and vascular functions, show diurnal oscillation. Circadian variations have been clearly shown in the occurrence of cardiovascular events such as acute myocardial infarction. Circadian rhythm strongly influences human biology and pathology. The identification and characterization of mammalian clock genes revealed that they are expressed almost everywhere throughout the body in a circadian manner. In contrast to the central clock in the suprac...

  5. What Are the Lungs?

    Science.gov (United States)

    ... Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A-Z Grants and Training Grants and Training ...

  6. Left bundle-branch block

    DEFF Research Database (Denmark)

    Risum, Niels; Strauss, David; Sogaard, Peter

    2013-01-01

    The relationship between myocardial electrical activation by electrocardiogram (ECG) and mechanical contraction by echocardiography in left bundle-branch block (LBBB) has never been clearly demonstrated. New strict criteria for LBBB based on a fundamental understanding of physiology have recently...

  7. The wild tapered block bootstrap

    DEFF Research Database (Denmark)

    Hounyo, Ulrich

    -based method in terms of asymptotic accuracy of variance estimation and distribution approximation. For stationary time series, the asymptotic validity, and the favorable bias properties of the new bootstrap method are shown in two important cases: smooth functions of means, and M-estimators. The first......-order asymptotic validity of the tapered block bootstrap as well as the wild tapered block bootstrap approximation to the actual distribution of the sample mean is also established when data are assumed to satisfy a near epoch dependent condition. The consistency of the bootstrap variance estimator for the sample......In this paper, a new resampling procedure, called the wild tapered block bootstrap, is introduced as a means of calculating standard errors of estimators and constructing confidence regions for parameters based on dependent heterogeneous data. The method consists in tapering each overlapping block...

  8. Recursion Relations for Conformal Blocks

    CERN Document Server

    Penedones, João; Yamazaki, Masahito

    2016-09-12

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension $\\Delta$ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in 1307.6856 for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  9. Defying gravity using Jenga™ blocks

    Science.gov (United States)

    Tan, Yin-Soo; Yap, Kueh-Chin

    2007-11-01

    This paper describes how Jenga™ blocks can be used to demonstrate the physics of an overhanging tower that appears to defy gravity. We also propose ideas for how this demonstration can be adapted for the A-level physics curriculum.

  10. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the reti......Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs......, the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer's formula and quantitative genetic models were used to determine the genetic component of variation. Results: The mean...... fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0...

  11. Novel block, graft and random copolymers for biomedical applications

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Jankova Atanasova, Katja; Tanaka, Masaru

    Despite the simple structure, poly(2-methoxyethyl acrylate) (PMEA) shows excellent blood compatibility [1]. Both the freezing-bound water (intermediate water: preventing the biocomponents from directly contacting the polymer surface) and non-freezing water on the polymer surface play important ro...... copolymers with MMA [4] utilizing ATRP. Here we present other block, graft and random copolymers of MEA intended for biomedical applications. These macromolecular architectures have been constructed by employing controlled radical polymerization methods such as RAFT and ATRP....... roles for this [2]. An artificial lung (oxygenator), already in use, is coated with high MW PMEA prepared by radical polymerization with AIBN [2]. To broaden the possibilities for designing biomedical devices [3] and inspired from these findings we first prepared homo polymers of MEA and their block...

  12. Immunosuppression in lung transplantation.

    Science.gov (United States)

    Scheffert, Jenna L; Raza, Kashif

    2014-08-01

    Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.

  13. Vascularization regenerative medicine and tissue engineering

    CERN Document Server

    Brey, Eric M

    2014-01-01

    A Complex and Growing Field The study of vascularization in tissue engineering and regenerative medicine (TERM) and its applications is an emerging field that could revolutionize medical approaches for organ and tissue replacement, reconstruction, and regeneration. Designed specifically for researchers in TERM fields, Vascularization: Regenerative Medicine and Tissue Engineering provides a broad overview of vascularization in TERM applications. This text summarizes research in several areas, and includes contributions from leading experts in the field. It defines the difficulties associated with multicellular processes in vascularization and cell-source issues. It presents advanced biomaterial design strategies for control of vascular network formation and in silico models designed to provide insight not possible in experimental systems. It also examines imaging methods that are critical to understanding vascularization in engineered tissues, and addresses vascularization issues within the context of specific...

  14. Vascular Malformations of the Orofacial Region

    Directory of Open Access Journals (Sweden)

    Daya K Jangam

    2010-01-01

    Full Text Available Vascular malformations are the benign lesion of the blood vessels or vascular elements and are considered errors of vascular morphogenesis, displaying abnormal dilatations, and channels but no increased cell turnover. Vascular malformations are always present at birth and enlarge in proportion to the growth of the child- They do not involute and remain throughout the patient′s life. 1 These lesions occur with equal sex predilection and do not favor any races. Vascular lesions of the face are not very common Most of the oral and oropharyngeal lesions tend to occur in the tongue and the floor of the mouth. 2 In most cases, the diagnosis of vascular malformations is based on clinical evaluation Here a case report is presented of 16-year-old male patient with vascular malformation of the orofacial region. The clinical presentation, radiological finding are discussed with emphasis on recent advances for diagnosis of the same.

  15. Curcumin inhibited HGF-induced EMT and angiogenesis through regulating c-Met dependent PI3K/Akt/mTOR signaling pathways in lung cancer

    Directory of Open Access Journals (Sweden)

    Demin Jiao

    2016-01-01

    Full Text Available The epithelial-mesenchymal transition (EMT and angiogenesis have emerged as two pivotal events in cancer progression. Curcumin has been extensively studied in preclinical models and clinical trials of cancer prevention due to its favorable toxicity profile. However, the possible involvement of curcumin in the EMT and angiogenesis in lung cancer remains unclear. This study found that curcumin inhibited hepatocyte growth factor (HGF-induced migration and EMT-related morphological changes in A549 and PC-9 cells. Moreover, pretreatment with curcumin blocked HGF-induced c-Met phosphorylation and downstream activation of Akt, mTOR, and S6. These effects mimicked that of c-Met inhibitor SU11274 or PI3 kinase inhibitor LY294002 or mTOR inhibitor rapamycin treatment. c-Met gene overexpression analysis further demonstrated that curcumin suppressed lung cancer cell EMT by inhibiting c-Met/Akt/mTOR signaling pathways. In human umbilical vein endothelial cells (HUVECs, we found that curcumin also significantly inhibited PI3K/Akt/mTOR signaling and induced apoptosis and reduced migration and tube formation of HGF-treated HUVEC. Finally, in the experimental mouse model, we showed that curcumin inhibited HGF-stimulated tumor growth and induced an increase in E-cadherin expression and a decrease in vimentin, CD34, and vascular endothelial growth factor (VEGF expression. Collectively, these findings indicated that curcumin could inhibit HGF-promoted EMT and angiogenesis by targeting c-Met and blocking PI3K/Akt/mTOR pathways.

  16. Protection against vascular leak in neprilysin transgenic mice with complex overexpression pattern.

    Science.gov (United States)

    Wick, Marilee J; Loomis, Zoe L; Harral, Julie W; Le, Mysan; Wehling, Carol A; Miller, York E; Dempsey, Edward C

    2016-12-01

    Neprilysin (NEP) is a cell surface metallopeptidase found in many tissues. Based mostly on pharmacological manipulations, NEP has been thought to protect blood vessels from plasma extravasation. We have suggested that NEP may protect against pulmonary vascular injury. However, these prior studies did not utilize mice which overexpress NEP. The aims of the present investigation were to develop and characterize doubly transgenic (DT) mice that overexpress NEP universally and conditionally, and to investigate the protective effect that overexpressed NEP may have against plasma extravasation in the vasculature. The duodenum, which is often used to assess vascular permeability, and in which the NEP protein was overexpressed in our DT mice two-fold, was selected as our experimental preparation. We found that substance P-induced plasma extravasation was decreased substantially (3.5-fold) in the duodenums of our doxycycline-treated DT mice, giving independent evidence of NEP's protective effects against plasma extravasation. Transgenic lung NEP protein was not stably expressed in the DT mice, so we were not able to test the effect of NEP overexpression in the lung. Although initially overexpressed nearly nine-fold at that site, pulmonary NEP protein overexpression eventually dissipated. Surprisingly, at a time when there was no lung transgenic NEP protein overexpression, lung NEP mRNA expression was still increased 23-fold, indicating that the expression defect probably is not transcriptional. These studies help to characterize our complex transgenic model of NEP overexpression and further demonstrate NEP's protective effects against plasma extravasation.

  17. Resveratrol inhibits vascular smooth muscle cell proliferation and induces apoptosis.

    Science.gov (United States)

    Poussier, Bertrand; Cordova, Alfredo C; Becquemin, Jean-Pierre; Sumpio, Bauer E

    2005-12-01

    In France, despite a high intake of dietary cholesterol and saturated fat, the cardiovascular death rate is one of the lowest among developed countries. This "French paradox" has been postulated to be related to the high red wine intake in France. The aim of this study was to determine the effects of resveratrol, a major polyphenol component of red wine, on vascular smooth muscle cell (SMC) proliferation in vitro. SMCs were exposed to 10(-6) to 10(-4) M resveratrol and cell proliferation was assessed by cell counting. Cell cycle analysis was done by treating cells with propidium iodide followed by flow-activated cell sorting. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. We demonstrate that resveratrol inhibited bovine aortic SMC proliferation in a dose-dependent manner. The lowest concentration of resveratrol resulting in a significant decrease in SMC proliferation compared with control was 10(-5) M. By flow cytometry, we observed a block in the G1-S phase of the SMC cycle. Resveratrol treatment also resulted in a dose-dependent apoptosis of SMCs but had no effects on SMC morphology. The results indicated that vascular SMC proliferation could be inhibited by resveratrol through a block on G1-S phase and by an increase in apoptosis. It supports the conjecture that red wine consumption may have a beneficial effect on cardiovascular mortality. Our results suggest that resveratrol inhibits, in a dose-dependent manner, smooth muscle cell proliferation, which may help to partially explain a beneficial effect of wine drinking. This inhibition is related to an early block in the cell cycle and also to a dose-dependent apoptotic effect. The present study demonstrates that resveratrol not only is an indirect marker of a healthy life style and alimentation but may also be directly responsible for the French paradox.

  18. Vascular Aging: Implications for Cardiovascular Disease and Therapy

    Science.gov (United States)

    Ghebre, Yohannes T; Yakubov, Eduard; Wong, Wing Tak; Krishnamurthy, Prasanna; Sayed, Nazish; Sikora, Andrew G; Bonnen, Mark D

    2017-01-01

    The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function. Intriguingly, the vessel wall, a biochemically active structure composed of collagen, connective tissue, smooth muscle and endothelial cells, is adversely affected by processes involved in premature or normal aging. Notably, the inner most layer of the vessel wall, the endothelium, becomes senescent and dysfunctional with advancing age. As a result, its ability to release vasoactive molecules such as acetylcholine (ACh), prostacyclin (PGI2), endothelium-derived hyperpolarizing factor (EDHF), and nitric oxide (NO) is reduced and the cellular response to these molecules is also impaired. By contrast, the vascular endothelium increases its generation and release of reactive oxygen (ROS) and nitrogen (RNS) species, vasoconstrictors such as endothelin (ET) and angiotensin (AT), and endogenous inhibitors of NO synthases (NOSs) to block NO. This skews the balance of the endothelium in favor of the release of highly tissue reactive and harmful molecules that promote DNA damage, telomere erosion, senescence, as well as stiffened and hardened vessel wall that is prone to the development of hypertension, diabetes, atherosclerosis and other cardiovascular risk factors. This Review discusses the impact of advancing age on cardiovascular health, and highlights the cellular and molecular mechanisms

  19. Morphometry of rodent lung following inhalation of 239PuO2

    International Nuclear Information System (INIS)

    Rhoads, K.

    1979-01-01

    Changes in lung structure following exposure of rats and hamsters to 239 PuO 2 were relatively small and few in number. However, significant radiation-induced changes were noted for volume of major airways and vascular areas in both species, and in the thickness of the alveolar air-blood barrier for hamsters

  20. Lack of evidence of CD40 ligand involvement in transfusion-related acute lung injury

    NARCIS (Netherlands)

    Tuinman, P. R.; Gerards, M. C.; Jongsma, G.; Vlaar, A. P.; Boon, L.; Juffermans, N. P.

    2011-01-01

    Activated platelets have been implicated in playing a major role in transfusion-related acute lung injury (TRALI), as platelets can trigger neutrophils, resulting in vascular damage. We hypothesized that binding of platelet CD40 ligand (CD40L) to endothelial CD40 is essential in the onset of TRALI.

  1. 78 FR 12767 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

    Science.gov (United States)

    2013-02-25

    ... Program Nos. 93.233, National Center for Sleep Disorders Research; 93.837, Heart and Vascular Diseases... Committee: National Heart, Lung, and Blood Institute Special Emphasis Panel; Evaluating Obstructive Sleep Apnea Dental Device Treatment. Date: March 15, 2013. Time: 8:30 a.m. to 5:00 p.m. Agenda: To review and...

  2. 76 FR 27068 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

    Science.gov (United States)

    2011-05-10

    ... Special Emphasis Panel, Resource Related Research Project in National Biological Sample Data Repository.... Date: June 2, 2011. Time: 1 p.m. to 4 p.m. Agenda: To review and evaluate contract proposals. Place... Sleep Disorders Research; 93.837, Heart and Vascular Diseases Research; 93.838, Lung Diseases Research...

  3. 75 FR 80831 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

    Science.gov (United States)

    2010-12-23

    ...-Care Assay for Engraftment Potential of Umbilical Cord Stem Cells. Date: January 28, 2011. Time: 2 p.m... Domestic Assistance Program Nos. 93.233, National Center for Sleep Disorders Research; 93.837, Heart and Vascular Diseases Research; 93.838, Lung Diseases Research; 93.839, Blood Diseases and Resources Research...

  4. 78 FR 77477 - National Heart, Lung, and Blood Institute; Notice of Closed Meeting

    Science.gov (United States)

    2013-12-23

    ... Emphasis Panel; Small Business Development of New Methods for Mitral Valve Repair. Date: January 10, 2014... Center for Sleep Disorders Research; 93.837, Heart and Vascular Diseases Research; 93.838, Lung Diseases Research; 93.839, Blood Diseases and Resources Research, National Institutes of Health, HHS). Dated...

  5. Measurement of pulmonary vascular resistance of Fontan candidates with pulmonary arterial distortion by means of pulmonary perfusion imaging

    International Nuclear Information System (INIS)

    Park, In-Sam; Mizukami, Ayumi; Tomimatsu, Hirofumi; Kondou, Chisato; Nakanishi, Toshio; Nakazawa, Makoto; Momma, Kazuo

    1998-01-01

    We measured the distribution of blood flow to the right (R) and left lung (L) by means of pulmonary perfusion imaging and calculated pulmonary vascular resistance (Rp) in 13 patients, whose right and left pulmonary artery pressures were different by 2 to 9 mmHg due to pulmonary arterial distortion (5 interruption, 8 stenosis). The right lung/left lung blood flow ratio was determined and from the ratio and the total pulmonary blood flow, which was determined using the Fick's principle, the absolute values of right and left pulmonary blood flow were calculated. Using the right and left pulmonary blood flow and the right and left pulmonary arterial pressures, right and left pulmonary vascular resistance were calculated, separately. Vascular resistance of the whole lung (Rp) was then calculated using the following equation. 1/(Rp of total lung)=1/(Rp of right lung)+1/(Rp of left lung). Rp calculated from this equation was 1.8+/-0.8 U·m 2 and all values were less than 3 U·m 2 (range 0.3-2.8). Rp estimated from the conventional method using the total pulmonary blood flow and pulmonary arterial pressures, without using the right/left blood flow ratio, ranging from 0.4 to 3.8 U·m 2 and 5 of 13 patients showed Rp>3 U·m 2 . All patients underwent Fontan operation successfully. These data indicated that this method is useful to estimate Rp and to determine the indication of Fontan operation in patients with pulmonary arterial distortions. (author)

  6. The lung communication network.

    Science.gov (United States)

    Losa, Davide; Chanson, Marc

    2015-08-01

    The different types of cells in the lung, from the conducting airway epithelium to the alveolar epithelium and the pulmonary vasculature, are interconnected by gap junctions. The specific profile of gap junction proteins, the connexins, expressed in these different cell types forms compartments of intercellular communication that can be further shaped by the release of extracellular nucleotides via pannexin1 channels. In this review, we focus on the physiology of connexins and pannexins and describe how this lung communication network modulates lung function and host defenses in conductive and respiratory airways.

  7. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  8. Contrast-enhanced ultrasonographic findings in three dogs with lung lobe torsion.

    Science.gov (United States)

    Caivano, Domenico; Birettoni, Francesco; Bufalari, Antonello; De Monte, Valentina; Angeli, Giovanni; Giorgi, Maria Elena; Patata, Valentina; Porciello, Francesco

    2016-03-01

    Lung lobe torsion is rare but life-threatening condition in the dog. Thoracic radiographs and conventional ultrasonography cannot be conclusive for the diagnosis, and computed tomography is useful but is limited by cost and availability. This report describes the findings of contrast-enhanced ultrasonography in 3 dogs with lung lobe torsion. Contrast-enhanced ultrasonography showed the absence or reduction of pulmonary vascularization secondary to twisting of the lung lobe around its bronchovascular pedicle in all three dogs. Moreover, contrast-enhanced ultrasonography distinguished partial pulmonary atelectasis from a lung lobe torsion. These preliminary results suggest that contrast-enhanced ultrasonography can improve the accuracy of conventional ultrasonography for detection of pulmonary blood flow compromise in dogs with lung lobe torsion.

  9. Agreement and repeatability of vascular reactivity estimates based on a breath-hold task and a resting state scan

    Science.gov (United States)

    Lipp, Ilona; Murphy, Kevin; Caseras, Xavier; Wise, Richard G.

    2015-01-01

    FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan. This study aimed to compare three breath-hold based analysis approaches (block design, sine–cosine regressor and CO2 regressor) and a resting state approach (CO2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO2 being recorded during both. Vascular reactivity was defined as CO2-related BOLD percent signal change/mm Hg change in CO2. Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity. We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment. PMID:25795342

  10. Lung cysts in chronic paracoccidioidomycosis.

    Science.gov (United States)

    Costa, André Nathan; Marchiori, Edson; Benard, Gil; Araújo, Mariana Sponholz; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases.

  11. Lung cysts in chronic paracoccidioidomycosis*

    Science.gov (United States)

    Costa, André Nathan; Marchiori, Edson; Benard, Gil; Araújo, Mariana Sponholz; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases. PMID:23857700

  12. The Danish Lung Cancer Registry

    DEFF Research Database (Denmark)

    Jakobsen, Erik; Rasmussen, Torben Riis

    2016-01-01

    AIM OF DATABASE: The Danish Lung Cancer Registry (DLCR) was established by the Danish Lung Cancer Group. The primary and first goal of the DLCR was to improve survival and the overall clinical management of Danish lung cancer patients. STUDY POPULATION: All Danish primary lung cancer patients since...... 2000 are included into the registry and the database today contains information on more than 50,000 cases of lung cancer. MAIN VARIABLES: The database contains information on patient characteristics such as age, sex, diagnostic procedures, histology, tumor stage, lung function, performance...... as a source for research regarding lung cancer in Denmark and in comparisons with other countries....

  13. Lung cysts in chronic paracoccidioidomycosis

    Directory of Open Access Journals (Sweden)

    Andre Nathan Costa

    2013-06-01

    Full Text Available On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%, indicating that patients with paracoccidioidomycosis can present with lung cysts on HRCT scans. Therefore, paracoccidioidomycosis should be included in the differential diagnosis of cystic lung diseases.

  14. Influence of size of emboli on extravascular lung water

    International Nuclear Information System (INIS)

    Dawson, C.A.; Rickaby, D.A.; Linehan, J.H.

    1989-01-01

    We examined the influence of the size of emboli on the vascular volume (QL) and extravascular volume (Qev) accessible to 3 HOH during a single pass through an isolated dog lung lobe using the double indicator-dilution method with 125I-human serum albumin as the vascular indicator. As successively more beads of a given diameter (58, 548, or 3,175 microns) were introduced into a lung lobe, a linear relationship between QL and Qev was obtained as they both decreased. The slope of the graph of QL vs. Qev with progressive embolism was directly proportional to the bead diameter. This suggested an approach for estimating the total vascular volume in vessels smaller than the diameter of the beads before embolization, referred to as Qm. If it is assumed that most of the transvascular diffusional exchange of 3 HOH occurs in vessels smaller than the smallest beads (mainly capillaries) and that vessel obstruction does not change the ratio of Qev to the perfused capillary volume, the slope of the plot of QL vs. Qev is an estimate of the fraction, Qm/QL, of the total vascular volume in vessels smaller than the bead diameter. In the dog lung lobes studied, Qm/QL was approximately 0.64 for 58-microns vessels, 0.75 for 548-microns vessels, and 0.82 for 3,175-microns vessels. The results suggest that, with occlusion of vessels greater than or equal to 58 microns, 3 HOH does not diffuse significantly into unperfused regions

  15. Analysis of Separated Flow over Blocked Surface

    Directory of Open Access Journals (Sweden)

    Onur YEMENİCİ

    2013-04-01

    Full Text Available In this study, the separated flow over flat and blocked surfaces was investigated experimentally. Velocity and turbulence intensity measurements were carried out by a constanttemperature hot wire anemometer and static pressure measurements by a micro-manometer. The flow separations and reattachments were occurred before the first block, on the first block, between blocks and after the last block, and the presence of the blocks significantly increased the turbulent intensity

  16. The BPD trio? Interaction of dysregulated PDGF, VEGF, and TGF signaling in neonatal chronic lung disease.

    Science.gov (United States)

    Oak, Prajakta; Hilgendorff, Anne

    2017-11-07

    The development of neonatal chronic lung disease (nCLD), i.e., bronchopulmonary dysplasia (BPD) in preterm infants, significantly determines long-term outcome in this patient population. Risk factors include mechanical ventilation and oxygen toxicity impacting on the immature lung resulting in impaired alveolarization and vascularization. Disease development is characterized by inflammation, extracellular matrix remodeling, and apoptosis, closely intertwined with the dysregulation of growth factor signaling. This review focuses on the causes and consequences of altered signaling in central pathways like transforming growth factor (TGF), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) driving these above indicated processes, i.e., inflammation, matrix remodeling, and vascular development. We emphasize the shared and distinct role of these pathways as well as their interconnection in disease initiation and progression, generating important knowledge for the development of future treatment strategies.

  17. Childhood Interstitial Lung Disease

    Science.gov (United States)

    ... process. Overview Researchers have only begun to study, define, and understand chILD in the last decade. Currently, ... This term refers to inhaling substances—such as food, liquid, or vomit—into the lungs. Inhaling these ...

  18. Eosinophilic Lung Disorders

    Science.gov (United States)

    ... in eosinophil number in the lung tissue. Treatment Treatment of acute eosinophilic pneumonia may require hospitalization. It may be necessary to support the person with assistance from a breathing machine. Treatment with intravenous (IV) steroids or other medications which ...

  19. Open lung biopsy

    Science.gov (United States)

    ... cancerous) tumors Cancer Certain infections (bacterial, viral, or fungal) Lung diseases (fibrosis) The procedure may help diagnose a number ... 20th ed. Philadelphia, PA: Elsevier; 2017:chap 57. Review Date 11/11/2016 Updated by: Mary C. ...

  20. Lung surgery - discharge

    Science.gov (United States)

    ... Lung biopsy - discharge; Thoracoscopy - discharge; Video-assisted thoracoscopic surgery - discharge; VATS - discharge ... milk) for 2 weeks after video-assisted thoracoscopic surgery and 6 to 8 weeks after open surgery. ...

  1. Diffuse cavitary lung lesions

    International Nuclear Information System (INIS)

    Grunzke, Mindy; Garrington, Timothy; Hayes, Kari; Bourland, Wendy

    2010-01-01

    An 11-year-old girl presented with a 2-month history of progressively worsening cough, daily fevers, and weight loss. A chest radiograph revealed multiple cystic cavitary lung lesions. An extensive infectious work-up was negative. Chest CT verified multiple cavitary lung lesions bilaterally, and [F-18]2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography with CT (PET/CT) showed increased uptake in the lung lesions as well as regional lymph nodes. Subsequent biopsy of an involved lymph node confirmed classical Hodgkin lymphoma, nodular sclerosis type. This case represents an unusual presentation for a child with Hodgkin lymphoma and demonstrates a role for 18 F-FDG PET/CT in evaluating a child with cavitary lung lesions. (orig.)

  2. Lung cancer imaging

    CERN Document Server

    Ravenel, James G

    2013-01-01

    This book provides a guide to the diagnosis, staging and overview of the management of lung cancer relevant to practicing radiologists so that they can better understand the decision making issues and provide more useful communication to treating physicians.

  3. [Interstitial lung diseases].

    Science.gov (United States)

    Junker, K; Brasch, F

    2008-11-01

    Interstitial lung diseases comprise a heterogeneous group of about 200 entities. In the classification of these diseases, diffuse parenchymal lung diseases with known cause, granulomatous diseases, and other specific interstitial lung diseases are separated from the important group of idiopathic interstitial pneumonias, which are classified according to the 2002 ATS/ERS consensus classification. Concerning the histological pattern, this classification differentiates between "usual interstitial pneumonia" (UIP), "nonspecific interstitial pneumonia" (NSIP), "organising pneumonia" (COP), "diffuse alveolar damage" (DAD), "respiratory bronchiolitis" (RB), "desquamative interstitial pneumonia" (DIP), "lymphocytic interstitial pneumonia" (LIP) and "unclassifiable interstitial pneumonias". A key message of this classification is that the pathologist will give the diagnosis of a histological pattern, whereas the final clinicopathologic diagnosis can be made only by the clinical pulmonologist after careful correlation with the clinical and radiologic features, which is essential in the diagnosis of interstitial lung diseases.

  4. Lungs in TSC

    Science.gov (United States)

    ... or pulmonary hypertension (high blood pressure in the arteries that supply the lungs). There have been only ... www.thoracic.org The LAM Foundation 4520 Cooper Road, Suite 300, Cincinnati, OH 45242 Phone: 513-777- ...

  5. Various semiclassical limits of torus conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Alkalaev, Konstantin [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of General and Applied Physics, Moscow Institute of Physics and Technology,Institutskiy per. 7, Dolgoprudnyi, Moscow region, 141700 (Russian Federation); Geiko, Roman [Mathematics Department, National Research University Higher School of Economics,Usacheva str. 6, Moscow, 119048 (Russian Federation); Rappoport, Vladimir [I.E. Tamm Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky ave. 53, Moscow, 119991 (Russian Federation); Department of Quantum Physics, Institute for Information Transmission Problems,Bolshoy Karetny per. 19, Moscow, 127994 (Russian Federation)

    2017-04-12

    We study four types of one-point torus blocks arising in the large central charge regime. There are the global block, the light block, the heavy-light block, and the linearized classical block, according to different regimes of conformal dimensions. It is shown that the blocks are not independent being connected to each other by various links. We find that the global, light, and heavy-light blocks correspond to three different contractions of the Virasoro algebra. Also, we formulate the c-recursive representation of the one-point torus blocks which is relevant in the semiclassical approximation.

  6. Lung cysts in chronic paracoccidioidomycosis*

    OpenAIRE

    Costa, André Nathan; Marchiori, Edson; Benard, Gil; Araújo, Mariana Sponholz; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    On HRCT scans, lung cysts are characterized by rounded areas of low attenuation in the lung parenchyma and a well-defined interface with the normal adjacent lung. The most common cystic lung diseases are lymphangioleiomyomatosis, Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that patients with paracoccidioidomy...

  7. Activation of the canonical bone morphogenetic protein (BMP pathway during lung morphogenesis and adult lung tissue repair.

    Directory of Open Access Journals (Sweden)

    Alexandros Sountoulidis

    Full Text Available Signaling by Bone Morphogenetic Proteins (BMP has been implicated in early lung development, adult lung homeostasis and tissue-injury repair. However, the precise mechanism of action and the spatio-temporal pattern of BMP-signaling during these processes remains inadequately described. To address this, we have utilized a transgenic line harboring a BMP-responsive eGFP-reporter allele (BRE-eGFP to construct the first detailed spatiotemporal map of canonical BMP-pathway activation during lung development, homeostasis and adult-lung injury repair. We demonstrate that during the pseudoglandular stage, when branching morphogenesis progresses in the developing lung, canonical BMP-pathway is active mainly in the vascular network and the sub-epithelial smooth muscle layer of the proximal airways. Activation of the BMP-pathway becomes evident in epithelial compartments only after embryonic day (E 14.5 primarily in cells negative for epithelial-lineage markers, located in the proximal portion of the airway-tree, clusters adjacent to neuro-epithelial-bodies (NEBs and in a substantial portion of alveolar epithelial cells. The pathway becomes activated in isolated E12.5 mesenchyme-free distal epithelial buds cultured in Matrigel suggesting that absence of reporter activity in these regions stems from a dynamic cross-talk between endoderm and mesenchyme. Epithelial cells with activated BMP-pathway are enriched in progenitors capable of forming colonies in three-dimensional Matrigel cultures.As lung morphogenesis approaches completion, eGFP-expression declines and in adult lung its expression is barely detectable. However, upon tissue-injury, either with naphthalene or bleomycin, the canonical BMP-pathways is re-activated, in bronchial or alveolar epithelial cells respectively, in a manner reminiscent to early lung development and in tissue areas where reparatory progenitor cells reside. Our studies illustrate the dynamic activation of canonical BMP

  8. MIGRAINE AND STROKE: VASCULAR COMORBIDITY

    Directory of Open Access Journals (Sweden)

    Donata eGuidetti

    2014-10-01

    Full Text Available Several comorbidities are associated to migraine.Recent meta-analyses have consistently demonstrated a relationship between migraine and stroke, which is well-defined for ischaemic stroke and migraine with aura, even stronger in females on oral contraceptives or smokers. However, there seems to be no clear-cut association between stroke in migraineurs and the common vascular risk factors, at least in the young adult population. Migraineurs also run an increased risk of hemorrhagic stroke, while the association between migraine and cardiovascular disease remains poorly defined.Another aspect is the relationship between migraine and the presence of silent brain lesions. It has been demonstrated that there is an increased frequency of ischaemic lesions in the white matter of migraineurs, especially silent infarcts in the posterior circulation territory in patients with at least 10 attacks per month. Although there is a higher prevalence of patent foramen ovale (PFO in migraineurs, the relationship between migraine and PFO remains controversial and PFO closure is not a recommended procedure to prevent migraine. As an increased frequency of cervical artery dissections has been observed in migrainous patients, it has been hypothesized that migraine may represent a predisposing factor for cervical artery dissection. There still remains the question as to whether migraine should be considered a true vascular disease or if the comorbidity between migraine and cerebrovascular disease may have underlying shared risk factors or pathophysiological mechanisms. Although further studies are required to clarify this issue, current evidence supports a clinical management where MA patients should be screened for other concomitant vascular risk factors and treated accordingly.

  9. Vascular dementia: Facts and controversies

    Directory of Open Access Journals (Sweden)

    Pavlović Aleksandra

    2013-01-01

    Full Text Available Vascular dementia (VaD is the second most frequent dementia after Alzheimer’s disease, and is diagnosed during lifetime in 20% of demented patients. Five­year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors for VaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step­by­step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class IIa recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer’s disease dementia. [Projekat Ministarstva nauke Republike Srbije, br. 175022 i br. 175033

  10. Dosimetric lung models

    International Nuclear Information System (INIS)

    James, A.C.; Roy, M.

    1986-01-01

    The anatomical and physiological factors that vary with age and influence the deposition of airborne radionuclides in the lung are reviewed. The efficiency with which aerosols deposit in the lung for a given exposure at various ages from birth to adulthood is evaluated. Deposition within the lung is considered in relation to the clearance mechanisms acting in different regions or compartments. The procedure for evaluating dose to sensitive tissues in lung and transfer to other organs that is being considered by the Task Group established by ICRP to review the Lung Model is outlined. Examples of the application of this modelling procedure to evaluate lung dose as a function of age are given, for exposure to radon daughters in dwellings, and for exposure to an insoluble 239 Pu aerosol. The former represents exposure to short-lived radionuclides that deliver relatively high doses to bronchial tissue. In this case, dose rates are marginally higher in children than in adults. Plutonium exposure represents the case where dose is predominantly delivered to respiratory tissue and lymph nodes. In this case, the life-time doses tend to be lower for exposure in childhood. Some of the uncertainties in this modelling procedure are noted

  11. Multiple cystic lung disease

    Directory of Open Access Journals (Sweden)

    Flavia Angélica Ferreira Francisco

    2015-12-01

    Full Text Available Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt–Hogg–Dubé; other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management.

  12. Spinal vascular malformations; Spinale Gefaessmalformationen

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, U. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2012-05-15

    Spinal vascular malformations are a group of rare diseases with different clinical presentations ranging from incidental asymptomatic findings to progressive tetraplegia. This article provides an overview about imaging features as well as clinical and therapeutic aspects of spinal arteriovenous malformations, cavernomas and capillary telangiectasia. (orig.) [German] Spinale Gefaessmalformationen sind eine Gruppe seltener Erkrankungen mit unterschiedlichen klinischen Praesentationen, die vom asymptomatischen Zufallsbefund bis zur progredienten Tetraparese reichen. Dieser Artikel gibt einen Ueberblick ueber radiologische Befunde sowie klinische und therapeutische Aspekte von spinalen arteriovenoesen Malformationen, Kavernomen und kapillaeren Teleangiektasien. (orig.)

  13. Vascular comorbidities in multiple sclerosis

    DEFF Research Database (Denmark)

    Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils

    2016-01-01

    and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique......To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case–control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980–2005 were identified from the Danish Multiple Sclerosis Registry...

  14. The Efficiency of Vascular Embolization Using Alginate Gel : An Experimental Study in Rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Woo Baek; Kang, Yeong Han [Dept. of Diagnostic Radiology, Daegu Catholic University Hospital, Daegu (Korea, Republic of); Kim, Jong Ki [Dept. of Biomedical Engineering, Daegu Catholic University, Daegu (Korea, Republic of)

    2009-03-15

    The purpose of this study was to investigate the applicability of poly-L-guluronic alginate (PGA) gel in vascular embolization with angiography simulation. To prepare a gel-forming PGA from no guluronate-rich Laminaria japonica, a new acid hydrolysis method was employed with a lower HCL concentration (0.03 M) and a shorter treatment time (5 min). The obtained PGAs were selected based on gel stability and viscosity. Glass aneurysm model was used to simulate gel embolization in vitro. Then, finally, the PGA was used to embolize the renal vascular system by using a rabbit model and angiography. Glass aneurysm model was made to simulate gel embolization procedure. PGA solution was injected from pump through 2-way catheter. Subsequent injection of CaCl{sub 2} successfully formed gels inside aneurysm model that conforming to its inner contour. In rabbit model, first, renal artery and aorta leading to the right kidney were ligated to block blood flow, then conventional contrast agent was injected through aorta to check the arterial patency to the left kidney. In sequential artery injection method, PGA and CaCl{sub 2} were injected through renal artery sequentially via a single catheter. Re-injection of contrast agent after removing ligated aorta showed blood flow to the right kidney but no flow in the left kidney. This result demonstrated a complete blocking of blood flow due to gel formation in vascular bed of the left kidney. Instillation of calcium alginate into aneurysm model and arterial system in vivo produced an embolization that better fills and conforms to the contour of aneurysms or blocking vascular bed completely. Therefore, PGA was effective endovascular occlusion materials and provide an efficiency of vascular angiography.

  15. The Efficiency of Vascular Embolization Using Alginate Gel : An Experimental Study in Rabbit

    International Nuclear Information System (INIS)

    Lee, Woo Baek; Kang, Yeong Han; Kim, Jong Ki

    2009-01-01

    The purpose of this study was to investigate the applicability of poly-L-guluronic alginate (PGA) gel in vascular embolization with angiography simulation. To prepare a gel-forming PGA from no guluronate-rich Laminaria japonica, a new acid hydrolysis method was employed with a lower HCL concentration (0.03 M) and a shorter treatment time (5 min). The obtained PGAs were selected based on gel stability and viscosity. Glass aneurysm model was used to simulate gel embolization in vitro. Then, finally, the PGA was used to embolize the renal vascular system by using a rabbit model and angiography. Glass aneurysm model was made to simulate gel embolization procedure. PGA solution was injected from pump through 2-way catheter. Subsequent injection of CaCl 2 successfully formed gels inside aneurysm model that conforming to its inner contour. In rabbit model, first, renal artery and aorta leading to the right kidney were ligated to block blood flow, then conventional contrast agent was injected through aorta to check the arterial patency to the left kidney. In sequential artery injection method, PGA and CaCl 2 were injected through renal artery sequentially via a single catheter. Re-injection of contrast agent after removing ligated aorta showed blood flow to the right kidney but no flow in the left kidney. This result demonstrated a complete blocking of blood flow due to gel formation in vascular bed of the left kidney. Instillation of calcium alginate into aneurysm model and arterial system in vivo produced an embolization that better fills and conforms to the contour of aneurysms or blocking vascular bed completely. Therefore, PGA was effective endovascular occlusion materials and provide an efficiency of vascular angiography.

  16. A generative modeling approach to connectivity-Electrical conduction in vascular networks

    DEFF Research Database (Denmark)

    Hald, Bjørn Olav

    2016-01-01

    The physiology of biological structures is inherently dynamic and emerges from the interaction and assembly of large collections of small entities. The extent of coupled entities complicates modeling and increases computational load. Here, microvascular networks are used to present a novel...... generative approach to connectivity based on the observation that biological organization is hierarchical and composed of a limited set of building blocks, i.e. a vascular network consists of blood vessels which in turn are composed by one or more cell types. Fast electrical communication is crucial...... to synchronize vessel tone across the vast distances within a network. We hypothesize that electrical conduction capacity is delimited by the size of vascular structures and connectivity of the network. Generation and simulation of series of dynamical models of electrical spread within vascular networks...

  17. Radial Coordinates for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2013-01-01

    We develop the theory of conformal blocks in CFT_d expressing them as power series with Gegenbauer polynomial coefficients. Such series have a clear physical meaning when the conformal block is analyzed in radial quantization: individual terms describe contributions of descendants of a given spin. Convergence of these series can be optimized by a judicious choice of the radial quantization origin. We argue that the best choice is to insert the operators symmetrically. We analyze in detail the resulting "rho-series" and show that it converges much more rapidly than for the commonly used variable z. We discuss how these conformal block representations can be used in the conformal bootstrap. In particular, we use them to derive analytically some bootstrap bounds whose existence was previously found numerically.

  18. Diversity Gain through Antenna Blocking

    Directory of Open Access Journals (Sweden)

    V. Dehghanian

    2012-01-01

    Full Text Available As part of the typical usage mode, interaction between a handheld receiver antenna and the operator's RF absorbing body and nearby objects is known to generate variability in antenna radiation characteristics through blocking and pattern changes. It is counterintuitive that random variations in blocking can result in diversity gain of practical applicability. This diversity gain is quantified from a theoretical and experimental perspective. Measurements carried out at 1947.5 MHz verify the theoretical predictions, and a diversity gain of 3.1 dB was measured through antenna blocking and based on the utilized measurement setup. The diversity gain can be exploited to enhance signal detectability of handheld receivers based on a single antenna in indoor multipath environments.

  19. Cryptanalysis of Selected Block Ciphers

    DEFF Research Database (Denmark)

    Alkhzaimi, Hoda A.

    , pseudorandom number generators, and authenticated encryption designs. For this reason a multitude of initiatives over the years has been established to provide a secure and sound designs for block ciphers as in the calls for Data Encryption Standard (DES) and Advanced Encryption Standard (AES), lightweight...... ciphers initiatives, and the Competition for Authenticated Encryption: Security, Applicability, and Robustness (CAESAR). In this thesis, we first present cryptanalytic results on different ciphers. We propose attack named the Invariant Subspace Attack. It is utilized to break the full block cipher...... on the family of lightweight block cipher SIMON that was published by the U.S National Security Agency (NSA). The ciphers are developed with optimization towards both hardware and software in mind. While the specification paper discusses design requirements and performance of the presented lightweight ciphers...

  20. Climatological features of blocking anticyclones

    International Nuclear Information System (INIS)

    Lupo, A.R.; Smith, P.J.; Oglesby, R.J.

    1994-01-01

    Several climatological studies have been previously performed using large observational data sets (i.e., 10 years or longer) in order to determine the predominant characteristics of blocking anticyclones, including favored development regions, duration, preferred seasonal occurrence, and frequency of occurrence. These studies have shown that blocking anticyclones occur most frequently from October to April over the eastern Atlantic and Pacific oceans downstream from both the North American and Asian continental regions and the storm track regions to the east of these continents. Some studies have also revealed the presence of a third region block formation in western Russia near 40 degrees E which is associated with another storm track region over the Mediterranean and western Asia

  1. Projectors, shadows, and conformal blocks

    Energy Technology Data Exchange (ETDEWEB)

    Simmons-Duffin, David [Jefferson Physical Laboratory, Harvard University,Cambridge, MA 02138 (United States)

    2014-04-24

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism' of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d-dimensions can be expressed as integrals over the projective null-cone in the “embedding space' ℝ{sup d+1,1}. Taking care with their analytic structure, these integrals can be evaluated in great generality, reducing the computation of conformal blocks to a bookkeeping exercise. To facilitate calculations in four-dimensional CFTs, we introduce techniques for writing down conformally-invariant correlators using auxiliary twistor variables, and demonstrate their use in some simple examples.

  2. [Pulmonary vascular remodeling in congenital cardiovascular abnormalities: an eternal topic].

    Science.gov (United States)

    Liu, Han-Min

    2013-10-01

    Pulmonary arterial hypertension (PAH) is one of the most severe complications of congenital heart defects with left to right shunt. Pulmonary vascular remodeling (PVR) is extremely essential in PAH. Therefore, prevention and reversion of PVR is one of the most important factors for improving quality of life for children suffering from PAH. In this article we reviewed the emerging research views on PVR from the disciplines of oncology and anti-tumor pharmacy. Two main sections were included. On the one hand, we introduced the "ATM signal turning point hypothesis" from the DNA damage response (DDR) mechanism research in oncology. The hypothesis suggests that the tumor-like proliferation of vascular smooth muscle cells might be the pathological basis of obstructive PAH. On the other hand, a new lung-targeted drug delivery system based on the fact that low concentration of anti-tumor drugs can inhibit angiogenesis without cellular toxicity was introduced. These new research directions could extend current practice in PVR therapy.

  3. The mitochondrial activation of silicate and its role in silicosis, black lung disease and lung cancer.

    Science.gov (United States)

    Hadler, H I; Cook, G L

    1979-01-01

    Silicate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxy-butyrate is the substrate. Uncoupling is blocked by rutamycin. Just as in the case when phosphate is combined with hydrazine, ATP, ADP, PPi, and Mg++ protect against hydrazine when silicate is combined with hydrazine. A high level of ADP in the absence of added phosphate, but in the presence of silicate, induces a pseudo state three of the mitochondria. Silicate, like sulfate and arsenate which have been reported previously, is activated by the enzymes which mediate oxidative phosphorylation. These results serve to explain a role for silicate in silicosis, black lung disease, and cancer. In addition, since there is suggestive evidence in the literature that lung tissue solubilizes asbestos fibers, these results not only expand the confluence between oxidative phosphorylation and chemical carcinogenesis but are correlated with the synergistic carcinogenicity of asbestos and smoking observed by epidemiologists.

  4. Projectors, Shadows, and Conformal Blocks

    OpenAIRE

    Simmons-Duffin, David

    2012-01-01

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the “shadow formalism” of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d -dimensions can be expressed as integrals over the projective null-cone in the “embedding space” $ \\mathbb{R} $ d +1,1 . Taking ...

  5. Pathophysiology of transfusion-related acute lung injury.

    Science.gov (United States)

    Looney, Mark R; Gilliss, Brian M; Matthay, Michael A

    2010-09-01

    The purpose of this review is to summarize the recent experimental and clinical literature on the pathogenesis of transfusion-related acute lung injury (TRALI). In both experimental and clinical TRALI, an immune priming step is generally necessary to produce lung injury. Experimental studies have used mainly lipopolysaccharide (LPS) as the priming step, whereas in clinical TRALI the specific priming events are currently being defined and include recent surgery and active infections. Experimental studies have modeled TRALI by using anti-major histocompatibility complex antibodies, antineutrophil antibodies, and also bioactive lipids isolated from stored human blood. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response and lung vascular injury. New work has focused on the interplay between neutrophils and platelets in the lung microcirculation. Finally, plasma mitigation strategies implemented in several countries are showing early promise in decreasing the incidence of TRALI from high plasma volume blood products. TRALI requires an immune priming step followed by transfusion of a blood product with either leukocyte allo-antibodies or biological response modifiers. TRALI invokes an acute immune response dominated by neutrophils interacting with platelets and the lung endothelium.

  6. Application of positron emission tomography in the lung

    International Nuclear Information System (INIS)

    Valind, S.O.; Wollmer, P.E.; Rhodes, C.G.

    1985-01-01

    The early application of positron emission tomography in the lung was mainly concerned with the investigation of the regional volume of the vascular and extravascular compartments, using measurements of fractional blood volume and lung density. However, in addition to its passive role in the exchange of oxygen and carbon dioxide, the lung exerts a number of active, metabolic functions such as the inactivation of circulating vasoactive compounds and the synthesis and release of biologically active substances. Furthermore, many of the pulmonary disorders originate at a cellular or metabolic level, or have metabolic consequences. Many of the substrates of biochemical reactions and the biologically active compounds, or their analogs, can be labeled with positron-emitting radioisotopes without disturbing their biological or biochemical characteristics. In combination with the development of the appropriate physiological and biochemical models, the quantitative measurements possible with PET provide a unique opportunity of regionally studying the metabolic processes of the lung of man in vivo. Hence, a range of different expressions of metabolism and of lung function can be evaluated and their interdependence can be studied regionally

  7. Fluorometry of ischemia reperfusion injury in rat lungs in vivo

    Science.gov (United States)

    Sepehr, R.; Staniszewski, K.; Jacobs, E. R.; Audi, S.; Ranji, Mahsa

    2013-02-01

    Previously we demonstrated the utility of optical fluorometry to evaluate lung tissue mitochondrial redox state in isolated perfused rats lungs under various chemically-induced respiratory states. The objective of this study was to evaluate the effect of acute ischemia on lung tissue mitochondrial redox state in vivo using optical fluorometry. Under ischemic conditions, insufficient oxygen supply to the mitochondrial chain should reduce the mitochondrial redox state calculated from the ratio of the auto-fluorescent mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavoprotein Adenine Dinucleotide). The chest of anesthetized, and mechanically ventilated Sprague-Dawley rat was opened to induce acute ischemia by clamping the left hilum to block both blood flow and ventilation to one lung for approximately 10 minutes. NADH and FAD fluorescent signals were recorded continuously in a dark room via a fluorometer probe placed on the pleural surface of the left lung. Acute ischemia caused a decrease in FAD and an increase in NADH, which resulted in an increase in the mitochondrial redox ratio (RR=NADH/FAD). Restoration of blood flow and ventilation by unclamping the left hilum returned the RR back to its baseline. These results (increase in RR under ischemia) show promise for the fluorometer to be used in a clinical setting for evaluating the effect of pulmonary ischemia-reperfusion on lung tissue mitochondrial redox state in real time.

  8. A new method of prefabricated vascularized allogenic bone grafts for maxillo-mandibular reconstruction

    International Nuclear Information System (INIS)

    Pill-Hoon Choung

    1999-01-01

    Although there are various applications of allogenic bone grafts, a new technique of prevascularized lyophilized allogenic bone grafting for maxillo-mandibular reconstruction will be presented. Allogenic bone has been made by author's protocol for jaw defects as a powder, chip or block bone type. The author used lyophilized allogenic bone grafts for discontinuity defects as a block bone. In those cases, neovascularization and resorption of the allogenic bone were important factors for success of grafting. To overcome the problems, the author designed the technique of prefabricated vascularization of allogenic bone, which was lyophilized cranium, with an application of bovine BMP or not. Lyophilized cranial bone was designed for the defects and was put into the scalp. After confirming a hot spot via scintigram several months later, vascularized allogenic bone was harvested pedicled on the parietotemporal fascia based on the superficial temporal artery and vein. Vascularized allogenic cranial bone was rotated into the defect and fixed rigidly. Postoperatively, there was no severe resorption and functional disturbance of the mandible. In this technique, BMP seems to be an important role to help osteogenesis and neovascularization. Eight patients underwent prefabricated vascularization of allogenic bone grafts. Among them, four cases of reconstruction in mandibular discontinuity defects and one case of reconstruction in maxillectomy defect underwent this method, which will be presented with good results. This method may be an alternative technique of microvascular free bone graft

  9. Vascular adaption to physical inactivity in humans

    OpenAIRE

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical inactivity, exercise decreases the risk for cardiovascular disease. This beneficial effect of exercise is partly due to changes in vascular function and structure. However, far less is known about vascular ...

  10. Cryptic vascular malformations involving the brainstem

    Energy Technology Data Exchange (ETDEWEB)

    Yeates, A.; Enzmann, D.

    1983-01-01

    Six patients with angiographically cryptic vascular malformations involving the brainstem were examined with computed tomography (CT). The clinical and CT findings of cryptic vascular malformations of the brainstem are described and distinguished from those of brainstem glioma and multiple sclerosis. Calcification within a brainstem lesion that displays relatively little mass effect and shows little contrast enhancement, particularly when associated with a long history of waxing and waning brainstem symptoms, should suggest a vascular malformation.

  11. Diffuse and vascular hepatic diseases

    International Nuclear Information System (INIS)

    Kreimeyer, S.; Grenacher, L.

    2011-01-01

    In addition to focal liver lesions, diffuse and vascular disorders of the liver represent a wide spectrum of liver diseases which are from the radiological point of view often difficult or nearly impossible to diagnose. Classical diagnostic methods are computed tomography and magnetic resonance imaging in addition to ultrasound. Diffuse parenchymal damage caused by diseases of various etiologies is therefore difficult to evaluate because it often lacks characteristic morphological features. For hepatic steatosis, hemochromatosis/siderosis as an example of a diffuse storage disease and sarcoidosis and candidiasis as infectious/inflammatory diseases, an image-based diagnosis is appropriate in some cases. For most diffuse liver diseases, however only nonspecific changes are visualized. Vascular pathologies of the liver, such as the Budd-Chiari syndrome and portal vein thrombosis, however, can usually be diagnosed very clearly using radiology and there is also a very effective interventional radiological treatment. Chronic diseases very often culminate in liver cirrhosis which is highly associated with an increased risk of liver cancer. (orig.) [de

  12. Microparticles, vascular function, and atherothrombosis.

    Science.gov (United States)

    Rautou, Pierre-Emmanuel; Vion, Anne-Clémence; Amabile, Nicolas; Chironi, Gilles; Simon, Alain; Tedgui, Alain; Boulanger, Chantal M

    2011-08-19

    Membrane-shed submicron microparticles (MPs) are released after cell activation or apoptosis. High levels of MPs circulate in the blood of patients with atherothrombotic diseases, where they could serve as a useful biomarker of vascular injury and a potential predictor of cardiovascular mortality and major adverse cardiovascular events. Atherosclerotic lesions also accumulate large numbers of MPs of leukocyte, smooth muscle cell, endothelial, and erythrocyte origin. A large body of evidence supports the role of MPs at different steps of atherosclerosis development, progression, and complications. Circulating MPs impair the atheroprotective function of the vascular endothelium, at least partly, by decreased nitric oxide synthesis. Plaque MPs favor local inflammation by augmenting the expression of adhesion molecule, such as intercellular adhesion molecule -1 at the surface of endothelial cell, and monocyte recruitment within the lesion. In addition, plaque MPs stimulate angiogenesis, a key event in the transition from stable to unstable lesions. MPs also may promote local cell apoptosis, leading to the release and accumulation of new MPs, and thus creating a vicious circle. Furthermore, highly thrombogenic plaque MPs could increase thrombus formation at the time of rupture, together with circulating MPs released in this context by activated platelets and leukocytes. Finally, MPs also could participate in repairing the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization.

  13. Neuroradiological findings in vascular dementia

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, Ali; Miaux, Yves; Suhy, Joyce; Pauls, Jon; Lopez, Ria [Synarc, Inc., Department of Radiology Services, San Francisco, CA (United States); Rovira-Canellas, Alex [Hospital General Universitari Vall d' Hebron, Unita de Resonancia Magnetica, Barcelona (Spain); Posner, Holly [Eisai, Inc., Teaneck, NJ (United States)

    2007-01-15

    There are multiple diagnostic criteria for vascular dementia (VaD) that may define different populations. Utilizing the criteria of the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) has provided improved consistency in the diagnosis of VaD. The criteria include a table listing brain imaging lesions associated with VaD. The different neuroradiological aspects of the criteria are reviewed based on the imaging data from an ongoing large-scale clinical trial testing a new treatment for VaD. The NINDS-AIREN criteria were applied by a centralized imaging rater to determine eligibility for enrollment in 1,202 patients using brain CT or MRI. Based on the above data set, the neuroradiological features that are associated with VaD and that can result from cerebral small-vessel disease with extensive leukoencephalopathy or lacunae (basal ganglia or frontal white matter), or may be the consequence of single strategically located infarcts or multiple infarcts in large-vessel territories, are illustrated. These features may also be the consequence of global cerebral hypoperfusion, intracerebral hemorrhage, or other mechanisms such as genetically determined arteriopathies. Neuroimaging confirmation of cerebrovascular disease in VaD provides information about the topography and severity of vascular lesions. Neuroimaging may also assist with the differential diagnosis of dementia associated with normal pressure hydrocephalus, chronic subdural hematoma, arteriovenous malformation or tumoral diseases. (orig.)

  14. Leaf hydraulics II: vascularized tissues.

    Science.gov (United States)

    Rockwell, Fulton E; Holbrook, N Michele; Stroock, Abraham D

    2014-01-07

    Current models of leaf hydration employ an Ohm's law analogy of the leaf as an ideal capacitor, neglecting the resistance to flow between cells, or treat the leaf as a plane sheet with a source of water at fixed potential filling the mid-plane, neglecting the discrete placement of veins as well as their resistance. We develop a model of leaf hydration that considers the average conductance of the vascular network to a representative areole (region bounded by the vascular network), and represent the volume of tissue within the areole as a poroelastic composite of cells and air spaces. Solutions to the 3D flow problem are found by numerical simulation, and these results are then compared to 1D models with exact solutions for a range of leaf geometries, based on a survey of temperate woody plants. We then show that the hydration times given by these solutions are well approximated by a sum of the ideal capacitor and plane sheet times, representing the time for transport through the vasculature and tissue respectively. We then develop scaling factors relating this approximate solution to the 3D model, and examine the dependence of these scaling factors on leaf geometry. Finally, we apply a similar strategy to reduce the dimensions of the steady state problem, in the context of peristomatal transpiration, and consider the relation of transpirational gradients to equilibrium leaf water potential measurements. © 2013 Published by Elsevier Ltd. All rights reserved.

  15. CIRSE Vascular Closure Device Registry

    International Nuclear Information System (INIS)

    Reekers, Jim A.; Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2011-01-01

    Purpose: Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods: The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results: Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0–14.5] for antegrade access and 1.8% (95% CI 1.1–2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only 5.9 cm, and two vessel occlusions. Conclusion: The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.

  16. Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat

    International Nuclear Information System (INIS)

    Rabinovitch, M.; Mullen, M.; Rosenberg, H.C.; Maruyama, K.; O'Brodovich, H.; Olley, P.M.

    1988-01-01

    Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, the authors investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. They instrumented the rats with indwelling cardiovascular catheters and compared the hemodynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. They then determine whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. They observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effects of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both antiotensin II and prostacyclin infusion similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins

  17. The aging lung

    Directory of Open Access Journals (Sweden)

    Lowery EM

    2013-11-01

    Full Text Available Erin M Lowery,1 Aleah L Brubaker,2 Erica Kuhlmann,1 Elizabeth J Kovacs31Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine at Loyola University Medical Center, 2Loyola University Stritch School of Medicine, 3Department of Surgery, Loyola University Medical Center, Maywood, IL, USAAbstract: There are many age-associated changes in the respiratory and pulmonary immune system. These changes include decreases in the volume of the thoracic cavity, reduced lung volumes, and alterations in the muscles that aid respiration. Muscle function on a cellular level in the aging population is less efficient. The elderly population has less pulmonary reserve, and cough strength is decreased in the elderly population due to anatomic changes and muscle atrophy. Clearance of particles from the lung through the mucociliary elevator is decreased and associated with ciliary dysfunction. Many complex changes in immunity with aging contribute to increased susceptibility to infections including a less robust immune response from both the innate and adaptive immune systems. Considering all of these age-related changes to the lungs, pulmonary disease has significant consequences for the aging population. Chronic lower respiratory tract disease is the third leading cause of death in people aged 65 years and older. With a large and growing aging population, it is critical to understand how the body changes with age and how this impacts the entire respiratory system. Understanding the aging process in the lung is necessary in order to provide optimal care to our aging population. This review focuses on the nonpathologic aging process in the lung, including structural changes, changes in muscle function, and pulmonary immunologic function, with special consideration of obstructive lung disease in the elderly.Keywords: aging, lung, pulmonary immunology, COPD

  18. Proatherogenic pathways leading to vascular calcification

    International Nuclear Information System (INIS)

    Mazzini, Michael J.; Schulze, P. Christian

    2006-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease

  19. Vascular nursing in Greece: luxury or necessity?

    Science.gov (United States)

    Georgakarakos, Efstratios; Bitza, Christina; Papanas, Nikolaos; Matsagkas, Miltiadis; Lazarides, Miltos K

    2013-09-01

    Although peripheral arterial disease is prevalent in the primary care setting, insufficient vascular education among nurses and physicians coupled with certain economic constraints undermines treatment efficacy. Moreover, the burden of advanced venous pathology such as posthrombotic syndrome, venous ulcers, and lymphedema remains suboptimally treated. This article advocates the development of a vascular nursing specialty as a means to improving vascular care especially nowadays, when health care providers dictate comprehensive and cost-effective nursing practice and patient management. It also presents the first attempt to organize a Vascular Nursing Educational Session in Greece.

  20. Main-chain supramolecular block copolymers.

    Science.gov (United States)

    Yang, Si Kyung; Ambade, Ashootosh V; Weck, Marcus

    2011-01-01

    Block copolymers are key building blocks for a variety of applications ranging from electronic devices to drug delivery. The material properties of block copolymers can be tuned and potentially improved by introducing noncovalent interactions in place of covalent linkages between polymeric blocks resulting in the formation of supramolecular block copolymers. Such materials combine the microphase separation behavior inherent to block copolymers with the responsiveness of supramolecular materials thereby affording dynamic and reversible materials. This tutorial review covers recent advances in main-chain supramolecular block copolymers and describes the design principles, synthetic approaches, advantages, and potential applications.