Sample records for blocks lung vascular

  1. Perioperative Management of Interscalene Block in Patients with Lung Disease

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    Eric S. Schwenk


    Full Text Available Interscalene nerve block impairs ipsilateral lung function and is relatively contraindicated for patients with lung impairment. We present a case of an 89-year-old female smoker with prior left lung lower lobectomy and mild to moderate lung disease who presented for right shoulder arthroplasty and insisted on regional anesthesia. The patient received a multimodal perioperative regimen that consisted of a continuous interscalene block, acetaminophen, ketorolac, and opioids. Surgery proceeded uneventfully and postoperative analgesia was excellent. Pulmonary physiology and management of these patients will be discussed. A risk/benefit discussion should occur with patients having impaired lung function before performance of interscalene blocks. In this particular patient with mild to moderate disease, analgesia was well managed through a multimodal approach including a continuous interscalene block, and close monitoring of respiratory status took place throughout the perioperative period, leading to a successful outcome.

  2. Vascular endothelial growth factor blocking agents in retinal vein occlusion

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    Chris Canning


    Full Text Available This paper summarises the current status of the use of vascular endothelial growth factor (VEGF blocking agents in retinal vein occlusion. There have been no randomised controlled trials comparing this treatment with the current standard treatment (largely laser so the lower grade evidence of single treatment case series and anecdotal reports are discussed. VEGF blockers are good at reducing macular oedema in the short term, do improve visual acuity in many cases, and do not seem to adversely affect the long term revascularisation that is necessary to overcome the vein occlusion. VEGF blocking agents are not used in isolation in this condition - they will remain an adjunct to systemic and other local treatments. The literature was reviewed in online searches of Embase and Ovid and the papers quoted are a representative sample of a larger body of publications.

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

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    Duan Yingli


    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

  4. Angiogenin and vascular endothelial growth factor expression in lungs of lung cancer patients. (United States)

    Rozman, Ales; Silar, Mira; Kosnik, Mitja


    BACKGROUND.: Lung cancer is the leading cause of cancer deaths. Angiogenesis is crucial process in cancer growth and progression. This prospective study evaluated expression of two central regulatory molecules: angiogenin and vascular endothelial growth factor (VEGF) in patients with lung cancer. PATIENTS AND METHODS.: Clinical data, blood samples and broncho-alveolar lavage (BAL) from 23 patients with primary lung carcinoma were collected. BAL fluid was taken from part of the lung with malignancy, and from corresponding healthy side of the lung. VEGF and angiogenin concentrations were analysed by an enzyme-linked immunosorbent assay. Dilution of bronchial secretions in the BAL fluid was calculated from urea concentration ratio between serum and BAL fluid. RESULTS.: We found no statistical correlation between angiogenin concentrations in serum and in bronchial secretions from both parts of the lung. VEGF concentrations were greater in bronchial secretions in the affected side of the lung than on healthy side. Both concentrations were greater than serum VEGF concentration. VEGF concentration in serum was in positive correlation with tumour size (p = 0,003) and with metastatic stage of disease (p = 0,041). There was correlation between VEGF and angiogenin concentrations in bronchial secretions from healthy side of the lung and between VEGF and angiogenin concentrations in bronchial secretions from part of the lung with malignancy. CONCLUSION.: Angiogenin and VEGF concentrations in systemic, background and local samples of patients with lung cancer are affected by different mechanisms. Pro-angiogenic activity of lung cancer has an important influence on the levels of angiogenin and VEGF.

  5. 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.

  6. Vascular endothelial growth factor co-ordinates proper development of lung epithelium and vasculature. (United States)

    Zhao, Liqing; Wang, Ke; Ferrara, Napoleone; Vu, Thiennu H


    The vasculature forms an intrinsic functional component of the lung and its development must be tightly regulated and coordinated with lung epithelial morphogenesis. Vascular endothelial growth factor (VEGF) and its receptors are highly expressed in a complementary pattern in the lungs during embryonic development. VEGF is expressed by epithelium and the receptors in the surrounding mesenchyme. To determine the function of VEGF in lung formation, we inhibited its activity using a soluble receptor in lung renal capsule grafts. Inhibition of VEGF results in inhibition of vascular development and significant alteration in epithelial development. Epithelial proliferation is inhibited, sacculation is impaired, and the epithelium undergoes apoptosis. Interestingly, when VEGF is attenuated, epithelial differentiation still proceeds, as shown by acquisition of both proximal and distal markers. These data show that VEGF co-ordinates epithelial and vascular development. It is required for the development of the lung vasculature and the vasculature is necessary for epithelial proliferation and morphogenesis, but not for cell differentiation.

  7. 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 impo

  8. Nanopatterned block copolymers for use as vascular biomaterials (United States)

    Silverstein, Joshua S.

    Manipulation of surface topography or chemistry has been a growing trend in efforts to enhance the properties of medical devices. Understanding the interactions of biomolecules with nanoengineered surfaces is vital to assess the safety and efficacy of devices that incorporate these structures. In this dissertation, a model block copolymer (BCP) system based on poly(styrene)-block-poly(1,2-butadiene) was systematically modified using photochemical thiol-ene chemistry. Poly(1,2-butadiene) molecular weight and thiol-ene ratios were systematically varied based on a model monomer, boc-cysteamine, to determine the efficiency of the reaction. The results demonstrate the polydispersity index of modified BCPs significantly increased when low thiol-ene ratios were employed and sometimes induced gelation of the reacted polymers. Using a tenfold excess of thiol, functionalizations between 60-90% were obtained for an acid, amine, amide, and a pharmaceutical with a pendant thiol. Calorimetry showed a 30-60 °C increase in the glass transition temperature of the daughter polymers. Subsequently, films were cast from solvents found suitable to forming self-assembled BCP thin films. The synthetic and processing approach allows for the formation of nanopatterned block copolymer films with controlled chemistries from a single source material. The BCPs were further characterized using water contact angle measurements and atomic force microscopy in liquid. Significantly decreased contact angles were caused by selective swelling of charged BCP domains. Protein (fibrinogen, albumin, cytochrome C, immunoglobulin G) adsorption experiments were conducted under static and dynamic conditions with a quartz crystal microbalance with dissipation. The results indicate that nanopatterned chemistry and experimental conditions strongly impact adsorption dynamics. Adsorption behavior was dependent both on protein structure and the characteristics of the surface. Depending on the structural stability

  9. The mast cell - B-cell axis in lung vascular remodeling and pulmonary hypertension. (United States)

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


    Over the 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 a) IL-6 was upregulated and colocalized with mast cells and was reduced by mast cell stabilizers, and b) 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 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.

  10. Segmental pulmonary vascular resistances during oleic acid lung injury in rabbits. (United States)

    Maarek, J M; Grimbert, F


    We studied in isolated rabbit lungs the effects of oleic acid (OA) injury on the segmental distribution of vascular resistance. Vascular occlusion pressures were measured in control and OA-injured preparations over 90 min. Capillary filtration coefficient KF,C increased from 0.61 (+/- 0.10) to 0.91 (+/- 0.14) g.min-1.mmHg-1.(100 g)-1 in OA-injured lungs whereas it remained constant in control lungs. Total pulmonary vascular resistance changed little in both control and OA-injured lungs. OA injury resulted in a 15% increase of the double occlusion capillary pressure. In addition, the contribution of the microvascular to the total vascular resistance rose from 8% to 22%. The increase in microvascular resistance was significant 15 min after OA on the arteriolar side and became significant 30 min later on the venular side. Oleic acid injury does not change the total pulmonary vascular resistance but alters the distribution of segmental resistances in the isolated rabbit lung, thereby contributing to the accumulation of lung water in this model of low pressure permeability edema.

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

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    Rebecca L. Heise


    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.

  12. 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.

  13. [The development of the system of blood flow block by using magnetic compression abdominal large vascular]. (United States)

    Yan, Xiaopeng; Lv, Yi; Ma, Feng; Ma, Jia; Wang, Haohua; Wang, Shanpei; Li, Dichen; Liu, Yaxiong; Jia, Shenli; Shi, Zongqian; Luo, Ruixue


    A new system of blood flow block for control of bleeding in abdominal operation is composed of an abdominal magnetic blocking unit, an abdominal external electromagnet unit and other non-magnetic operation instrument. The abdominal external electromagnetic unit is placed in advance in the operation bed. The abdominal magnetic blocking unit can be placed directly on the ventral of the large vessels when need to blocking the abdominal large vessels during the operation. According to the non-contact suction characteristics of magnetic materials, the two magnetic units will attract each other and compression the vessels. Using this system for vascular occlusion does not need clear exposure and without separating vessel. There is the advantage of rapid, accurate and reliable for the system.

  14. Targeting of the pulmonary capillary vascular niche promotes lung alveolar repair and ameliorates fibrosis. (United States)

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


    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.

  15. Medical image of the week: lung cancer with vascular invasion

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    Malo J


    Full Text Available A 73-year-old woman presented to the emergency department with seizures and a subacute history of mild dyspnea on exertion. Her admission chest x-ray demonstrated a large right upper lobe lung mass, and MRI of the brain demonstrated multiple bilateral enhancing lesions concerning for a cardiac embolic source. Representative axial (Figure 1A and coronal (Figure 1B images from her chest CT scan demonstrate tumor invading the left atrium via the right superior pulmonary vein (arrow. The tumor was confirmed to be small cell carcinoma of the lung.

  16. Pigment epithelium-derived factor mediates impaired lung vascular development in neonatal hyperoxia. (United States)

    Chetty, Anne; Bennett, Michelle; Dang, Linh; Nakamura, Daisy; Cao, Gong-Jie; Mujahid, Sana; Volpe, MaryAnn; Herman, Ira; Becerra, S Patricia; Nielsen, Heber C


    Bronchopulmonary dysplasia is a chronic lung disease of preterm infants characterized by arrested microvascularization and alveolarization. Studies show the importance of proangiogenic factors for alveolarization, but the importance of antiangiogenic factors is unknown. We proposed that hyperoxia increases the potent angiostatin, pigment epithelium-derived factor (PEDF), in neonatal lungs, inhibiting alveolarization and microvascularization. Wild-type (WT) and PEDF(-/-) mice were exposed to room air (RA) or 0.9 fraction of inspired oxygen from Postnatal Day 5 to 13. PEDF protein was increased in hyperoxic lungs compared with RA-exposed lungs (P epithelium. Hyperoxia reduced alveolarization in WT mice (P lung microvascularization by vascular endothelial growth factor and PEDF was studied in vitro using MFLM-91U cells, a fetal mouse lung endothelial cell line. Vascular endothelial growth factor stimulation of proliferation, migration, and capillary tube formation was inhibited by PEDF. MFLM-91U cells exposed to conditioned medium (CM) from E17 fetal mouse lung type II (T2) cells cultured in 0.9 fraction of inspired oxygen formed fewer capillary tubes than CM from T2 cells cultured in RA (hyperoxia CM, 51 ± 10% of RA CM, P < 0.05), an effect abolished by PEDF antibody. We conclude that PEDF mediates reduced vasculogenesis and alveolarization in neonatal hyperoxia. Bronchopulmonary dysplasia likely results from an altered balance between pro- and antiangiogenic factors.

  17. [Non-tumoral vascular disorders of the lung in the adulthood]. (United States)

    Orsini, B; Doddoli, C; Brioude, G; D'Journo, X-B; Trousse, D; Gaubert, J-Y; Thomas, P-A


    Non-tumoral vascular disorders of the lung are multiple, even if cases diagnosed in the adulthood are rare. They include congenital or acquired conditions, which related symptoms, if present, are non specific. This explains why their diagnosis is challenging and usually delayed. Surgery is the cornerstone of their treatment, although interventional radiology represents currently a less invasive alternative option for some of them.

  18. Pressure- and flow-controlled media perfusion differently modify vascular mechanics in lung decellularization. (United States)

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


    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 (pperfusion (from 49.9±3.3 and 79.5±5.1 in baseline to a maximum of 114.4±13.9 and 211.7±70.5 (pperfusion mechanics 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.

  19. Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension (United States)

    Phan, Carole; Seferian, Andrei; Huertas, Alice; Thuillet, Raphaël; Sattler, Caroline; Le Hiress, Morane; Tamura, Yuichi; Jutant, Etienne-Marie; Chaumais, Marie-Camille; Bouchet, Stéphane; Manéglier, Benjamin; Molimard, Mathieu; Rousselot, Philippe; Sitbon, Olivier; Simonneau, Gérald; Montani, David; Humbert, Marc


    Pulmonary arterial hypertension (PAH) is a life-threatening disease that can be induced by dasatinib, a dual Src and BCR-ABL tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). Today, key questions remain regarding the mechanisms involved in the long-term development of dasatinib-induced PAH. Here, we demonstrated that chronic dasatinib therapy causes pulmonary endothelial damage in humans and rodents. We found that dasatinib treatment attenuated hypoxic pulmonary vasoconstriction responses and increased susceptibility to experimental pulmonary hypertension (PH) in rats, but these effects were absent in rats treated with imatinib, another BCR-ABL tyrosine kinase inhibitor. Furthermore, dasatinib treatment induced pulmonary endothelial cell apoptosis in a dose-dependent manner, while imatinib did not. Dasatinib treatment mediated endothelial cell dysfunction via increased production of ROS that was independent of Src family kinases. Consistent with these findings, we observed elevations in markers of endothelial dysfunction and vascular damage in the serum of CML patients who were treated with dasatinib, compared with CML patients treated with imatinib. Taken together, our findings indicate that dasatinib causes pulmonary vascular damage, induction of ER stress, and mitochondrial ROS production, which leads to increased susceptibility to PH development. PMID:27482885

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

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    Mi Ra Kim


    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.

  1. Clinical implications for Vascular Endothelial Growth Factor in the lung: friend or foe?

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    Gourgoulianis Konstantinos I


    Full Text Available Abstract Vascular endothelial growth factor (VEGF is a potent mediator of angiogenesis which has multiple effects in lung development and physiology. VEGF is expressed in several parts of the lung and the pleura while it has been shown that changes in its expression play a significant role in the pathophysiology of some of the most common respiratory disorders, such as acute lung injury, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, idiopathic pulmonary fibrosis, pulmonary hypertension, pleural disease, and lung cancer. However, the exact role of VEGF in the lung is not clear yet, as there is contradictory evidence that suggests either a protective or a harmful role. VEGF seems to interfere in a different manner, depending on its amount, the location, and the underlying pathologic process in lung tissue. The lack of VEGF in some disease entities may provide implications for its substitution, whereas its overexpression in other lung disorders has led to interventions for the attenuation of its action. Many efforts have been made in order to regulate the expression of VEGF and anti-VEGF antibodies are already in use for the management of lung cancer. Further research is still needed for the complete understanding of the exact role of VEGF in health and disease, in order to take advantage of its benefits and avoid its adverse effects. The scope of the present review is to summarize from a clinical point of view the changes in VEGF expression in several disorders of the respiratory system and focus on its diagnostic and therapeutic implications.

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

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    McLoughlin Paul


    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

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

    LENUS (Irish Health Repository)

    Sands, Michelle


    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

  4. Activation of adherent vascular neutrophils in the lung during acute endotoxemia

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    Laskin Jeffrey D


    Full Text Available Abstract Background Neutrophils constitute the first line of defense against invading microorganisms. Whereas these cells readily undergo apoptosis under homeostatic conditions, their survival is prolonged during inflammatory reactions and they become biochemically and functionally activated. In the present study, we analyzed the effects of acute endotoxemia on the response of a unique subpopulation of neutrophils tightly adhered to the lung vasculature. Methods Rats were treated with 5 mg/kg lipopolysaccharide (i.v. to induce acute endotoxemia. Adherent neutrophils were isolated from the lung vasculature by collagenase digestion and sequential filtering. Agarose gel electrophoresis, RT-PCR, western blotting and electrophoretic mobility shift assays were used to evaluate neutrophil activity. Results Adherent vascular neutrophils isolated from endotoxemic animals exhibited decreased apoptosis when compared to cells from control animals. This was associated with a marked increase in expression of the anti-apoptotic protein, Mcl-1. Cells isolated 0.5–2 hours after endotoxin administration were more chemotactic than cells from control animals and expressed increased tumor necrosis factor-alpha and cyclooxygenase-2 mRNA and protein, demonstrating that they are functionally activated. Endotoxin treatment of the animals also induced p38 and p44/42 mitogen activated protein kinases in the adherent lung neutrophils, as well as nuclear binding activity of the transcription factors, NF-κB and cAMP response element binding protein. Conclusion These data demonstrate that adherent vascular lung neutrophils are highly responsive to endotoxin and that pathways regulating apoptosis and cellular activation are upregulated in these cells.

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

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    Brittany M. Salter


    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.

  6. Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma. (United States)

    Togashi, Yosuke; Masago, Katsuhiro; Kubo, Takeshi; Fujimoto, Daichi; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Togashi, Kaori; Mishima, Michiaki


    Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P area (P area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency.

  7. HRCT of the lung in collagen vascular diseases; HRCT der Lunge bei Kollagenosen

    Energy Technology Data Exchange (ETDEWEB)

    Diederich, S. [Inst. fuer Klinische Radiologie, Westfaelische Wilhelms-Univ., Muenster (Germany); Roos, N. [Inst. fuer Klinische Radiologie, Westfaelische Wilhelms-Univ., Muenster (Germany); Schmitz-Linneweber, B. [Medizinische Klinik B, Westfaelische Wilhelms-Univ., Muenster (Germany); Gaubitz, M. [Medizinische Klinik B, Westfaelische Wilhelms-Univ., Muenster (Germany); Peters, P.E. [Inst. fuer Klinische Radiologie, Westfaelische Wilhelms-Univ., Muenster (Germany)


    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.) [Deutsch] Die Kollagenosen koennen als systemische Bindegewebserkrankungen auch zu einem breiten Spektrum pathologischer Veraenderungen am Respirationstrakt fuehren, wobei sich Art und Ausmass der Manifestationen innerhalb einzelner Entitaeten und zwischen verschiedenen Krankheitsbildern erheblich unterscheiden koennen. In der vorliegenden Uebersicht werden die entsprechenden Befunde von Thoraxuebersichtsaufnahme und insbesondere hochaufloesender Computertomographie (HRCT) beschrieben. Beruecksichtigt werden dabei die fibrosierende Alveolitis (Alveolitis, interstitielle Pneumonie, Lungenfibrose), bronchiale (Bronchitis/Bronchiolitis, Bronchiektasen), pleurale und vaskulaere Manifestationen sowie Lymphadenopathie und therapie-induzierte Befunde. Typische Befundmuster

  8. 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:


    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.

  9. A block matching-based registration algorithm for localization of locally advanced lung tumors (United States)

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


    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 cm3), 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

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

    LENUS (Irish Health Repository)

    Korpanty, Grzegorz


    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.

  11. GPU-accelerated Block Matching Algorithm for Deformable Registration of Lung CT Images. (United States)

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


    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.

  12. Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension (United States)

    Galambos, Csaba; Minic, Angela D.; Bush, Douglas; Nguyen, Dominique; Dodson, Blair; Seedorf, Gregory; Abman, Steven H.


    Background and Aims Infants with Down syndrome (DS) or Trisomy 21, are at high risk for developing pulmonary arterial hypertension (PAH), but mechanisms that increase susceptibility are poorly understood. Laboratory studies have shown that early disruption of angiogenesis during development impairs vascular and alveolar growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors, including collagen18a1 (endostatin, ES), ß-amyloid peptide (BAP) and Down Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs from subjects with DS are characterized by early over-expression of anti-angiogenic factors and have abnormal lung vascular growth in utero. Methods Human fetal lung tissue from DS and non-DS subjects were obtained from a biorepository. Quantitative reverse transcriptase PCR (qRT-PCR) was performed to assay 84 angiogenesis-associated genes and individual qRT-PCR was performed for ES, amyloid protein precursor (APP) and DSCR1. Western blot analysis (WBA) was used to assay lung ES, APP and DSCR-1 protein contents. Lung vessel density and wall thickness were determined by morphometric analysis. Results The angiogenesis array identified up-regulation of three anti-angiogenic genes: COL18A1 (ES), COL4A3 (tumstatin) and TIMP3 (tissue inhibitor of metallopeptidase 3) in DS lungs. Single qRT-PCR and WBA showed striking elevations of ES and APP mRNA (p = 0.022 and p = 0.001) and protein (p = 0.040 and p = 0.002; respectively). Vessel density was reduced (p = 0.041) and vessel wall thickness was increased in DS lung tissue (p = 0.033) when compared to non-DS subjects. Conclusions We conclude that lung anti-angiogenic factors, including COL18A1 (ES), COL4A3, TIMP3 and APP are over-expressed and fetal lung vessel growth is decreased in subjects with DS. We speculate that increased fetal lung anti-angiogenic factor expression due to trisomy 21 impairs lung vascular growth and signaling, which impairs alveolarization and

  13. Abnormal expression of vascular endothelial growth factor (VEGF) and its clinical features in tissues of human lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xinhua Wu; Dengfu Yao; Gongshen Shi; Liwei Qiu; Wei Wu; Songshi Ni; Xueguang Zhang


    Objective: Angiogennesis, the formation of new blood vessels from the existing vascular bed, is essential step for growth and invasion of primary tumor. Vascular endothelial growth-factor (VEGF) is known to play crucial role in tumor angiogenesis. In the present study, we investigate the expression of VEGF and VEGF-mRNA in the angiogennesis, metastasis and prognosis of lung cancer.Methods: The VEGF cellular distributions and expression in 38 specimens of patients with lung cancer were investigated with immunohistochemistry stain technology. The total RNAs in 38 tissues of lung cancer was measured, then the levels of VEGF-mRNA expression were analyzed by a reverse-transcription polymerase chain reaction (RT-PCR) assay. The levels of VEGF in sera of patients with lung cancer, benign lung diseases and healthy controls were detected through Enzyme linked immunosorbent assay (ELISA) method. Results: The VEGF positive stain was 76% in 38 cases of lung cancer specimens. The 89% rate of VEGF stain was found for clinical stage Ⅲ cases and 92%for stage Ⅳ lung cancers. The significantly higher expression of VEGF was evidenced in patients with lymph node metastasis (84 % ), distant metastasis (90%), and lung cancers with lower histological differentiation (89%), respectively. The expression level of total RNA was significantly higher in patients with lung cancers than that in their paracancerous or distant lung tissues. The VEGF expressions were tightly correlated with total RNA concentration of lung carcinoma ( P < 0.01 ). The predominant expressions of VEGF121 and VEGF165 gene fragments were found in lung cancer specimens by RT-PCR analysis. No significant difference of serum VEGF levels was detected between cases with lung cancer and patients with benign diseases. However, the VEGF level of cases with benign diseases was decreased significantly after patients with anti-inflammation medication. Conclusion: The present data suggested that the tumor tissue VEGF

  14. Application of Blocking Unilateral Main Pulmonary Artery in Pulmonary Lobectomy of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Fei Gao; Yunchao Huang; Lixia Liang; Anning Chen; Tierong Zhao


    OBJECTIVE To explore the application of blocking the unilateral main pulmonary artery (MPA) in pulmonary lobectomy (PL) for patients with stage Ⅱand Ⅲ lung cancer, and to retrospectively analyze the methods of surgery for blocking the unilateral main pulmonary artery, perioperative indications, intraoperative concerns and postoperative cardio-pulmonary complications. METHODS During a period from January 2006 to January 2008, intra-pericardial, or extra-pericardial separation and blockade of the left or right MPA followed by completion of various PLs were conducted for 30 lung cancer patients in stage-Ⅱ to Ⅲ with ill- defined anatomic structure of the pulmonary hilum and difficult pulmonary angiodiastasis.RESULTS In the 30 patients, 5 were diagnosed as stage-Ⅱb, 11 stage-Ⅲa, and 14 stage-Ⅲb. During the surgery, giant tumors at the superior pulmonary lobe, with a diameter of over 10 cm, were seen in 13 cases, in which tumor invasion in the extra-pericardiac pulmonary artery was found in 5 cases. Hilar lymphadenectasis with severe tumor adhesion to pulmonary blood vessel could be seen in 20 cases and partial tumorous invasion in the pericardium in 7. In most of the cases, adhesions existed around the tumor, aorta, superior vena, and azygous vein. Invasion of the laryngeal and vagus nerves on the left side was found in 3 cases. Of the 30 patients, simple PL was conducted in 12, and sleeve lobectomy combined with a pulmonary arterioplasty in 18 cases. With a blockade of unilateral MPA, no intraoperative hemorrhea of pulmonary blood vessels occurred during surgery, when there was a clear surgical field of vision. Both PL and lymphadenectomy were smoothly completed in the 30 patients. The healthy pulmonary lobes with normal function were kept and total pneumonectomy was avoided. The time of blocking the pulmonary artery ranged from 10 to 30 min, and intraoperative blood loss was from 200 to 300 ml. Postoperative complicated acute pulmonary edema occurred in

  15. Evidence for mRNA expression of vascular endothelial growth factor by X-ray irradiation in a lung squamous carcinoma cell line. (United States)

    Ando, S; Nojima, K; Majima, H; Ishihara, H; Suzuki, M; Furusawa, Y; Yamaguchi, H; Koike, S; Ando, K; Yamauchi, M; Kuriyama, T


    Vascular endothelial growth factor (VEGF) is a multipotent cytokine which plays an important role in various angiogenic conditions as well as in some tumor behaviors. Here we examined the induction of VEGF mRNA by X-ray irradiation in a lung squamous cell carcinoma cell line (RERF-LC-AI). Irradiating the cells with 15 Gy X-rays significantly increased the mRNA expression up to 2.5-fold of control at a post-irradiation time of 16-24 h. The induction of VEGF mRNA by X-ray irradiation was completely blocked by treating cells with either genistein (Src tyrosine kinase inhibitor) or H7 (protein kinase C inhibitor). This suggests that the mechanism of induction might be concerned with the pathway which triggers Src tyrosine kinase of the cell surface and the protein kinase C pathway.

  16. Contribution of ultrasound-guided fine-needle aspiration cell blocks of metastatic supraclavicular lymph nodes to the diagnosis of lung cancer

    Directory of Open Access Journals (Sweden)

    Hai-Ying Tian


    Conclusion: Cell-block samples from US-guided FNA is a promising, relatively noninvasive technique to provide additional information in lung cancer diagnosis. Analysis of cell blocks allows for genetic analysis of the patients with supraclavicular lymph nodes metastasis.


    Institute of Scientific and Technical Information of China (English)

    ZHANG Lijian; YANG Guoli; XIE Yuquan; XU Weiguo


    Objective: Tumor growth depends on angiogenesis.The aim of this paper is to clarify the relationship between the expression of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) and the angiogenesis, or growth, or invasion and prognostic value in Non-Small Cell Lung Cancer (NSCLC).Methods: Microvessei quantification and expression of VEGF was performed immunohistochemically, using multiclonal antibodies against endothelial protein factor Ⅷ-related antigen (F-Ⅷ antigen, or factor Ⅷ) for evaluating the angiogenesis; against VEGF antigen for the expression of VEGF. Results: A total of 53 patients with NSCLC after the radical resection were evaluated.The patients with high and low expression of VEGF were 33 and 20, respectively. A significant higher microvessel density (MVD) was observed in the tumors with high expression of VEGF compared with the tumors with low expression of it (12.17±2.57/mm2 vs 6.01±1.161/mm2, rank sum test, P<0.01). There were 29patients with lymphonodes metastasis in the high expression VEGF/VPF (29/33, 87.88%) group, and 9patients in the low (9/20, 45%) group. There was good correlation between MVD and expression of VEGF (chisquare tests, P<0.001). The overall 5 years survival for 53 patients was 20.75±5.78%; that of the high expression of the VEGF group was 3.03±2.98%; that of the low group was 36.36±13.94%, by Log rank test, P=0.0001.The difference between them had a high significance.There was good correlation between the survival and the expression of VEGF. By the COX's proportional hazard model analysis, the expression of VEGF and MVD was considered to be an independent marker of the prognosis in non-small cell lung cancer. Conclusion: the expression of VEGF has a significant correlation with MVD, growth, invasion, and lymph node metastasis. The increasing of the node metastasis and the size of tumor accompanied the increasing of VEGF/VPF. The cancer patient with higher VEGF and MVD expression might

  18. 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.

  19. Targeting vascular NADPH oxidase 1 blocks tumor angiogenesis through a PPARα mediated mechanism. (United States)

    Garrido-Urbani, Sarah; Jemelin, Stephane; Deffert, Christine; Carnesecchi, Stéphanie; Basset, Olivier; Szyndralewiez, Cédric; Heitz, Freddy; Page, Patrick; Montet, Xavier; Michalik, Liliane; Arbiser, Jack; Rüegg, Curzio; Krause, Karl Heinz; Imhof, Beat A; Imhof, Beat


    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.

  20. Preparation of cell blocks for lung cancer diagnosis and prediction: protocol and experience of a high-volume center. (United States)

    Kossakowski, Claudia A; Morresi-Hauf, Alicia; Schnabel, Philipp A; Eberhardt, Ralf; Herth, Felix J F; Warth, Arne


    Minimally invasive diagnostic techniques are increasingly being used to obtain specimens for pathological diagnosis and prediction. Referring to lung cancer, both endobronchial and endoesophageal ultrasound are used worldwide as diagnostic routine methods. Consequently, an increasing number of pathological samples are cytological and fewer are histological. On the other hand, the requirements for specific and sensitive tumor subtyping complemented by predictive analyses are steadily increasing and are an essential basis for evidence-based treatment decisions. In this article we focus on the cell block method as a helpful tool for diagnostic and predictive analyses in lung cancer and point out its advantages and disadvantages in comparison to conventional cytological and biopsy specimens. Furthermore, we retrospectively analyze the diagnostic results of the cell block method in a high-volume center over 5 years. The main advantages of cell blocks are the availability of established and validated protocols, archiving and the opportunity to have serial sections from the same specimens to provide or repeat molecular analyses. Actually, in case of tumor progression, even additional biomarkers can be tested using the original cell block when re-biopsies are not feasible. The cell block method should be considered as a reliable, complimentary approach to conventional cytological or biopsy procedures, which is helpful to fulfill the increasing requirements of high-quality diagnostics and prediction.

  1. 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)


    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.

  2. Thiazolidinediones enhance vascular endothelial growth factor expression and induce cell growth inhibition in non-small-cell lung cancer cells


    Yoshizaki Yumiko; Kumei Shima; Tanno Sachie; Motomura Wataru; Yoshizaki Takayuki; Tanno Satoshi; Okumura Toshikatsu


    Abstract Background It is known that thiazolidinediones are involved in regulating the expression of various genes, including the vascular endothelial growth factor (VEGF) gene via peroxisome proliferator-activated receptor γ (PPARγ); VEGF is a prognostic biomarker for non-small-cell lung cancer (NSCLC). Methods In this study, we investigated the effects of troglitazone and ciglitazone on the mRNA expression of VEGF and its receptors in human NSCLC cell lines, RERF-LC-AI, SK-MES-1, PC-14, and...

  3. Lung-homing of endothelial progenitor cells and airway vascularization is only partially dependant on eosinophils in a house dust mite-exposed mouse model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Nirooya Sivapalan

    Full Text Available Asthmatic responses involve a systemic component where activation of the bone marrow leads to mobilization and lung-homing of progenitor cells. This traffic may be driven by stromal cell derived factor-1 (SDF-1, a potent progenitor chemoattractant. We have previously shown that airway angiogenesis, an early remodeling event, can be inhibited by preventing the migration of endothelial progenitor cells (EPC to the lungs. Given intranasally, AMD3100, a CXCR4 antagonist that inhibits SDF-1 mediated effects, attenuated allergen-induced lung-homing of EPC, vascularization of pulmonary tissue, airway eosinophilia and development of airway hyperresponsiveness. Since SDF-1 is also an eosinophil chemoattractant, we investigated, using a transgenic eosinophil deficient mouse strain (PHIL whether EPC lung accumulation and lung vascularization in allergic airway responses is dependent on eosinophilic inflammation.Wild-type (WT BALB/c and eosinophil deficient (PHIL mice were sensitized to house dust mite (HDM using a chronic exposure protocol and treated with AMD3100 to modulate SDF-1 stimulated progenitor traffic. Following HDM challenge, lung-extracted EPCs were enumerated along with airway inflammation, microvessel density (MVD and airway methacholine responsiveness (AHR.Following Ag sensitization, both WT and PHIL mice exhibited HDM-induced increase in airway inflammation, EPC lung-accumulation, lung angiogenesis and AHR. Treatment with AMD3100 significantly attenuated outcome measures in both groups of mice. Significantly lower levels of EPC and a trend for lower vascularization were detected in PHIL versus WT mice.This study shows that while allergen-induced lung-homing of endothelial progenitor cells, increased tissue vascularization and development lung dysfunction can occur in the absence of eosinophils, the presence of these cells worsens the pathology of the allergic response.

  4. A 3D Poly(ethylene glycol)-based Tumor Angiogenesis Model to Study the Influence of Vascular Cells on Lung Tumor Cell Behavior (United States)

    Roudsari, Laila C.; Jeffs, Sydney E.; Witt, Amber S.; Gill, Bartley J.; West, Jennifer L.


    Tumor angiogenesis is critical to tumor growth and metastasis, yet much is unknown about the role vascular cells play in the tumor microenvironment. In vitro models that mimic in vivo tumor neovascularization facilitate exploration of this role. Here we investigated lung adenocarcinoma cancer cells (344SQ) and endothelial and pericyte vascular cells encapsulated in cell-adhesive, proteolytically-degradable poly(ethylene) glycol-based hydrogels. 344SQ in hydrogels formed spheroids and secreted proangiogenic growth factors that significantly increased with exposure to transforming growth factor beta 1 (TGF-β1), a potent tumor progression-promoting factor. Vascular cells in hydrogels formed tubule networks with localized activated TGF-β1. To study cancer cell-vascular cell interactions, we engineered a 2-layer hydrogel with 344SQ and vascular cell layers. Large, invasive 344SQ clusters (area > 5,000 μm2, circularity culture system as a platform for studying tumor vascularization.

  5. Sorafenib inhibits tumor growth and vascularization of rhabdomyosarcoma cells by blocking IGF-1R-mediated signaling

    Directory of Open Access Journals (Sweden)

    Wessen Maruwge


    Full Text Available Wessen Maruwge1, Pádraig D’Arcy1, Annika Folin1,2, Slavica Brnjic1, Johan Wejde1, Anthony Davis1, Fredrik Erlandsson3, Jonas Bergh1,2, Bertha Brodin11Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; 2Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden; 3Bayer Pharmaceutical Corporation, SwedenAbstract: The growth of many soft tissue sarcomas is dependent on aberrant growth factor signaling, which promotes their proliferation and motility. With this in mind, we evaluated the effect of sorafenib, a receptor tyrosine kinase inhibitor, on cell growth and apoptosis in sarcoma cell lines of various histological subtypes. We found that sorafenib effectively inhibited cell proliferation in rhabdomyosarcoma, synovial sarcoma and Ewing’s sarcoma with IC50 values <5 µM. Sorafenib effectively induced growth arrest in rhabdomyosarcoma cells, which was concurrent with inhibition of Akt and Erk signaling. Studies of ligand-induced phosphorylation of Erk and Akt in rhabdomyosarcoma cells showed that insulin-like growth factor-1 is a potent activator, which can be blocked by treatment with sorafenib. In vivo sorafenib treatment of rhabdomyosarcoma xenografts had a significant inhibitory effect on tumor growth, which was associated with inhibited vascularization and enhanced necrosis in the adjacent tumor stroma. Our results demonstrate that in vitro and in vivo growth of rhabdomyosarcoma can be suppressed by treatment with sorafenib, and suggests the possibilities of using sorafenib as a potential adjuvant therapy for the treatment of rhabdomyosarcoma.Keywords: soft tissue sarcoma, kinase inhibitors, targeted therapy, vascularization

  6. A 3D Poly(ethylene glycol)-based Tumor Angiogenesis Model to Study the Influence of Vascular Cells on Lung Tumor Cell Behavior


    Laila C. Roudsari; Jeffs, Sydney E.; Witt, Amber S.; Gill, Bartley J.; West, Jennifer L.


    Tumor angiogenesis is critical to tumor growth and metastasis, yet much is unknown about the role vascular cells play in the tumor microenvironment. In vitro models that mimic in vivo tumor neovascularization facilitate exploration of this role. Here we investigated lung adenocarcinoma cancer cells (344SQ) and endothelial and pericyte vascular cells encapsulated in cell-adhesive, proteolytically-degradable poly(ethylene) glycol-based hydrogels. 344SQ in hydrogels formed spheroids and secreted...

  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


    ]anti-ICAM-1 to airway surfaces increased 11-fold in a TNF-alpha-dependent manner. In situ hybridization and immunohistochemical analyses of lung tissue revealed ICAM-1 upregulation in the bronchiolar epithelium and in peribronchiolar smooth muscle. Soluble ICAM-1 could also be detected in bronchoalveolar......Airway instillation of bacterial lipopolysaccharide (LPS) into rat lungs induces neutrophil accumulation, which is known to be intercellular adhesion molecule-1 (ICAM-1)-dependent. In the present study, ICAM-1 messenger RNA (mRNA) of whole lung was found to increase by 20-fold in this inflammatory...... model. This increase was reduced by 81% after treatment of animals with anti-tumor necrosis factor-alpha (TNF-alpha) antibody and by 37% after treatment with anti-interleukin-1 (IL-1) antibody. The same interventions reduced whole-lung ICAM-1 protein by 85% and 25%, respectively. The studies were...

  8. Unstructured hexahedral mesh generation of complex vascular trees using a multi-block grid-based approach. (United States)

    Bols, Joris; Taelman, L; De Santis, G; Degroote, J; Verhegghe, B; Segers, P; Vierendeels, J


    The trend towards realistic numerical models of (pathologic) patient-specific vascular structures brings along larger computational domains and more complex geometries, increasing both the computation time and the operator time. Hexahedral grids effectively lower the computational run time and the required computational infrastructure, but at high cost in terms of operator time and minimal cell quality, especially when the computational analyses are targeting complex geometries such as aneurysm necks, severe stenoses and bifurcations. Moreover, such grids generally do not allow local refinements. As an attempt to overcome these limitations, a novel approach to hexahedral meshing is proposed in this paper, which combines the automated generation of multi-block structures with a grid-based method. The robustness of the novel approach is tested on common complex geometries, such as tree-like structures (including trifurcations), stenoses, and aneurysms. Additionally, the performance of the generated grid is assessed using two numerical examples. In the first example, a grid sensitivity analysis is performed for blood flow simulated in an abdominal mouse aorta and compared to tetrahedral grids with a prismatic boundary layer. In the second example, the fluid-structure interaction in a model of an aorta with aortic coarctation is simulated and the effect of local grid refinement is analyzed.

  9. Blocking the 4-1BB Pathway Ameliorates Crystalline Silica-induced Lung Inflammation and Fibrosis in Mice. (United States)

    Li, Chao; Du, Sitong; Lu, Yiping; Lu, Xiaowei; Liu, Fangwei; Chen, Ying; Weng, Dong; Chen, Jie


    Long term pulmonary exposure to crystalline silica leads to silicosis that manifests progressive interstitial fibrosis, eventually leading to respiratory failure and death. Despite efforts to eliminate silicosis, clinical cases continue to occur in both developing and developed countries. The exact mechanisms of crystalline silica-induced pulmonary fibrosis remain elusive. Herein, we find that 4-1BB is induced in response to crystalline silica injury in lungs and that it is highly expressed during development of experimental silicosis. Therefore, we explore the role of 4-1BB pathway during crystalline silica-induced lung injury and find that a specific inhibitor blocking the pathway could effectively alleviate crystalline silica-induced lung inflammation and subsequent pulmonary fibrosis in vivo. Compared to controls, the treated mice exhibited reduced Th1 and Th17 responses. The concentrations of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-17A following crystalline silica challenge were also reduced in inhibitor-treated mice. Although there was no significant alteration in Th2 cytokines of IL-4 and IL-13, another type of pro-fibrogenic cell, regulatory T cell (Treg) was significantly affected. In addition, one of the major participants in fibrogenesis, fibrocyte recruited less due to the blockade. Furthermore, we demonstrated the decreased fibrocyte recruitment was associated with chemokine reductions in lung. Our study discovers the 4-1BB pathway signaling enhances inflammatory response and promotes pulmonary fibrosis induced by crystalline silica. The findings here provide novel insights into the molecular events that control crystalline silica-induced lung inflammation and fibrosis through regulating Th responses and the recruitment of fibrocytes in crystalline silica-exposed lung.

  10. Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Qian-yi Peng; Yu Zou; Li-Na Zhang; Mei-Lin Ai; Wei Liu; Yu-Hang Ai


    Background:Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality.Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI,and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization.The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown.This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI.Methods:Septic rat models were established by cecal ligation and puncture (CLP).Rats were divided into the sham group,the CLP group,and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group.Nicotinamide adenine dinucleotide (NAD+),cADPR,CD38,and intracellular Ca2+ levels in the lung tissues were measured at 6,12,24,and 48 h after CLP surgery.Lung histologic injury,tumor necrosis factor (TNF)-α,malondialdehyde (MDA) levels,and superoxide dismutase (SOD) activities were measured.Results:NAD+,cADPR,CD38,and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery.Treatment with 8-Br-cADPR,a specific inhibitor of cADPR,significantly reduced intracellular Ca2+ levels (P =0.007),attenuated lung histological injury (P =0.023),reduced TNF-α and MDA levels (P < 0.001 and P =0.002,respectively) and recovered SOD activity (P =0.031) in the lungs of septic rats.Conclusions:The CD38/cADPR pathway is activated in the lungs of septic rats,and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI.

  11. 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: [Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)


    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.

  12. 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


    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.

  13. 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


    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...

  14. The H2S-generating enzymes cystathionine β-synthase and cystathionine γ-lyase play a role in vascular development during normal lung alveolarization. (United States)

    Madurga, Alicia; Golec, Anita; Pozarska, Agnieszka; Ishii, Isao; Mižíková, Ivana; Nardiello, Claudio; Vadász, István; Herold, Susanne; Mayer, Konstantin; Reichenberger, Frank; Fehrenbach, Heinz; Seeger, Werner; Morty, Rory E


    The gasotransmitter hydrogen sulfide (H2S) is emerging as a mediator of lung physiology and disease. Recent studies revealed that H2S administration limited perturbations to lung structure in experimental animal models of bronchopulmonary dysplasia (BPD), partially restoring alveolarization, limiting pulmonary hypertension, limiting inflammation, and promoting epithelial repair. No studies have addressed roles for endogenous H2S in lung development. H2S is endogenously generated by cystathionine β-synthase (Cbs) and cystathionine γ-lyase (Cth). We demonstrate here that the expression of Cbs and Cth in mouse lungs is dynamically regulated during lung alveolarization and that alveolarization is blunted in Cbs(-/-) and Cth(-/-) mouse pups, where a 50% reduction in the total number of alveoli was observed, without any impact on septal thickness. Laser-capture microdissection and immunofluorescence staining indicated that Cbs and Cth were expressed in the airway epithelium and lung vessels. Loss of Cbs and Cth led to a 100-500% increase in the muscularization of small- and medium-sized lung vessels, which was accompanied by increased vessel wall thickness, and an apparent decrease in lung vascular supply. Ablation of Cbs expression using small interfering RNA or pharmacological inhibition of Cth using propargylglycine in lung endothelial cells limited angiogenic capacity, causing a 30-40% decrease in tube length and a 50% decrease in number of tubes formed. In contrast, exogenous administration of H2S with GYY4137 promoted endothelial tube formation. These data confirm a key role for the H2S-generating enzymes Cbs and Cth in pulmonary vascular development and homeostasis and in lung alveolarization.

  15. CD147 deficiency blocks IL-8 secretion and inhibits lung cancer-induced osteoclastogenesis. (United States)

    Wang, Hongkai; Zhuo, Yunyun; Hu, Xu; Shen, Weiwei; Zhang, Ying; Chu, Tongwei


    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.

  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

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    Yuan LV


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

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    Kunlin Cao


    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.

  18. The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor. (United States)

    Tong, Fei; Tang, Xiangyuan; Li, Xin; Xia, Wenquan; Liu, Daojun


    The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF) as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG-b-(PELG-g-PLL) complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL) preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG-b-(PELG-g-PLL) significantly improved this effect.

  19. The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (United States)

    Tong, Fei; Tang, Xiangyuan; Li, Xin; Xia, Wenquan; Liu, Daojun


    The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF) as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG-b-(PELG-g-PLL) complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF) were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL) preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG-b-(PELG-g-PLL) significantly improved this effect. PMID:27175073

  20. 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.;


    We have recently shown that adoptively transferred, IL-2-activated natural killer (A-NK) cells are able to eliminate well-established B16-F10.P1 melanoma lung metastases. However, some B16-F10.P1 lung metastases were resistant to infiltration by the A-NK cells and also resistant to the A-NK cell....... 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...

  1. 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

    Institute of Scientific and Technical Information of China (English)

    YUAN Jia-min; YANG Xiao-hu; FU Shu-kun; YUAN Chao-qun; CHEN Kai; LI Jia-yi; LI Quan


    Background 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.Methods 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 ReviewManager 5.1.0 System (Cochrane Library).Results 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 <0.00001),decreased incidence of vascular puncture during block performance (RR 0.13,95% CI 0.06-0.27,P <0.00001),decreased the risk of complete hemi-diaphragmatic paresis (RR 0.09,95% CI 0.03-0.52,,P=0.0001).Conclusions 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.

  2. Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists. (United States)

    Lin, Yu-Jung; Lin, You Shuei; Lai, Ching Jung; Yuan, Zung Fan; Ruan, Ting; Kou, Yu Ru


    The terminals of vagal lung C fibers (VLCFs) express various types of pharmacological receptors that are important to the elicitation of airway reflexes and the development of airway hypersensitivity. We investigated the blockade of the reflex and afferent responses of VLCFs to intravenous injections of agonists using perivagal treatment with antagonists (PAT) targeting the transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors in anesthetized rats. Blockading these responses via perivagal capsaicin treatment (PCT), which blocks the neural conduction of C fibers, was also studied. We used capsaicin, α,β-methylene-ATP, and phenylbiguanide as the agonists, and capsazepine, iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate, and tropisetron as the antagonists of transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors, respectively. We found that each of the PATs abolished the VLCF-mediated reflex apnea evoked by the corresponding agonist, while having no effect on the response to other agonists. Perivagal vehicle treatment failed to produce any such blockade. These blockades had partially recovered at 3 h after removal of the PATs. In contrast, PCT abolished the reflex apneic response to all three agonists. Both PATs and PCT did not affect the myelinated afferent-mediated apneic response to lung inflation. Consistently, our electrophysiological studies revealed that each of the PATs prevented the VLCF responses to the corresponding agonist, but not to any other agonist. PCT inevitably prevented the VLCF responses to all three agonists. Thus these PATs selectively blocked the stimulatory action of corresponding agonists on the VLCF terminals via mechanisms that are distinct from those of PCT. PAT may become a novel intervention for studying the pharmacological modulation of VLCFs.

  3. Thiazolidinediones enhance vascular endothelial growth factor expression and induce cell growth inhibition in non-small-cell lung cancer cells

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    Yoshizaki Yumiko


    Full Text Available Abstract Background It is known that thiazolidinediones are involved in regulating the expression of various genes, including the vascular endothelial growth factor (VEGF gene via peroxisome proliferator-activated receptor γ (PPARγ; VEGF is a prognostic biomarker for non-small-cell lung cancer (NSCLC. Methods In this study, we investigated the effects of troglitazone and ciglitazone on the mRNA expression of VEGF and its receptors in human NSCLC cell lines, RERF-LC-AI, SK-MES-1, PC-14, and A549. These mRNA expressions were evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR analysis. We also studied the effect of Je-11, a VEGF inhibitor, on the growth of these cells. Results In NSCLC cells, thiazolidinediones increased the mRNA expression of VEGF and neuropilin-1, but not that of other receptors such as fms-like tyrosine kinase and kinase insert domain receptor-1. Furthermore, the PPARγ antagonist GW9662 completely reversed this thiazolidinedione-induced increase in VEGF expression. Furthermore, the addition of VEGF inhibitors into the culture medium resulted in the reversal of thiazolidinedione-induced growth inhibition. Conclusions Our results indicated that thiazolidinediones enhance VEGF and neuropilin-1 expression and induce the inhibition of cell growth. We propose the existence of a pathway for arresting cell growth that involves the interaction of thiazolidinedione-induced VEGF and neuropilin-1 in NSCLC.

  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;


    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...

  5. The effect of insulin-loaded linear poly(ethylene glycol-brush-like poly(L-lysine block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor

    Directory of Open Access Journals (Sweden)

    Tong F


    Full Text Available Fei Tong, Xiangyuan Tang, Xin Li, Wenquan Xia, Daojun Liu Department of Chemistry, Medical College, Shantou University, Shantou, People’s Republic of China Abstract: The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol-brush-like poly(L-lysine block copolymer poly(ethylene glycol-b-(poly(ethylenediamine L-glutamate-g-poly(L-lysine (PEG-b-(PELG-g-PLL on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor (HIF as compared to free insulin. Sprague Dawley rats were pretreated with 30 U/kg insulin or insulin/PEG-b-(PELG-g-PLL complex, and then subjected to 45 minutes of ischemia and 24 hours of reperfusion. The blood and lungs were collected, the level of serum creatinine and blood urea nitrogen were measured, and the dry/wet lung ratios, the activity of superoxide dismutase and myeloperoxidase, the content of methane dicarboxylic aldehyde and tumor necrosis factor-α, and the expression of HIF-1α and vascular endothelial growth factor (VEGF were measured in pulmonary tissues. Both insulin and insulin/PEG-b-(PELG-g-PLL preconditioning improved the recovery of renal function, reduced pulmonary oxidative stress injury, restrained inflammatory damage, and downregulated the expression of HIF-1α and VEGF as compared to ischemia/reperfusion group, while insulin/PEG-b-(PELG-g-PLL significantly improved this effect. Keywords: insulin, block copolymer, RI/RILI, HIF-1α, VEGF

  6. PPAR-γ Activation Inhibits Angiogenesis by Blocking ELR+CXC Chemokine Production in Non-small Cell Lung Cancer

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    Venkateshwar G. Keshamouni


    Full Text Available Activation of peroxisome proliferator-activated receptor-γ (PPAR-γ results in inhibition of tumor growth in various types of cancers, but the mechanism(s by which PPAR-γ induces growth arrest has not been completely defined. In a recent study, we demonstrated that treatment of A549 (human non small cell lung cancer cell line tumor-bearing SCID mice with PPAR-γ ligands troglitazone (Tro and pioglitazone significantly inhibits primary tumor growth. In this study, immunohistochemical analysis of Tro-treated and Pio-treated tumors with factor VIII antibody revealed a significant reduction in blood vessel density compared to tumors in control animals, suggesting inhibition of angiogenesis. Further analysis showed that treatment of A549 cells in vitro with Tro or transient transfection of A549 cells with constitutively active PPAR-γ (VP16-PPAR-γ construct blocked the production of the angiogenic ELR +CXC chemokines IL-8 (CXCL8, ENA-78 (CXCL5, Gro-α (CXCL1. Similarly, an inhibitor of NF-ΚB activation (PDTC also blocked CXCL8, CXCL5, CXCL1 production, consistent with their NF-ΚB-dependent regulation. Conditioned media from A549 cells induce human microvascular endothelial cell (HMVEC chemotaxis. However, conditioned media from Tro-treated A549 cells induced significantly less HMVEC chemotaxis compared to untreated A549 cells. Furthermore, PPAR-γ activation inhibited NF-ΚB transcriptional activity, as assessed by TransAM reporter gene assay. Collectively, our data suggest that PPAR-γ ligands can inhibit tumor-associated angiogenesis by blocking the production of ELR+CXC chemokines, which is mediated through antagonizing NF-ΚB activation. These antiangiogenic effects likely contribute to the inhibition of primary tumor growth by PPAR-γ ligands.

  7. Effects of COX-2 inhibition on expression of vascular endothelial growth factor and interleukin-8 in lung cancer cells

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    Yu Danny CW


    Full Text Available Abstract Background Cyclooxygenase (COX-2 has been implicated in tumour progression, angiogenesis and metastasis in non-small cell lung cancer (NSCLC. We speculated that inhibition of COX-2 activity might reduce expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF and interleukin-8 (IL-8 in lung cancer cells. Methods The levels of IL-8, VEGF and prostaglandin E2 (PGE2 were measured by ELISA. Expression of COX-1 and COX-2 was determined by Western blotting. Inhibition or knockdown of COX-2 was achieved by treating NSCLC cells with specific COX-2 inhibitor NS-398 or COX-2 siRNA, respectively. Results We found that NSCLC cell lines produced more IL-8 than VEGF (p 2 was significantly higher in NSCLC cell lines than SCLC cell lines (p 2 production. VEGF was significantly reduced following the treatment of NS-398 in A549 (by 31% and MOR/P (by 47% cells lines which expressing strong COX-2, but not in H460 cell line which expressing very low COX-2. However, IL-8 was not reduced in these cell lines. To confirm these results, we knocked down COX-2 expression with COX-2 siRNA in these cell lines. VEGF was significantly decreased in A549 (by 24% and in MOR/P (by 53%, but not in H460 whereas IL-8 was not affected in any cell line. Conclusion We conclude that NSCLC cells produce much higher levels of IL-8 than SCLC cells whereas both NSCLC and SCLC cells produce similar levels of VEGF. COX-2 is only expressed in NSCLC cells, but not in SCLC cells. VEGF is produced in both NSCLC and SCLC cells regardless of COX-2 expression. However, VEGF production is, at least partly, COX-2 dependent in NSCLC cells expressing COX-2. In contrast, IL-8 production is COX-2 independent in both NSCLC and SCLC cells. We speculate that combined targeting of COX-2 and IL-8 may be useful in the treatment of patients with NSCLC and targeting VEGF may be useful in the treatment of patients with SCLC.

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

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    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.

  9. 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)


    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.)

  10. Mitogenesis of Vascular Smooth Muscle Cell Stimulated by Platelet-Derived Growth Factor-bb Is Inhibited by Blocking of Intracellular Signaling by Epigallocatechin-3-O-Gallate

    Directory of Open Access Journals (Sweden)

    Mi Hee Lee


    Full Text Available Epigallocatechin gallate (EGCG is known to exhibit antioxidant, antiproliferative, and antithrombogenic effects and reduce the risk of cardiovascular diseases. Key events in the development of cardiovascular disease are hypertrophy and hyperplasia according to vascular smooth muscle cell proliferation. In this study, we investigated whether EGCG can interfere with PDGF-bb stimulated proliferation, cell cycle distribution, and the gelatinolytic activity of MMP and signal transduction pathways on RAOSMC when it was treated in two different ways—cotreatment with PDGF-bb and pretreatment of EGCG before addition of PDGF-bb. Both cotreated and pretreated EGCG significantly inhibited PDGF-bb induced proliferation, cell cycle progression of the G0/G1 phase, and the gelatinolytic activity of MMP-2/9 on RAOSMC. Also, EGCG blocked PDGF receptor-β (PDGFR-β phosphorylation on PDGF-bb stimulated RAOSMC under pretreatment with cells as well as cotreatment with PDGF-bb. The downstream signal transduction pathways of PDGFR-β, including p42/44 MAPK, p38 MAPK, and Akt phosphorylation, were also inhibited by EGCG in a pattern similar to PDGFR-β phosphorylation. These findings suggest that EGCG can inhibit PDGF-bb stimulated mitogenesis by indirectly and directly interrupting PDGF-bb signals and blocking the signaling pathway via PDGFR-β phosphorylation. Furthermore, EGCG may be used for treatment and prevention of cardiovascular disease through blocking of PDGF-bb signaling.

  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


    -related effects. Methods: Associations between vascular and lung function, inflammation markers and exposure in terms of particle number concentration (PNC; d = 10-300 nm) were studied in a cross-sectional design with personal and home indoor monitoring in the Western Copenhagen Area, Denmark. During 48-h, PNC...... 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...... tonometry, blood pressure and biomarkers of inflammation including C-reactive protein, and leukocyte counts with subdivision in neutrophils, eosinophils, monocytes, and lymphocytes in blood. Results: PNC from personal and stationary home monitoring showed weak correlation (r = 0.15, p = 0.24). Personal UFP...

  12. CCL21/CCR7 up-regulate vascular endothelial growth factor-D expression via ERK pathway in human non-small cell lung cancer cells. (United States)

    Sun, Limei; Zhang, Qingfu; Li, Yang; Tang, Na; Qiu, Xueshan


    Lymphangiogenesis has received considerable attention and become a new research hotspot of tumor metastasis. Recently, C-C chemokine receptor 7 (CCR7) is known to promote metastasis of non-small cell lung cancer (NSCLC) cells into lymph nodes. In this study, we investigated the relationship between CCL21/CCR7 and the lymphangiogenic factor vascular endothelial growth factor (VEGF)-D in human lung cancer cells and its impact on patients' prognosis. We found that CCL21/CCR7 increase the expression of VEGF-D in NSCLC Cell Lines through induced ERK1/2 and Akt phosphorylation. In addition, our study found that the expression levels of CCR7 and CCL21 were correlated with VEGF-D, lymphatic vessels density (LVD), clinical stages, lymph node metastasis, and patient Survival in 90 human non-small cell lung cancer (NSCLC) specimens. Taken together, our results provide evidence that CCL21/CCR7 induce VEGF-D up-regulation and promote lymphangiogenesis via ERK/Akt pathway in lung cancer.

  13. Effects of JAM-A deficiency or blocking antibodies on neutrophil migration and lung injury in a murine model of ALI. (United States)

    Lakshmi, Sowmya P; Reddy, Aravind T; Naik, Meghna U; Naik, Ulhas P; Reddy, Raju C


    Transmigration of neutrophils (PMNs) from the vasculature into inflamed tissues, mediated by interactions between PMNs and adhesion molecules on endothelial cells, is an essential aspect of inflammation. The crucial adhesion molecules include junctional adhesion molecule (JAM)-A. Investigation of the role of this molecule in models of inflammatory disease has been limited, however, and results in different disease models have varied. No previous study has addressed JAM-A in lung disease or effects on oxidant stress and proinflammatory cytokines. We use JAM-A knockout mice and blocking antibodies to investigate the role of JAM-A in a murine model of acute lung injury (ALI). With either experimental system, we find that absence of JAM-A activity significantly reduces migration of PMNs into the alveolar space, with a resulting decrease in oxidative stress. However, there is no reduction in whole lung activity of PMN-associated myeloperoxidase, presumably reflecting the histologically observed retention of PMNs in lung tissue. Activity of these retained PMNs may account for our failure to find significant change in markers of lung oxidative stress or cytokine and chemokine levels in plasma, lung, and bronchoalveolar lavage fluid. We likewise see no JAM-A-related changes in markers of capillary permeability or lung injury. A similar lack of congruence between effects on PMN migration and tissue injury has been reported in other disease models and for other adhesion molecules in models of ALI. Our results thus confirm the crucial role of JAM-A in PMN transmigration but demonstrate that transmigration is not essential for other aspects of inflammation or for lung injury in ALI.

  14. 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)


    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 mo

  15. Astragalus polysaccharides suppress ICAM-1 and VCAM-1 expression in TNF-α-treated human vascular endothelial cells by blocking NF-KB activation

    Institute of Scientific and Technical Information of China (English)

    Yu-ping ZHU; Tao SHEN; Ya-jun LIN; Bei-dong CHEN; Yang RUAN; Yuan CAO; Yue QIAO


    Aim:To investigate the effects ofAstragalus polysaccharides (APS) on tumor necrosis factor (TNF)-α-induced inflammatory reactions in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanisms.Methods:HUVECs were treated with TNF-α for 24 h.The amounts of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) were determined with Western blotting.HUVEC viability and apoptosis were detected using cell viability assay and Hoechst staining,respectively.Reactive oxygen species (ROS) production was measured by DHE staining.Monocyte and HUVEC adhesion assay was used to detect endothelial cell adhesive function.NF-KB activation was detected with immunofluorescence.Results:TNF-α (1-80 ng/mL) caused dose-and time-dependent increases of ICAM-1 and VCAM-1 expression in HUVECs,accompanied by significant augmentation of IKB phosphorylation and NF-KB translocation into the nuclei.Pretreatment with APS (10 and 50 μg/mL)significantly attenuated TNFα-induced upregulation of ICAM-1,VCAM-1,and NF-KB translocation.Moreover,APS significantly reduced apoptosis,ROS generation and adhesion function damage in TNF-α-treated HUVECs.Conclusion:APS suppresses TNFα-induced adhesion molecule expression by blocking NF-KB signaling and inhibiting ROS generation in HUVECs.The results suggest that APS may be used to treat and prevent endothelial cell injury-related diseases.

  16. Discovery of a novel class of targeted kinase inhibitors that blocks protein kinase C signaling and ameliorates retinal vascular leakage in a diabetic rat model. (United States)

    Grant, Stephan; Tran, Phong; Zhang, Qin; Zou, Aihua; Dinh, Dac; Jensen, Jordan; Zhou, Sue; Kang, Xiaolin; Zachwieja, Joseph; Lippincott, John; Liu, Kevin; Johnson, Sarah Ludlum; Scales, Stephanie; Yin, Chunfeng; Nukui, Seiji; Stoner, Chad; Prasanna, Ganesh; Lafontaine, Jennifer; Wells, Peter; Li, Hui


    Protein kinase C (PKC) family members such as PKCbetaII may become activated in the hyperglycemic state associated with diabetes. Preclinical and clinical data implicate aberrant PKC activity in the development of diabetic microvasculature abnormalities. Based on this potential etiological role for PKC in diabetic complications, several therapeutic PKC inhibitors have been investigated in clinical trials for the treatment of diabetic patients. In this report, we present the discovery and preclinical evaluation of a novel class of 3-amino-pyrrolo[3,4-c]pyrazole derivatives as inhibitors of PKC that are structurally distinct from the prototypical indolocarbazole and bisindolylmaleimide PKC inhibitors. From this pyrrolo-pyrazole series, several compounds were identified from biochemical assays as potent, ATP-competitive inhibitors of PKC activity with high specificity for PKC over other protein kinases. These compounds were also found to block PKC signaling activity in multiple cellular functional assays. PF-04577806, a representative from this series, inhibited PKC activity in retinal lysates from diabetic rats stimulated with phorbol myristate acetate. When orally administered, PF-04577806 showed good exposure in the retina of diabetic Long-Evans rats and ameliorated retinal vascular leakage in a streptozotocin-induced diabetic rat model. These novel PKC inhibitors represent a promising new class of targeted protein kinase inhibitors with potential as therapeutic agents for the treatment of patients with diabetic microvascular complications.

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

    Directory of Open Access Journals (Sweden)

    Jonas J. Heymann


    Full Text Available 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.

  18. Effect of stellate block on vasomotor factor, vascular endothelial nitricoxide synthase and pulmonary arterial pressure in rabbits with hypoxic pulmonary artery hypertension

    Institute of Scientific and Technical Information of China (English)

    Shunhou He; Qing Li; Sen Chen; Qingxiu Wang


    BACKGROUND: At present, inhalation of nitrogen monoxidum (NO) or other angiotenic is widely used to cure hypoxic pulmonary artery hypertension. In addition, recent researches demonstrate that postganglionic fiber of stellate ganglion can regulate contents of blood vessel endothelium-calcitonin gene-related peptide (BE-CGRP) and nitricoxide synthase (NOS) in lung tissue. Therefore, stellate ganglion which is blocked with the local anesthetic may cause therapeutic effects on hypoxic pulmonary artery hypertension.OBJECTIVE: To observe the effects of stellate block on calcitonin gene-related peptide (CGRP) of vasodilation factors, prostacyclin, endothelin-1 of vasoconstriction factors, thromboxan, blood vessel endothelium-nitricoxide synthase (BE-NOS) and mean arterial pressure of lung tissue in rabbits with hypoxic pulmonary artery hypertension.DESIGN: Randomly controlled animal study.SETTING: Neurological Institute of Taihe Hospital Affiliated to Yunyang Medical College.MATERIALS: A total of 24 adult Japanese rabbits of both genders and weighing 2.3 - 2.6 kg were provided by Animal Experimental Center of Hubei Academy of Medical Science. SP kit was provided by Beijing Zhongshan Biotechnology Co., Ltd.; moreover, kits of endothelin-1, CGRP, prostacyclin and thromboxan were provided by Radioimmunity Institute, Scientific and Technological Developing Center, General Hospital of Chinese PLA, and color image analytical system (Leica-Q500IW) was made in Germany.METHODS: The experiment was carried out in the Neurological Institute of Taihe Hospital affiliated to Yunyang Medical College from February to December 2002, ① Rabbits were performed with aseptic manipulation to exposure left stellate ganglion and then it was put in epidural catheter for 1 week. In addition,one end of epidural catheter was fixed near by stellate ganglion and the other end was fixed through dorsal neck. All rabbits were randomly divided into 4 groups, including normal control group, stellate block

  19. 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


    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.

  20. Fangchinoline inhibits the proliferation of SPC-A-1 lung cancer cells by blocking cell cycle progression. (United States)

    Luo, Xue; Peng, Jian-Ming; Su, Lan-DI; Wang, Dong-Yan; Yu, You-Jiang


    Fangchinoline (Fan) is a bioactive compound isolated from the Chinese herb Stephania tetrandra S. Moore (Fen Fang Ji). The aim of the present study was to investigate the effect of Fan on the proliferation of SPC-A-1 lung cancer cells, and to define the associated molecular mechanisms. Following treatment with Fan, Cell Counting Kit-8, phase contrast imaging and Giemsa staining assays were used to detect cell viability; flow cytometry was performed to analyze the cell cycle distribution; and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to investigate changes in the expression levels of cell cycle-associated genes and proteins. In the present study, treatment with Fan markedly inhibited the proliferation of SPC-A-1 lung cancer cells and significantly increased the percentage of cells in the G0/G1 phase of the cell cycle in a dose-dependent manner (PSPC-A-1 lung cancer cells and induced cell cycle arrest at the G0/G1 phase. These effects may be mediated by the downregulation of cellular CDK4, CDK6 and cyclin D1 levels, thus leading to hypophosphorylation of Rb and subsequent suppression of E2F-1 activity. Therefore, the present results suggest that Fan may be a potential drug candidate for the prevention of lung cancer.

  1. The Role of Anion Exchanger on Pulmonary Vascular Response to Sustained Alveolar Hypoxia in the Isolated Perfused Rabbit Lung

    Directory of Open Access Journals (Sweden)

    Farzaneh Ketabchi


    Full Text Available Background: Some respiratory diseases may induce alveolar hypoxia thereby hypoxic pulmonary vasoconstriction (HPV. However, the mechanisms of this physiologic phenomenon are not fully understood. This study was the first to investigate the role of anion exchanger in sustained HPV. Methods: Experiments were performed in the isolated perfused rabbit lung. After preparation, the lungs were divided into six groups: two DIDS (4,4-diisothiocyanostilbene 2,2-disulfonic acid, anion exchanger inhibitor-treated [200 µM (n=5 or 400 µM (n=3] hypoxic groups, two HCO3- free hypoxic groups, one control hypoxic group (n=7 and one control normoxic group (n=4. DIDS were added to the perfusate at 10 minutes before starting the experiments. In the HCO3- free groups, HEPES (4-(2-Hydroxyethylpiperazine-1-ethanesulfonic acid were added to the perfusate instead of bicarbonate. Furthermore, in the HEPES1 (n=4 and HEPES2 (n=4 groups, the lungs were ventilated with hypoxic gas with or without CO2, respectively. Results: Ventilation of the lungs with hypoxic gas resulted in biphasic HPV, the acute (0-20 minutes and sustained (20-60 minutes phases. No alteration in both phases of HPV was detected by DIDS (200 µM. However, DIDS (400 µM, extended the ascending part of acute HPV until min 24. Both phases of HPV were decreased in the HEPES1 group. However, in the HEPES 2 group, HPV tended to increase during the rising part of the acute phase of HPV. Conclusions: Since DIDS (400 µM extended acute phase of HPV, and HCO3- free perfusate buffer enhanced rising phase of it, therefore it can be suggested that anion exchanger may modulate HPV especially during the acute phase. The abstract of this article was presented as a poster in the congress of European Respiratory Society (ERS on Monday, 08 September 2014, Munich, Germany and was published in the ERJ September 1, 2014 vol. 44 no. Suppl 58 P2343.

  2. Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs

    Directory of Open Access Journals (Sweden)

    Shimodaira Kayoko


    Full Text Available Abstract Background Idiopathic pulmonary arterial hypertension (IPAH continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. Methods Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. Results Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. Conclusions Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease.

  3. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) is decreased in lung cancer patients showing progression: a pilot study. (United States)

    Yilmaztepe, A; Ulukaya, E; Zik, B; Yagci, A; Sevimli, A; Yilmaz, M; Erdogan, B Bahadir; Koc, M; Akgoz, S; Karadag, M; Tokullugil, A


    Tumor growth and metastasis depend on angiogenesis, and the vascular endothelial growth factor (VEGF) is known to be one of the most important angiogenic factors although the knowledge about its receptors is limited. We, therefore, investigated the treatment-related changes both in the level of the soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in the serum by ELISA and the expression of VEGFR-1 in cancer tissues by immunohistochemistry. The serum levels were studied in 38 lung cancer patients, and 55 control subjects (21 benign disease and 34 healthy subjects) before the chemotherapy. The treatment-related changes in serum sVEGFR-1 were evaluated in 15 patients 24 and 48 hours after treatment. In addition to serum analysis, the tissue expressions were evaluated in 32 patients before treatment. The treatment-related changes in tissue VEGFR-1 expressions were evaluated in only 12 patients 24 hours after treatment. We observed no significant difference in terms of serum sVEGFR-1 levels between malignant and nonmalignant groups (p > 0.05). There were no significant differences in the levels of sVEGFR-1 before and after treatment (p > 0.05). However, there was a significant difference between sVEGFR-1 levels in the groups (regressive, stable, progressive) classified according to the response to therapy (p = 0.043). A significant difference also was present between the expression levels of tissue VEGFR-1 in the same groups (p = 0.037). As a conclusion, we suggest that prechemotherapy sVEGFR-1 can be helpful for prediction of long-term response to therapy, but it should be studied in larger groups to elucidate its benefit in clinics.

  4. [Astaxanthin inhibits proliferation and promotes apoptosis of A549 lung cancer cells via blocking JAK1/STAT3 pathway]. (United States)

    Wu, Chuntao; Zhang, Jinji; Liu, Tienan; Jiao, Guimei; Li, Changzai; Hu, Baoshan


    Objective To investigate the anti-tumor effects of astaxanthin on A549 lung cancer cells and the related mechanisms. Methods A549 cells were cultured with various concentrations of astaxanthin (20, 40, 60, 80, 100 μmol/L), and DMSO at the same concentrations served as vehicle controls. The viability of A549 cells was detected by CCK-8 assay; cell cycle and apoptosis were observed by flow cytometry; and the expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), signal transducers and activators of transcription 3 (STAT3), and Janus kinase 1 (JAK1) were evaluated by Western blotting. Results CCK-8 assay showed that astaxanthin decreased the proliferation of A549 cells in a dose-dependent manner. Flow cytometry showed that astaxanthin increased the number of cells in the G0/G1 phase and induced apoptosis in A549 cells. Western blotting showed that astaxanthin up-regulated the expression of Bax and down-regulated the expressions of Bcl-2, STAT3 and JAK1. Conclusion Astaxanthin functions as a potent inhibitor of A549 lung cancer cell growth by targeting JAK1/STAT3 signaling pathway.

  5. Nuclear localization of vascular endothelial growth factor-D and regulation of c-Myc-dependent transcripts in human lung fibroblasts. (United States)

    El-Chemaly, Souheil; Pacheco-Rodriguez, Gustavo; Malide, Daniela; Meza-Carmen, Victor; Kato, Jiro; Cui, Ye; Padilla, Philip I; Samidurai, Arun; Gochuico, Bernadette R; Moss, Joel


    Lymphangiogenesis and angiogenesis are processes that are, in part, regulated by vascular endothelial growth factor (VEGF)-D. The formation of lymphatic structures has been implicated in multiple lung diseases, including pulmonary fibrosis. VEGF-D is a secreted protein produced by fibroblasts and macrophages, which induces lymphangiogenesis by signaling via VEGF receptor-3, and angiogenesis through VEGF receptor-2. VEGF-D contains a central VEGF homology domain, which is the biologically active domain, with flanking N- and C-terminal propeptides. Full-length VEGF-D (∼ 50 kD) is proteolytically processed in the extracellular space, to generate VEGF homology domain that contains the VEGF-D receptor-binding sites. Here, we report that, independent of its cell surface receptors, full-length VEGF-D accumulated in nuclei of fibroblasts, and that this process appears to increase with cell density. In nuclei, full-length VEGF-D associated with RNA polymerase II and c-Myc. In cells depleted of VEGF-D, the transcriptionally regulated genes appear to be modulated by c-Myc. These findings have potential clinical implications, as VEGF-D was found in fibroblast nuclei in idiopathic pulmonary fibrosis, a disease characterized by fibroblast proliferation. These findings are consistent with actions of full-length VEGF-D in cellular homeostasis in health and disease, independent of its receptors.

  6. Vascular Cures (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  7. Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation. (United States)

    Barman, S A; Senteno, E; Smith, S; Taylor, A E


    Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.

  8. Blocking TGF-β expression inhibits silica particle-induced epithelial-mesenchymal transition in human lung epithelial cells. (United States)

    Rong, Yi; Shen, Yan; Zhang, Zhihong; Cui, Xiuqing; Xiao, Lili; Liu, Yuewei; Luo, Xin; Chen, Weihong


    The main characteristic of silicosis is irreversible fibrosis. Certain studies have shown that epithelial-mesenchymal transition (EMT) regulated by transforming growth factor-β (TGF-β) is involved in fibrosis. Thus, we suggest that TGF-β regulated EMT may play an important role in silicosis. In this study, we determined the expression of TGF-β-Smad2/3, EMT- and ECM-related markers in lung epithelial cells treated with silica particle by RT-PCR, western-blot and ELISA. In order to explore the role of TGF-β, we used TGF-β inhibitor in the cell model. We found that the cells lost the expression of epithelial phenotypic markers and acquired increased expression of mesenchymal cells markers with ECM deposition after treatment with silica particle. Moreover, the changes of EMT-related event was restricted in response to TGF-β inhibitor. These findings suggest that EMT is essentially involved in the pathogenesis of fibrosis induced by silica particles and down-regulating the TGF-β expression can inhibit the process of EMT.

  9. 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


    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

  10. Ultrasound -- Vascular (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Vascular Vascular ultrasound uses sound waves to evaluate ... the limitations of Vascular Ultrasound? What is Vascular Ultrasound? Ultrasound is safe and painless, and produces pictures ...

  11. Analysis of Expression of Vascular Endothelial Growth Factor A and Hypoxia Inducible Factor-1alpha in Patients Operated on Stage I Non-Small-Cell Lung Cancer (United States)

    Honguero Martínez, Antonio Francisco; Arnau Obrer, Antonio; Figueroa Almánzar, Santiago; León Atance, Pablo; Guijarro Jorge, Ricardo


    Objectives. Recent studies show that expression of hypoxia inducible factor-1alpha (HIF-1α) favours expression of vascular endothelial growth factor A (VEGF-A), and these biomarkers are linked to cellular proliferation, angiogenesis, and metastasis in different cancers. We analyze expression of HIF-1α and VEGF-A to clinicopathologic features and survival of patients operated on stage I non-small-cell lung cancer. Methodology. Prospective study of 52 patients operated on with stage I. Expression of VEGF-A and HIF-1α was performed through real-time quantitative polymerase chain reaction (qRT-PCR). Results. Mean age was 64.7 and 86.5% of patients were male. Stage IA represented 23.1% and stage IB 76.9%. Histology classification was 42.3% adenocarcinoma, 34.6% squamous cell carcinoma, and 23.1% others. Median survival was 81.0 months and 5-year survival 67.2%. There was correlation between HIF-1α and VEGF-A (P = 0.016). Patients with overexpression of HIF-1α had a tendency to better survival with marginal statistical significance (P = 0.062). Patients with overexpression of VEGF-A had worse survival, but not statistically significant (P = 0.133). Conclusion. The present study revealed that VEGF-A showed correlation with HIF-1α. HIF-1α had a tendency to protective effect with a P value close to statistical significance. VEGF-A showed a contrary effect but without statistical significance. PMID:26316946

  12. Types of Heart Block (United States)

    ... P wave as it normally would. If an electrical signal is blocked before it reaches the ventricles, they won't contract and pump blood to the lungs and the rest of the body. Second-degree heart block is divided into two ...

  13. Pneumectomia utilizando sutura em bloco do hilo pulmonar por grampeador linear em cães Lung hilum pneumonectomy in dogs using linear stapler block suture

    Directory of Open Access Journals (Sweden)

    Afonso Akio Shiozaki


    assisted operations the dissection difficulties can inhibit the resection through this procedure thus forcing the surgeon to convert it to open toracotomy. The improvements of the surgical staples technical quality in the 1990s were so important that they have been considered also possibly efficient in simultaneous sutures of lung hilum structures thus replacing individualized dissection of its components in lung resections. The aim of this study was to verify the effect al lung hilum mechanical block suture. Twelve adult half-breed male dogs were submitted pneumonectomy through simultaneous suture of the lung hilum. They were separated into two groups of six animals each and were observed one for seven and the other for fourteen postoperatory days according to previously prepared protocols to verify macro and microscopic aspects. The access was opened through a lateral toracotomy on the anesthetized animal maintained in mechanical ventilation. The simultaneous suture of the lung hilum was carried out with only one shot of the sharp linear 60mm stapler. No death occurrence, suture dehiscence arterial or vein fistulas were verified. One of the animals presented an abscess in the suture line without developing fistulas or dehiscence. The postoperatory evolution was considered good in tem of the animals (83.3% and regular in two (16.7% that presented small incision abscesses. The data led to the conclusion that this suture technique is feasible, fast and presents good results but needs further studies to corroborate these results.

  14. 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)


    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

  15. Research Advances of the Relationship between Vascular Endothelial Growth Factor and Non-small Cell Lung Cancer%血管内皮生长因子与非小细胞肺癌关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    李高峰; 段林灿; 陈明清


    血管内皮生长因子(vascular endothelial growth factor,VEGF)是作用最强、特异性最高的血管生成调控因子.非小细胞肺癌(non-small cell lung carcinoma.,NSCLC)易于早期转移的生物学特性与VEGF的作用相关.就VEGF与NSCLC的发生、发展、预后关系和作为治疗靶点的价值研究领域的最新进展进行综述.

  16. Systemic complement activation, lung injury, and products of lipid peroxidation.


    Ward, P. A.; Till, G O; Hatherill, J. R.; Annesley, T M; Kunkel, R G


    Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxid...

  17. 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


    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.

  18. Application of Laser Level Meter in the Locating of Lung Block in Total Body Irradiation%十字激光水平仪在全身放疗肺挡铅定位中的应用

    Institute of Scientific and Technical Information of China (English)

    余建荣; 李珍


    In this paper, a laser level meter was used to implement the accurate locating of lung block in total body irradiation (TBI) instead of the light field system of linear accelerator. Compared with traditional locating methods, this method is an easy and effective technique to improve the lung shielding precision in TBI.%本文采用十字激光水平仪代替直线加速器光野系统,用于全身放疗(TBI)中肺挡块精确位置的确定。与传统方法相比,该方法操作简单、实用性强,可有效提高肺屏蔽精度。

  19. The effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(l-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor


    Tong F; Tang XY; Li X.; Xia WQ; Liu DJ


    Fei Tong, Xiangyuan Tang, Xin Li, Wenquan Xia, Daojun Liu Department of Chemistry, Medical College, Shantou University, Shantou, People’s Republic of China Abstract: The aim of this study was to observe the therapeutic effect of insulin-loaded linear poly(ethylene glycol)-brush-like poly(L-lysine) block copolymer poly(ethylene glycol)-b-(poly(ethylenediamine L-glutamate)-g-poly(L-lysine)) (PEG-b-(PELG-g-PLL) on renal ischemia/reperfusion-induced lung injury through downregulating ...

  20. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension (United States)

    Bertero, Thomas; Oldham, William M.; Cottrill, Katherine A.; Pisano, Sabrina; Vanderpool, Rebecca R.; Yu, Qiujun; Zhao, Jingsi; Tai, Yiyin; Tang, Ying; Zhang, Ying-Yi; Rehman, Sofiya; Sugahara, Masataka; Qi, Zhi; Gorcsan, John; Vargas, Sara O.; Saggar, Rajan; Saggar, Rajeev; Wallace, W. Dean; Ross, David J.; Haley, Kathleen J.; Parikh, Victoria N.; De Marco, Teresa; Hsue, Priscilla Y.; Morris, Alison; Simon, Marc A.; Norris, Karen A.; Gaggioli, Cedric; Loscalzo, Joseph; Fessel, Joshua; Chan, Stephen Y.


    Dysregulation of vascular stiffness and cellular metabolism occurs early in pulmonary hypertension (PH). However, the mechanisms by which biophysical properties of the vascular extracellular matrix (ECM) relate to metabolic processes important in PH remain undefined. In this work, we examined cultured pulmonary vascular cells and various types of PH-diseased lung tissue and determined that ECM stiffening resulted in mechanoactivation of the transcriptional coactivators YAP and TAZ (WWTR1). YAP/TAZ activation modulated metabolic enzymes, including glutaminase (GLS1), to coordinate glutaminolysis and glycolysis. Glutaminolysis, an anaplerotic pathway, replenished aspartate for anabolic biosynthesis, which was critical for sustaining proliferation and migration within stiff ECM. In vitro, GLS1 inhibition blocked aspartate production and reprogrammed cellular proliferation pathways, while application of aspartate restored proliferation. In the monocrotaline rat model of PH, pharmacologic modulation of pulmonary vascular stiffness and YAP-dependent mechanotransduction altered glutaminolysis, pulmonary vascular proliferation, and manifestations of PH. Additionally, pharmacologic targeting of GLS1 in this model ameliorated disease progression. Notably, evaluation of simian immunodeficiency virus–infected nonhuman primates and HIV-infected subjects revealed a correlation between YAP/TAZ–GLS activation and PH. These results indicate that ECM stiffening sustains vascular cell growth and migration through YAP/TAZ-dependent glutaminolysis and anaplerosis, and thereby link mechanical stimuli to dysregulated vascular metabolism. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in PH. PMID:27548520

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


    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.

  2. Detection of vascular endothelial growth factor in exhaled breath condensate and its research progress in lung diseases%呼出气冷凝液中VEGF的检测在肺部疾病中的研究进展

    Institute of Scientific and Technical Information of China (English)

    黄磊; 陈建荣; 陈金亮


    Exhaled breath condensate analysis is a novel technology of analysing the biomarkers of lung diseases.There are many advantages,such as noninvasiveness,simple collection and good repeatability,etc.Vascular endothelial growth factor (VEGF) is one of the markers,which can evaluate of airway inflammation and oxidative stress in lung diseases.The article reviews collection of exhaled breath condensate,related biological property of VEGF and recent clinic advances of VEGF in exhaled breath condensate.%呼出气冷凝液(EBC)检测是一种用来检测呼吸道生物标记物的新技术,具有无创、操作简单、可重复进行等特点.血管内皮生长因子(VEGF)是反映肺部疾病炎症反应及氧化应激变化的标志物之一.现就EBC的收集、VEGF相关生物学特性及在肺部疾病中检测EBC中VEGF水平的临床研究进展进行综述.

  3. 以血管内皮生长因子及其受体为靶向的肺癌放射性核素显像%Lung cancer radionuclide imaging targeting at vascular endothelial growth factor and its receptor

    Institute of Scientific and Technical Information of China (English)

    夏俊勇; 王火强


    The lung cancer must establish an angiogenesis to grow,to invade,and to metastasize,in which vascular endothelial factor(VEGF)is the most functional and special adjusting factor and play an important role.So anticancer by inhibiting the expression,activity and signal conduction of VEGF become one of the new and effective methods.Meanwhile,radionuclide imaging targeting at VEGF and its receptor not only can display the angiogenesis of lung cancer,but also has profound meaning in the early diagnosis,the correct staging,and the prognosis of lung cancer.%肺癌的持续生长、侵袭转移与新生血管生成密切相关,在新生血管生成过程中,血管内皮生长因子(VEGF)是作用最强、特异性最高的调控因子.因此,通过对其表达、活性及效应等方面进行有效抑制而达到治疗肺癌的目的 ,是近年来抗肺癌治疗的新方法和手段之一.同时,以VEGF及其受体为靶向的放射性核素显像,不仅可以显示肺癌的血管生成,而且在肺癌的早期诊断、正确分期及预后等方面均具有重要意义.

  4. Rock blocks


    Turner, W.


    Consider representation theory associated to symmetric groups, or to Hecke algebras in type A, or to q-Schur algebras, or to finite general linear groups in non-describing characteristic. Rock blocks are certain combinatorially defined blocks appearing in such a representation theory, first observed by R. Rouquier. Rock blocks are much more symmetric than general blocks, and every block is derived equivalent to a Rock block. Motivated by a theorem of J. Chuang and R. Kessar in the case of sym...

  5. [Vascular dementia

    NARCIS (Netherlands)

    Leeuw, H.F. de; Gijn, J. van


    Vascular dementia is one of the most frequently occurring dementia syndromes. Its prevalence is about 5% among subjects above 85 years of age. Elevated blood pressure and atherosclerosis are the most important risk factors. According to international criteria, vascular dementia usually occurs within

  6. Functional high-resolution computed tomography of pulmonary vascular and airway reactions. Experimental results. Funktionelle HR-CT der Lunge. Experimentelle Untersuchungen pulmonaler Gefaess- und Atemwegsreaktionen

    Energy Technology Data Exchange (ETDEWEB)

    Herold, C.J. (Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria) Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology); Brown, R.H. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Physiology); Wetzel, R.C.; Herold, S.M. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Anesthesiology and Intensive Care Medicine); Zeerhouni, E.A. (Johns Hopkins Medical Institutions, Baltimore, MD (United States). Dept. of Radiology)


    We describe the use of high-resolution computed tomography (HRCT) for assessment of the function of pulmonary vessels and airways. With its excellent spatial resolution, HRCT is able to demonstrate pulmonary structures as small as 300 [mu]m and can be used to monitor changes following various stimuli. HRCT also provides information about structures smaller than 300 [mu]m through measurement of parenchymal background density. To date, sequential, spiral and ultrafast HRCT techniques have been used in a variety of challenges to gather information about the anatomical correlates of traditional physiological measurements, thus making anatomical-physiological correlation possible. HRCT of bronchial reactivity can demonstrate the location and time course of aerosol-induced broncho-constriction and may show changes not apparent on spirometry. HRCT of the pulmonary vascular system visualized adaptations of vessels during hypoxia and intravascular volume loading and elucidates cardiorespiratory interactions. Experimental studies provide a basis for potential clinical applications of this method. (orig.).

  7. Caffeine's Vascular Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Darío Echeverri


    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.

  8. 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


    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.

  9. [A complete ventilation-perfusion mismatch following one-sided lung transplantation and postoperative hemothorax]. (United States)

    Jellinek, H; Klepetko, W; Hiesmayr, M


    Eight days after single-lung transplantation for pulmonary hypertension, a patient presented with a hemothorax on the side of the transplanted lung that required acute thoracotomy. Pulmonary artery pressure had decreased from 78/32/58 mmHg prior to the transplant to 42/18/27 mmHg on the 2nd postoperative day. Therefore, a predominance of perfusion to the transplanted lung was expected. During induction of anesthesia, in spite of ventilation with pure oxygen the patient developed a hypoxic cardiac arrest (paO2 26 mmHg, 40% saturation measured by pulse oximetry) requiring external chest compression. Auscultation and chest movements suggested that the transplanted lung was not ventilated. Because blood flow went mainly to the transplanted lung, ventilation of the native lung was almost totally dead-space ventilation. To enable ventilation of the compressed transplanted lung, the patient was intubated using a single-lumen bronchial blocker tube to block the mainstem bronchus of the native lung. The transplanted lung could then be ventilated. Saturation increased and epinephrine re-established a stable circulation; 2500 ml blood were removed from the pleura without further complications. On the 7th postoperative day the patient was discharged from the intensive care unit without neurological deficits. A perfusion scan 28 days post-transplant revealed 89% of the perfusion going to the transplanted lung. Atelectasis of this lung resulted in a large intrapulmonary right-to-left shunt. Hypoxic pulmonary vasoconstriction could not ameliorate the shunt because of the high pulmonary vascular resistance of the native lung.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Fibroblast Growth Factor Receptor 1 (FGFR1), Partly Related to Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and Microvessel Density, is an Independent Prognostic Factor for Non-Small Cell Lung Cancer (United States)

    Pu, Dan; Liu, Jiewei; Li, Zhixi; Zhu, Jiang; Hou, Mei


    Background This study aimed to explore the correlation between FGFR1 and clinical features, including survival analysis and the promotion of angiogenesis by fibroblast growth factor receptor 1 (FGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2). FGFR1 gene amplification has been found in non-small cell lung cancer (NSCLC). However, the prognostic value of FGFR1 and the correlation between FGFR1 and clinical features are still controversial. Material/Methods A total of 92 patients with NSCLC who underwent R0 resection between July 2006 and July 2008 were enrolled in the study. The expression of FGFR1, VEGFR2, and CD34 was detected by immunohistochemistry. The correlations between the aforementioned markers and the patients’ clinical features were analyzed by the chi-square test. The impact factors of prognosis were evaluated by Cox regression analyses. Results The expression ratios of FGFR1 and VEGFR2 were 26.1% and 43.4%, respectively. The intensity of FGFR1 expression was related to VEGFR2 and histopathology. To some extent, the average microvessel density (MVD) had correlation to the expression of FGFR1 and VGEFR2. The pathological stages III–IV and high expression of FGFR1 were found to be independent prognostic factors. Conclusions The expression intensity of FGFR1 and VEGFR2 was associated with MVD, and the expression of FGFR1 is one of the independent prognostic indicators for NSCLC. PMID:28088809

  11. vascular hemiplegia


    Voto Bernales, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú


    The vascular hemiplegia is the functional disorder of a lateral half of the body produced by alterations of cerebral vessels. Should review the concepts of this common condition, with the dual aim of expanding its nosographic value and considering the hemiplegic patient as worthy of the highest professional care La hemiplejia vascular, es el trastorno funcional de una mitad lateral del cuerpo producido por alteraciones de los vasos cerebrales. Conviene revisar los conceptos sobre esta frec...

  12. 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)


    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

  13. Novel agents in the management of lung cancer.

    LENUS (Irish Health Repository)

    Kennedy, B


    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.

  14. Population Blocks. (United States)

    Smith, Martin H.


    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…

  15. Injury to the Developing Lung: experimental and clinic al aspects

    NARCIS (Netherlands)

    I.K.M. Reiss (Irwin)


    textabstractInjury to the developing lung or disturbance of normal lung development may lead to a chronic lung disease, bronchopulmonary dysplasia (BPD), which may have long-term effects. BPD is characterized by an arrest of development of the lung and the pulmonary vascular system and occurs in aro

  16. Mitochondrial H2O2 in Lung Antigen-Presenting Cells Blocks NF-κB Activation to Prevent Unwarranted Immune Activation. (United States)

    Khare, Anupriya; Raundhal, Mahesh; Chakraborty, Krishnendu; Das, Sudipta; Corey, Catherine; Kamga, Christelle K; Quesnelle, Kelly; St Croix, Claudette; Watkins, Simon C; Morse, Christina; Oriss, Timothy B; Huff, Rachael; Hannum, Rachel; Ray, Prabir; Shiva, Sruti; Ray, Anuradha


    Inhalation of environmental antigens such as allergens does not always induce inflammation in the respiratory tract. While antigen-presenting cells (APCs), including dendritic cells and macrophages, take up inhaled antigens, the cell-intrinsic molecular mechanisms that prevent an inflammatory response during this process, such as activation of the transcription factor NF-κB, are not well understood. Here, we show that the nuclear receptor PPARγ plays a critical role in blocking NF-κB activation in response to inhaled antigens to preserve immune tolerance. Tolerance induction promoted mitochondrial respiration, generation of H2O2, and suppression of NF-κB activation in WT, but not PPARγ-deficient, APCs. Forced restoration of H2O2 in PPARγ-deficient cells suppressed IκBα degradation and NF-κB activation. Conversely, scavenging reactive oxygen species from mitochondria promoted IκBα degradation with loss of regulatory and promotion of inflammatory T cell responses in vivo. Thus, communication between PPARγ and the mitochondria maintains immune quiescence in the airways.

  17. An efficient Trojan delivery of tetrandrine by poly(N-vinylpyrrolidone-block-poly(ε-caprolactone (PVP-b-PCL nanoparticles shows enhanced apoptotic induction of lung cancer cells and inhibition of its migration and invasion

    Directory of Open Access Journals (Sweden)

    Xu H


    Full Text Available Huae Xu,1,2 Zhibo Hou,3 Hao Zhang,4 Hui Kong,2 Xiaolin Li,4 Hong Wang,2 Weiping Xie21Department of Pharmacy, 2Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, People's Republic of China; 4Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of ChinaAbstract: Earlier studies have demonstrated the promising antitumor effect of tetrandrine (Tet against a series of cancers. However, the poor solubility of Tet limits its application, while its hydrophobicity makes Tet a potential model drug for nanodelivery systems. We report on a simple way of preparing drug-loaded nanoparticles formed by amphiphilic poly(N-vinylpyrrolidone-block-poly(ε-caprolactone (PVP-b-PCL copolymers with Tet as a model drug. The mean diameters of Tet-loaded PVP-b-PCL nanoparticles (Tet-NPs were between 110 nm and 125 nm with a negative zeta potential slightly below 0 mV. Tet was incorporated into PVP-b-PCL nanoparticles with high loading efficiency. Different feeding ratios showed different influences on sizes, zeta potentials, and the drug loading efficiencies of Tet-NPs. An in vitro release study shows the sustained release pattern of Tet-NPs. It is shown that the uptake of Tet-NPs is mainly mediated by the endocytosis of nanoparticles, which is more efficient than the filtration of free Tet. Further experiments including fluorescence activated cell sorting and Western blotting indicated that this Trojan strategy of delivering Tet in PVP-b-PCL nanoparticles via endocytosis leads to enhanced induction of apoptosis in the non-small cell lung cancer cell A549 line; enhanced apoptosis is achieved by inhibiting the expression of anti-apoptotic Bcl-2 and Bcl-xL proteins. Moreover, Tet-NPs more efficiently inhibit the ability of cell migration and

  18. Vascular Disease Foundation (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  19. What Is Vascular Disease? (United States)

    ... Contact Us Vascular Disease What is Vascular Disease? Education and Awareness Vascular Diseases Abdominal Aortic Aneurysm Aortic Dissection Arteriovenous Malformation Atherosclerosis Buerger's Disease Carotid Artery Disease ...

  20. Vascular emergencies. (United States)

    Semashko, D C


    This article reviews the initial assessment and emergent management of several common as well as uncommon vascular emergencies. Aortic dissection, aneurysms, and arterial occlusive disease are familiar but challenging clinical entities. Less frequently encountered conditions are also discussed including an aortic enteric fistula, mesenteric venous thrombosis, phlegmasia alba dolens, and subclavian vein thrombosis.

  1. 温肺化瘀定喘用于小儿风寒闭肺证病毒性毛细支气管炎的临床疗效及安全性分析%Clinical Efficacy and Safety of Lung Warming, Stasis Transforming and Panting Stabilizing for Wind-cold Blocking Lung-type Viral Bronchiolitis in Children

    Institute of Scientific and Technical Information of China (English)



    Objective To explore the efficacy and safety of the method of lung warming, stasis transforming and panting stabilizing in treating wind-cold blocking lung-type viral bronchiolitis in Children. Methods 42 children with viral bronchiolitis admitted to our hospital during April 2013 and April 2014 were selected as the observation group in which the method of lung warming, stasis transforming and panting stabilizing was used, and 42 other children with the same disease admitted to our hospital during the same period were selected as the control group in which the inhalation therapy was used. The clinical efficacy and safety of the two groups were compared. Results The therapeutic effect of the two groups were 92.9% and 90.5%,P>0.05; the time of fever, cough, wheeze extinction of the observation group were shorter than those of the control group, P0.05);观察组发热、咳嗽、憋喘消退时间均短于对照组(P>0.05);观察组复发率为2.6%,明显低于对照组的15.8%(P>0.05);均未发生严重药物不良反应。结论该疗法治疗小儿风寒闭肺证病毒性毛细支气管炎的临床疗效确切,可短期内改善临床症状,且用药安全性较高。

  2. Zitongdong Block

    Institute of Scientific and Technical Information of China (English)


    @@ The Zitongdong Block (Eastern Zitong Block) is located in the northwest of the Sichuan Basin. Tectonically, it is situated in the east part of Zitong Depression, southeast of mid-Longmenshan folded and faulted belt( as shown on Fig. 8 ), covering an area of 1 730 km2. The traffic is very convenient, the No. 108 national highway passes through the north of the block. Topographically, the area belongs to low hilly land at the elevation of 500-700 m.

  3. Blocking the L-type Ca2+ channel (Cav 1.2) is the key mechanism for the vascular relaxing effect of Pterodon spp. and its isolated diterpene methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate. (United States)

    de Fátima Reis, Carolina; de Andrade, Daniela Medeiros Lobo; Junior Neves, Bruno; de Almeida Ribeiro Oliveira, Leandra; Pinho, José Felippe; da Silva, Leidiane Pinha; Dos Santos Cruz, Jader; Bara, Maria Teresa Freitas; Andrade, Carolina Horta; Rocha, Matheus Lavorenti


    Pterodon spp. Vogel (Fabaceae), popularly known as "sucupira", has ethnopharmacological application which is described as having antispasmodic and relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could induce smooth muscle relaxation. So, this study investigated the mechanisms involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl-6α-acetoxy-7β-hydroxyvouacapan-17β-oate). Vascular reactivity experiments were performed using rat aortic rings (n=5-8) with (E+) or without endothelium (E-) in an isolated bath organ. The SOR (0-56 μg/mL) relaxed phenylephrine (E+: 86.7±7.1%; E-: 92.3±4.7%) and KCl contracted rings (E-: 97.1±2.8%). In the same way, diterpene (0-48 μg/mL) also relaxed phenylephrine (E+: 94.5±3.6%; E-: 92.2±3.4%) and KCl contracted rings (E-: 99.7±0.2%). The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca2+-ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene-induced vasorelaxation. SOR and diterpene significantly reduced CaCl2-induced contraction stimulated by Bay K8644 (1 μM), phenylephrine (0.1 μM) or KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Cav 1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Cav 1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca2+ channel (Cav 1.2).

  4. Zitongxi Block

    Institute of Scientific and Technical Information of China (English)


    @@ Zitongxi Block (Western Zitong Block), is located in Zitong County, northwest of Sichuan Province (as shown on Fig. 8 ). Geologically. it is situated in the Zitong Depression, southwest of the middle Longmenshan faulted and folded belt, covering an area of 1 830 km2. Transportation is very convenient. A crisscross network of highways run through the block and the Baocheng railway is nearby. The climate is moderate. Most area belongs to hilly land with the elevation of 500-600 m.The Tongjiang River runs across the area.

  5. Chengzikou Block

    Institute of Scientific and Technical Information of China (English)


    @@ Chengzikou Block is located in the north of Hekou district, Dongying City, Shandong Province, adjacent to Bohai Bay. It can be geographically divided into three units: onshore, transitional zone and offshore ultrashallow zone, totally covering an area of 470 km2. The southern onshore area is low and gentle in topography;the northern shallow sea is at water depths of 2-8 m below sea level, and the transitional zone occupies more than 60% of the whole block. The climate belongs to temperate zone with seasonal wind. Highways are welldeveloped here, and the traffic is very convenient. The Chengzikou Block is about 80 km away from Dongying City and 290 km from Jinan City in the south. The northern offshore area of the block is 160 km away from Longkou port in the east and only 38 km away in the west from Zhuangxi port.

  6. Longmenshan Block

    Institute of Scientific and Technical Information of China (English)


    @@ Longmenshan Block is located in Jiange County of Jiangyou City in the northwest of Sichuan Basin. covering an area of 2 628 km2. Geologically, it is situated in the Mid-Longmenshan fault and fold belt, neighbouring Zitong Depression in its southeast. There are mountains surrounding its northwest , the rest area being hilly land,with the elevation of 500-700 m. The BaoCheng railway and the No. 108 highway run through the block, the traffic is very convenient.

  7. Guidance molecules in lung cancer


    Nasarre, Patrick; Potiron, Vincent; Drabkin, Harry; Roche, Joëlle


    Guidance molecules were first described in the nervous system to control axon outgrowth direction. They are also widely expressed outside the nervous system where they control cell migration, tissue development and establishment of the vascular network. In addition, they are involved in cancer development, tumor angiogenesis and metastasis. This review is primarily focused on their functions in lung cancer and their involvement in lung development is also presented. Five guidance molecule fam...

  8. 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: [Centro Hospitalar Lisboa Norte, EPE, Lisboa (Portugal)


    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)

  9. Lung transplant (United States)

    Solid organ transplant - lung ... the chance that the body will reject the transplant . Lungs can also be given by living donors. ... the person who is receiving it. During lung transplant surgery, you are asleep and pain-free (under ...

  10. VEGFA variants are associated with pre-school lung function, but not neonatal lung function

    DEFF Research Database (Denmark)

    Kreiner-Møller, E; Chawes, B L K; Vissing, N H;


    Vascular endothelial growth factor (VEGF) is implicated in airway remodelling and asthma development. We studied VEGFA gene variants and plasma levels and the development of lung function, bronchial hyperresponsiveness and asthma in childhood....

  11. Chadong Block

    Institute of Scientific and Technical Information of China (English)


    @@ The Chadong Block, located in the east of Qaidam Basin, Qinghai Province, covers an area of 12 452 km2. It is bounded by Kunlum Mountains in the south and the northwest is closely adjacent to Aimunike Mountain.Rivers are widely distributed, which always run in NWSE direction, including the Sulunguole, Qaidam and Haluwusu Rivers. The traffic condition is good, the Qinghai-Tibet highway stretching through the whole area and the Lan-Qing railway, 20-50 km away from the block, passing from north to west. A lot of Mongolia minority people have settled there, of which herdsmen always live nearby the Qaidam River drainage area.

  12. Influence of general anesthesia combined with epidural block on gas exchang during one-lung ventilation in patients undergoing thoracic surgery%硬膜外阻滞复合全麻对单肺通气期间气体交换的影响

    Institute of Scientific and Technical Information of China (English)

    赵念峰; 杨建香; 刘功俭


    Objective To evaluate the effects of general anesthesia combined with throacic epidural block on pulmonary gas ex-change during one-lung ventilation in patients undergoing thoracic surgery. Methods Eighty patients of ASA Ⅰ-Ⅱ undergoing electivethroacic surgery were randomly divided into two Groups (n = 40 ) receiving combined genera] anesthesia with throacic epidural block(group A ) or general anesthesia (group B ). MAP, HR, SpO2, PETCO2, VT, Paw were monitored at both bronps. Arterial andmixed vein blood gas were analyzed and Qs/Qt ,A-aDO2,Vd/Vt were calculated in both groups at 20 rain ( T1 ) before one-lung ventila-tion and 30 min( T2 ), 60 min( T3 ), as well as 120 min ( T4 ) after one-lung ventilation. Results In both groups, Paw and Qs/Qt in-creased while PaO2 decreased significantly at T2-4, ( P0.05);与B组相比,A组T2-4时的Qs/Qt增加(P0.05).结论 单肺通气期间硬膜外阻滞复合全麻对肺换气功能有影响,使Qs/Qt增加,PaO2下降,A-aDO2增大;对肺泡通气功能指标Vd/Vt影响甚微.

  13. Stimulation of neoplastic mouse lung cell proliferation by alveolar macrophage-derived, insulin-like growth factor-1 can be blocked by inhibiting MEK and PI3K activation

    Directory of Open Access Journals (Sweden)

    Malkinson Alvin M


    Full Text Available Abstract Background Worldwide, lung cancer kills more people than breast, colon and prostate cancer combined. Alterations in macrophage number and function during lung tumorigenesis suggest that these immune effector cells stimulate lung cancer growth. Evidence from cancer models in other tissues suggests that cancer cells actively recruit growth factor-producing macrophages through a reciprocal signaling pathway. While the levels of lung macrophages increase during tumor progression in mouse models of lung cancer, and high pulmonary macrophage content correlates with a poor prognosis in human non-small cell lung cancer, the specific role of alveolar macrophages in lung tumorigenesis is not clear. Methods After culturing either an immortalized lung macrophage cell line or primary murine alveolar macrophages from naïve and lung-tumor bearing mice with primary tumor isolates and immortalized cell lines, the effects on epithelial proliferation and cellular kinase activation were determined. Insulin-like growth factor-1 (IGF-1 was quantified by ELISA, and macrophage conditioned media IGF-1 levels manipulated by IL-4 treatment, immuno-depletion and siRNA transfection. Results Primary macrophages from both naïve and lung-tumor bearing mice stimulated epithelial cell proliferation. The lungs of tumor-bearing mice contained 3.5-times more IGF-1 than naïve littermates, and media conditioned by freshly isolated tumor-educated macrophages contained more IGF-1 than media conditioned by naïve macrophages; IL-4 stimulated IGF-1 production by both macrophage subsets. The ability of macrophage conditioned media to stimulate neoplastic proliferation correlated with media IGF-1 levels, and recombinant IGF-1 alone was sufficient to induce epithelial proliferation in all cell lines evaluated. Macrophage-conditioned media and IGF-1 stimulated lung tumor cell growth in an additive manner, while EGF had no effect. Macrophage-derived factors increased p-Erk1/2, p

  14. Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. (United States)

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


    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.

  15. 血管外肺水指数和肺血管通透性指数与急性呼吸窘迫综合征严重程度的相关性%Correlation of severity classification of acute respiratory distress syndrome by the Berlin definition with extra vascular lung water index and pulmonary vascular permeability index

    Institute of Scientific and Technical Information of China (English)

    朱金源; 王晓红; 杨晓军; 王晓麒; 马希刚


    目的 探讨血管外肺水指数(EVLWI)和肺血管通透性指数(PVPI)与急性呼吸窘迫综合征(ARDS)柏林定义严重程度分级的关系.方法 对2012年7月至2014年7月收住宁夏医科大学总医院ICU符合ARDS柏林定义的患者70例,依据ARDS柏林定义分为轻度组(20例)、中度组(30例)和重度组(20例).记录患者入院24 h内急性生理和慢性健康状况(APACHEⅡ)评分和序贯器官衰竭(SOFA)评分,脉搏指示剂持续心排血量监测技术(PiCCO)监测3组患者入院1~4dEVLWI和PVPI,并绘制受试者工作特征曲线(ROC曲线),比较ROC曲线下面积(AUC).同步行血气分析并计算氧合指数(OI),分析EVLWI和PVPI与OI的相关性.结果 轻、中和重度组ARDS患者不同时相点EVLWI、PVPI及OI的组间比较:随着ARDS严重程度的分级加重,3组患者任一时相点EVLWI和PVPI均明显升高,OI明显降低(均P<0.05).轻、中和重度组ARDS患者EVLWI、PVPI及OI动态变化趋势的组内比较:轻度组1~4 d EVLWI和PVPI随时间逐渐下降(均P<0.05),中度组仅PVPI下降,EVLWI无明显下降(P>0.05),重度组EVLWI和PVPI均无明显下降趋势(均P>0.05),而3组1~4 d OI随时间变化均有升高(均P<0.01).3组ARDS患者1~4 d PVPI对预后评价的AUC分别为0.594、0.643、0.723和0.816,以入院第4天PVPI>2.95作为判断预后的最佳临界值,其敏感度为70%,特异度为92%.3组所有ARDS患者1~4 d EVLWI和PVPI与OI呈现明显的负相关[(r=-0.685,P=0.000)和(r=-0.631,P=0.000)].结论 EVLWI和PVPI能够良好的反映ARDS柏林定义严重程度分级,且PVPI的动态变化趋势优于EVLWI.%Objective To explore the correlation of severity classification of acute respiratory distress syndrome (ARDS) by the Berlin definition with extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI).Methods A total of 70 cases with ARDS at intensive care unit of our hospital from July 2012 to July 2014 were divided into three

  16. Branding of vascular surgery. (United States)

    Perler, Bruce A


    The Society for Vascular Surgery surveyed primary care physicians (PCPs) to understand how PCPs make referral decisions for their patients with peripheral vascular disease. Responses were received from 250 PCPs in 44 states. More than 80% of the respondents characterized their experiences with vascular surgeons as positive or very positive. PCPs perceive that vascular surgeons perform "invasive" procedures and refer patients with the most severe vascular disease to vascular surgeons but were more than twice as likely to refer patients to cardiologists, believing they are better able to perform minimally invasive procedures. Nevertheless, PCPs are receptive to the notion of increasing referrals to vascular surgeons. A successful branding campaign will require considerable education of referring physicians about the totality of traditional vascular and endovascular care increasingly provided by the contemporary vascular surgical practice and will be most effective at the local grassroots level.

  17. Vascular endothelial-cadherin downregulation as a feature of endothelial transdifferentiation in monocrotaline-induced pulmonary hypertension. (United States)

    Nikitopoulou, Ioanna; Orfanos, Stylianos E; Kotanidou, Anastasia; Maltabe, Violetta; Manitsopoulos, Nikolaos; Karras, Panagiotis; Kouklis, Panos; Armaganidis, Apostolos; Maniatis, Nikolaos A


    Increased pulmonary vascular resistance in pulmonary hypertension (PH) is caused by vasoconstriction and obstruction of small pulmonary arteries by proliferating vascular cells. In analogy to cancer, subsets of proliferating cells may be derived from endothelial cells transitioning into a mesenchymal phenotype. To understand phenotypic shifts transpiring within endothelial cells in PH, we injected rats with alkaloid monocrotaline to induce PH and measured lung tissue levels of endothelial-specific protein and critical differentiation marker vascular endothelial (VE)-cadherin. VE-cadherin expression by immonoblotting declined significantly 24 h and 15 days postinjection to rebound to baseline at 30 days. There was a concomitant increase in transcriptional repressors Snail and Slug, along with a reduction in VE-cadherin mRNA. Mesenchymal markers α-smooth muscle actin and vimentin were upregulated by immunohistochemistry and immunoblotting, and α-smooth muscle actin was colocalized with endothelial marker platelet endothelial cell adhesion molecule-1 by confocal microscopy. Apoptosis was limited in this model, especially in the 24-h time point. In addition, monocrotaline resulted in activation of protein kinase B/Akt, endothelial nitric oxide synthase (eNOS), nuclear factor (NF)-κB, and increased lung tissue nitrotyrosine staining. To understand the etiological relationship between nitrosative stress and VE-cadherin suppression, we incubated cultured rat lung endothelial cells with endothelin-1, a vasoconstrictor and pro-proliferative agent in pulmonary arterial hypertension. This resulted in activation of eNOS, NF-κB, and Akt, in addition to induction of Snail, downregulation of VE-cadherin, and synthesis of vimentin. These effects were blocked by eNOS inhibitor N(ω)-nitro-l-arginine methyl ester. We propose that transcriptional repression of VE-cadherin by nitrosative stress is involved in endothelial-mesenchymal transdifferentiation in experimental PH.

  18. Comparison of risk of tumor invasion and metastasis under paravertebral block combined with general anesthesia versus general anesthesia in the patients undergoing radical lung cancer resection performed via video-assisted thoracoscope:plasma VEGF and M%椎旁神经阻滞联合全麻与全麻下胸腔镜肺癌根治术病人肿瘤侵袭和转移风险的比较:VEGF和MMP-9血浓度

    Institute of Scientific and Technical Information of China (English)

    陈冀衡; 范志毅; 张云霄; 金云玉; 李萍


    Objective To compare the risk of tumor invasion and metastasis under paravertebral block (PVB) combined with general anesthesia versus general anesthesia in the patients undergoing radical resection for lung cancer performed via video-assisted thoracoscope in terms of plasma concentrations of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9).Methods Forty ASA physical status Ⅰ or Ⅱ patients of both sexes,aged 30-64 yr,with body mass index of 18-25 kg/m2,scheduled for elective radical resection for lung cancer performed via video-assisted thoracoscope,were randomly divided into 2 groups (n =20 each) using a random number table:general anesthesia group (group G) and PVB combined with general anesthesia (group PG).PVB of T4-7 was performed successfully with local injection of 0.375% ropivacaine 5 ml before induction of anesthesia.Double-lumen endotracheal tube was placed after induction of anesthesia,and the patients were mechanically ventilated.Anesthesia was maintained with inhalation of sevoflurane (end-tidal concentration 1%-2%),and intravenous infusion of remifentanil 0.2-0.3 μg · kg-1 · min-1,and intermittent intravenous boluses of atracurium.Before anesthesia and at 24 h after surgery,the venous blood samples were collected for measurement of plasma concentrations of VEGF and MMP-9.Results The plasma VEGF and MMP-9 concentrations were significantly lower after surgery in group PG than in group G.Conclusion PVB combined with general anesthesia significantly decreases the risk of tumor invasion and metastasis in the patients undergoing radical lung cancer resection performed via video-assisted thoracoscope in comparison to general anesthesia.%目的 采用血管内皮生长因子(VEGF)和基质金属蛋白酶-9(MMP-9)血浓度,比较椎旁神经阻滞联合全麻与全麻下胸腔镜肺癌根治术病人肿瘤侵袭和转移风险.方法 择期行胸腔镜肺癌根治术病人40例,年龄30 ~ 64岁,性别不限,BMI 18

  19. Lung function

    Institute of Scientific and Technical Information of China (English)


    2005200 The effect of body position changes on lung function, lung CT imaging and pathology in an oleic acid induced acute lung injury model. JI Xin-ping (戢新平), et al. Dept Emergency, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Tuberc Respir Dis, 2005;28(1) :33-36. Objective: To study the effect of body position changes on lung mechanics, oxygenation, CT images and pathology in an oleic acid-induced acute lung injury (ALl) model. Methods: The study groups con-

  20. Society for Vascular Medicine (United States)

    ... Certification with this new online course from the Society for Vascular Medicine. Learn more. Looking for a ... jobs are listed right now. Copyright © 2016 The Society for Vascular Medicine. All Rights Reserved.

  1. 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


    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) ...

  2. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

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


    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...... patients (P analysis showed that vascular grading contributed with independent prognostic value in all patients (P

  3. Open lung biopsy (United States)

    ... CT scan Disseminated tuberculosis Granulomatosis with polyangiitis Lung cancer - small cell Lung disease Lung needle biopsy Malignant mesothelioma Pulmonary tuberculosis Rheumatoid lung disease Sarcoidosis Simple pulmonary eosinophilia ...

  4. Cellular senescence in normal and premature lung aging. (United States)

    Bartling, B


    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.


    Directory of Open Access Journals (Sweden)

    Mykea Mcknight


    Full Text Available Plant based products represent a promising alternative to conventional treatments for inflammation. Moringa oleifera Lam is a tree rich in proteins, vitamins, minerals and a variety of phytochemcals with health benefits. Among the reported health benefits are antioxidant and anti-inflammatory properties. The purpose of this study was to investigate whether tea brewed from dried Moringa leaves would abrogate inflammation in a mouse model of acute lung inflammation induced by LPS or extracts prepared from dust collected from a swine confinement facility (DE. Mice were offered water or Moringa tea for seven days. Tea consumption was significantly greater than that of water consumption on days 1 and 6, but there were no significant differences in weight gain or food consumption. On day seven, mice from both groups were forced to inhale, via intranasal challenge, either Phosphate Buffered Saline (PBS, Lipopolysaccharide (LPS [10 µg mL-1] or DE [10%]. Compared to mice that drank water, mice that drank Moringa tea had significantly less protein (p<0.05 and cellular influx (p<0.0001 into the lung after inhalation of 10% DE. No difference in neutrophil migration into the lungs of water and M. tea groups after LPS or DE challenge was detected. But mice that drank tea had significantly (p<0.05 more neutrophils with apoptotic morphology after DE challenge. TNF-α expression 24 h after inhalation of 10% DE, was significantly higher (p<0.05 in lungs of M. tea mouse group as compared to water group. This increase in TNF-α was accompanied by higher levels of pro and anti-inflammatory cytokines. Finally, activation of c-Jun N-terminal Kinase (JNK in lungs of M. tea+DE group 24 h post inhalation was decreased. Taken together these results suggest that Moringa oleifera leaf tea exerts anti-inflammatory properties on acute lung inflammation induced by swine confinement dust through a mechanism involving neutrophil regulation and JNK

  6. 参附注射液对肺叶切除术患者血流动力学及血气分析指标的影响%Effect of Shenfu Injection on Hemodynamics and Blood Gas Analysis in Patients Undergoing Lobectomy of Lung combined Epidural Block and General Anesthesia

    Institute of Scientific and Technical Information of China (English)

    李晓征; 李界平; 王强; 于海芳; 张芸


    目的:探讨参附注射液对全麻复合胸段硬膜外阻滞下行肺叶切除术患者血流动力学及血气分析指标的影响.方法:将60例拟在胸段硬膜外阻滞复合全麻下肺叶切除术病人,随机双盲法分为参附组(n=30)及对照组(n=30),参附组在麻醉诱导前静脉输注参附注射液1.5 mL/kg;对照组以同样速度输注等量的生理盐水.结果:与对照组相比,参附组的MAP、HR在诱导后5 min(T1)、手术探查时(T2)、单肺通气30 min(T3)、单肺通气60 min(T4)及关胸前冲洗胸腔时(T5)升高(P< 0.05),术中麻黄碱、阿托品的使用量及输液总量减少(P< 0.05),PaO2在T3、T4 时较对照组升高(P< 0.05),麻醉药物用量等两组比较无差异(P> 0.05).结论:参附注射液对胸段硬膜外阻滞复合全麻下肺叶切除术患者血流动力学变化具有稳定作用,可改善单肺通气期间血气分析指标.%Objective To investigate the effect of Shenfu Injection on hemodynamics and blood gas analysis in patients undergoing lobectoiny oi lung combined thoracic epidural block and general anesthesia.Methods A double blind trail was conducted on 60 patients undergoing lobectomy of lung combined thoracic epidural block and general anesthesia.The patients were randomly divided into Shenfu Injection group (n=30) and control group (n=30). In the Shenfu Injection group, 1.5 mL/kg Shenfu Injection diluted with 250 mL saline were given before anesthesia introduction. In the control group, equal saline were given at the same time. The following indexes were observed: (1) MAP,HR and CVP at the time before anesthesia introduction (TO), after anesthesia introduction for 5 minutes(T1), surgical exploration(T2),after one-lung ventilation for 30 minutes(T3), after one-lung ventilation for 60 minutes(T4), rinse chest(T5) and the end of operation(T6).(2)the dose of atropine and ephedrine, the amount of intraoperative transfusion,blood loss, urine volume and duration of surgery.(3) the

  7. CD147、血管内皮生长因子C在肺鳞状细胞癌和腺癌中的表达及其临床意义%Expression of CD147, vascular endothelial growth factor C in lung squamous cell carcinoma and adenocarcinoma and their clinical significances

    Institute of Scientific and Technical Information of China (English)

    吴强; 张祥海


    Objective To discuss the relationships between expression levels of CD147 and vascular endothelial growth factor C (VEGF-C) in lung squamous cell carcinoma and adenocarcinoma and the clinicopathological features.Methods The expression of CD147 and VEGF-C in 57 lung cancer tissues was detected by immunohistochemical method.Results The positive expression rates of CD147 and VEGF-C in 57 lung cancer tissues were 63.16 % (36/57),66.67 % (38/57) respectively.The expression of CD147 and VEGF-C in lung squamous cell carcinoma and adenocarcinoma had no statistical difference (both P > 0.05).The expression of CD147 and VEGF-C in lung squarnous cell carcinoma and adenocarcinoma had relationship with lymph node metastasis and tumor TNM stage (all P < 0.05),however they had not correlation with the patient' s age,sex,smoking and tumor cell differentiation extent irrelevant (all P > 0.05).The expression of CD147 was related positively with VEGF-C (P < 0.01).Conclusions CD147 and VEGF-C play important roles in the progression and metastasis of lung squamous cell carcinoma and adenocarcinoma,which may have a synergistic effect.The joint detection of CD147 and VEGF-C can be used as a useful prognostic indicator in patients with lung cancer.%目的 探讨CD147和血管内皮生长因子C(VEGF-C)在肺鳞状细胞癌、腺癌中的表达水平与临床病理特征之间的联系以及相互关系.方法 运用免疫组织化学法对57例肺癌组织进行CD147和VEGF-C检测.结果 57例肺癌组织中,CD147和VEGF-C的阳性表达率分别为63.16 %(36/57)、66.67%(38/57).肺鳞状细胞癌组和腺癌组CD147和VEGF-C表达差异均无统计学意义(均P>0.05).肺鳞状细胞癌、腺癌中CD147和VEGF-C的表达与肿瘤淋巴结转移及TNM分期有相关性(均P< 0.05),而与患者年龄、性别、吸烟及肿瘤细胞分化程度无相关性(均P> 0.05).CD147与VEGF-C的表达呈正相关(P<0.01).结论 CD147和VEGF-C在肺鳞状细胞癌、腺癌

  8. [HRCT patterns of the most important interstitial lung diseases

    NARCIS (Netherlands)

    Schaefer-Prokop, C.M.


    Interstitial lung diseases are a mixed group of diffuse parenchymal lung diseases which can have an acute or chronic course. Idiopathic diseases and diseases with an underlying cause (e.g. collagen vascular diseases) share the same patterns. Thin section computed tomography (CT) plays a central role

  9. Nitric oxide and carbon monoxide diffusing capacity of the lung

    NARCIS (Netherlands)

    Lee, I. van der


    The single breath diffusion capacity of the lung for carbon monoxide (DLCO) is measure for gas uptake by the lung, and consists of a membrane and a vascular component. Nitric oxide (NO) binds 400 times faster to hemoglobin than carbon monoxide, thus the uptake of NO by the blood is very large. There

  10. Lung Pathology in Antiphospholipid Syndrome

    Directory of Open Access Journals (Sweden)

    T. M. Reshetnyak


    Full Text Available Functional lesions of organs depend on the size of a diseased vessel and frequently require the use of intensive therapy methods. The commonest manifestation of antiphospholipid syndrome (APS is deep vein thrombosis of the leg and pulmonary thromboembolism (PTE.Objective: to estimate the frequency of lung lesions in primary APS (PAPS, secondary (in the presence of systemic lupus erythematosus (SLE and catastrophic APS and to assess a relationship between lung pathology and other clinical and laboratory manifestations of the disease.Subjects and methods. The study covered 372 patients followed up at the Institute of Rheumatology, Russian Academy of Medical Sciences, since 1990, of whom 290 and 82 patients had SLE and PAPS, respectively. Among the 290 patients with SLE, there were 96 males and 194 females. At the moment of the study, the patients’ age was 31.2±11.1 years and the duration of the disease was 8.6±7.2 years. The group of patients with PAPS comprised 20 males and 62 females. Their mean age was 35.6±9.9 years and the duration of the disease was 11.9±8.5 years. Thrombotic events were verified only by instrumental studies. Lung pathology was instrumentally confirmed; all the patients underwent lung X-ray study, if required, scintigraphy and computed tomography.Results. Lung lesion associated with the pathology of vessels was revealed in 28% of the examined patients (105/372. There were prevalent patients with PTE, followed by the development of lung infarcts, which was present in 96 (91% of the 105 patients with pulmonary vascular pathology. Autopsy revealed pulmonary microangiopathy was in 12 patients, which was concurrent with focal pneumonia in 7 of them, with pneumonitis and exudative pleuritis in 5. Hemorrhagic alveolitis detected at autopsy in combination with occlusions of the pulmonary arterioles was in 3 patients who had been diagnosed as having thromboembolism of small branches of the pulmonary artery. Thrombosis of the

  11. Lung density

    DEFF Research Database (Denmark)

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


    breathing in the sitting position ranged from 0.25 to 0.37 Subnormal values were found in patients with emphsema. In patients with pulmonary congestion and edema, lung density values ranged from 0.33 to 0.93 The lung density measurement correlated well with the findings in chest radiographs...

  12. Lung Cancer (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 ...

  13. Lung transplantation (United States)

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel


    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  14. Lung Oxidative Damage by Hypoxia

    Directory of Open Access Journals (Sweden)

    O. F. Araneda


    Full Text Available One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described.

  15. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

    Directory of Open Access Journals (Sweden)

    Israel L. Medeiros


    Full Text Available OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98. The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035. The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816. The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87. The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0, and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71. CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

  16. Matrix metalloproteinase/tissue inhibitor of metalloproteinase,vascular endothelial growth factor with invasion and metastasis of lung cancer%MMP/TIMP、VEGF与肺癌的浸润和转移

    Institute of Scientific and Technical Information of China (English)

    赵志芳; 陈刚


    肺癌的浸润和转移与基质金属蛋白酶(matrix metalloproteinase,MMP)及其抑制剂基质金属蛋白酶组织抑制剂(tissue inhibitor of metalloproteinase,TIMP)、血管内皮生长因子(vascular endothelial growth factor,VEGF)等多因素密切相关,深入研究肺癌中MMP/TIMP及VEGF的表达与功能,揭示肺癌的浸润与转移的机制,可为评估肺癌的浸润、转移及预后提供重要的参考指标.

  17. Lung Cancer Screening (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 ...

  18. Lung Cancer Prevention (United States)

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease in ...

  19. What Is Lung Cancer? (United States)

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  20. Aldosterone and vascular damage. (United States)

    Duprez, D; De Buyzere, M; Rietzschel, E R; Clement, D L


    Although the aldosterone escape mechanism is well known, aldosterone has often been neglected in the pathophysiologic consequences of the activated renin-angiotensin-aldosterone system in arterial hypertension and chronic heart failure. There is now evidence for vascular synthesis of aldosterone aside from its secretion by the adrenal cortex. Moreover, aldosterone is involved in vascular smooth muscle cell hypertrophy and hyperplasia, as well as in vascular matrix impairment and endothelial dysfunction. The mechanisms of action of aldosterone may be either delayed (genomic) or rapid (nongenomic). Deleterious effects of aldosterone leading to vascular target-organ damage include (besides salt and water retention) decreased arterial and venous compliance, increased peripheral vascular resistance, and impaired autonomic vascular control due to baroreflex dysfunction.

  1. Vascular effects of multiwalled carbon nanotubes in dyslipidemic ApoE-/- mice and cultured endothelial cells

    DEFF Research Database (Denmark)

    Cao, Yi; Jacobsen, Nicklas Raun; Danielsen, Pernille Høgh;


    Accumulating evidences indicate that pulmonary exposure to carbon nanotubes (CNTs) is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of 2 types of multiwalled CNTs (MWCNTs) in apolipoprotein E(-/-) mice,...

  2. Ultrasound guided supraclavicular block.

    LENUS (Irish Health Repository)

    Hanumanthaiah, Deepak


    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.

  3. Vascular Cognitive Impairment. (United States)

    Dichgans, Martin; Leys, Didier


    Cerebrovascular disease typically manifests with stroke, cognitive impairment, or both. Vascular cognitive impairment refers to all forms of cognitive disorder associated with cerebrovascular disease, regardless of the specific mechanisms involved. It encompasses the full range of cognitive deficits from mild cognitive impairment to dementia. In principle, any of the multiple causes of clinical stroke can cause vascular cognitive impairment. Recent work further highlights a role of microinfarcts, microhemorrhages, strategic white matter tracts, loss of microstructural tissue integrity, and secondary neurodegeneration. Vascular brain injury results in loss of structural and functional connectivity and, hence, compromise of functional networks within the brain. Vascular cognitive impairment is common both after stroke and in stroke-free individuals presenting to dementia clinics, and vascular pathology frequently coexists with neurodegenerative pathology, resulting in mixed forms of mild cognitive impairment or dementia. Vascular dementia is now recognized as the second most common form of dementia after Alzheimer's disease, and there is increasing awareness that targeting vascular risk may help to prevent dementia, even of the Alzheimer type. Recent advances in neuroimaging, neuropathology, epidemiology, and genetics have led to a deeper understanding of how vascular disease affects cognition. These new findings provide an opportunity for the present reappraisal of vascular cognitive impairment. We further briefly address current therapeutic concepts.

  4. Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons. (United States)

    Fortuna, Vitor; Pardanaud, Luc; Brunet, Isabelle; Ola, Roxana; Ristori, Emma; Santoro, Massimo M; Nicoli, Stefania; Eichmann, Anne


    The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation.

  5. Block Cipher Analysis

    DEFF Research Database (Denmark)

    Miolane, Charlotte Vikkelsø

    Block ciphersarecryptographicprimitivesthatoperateon fixed sizetexts(blocks). Mostdesigns aim towards secure andfastencryption oflarge amounts ofdata. Block ciphers also serve as the building block of a number of hash functions and message authentication codes(MAC).Thetask of cryptanalysisisto en...... on small scale variants of AES. In the final part of the thesis we present a new block cipher proposal Present and examine its security against algebraic and differential cryptanalysis in particular.......Block ciphersarecryptographicprimitivesthatoperateon fixed sizetexts(blocks). Mostdesigns aim towards secure andfastencryption oflarge amounts ofdata. Block ciphers also serve as the building block of a number of hash functions and message authentication codes(MAC).Thetask of cryptanalysisisto...... ensurethat no attack violatesthe securitybounds specifiedbygeneric attack namely exhaustivekey search and table lookup attacks. This thesis contains a general introduction to cryptography with focus on block ciphers and important block cipher designs, in particular the Advanced Encryption Standard...

  6. Poikiloderma vasculare atrophicans

    Directory of Open Access Journals (Sweden)

    Padmavathy L


    Full Text Available A 65 year old lady presented with generalised pruritus and discolouration of skin and mucous membranes of 5 years duration. The histopathology from the cutaneous lesions revealed features suggestive of poikiloderma vasculare atrophicans (PVA. Investigations did not reveal any underlying connective tissue disease,lymphoma or systemic disease. A diagnosis of idiopathic poikiloderma vasculare atrophicans was made.

  7. Lung Transplant (United States)

    ... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...

  8. [Vascular factors in glaucoma]. (United States)

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


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

  9. Hedgehog信号通路阻断对人胃癌细胞SGC-7901侵袭和血管内皮生长因子表达的影响%Effect of Hedgehog Signal Pathway Blocking on Invasion and Vascular Endothelial Growth Factor Expression of Human Gastric Cancer SGC-7901 Cells

    Institute of Scientific and Technical Information of China (English)

    欧阳小波; 郝亚琴; 王立


    目的 探讨Hedgehog(Hh)信号通路阻断对人胃癌细胞SGC-7901侵袭的影响及其可能的机制.方法 免疫荧光检测Hh信号通路分子Shh和Gli 1蛋白在SGC-7901细胞中的表达;用不同浓度((2.5、5、10μmol/L)的Hh信号通路特异性阻断剂环靶明作用SGC-7901细胞48 h后,Transwell小室试验检测SGC-7901细胞的侵袭能力,半定量RT-PCR检测SGC-7901细胞中Shh、Gli 1和血管内皮生长因子(VEGF)基因mRNA的表达.结果 Shh和Gli 1蛋白在SGC-7901细胞中高表达;环靶明能显著抑制SGC-7901细胞的侵袭,且呈剂量依赖性;Hh信号通路阻断后,SGC-7901细胞中Shh基因mRNA的表达水平无明显改变,Gli 1和VEGF基因mRNA的表达水平显著下降.结论 Hh信号通路分子在SGC-7901细胞中高表达,阻断Hh信号通路可以抑制SGC-7901细胞的侵袭,可能是通过抑制Glil下调VEGF起作用.%Objective To investigate the effect of Hedgehog (Hh) signal pathway blocking on invasion and vascular endothelial growth factor (VEGF) expression of human gastric cancer SGC-7901 cells as well as the relevant mechanism. Methods The expressions of Hh signal pathway molecules Shh and Gli1 proteins were determined by IFA. SGC-7901 cells were treated with cyclopamine, a specific blocker of Hh signal pathway, at various concentrations (2. 5, 5 and 10 μmol/L) for 48 h, then determined for invasion ability by Transwell test, and for expressions of Shh, Gli1 and VEGF mRNAs by semi-quantitative RT-PCR. Results Shh and Gli1 proteins were highly expressed in SGC-7901 cells. Cyclopamine showed a dosage-dependent inhibitory effect on the invasion of SGC-7901 cells. After Hh signal pathway blocking, the Shh mRNA level in SGC-7901 cells showed no significant change,while the Gli1 and VEGF mRNA levels decreased significantly. Conclusion Hh signal pathway molecules were highly expressed in SGC-7901 cells. Hh signal pathway blocking inhibited the invasion of SGC-7901 cells by a possible mechanism of down

  10. Neuropilin-1 mediates vascular permeability independently of vascular endothelial growth factor receptor-2 activation. (United States)

    Roth, Lise; Prahst, Claudia; Ruckdeschel, Tina; Savant, Soniya; Weström, Simone; Fantin, Alessandro; Riedel, Maria; Héroult, Mélanie; Ruhrberg, Christiana; Augustin, Hellmut G


    Neuropilin-1 (NRP1) regulates developmental and pathological angiogenesis, arteriogenesis, and vascular permeability, acting as a coreceptor for semaphorin 3A (Sema3A) and the 165-amino acid isoform of vascular endothelial growth factor A (VEGF-A165). NRP1 is also the receptor for the CendR peptides, a class of cell- and tissue-penetrating peptides with a specific R-x-x-R carboxyl-terminal motif. Because the cytoplasmic domain of NRP1 lacks catalytic activity, NRP1 is mainly thought to act through the recruitment and binding to other receptors. We report here that the NRP1 intracellular domain mediates vascular permeability. Stimulation with VEGF-A165, a ligand-blocking antibody, and a CendR peptide led to NRP1 accumulation at cell-cell contacts in endothelial cell monolayers, increased cellular permeability in vitro and vascular leakage in vivo. Biochemical analyses, VEGF receptor-2 (VEGFR-2) silencing, and the use of a specific VEGFR blocker established that the effects induced by the CendR peptide and the antibody were independent of VEGFR-2. Moreover, leakage assays in mice expressing a mutant NRP1 lacking the cytoplasmic domain revealed that this domain was required for NRP1-induced vascular permeability in vivo. Hence, these data define a vascular permeability pathway mediated by NRP1 but independent of VEGFR-2 activation.

  11. Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in chronic hypoxia- and antigen-mediated pulmonary vascular remodeling

    Directory of Open Access Journals (Sweden)

    Angelini Daniel J


    Full Text Available Abstract Background Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in explaining this differential response. Methods We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung. Results Chronic hypoxia increased both mean pulmonary artery pressure (mPAP and right ventricular (RV hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue. Conclusions The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.

  12. 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"


    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 ...

  13. Pulmonary manifestations of the collagen vascular diseases. (United States)

    Wiedemann, H P; Matthay, R A


    The collagen vascular diseases are a heterogeneous group of immunologically mediated inflammatory disorders. The organs and tissues that compose the respiratory system are frequently affected by these diseases. Potential targets of the inflammation and injury include the lung parenchyma, tracheobronchial tree, pulmonary vasculature, pleura, larynx, and respiratory muscles. In this article, the spectrum of respiratory disease caused by systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis, mixed connective tissue disease, ankylosing spondylitis, relapsing polychondritis, and Sjögren's syndrome is reviewed. Where appropriate, therapeutic options are discussed.


    Directory of Open Access Journals (Sweden)

    Ananth Bhandary


    Full Text Available Hereditary hemorrhagic telangeiectasia (HHT is an autosomal dominant genetic disorder that leads to vascular malformations. It was first recognized in the 19th century as a familial disorder with abnormal vascular structures causing bleeding from the nose and gastrointestinal tract. HHT is characterized by telangiectatic lesions of the nose, lips, lungs, brain, and spinal cord. The reported incidence in Europe and Japan is between 1:5000 and 1:8000; but is widely variable in other regions. It is seen more frequently in whites. Ocular involvement has been reported in patients with HHT. Although conjunctival telangiectasia is the most common manifestation, rarely intraocular vascular lesions such as retinal telangiectasia and arteriovenous malformations in the retina, are seen. We describe a patient with HHT who had an abnormal unilateral retinal vascular abnormality along with tortuous conjunctival vasculature in the other eye, which has not been reported till date

  15. Pretreatment with recombinant human vascular endothelial growth factor virus replication and inflammation in a perinatal lamb model of RSV infection (United States)

    Vascular endothelial growth factor (VEGF) is increasingly recognized as a perinatal regulator of lung maturation and surfactant protein expression. Innate immune components including surfactant proteins A and D, and beta defensins have putative antimicrobial activity against pulmonary pathogens inc...

  16. Interstitial Lung Diseases (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 ...

  17. Lung Carcinoid Tumor: Surgery (United States)

    ... Disease Lung Carcinoid Tumor Treating Lung Carcinoid Tumors Surgery to Treat Lung Carcinoid Tumors Surgery is the ... be cured by surgery alone. Types of lung surgery Different operations can be used to treat (and ...

  18. Lung cancer - small cell (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 ...

  19. Intracranial Vascular Treatments (United States)

    ... full size with caption Related Articles and Media Gamma Knife Linear Accelerator Catheter Embolization Angioplasty and Vascular Stenting Proton Therapy Radiation Dose in X-Ray and CT Exams Stereotactic ...

  20. Congenital Vascular Malformation (United States)

    ... also be effective for small, localized birthmarks (port wine stains). Patients with a rare venous malformation (Kleppel– ... 3) non-profit organization focused on providing public education and improving awareness about vascular diseases. For more ...

  1. Stem cell factor improves lung recovery in rats following neonatal hyperoxia-induced lung injury (United States)

    Miranda, Luis F.; Rodrigues, Claudia O.; Ramachandran, Shalini; Torres, Eneida; Huang, Jian; Klim, Jammie; Hehre, Dorothy; McNiece, Ian; Hare, Joshua M.; Suguihara, Cleide Y.; Young, Karen C.


    BACKGROUND Stem cell factor (SCF) and its receptor, c-kit, are modulators of angiogenesis. Neonatal hyperoxia-induced lung injury (HILI) is characterized by disordered angiogenesis. The objective of this study was to determine whether exogenous SCF improves recovery from neonatal HILI by improving angiogenesis. METHODS Newborn rats assigned to normoxia (RA: 20.9% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to 15, received daily injections of SCF 100 µg/kg or placebo (PL) from P15 to P21. Lung morphometry was performed at P28. Capillary tube formation in SCF-treated hyperoxia-exposed pulmonary microvascular endothelial cells (HPMECs) was determined by Matrigel assay. RESULTS As compared with RA, hyperoxic-PL pups had decrease in alveolarization and in lung vascular density, and this was associated with increased right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and vascular remodeling. In contrast, SCF-treated hyperoxic pups had increased angiogenesis, improved alveolarization, and attenuation of pulmonary hypertension as evidenced by decreased RVSP, right ventricular hypertrophy, and vascular remodeling. Moreover, in an in vitro model, SCF increased capillary tube formation in hyperoxia-exposed HPMECs. CONCLUSION Exogenous SCF restores alveolar and vascular structure in neonatal rats with HILI by promoting neoangiogenesis. These findings suggest a new strategy to treat lung diseases characterized by dysangiogenesis. PMID:24153399

  2. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari


    Full Text Available The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS’s role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

  3. [Complex vascular access]. (United States)

    Mangiarotti, G; Cesano, G; Thea, A; Hamido, D; Pacitti, A; Segoloni, G P


    Availability of a proper vascular access is a basic condition for a proper extracorporeal replacement in end-stage chronic renal failure. However, biological factors, management and other problems, may variously condition their middle-long term survival. Therefore, personal experience of over 25 years has been critically reviewed in order to obtain useful information. In particular "hard" situations necessitating complex procedures have been examined but, if possible, preserving the peripherical vascular features.

  4. Ageing and vascular ageing



    There is an age related decline in various physiological processes. Vascular ageing is associated with changes in the mechanical and the structural properties of the vascular wall, which leads to the loss of arterial elasticity and reduced arterial compliance. Arterial compliance can be measured by different parameters like pulse wave velocity, augmentation index, and systemic arterial compliance. There is evidence that arterial compliance is reduced in disease states such as hypertension, di...

  5. Clinical outcome of en-block resection and reconstruction with nonvascularized fibular autograft for the treatment of giant cell tumor of distal radius

    Directory of Open Access Journals (Sweden)

    Mohammad H Taraz-Jamshidi


    Full Text Available Background: Although giant cell tumor (GCT is considered to be a primary benign bone tumor, its aggressive behavior makes its diagnosis and treatment, difficult and challenging. This is especially true in distal radius where GCT appears to be more aggressive and difficult to control locally. We report our clinical outcome of en-block resection and reconstruction with non-vascularized fibular autograft in 15 patients with distal radius GCT. Materials and Methods: We retrospectively reviewed 15 patients with GCT (Grade 2 and 3 of distal radius who were treated with en-block resection and non-vascularized fibular autograft. Five of 15 were recurrent GCT treated initially with extended curettage; local adjuvant therapy and filling the cavity with cement or bone graft. We followed the patients for mean 7.2 years post operation (range: 4-11 years. Patients were evaluated post operation with clinical examination, plain radiography of distal radius and chest X-ray and/or computed tomography scan. Furthermore pain, function, range of motion and grip strength of the affected limb were evaluated and mMayo wrist score was assessed. Results: A total of 11 patients were women and 4 were men. Mean age of patients was 29 years (range: 19-48. We had no lung metastasis and bony recurrence occurred in one patient (6.6%. Nearly 53.3% of patients had excellent or good functional wrist score, 80% of the patients were free of pain or had only occasional pain and 80% of patients returned to work. Mean range of motion of the wrist was 77° of flexion-extension and mean grip strength was 70% of the normal hand. Conclusion: En-block resection of distal radius GCT and reconstruction with non-vascularized fibular autograft is an effective technique for treatment in local control of the tumor and preserving function of the limb.

  6. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks (United States)

    Kang, Tae-Yun; Hong, Jung Min; Jung, Jin Woo; Kang, Hyun-Wook; Cho, Dong-Woo


    We used indirect stereolithography (SL) to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture. PMID:27228079

  7. Construction of Large-Volume Tissue Mimics with 3D Functional Vascular Networks.

    Directory of Open Access Journals (Sweden)

    Tae-Yun Kang

    Full Text Available We used indirect stereolithography (SL to form inner-layered fluidic networks in a porous scaffold by introducing a hydrogel barrier on the luminal surface, then seeded the networks separately with human umbilical vein endothelial cells and human lung fibroblasts to form a tissue mimic containing vascular networks. The artificial vascular networks provided channels for oxygen transport, thus reducing the hypoxic volume and preventing cell death. The endothelium of the vascular networks significantly retarded the occlusion of channels during whole-blood circulation. The tissue mimics have the potential to be used as an in vitro platform to examine the physiologic and pathologic phenomena through vascular architecture.

  8. Vascular compression syndromes. (United States)

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


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

  9. Carbon monoxide and bile pigments: surprising mediators of vascular function. (United States)

    Durante, William


    Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.

  10. NHLBI viewpoint: Lung health and disease prevention research starting in childhood. (United States)

    Blaisdell, Carol J; Weinmann, Gail G


    Lung health begins in utero when the complex structure of the airway, alveolar, and vascular structures are formed. To really impact the United States and global burden of chronic lung diseases in both adults and children, we must understand normal and abnormal development, the outcomes of disrupted development, and the effects of in utero and postnatal exposures on lung health. With increasing recognition of early life origins of adult diseases,(1) it is important to know what early events and interventions can alter the trajectory of lung development, growth, and decline to help promote lung health and reduce chronic lung disease.

  11. Effect of vitamin E on lung development and vascular remodeling in fetal rats with congenital diaphragmatic hernia%维生素E对先天性膈疝大鼠模型胎仔肺发育及肺血管重构的影响

    Institute of Scientific and Technical Information of China (English)

    林涵; 王銮虹; 刘文英; 王学军; 吉毅; 杨纲


    Objective To discuss the effect of vitamin E on lung development and vascular remodeling in fetal rats with congenital diaphragmatic hernia (CDH). Methods Eighteen pregnant SD rats were randomly divided into 3 groups; control group, CDH group and intervention group. Rats in CDH group and intervention group underwent intragastric administration with nitrofen 125 mg ( soluble in olive oil 2 ml). Rats in control group were given olive oil 2 ml. Rats in intervention group were given vitamin E 140 mg/kg ( soluble in alcohol 2 ml) q. D for 3 days from the 11 th day of pregnancy. CDH group and intervention group were given alcohol 2 ml. Results Incidence of teratogenesis caused by diaphragmatic hernia in intervention group was less than that in CDH group (46. 34% vs 66. 67% , P<0. 05 ). Fetal rats in control group and CDH group showed similar lung development. The lung weight/body weight ratio, axial gland alveolus count ( RAC) , pulmonary alveolus area proportion and pulmonary alveolus area ratio in intervention group were significantly higher than those in CDH group [(3.45±0.58) mg/g vs (2.36±0.61) mg/g,4.4±0.3 vs2.3±0.2, (63.7±5.6)% vs ( 46. 5 ±7. 3) % , (45 ±6)% vs(27±6.7)%,P<0.01]. The alveolar septum area ratio in intervention group was significantly lower than that in CDH group [(45±6.8)% vs (63±8.3)% , P < 0.01]. The mean media thickness percentage of pre-acinar pulmonary arteries and that of intra-acinar pulmonary arteries of fetal rats in intervention group were significantly lower than those in CDH group [(22. 1±2.2)% vs (24.3±4.0)% , (17.6±2.8)% vs (21.5±2.9)% , P < 0.01 ]. The proportion of non-muscle arteries in IAPA per unit of visual field in intervention group was significantly higher than that in CDH group [(79.4±3.2)% vs (71.6±3.3)%, P< 0.01]. Conclusions Prenatal treatment with vitamin E can decrease the incidence of CDH, which may improve the lung development and inhibit the vascular remodeling in lung.%目的 探讨维生素E对先

  12. Effects of sildenafil on pulmonary hypertension and exercise tolerance in severe cystic fibrosis-related lung disease. (United States)

    Montgomery, Gregory S; Sagel, Scott D; Taylor, Amy L; Abman, Steven H


    Cystic fibrosis (CF) patients with advanced lung disease are at risk for developing pulmonary vascular disease and pulmonary hypertension, characterized by progressive exercise intolerance beyond the exercise-limiting effects of airways disease in CF. We report on a patient with severe CF lung disease who experienced clinically significant improvements in exercise tolerance and pulmonary hypertension without changing lung function during sildenafil therapy.

  13. HABP2 is a Novel Regulator of Vascular Integrity (United States)

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


    Objective We evaluated the role of the extracellular serine protease, Hyaluronic Acid Binding Protein 2 (HABP2), in vascular barrier regulation. Methods and Results Using immunoblot and immunohistochemical analysis, we observed that lipopolysaccharide (LPS)-induces HABP2 expression in murine lung endothelium in vivo and in human pulmonary microvascular endothelial cell (HPMVEC) in vitro. High molecular weight hyaluronan (HMW-HA, ~1 million Da) decreased HABP2 protein expression in HPMVEC and decreased purified HABP2 enzymatic activity whereas low MW HA (LMW-HA, ~2,500 Da) increased these activities. The effects of LMW-HA on HABP2 activity, but not HMW-HA, were inhibited with a peptide of the polyanion binding domain (PABD) of HABP2. Silencing (siRNA) HABP2 expression augmented HMW-HA-induced EC barrier enhancement and inhibited LPS and LMW-HA-mediated EC barrier disruption, results which were reversed with overexpression of HABP2. Silencing PAR receptors 1 and 3, RhoA or ROCK expression attenuated LPS, LMW-HA and HABP2-mediated EC barrier disruption. Utilizing murine models of acute lung injury, we observed that LPS- and ventilator-induced pulmonary vascular hyper-permeability were significantly reduced with vascular silencing (siRNA) of HABP2. Conclusions HABP2 negatively regulates vascular integrity via activation of PAR receptor/RhoA/ROCK signaling and represents a potentially useful therapeutic target for syndromes of increased vascular permeability. PMID:20042707

  14. 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: [Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Xi' an 710032 (China)


    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.

  15. Lung surgery (United States)

    ... are thoracotomy and video-assisted thoracoscopic surgery (VATS). Robotic surgery may also be used. Lung surgery using a ... clot from the pulmonary artery ( pulmonary embolism ) Treat complications of tuberculosis Video-assisted thoracoscopic surgery can be used to treat many of these ...

  16. [Humidifier lung]. (United States)

    Gerber, P; de Haller, R; Pyrozynski, W J; Sturzenegger, E R; Brändli, O


    Breathing air from a humidifier or an air conditioning unit contaminated by various microorganisms can cause an acute lung disease involving fever, cough and dyspnea, termed "humidifier fever". This type of hypersensitivity pneumonitis was first described in 1959 by PESTALOZZI in the Swiss literature and subsequently by BANASZAK et al. in the Anglo-American. Here a chronic form of this disease which led to pulmonary fibrosis is described: A 37-year-old woman who works in a cheese shop presented with dyspnea which had been progressive over two years, weight loss, a diffuse reticular pattern radiographically and a severe restrictive defect in lung function tests. Open lung biopsy revealed chronic interstitial and alveolar inflammation with non-caseating granulomas and fibrotic changes. Circulating immune complexes and precipitins against the contaminated humidifier water and cheese mites were found, but no antibodies suggesting legionnaires' disease. Two out of five otherwise healthy employees of this cheese shop, where a new humidifying system had been installed 7 years earlier, also had precipitins against the contaminated water from the humidifier and the cheese mites. Despite ending of exposure and longterm steroid and immunosuppressive therapy, the signs and symptoms of pulmonary fibrosis persisted. Contrary to the acute disease, this chronic form is termed "humidifier lung". The importance is stressed of investigating the possibility of exposure to contaminated humidifiers or air conditioning units in all cases of newly detected pulmonary fibrosis.

  17. Lung cancer

    DEFF Research Database (Denmark)

    Hansen, H H; Rørth, M


    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...

  18. Total Spinal Block after Thoracic Paravertebral Block. (United States)

    Beyaz, Serbülent Gökhan; Özocak, Hande; Ergönenç, Tolga; Erdem, Ali Fuat; Palabıyık, Onur


    Thoracic paravertebral block (TPVB) can be performed with or without general anaesthesia for various surgical procedures. TPVB is a popular anaesthetic technique due to its low side effect profile and high analgesic potency. We used 20 mL of 0.5% levobupivacaine for a single injection of unilateral TPVB at the T7 level with neurostimulator in a 63 year old patient with co-morbid disease who underwent cholecystectomy. Following the application patient lost consciousness, and was intubated. Haemodynamic instability was normalised with rapid volume replacement and vasopressors. Anaesthetic drugs were stopped at the end of the surgery and muscle relaxant was antagonised. Return of mucle strenght was shown with neuromuscular block monitoring. Approximately three hours after TPVB, spontaneous breathing started and consciousness returned. A total spinal block is a rare and life-threatening complication. A total spinal block is a complication of spinal anaesthesia, and it can also occur after peripheral blocks. Clinical presentation is characterised by hypotension, bradicardia, apnea, and cardiac arrest. An early diagnosis and appropriate treatment is life saving. In this case report, we want to present total spinal block after TPVB.

  19. Depleted energy charge and increased pulmonary endothelial permeability induced by mitochondrial complex I inhibition are mitigated by coenzyme Q1 in the isolated perfused rat lung. (United States)

    Bongard, Robert D; Yan, Ke; Hoffmann, Raymond G; Audi, Said H; Zhang, Xiao; Lindemer, Brian J; Townsley, Mary I; Merker, Marilyn P


    Mitochondrial dysfunction is associated with various forms of lung injury and disease that also involve alterations in pulmonary endothelial permeability, but the relationship, if any, between the two is not well understood. This question was addressed by perfusing isolated intact rat lung with a buffered physiological saline solution in the absence or presence of the mitochondrial complex I inhibitor rotenone (20 μM). Compared to control, rotenone depressed whole lung tissue ATP from 5.66 ± 0.46 (SEM) to 2.34 ± 0.15 µmol · g(-1) dry lung, with concomitant increases in the ADP:ATP and AMP:ATP ratios. Rotenone also increased lung perfusate lactate (from 12.36 ± 1.64 to 38.62 ± 3.14 µmol · 15 min(-1) perfusion · g(-1) dry lung) and the lactate:pyruvate ratio, but had no detectable impact on lung tissue GSH:GSSG redox status. The amphipathic quinone coenzyme Q1 (CoQ1; 50 μM) mitigated the impact of rotenone on the adenine nucleotide balance, wherein mitigation was blocked by NAD(P)H-quinone oxidoreductase 1 or mitochondrial complex III inhibitors. In separate studies, rotenone increased the pulmonary vascular endothelial filtration coefficient (Kf) from 0.043 ± 0.010 to 0.156 ± 0.037 ml · min(-1) · cm H2O(-1) · g(-1) dry lung, and CoQ1 protected against the effect of rotenone on Kf. A second complex I inhibitor, piericidin A, qualitatively reproduced the impact of rotenone on Kf and the lactate:pyruvate ratio. Taken together, the observations imply that pulmonary endothelial barrier integrity depends on mitochondrial bioenergetics as reflected in lung tissue ATP levels and that compensatory activation of whole lung glycolysis cannot protect against pulmonary endothelial hyperpermeability in response to mitochondrial blockade. The study further suggests that low-molecular-weight amphipathic quinones may have therapeutic utility in protecting lung barrier function in mitochondrial insufficiency.

  20. Generalized Block Failure

    DEFF Research Database (Denmark)

    Jönsson, Jeppe


    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...... yield lines around the block leads to simple interaction formulas similar to other interaction formulas in the codes.......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...

  1. 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


    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.

  2. Ageing and vascular ageing (United States)

    Jani, B; Rajkumar, C


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

  3. Chemerin Regulates Crosstalk Between Adipocytes and Vascular Cells Through Nox. (United States)

    Neves, Karla Bianca; Nguyen Dinh Cat, Aurelie; Lopes, Rheure Alves Moreira; Rios, Francisco Jose; Anagnostopoulou, Aikaterini; Lobato, Nubia Souza; de Oliveira, Ana Maria; Tostes, Rita C; Montezano, Augusto C; Touyz, Rhian M


    Adipocytes produce adipokines, including chemerin, a chemoattractant that mediates effects through its ChemR23 receptor. Chemerin has been linked to endothelial dysfunction and vascular injury in pathological conditions, such as obesity, diabetes mellitus, and hypertension. Molecular mechanisms underlying this are elusive. Here we assessed whether chemerin through redox-sensitive signaling influences molecular processes associated with vascular growth, apoptosis, and inflammation. Human microvascular endothelial cells and vascular smooth muscle cells were stimulated with chemerin (50 ng/mL). Chemerin increased generation of reactive oxygen species and phosphorylation of mitogen-activated protein kinases, effects that were inhibited by ML171, GKT137831 (Nox inhibitors), and N-acetylcysteine (reactive oxygen species scavenger). Chemerin increased mRNA expression of proinflammatory mediators in vascular cells and increased monocyte-to-endothelial cell attachment. In human vascular smooth muscle cells, chemerin induced phosphorylation of mitogen-activated protein kinases and stimulated proliferation (increased proliferating cell nuclear antigen expression [proliferation marker] and BrdU incorporation [proliferation assay]). Chemerin decreased phosphatidylinositol 3-kinase/protein kinase B activation and increased TUNEL-positive human vascular smooth muscle cells. In human microvascular endothelial cells, chemerin reduced endothelial nitric oxide synthase activity and nitric oxide production. Adipocyte-conditioned medium from obese/diabetic mice (db/db), which have elevated chemerin levels, increased reactive oxygen species generation in vascular smooth muscle cells, whereas adipocyte-conditioned medium from control mice had no effect. Chemerin actions were blocked by CCX 832, a ChemR23 inhibitor. Our data demonstrate that chemerin, through Nox activation and redox-sensitive mitogen-activated protein kinases signaling, exerts proapoptotic, proinflammatory, and

  4. 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.


    Institute of Scientific and Technical Information of China (English)

    黄廷祝; 黎稳


    The block H-matrices are studied by the concept of G-functions, several concepts of block matrices are introduced. Equivalent characters of block H-matrices are obtained. Spectrum localizations claracterized by Gfunctions for block matrices are got.

  6. Differing patterns of P-selectin expression in lung injury

    DEFF Research Database (Denmark)

    Bless, N M; Tojo, S J; Kawarai, H


    Using two models of acute lung inflammatory injury in rats (intrapulmonary deposition of immunoglobulin G immune complexes and systemic activation of complement after infusion of purified cobra venom factor), we have analyzed the requirements and patterns for upregulation of lung vascular P......-selectin. In the immune complex model, upregulation of P-selectin was defined by Northern and Western blot analysis of lung homogenates, by immunostaining of lung tissue, and by vascular fixation of 125I-labeled anti-P-selectin. P-selectin protein was detected by 1 hour (long before detection of mRNA) and expression......-selectin was dependent on an intact complement system, and the presence of blood neutrophils was susceptible to the antioxidant dimethyl sulfoxide and required C5a but not tumor necrosis factor alpha. In contrast, in the cobra venom factor model, upregulation of P-selectin, which is C5a dependent, was also dimethyl...

  7. Lymphatic function is required prenatally for lung inflation at birth (United States)

    Jakus, Zoltán; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.


    Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants. PMID:24733830

  8. Block TERM factorization of block matrices

    Institute of Scientific and Technical Information of China (English)

    SHE Yiyuan; HAO Pengwei


    Reversible integer mapping (or integer transform) is a useful way to realize Iossless coding, and this technique has been used for multi-component image compression in the new international image compression standard JPEG 2000. For any nonsingular linear transform of finite dimension, its integer transform can be implemented by factorizing the transform matrix into 3 triangular elementary reversible matrices (TERMs) or a series of single-row elementary reversible matrices (SERMs). To speed up and parallelize integer transforms, we study block TERM and SERM factorizations in this paper. First, to guarantee flexible scaling manners, the classical determinant (det) is generalized to a matrix function, DET, which is shown to have many important properties analogous to those of det. Then based on DET, a generic block TERM factorization,BLUS, is presented for any nonsingular block matrix. Our conclusions can cover the early optimal point factorizations and provide an efficient way to implement integer transforms for large matrices.

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

    Vidrio, H; Hong, E


    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. Massive hemothorax: A rare complication after supraclavicular brachial plexus block. (United States)

    Singh, Shiv Kumar; Katyal, Surabhi; Kumar, Amit; Kumar, Pawan


    Plexus block is the preferred anesthesia plan for upper limb surgeries. Among the known complications, hematoma formation following the vascular trauma is often occur but this complication is frequently underreported. We present a case where a massive hemothorax developed post operatively in a patient who underwent resection of giant cell tumor of the right hand radius bone followed by arthroplasty under brachial plexus block using supraclavicular approach. This case report attempts to highlight the essence of remaining vigilant postoperatively for first initial days after brachial plexus block, especially after failed or multiple attempts. Ultrasound guided technique in combination with nerve stimulator has proven to be more reliable and safer than traditional techniques.


    Institute of Scientific and Technical Information of China (English)

    李鲲; 葛银林; 张金玉


    目的 应用化学修饰的小干扰RNA(siRNA)阻断裸鼠乳癌移植瘤中血管内皮生长因子C(VEGF-C)基因, 探讨其对人乳癌MCF-7裸鼠移植瘤生长的影响.方法 于雌裸鼠皮下种植MCF-7细胞,将成瘤阳性的裸鼠随机分为VEGF-C siRNA处理组、脂质体组和对照组,每组5只.VEGF-C siRNA处理组肿瘤局部注射VEGF-C siRNA 1 mg/kg和PEITM,脂质体组肿瘤局部注射PEITM和PBS,对照组仅注射PBS,每3 d注射1次,连续注射8次.22 d后拉颈处死全部动物, 取肿瘤,采用半定量 RT-PCR 分析VEGF-C mRNA水平,Western blotting检测VEGF-C蛋白表达水平.结果 VEGF-C siRNA处理组瘤组织的增长受到明显抑制,VEGF-C基因的mRNA和蛋白表达水平显著降低(F=73.64~197.15,q=8.74~25.56,P<0.05).对照组各指标无显著变化.结论 化学修饰的siRNA介导的RNAi在体内能成功下调人乳癌裸鼠移植瘤中VEGF-C基因的表达, 抑制肿瘤的生长,是潜在的肿瘤基因治疗新方法.%Objective Using chemically-modified siRNA technique, vascular endothelial growth factor-C (VEGF-C) gene in transplanted breast cancer in nude mice was blocked and its effects on the growth of transplanted tumor investigated. MethodsHuman breast cancer cells MCF-7 were subcutaneously transplanted into the female mice, those with tumor-positive were rando-mized to three groups as VEGF-C siRNA, liposome and control, with five mice in each group. For VEGF-C siRNA group: VEGF-C siRNA 1 mg/kg and in vivo jetPEITM were injected locally; for liposome group: intra-tumor injection of in vivo jetPEITM and PBS was done; for control group: PBS alone was given. The medication was given every three days for eight times. The experimental animals were sacrificed 22 days later and tumors taken. Semiquantitative RT-PCR was applied for VEGF-C Mrna detection, and Western blotting for VEGF-C. Results The growth of tumor in VEGF-C siRNA group was greatly inhibited, the expressions of VEGF-C gene and protein

  12. Lesson Thirteen Trifascicular Block

    Institute of Scientific and Technical Information of China (English)

    鲁端; 王劲


    @@ A complete trifascicular block would result in complete AV block. The idio ventricular rhythm has a slower rate and a wide QRS complex because the pacemaker is located at the peripheral part of the conduction system distal to the sites of the block1. Such a rhythm may be difficult to differentiate from bifascicular or bundle branch block combined with complete block at a higher level such as the AV node or His bundle2. Besides a slower ventricular rate, a change in the morphology of the QRS complex from a previous known bifascicular pattern would be strongly suggestive of a trifascicular origin of the complete AV block3. A His bundle recording is required for a definitive diagnosis, however.

  13. Angiogenesis inhibitors under study for the treatment of lung cancer. (United States)

    Shepherd, Frances A; Sridhar, Srikala S


    Several classes of agents now exist that target the different steps involved in angiogenesis. These include drugs inhibiting matrix breakdown, the matrix metalloproteinase inhibitors (MMPIs), such as marimastat, prinomastat, BMS275291, BAY12-9566, and neovastat. Trials of this class of agents have all been negative to date. Drugs that block endothelial cell signaling via vascular endothelial growth factor (VEGF) and its receptor (VEGFR) including rhuMAb VEGF, SU5416, SU6668, ZD6474, CP-547,632 and ZD4190 are all in earlier stages of clinical trial. Drugs that are similar to endogenous inhibitors of angiogenesis including interferons have also been evaluated without success. Endostatin has been shown to have an acceptable toxicity profile, but clinical evidence of activity has not yet been demonstrated. There has also been renewed interest in thalidomide. Drugs such as squalamine, celecoxib, ZD6126, TNP-470 and those targeting the integrins are also being evaluated in lung cancer. Despite early enthusiasm for many of these agents, Phase III trials have not yet demonstrated significant increases in overall survival and toxicity remains an issue. It is hoped that as our understanding of the complex process of angiogenesis increases, so will our ability to design more effective targeted therapies.

  14. 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.

  15. Staging of Lung Cancer (United States)

    ... is important for two reasons. First, staging your lung cancer helps decide which therapy (or therapies) should be used. Second, lung cancer ... 422-6237 small-cell-lung/Patient/page2 National Lung ...

  16. Assessment of lung tumor response by perfusion CT. (United States)

    Coche, E


    Perfusion CT permits evaluation of lung cancer angiogenesis and response to therapy by demonstrating alterations in lung tumor vascularity. It is advocated that perfusion CT performed shortly after initiating therapy may provide a better evaluation of physiological changes rather than the conventional size assessment obtained with RECIST. The radiation dose,the volume of contrast medium delivered to the patient and the reproducibility of blood flow parameters remain an issue for this type of investigation.

  17. Surgical technique for lung retransplantation in the mouse


    Li, Wenjun; Goldstein, Daniel R.; Bribriesco, Alejandro C.; Nava, Ruben G.; Spahn, Jessica H.; Wang, Xingan; Gelman, Andrew E.; Krupnick, Alexander S.; Kreisel, Daniel


    Microsurgical cuff techniques for orthotopic vascularized murine lung transplantation have allowed for the design of studies that examine mechanisms contributing to the high failure rate of pulmonary grafts. Here, we provide a detailed technical description of orthotopic lung retransplantation in mice, which we have thus far performed in 144 animals. The total time of the retransplantation procedure is approximately 55 minutes, 20 minutes for donor harvest and 35 minutes for the implantation,...

  18. Effect of CC chemokine receptor 7 and vascular endothelial growth factor-C expression on lymph node metastatic potentiality of non-small cell lung cancer%CC趋化因子受体7、血管内皮生长因子-C表达对非小细胞肺癌淋巴结转移潜能的影响

    Institute of Scientific and Technical Information of China (English)

    陈钢; 刘相燕; 王洲; 刘凡英


    目的 观察CC趋化因子受体7(CCR7)及血管内皮生长因子-C(VEGF-C)的表达对非小细胞肺癌(NSCLC)淋巴结转移潜能的影响.方法 临床收集行肺癌完全切除加系统淋巴结清扫的55例NSCLC患者的肺癌组织、淋巴结组织及正常肺组织标本.逆转录-聚合酶链反应(RT-PCR)检测CCR7及VEGF-C mRNA的表达;免疫组织化学检测CCR7及VEGF-C蛋白的表达.应用x2检验比较CCR7及VEGF-C表达差异,并应用Logistic回归分析判定肺癌淋巴结转移的独立相关因素.结果 肺癌组织中有39例(70.9%) CCR7 mRNA及32例(58.2%) VEGF-C mRNA表达阳性,有38例(69.1%) CCR7蛋白及29例(52.7%) VEGF-C蛋白表达阳性,且均与淋巴结转移密切相关(P<0.05).33例有转移的淋巴结中CCR7、VEGF-C mRNA的阳性表达率分别为84.8%、66.7%,分别明显高于无转移的淋巴结(27.3%、18.2%,P<0.05).Logistic多因素回归分析结果显示:肺癌组织中CCR7 mRNA的阳性表达[比值比(OR)=10.275,P<0.01]及VEGF-C mRNA的阳性表达(OR=5.550,P<0.05)是NSCLC患者淋巴结转移的独立危险因素.结论 CCR7及VEGF-C在NSCLC患者的肺癌组织及淋巴结转移灶中表达均明显增高,并与肺癌淋巴结转移密切相关;CCR7及VEGF-C的表达可能促进了NSCLC淋巴结转移.%Objective To explore the effects of CC chemokine receptor 7 (CCR7) and vascular endothelial growth factor-C (VEGF-C) expression on lymph node metastatic potentiality of non-small cell lung cancer (NSCLC).Methods The samples of cancer tissues,lymph nodes and normal lung tissues from 55 patients with NSCLC who underwent complete resection were examined by using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry to detect CCR7 and VEGF-C expression.The difference in the CCR7 and VEGF-C expression was compared by x2 test.Logistic regression analysis was performed to determine the independent risk factors of lymph node metastasis of NSCLC.Re sults In

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

    Directory of Open Access Journals (Sweden)

    Goldenberg Anna


    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

  20. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav


    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

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

    DEFF Research Database (Denmark)

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


    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....../-) mice showed 43% reduced responses to the soluble guanylate cyclase (sGC) stimulator sodium nitroprusside (SNP). Inhibition of phosphodiesterase (PDE) 1 and 5 normalized SNP-relaxing effects in Ercc1(d/-) to wild-type (WT) levels. PDE1C levels were increased in lung and aorta. cGMP hydrolysis by PDE...

  2. Rapid remodeling of airway vascular architecture at birth. (United States)

    Ni, Amy; Lashnits, Erin; Yao, Li-Chin; Baluk, Peter; McDonald, Donald M


    Recent advances have documented the development of lung vasculature before and after birth, but less is known of the growth and maturation of airway vasculature. We sought to determine whether airway vasculature changes during the perinatal period and when the typical adult pattern develops. On embryonic day 16.5 mouse tracheas had a primitive vascular plexus unlike the adult airway vasculature, but instead resembling the yolk sac vasculature. Soon after birth (P0), the primitive vascular plexus underwent abrupt and extensive remodeling. Blood vessels overlying tracheal cartilage rings regressed from P1 to P3 but regrew from P4 to P7 to form the hierarchical, segmented, ladder-like adult pattern. Hypoxia and HIF-1α were present in tracheal epithelium over vessels that survived but not where they regressed. These findings reveal the plasticity of airway vasculature after birth and show that these vessels can be used to elucidate factors that promote postnatal vascular remodeling and maturation.

  3. Lung infection

    Institute of Scientific and Technical Information of China (English)


    950304 The diagnosis and treatment of pulmonaryaspergilloma in the aged—a report of 17 cases.LI Di-anqin(李殿清),et al.Henan Provincial Pulmon DisHosp,Zhengzhou,450003.Chin J Geriatr 1994;13(6):338-339.Seventeen cases of pulmonary aspergilloma in theaged were reported.The primary diseases were pul-monary tuberculosis in 14 cases and pulmonary cyst,cancer of lung and pulmonary abscess in one each.In14 cases,the clinical manifestation was frequenthemoptysis;the occurrence rate was 82.4%.Among

  4. Targeting angiogenesis: a review of angiogenesis inhibitors in the treatment of lung cancer. (United States)

    Sridhar, Srikala S; Shepherd, Frances A


    It has now been almost 30 years since Dr J. Folkman first proposed that inhibition of angiogenesis could play a key role in treating cancer; however, it is only recently that anti-angiogenesis agents have entered the clinical setting. The search for novel therapies is particularly important in lung cancer, where the majority of patients succumb to their disease despite aggressive treatments. Several classes of agents now exist that target the different steps involved in angiogenesis. These include drugs inhibiting matrix breakdown, the matrix metalloproteinase inhibitors (MMPIs), such as marimastat, prinomastat, BMS275291, BAY12-9566, and neovastat drugs that block endothelial cell signaling via vascular endothelial growth factor (VEGF) and its receptor (VEGFR) including rhuMAb VEGF, SU5416, SU6668, ZD6474, CP-547,632 and ZD4190. Drugs that are similar to endogenous inhibitors of angiogenesis including endostatin, angiostatin and interferons. There has also been renewed interest in thalidomide. Drugs such as squalamine, celecoxib, ZD6126, TNP-470 and those targeting the integrins are also being evaluated in lung cancer. Despite early enthusiasm for many of these agents, Phase III trials have not yet demonstrated significant increases in overall survival and toxicity remains an issue. It is hoped that as our understanding of the complex process of angiogenesis increases, so will our ability to design more effective targeted therapies.

  5. [Bundle-branch block depending on the heart rate]. (United States)

    Apostolov, L


    Five patients are reported, admitted to the hospital, with diseases predominantly of the cardio-vascular system. During the electrocardiographic examinations bundle branch block was established, depending on heart rate. It fluctuated within the physiological limits from 50 to 90/min. In three of the patients, the bundle branch block appeared with the quickening of the heart rate (tachycardia-depending bundle branch block) and in two of the patients--the bundle branch block appeared during the slowing down of the heart action and disappeared with its quickening (bradicardia-depending bundle branch block). A brief literature review is presented and attention is paid to the possible diagnostic errors and the treatment mode of those patients with cardiac tonic and antiarrhythmic medicaments.

  6. Ex vivo lung perfusion in Brazil

    Directory of Open Access Journals (Sweden)

    Luis Gustavo Abdalla


    Full Text Available Objective: To evaluate the use of ex vivo lung perfusion (EVLP clinically to prepare donor lungs for transplantation. Methods: A prospective study involving EVLP for the reconditioning of extended-criteria donor lungs, the criteria for which include aspects such as a PaO2/FiO2 ratio < 300 mmHg. Between February of 2013 and February of 2014, the lungs of five donors were submitted to EVLP for up to 4 h each. During EVLP, respiratory mechanics were continuously evaluated. Once every hour during the procedure, samples of the perfusate were collected and the function of the lungs was evaluated. Results: The mean PaO2 of the recovered lungs was 262.9 ± 119.7 mmHg at baseline, compared with 357.0 ± 108.5 mmHg after 3 h of EVLP. The mean oxygenation capacity of the lungs improved slightly over the first 3 h of EVLP-246.1 ± 35.1, 257.9 ± 48.9, and 288.8 ± 120.5 mmHg after 1, 2, and 3 h, respectively-without significant differences among the time points (p = 0.508. The mean static compliance was 63.0 ± 18.7 mmHg, 75.6 ± 25.4 mmHg, and 70.4 ± 28.0 mmHg after 1, 2, and 3 h, respectively, with a significant improvement from hour 1 to hour 2 (p = 0.029 but not from hour 2 to hour 3 (p = 0.059. Pulmonary vascular resistance remained stable during EVLP, with no differences among time points (p = 0.284. Conclusions: Although the lungs evaluated remained under physiological conditions, the EVLP protocol did not effectively improve lung function, thus precluding transplantation.

  7. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation. (United States)

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N


    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation.

  8. 76 FR 55077 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings (United States)


    ... Research Implementation Program II Review. Date: September 26, 2011. Time: 8:30 a.m. to 5 p.m. Agenda: To..., Lung, and Blood Institute Special Emphasis Panel; NHLBI--Bio-Specimen Repository Exploratory Grants... Disorders Research; 93.837, Heart and Vascular Diseases Research; 93.838, Lung Diseases Research;...

  9. Blocked Urethral Valves (United States)

    ... Blocked Urethral Valves Health Issues Listen Español Text Size Email Print Share Blocked Urethral Valves Page Content Article Body Urine leaves the bladder through a tube called the urethra, which in boys passes through the penis. Rarely, small membranes form across the urethra in ...

  10. Related Drupal Nodes Block

    NARCIS (Netherlands)

    Van der Vegt, Wim


    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. Inde

  11. Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Abigail Hielscher

    Full Text Available The extracellular matrix (ECM has been demonstrated to facilitate angiogenesis. In particular, fibronectin has been documented to activate endothelial cells, resulting in their transition from a quiescent state to an active state in which the cells exhibit enhanced migration and proliferation. The goal of this study is to examine the role of polymerized fibronectin during vascular tubulogenesis using a 3 dimensional (3D cell-derived de-cellularized matrix. A fibronectin-rich 3D de-cellularized ECM was used as a scaffold to study vascular morphogenesis of endothelial cells (ECs. Confocal analyses of several matrix proteins reveal high intra- and extra-cellular deposition of fibronectin in formed vascular structures. Using a small peptide inhibitor of fibronectin polymerization, we demonstrate that inhibition of fibronectin fibrillogenesis in ECs cultured atop de-cellularized ECM resulted in decreased vascular morphogenesis. Further, immunofluorescence and ultrastructural analyses reveal decreased expression of stromal matrix proteins in the absence of polymerized fibronectin with high co-localization of matrix proteins found in association with polymerized fibronectin. Evaluating vascular kinetics, live cell imaging showed that migration, migration velocity, and mean square displacement, are disrupted in structures grown in the absence of polymerized fibronectin. Additionally, vascular organization failed to occur in the absence of a polymerized fibronectin matrix. Consistent with these observations, we tested vascular morphogenesis following the disruption of EC adhesion to polymerized fibronectin, demonstrating that block of integrins α5β1 and αvβ3, abrogated vascular morphogenesis. Overall, fibronectin deposition in a 3D cell-derived de-cellularized ECM appears to be imperative for matrix assembly and vascular morphogenesis.

  12. Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling.

    Directory of Open Access Journals (Sweden)

    Shyh-Jong Wu

    Full Text Available Vascular remodelling is a critical vasculopathy found in atheromatous diseases and allograft failures. The local renin angiotensin system (RAS has been implicated in vascular remodelling. However, the mechanisms by which the augmented local RAS is associated with the initial event of endothelial cell apoptosis in injured vasculature remain undefined. We induced the apoptosis of human umbilical vein endothelial cells (HUVECs and vascular smooth muscle cells (VSMCs through serum starvation (SS. After the cells were subjected to SS, we found that the mRNA expression of angiotensinogen (AGT was increased by >3-fold in HUVECs and by approximately 2.5-fold in VSMCs. In addition, the expression of angiotensin-converting enzyme (ACE mRNA was increased in VSMCs but decreased to 50% in HUVECs during the same apoptotic process. Increases in the expression of AGT protein and angiotensin II (Ang II were found in a serum-free medium conditioned by HUVECs (SSC. The increased Ang II was suppressed using lisinopril (an ACE inhibitor treatment. Moreover, the activation of ERK1/2 induced by the SSC in VSMCs was also suppressed by losartan. In conclusion, we first demonstrated that the augmented AGT released from apoptotic endothelial cells acts as a vital progenitor of Ang II to accelerate vascular remodelling, and we suggest that blocking local augmented Ang II might be an effective strategy for restraining intimal hyperplasia.

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

    Directory of Open Access Journals (Sweden)

    Jianbo He


    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.

  14. Sex Steroids Block the Initiation of Atherosclerosis. (United States)

    Naftolin, Frederick; Mehr, Holly; Fadiel, Ahmed


    Atherosclerosis is the main cause of death in men and women. This so-called "hardening of the arteries" results from advanced atherogenesis, the accumulation and death of subendothelial fat-laden macrophages (vascular plaque). The macrophages are attracted as the result of signals from injured vessels recruiting and activating cells to quell the injury by inflammation. Among the recruited cells are circulating monocytes that may be captured by the formation of neural cell adhesion molecule (nCAM) tethers between the monocytes and vascular endothelium; the tethers are dependent on electrostatic binding between distal segments of apposed nCAM molecules. The capture of monocytes is followed by their entry into the subendothelial area as macrophages, many of which will remain and become the fat-laden foam cells in vascular plaque. Neural cell adhesion molecules are subject to sialylation that blocks their electrostatic binding. We showed that estradiol-induced nCAM sialylases are present in vascular endothelial cells and tested whether sex steroid pretreatment of human vascular endothelium could inhibit the capture of monocytes. Using in vitro techniques, pretreatment of human arterial endothelial cells with estradiol, testosterone, dehydroepiandrosterone and dihydrotestosterone all induced sialylation of endothelial cells and, in a dose-response manner, reduced the capture of monocytes. Steroid hormones are protective against atherogenesis and its sequellae. Sex steroid depletion is associated with atherosclerosis. Based on this knowledge plus our results using sex steroid pretreatment of endothelial cells, we propose that the blockade of the initial step in atherogenesis by sex steroid-induced nCAM sialylation may be crucial to hormonal prevention of atherosclerosis.

  15. Belatacept for Maintenance Immunosuppression in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Christine Hui PharmD


    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.

  16. The Block Neighborhood

    CERN Document Server

    Arrighi, Pablo


    We define the block neighborhood of a reversible CA, which is related both to its decomposition into a product of block permutations and to quantum computing. We give a purely combinatorial characterization of the block neighborhood, which helps in two ways. First, it makes the computation of the block neighborhood of a given CA relatively easy. Second, it allows us to derive upper bounds on the block neighborhood: for a single CA as function of the classical and inverse neighborhoods, and for the composition of several CAs. One consequence of that is a characterization of a class of "elementary" CAs that cannot be written as the composition of two simpler parts whose neighborhoods and inverse neighborhoods would be reduced by one half.

  17. Strategies for lung regeneration

    Directory of Open Access Journals (Sweden)

    Thomas H. Petersen


    Full Text Available Due to the limited ability of the adult lung to regenerate and the frequency of lung disease, the lung is a tissue that can especially benefit from regenerative medicine. Prospects for lung regeneration have made great strides in the past year. In this review, we summarize recent progress and key challenges for approaches in lung regenerative medicine. With a focus on the matrix components critical for the development of regenerative lung tissues, we discuss possible cell sources for lung regeneration, key matrix effects on cell repopulation, and physical stimuli that will aid in the growth of lung tissues in vitro.

  18. DANCE in developing and injured lung. (United States)

    Jean, Jyh-Chang; Eruchalu, Ifeanyi; Cao, Yu Xia; Joyce-Brady, Martin


    We identified rat developing arteries and neural crest derivatives with multiple epidermal growth factor-like domains (DANCE) as a developmentally regulated gene using suppression-subtractive hybridization. Northern analysis confirmed a fivefold induction of this mRNA transcript between fetal day 18 and 20 that persisted through postnatal day 17. The level was declining at postnatal day 21 and was similar in adult lung to that at fetal day 18. In adults DANCE mRNA abundance was highest in lung, kidney, and spleen, lower in heart, skeletal muscle, and brain, but absent from liver and thymus. It was abundant in pulmonary artery endothelium and a lung epithelial type 2 cell line, barely detectable in vascular smooth muscle, and absent in fibroblasts. In situ hybridization revealed a regulated pattern of expression in endothelial cells of fetal, postnatal, and adult lung. Because DANCE mRNA was inducible in systemic arteries during recovery from injury, we searched for induction in lung injured by hyperoxia. Mouse DANCE mRNA abundance was unchanged during an acute 3-day exposure period, induced threefold 5 days into the recovery phase, and returned to baseline at days 8, 11, and 14. In situ hybridization at day 5 suggested a diffuse pattern of induction. DANCE may play a role in lung endothelial cell biology during development repair after injury.

  19. Neurobiology of Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Ana-Maria Enciu


    Full Text Available Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach.

  20. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao


    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.

  1. [Vascular endothelial Barrier Function]. (United States)

    Ivanov, A N; Puchinyan, D M; Norkin, I A


    Endothelium is an important regulator of selective permeability of the vascular wall for different molecules and cells. This review summarizes current data on endothelial barrier function. Endothelial glycocalyx structure, its function and role in the molecular transport and leukocytes migration across the endothelial barrier are discussed. The mechanisms of transcellular transport of macromolecules and cell migration through endothelial cells are reviewed. Special section of this article addresses the structure and function of tight and adherens endothelial junction, as well as their importance for the regulation of paracellular transport across the endothelial barrier. Particular attention is paid to the signaling mechanism of endothelial barrier function regulation and the factors that influence on the vascular permeability.

  2. Adhesion in vascular biology



    The vasculature delivers vital support for all other tissues by supplying oxygen and nutrients for growth and by transporting the immune cells that protect and cure them. Therefore, the microvasculature developed a special barrier that is permissive for gasses like oxygen and carbon dioxide, while fluids are kept inside and pathogens are kept out. While maintaining this tight barrier, the vascular wall also allows immune cells to exit at sites of inflammation or damage, a process that is call...

  3. Risks of Lung Cancer Screening (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 ...

  4. Radiation Therapy for Lung Cancer (United States)

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association Lung Cancer Alliance Lung Cancer Online www. ...

  5. Surgical technique for lung retransplantation in the mouse (United States)

    Li, Wenjun; Goldstein, Daniel R.; Bribriesco, Alejandro C.; Nava, Ruben G.; Spahn, Jessica H.; Wang, Xingan; Gelman, Andrew E.; Krupnick, Alexander S.


    Microsurgical cuff techniques for orthotopic vascularized murine lung transplantation have allowed for the design of studies that examine mechanisms contributing to the high failure rate of pulmonary grafts. Here, we provide a detailed technical description of orthotopic lung retransplantation in mice, which we have thus far performed in 144 animals. The total time of the retransplantation procedure is approximately 55 minutes, 20 minutes for donor harvest and 35 minutes for the implantation, with a success rate exceeding 95%. The mouse lung retransplantation model represents a novel and powerful tool to examine how cells that reside in or infiltrate pulmonary grafts shape immune responses. PMID:23825768

  6. COSMOS 2044: Lung morphology study, experiment K-7-28 (United States)

    Elliott, Ann R.; Mathieu-Costello, Odile; West, John B.


    Researchers examined the effect of microgravity during spaceflight on lung tissue. The ultrastructure of the left lungs of 5 Czechoslovakian Wister rats flown on the 13 day, 19+ hour Cosmos 2044 mission was examined and compared to 5 vivarium and 5 synchronous controls at 1-g conditions, and 5 rats exposed to 14 days of tail suspension. Pulmonary hemorrage and alveolar adema of unknown origin occurred to a greater extent in the flight, tail-suspended, and synchronous control animals, and in the dorsal regions of the lung when compared with the vivarium controls. The cause of these changes, which are possibly due to an increase in pulmonary vascular pressure, requires further investigation.

  7. Design and Simulation of Jet-driven Vascular Robot

    Directory of Open Access Journals (Sweden)

    Jiang Fan


    Full Text Available For driven and adjustment attitude shortcomings of the existing vascular robot, a jet-driven vascular robot is designed, consists of the upper and lower shell, micro-batteries, variable pump, radio control block, 12 suction nozzles, 24 2/2-way solenoid valves and operation mechanism. The propel force of jet-driven, pressure in elastic capsule, propulsive efficiency and other parameters of vascular robot are analyzed, the propulsive efficiency is 41.6% in initial calculation. The flow path control method of robot posture adjustment in vascular is obtained. CFD technology is used to analyze the flows with capsule contraction and expansion of variable pump and the external flow field characteristics of vascular robot under the moving mode and the posture adjustment. The results show that the contraction and expansion of the variable pump can jet and suck the fluid, to drive vascular robot go straight in blood vessel, in the same time, the pressure field and velocity field under condition of pitch and roll, is met to the movement trend of the robot correspondingly.

  8. 星状神经节阻滞对家兔单肺通气期间氧合及肺内分流的影响%Effects of stellate ganglion block on intrapulmonary shunt and oxygenation during one-lung ventilation of rabbit

    Institute of Scientific and Technical Information of China (English)

    刘洋; 郭伟; 吕娜; 章健萍; 杨大威; 郭建荣


    目的:观察星状神经节阻滞( SGB)对单肺通气期间氧合及肺内分流的影响。方法健康成年大耳白兔在基础麻醉下暴露右侧星状神经节,置入并固定硬膜外导管。置管3 d后,选择24只随机分为两组:SGB组( n=12),在基础麻醉前10 min自硬膜外导管注射0.25%布比卡因0.5 mL;对照组(n=12),经导管注射生理盐水0.5 mL。行气管切开插入气管导管控制呼吸,继而将导管插入右侧支气管行单肺通气。维持麻醉,连续监测心率(HR)、平均动脉压(MAP)、平均肺动脉压(MPAP)。分别于基础麻醉后(T0)、双肺通气15 min(T1)、单肺通气15 min( T2)、30 min( T3)、60 min( T4)、120 min( T5)、恢复双肺通气30 min( T6)时抽取动脉血和混合静脉血血样测定血气,通过公式计算肺内分流量( Qs/Qt)和全身氧合情况。结果两组家兔术前单肺通气后肺内分流均增加( P<0.05),Qs/Qt在T3、T4时对照组高于SGB组(P均<0.05)。单肺通气期间两组PaO2较双肺通气时均明显下降(P均<0.05),T3时点降至最低,之后逐渐回升;T2、T3、T4时点对照组较SGB组PaO2显著降低(P均<0.05)。全麻机械通气使MPAP上升(P<0.05),T3、T4时点对照组较SGB组MPAP升高明显(P均<0.05)。结论星状神经节阻滞不明显增加同侧单肺通气期间的肺内分流,有利于改善单肺期间的氧合,减少术中低氧血症的发生。%Objective To observe the effects of stellate ganglion block on oxygenation and intrapulmonary shunt dur -ing one-lung ventilation ( OLV) of rabbit .Methods Healthy adult rabbits were exposed right stellate ganglion under basal anesthesia , an epidural catheter was placed and fixed .3 days later , twenty-four healthy rabbits were randomly divided into 2 groups:SGB group (n=12), 0.25%bupivacaine 0.5 mL was injected through the epidural

  9. Sampling for stereology in lungs

    Directory of Open Access Journals (Sweden)

    J. R. Nyengaard


    Full Text Available The present article reviews the relevant stereological estimators for obtaining reliable quantitative structural data from the lungs. Stereological sampling achieves reliable, quantitative information either about the whole lung or complete lobes, whilst minimising the workload. Studies have used systematic random sampling, which has fixed and constant sampling probabilities on all blocks, sections and fields of view. For an estimation of total lung or lobe volume, the Cavalieri principle can be used, but it is not useful in estimating individual cell volume due to various effects from over- or underprojection. If the number of certain structures is required, two methods can be used: the disector and the fractionator. The disector method is a three-dimensional stereological probe for sampling objects according to their number. However, it may be affected on tissue deformation and, therefore, the fractionator method is often the preferred sampling principle. In this method, a known and predetermined fraction of an object is sampled in one or more steps, with the final step estimating the number. Both methods can be performed in a physical and optical manner, therefore enabling cells and larger lung structure numbers (e.g. number of alveoli to be estimated. Some estimators also require randomisation of orientation, so that all directions have an equal chance of being chosen. Using such isotropic sections, surface area, length, and diameter can be estimated on a Cavalieri set of sections. Stereology can also illustrate the potential for transport between two compartments by analysing the barrier width. Estimating the individual volume of cells can be achieved by local stereology using a two-step procedure that first samples lung cells using the disector and then introduces individual volume estimation of the sampled cells. The coefficient of error of most unbiased stereological estimators is a combination of variance from blocks, sections, fields

  10. CXCR4 Blockade Attenuates Hyperoxia Induced Lung Injury in Neonatal Rats (United States)

    Drummond, Shelley; Ramachandran, Shalini; Torres, Eneida; Huang, Jian; Hehre, Dorothy; Suguihara, Cleide; Young, Karen C.


    Background Lung inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1) and its receptor chemokine receptor 4 (CXCR4) modulate the inflammatory response. Whether antagonism of CXCR4 will alleviate lung inflammation in neonatal hyperoxia-induced lung injury is unknown. Objective To determine whether CXCR4 antagonism would attenuate lung injury in rodents with experimental BPD by decreasing pulmonary inflammation. Methods Newborn rats exposed to normoxia (RA) or hyperoxia (FiO2=0.9) from postnatal day 2 (P2)-P16 were randomized to receive the CXCR4 antagonist, AMD3100 or placebo (PL) from P5 to P15. Lung alveolarization, angiogenesis, and inflammation were evaluated at P16. Results As compared to RA, hyperoxic-PL pups had a decrease in alveolarization, reduced lung vascular density and increased lung inflammation. In contrast, AMD3100-treated hyperoxic pups had improved alveolarization and increased angiogenesis. This improvement in lung structure was accompanied by a decrease in bronchoalveolar lavage fluid macrophage and neutrophil count and reduced lung myeloperoxidase activity. Conclusion CXCR4 antagonism decreases lung inflammation and improves alveolar as well as vascular structure in neonatal rats with experimental BPD. These findings suggest a novel therapeutic strategy to alleviate lung injury in preterm infants with BPD. PMID:25825119

  11. Block copolymer battery separator (United States)

    Wong, David; Balsara, Nitash Pervez


    The invention herein described is the use of a block copolymer/homopolymer blend for creating nanoporous materials for transport applications. Specifically, this is demonstrated by using the block copolymer poly(styrene-block-ethylene-block-styrene) (SES) and blending it with homopolymer polystyrene (PS). After blending the polymers, a film is cast, and the film is submerged in tetrahydrofuran, which removes the PS. This creates a nanoporous polymer film, whereby the holes are lined with PS. Control of morphology of the system is achieved by manipulating the amount of PS added and the relative size of the PS added. The porous nature of these films was demonstrated by measuring the ionic conductivity in a traditional battery electrolyte, 1M LiPF.sub.6 in EC/DEC (1:1 v/v) using AC impedance spectroscopy and comparing these results to commercially available battery separators.

  12. Hawaii Census 2000 Blocks (United States)

    U.S. Environmental Protection Agency — This data layer represents Census 2000 demographic data derived from the PL94-171 redistricting files and SF3. Census geographic entities include blocks, blockgroups...

  13. Steroidal neuromuscular blocking agents

    NARCIS (Netherlands)

    Wierda, JMKH; Mori, K; Ohmura, A; Toyooka, H; Hatano, Y; Shingu, K; Fukuda, K


    Since 1964 approximately 20 steroidal neuromuscular blocking agents have been evaluated clinically. Pancuronium, a bisquaternary compound designed on the drawingboard, was the first steroidal relaxant introduced into clinical practice worldwide in the 1970's. Although a major improvement, pancuroniu

  14. Superalloy Lattice Block Structures (United States)

    Nathal, M. V.; Whittenberger, J. D.; Hebsur, M. G.; Kantzos, P. T.; Krause, D. L.


    Initial investigations of investment cast superalloy lattice block suggest that this technology will yield a low cost approach to utilize the high temperature strength and environmental resistance of superalloys in lightweight, damage tolerant structural configurations. Work to date has demonstrated that relatively large superalloy lattice block panels can be successfully investment cast from both IN-718 and Mar-M247. These castings exhibited mechanical properties consistent with the strength of the same superalloys measured from more conventional castings. The lattice block structure also accommodates significant deformation without failure, and is defect tolerant in fatigue. The potential of lattice block structures opens new opportunities for the use of superalloys in future generations of aircraft applications that demand strength and environmental resistance at elevated temperatures along with low weight.

  15. 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.;


    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...

  16. Lung gallium scan (United States)

    Gallium 67 lung scan; Lung scan; Gallium scan - lung; Scan - lung ... Gallium is injected into a vein. The scan will be taken 6 to 24 hours after the gallium is injected. (Test time depends on whether your condition is acute or chronic .) ...

  17. Three-Dimensions Segmentation of Pulmonary Vascular Trees for Low Dose CT Scans (United States)

    Lai, Jun; Huang, Ying; Wang, Ying; Wang, Jun


    Due to the low contrast and the partial volume effects, providing an accurate and in vivo analysis for pulmonary vascular trees from low dose CT scans is a challenging task. This paper proposes an automatic integration segmentation approach for the vascular trees in low dose CT scans. It consists of the following steps: firstly, lung volumes are acquired by the knowledge based method from the CT scans, and then the data are smoothed by the 3D Gaussian filter; secondly, two or three seeds are gotten by the adaptive 2D segmentation and the maximum area selecting from different position scans; thirdly, each seed as the start voxel is inputted for a quick multi-seeds 3D region growing to get vascular trees; finally, the trees are refined by the smooth filter. Through skeleton analyzing for the vascular trees, the results show that the proposed method can provide much better and lower level vascular branches.

  18. Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

    Directory of Open Access Journals (Sweden)

    E.R. Parra


    Full Text Available In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1 and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF. Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci, severe (mural fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

  19. MRI evaluation of vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Yicheng Liu; Hongxing Zhang; Wei Huang; Wenjun Wan; Hongfen Peng


    OBJECTTVE: To explain the association between vascular dementia and the cranial MRI manifestations, and recognize the value of cranial MRI in the early diagnosis of vascular dementia and the assessment of disease conditions.DATA SOURCES: Pubmed database was searched to identify articles about the cranial MRI manifestations of patients with vascular dementia published in English from January 1992 to June 2006 by using the key words of "MRI, vascular dementia". Others were collected by searching the name of journals and title of articles in the Chinese full-text journal database.STUDY SELECTTON: The collected articles were primarily checked, those correlated with the cranial MRI manifestations of patients with vascular dementia were selected, while the obviously irrelative ones were excluded, and the rest were retrieved manually, the full-texts were searched.DATA EXTRACTION: Totally 255 articles were collected, 41 of them were involved, and the other 214 were excluded.DATA SYNTHESIS: MRI can be taken as one of the effective methods for the early diagnosis and disease evaluation of vascular dementia. White matter lesions are the important risk factors of vascular dementia.Vascular dementia is accompanied by the atrophy of related brain sites, but further confirmation is needed to investigate whether there is significant difference. MRI can be used to quantitatively investigate the infarcted sites and sizes of patients with vascular dementia after infarction, but there is still lack of systematic investigation on the association of the infarcted sites and sizes with the cognitive function of patients with vascular dementia.CONCLUSTON: Cranial MRI can detect the symptoms of vascular dementia at early period, so that corresponding measures can be adopted to prevent and treat vascular dementia in time.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  1. Vascular dysfunction in preeclampsia. (United States)

    Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T


    Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review.

  2. CT in vascular pathologies

    Energy Technology Data Exchange (ETDEWEB)

    Bartolozzi, C.; Neri, E.; Caramella, D. [Diagnostic and Interventional Radiology Department of Oncology, University of Pisa, Via Roma 67, I-56100 Pisa (Italy)


    Since the introduction of helical scanners, CT angiography (CTA) has achieved an essential role in many vascular applications that were previously managed with conventional angiography. The performance of CTA is based on the accurate selection of collimation width, pitch, reconstruction spacing and scan delay, which must be modulated on the basis of the clinical issue. However, the major improvement of CT has been provided by the recent implementation of many post-processing techniques, such as multiplanar reformatting, shaded surface display, maximum intensity projections, 3D perspectives of surface and volume rendering, which simulate virtual intravascular endoscopy. The integration of the potentialities of the scanner and of the image processing techniques permitted improvement of: (a) the evaluation of aneurysms, dissection and vascular anomalies involving the thoracic aorta; (b) carotid artery stenosis; (c) aneurysms of abdominal aorta; (d) renal artery stenosis; (e) follow-up of renal artery stenting; and (f) acute or chronic pulmonary embolism. Our experience has shown that the assessment of arterial pathologies with CTA requires the integration of 3D post-processing techniques in most applications. (orig.) With 4 figs., 34 refs.

  3. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler


    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.

  4. Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination. (United States)

    Zhan, Zhenzhen; Xie, Xuefeng; Cao, Hao; Zhou, Xiaohui; Zhang, Xu Dong; Fan, Huimin; Liu, Zhongmin


    Autophagy contributes to the pathogenesis of cancer, whereas toll-like receptors (TLRs) also play an important role in cancer development and immune escape. However, little is known about the potential interaction between TLR signaling and autophagy in cancer cells. Here we show that autophagy induced by TLR4 or TLR3 activation enhances various cytokine productions through promoting TRAF6 (TNF receptor-associated factor 6, E3 ubiquitin protein ligase) ubiquitination and thus facilitates migration and invasion of lung cancer cells. Stimulation of TLR4 and TLR3 with lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid [poly(I:C)] respectively triggered autophagy in lung cancer cells. This was mediated by the adaptor protein, toll-like receptor adaptor molecule 1 (TICAM1/TRIF), and was required for TLR4- and TLR3-induced increases in the production of IL6, CCL2/MCP-1 [chemokine (C-C motif) ligand 2], CCL20/MIP-3α [chemokine (C-C motif) ligand 20], VEGFA (vascular endothelial growth factor A), and MMP2 [matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase)]. These cytokines appeared to be necessary for enhanced migration and invasion of lung cancer cells upon TLR activation. Remarkably, inhibition of autophagy by chemical or genetic approaches blocked TLR4- or TLR3-induced Lys63 (K63)-linked ubiquitination of TRAF6 that was essential for activation of MAPK and NFKB (nuclear factor of kappa light polypeptide gene enhancer in B-cells) pathways, both of which were involved in the increased production of the cytokines. Collectively, these results identify induction of autophagy by TLR4 and TLR3 as an important mechanism that drives lung cancer progression, and indicate that inhibition of autophagy may be a useful strategy in the treatment of lung cancer.

  5. [Interstitial lung diseases. The pattern is important]. (United States)

    Fink, L


    Interstitial lung diseases (ILDs) comprise a number of rare entities with an estimated incidence of 10-25 per 100,000 inhabitants but the incidence greatly increases beyond the age of 65 years. The prognosis depends on the underlying cause. The fibrotic disorders show a set of radiological and histopathological patterns that are distinct but not entirely specific. In the absence of a clear clinical picture and consistent high resolution computed tomography (HRCT) findings, patients are advised to undergo surgical lung biopsies from two or three lung lobes (or transbronchial biopsies) to determine the histopathological pattern. The ILDs are differentiated into disorders of known causes (e.g. collagen vascular disease, drug-related), idiopathic interstitial pneumonia (IIP), granulomatous ILDs (e.g. sarcoidosis) and other forms of ILD (e.g. Langerhans' cell histiocytosis). The IIPs encompass idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, cryptogen organizing pneumonia, lymphocytic interstitial pneumonia and acute interstitial pneumonia. Additionally, a category of unclassified interstitial pneumonia exists. The pathologist has to recognize and address the histopathological pattern. In a multidisciplinary discussion the disorder is allocated to a clinicopathological entity and the histopathological pattern plays a major role in the classification of the entity. Recognition of the underlying pattern and the respective histopathological differential diagnoses is important as the therapy varies depending on the cause and ranges from elimination of the stimulus (if possible) to antifibrotic drug therapy up to preparation for lung transplantation.

  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)


    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. Porphyrin analogues as novel antagonists of fibroblast growth factor and vascular endothelial growth factor receptor binding that inhibit endothelial cell proliferation, tumor progression, and metastasis. (United States)

    Aviezer, D; Cotton, S; David, M; Segev, A; Khaselev, N; Galili, N; Gross, Z; Yayon, A


    Fibroblast growth factors (FGFs) and vascular endothelial growth factor (VEGF) play a pivotal role in the multistep pathway of tumor progression, metastasis, and angiogenesis. We have identified a porphyrin analogue, 5,10,15,20-tetrakis(methyl-4-pyridyl)-21H,23H-porphine-tetra -p-tosylate salt (TMPP), as a potent inhibitor of FGF2 and VEGF receptor binding and activation. TMPP demonstrated potent inhibition of binding of soluble FGF receptor 1 (FGFR1) to FGF2 immobilized on heparin at submicromolar concentrations. TMPP inhibits binding of radiolabeled FGF2 to FGFR in a cell-free system as well as to cells genetically engineered to express FGFR1. Furthermore, TMPP also inhibits the binding of VEGF to its tyrosine kinase receptor in a dose-dependent manner. In an in vitro angiogenic assay measuring the extent of endothelial cell growth, tube formation, and sprouting, TMPP dramatically reduced the extent of the FGF2-induced endothelial cell outgrowth and differentiation. In a Lewis lung carcinoma model, mice receiving TMPP showed a marked inhibition of both primary tumor progression and lung metastases development, with nearly total inhibition of the metastatic phenotype upon alternate daily injections of TMPP at 25 microg/g of body mass. Finally, novel meso-pyridylium-substituted, nonsymmetric porphyrins, as well as a novel corrole-based derivative, with >50-fold increase in activity in vitro, had a significantly improved efficacy in blocking tumor progression and metastasis in vivo.

  8. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs. (United States)

    Elomaa, Laura; Yang, Yunzhi Peter


    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.

  9. Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells. (United States)

    Nojiri, Takashi; Hosoda, Hiroshi; Tokudome, Takeshi; Miura, Koichi; Ishikane, Shin; Otani, Kentaro; Kishimoto, Ichiro; Shintani, Yasushi; Inoue, Masayoshi; Kimura, Toru; Sawabata, Noriyoshi; Minami, Masato; Nakagiri, Tomoyuki; Funaki, Soichiro; Takeuchi, Yukiyasu; Maeda, Hajime; Kidoya, Hiroyasu; Kiyonari, Hiroshi; Shioi, Go; Arai, Yuji; Hasegawa, Takeshi; Takakura, Nobuyuki; Hori, Megumi; Ohno, Yuko; Miyazato, Mikiya; Mochizuki, Naoki; Okumura, Meinoshin; Kangawa, Kenji


    Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients; however, surgery is often accompanied with trauma, which can promote early recurrence by provoking detachment of tumor cells into the blood stream or inducing systemic inflammation or both. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to NPR1 [also called guanylyl cyclase-A (GC-A) receptor]. In mouse models, we found that metastasis of GC-A-nonexpressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specific GC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. We examined the effect of ANP on tumor metastasis in mice treated with lipopolysaccharide, which mimics systemic inflammation induced by surgical stress. ANP inhibited the adhesion of cancer cells to pulmonary arterial and micro-vascular endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells.

  10. Right bundle branch block

    DEFF Research Database (Denmark)

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


    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.......60-1.62). The presence of IRBBB was not associated with any adverse outcome.ConclusionIn this cohort study, RBBB and IRBBB were two to three times more common among men than women. Right bundle branch block was associated with increased cardiovascular risk and all-cause mortality, whereas IRBBB was not. Contrary...

  11. Noninvasive measurement of lung carbon-11-serotonin extraction in man

    Energy Technology Data Exchange (ETDEWEB)

    Coates, G.; Firnau, G.; Meyer, G.J.; Gratz, K.F. (McMaster Univ. Medical Centre, Hamilton, Ontario (Canada))


    The fraction of serotonin extracted on a single passage through the lungs is being used as an early indicator of lung endothelial damage but the existing techniques require multiple arterial blood samples. We have developed a noninvasive technique to measure lung serotonin uptake in man. We utilized the double indicator diffusion principle, a positron camera, {sup 11}C-serotonin as the substrate, and {sup 11}CO-erythrocytes as the vascular marker. From regions of interest around each lung, we recorded time-activity curves in 0.5-sec frames for 30 sec after a bolus injection of first the vascular marker {sup 11}CO-erythrocytes and 10 min later {sup 11}C-serotonin. A second uptake measurement was made after imipramine 25-35 mg was infused intravenously. In three normal volunteers, the single-pass uptake of {sup 11}C-serotonin was 63.9% +/- 3.6%. This decreased in all subjects to a mean of 53.6% +/- 1.4% after imipramine. The rate of lung washout of {sup 11}C was also significantly prolonged after imipramine. This noninvasive technique can be used to measure lung serotonin uptake to detect early changes in a variety of conditions that alter the integrity of the pulmonary endothelium.

  12. Current status of vascularized composite tissue allotransplantation

    Directory of Open Access Journals (Sweden)

    Karoline Edtinger


    Full Text Available Vascularized composite tissue allotransplantation (VCA offers treatment options of complex functional deficiencies that cannot be repaired with conventional reconstructive methods. VCAs consist of blocks of functional units comprising different tissue types such as skin, bone, muscle, nerves, blood vessels, tendons, ligaments and others, and are thus substantially different from the composition of organ transplants. The field of VCA has made fascinating progresses in the recent past. Among other VCAs, numerous successful hand, face and limb transplants have been performed in the world. At the same time, specific questions in regard to innate and adaptive immunity, consequences of ischemia/reperfusion injury, immunosuppression, preservation, and regenerative capacity remain. In spite of this, the field is poised to make significant advances in the near future.

  13. Foetal vascular responses to thromboxane receptor blockade

    Directory of Open Access Journals (Sweden)

    B. A. Meyer


    Full Text Available We hypothesized that foetal administration of SQ-29,548, a putative thromboxane receptor blocker, would prevent foeto–placental vasoconstriction produced by the thromboxane mimic U46619. Arterial blood gases, continuous monitoring of maternal and foetal heart rates and blood pressures were performed in chronically catheterized pregnant ewes. Foetal blood flows and vascular resistance were determined with radioactive microspheres. SQ-29,548 effectively blocked the expected vasoconstrictive effects of thromboxane. However, prolonged infusion of SQ-29,548 resulted in significant decreases in umbilical–placental blood flow and foetal mean arterial pressure. This was accompanied by a respiratory acidemia. Potential therapy for the vasoconstrictive disorders of pregnancy with SQ-29,548 awaits further investigation of its intrinsic vasoactive properties in the umbilical–placental vasculature.

  14. Lung No dules Detection in CT Images Using Gestalt-Based Algorithm

    Institute of Scientific and Technical Information of China (English)

    QIU Shi; WEN Desheng; CUI Ying; FENG Jun


    To overcome low accuracy and high false positive of existing computer-aided lung nodules detec-tion. We propose a novel lung nodule detection scheme based on the Gestalt visual cognition theory. The pro-posed scheme involves two parts which simulate human eyes cognition features such as simplicity, integrity and classification. Firstly, lung region was segmented from lung Computed tomography (CT) sequences. Then local three-dimensional information was integrated into the Maximum intensity projection (MIP) images from axial, coronal and sagittal profiles. In this way, lung nodules and vascular are strengthened and discriminated based on pathologic image characteristics of lung nodules. The experimental database includes fifty-three high resolution CT images contained lung nodules, which had been confirmed by biopsy. The experimental results show that, the accuracy rate of the proposed algorithm achieves 91.29%. The proposed frame-work improves performance and computation speed for computer aided nodules detection.

  15. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings


    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 ...

  16. The vascular secret of Klotho

    DEFF Research Database (Denmark)

    Lewin, Ewa; Olgaard, Klaus


    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 ...

  17. Vascularity in the reptilian spectacle. (United States)

    Mead, A W


    Vascularization of the spectacle or brille of the reptile was demonstrated by biomicroscopy, histology, fluorescein (in vivo), and Microfil silicone rubber (in situ) injections. This unusual vascularity provides new evidence for reassessment of the origin and development of this structure, and a useful tool with which to do so.

  18. Contaminated soil concrete blocks

    NARCIS (Netherlands)

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


    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 ord

  19. Effects of Block Scheduling

    Directory of Open Access Journals (Sweden)

    William R. Veal


    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.

  20. Concrete Block Pavements (United States)


    1967, Cedergren 1974, Federal Highway .’,U .. V,47 -’":: 37 Administration 1980). Block pavements have essentially the same prob- lems with moisture...Vicksburg, Miss. Cedergren , H. R. 1974. Drainage of Highway and Airfield Pavements, John Wiley and Sons, New VOk. I Cement and Concrete Association

  1. Block That Pain! (United States)

    ... along with the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institute of General Medical Sciences (NIGMS). This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major ...

  2. Genetics Home Reference: lung cancer (United States)

    ... neoplasm of lung malignant tumor of lung pulmonary cancer pulmonary carcinoma pulmonary neoplasms respiratory carcinoma Related Information How are genetic conditions and genes named? Additional Information & Resources ... Encyclopedia: Lung Cancer--Non-Small Cell Encyclopedia: Lung Cancer--Small Cell ...

  3. Thoracic sympathetic block reduces respiratory system compliance

    Directory of Open Access Journals (Sweden)

    Fábio Ely Martins Benseñor

    Full Text Available CONTEXT AND OBJECTIVE: Thoracic epidural anesthesia (TEA following thoracic surgery presents known analgesic and respiratory benefits. However, intraoperative thoracic sympathetic block may trigger airway hyperreactivity. This study weighed up these beneficial and undesirable effects on intraoperative respiratory mechanics. DESIGN AND SETTING: Randomized, double-blind clinical study at a tertiary public hospital. METHODS: Nineteen patients scheduled for partial lung resection were distributed using a random number table into groups receiving active TEA (15 ml 0.5% bupivacaine, n = 9 or placebo (15 ml 0.9% saline, n = 10 solutions that also contained 1:200,000 epinephrine and 2 mg morphine. Under general anesthesia, flows and airway and esophageal pressures were recorded. Pressure-volume curves, lower inflection points (LIP, resistance and compliance at 10 ml/kg tidal volume were established for respiratory system, chest wall and lungs. Student’s t test was performed, including confidence intervals (CI. RESULTS: Bupivacaine rose 5 ± 1 dermatomes upwards and 6 ± 1 downwards. LIP was higher in the bupivacaine group (6.2 ± 2.3 versus 3.6 ± 0.6 cmH2O, p = 0.016, CI = -3.4 to -1.8. Respiratory system and lung compliance were higher in the placebo group (respectively 73.3 ± 10.6 versus 51.9 ± 15.5, p = 0.003, CI = 19.1 to 23.7; 127.2 ± 31.7 versus 70.2 ± 23.1 ml/cmH2O, p < 0.001, CI = 61 to 53. Resistance and chest wall compliance showed no difference. CONCLUSION: TEA decreased respiratory system compliance by reducing its lung component. Resistance was unaffected. Under TEA, positive end-expiratory pressure and recruitment maneuvers are advisable.

  4. Metabolic Functions of the Lung, Disorders and Associated Pathologies. (United States)

    Alvarado, Alcibey; Arce, Isabel


    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth's atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration.

  5. Vascular Differences Detected by MRI for Metastatic Versus Nonmetastatic Breast and Prostate Cancer Xenografts

    Directory of Open Access Journals (Sweden)

    Zaver M. Bhujwalla


    Full Text Available Several studies have linked vascular density, identified in histologic sections, to “metastatic risk.” Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if human breast and prostate cancer xenograffs preselected for differences in invasive and metastatic characteristics established correspondingly different vascular volume and permeability, quantified here with noninvasive MRI of the intravascular contrast agent albumin-GdDTPA. Tumor vascular volume and permeability of human breast and prostate cancer xenografts were characterized using MRI. Parallel studies confirmed the invasive behavior of these cell lines. Vascular endothelial growth factor (VEGF expression in the cell lines was measured using ELISA and Western blots. Metastasis to the lungs was evaluated with spontaneous as well as experimental assay. Metastatic tumors formed vasculature with significantly higher permeability or vascular volume (P < .05, two-sided unpaired t test. The permeability profile matched VEGF expression. Within tumors, regions of high vascular volume usually exhibited low permeability whereas regions of low vascular volume exhibited high permeability. We observed that although invasion was necessary, without adequate vascularization it was not sufficient for metastasis to occur.

  6. Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

    Institute of Scientific and Technical Information of China (English)

    Wei-ming YAN; Jia-quan HUANG; Xiao-ping LUO; Qin NING


    To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

  7. Citicoline in vascular cognitive impairment and vascular dementia after stroke. (United States)

    Alvarez-Sabín, Jose; Román, Gustavo C


    Cognitive decline after stroke is more common than stroke recurrence. Stroke doubles the risk of dementia and is a major contributor to vascular cognitive impairment and vascular dementia. Neuropathological studies in most cases of dementia in the elderly reveal a large load of vascular ischemic brain lesions mixed with a lesser contribution of neurodegenerative lesions of Alzheimer disease. Nonetheless, few pharmacological studies have addressed vascular cognitive impairment and vascular dementia after stroke. Citicoline has demonstrated neuroprotective effects in acute stroke and has been shown to improve cognition in patients with chronic cerebrovascular disease and in some patients with Alzheimer disease. A recent trial lasting 6 months in patients with first-ever ischemic stroke showed that citicoline prevented cognitive decline after stroke with significant improvement of temporal orientation, attention, and executive function. Experimentally, citicoline exhibits neuroprotective effects and enhances neural repair. Citicoline appears to be a safe and promising alternative to improve stroke recovery and could be indicated in patients with vascular cognitive impairment, vascular dementia, and Alzheimer disease with significant cerebrovascular disease.

  8. Lungs and Respiratory System (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 ...

  9. Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development. (United States)

    Magnusson, Peetra; Rolny, Charlotte; Jakobsson, Lars; Wikner, Charlotte; Wu, Yan; Hicklin, Daniel J; Claesson-Welsh, Lena


    We have employed embryoid bodies derived from murine embryonal stem cells to study effects on vascular development induced by fibroblast growth factor (FGF)-2 and FGF receptor-1, in comparison to the established angiogenic factor vascular endothelial growth factor (VEGF)-A and its receptor VEGF receptor-2. Exogenous FGF-2 promoted formation of morphologically distinct, long slender vessels in the embryoid bodies, whereas VEGF-A-treated bodies displayed a compact plexus of capillaries. FGF-2 stimulation of embryonal stem cells under conditions where VEGF-A/VEGFR-2 function was blocked, led to formation of endothelial cell clusters, which failed to develop into vessels. FGFR-1(-/-) embryoid bodies responded to VEGF-A by establishment of the characteristic vascular plexus, but FGF-2 had no effect on vascular development in the absence of FGFR-1. The FGFR-1(-/-) embryoid bodies displayed considerably increased basal level of vessel formation, detected by immunohistochemical staining for platelet-endothelial cell adhesion molecule (PECAM)/CD31. This basal vascularization was blocked by neutralizing antibodies against VEGFR-2 or VEGF-A and biochemical analyses indicated changes in regulation of VEGFR-2 in the absence of FGFR-1 expression. We conclude that VEGF-A/VEGFR-2-dependent vessel formation occurs in the absence of FGF-2/FGFR-1, which, however, serve to modulate vascular development.

  10. Novel block, graft and random copolymers for biomedical applications

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Jankova Atanasova, Katja; Tanaka, Masaru;

    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...... 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....

  11. Mechanisms of oxidative stress and vascular dysfunction (United States)

    Nedeljkovic, Z; Gokce, N; Loscalzo, J


    The endothelium regulates vascular homoeostasis through local elaboration of mediators that modulate vascular tone, platelet adhesion, inflammation, fibrinolysis, and vascular growth. Impaired vascular function contributes to the pathogenesis of atherosclerosis and acute coronary syndromes. There is growing pathophysiological evidence that increased generation of reactive oxygen species and oxidative stress participates in proatherogenic mechanisms of vascular dysfunction and atherothrombosis. In this review, the role of oxidative stress in mechanisms of vascular dysfunction is discussed, and potential antioxidant strategies are reviewed. PMID:12743334

  12. Role of endothelin in uteroplacental circulation and fetal vascular function. (United States)

    Paradis, Alexandra; Zhang, Lubo


    Endothelins are 21-amino acid peptides involved in vascular homeostasis. Three types of peptide have been identified, with endothelin-1 (ET-1) being the most potent vasoconstrictor currently known. Two endothelin receptor subtypes are found in various tissues, including the brain, heart, blood vessel, lung, and placenta. The ETA-receptor is associated with vasoconstriction in vascular smooth muscle. Conversely, the ETB-receptor can elicit a vasoconstrictor effect in vascular smooth muscle and a vasodilator effect via its action in endothelial cells. Both receptors play a key role in maintaining circulatory homeostasis and vascular function. Changes in ET-1 expression are found in various disease states, and overexpression of ET-1 is observed in hypertension and preeclampsia in pregnancy. Placental localization of ET-1 implies a key role in regulating the uteroplacental circulation. Additionally, ET-1 is important in the fetal circulation and is involved in the pulmonary circulation and closure of the ductus arteriosus after birth, as well as fetal growth constriction in utero. ET receptor antagonists and nitric oxide donors may provide therapeutic potential in treating conditions associated with overexpression of ET and hypertension.

  13. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    Directory of Open Access Journals (Sweden)

    Xiaomei Feng

    Full Text Available Rats with Metabolic Syndrome (MetaS have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S. aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS and high capacity runner (HCR rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF, and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  14. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome. (United States)

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G; Britton, Steven L; Hellman, Judith


    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  15. [The future of vascular medicine]. (United States)

    Kroeger, K; Luther, B


    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.

  16. Vascular effects of ambient pollutant particles and metals. (United States)

    Huang, Yuh-Chin T; Ghio, Andrew J


    Exposure to ambient pollutant particle (APP) is associated with increased cardiovascular morbidity and mortality. Recent evidence indicates that APP-induced vasoconstriction may be an important mechanism. APP constricts systemic arteries and increases blood pressure in human. APP decreases the diameter of pulmonary arterioles in animals. Intratracheal instillation of APP increases pulmonary artery resistance in isolated buffer-perfused lungs, and APP constricts isolated arterial rings. APP-induced vasoconstriction may be secondary to the release of inflammatory mediators from lung cells, which then activate vascular endothelial and smooth muscle cells. The vasoconstriction may also be caused by alterations in autonomic nervous system balance. Some soluble metals (e.g., vanadium) can produce acute vasoconstriction in in vitro and in vivo systems, and contribute to the systemic health effects of APP since they can more easily permeate the alveolar-capillary membrane than the whole particle. Both APP and its associated metals have been shown to enhance the release of endothelin 1 and reactive oxygen species, activate epithelial growth factor receptor and mitogen-activated protein kinases, and inhibit nitric oxide vasodilator activity. The vasoactive properties of APP and metals raised the possibility that patients with vascular diseases may be more susceptible to APP-induced adverse health effects, and that people who are regularly exposed to high amount of metals, e.g., vanadium contained in certain dietary and muscle-building regimens or in the air of boiler making plants, may have increased risk for vascular diseases. Understanding how metals induce vasoconstriction may lead to the development of novel vasodilator therapies for vascular diseases.

  17. MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

    Directory of Open Access Journals (Sweden)

    Shames David S


    Full Text Available Abstract Background MFSD2A (major facilitator superfamily domain containing 2 gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer. Results Here we show that MFSD2A expression is strongly downregulated in non-small cell lung cancer cell lines of different histotypes and in primary lung adenocarcinomas. Experimental modulation of MFSD2A in lung cancer cells is associated with alteration of mRNA levels of genes involved in cell cycle control and interaction with the extracellular matrix. Exogenous expression of MFSD2A in lung cancer cells induced a G1 block, impaired adhesion and migration in vitro, and significantly reduced tumor colony number in vitro (4- to 27-fold, P in vivo (~3-fold, P Conclusion Together these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.

  18. Recovery from blocking between outcomes. (United States)

    Wheeler, Daniel S; Miller, Ralph R


    Contemporary associative learning research largely focuses on cue competition phenomena that occur when 2 cues are paired with a common outcome. Little research has been conducted to investigate similar phenomena occurring when a single cue is trained with 2 outcomes. Three conditioned lick suppression experiments with rats assessed whether treatments known to alleviate blocking between cues would also attenuate blocking between outcomes. In Experiment 1, conditioned responding recovered from blocking between outcomes when a long retention interval was interposed between training and testing. Experiment 2 obtained recovery from blocking between outcomes when the blocking outcome was extinguished after the blocking treatment. In Experiment 3, a recovery from blocking between outcomes occurred when a reminder stimulus was presented in a novel context prior to testing. Collectively, these studies demonstrate that blocking of outcomes, like blocking of cues, appears to be caused by a deficit in the expression of an acquired association.


    Directory of Open Access Journals (Sweden)

    Komang Mega Puspadisari


    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.

  20. Vasculogenic mimicry in small cell lung cancer. (United States)

    Williamson, Stuart C; Metcalf, Robert L; Trapani, Francesca; Mohan, Sumitra; Antonello, Jenny; Abbott, Benjamin; Leong, Hui Sun; Chester, Christopher P E; Simms, Nicole; Polanski, Radoslaw; Nonaka, Daisuke; Priest, Lynsey; Fusi, Alberto; Carlsson, Fredrika; Carlsson, Anders; Hendrix, Mary J C; Seftor, Richard E B; Seftor, Elisabeth A; Rothwell, Dominic G; Hughes, Andrew; Hicks, James; Miller, Crispin; Kuhn, Peter; Brady, Ged; Simpson, Kathryn L; Blackhall, Fiona H; Dive, Caroline


    Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (Pcisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.


    Institute of Scientific and Technical Information of China (English)

    李春盛; 桂培春; 何新华


    Objeaive. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaeeharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasoue group.Macroscopic and histopathological e~aminatiom were performed and biological markers were measured for the lung specimem. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA. Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P < 0.01),demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasoue and rhubarb emfld decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P< 0.01, P < 0.05) ; the correslxmding pathologic changes of lung tissues and the biological markers of the lung injury were simifieantlv decreased or ameliorated. Conclusions. The increase of the expression d ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI.The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM-1 m


    Institute of Scientific and Technical Information of China (English)


    Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM-1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury.Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA.Results. In the lung tissues, the ICAM-1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<0.01), demonstrating the expression of ICAM-1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<0.01, P<0.05); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated.Conclusions. The increase of the expression of ICAM-1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM

  3. Horseshoe lung associated with left-lung hypoplasia, left pulmonary artery sling and bilateral agenesis of upper lobe bronchi. (United States)

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


    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.

  4. 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)


    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.)

  5. Managing access block. (United States)

    Cameron, Peter; Scown, Paul; Campbell, Donald


    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.

  6. Endotoxin increases pulmonary vascular protein permeability in the dog

    Energy Technology Data Exchange (ETDEWEB)

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


    Endotoxin increases pulmonary vascular permeability consistently in some species but fails to reliably cause injury in the dog. We wondered whether this phenomenon depended on the method of injury assessment, as others have relied on edema measurement; we quantified injury by monitoring the rate of extravascular protein accumulation. /sup 113m/In-labeled protein and /sup 99m/Tc-labeled erythrocytes were injected into anesthetized dogs and monitored by an externally placed lung probe. A protein leak index, the rate of extravascular protein accumulation, was derived from the rate of increase in lung protein counts corrected for changes in intravascular protein activity. After administration of 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.

  7. 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.

  8. Role of lymphangiogenesis in lung cancer.

    Directory of Open Access Journals (Sweden)

    Renata Jankowska


    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.

  9. Lung cancer-a fractal viewpoint. (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


    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.

  10. Drug induced lung disease - amiodarone in focus

    Directory of Open Access Journals (Sweden)

    Vasić Nada R.


    Full Text Available More than 380 medications are known to cause pulmonary toxicity. Selected drugs that are important causes of pulmonary toxicity fall into the following classes: cytotoxic, cardiovascular, anti-inflammatory, antimicrobial, illicit drugs, miscellaneous. The adverse reactions can involve the pulmonary parenchyma, pleura, the airways, pulmonary vascular system, and mediastinum. Drug-induced lung diseases have no pathognomonic clinical, laboratory, physical, radiographic or histological findings. A drug-induced lung disease is usually considered a diagnosis of exclusion of other diseases. The diagnosis of drug-mediated pulmonary toxicity is usually made based on clinical findings. In general, laboratory analyses do not help in establishing the diagnosis. High-resolution computed tomography scanning is more sensitive than chest radiography for defining radiographic abnormalities. The treatment of drug-induced lung disease consists of immediate discontinuation of the offending drug and appropriate management of the pulmonary symptoms. Glucocorticoids have been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. Before starting any medication, patients should be educated about the potential adverse effects of the drug. Amiodarone is an antiarrhythmic agent used in the treatment of many types of tachyarrhythmia. Amiodarone-caused pulmonary toxicity is a well-known side effect (complication of this medication. The incidence of amiodarone-induced lung disease is approximately 5-7%.

  11. Tissue plasminogen activator attenuates ventilatorinduced lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liang-ti HUANG; Hsiu-chu CHOU; Leng-fang WANG; Chung-ming CHEN


    Aim:To test the hypothesis that the tissue plasminogen activator (tPA) may counteract the inhibitory effect ot plasminogen activator inhibitors (PAI) and attenuate lung injury in a rat model of ventilator-induced lung injury (VILI).Methods:Adult male Sprague-Dawley rats were ventilated with a HVZP (high-volume zero PEEP) protocol for 2 h at a tidal volume of 30 ml/kg,a respiratory rate of 25 breaths/min,and an inspired oxygen fraction of 21%.The rats were divided into 3 groups (n=7 for each):HVZP+tPA group receiving tPA (1.25 mg/kg,iv) 15 min before ventilation,HVZP group receiving HVZP+vehicle injection,and a control group receiving no ventilation.After 2 h of ventilation,the rats were killed; blood and lungs were collected for biochemical and histological analyses.Results:HVZP ventilation significantly increased total protein content and the concentration of macrophage inflammatory protein-2 (MIP-2) in the bronchoalveolar lavage fluid (BALF) as well as the lung injury score.Rats that received HVZP ventilation had significantly higher lung PAI-1 mRNA expression,plasma PAI-1and plasma D-dimer levels than the control animals,tPA treatment significantly reduced the BALF total protein and the lung injury score as compared to the HVZP group,tPA treatment also significantly decreased the plasma D-dimer levels and the HVZP ventilation-induced lung vascular fibrin thrombi,tPA treatment showed no effect on MIP-2 level in BALF.Conclusion:These results demonstrate that VILI increases lung PAI-1 mRNA expression,plasma levels of PAI-1 and D-limers,lung injury score and vascular fibrin deposition,tPA can attenuate VILI by decreasing capillary-alveolar protein leakage as well as local and systemic coagulation as shown by decreased lung vascular fibrin deposition and plasma D-dimers.

  12. Vascular graft infections with Mycoplasma

    DEFF Research Database (Denmark)

    Levi-Mazloum, Niels Donald; Skov Jensen, J; Prag, J;


    Vascular graft infection is one of the most serious complications in vascular surgery. It is associated with mortality rates ranging from 25% to 75% and with morbidity in the form of amputation in approximately 30% of patients. Staphylococcus aureus is the leading pathogen. With conventional...... laboratory techniques, the percentage of culture-negative yet grossly infected vascular grafts seems to be increasing and is not adequately explained by the prior use of antibiotics. We have recently reported the first case of aortic graft infection with Mycoplasma. We therefore suggest the hypothesis...... that the large number of culture-negative yet grossly infected vascular grafts may be due to Mycoplasma infection not detected with conventional laboratory technique....

  13. Block Transfer Handbook: Constructing and Negotiating Block Transfer Agreements. (United States)

    Finlay, Finola

    The purpose of this handbook is to provide resources for institutions or articulation committees who are engaged in the task of investigating the feasibility of block transfer agreements. Block transfer is the process whereby a block of credits is granted to students who have successfully completed a certificate, diploma, or cluster of courses…

  14. Soluble ICAM-1 activates lung macrophages and enhances lung injury

    DEFF Research Database (Denmark)

    Schmal, H; Czermak, B J; Lentsch, A B


    production of TNF-alpha and the CXC chemokine, macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages exhibited cytokine responses to both sICAM-1 and immobilized sICAM-1, while rat PBMCs failed to demonstrate similar responses. Exposure of alveolar macrophages to sICAM-1 resulted in NFkappa...... of TNF-alpha and MIP-2 and increased neutrophil recruitment. Therefore, through engagement of beta2 integrins, sICAM-1 enhances alveolar macrophage production of MIP-2 and TNF-alpha, the result of which is intensified lung injury after intrapulmonary disposition of immune complexes.......B activation (which was blocked by the presence of the aldehyde peptide inhibitor of 28S proteosome and by genistein, a tyrosine kinase inhibitor). As expected, cross-linking of CD18 on macrophages with Ab resulted in generation of TNF-alpha and MIP-2. This response was also inhibited in the presence...

  15. Multimodality imaging of vascular anomalies. (United States)

    Restrepo, Ricardo


    Vascular malformations and hemangiomas are common in children but remain a source of confusion during diagnosis, in part because of the lack of a uniform terminology. With the existing treatments for hemangiomas and vascular malformations, it is important to make the correct diagnosis initially to prevent adverse physical and emotional sequelae in not only the child but also the family. The diagnosis of vascular malformations is made primarily by the clinician and based on the physical exam. Imaging is carried out using predominantly ultrasound (US) and magnetic resonance imaging (MRI), which are complementary modalities. In most cases of vascular anomalies, US is the first line of imaging as it is readily available, less expensive, lacks ionizing radiation and does not require sedation. MRI is also of great help for further characterizing the lesions. Conventional arteriography is reserved for cases that require therapeutic intervention, more commonly for arteriovenous malformations. Radiographs usually play no role in diagnosing vascular anomalies in children. In this article, the author describes the terminology and types of hemangiomas and vascular malformations and their clinical, histological features, as well as the imaging approach and appearance.

  16. Demographic Data - MDC_Block (United States)

    NSGIC GIS Inventory (aka Ramona) — 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...

  17. Habitat Blocks and Wildlife Corridors (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...

  18. 血管外肺水指数和肺血管通透性指数评估重症患者急性呼吸窘迫综合征程度的可靠性%Reliability of extravascular lung water index and pulmonary vascular permeability index in assessing severity of acute respiratory distress syndrome in critically ill patients

    Institute of Scientific and Technical Information of China (English)

    胡雪珍; 龚裕强; 杨鹏; 孙来芳; 徐峰


    目的 探讨血管外肺水指数(EVLWI)和肺血管通透性指数(PVPI)评估重症患者急性呼吸窘迫综合征(ARDS)程度的可靠性.方法 选择本院EICU住院治疗的ARDS患者46例,年龄18~72岁,体重46~ 72 kg,性别不限,急性生理与慢性健康评分11 ~25分.将患者分成3组:重度组(n=16):氧合指数(PaO2/FiO2)≤100 mmHg;中度组(n=14):100 mmHg <PaO2/FiO2≤200 mmHg;轻度组(n=16):200 mmHg <PaO2/FiO2≤300 mmHg.于治疗前、诊断ARDS后24和72 h时测量PVPI和EVLWI、心指数(CI)、胸腔内血容量指数(ITBVI),并行血气分析,计算PaO2/FiO2.记录患者入院28 d的病死情况.PVPI、EVLWI与PaO2/FiO2、ITBVI和CI进行Pearson相关分析.结果 与轻度组比较,中度组及重度组患者各时点PVPI、EVLWI和28 d病死率升高(P<0.05);与中度组比较,重度组患者各时点PVPI、EVLWI和28 d病死率升高(P<0.05).PVPI与EVLWI和PaO2/FiO2的相关系数分别为0.778和-0.437(P<0.05),与CI和ITBVI无相关性(P>0.05);EVLWI与PaO2/FiO2和ITBVI的相关系数分别为-0.448,0.347(P< 0.05).PVPI和PaO2/FiO2的相关系数与EVLWI和PaO2/FiO2的相关系数比较差异无统计学意义(P<0.05).结论 PVPI和EVLWI均可评估重症患者ARDS程度,可靠性一致.%Objective To investigate the reliability of extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) in assessing the severity of acute respiratory distress syndrome (ARDS) in critically ill patients.Methods Forty-six patients with ARDS,who were admitted in our emergency intensive care unit,aged 18-72 yr,weighing 46-72 kg,of Acute Physiology and Chronic Health Evaluation Ⅱ score 11-25,were divided into 3 groups:PaO2/FiO2 ≤ 100 mmHg severe group (n =16);100 mmHg <PaO2/FiO2 ≤ 200 mmHg moderate group (n =14);200 mmHg <PaO2/FiO2 ≤ 300 mmHg mild group (n=16).Before treatment,and at 24 and 72 h after diagnosis of ARDS,PVPI,EVLWI,cardiac index (CI),and intrathoracic blood volume index (ITBVI

  19. Role of endogenous nitric oxide on PAF-induced vascular and respiratory effects

    Directory of Open Access Journals (Sweden)

    M. Clement


    Full Text Available The role of endogenous nitric oxide (NO on vascular and respiratory smooth muscle basal tone was evaluated in six anaesthetized, paralysed, mechanically ventilated pigs. The involvement of endogenous NO in PAF-induced shock and airway hyperresponsiveness was also studied. PAF (50 ng/kg, i.v. was administered before and after pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v., an NO synthesis inhibitor. PAF was also administered to three of these pigs after indomethacin infusion (3 mg/kg, i.v.. In normal pigs, L-NAME increased systemic and pulmonary vascular resistances, caused pulmonary hypertension and reduced cardiac output and stroke volume. The pulmonary vascular responses were correlated with the increase in static and dynamic lung elastances, without changing lung resistance. Inhibition of NO synthesis enhanced the PAF-dependent increase in total, intrinsic and viscoelastic lung resistances, without affecting lung elastances or cardiac activity. The systemic hypotensive effect of PAF was not abolished by pretreatment with L-NAME or indomethacin. This indicates that systemic hypotension is not correlated with the release of endogenous NO or prostacyclines. Indomethacin completely abolished the PAF-dependent respiratory effects.

  20. Unevenness of lung perfusion images and pulmonary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Teshima, Takeo; Isawa, Toyoharu; Hirano, Tomio; Anazawa, Yoshiki; Miki, Makoto; Konno, Kiyoshi; Motomiya, Masakichi (Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis and Cancer)


    The purpose of the study was to quantify the unevenness of perfusion distribution in the lungs in conjunction with underlying lung pathology. Twenty-one parameters as described previously were defined out of horizontal radioactive count profiles on perfusion lung image data taken in 64x64 matrixes. Principal component analysis has revealed that the 1st component or Z1 is represented by AREA, the area of the lung, and ANG, the slope of the mean count profile, Z2, by N, the number of peaks, Z3 and Z4, by YG and XG, the barycentric coordinates of count distribution, Z5, by MAC, the maximal count and Z6, by CSD, the degree of scatter in count from the peak count. How those parameters differ in each lung pathology has been determined from 657 lung perfusion image data. In pulmonary emphysema, the lung volumes are larger than those in normal subjects. The AREA and ANG were consequently larger in value and N was also significantly larger, indicating the increased regional alveolar pressure and the compressed or destroyed vascular beds. In diffuse panbronchiolitis (DPB), N was increased probably because the distal airways were either narrowed or obstructed by inflammatory processes inducing regional alveolar hypoxia and/or alveolar hyperinflation. In fibrosis, both AREA and N were significantly smaller. In congestive heart failure with postcapillary pulmonary hypertension, YG was smaller probably because of 'reversal of perfusion'. In pulmonary sarcoidosis, an increase in YG was the only abnormality. (author).

  1. Porous block nanofiber composite filters

    Energy Technology Data Exchange (ETDEWEB)

    Ginley, David S.; Curtis, Calvin J.; Miedaner, Alexander; Weiss, Alan J.; Paddock, Arnold


    Porous block nano-fiber composite (110), a filtration system (10) and methods of using the same are disclosed. An exemplary porous block nano-fiber composite (110) includes a porous block (100) having one or more pores (200). The porous block nano-fiber composite (110) also includes a plurality of inorganic nano-fibers (211) formed within at least one of the pores (200).

  2. Properties of blocked linear systems. (United States)

    Chen, Weitian; Anderson, Brian D O; Deistler, Manfred; Filler, Alexander


    This paper presents a systematic study on the properties of blocked linear systems that have resulted from blocking discrete-time linear time invariant systems. The main idea is to explore the relationship between the blocked and the unblocked systems. Existing results are reviewed and a number of important new results are derived. Focus is given particularly on the zero properties of the blocked system as no such study has been found in the literature.

  3. Appropriate schemata and building blocks

    Institute of Scientific and Technical Information of China (English)

    Yang Haijun; Li Minqiang


    Appropriate schemata as a novel concept to characterize building blocks are introduced, and then, the traits of appropriate schemata are presented. The effects of building blocks by search operators are analyzed. Hence, the experiments on RR-8X8 are employed to verify that appropriate schemata construct the building blocks. The validity of appropriate schemata and building blocks from the views of theory and practice is presented.

  4. Blocking the Hawking radiation

    DEFF Research Database (Denmark)

    Autzen, M.; Kouvaris, C.


    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....

  5. 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.

  6. Correlation between US and MRI for prenatal lung volumetry in diaphragmatic hernia, and use of Doppler to identify the ipsilateral lung cap

    Energy Technology Data Exchange (ETDEWEB)

    Castellote, Amparo; Mencho, Sandra; Cadavid, Lina; Piqueras, Joaquim; Enriquez, Goya [University Children' s Hospital Vall d' Hebron, Department of Pediatric Radiology, Barcelona (Spain); Carreras, Elena; Higueras, Teresa [University Hospital Vall d' Hebron, Department of Obstetrics and Gynecology, Barcelona (Spain)


    Pulmonary hypoplasia is a common cause of neonatal death. To describe the correlation between relative fetal lung volume (RFLV) and lung-to-head ratio (LHR) in fetuses with unilateral diaphragmatic hernia. Additionally, to describe identification of the ipsilateral lung cap by power Doppler. Single-institution study of consecutive fetuses with diaphragmatic hernia. LHR (by US) and RFLV (by MRI) were correlated in fetuses with and without an ipsilateral lung cap seen at MRI. In four, color/power Doppler was used to follow the pulmonary artery of the ipsilateral lung to identify the compressed cap. The study included 48 fetuses of 20-38 weeks' gestational age (mean, 26 weeks). Mean LHR was 1.52 (range, 0.6-3) in fetuses with a lung cap and 1.15 (range, 0.6-2.58) in fetuses without (P = 0.043). Mean RFLV was 47.4% (range, 18-80%) in fetuses with and 32.9% (range, 14-57%) in fetuses without a lung cap (P = 0.005). RFLV and LHR correlated (r = 0.41, P = 0.01 in those with a cap; r = 0.50, P = 0.05 in those without). Power Doppler identified the ipsilateral lung cap and pulsed Doppler confirmed pulmonary vascularization in four of four fetuses. LHR underestimates lung volume in fetuses with an ipsilateral lung cap. Power Doppler may be useful for identifying the cap. (orig.)

  7. Property Blocks: Games and Activities. (United States)

    Humphreys, Alan, Ed.; Dailey, Jean, Ed.

    This pamphlet describes the property blocks produced by MINNEMAST, and discusses their use in the development of thinking processes. Classification systems, including block diagrams and tree diagrams, are discussed. Sixteen classroom activities and eleven games which use the blocks are described. Suggestions to the teacher for further reading are…

  8. Protective Effect of Rhubarb on Endotoxin-Induced Acute Lung Injury

    Institute of Scientific and Technical Information of China (English)

    李春盛; 周景; 桂培春; 何新华


    To approach the mechanism of lipopolysaccharide (LPS) in causing acute lung injury (ALI) and the protective effect of rhubarb and dexamethasone, lung specimens were examined with macroscopy, microscopy, electron microscopy and the biological markers of ALI including lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary capillary permeability and pulmonary alveolar permeability index were observed. The mechanism of the ALI is mainly due to direct injury of alveolar epithelium and pulmonary vascular endothelium. Rhubarb and dexamethasone could significantly reduce the edema of the lung tissue, decrease the red blood cell exudation, neutrophil infiltration and plasma protein exudation in the alveoli and all the biological markers in comparison with the ALI model rats, indicating they have protective action on vascular endothelium and alveolar epithelium.

  9. Methylene Blue for Vasoplegia When on Cardiopulmonary Bypass During Double-Lung Transplantation. (United States)

    Carley, Michelle; Schaff, Jacob; Lai, Terrance; Poppers, Jeremy


    Vasoplegia syndrome, characterized by hypotension refractory to fluid resuscitation or high-dose vasopressors, low systemic vascular resistance, and normal-to-increased cardiac index, is associated with increased morbidity and mortality after cardiothoracic surgery. Methylene blue inhibits inducible nitric oxide synthase and guanylyl cyclase, and has been used to treat vasoplegia during cardiopulmonary bypass. However, because methylene blue is associated with increased pulmonary vascular resistance, its use in patients undergoing lung transplantion has been limited. Herein, we report the use of methylene blue to treat refractory vasoplegia during cardiopulmonary bypass in a patient undergoing double-lung transplantation.

  10. Repetitive prenatal glucocorticoids increase lung endothelial nitric oxide synthase expression in ovine fetuses delivered at term. (United States)

    Grover, T R; Ackerman, K G; Le Cras, T D; Jobe, A H; Abman, S H


    Antenatal administration of glucocorticoids has been shown to improve postnatal lung function after preterm birth in the ovine fetus. Mechanisms of steroid-induced lung maturation include increased surfactant production and altered parenchymal lung structure. Whether steroid treatment also affects lung vascular function is unclear. Because nitric oxide contributes to the fall in pulmonary vascular resistance at birth, we hypothesized that the improvement of postnatal lung function of preterm lambs after treatment with prenatal glucocorticoids may be in part caused by an increase in endothelial nitric oxide synthase (eNOS) activity. To determine whether glucocorticoid treatment increases lung eNOS expression, we measured eNOS protein content by Western blot analysis of distal lung homogenates and immunostaining of formalin-fixed lungs from ovine fetuses delivered at preterm and term gestation after prenatal administration of glucocorticoids. Treatment protocols were followed in which ewes were treated with intramuscular betamethasone (0.5 mg/kg) at single or multiple doses at weekly intervals, and fetuses were delivered at 125, 135, or 145 d gestation. All groups were compared with saline-treated controls. Western blot analysis of whole lung homogenates demonstrated a 4-fold increase in eNOS protein content in lambs treated with repetitive doses of glucocorticoids and delivery at term (145 d; p preterm ages (125 and 135 d). Immunostaining showed eNOS predominantly in the vascular endothelium in all vessel sizes. Pattern of staining was not altered by treatment with antenatal glucocorticoids. We conclude that maternal treatment with glucocorticoids increases lung eNOS content after multiple doses and delivery at term gestation. We speculate that antenatal glucocorticoids may up-regulate eNOS but that the timing and duration of steroid administration appears to be critical to this response.

  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. Vascular Endothelial Growth Factor Receptor-3 Directly Interacts with Phosphatidylinositol 3-Kinase to Regulate Lymphangiogenesis (United States)

    Coso, Sanja; Zeng, Yiping; Opeskin, Kenneth; Williams, Elizabeth D.


    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. PMID:22745786

  13. Surgical issues in lung transplantation: options, donor selection, graft preservation, and airway healing. (United States)

    Daly, R C; McGregor, C G


    To present an overview of the surgical issues in lung transplantation, including the historical context and the rationale for choosing a particular procedure for a specific patient, we reviewed and summarized the current medical literature and our personal experience. Several surgical options are available, including single lung transplantation; double lung transplantation; heart-lung transplantation; bilateral, sequential single lung transplantation; and (recently) single lobe transplantation. Although single lung transplantation is preferred for maximal use of the available organs, bilateral lung transplantation is necessary for septic lung diseases and may be appropriate for pulmonary hypertension and bullous emphysema. Heart-lung transplantation is performed for Eisenmenger's syndrome and for primary pulmonary hypertension with severe right ventricular failure. General factors for consideration in assessment of compatibility of the donor and potential recipient include ABO blood group, height (the donor should be within +/- 20% of the recipient's height), and length of the lungs (determined on an anteroposterior chest roentgenogram). Graft preservation and minimal duration of ischemia are important. Complications associated with airway healing are related to ischemia of the donor bronchus. We have addressed the issue of donor bronchial ischemia by direct revascularization of the donor bronchial arteries with use of the recipient's internal thoracic artery. Currently, lung transplantation offers a realistic therapeutic option to patients with end-stage pulmonary parenchymal or vascular disease.

  14. Center-blocked field technique for treatment of extensive chest wall disease

    Energy Technology Data Exchange (ETDEWEB)

    Podgorsak, E.B.; Pla, M.; Kim, T.H.; Freeman, C.R.


    Our treatment technique for patients with extensive chest wall disese is presented. A rotational center-blocked radiation field is used to cover the large tumor volume to a dose with +/- 10% while sparing the lungs and the spinal cord. The center block is tapered to match both the patient's mediastinal slope in the sagittal plane and the outline of the lungs in the coronal plane. Ten patients treated with this technique to a tumor dose of 50 Gy tolerated the treatment well, despite a high integral dose. The local responses were excellent, particularly in view of the initial extent of the disease.

  15. Humanoid by ROBO-BLOCK (United States)

    Niimi, Hirofumi; Koike, Minoru; Takeuchi, Seiichi; Douhara, Noriyoshi


    Humanoid by ROBO-BLOCK (robot block system) and the rational formula of robots were proposed. ROBO-BLOCK is composed of servo motors, the parts for servomotor rotor, the brackets for servomotor fixation, the board parts and the controllers. A robot can be assembled easily by ROBO-BLOCK. Meanwhile, it is convenient when the structure of the robot can be described easily as a character. The whole structure of the robot is expressed as rational formula of the robot to show molecule structure in chemistry. ROBO-BLOCK can be useful for not only the research but also the education. Creative student experiment was done in the college of industrial technology.

  16. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter


    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...

  17. Vascular calcification: Inducers and inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Donghyun, E-mail: [Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756 (Korea, Republic of)


    Highlights: {center_dot} Types of vascular calcification processes. {center_dot} Inducers of vascular calcification. {center_dot} Inhibitors of vascular calcifications. {center_dot} Clinical utility for vascular calcification therapy. {center_dot} Implications for the development of new tissue engineering strategies. - Abstract: Unlike the traditional beliefs, there are mounting evidences suggesting that ectopic mineral depositions, including vascular calcification are mostly active processes, many times resembling that of the bone mineralization. Numbers of agents are involved in the differentiation of certain subpopulation of smooth muscle cells (SMCs) into the osteoblast-like entity, and the activation and initiation of extracellular matrix ossification process. On the other hand, there are factors as well, that prevent such differentiation and ectopic calcium phosphate formation. In normal physiological environments, activities of such procalcific and anticalcific regulatory factors are in harmony, prohibiting abnormal calcification from occurring. However, in certain pathophysiological conditions, such as atherosclerosis, chronic kidney disease (CKD), and diabetes, such balances are altered, resulting in abnormal ectopic mineral deposition. Understanding the factors that regulate the formation and inhibition of ectopic mineral formation would be beneficial in the development of tissue engineering strategies for prevention and/or treatment of such soft-tissue calcification. Current review focuses on the factors that seem to be clinically relevant and/or could be useful in developing future tissue regeneration strategies. Clinical utilities and implications of such factors are also discussed.

  18. Vascular potassium channels in NVC. (United States)

    Yamada, K


    It has long been proposed that the external potassium ion ([K(+)]0) works as a potent vasodilator in the dynamic regulation of local cerebral blood flow. Astrocytes may play a central role for producing K(+) outflow possibly through calcium-activated potassium channels on the end feet, responding to a rise in the intracellular Ca(2+) concentration, which might well reflect local neuronal activity. A mild elevation of [K(+)]0 in the end feet/vascular smooth muscle space could activate Na(+)/K(+)-ATPase concomitant with inwardly rectifying potassium (Kir) channels in vascular smooth muscle cells, leading to a hyperpolarization of vascular smooth muscle and relaxation of smooth muscle actin-positive vessels. Also proposed notion is endothelial calcium-activated potassium channels and/or inwardly rectifying potassium channel-mediated hyperpolarization of vascular smooth muscle. A larger elevation of [K(+)]0, which may occur pathophysiologically in such as spreading depression or stroke, can trigger a depolarization of vascular smooth muscle cells and vasoconstriction instead.

  19. Acidente vascular cerebral e demência vascular no idoso


    Ionel, Cristina


    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 ...

  20. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter


    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....

  1. Spintronics: Conceptual Building Blocks (United States)

    Ansermet, J.-Ph.

    The purpose of this introduction to spintronics is to provide some elementary description of its conceptual building blocks. Thus, it is intended for a newcomer to the field. After recalling rudimentary descriptions of spin precession and spin relaxation, spin-dependent transport is treated within the Boltzmann formalism. This suffices to introduce key notions such as the spin asymmetry of the conductivities in the two-current model, the spin diffusion length, and spin accumulation. Two basic mechanisms of spin relaxation are then presented, one arising from spin-orbit scattering and the other from electron-magnon collisions. Finally, the action of a spin-polarized current on magnetization is presented in a thermodynamics framework. This introduces the notion of spin torque and the characteristic length scale over which the transverse spin polarization of conduction electron decays as it is injected into a magnet.

  2. Photovoltaic building blocks

    DEFF Research Database (Denmark)

    Hanberg, Peter Jesper; Jørgensen, Anders Michael


    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...... 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...

  3. 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:


    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.

  4. Atomic Basic Blocks (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.

  5. Assessment Value of Extravascular Lung Water Index and Pulmonary Vascular Permeability Index on Illness Severity and Prognosis of Patients With Septic Shock%血管外肺水指数和肺血管通透性指数对脓毒性休克患者病情及预后的评估价值研究

    Institute of Scientific and Technical Information of China (English)

    陶飞; 胡桂芳; 邓烈华; 姚华国


    预后的指标。%Objective To analyze the assessment value of extravascular lung water index(EVLWI) and pulmonary vascular permeability index(PVPI)on illness severity and prognosis of patients with septic shock. Methods From March 2011 to December 2015,a total of 57 patients with septic shock were selected in the Intensive Care Unit(ICU),Central Hospital of Chancheng District,Foshan;in the ICU,the Affiliated Hospital of Guangdong Medical College. According to the prognosis after 28 days of admission,all of the 57 patients were divided into survivor group(n = 41)and death group(n = 16),EVLWI and PVPI were compared between the two groups after 1 day,2 days and 3 days of admission of ICU,and their correlations with APACHEⅡ score,with SOFA score were analyzed,ROC curve was drawn to evaluate the assessment value of EVLWI and PVPI on prognosis of patients with septic shock. Results No statistically significant differences of EVLWI was found between the two groups after 1 day of admission of ICU( P ﹥ 0. 05);EVLWI of death group was statistically significantly higher than that of survivor group after 2 days and 3 days of admission of ICU,respectively( P < 0. 05);PVPI of death group was statistically significantly higher than that of survivor group after 1 day,2 days and 3 days of admission of ICU,respectively(P < 0. 05). Of survivor group,EVLWI and PVPI after 2 days and 3 days of admission of ICU were statistically significantly lower than those after 1 day of admission of ICU,EVLWI and PVPI after 3 day of admission of ICU were statistically significantly lower than those after 2 days of admission of ICU(P < 0. 05);of death group,there was no statistically significant differences of EVLWI or PVPI after 1 day,2 days or 3 days of admission of ICU( P ﹥ 0. 05). Spearman rank correlation analysis showed that,EVLWI was positively correlated with APACHEⅡ score,SOFA score of patients with septic shock,respectively(rs = 0. 531,0. 625,P <0. 05);PVPI was positively

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

    NARCIS (Netherlands)

    S. Tuinman (Sietske); A.D. Cornet (Alexander); M.T. Kuipers (Maria); A.P.J. Vlaar (Alexander); M.J. Schultz (Marcus); A. Beishuizen (Auke); A.B.J. Groeneveld (Johan); N.P. Juffermans (Nicole)


    textabstractBackground: Cardiac surgery is frequently complicated by an acute vascular lung injury and this may be mediated, at least in part, by the (soluble) receptor for advanced glycation end products (sRAGE).Methods: In two university hospital intensive care units, circulating sRAGE was measure

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

    Directory of Open Access Journals (Sweden)

    Junghyun Kim


    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.

  8. Laminins and retinal vascular development. (United States)

    Edwards, Malia M; Lefebvre, Olivier


    The mechanisms controlling vascular development, both normal and pathological, are not yet fully understood. Many diseases, including cancer and diabetic retinopathy, involve abnormal blood vessel formation. Therefore, increasing knowledge of these mechanisms may help develop novel therapeutic targets. The identification of novel proteins or cells involved in this process would be particularly useful. The retina is an ideal model for studying vascular development because it is easy to access, particularly in rodents where this process occurs post-natally. Recent studies have suggested potential roles for laminin chains in vascular development of the retina. This review will provide an overview of these studies, demonstrating the importance of further research into the involvement of laminins in retinal blood vessel formation.

  9. Fetal origin of vascular aging

    Directory of Open Access Journals (Sweden)

    Shailesh Pitale


    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.

  10. 6 Common Cancers - Lung Cancer (United States)

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents For ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next ...

  11. Vascular Injury in Orthopedic Trauma. (United States)

    Mavrogenis, Andreas F; Panagopoulos, George N; Kokkalis, Zinon T; Koulouvaris, Panayiotis; Megaloikonomos, Panayiotis D; Igoumenou, Vasilios; Mantas, George; Moulakakis, Konstantinos G; Sfyroeras, George S; Lazaris, Andreas; Soucacos, Panayotis N


    Vascular injury in orthopedic trauma is challenging. The risk to life and limb can be high, and clinical signs initially can be subtle. Recognition and management should be a critical skill for every orthopedic surgeon. There are 5 types of vascular injury: intimal injury (flaps, disruptions, or subintimal/intramural hematomas), complete wall defects with pseudoaneurysms or hemorrhage, complete transections with hemorrhage or occlusion, arteriovenous fistulas, and spasm. Intimal defects and subintimal hematomas with possible secondary occlusion are most commonly associated with blunt trauma, whereas wall defects, complete transections, and arteriovenous fistulas usually occur with penetrating trauma. Spasm can occur after either blunt or penetrating trauma to an extremity and is more common in young patients. Clinical presentation of vascular injury may not be straightforward. Physical examination can be misleading or initially unimpressive; a normal pulse examination may be present in 5% to 15% of patients with vascular injury. Detection and treatment of vascular injuries should take place within the context of the overall resuscitation of the patient according to the established principles of the Advanced Trauma Life Support (ATLS) protocols. Advances in the field, made mostly during times of war, have made limb salvage the rule rather than the exception. Teamwork, familiarity with the often subtle signs of vascular injuries, a high index of suspicion, effective communication, appropriate use of imaging modalities, sound knowledge of relevant technique, and sequence of surgical repairs are among the essential factors that will lead to a successful outcome. This article provides a comprehensive literature review on a subject that generates significant controversy and confusion among clinicians involved in the care of trauma patients. [Orthopedics. 2016; 39(4):249-259.].

  12. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro


    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.

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

    Directory of Open Access Journals (Sweden)

    Joshua J Field

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease.

  14. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification]. (United States)

    Kurabayashi, Masahiko


    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  15. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings


    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 we...... of the tissue are supplied. A set of model parameters uniquely determine the model dynamics, and we have identified the region of the best-performing model parameters (a global optimum). This region is surrounded in parameter space by less optimal model parameter values, and this separation is characterized...

  16. Vascular Reconstruction in Hepatic Malignancy. (United States)

    Berumen, Jennifer; Hemming, Alan


    With surgery for hepatic malignancy, there are poor options for chemotherapy; many patients are deemed unresectable because of vascular involvement or location of tumors. Over the past few decades, advances in surgical technique have allowed resection of these tumors with vascular reconstruction to achieve negative margins and improve chances for survival. This article reviews those reconstruction techniques and outcomes in detail, including in situ perfusion and ex vivo liver surgery, and provides a discussion of implications and operative planning for patients with hepatic malignancy in order to provide surgeons with better understanding of these complicated operations.

  17. [Severe hypoxemic respiratory insufficiency in a patient with hepato-pulmonary syndrome coexisting with interstitial lung disease of unknown etiology]. (United States)

    Gorzkowska-Pasik, Katarzyna; Wiatr, Elżbieta; Burakowska, Barbara; Nowicka, Urszula; Kober, Jarosław; Malong, Przemysław; Pasik, Piotr; Folcik, Krystyna


    The coexistence of the interstitial lung disease and respiratory failure is rarely associated with extrapulmonary pathology. In patients with liver cirrhosis, hypoxemia may develop in the course of hepato-pulmonary syndrome (HPS), but radiological pathology seen in the course of HPS is of vascular origin, and thus typically not classified as interstitial lung disease. We present a patient with severe hypoxemic respiratory insufficiency in whom hepato-pulmonary syndrome coexisted with interstitial lung disease of unknown etiology. The mechanisms of hypoxemia in the course of hepatic diseases and reasons of possible coincidence of lung and hepatic pathology are discussed.

  18. Large Block Test Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lin, W


    This report documents the Large-Block Test (LBT) conducted at Fran Ridge near Yucca Mountain, Nevada. The LBT was a thermal test conducted on an exposed block of middle non-lithophysal Topopah Spring tuff (Tptpmn) and was designed to assist in understanding the thermal-hydrological-mechanical-chemical (THMC) processes associated with heating and then cooling a partially saturated fractured rock mass. The LBT was unique in that it was a large (3 x 3 x 4.5 m) block with top and sides exposed. Because the block was exposed at the surface, boundary conditions on five of the six sides of the block were relatively well known and controlled, making this test both easier to model and easier to monitor. This report presents a detailed description of the test as well as analyses of the data and conclusions drawn from the test. The rock block that was tested during the LBT was exposed by excavation and removal of the surrounding rock. The block was characterized and instrumented, and the sides were sealed and insulated to inhibit moisture and heat loss. Temperature on the top of the block was also controlled. The block was heated for 13 months, during which time temperature, moisture distribution, and deformation were monitored. After the test was completed and the block cooled down, a series of boreholes were drilled, and one of the heater holes was over-cored to collect samples for post-test characterization of mineralogy and mechanical properties. Section 2 provides background on the test. Section 3 lists the test objectives and describes the block site, the site configuration, and measurements made during the test. Section 3 also presents a chronology of events associated with the LBT, characterization of the block, and the pre-heat analyses of the test. Section 4 describes the fracture network contained in the block. Section 5 describes the heating/cooling system used to control the temperature in the block and presents the thermal history of the block during the test

  19. Bone Marrow-Derived c-kit+ Cells Attenuate Neonatal Hyperoxia-Induced Lung Injury (United States)

    Ramachandran, Shalini; Suguihara, Cleide; Drummond, Shelley; Chatzistergos, Konstantinos; Klim, Jammie; Torres, Eneida; Huang, Jian; Hehre, Dorothy; Rodrigues, Claudia O.; McNiece, Ian K.; Hare, Joshua M.; Young, Karen C.


    Recent studies suggest that bone marrow (BM)-derived stem cells have therapeutic efficacy in neonatal hyperoxia-induced lung injury (HILI). c-kit, a tyrosine kinase receptor that regulates angiogenesis, is expressed on several populations of BM-derived cells. Preterm infants exposed to hyperoxia have decreased lung angiogenesis. Here we tested the hypothesis that administration of BM-derived c-kit+ cells would improve angiogenesis in neonatal rats with HILI. To determine whether intratracheal (IT) administration of BM-derived c-kit+ cells attenuates neonatal HILI, rat pups exposed to either normobaric normoxia (21% O2) or hyperoxia (90% O2) from postnatal day (P) 2 to P15 were randomly assigned to receive either IT BM-derived green fluorescent protein (GFP)+ c-kit− cells (PL) or BM-derived GFP+ c-kit+ cells on P8. The effect of cell therapy on lung angiogenesis, alveolarization, pulmonary hypertension, vascular remodeling, cell proliferation, and apoptosis was determined at P15. Cell engraftment was determined by GFP immunostaining. Compared to PL, the IT administration of BM-derived c-kit+ cells to neonatal rodents with HILI improved alveolarization as evidenced by increased lung septation and decreased mean linear intercept. This was accompanied by an increase in lung vascular density, a decrease in lung apoptosis, and an increase in the secretion of proangiogenic factors. There was no difference in pulmonary vascular remodeling or the degree of pulmonary hypertension. Confocal microscopy demonstrated that 1% of total lung cells were GFP+ cells. IT administration of BM-derived c-kit+ cells improves lung alveolarization and angiogenesis in neonatal HILI, and this may be secondary to an improvement in the lung angiogenic milieu. PMID:23759597

  20. Lung alveolar epithelium and interstitial lung disease. (United States)

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic


    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  1. Lycopene and Lung Cancer (United States)

    Although epidemiological studies have shown dietary intake of lycopene is associated with decreased risk of lung cancer, the effect of lycopene on lung carcinogenesis has not been well studied. A better understanding of lycopene metabolism and the mechanistic basis of lycopene chemoprevention must ...

  2. Lung Cancer Indicators Recurrence (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

  3. Lung transplant - slideshow (United States)

    ... this page: // Lung transplant - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 out of ... to slide 5 out of 5 Overview The lungs, which reside in the thorax, or chest cavity, ...

  4. MRI of the lung

    Energy Technology Data Exchange (ETDEWEB)

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


    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.)

  5. Lung needle biopsy (United States)

    ... biopsy Lung tissue biopsy References Ettinger DS. Lung cancer and other pulmonary neoplasms. In: Goldman L, Schafer AI, eds. Goldman's ... 2010:chap 47. Read More Aspiration ... by: Denis Hadjiliadis, MD, Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, ...

  6. Lung cancer in women

    Directory of Open Access Journals (Sweden)

    Barrera-Rodriguez R


    Full Text Available Raúl Barrera-Rodriguez,1 Jorge Morales-Fuentes2 1Biochemistry and Environmental Medicine Laboratory, National Institute of Respiratory Disease, 2Lung Cancer Medical Service, National Institute of Respiratory Disease, Tlalpan, Mexico City, Distrito Federal, Mexico Both authors contributed equally to this workAbstract: Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer.Keywords: lung cancer, adenocarcinoma, women, genetic susceptibility, genetic differences, tobacco

  7. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H


    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...

  8. Concise review: current status of stem cells and regenerative medicine in lung biology and diseases. (United States)

    Weiss, Daniel J


    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.

  9. Evaluation of Angiogenesis Using Micro-Computed Tomography in a Xenograft Mouse Model of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Rajkumar Savai


    Full Text Available Quantitative evaluation of lung tumor angiogenesis using immunohistochemical techniques has been limited by difficulties in generating reproducible data. To analyze intrapulmonary tumor angiogenesis, we used high-resolution micro-computed tomography (micro-CT of lung tumors of mice inoculated with mouse Lewis lung carcinoma (LLC1 or human adenocarcinoma (A549 cell lines. The lung vasculature was filled with the radiopaque silicone rubber, Microfil, through the jugular vein (in vivo application or pulmonary artery (ex vivo application. In addition, human adenocarcinoma lung tumor-bearing mice treated site-specifically with humanized monoclonal antibody (bevacizumab against vascular endothelial growth factor. Quantitative analysis of lung tumor microvessels imaged with micro-CT showed that more vessels (mainly small, <0.02 mm2 were filled using the in vivo (5.4% compared with the ex vivo (2.1% method. Furthermore, bevacizumab-treated lung tumor-bearing mice showed significantly reduced lung tumor volume and lung tumor angiogenesis compared with untreated mice as assessed by micro-CT. Interestingly, microvascularization of mainly the smaller vessels (<0.02 mm2 was reduced after bevacizumab treatment. This observation with micro-CT was nicely correlated with immunohistochemical measurement of microvessels. Therefore, micro-CT is a novel method for investigating lung tumor angiogenesis, and this might be considered as an additional complementary tool for precise quantification of angiogenesis.

  10. Angiotensin II type 2 receptor ligand PD123319 attenuates hyperoxia-induced lung and heart injury at a low dose in newborn rats. (United States)

    Wagenaar, Gerry T M; Sengers, Rozemarijn M A; Laghmani, El Houari; Chen, Xueyu; Lindeboom, Melissa P H A; Roks, Anton J M; Folkerts, Gert; Walther, Frans J


    Intervening in angiotensin (Ang)-II type 2 receptor (AT2) signaling may have therapeutic potential for bronchopulmonary dysplasia (BPD) by attenuating lung inflammation and preventing arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We first investigated the role of AT2 inhibition with PD123319 (0.5 and 2 mg·kg(-1)·day(-1)) on the beneficial effect of AT2 agonist LP2-3 (5 μg/kg twice a day) on RVH in newborn rats with hyperoxia-induced BPD. Next we determined the cardiopulmonary effects of PD123319 (0.1 mg·kg(-1)·day(-1)) in two 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 lung and heart histopathology, fibrin deposition, vascular leakage, and differential mRNA expression. Ten days of coadministration of LP2-3 and PD123319 abolished the beneficial effects of LP2-3 on RVH in experimental BPD. In the early treatment model PD123319 attenuated cardiopulmonary injury by reducing alveolar septal thickness, pulmonary influx of inflammatory cells, including macrophages and neutrophils, medial wall thickness of small arterioles, and extravascular collagen III deposition, and by preventing RVH. In the late treatment model PD123319 diminished PAH and RVH, demonstrating that PAH is reversible in the neonatal period. At high concentrations PD123319 blocks the beneficial effects of the AT2-agonist LP2-3 on RVH. At low concentrations PD123319 attenuates cardiopulmonary injury by reducing pulmonary inflammation and fibrosis and preventing PAH-induced RVH but does not affect alveolar and vascular development in newborn rats with experimental BPD.

  11. Cigarette smoke regulates VEGFR2-mediated survival signaling in rat lungs

    Directory of Open Access Journals (Sweden)

    Stevenson Christopher S


    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.

  12. Dimensional Reduction for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs


    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 3d conformal blocks as an infinite sum over 2F1 hypergeometric functions with closed-form coefficients.

  13. Immunotherapy in Lung Cancer. (United States)

    Castellanos, Emily H; Horn, Leora


    Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

  14. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot


    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.

  15. Common blocks for ASQS(12

    Directory of Open Access Journals (Sweden)

    Lorenzo Milazzo


    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.

  16. Oxidative Stress and Lung Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Renata Salatti Ferrari


    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.

  17. 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: [Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 (United States)


    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.

  18. Estimation of Lung Ventilation (United States)

    Ding, Kai; Cao, Kunlin; Du, Kaifang; Amelon, Ryan; Christensen, Gary E.; Raghavan, Madhavan; Reinhardt, Joseph M.

    Since the primary function of the lung is gas exchange, ventilation can be interpreted as an index of lung function in addition to perfusion. Injury and disease processes can alter lung function on a global and/or a local level. MDCT can be used to acquire multiple static breath-hold CT images of the lung taken at different lung volumes, or with proper respiratory control, 4DCT images of the lung reconstructed at different respiratory phases. Image registration can be applied to this data to estimate a deformation field that transforms the lung from one volume configuration to the other. This deformation field can be analyzed to estimate local lung tissue expansion, calculate voxel-by-voxel intensity change, and make biomechanical measurements. The physiologic significance of the registration-based measures of respiratory function can be established by comparing to more conventional measurements, such as nuclear medicine or contrast wash-in/wash-out studies with CT or MR. An important emerging application of these methods is the detection of pulmonary function change in subjects undergoing radiation therapy (RT) for lung cancer. During RT, treatment is commonly limited to sub-therapeutic doses due to unintended toxicity to normal lung tissue. Measurement of pulmonary function may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy. This chapter reviews the basic measures to estimate regional ventilation from image registration of CT images, the comparison of them to the existing golden standard and the application in radiation therapy.

  19. Eikonalization of Conformal Blocks

    CERN Document Server

    Fitzpatrick, A Liam; Walters, Matthew T; Wang, Junpu


    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the $t$-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the `eikonalization' of conformal blocks. We show that when an operator $T$ appears in the OPE $\\mathcal{O}(x) \\mathcal{O}(0)$, then the large spin $\\ell$ Fock space states $[TT \\cdots T]_{\\ell}$ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an $\\langle \\mathcal{O} \\mathcal{O} \\mathcal{O} \\mathcal{O} \\rangle$ correlator build the classical `$T$ field' in the dual AdS description. In some limits the sum of all Fock space exchanges can be represented as the exponential of a single $T$ exchange in the 4-pt correlator of $\\mathcal{O}$. Our results should be useful for systematizing $1/\\ell$ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading $\\log \\ell$...

  20. Adductor Canal Block versus Femoral Nerve Block and Quadriceps Strength

    DEFF Research Database (Denmark)

    Jæger, Pia Therese; Nielsen, Zbigniew Jerzy Koscielniak; Henningsen, Lene Marianne;


    : The authors hypothesized that the adductor canal block (ACB), a predominant sensory blockade, reduces quadriceps strength compared with placebo (primary endpoint, area under the curve, 0.5-6 h), but less than the femoral nerve block (FNB; secondary endpoint). Other secondary endpoints were...

  1. [Vascular access guidelines for hemodialysis]. (United States)

    Rodríguez Hernández, J A; González Parra, E; Julián Gutiérrez, J M; Segarra Medrano, A; Almirante, B; Martínez, M T; Arrieta, J; Fernández Rivera, C; Galera, A; Gallego Beuter, J; Górriz, J L; Herrero, J A; López Menchero, R; Ochando, A; Pérez Bañasco, V; Polo, J R; Pueyo, J; Ruiz, Camps I; Segura Iglesias, R


    Quality of vascular access (VA) has a remarkable influence in hemodialysis patients outcomes. Dysfunction of VA represents a capital cause of morbi-mortality of these patients as well an increase in economical. Spanish Society of Neprhology, aware of the problem, has decided to carry out a revision of the issue with the aim of providing help in comprehensión and treatment related with VA problems, and achieving an homogenization of practices in three mayor aspects: to increase arteriovenous fistula utilization as first vascular access, to increment vascular access monitoring practice and rationalise central catheters use. We present a consensus document elaborated by a multidisciplinar group composed by nephrologists, vascular surgeons, interventional radiologysts, infectious diseases specialists and nephrological nurses. Along six chapters that cover patient education, creation of VA, care, monitoring, complications and central catheters, we present the state of the art and propose guidelines for the best practice, according different evidence based degrees, with the intention to provide help at the professionals in order to make aproppiate decissions. Several quality standars are also included.

  2. Vascular aspects of multiple sclerosis

    NARCIS (Netherlands)

    D'haeseleer, Miguel; Cambron, Melissa; Vanopdenbosch, Ludo; De Keyser, Jacques


    Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial dy

  3. Effect of hyperoxia on the airway and vascular development in fetal lung and the intervention of dexamethasone%高氧对胎儿肺气道及血管发育的影响及地塞米松的干预作用

    Institute of Scientific and Technical Information of China (English)

    李娟; 刘博


    目的 探讨高氧对人胎儿肺泡及肺血管发育的影响及地塞米松的干预作用.方法 假腺体期胎儿肺组织分别于高氧(95 96O2,5%CO2)及正常氧(21%O2,5%CO2)中培养72 h,两组又分别同时加入地塞米松(10-6mol/L),对照组以相同浓度乙醇代替.收获的肺组织分别以细胞角蛋白和CD31确定上皮细胞及内皮细胞,用图像分析系统计算出气道厚度、气道占组织百分比、血管距最近气道距离、血管占间质比例.结果 空气培养72 h,肺结构与新鲜肺组织比较无明显变化;高氧组气道明显扩张.上皮明显变薄,气道所占比例明显增加(P<0.05).高氧组肺间质毛细血管明显靠近气道(50μm),该组血管所占面积(4.0%)明显小于正常氧(4.2%)和高氧+地塞米松组(5.4%)(P<0.05).地塞米松可抑制高氧对肺组织的不良效应.结论 高氧导致胎儿肺组织气道简单化及间质血管减少;地塞米松可阻止这些变化,促进肺成熟.%Objective To investigate the effects of dexamethasone on the airway development and vasculogenesis in cultured human fetal lung exposed to hyperoxia.Methods Human fetal lung at the pseudoglandular stage of development were cultured either in normoxia(21%O2,5%CO2)or hyperoxia(95%O2,5% CO2)for 72 hours.Dexamethasone was added into the culture medium at the concentration of 10-6 mol/L.Whereas ethanol at the same concentration was as control.Harvested tissue wss stained for pancytokeratin to I dentify epithelial cells.CD31 aS a specific antibody of endothelial cell.The effects of lung morphometry were analyzed using computer-assisted image analysis software to ealeuhte the thickness of airways,surface area occupied by airways and the distance of vessels to the nearest airway as well as the surface area of blood vessels.Results The lung architecture remained largely unchanged in normoxia for 72 hours culture,whereas hyperoxic culture of lungs resulted in significant dilation of airways and thinning of

  4. SIRT1 regulates endothelial Notch signaling in lung cancer.

    Directory of Open Access Journals (Sweden)

    Mian Xie

    Full Text Available BACKGROUND: Sirtuin 1 (SIRT1 acts as a key regulator of vascular endothelial homeostasis, angiogenesis, and endothelial dysfunction. However, the underlying mechanism for SIRT1-mediated lung carcinoma angiogenesis remains unknown. Herein, we report that the nicotinamide adenine dinucleotide 1 (NAD1-dependent deacetylase SIRT1 can function as an intrinsic negative modulator of Delta-like ligand 4 (DLL4/Notch signaling in Lewis lung carcinoma (LLC xenograft-derived vascular endothelial cells (lung cancer-derived ECs. PRINCIPAL FINDINGS: SIRT1 negatively regulates Notch1 intracellular domain (N1IC and Notch1 target genes HEY1 and HEY2 in response to Delta-like ligand 4 (DLL4 stimulation. Furthermore, SIRT1 deacetylated and repressed N1IC expression. Quantitative chromatin immunoprecipitation (qChIP analysis and gene reporter assay demonstrated that SIRT1 bound to one highly conserved region, which was located at approximately -500 bp upstream of the transcriptional start site of Notch1,and repressed Notch1 transcription. Inhibition of endothelial cell growth and sprouting angiogenesis by DLL4/Notch signaling was enhanced in SIRT1-silenced lung cancer-derived EC and rescued by Notch inhibitor DAPT. In vivo, an increase in proangiogenic activity was observed in Matrigel plugs from endothelial-specific SIRT1 knock-in mice. SIRT1 also enhanced tumor neovascularization and tumor growth of LLC xenografts. CONCLUSIONS: Our results show that SIRT1 facilitates endothelial cell branching and proliferation to increase vessel density and promote lung tumor growth through down-regulation of DLL4/Notch signaling and deacetylation of N1IC. Thus, targeting SIRT1 activity or/and gene expression may represent a novel mechanism in the treatment of lung cancer.

  5. Subclinical hypothyroidism after vascular complicated pregnancy

    NARCIS (Netherlands)

    Zanden, M. van der; Hop-de Groot, R.J.; Sweep, F.C.; Ross, H.A.; Heijer, M. den; Spaanderman, M.E.A.


    OBJECTIVE: Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions. METH

  6. Vascular injury in the United kingdom. (United States)

    Stannard, Adam; Brohi, Karim; Tai, Nigel


    Surgeons working within the United Kingdom's National Health Service have an established history of clinical innovation, research, and development in the field of vascular surgery but lack a unified trauma system to deliver optimal care for patients with vascular injury. The low incidence of vascular trauma, combined with lack of regional trauma systems, works against optimal delivery of care to the polytrauma patient. Providing care, robust data capture, and opportunities for training and education in vascular injury lag behind other elective domains of vascular practice. The challenge is to define ideal care pathways, referral networks, and standards of practice and to integrate the care of such patients. In 2010, a trauma system for London was introduced; it has provided vascular surgeons with a unique opportunity to study and advance the care of patients with vascular injury. This article discusses developing trauma network issues, particularly the organization and evolution of vascular trauma services in the United Kingdom.

  7. 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)


    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.)

  8. [Lung hyperinflation after single lung transplantation to treat emphysema]. (United States)

    Samano, Marcos Naoyuki; Junqueira, Jader Joel Machado; Teixeira, Ricardo Henrique de Oliveira Braga; Caramori, Marlova Luzzi; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli


    Despite preventive measures, lung hyperinflation is a relatively common complication following single lung transplantation to treat pulmonary emphysema. The progressive compression of the graft can cause mediastinal shift and respiratory failure. In addition to therapeutic strategies such as independent ventilation, the treatment consists of the reduction of native lung volume by means of lobectomy or lung volume reduction surgery. We report two cases of native lung hyperinflation after single lung transplantation. Both cases were treated by means of lobectomy or lung volume reduction surgery.

  9. Two Decades of Progress in Vascular Medicine


    Leeper, Nicholas J.; Lee, Jason T.; Cooke, John P.


    Twenty years has passed since our first call for a new specialty in Vascular Medicine(1). This proposal was motivated by novel insights into vascular disease, advances in diagnostics and therapies directed toward the vasculature, and a growing population of patients with vascular disease. Now, with two decades of perspective, we reaffirm the call for Vascular Medicine, highlight the field’s early successes, and provide our vision for the future of the specialty.

  10. Diagnosis advances in vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Hua Zhou; Zhong Zhao


    Vascular cognitive impairment(VCI) encompasses the entire range of cognitive deficits associated with cerebrovascular disease(CVD), from mild deficits with little or no functional impairment, such as vascular cognitive impairment-no dementia(VCIND), to full-blown vascular dementia(VaD). Accurate diagnosis of vascular cognitive impairment is important but may be difficult. In this review we report advances in VCI in the following areas: etiology, subtypes, neuropsychology, biomarkers, neuroimaging, and diagnostic criteria.

  11. Robust method for extracting the pulmonary vascular trees from 3D MDCT images (United States)

    Taeprasartsit, Pinyo; Higgins, William E.


    Segmentation of pulmonary blood vessels from three-dimensional (3D) multi-detector CT (MDCT) images is important for pulmonary applications. This work presents a method for extracting the vascular trees of the pulmonary arteries and veins, applicable to both contrast-enhanced and unenhanced 3D MDCT image data. The method finds 2D elliptical cross-sections and evaluates agreement of these cross-sections in consecutive slices to find likely cross-sections. It next employs morphological multiscale analysis to separate vessels from adjoining airway walls. The method then tracks the center of the likely cross-sections to connect them to the pulmonary vessels in the mediastinum and forms connected vascular trees spanning both lungs. A ground-truth study indicates that the method was able to detect on the order of 98% of the vessel branches having diameter >= 3.0 mm. The extracted vascular trees can be utilized for the guidance of safe bronchoscopic biopsy.

  12. Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response. (United States)

    Chen, Xueyu; Walther, Frans J; Sengers, Rozemarijn M A; Laghmani, El Houari; Salam, Asma; Folkerts, Gert; Pera, Tonio; Wagenaar, Gerry T M


    Because therapeutic options are lacking for bronchopulmonary dysplasia (BPD), there is an urgent medical need to discover novel targets/drugs to treat this neonatal chronic lung disease. Metformin, a drug commonly used to lower blood glucose in type 2 diabetes patients, may be a novel therapeutic option for BPD by reducing pulmonary inflammation and fibrosis and improving vascularization. We investigated the therapeutic potential of daily treatment with 25 and 100 mg/kg metformin, injected subcutaneously in neonatal Wistar rats with severe experimental BPD, induced by continuous exposure to 100% oxygen for 10 days. Parameters investigated included survival, lung and heart histopathology, pulmonary fibrin and collagen deposition, vascular leakage, right ventricular hypertrophy, and differential mRNA expression in the lungs of key genes involved in BPD pathogenesis, including inflammation, coagulation, and alveolar development. After daily metformin treatment rat pups with experimental BPD had reduced mortality, alveolar septum thickness, lung inflammation, and fibrosis, demonstrated by a reduced influx of macrophages and neutrophils and hyperoxia-induced collagen III and fibrin deposition (25 mg/kg), as well as improved vascularization (100 mg/kg) compared with control treatment. However, metformin did not ameliorate alveolar enlargement, small arteriole wall thickening, vascular alveolar leakage, and right ventricular hypertrophy. In conclusion metformin prolongs survival and attenuates pulmonary injury by reducing pulmonary inflammation, coagulation, and fibrosis but does not affect alveolar development or prevent pulmonary arterial hypertension and right ventricular hypertrophy in neonatal rats with severe hyperoxia-induced experimental BPD.

  13. 78 FR 77477 - National Heart, Lung, and Blood Institute; Notice of Closed Meeting (United States)


    ... Business Development of New Methods for Mitral Valve Repair. Date: January 10, 2014. Time: 2:00 p.m. to 5... 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: December 17,...

  14. 76 FR 37134 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings (United States)


    ... Enhancement Grants for Stem Cell Research. Date: July 25, 2011. Time: 1 p.m. to 3 p.m. Agenda: To review and... Blood Institute Special Emphasis Panel, Short Term Research Training Program. Date: July 20, 2011. Time... Sleep Disorders Research; 93.837, Heart and Vascular Diseases Research; 93.838, Lung Diseases...

  15. 77 FR 1941 - National Heart, Lung, and Blood Institute; Notice of Closed Meeting (United States)


    ... Enhancement Grants for Stem Cell Research. Date: February 1, 2012. Time: 1 p.m. to 3 p.m. Agenda: To review... 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...

  16. 78 FR 7795 - National Heart, Lung, and Blood Institute; Notice of Closed Meeting (United States)


    ... grant application in rat embryonic stem cell lines. Date: February 21, 2013. Time: 1:00 p.m. to 3:00 p.m... . (Catalogue of Federal 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...

  17. 77 FR 30542 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings (United States)


    ... Enhancement Grants for Stem Cell Research Date: June 13, 2012. Time: 1 p.m. to 4 p.m. Agenda: To review and... Federal 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...

  18. 75 FR 65498 - National Heart, Lung, and Blood Institute; Notice of Closed Meeting (United States)


    ... Awards for Stem Cell Research. Date: November 10, 2010. Time: 12:30 p.m. to 3:30 p.m. Agenda: To review... 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,...

  19. 76 FR 20358 - National Heart, Lung, and Blood Institute; Notice of Closed Meeting (United States)


    ... Award for Stem Cell Research. Date: May 4, 2011. Time: 12:30 p.m. to 3 p.m. Agenda: To review and... 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,...

  20. 77 FR 63844 - National Heart, Lung, and Blood Institute; Notice of Closed Meeting (United States)


    ... Repository Exploratory Grants. Date: November 7, 2012. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and... 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,...

  1. Extra corporeal membrane oxygenation in newborns : implications for brain and lung

    NARCIS (Netherlands)

    Heijst, Adrianus Franciscus Jacobus van


    Extracorporeal membrane oxygenation (ECMO) is a rescue treatment for newborns with severe respiratory insufficiency. In veno-arterial ECMO, venous blood is drained from the right atrium, oxygenated in an artificial lung and reinfused in the aorta. For vascular access the right internal jugular vein

  2. Block Transfer Agreement Evaluation Project (United States)

    Bastedo, Helena


    The objective of this project is to evaluate for the British Columbia Council on Admissions and Transfer (BCCAT) the effectiveness of block transfer agreements (BTAs) in the BC Transfer System and recommend steps to be taken to improve their effectiveness. Findings of this study revealed that institutions want to expand block credit transfer;…

  3. Four-block beam collimator

    CERN Multimedia


    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.)

  4. OPAL Various Lead Glass Blocks

    CERN Multimedia

    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.

  5. Block storage subsystem performance analysis

    CERN Document Server

    CERN. Geneva


    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.

  6. Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis. (United States)

    Pezzella, F; Pastorino, U; Tagliabue, E; Andreola, S; Sozzi, G; Gasparini, G; Menard, S; Gatter, K C; Harris, A L; Fox, S; Buyse, M; Pilotti, S; Pierotti, M; Rilke, F


    Neoplastic growth is usually dependent on blood supply, and it is commonly accepted that this is provided by the formation of new vessels. However, tumors may be able to grow without neovascularization if they find a suitable vascular bed available. We have investigated the pattern of vascularization in a series of 500 primary stage I non-small-cell lung carcinomas. Immunostaining of endothelial cells has highlighted four distinct patterns of vascularization. Three patterns (which we called basal, papillary, and diffuse) have in common the destruction of normal lung and the production of newly formed vessels and stroma. The fourth pattern, which we called alveolar or putative nonangiogenic, was observed in 16% (80/500) of the cases and is characterized by lack of parenchymal destruction and absence of both tumor associated stroma and new vessels. The only vessels present were the ones in the alveolar septa, and their presence highlighted, through the whole tumor, the lung alveoli filled up by the neoplastic cells. This observation suggests that, if an appropriate vascular bed is available, a tumor can exploit it and grows without inducing neo-angiogenesis. This could have implications for strategies aimed at inhibiting tumor growth by vascular targeting or inhibition of angiogenesis.

  7. Segmentation of interstitial lung disease patterns in HRCT images (United States)

    Dash, Jatindra K.; Madhavi, Vaddepalli; Mukhopadhyay, Sudipta; Khandelwal, Niranjan; Kumar, Prafulla


    Automated segmentation of pathological bearing region is the first step towards the development of lung CAD. Most of the work reported in the literature related to automated analysis of lung tissue aims towards classification of fixed sized block into one of the classes. This block level classification of lung tissues in the image never results in accurate or smooth boundaries between different regions. In this work, effort is taken to investigate the performance of three automated image segmentation algorithms those results in smooth boundaries among lung tissue patterns commonly encountered in HRCT images of the thorax. A public database that consists of HRCT images taken from patients affected with Interstitial Lung Diseases (ILDs) is used for the evaluation. The algorithms considered are Markov Random Field (MRF), Gaussian Mixture Model (GMM) and Mean Shift (MS). 2-fold cross validation approach is followed for the selection of the best parameter value for individual algorithm as well as to evaluate the performance of all the algorithms. Mean shift algorithm is observed as the best performer in terms of Jaccard Index, Modified Hausdorff Distance, accuracy, Dice Similarity Coefficient and execution speed.

  8. Bioengineering Lungs for Transplantation. (United States)

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Ott, Harald C


    Whole lung extracellular matrix scaffolds can be created by perfusion of cadaveric organs with decellularizing detergents, providing a platform for organ regeneration. Lung epithelial engineering must address both the proximal airway cells that function to metabolize toxins and aid mucociliary clearance and the distal pneumocytes that facilitate gas exchange. Engineered pulmonary vasculature must support in vivo blood perfusion with low resistance and intact barrier function and be antithrombotic. Repopulating the native lung matrix with sufficient cell numbers in appropriate anatomic locations is required to enable organ function.

  9. Microgravity and the lung (United States)

    West, John B.


    Results are presented from studies of the effect of microgravity on the lungs of rats flown on the Cosmos 2044 mission, and from relevant laboratory experiments. The effects of microgravity fall into five categories: topographical structure and function, the lung volumes and mechanics, the intrathoracic blood pressures and volumes, the pulmonary deposition of aerosol, and denitrogenaton during EVA. The ultrastructure of the left lungs of rats flown for 14 days on the Cosmos 2044 spacecraft and that of some tail-suspended rats disclosed presence of red blood cells in the alveolar spaces, indicating that pulmonary hemorrhage and pulmonary edema occurred in these rats. Possible causes for this phenomenon are discussed.

  10. Herniation of malignant lung cavity

    Institute of Scientific and Technical Information of China (English)

    Saurabh Kumar Singh; Rakesh Bhargava; Zuber Ahmad; Deepak K.Pandey; Shirin Naaz; Vibhanshu Gupta


    @@ Hernia of the lung is defined as a protrusion of lung tissue,covered by parietal and visceral pleurae,through an abnormal opening in the chest wall,diaphragm or mediastinum.1 It is a relatively uncommon condition.We report a case of lung hernia following cavitation in malignant lung mass.

  11. Avaliação ultrassonográfica da anomalia vascular portossistêmica em cão: relato de caso Ultrasonographic evaluation of portosystemic vascular anomaly in dog: a case report

    Directory of Open Access Journals (Sweden)

    M.A.R. Feliciano


    Full Text Available Relata-se a avaliação ultrassonográfica, com auxílio do Doppler em cores, da anomalia vascular portossistêmica em um cão da raça Poodle Toy, que apresentou edema pulmonar e alterações gastrintestinais. Ao exame ultrassonográfico, foram observados vasos portais dilatados e tortuosos. Esses resultados associados aos achados clínicos e laboratoriais permitem identificar a anomalia vascular portossistêmica no paciente.It was reported the ultrasonographic evaluation, assisted to Doppler color, of the portosystemic vascular anomaly in a Poodle Toy dog. The dog was referred with lung edema and gastrointestinal alterations. At ultrasonographic exam, portal vessels were extended and tortuous. These findings associated to clinical and laboratorial findings, allowed to identify the vascular portosystemic anomaly in the patient.

  12. 不同季节穴位贴敷对寒痰阻肺型慢性阻塞性肺病稳定期疗效观察%Observation of the therapeutic effect on COPD of cold phlegm blocking the lung type at stable stage treated with acupoint sticking therapy in different season

    Institute of Scientific and Technical Information of China (English)

    杨淑荃; 石文英; 曹越; 章薇; 李金香; 娄必丹; 李晓平; 李武; 黄香红; 刘兴平; 杨礼白


    目的:系统观察三伏、三九不同季节穴位贴敷治疗寒痰阻肺型慢性阻塞性肺病(COPD)稳定期的临床效果,为COPD的治疗提供新的临床思路和理论依据.方法:将符合入选标准的COPD稳定期患者150例,随机分为伏九组、三伏组和三九组,每组50例,各组用相同成分和剂量的药物(白芥子、甘遂、细辛、延胡索、肉桂、生姜汁)做成药饼,在肺俞、肾俞、大椎、天突、膻中、中府穴位上分别行穴位贴敷治疗,三伏组于每夏初伏、中伏、末伏第1天各贴敷1次,计3次;三九组于每冬一九、二九、三九第1天各贴敷1次,计3次;伏九组于夏季三伏、冬季三九第1天各贴敷1次,计6次.从综合临床疗效、生存质量(症状评分、活动限制评分、对日常生活影响评分)、疾病发作次数及肺功能4个方面进行疗效评定.结果:伏九组总有效率为88.0%(46/50),优于三伏组的76.0%(38/50)、三九组的70.0%(35/50)(P<0.01,P<0.001).各组治疗后疾病发作次数、临床症状积分、肺功能指标均较治疗前明显改善(均P<0.01),伏九组以上各指标较其他两组改善更明显(P<0.01,P<0.001),除用力肺活量(FVC)指标外,三伏组临床症状积分与肺功能指标亦较三九组改善显著(P<0.05,P<0.001).结论:不同季节穴位贴敷对COPD稳定期患者皆具有较好的临床疗效,能降低其疾病发作次数,提高患者的生存质量,改善其肺功能,但伏九贴敷优于单纯的三伏贴敷和三九贴敷,三伏贴敷又优于三九贴敷.%Objective To systematically observe the clinical effect on chronic obstructive pulmonary disease (COPD) at the stable stage, differentiated as cold phlegm blocking the lung type, treated with acupoint sticking therapy during the dog days and the three nine-day periods after the winter solstice so as to propose the latest clinical idea and theoretic evidence for the treatment of COPD. Methods One hundred and fifty

  13. Near-infraread spectroscopy during peripheral vascular surgery

    DEFF Research Database (Denmark)

    Schroeder, Torben Veith; Eiberg, Jonas Peter; Vogt, Katja;


    Original,Near-infraread spectroscopy,Vascular disease,Vascular by-pass surgery,Perioperative oxymetry......Original,Near-infraread spectroscopy,Vascular disease,Vascular by-pass surgery,Perioperative oxymetry...

  14. Long-range enhancers modulate Foxf1 transcription in blood vessels of pulmonary vascular network. (United States)

    Seo, Hyejin; Kim, Jinsun; Park, Gi-Hee; Kim, Yuri; Cho, Sung-Won


    Intimate crosstalk occurs between the pulmonary epithelium and the vascular network during lung development. The transcription factor forkhead box f1 (Foxf1) is expressed in the lung mesenchyme and plays an indispensable role in pulmonary angiogenesis. Sonic hedgehog (Shh), a signalling molecule, is expressed in lung epithelium and is required to establish proper angiogenesis. It has been suggested that Foxf1, a downstream target of the Shh signalling pathway, mediates interaction between angiogenesis and the epithelium in lung. However, there has been no clear evidence showing the mechanism how Foxf1 is regulated by Shh signalling pathway during lung development. In this study, we investigated the lung-specific enhancers of Foxf1 and the Gli binding on the enhancers. At first, we found three evolutionarily conserved Foxf1 enhancers, two of which were long-range enhancers. Of the long-range enhancers, one demonstrated tissue-specific activity in the proximal and distal pulmonary blood vessels, while the other one demonstrated activity only in distal blood vessels. At analogous positions in human, these long-range enhancers were included in a regulatory region that was reportedly repeatedly deleted in alveolar capillary dysplasia with misalignment of pulmonary vein patients, which indicates the importance of these enhancers in pulmonary blood vessel formation. We also determined that Gli increased the activity of one of these long-range enhancers, which was specific to distal blood vessel, suggesting that Shh regulates Foxf1 transcription in pulmonary distal blood vessel formation.

  15. JAM-C promotes lymphangiogenesis and nodal metastasis in non-small cell lung cancer. (United States)

    Hao, SongNan; Yang, YanMei; Liu, Yan; Yang, ShuCai; Wang, Geng; Xiao, JianBing; Liu, HuiDong


    This study aims to investigate lymphatic metastasis-related genes in non-small cell lung carcinomas (NSCLC). NSCLC tissue was analyzed for expression of junctional adhesion molecule-C (JAM-C) protein. Our data revealed novel associations between JAM-C overexpression in primary tumors and lymphatic microvessel density (LMVD), lymph node metastasis, and poorer overall survival and recurrence-free survival. We used the highly metastatic human lung adenocarcinoma cell line Anip973 and its parental line AGZY83-a, which has a low metastatic capacity, in vivo and vitro. We found that JAM-C played an important role in different metastasis capacity of lymph node. JAM-C affected tumor growth, LNM, JAM-C, VEGF-C, vasculature, and ERK1/2 phosphorylation (p-ERK1/2). β1 integrin was involved in lymph node metastasis. Moreover, JAM-C knockdown in highly metastatic Anip973 decreased cell migration in scratch-wound assays. The JAM-C knockdown in Anip973 cells and JAM-C cDNA in AGZY83-a cells regulated the vascular endothelial growth factor C (VEGF-C) expression. Immunofluorescence showed that blocked VEGF-C expression in JAM-C shRNA Anip973 cells were restored after JAM-C treatment. JAM-C-induced VEGF-C in JAM-C cDNA AGZY83-a cells was also effectively inhibited by treatment with an antibody specifically against JAM-C. Use of media from Anip973 cells, AGZY83-a, and A549cells lung cancer cells that overexpressed or downregulated JAM-C was demonstrated to affect activity of VEGF-C-induced β1 integrin subunit or ERK activity in human dermal lymphatic endothelial cells (HDLEC) treated with VEGF-C or inhibitory antibody to JAM-C. Overall, these results indicate that JAM-C could mediate metastasis as it contributes to VEGF-C expression in cancer cells. JAM-C affects β1and ERK activation in HDLEC, thus promoting lymphangiogenesis and nodal metastasis. Our findings indicate that JAM-C may be a therapeutic target for preventing and treating lymphatic metastases.

  16. Expression and cell-specific localization of cholecystokinin receptors in rat lung

    Institute of Scientific and Technical Information of China (English)

    Bin Cong; Shu-Jin Li; Yi-Ling Ling; Yu-Xia Yao; Zhen-Yong Gu; Jun-xia Wang; Hong-Yu You


    AIM: To elucidate whether CCK receptors exist in lung tissues and their precise cellular localization in the lung. METHODS: CCK-AR and CCK-BR mRNA expression andcellular distribution in the rat lung were detected by highly sensitive method of in situ reverse transcription-polymerase chain reaction (RT-PCR) and conventional in situ hybridization. RESULTS: CCK-AR and CCK-BR gene positive signals were observed in bronchial epithelial cells, alveolar epithelial cells,pulmonary macrophages and vascular endothelial cells of the rats' lung byin situ RT-PCR. The hybridization signals of CCK-AR were relatively faint. By in situ hybridization,however, only the signals of CCK-BR but not CCK-AR were detected in the lung, and the positive staining was only found in vascular endothelial cells and macrophages. CONCLUSION: CCK-AR and CCK-BR gene were present in pulmonary vascular endothelial cells, macrophages, bronchial epithelial cells and alveolar epithelial cells, which play an important role in mediating the regulatory actions of CCK-8on these cells.

  17. Locally vascularized pelvic accessory spleen. (United States)

    Iorio, F; Frantellizzi, V; Drudi, Francesco M; Maghella, F; Liberatore, M


    Polysplenism and accessory spleen are congenital, usually asymptomatic anomalies. A rare case of polysplenism with ectopic spleen in pelvis of a 67-year-old, Caucasian female is reported here. A transvaginal ultrasound found a soft well-defined homogeneous and vascularized mass in the left pelvis. Patient underwent MRI evaluation and contrast-CT abdominal scan: images with parenchymal aspect, similar to spleen were obtained. Abdominal scintigraphy with 99mTc-albumin nanocolloid was performed and pelvic region was studied with planar scans and SPECT. The results showed the presence of an uptake area of the radiopharmaceutical in the pelvis, while the spleen was normally visualized. These findings confirmed the presence of an accessory spleen with an artery originated from the aorta and a vein that joined with the superior mesenteric vein. To our knowledge, in the literature, there is just only one case of a true ectopic, locally vascularized spleen in the pelvis.

  18. Endoluminal vascular prostheses; Endoluminale Gefaessprothesen

    Energy Technology Data Exchange (ETDEWEB)

    Vorwerk, D. [Klinikum Ingolstadt (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Schuermann, K. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik


    Endoluminal vascular prostheses that can be implanted by percutaneous routes represent the most recent development in vascular interventional radiology. Various commercially available types of prosthesis are presented and the construction principles and applications are described. At present secure indications for the implantation of endoluminal prostheses are limited to the elimination of aneurysms and arteriovenous fistulae of the large vessels near the trunk in sections that do not cross a joint. The wide use in peripheral occlusive diseases cannot yet be recommended because confirmed data are not available. (orig.) [German] Endoluminale Gefaessprothesen, die perkutan implantierbar sind, stellen die juengste Entwicklung in der vaskulaeren interventionellen Radiologie dar. Verschiedene kommerziell erhaeltliche Prothesentypen werden vorgestellt, ihr Konstruktionsprinzip und ihre Applikation erlaeutert. Die gesicherten Indikationen zur endoluminalen Prothesenimplantation beschraenken sich zur Zeit auf die Ausschaltung von Aneurysmen und arteriovenoesen Fisteln der grossen stammnahen Gefaesse in nichtgelenkueberkreuzenden Abschnitten. Die breite Anwendung bei der peripheren Verschlusskrankheit hingegen kann nicht empfohlen werden, solange gesicherte Daten fehlen. (orig.)

  19. Vascular instruction of pancreas development. (United States)

    Cleaver, Ondine; Dor, Yuval


    Blood vessels course through organs, providing them with essential nutrient and gaseous exchange. However, the vasculature has also been shown to provide non-nutritional signals that play key roles in the control of organ growth, morphogenesis and homeostasis. Here, we examine a decade of work on the contribution of vascular paracrine signals to developing tissues, with a focus on pancreatic β-cells. During the early stages of embryonic development, blood vessels are required for pancreas specification. Later, the vasculature constrains pancreas branching, differentiation and growth. During adult life, capillaries provide a vascular niche for the maintenance of β-cell function and survival. We explore the possibility that the vasculature constitutes a dynamic and regionalized signaling system that carries out multiple and changing functions as it coordinately grows with the pancreatic epithelial tree.

  20. Automated segmentation refinement of small lung nodules in CT scans by local shape analysis. (United States)

    Diciotti, Stefano; Lombardo, Simone; Falchini, Massimo; Picozzi, Giulia; Mascalchi, Mario


    One of the most important problems in the segmentation of lung nodules in CT imaging arises from possible attachments occurring between nodules and other lung structures, such as vessels or pleura. In this report, we address the problem of vessels attachments by proposing an automated correction method applied to an initial rough segmentation of the lung nodule. The method is based on a local shape analysis of the initial segmentation making use of 3-D geodesic distance map representations. The correction method has the advantage that it locally refines the nodule segmentation along recognized vessel attachments only, without modifying the nodule boundary elsewhere. The method was tested using a simple initial rough segmentation, obtained by a fixed image thresholding. The validation of the complete segmentation algorithm was carried out on small lung nodules, identified in the ITALUNG screening trial and on small nodules of the lung image database consortium (LIDC) dataset. In fully automated mode, 217/256 (84.8%) lung nodules of ITALUNG and 139/157 (88.5%) individual marks of lung nodules of LIDC were correctly outlined and an excellent reproducibility was also observed. By using an additional interactive mode, based on a controlled manual interaction, 233/256 (91.0%) lung nodules of ITALUNG and 144/157 (91.7%) individual marks of lung nodules of LIDC were overall correctly segmented. The proposed correction method could also be usefully applied to any existent nodule segmentation algorithm for improving the segmentation quality of juxta-vascular nodules.

  1. Managing Vascular Tumors-Open Approaches. (United States)

    Schmalbach, Cecelia E; Gourin, Christine


    The most common vascular tumors encountered by the otolaryngologist are rare chromaffin cell tumors termed paragangliomas. Within the head and neck region, they commonly arise from the carotid body, vagus nerve (glomus vagale), and jugular vein (glomus jugulare). Other vascular head and neck tumors include sinonasal malignancies, because of proximity to or involvement of the pterygoid plexus as well as the rich vascularity of the sinonasal mucosa; juvenile nasopharyngeal angiofibroma, a vascular tumor of male adolescents; unusual vascular tumors such as hemangiopericytoma; and metastatic renal cell cancer, which has a proclivity for an unusually rich blood supply.

  2. PEComa of the lung

    Directory of Open Access Journals (Sweden)

    Vijayabhaskar R


    Full Text Available Perivascular epithelioid cell tumor (PEComa, also called clear cell ′′sugar′′ tumor of the lung, is a rare benign tumor arising from perivascular epithelioid cells (PECs. We report a case of a 15-year-old boy who presented with right lower lobe lesion which turned out to be a clear cell tumor of the lung. An [18F]-fluoro-2-deoxy-D-glucose (FDG - positron emission tomography (PET scan revealed mild FDG uptake in the lung lesion (SUV< 1 with no active uptake elsewhere in the body. We discuss the clinical, radiologic and immunohistochemical features of clear cell ′′sugar′′ tumor of lung and compare them with published literature.

  3. Immunotherapy for lung cancer. (United States)

    Steven, Antonius; Fisher, Scott A; Robinson, Bruce W


    Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

  4. American Lung Association (United States)

    ... Latest News American Lung Association Pledges to Fight Trump Administration Assault on Clean Air and Climate Protections March 28, 2017 In response to President Trump's announcement on climate change, Harold P. Wimmer, National ...

  5. How Lungs Work (United States)

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  6. Protecting Your Lungs (United States)

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  7. Nutrition for Lung Cancer (United States)

    ... seeds removed such as applesauce, canned peaches or bananas Breads, crackers and pasta made with refined white ... Downloadable Resources & Video Library Reports Lung Cancer Fact Sheet Our Researchers & Teams Latest News Sign up for ...

  8. Hydrogen sulfide and vascular relaxation

    Institute of Scientific and Technical Information of China (English)

    SUN Yan; TANG Chao-shu; DU Jun-bao; JIN Hong-fang


    Objective To review the vasorelaxant effects of hydrogen sulfide (H2S) in arterial rings in the cardiovascular system under both physiological and pathophysiological conditions and the possible mechanisms involved.Data sources The data in this review were obtained from Medline and Pubmed sources from 1997 to 2011 using the search terms "hydrogen sulfide" and ""vascular relaxation".Study selection Articles describing the role of hydrogen sulfide in the regulation of vascular activity and its vasorelaxant effects were selected.Results H2S plays an important role in the regulation of cardiovascular tone.The vasomodulatory effects of H2S depend on factors including concentration,species and tissue type.The H2S donor,sodium hydrosulfide (NarS),causes vasorelaxation of rat isolated aortic rings in a dose-dependent manner.This effect was more pronounced than that observed in pulmonary arterial rings.The expression of KATP channel proteins and mRNA in the aortic rings was increased compared with pulmonary artery rings.H2S is involved in the pathogenesis of a variety of cardiovascular diseases.Downregulation of the endogenous H2S pathway is an important factor in the pathogenesis of cardiovascular diseases.The vasorelaxant effects of H2S have been shown to be mediated by activation of KATP channels in vascular smooth muscle cells and via the induction of acidification due to activation of the CI/HCO3 exchanger.It is speculated that the mechanisms underlying the vasoconstrictive function of H2S in the aortic rings involves decreased NO production and inhibition of cAMP accumulation.Conclusion H2S is an important endogenous gasotransmitter in the cardiovascular system and acts as a modulator of vascular tone in the homeostatic regulation of blood pressure.

  9. Screening for lung cancer

    DEFF Research Database (Denmark)

    Infante, Maurizio V; Pedersen, Jesper H


    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...... trials underway in Europe and in the USA. Our purpose is to update the readers on recent progress in medical knowledge in this field....

  10. Interstitial lung disease

    Institute of Scientific and Technical Information of China (English)


    2008429 The predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis/dermatomyositis. WANG Peizhen(王培珍), et al. Dept Rheumatol & Immunol, Changhai Hosp, Milit Med Univ, Shanghai 200433. Chin J Tuberc Respir Dis 2008;31(6):417-420. Objective To analyze the predictive factors and the unfavourable prognostic factors of interstitial lung disease (ILD) in patients with polymyositis

  11. Thoracic Block Technique Associated with Positive End-Expiratory Pressure in Reversing Atelectasis

    Directory of Open Access Journals (Sweden)

    Luciana Carnevalli Pereira


    Full Text Available A preschool four-year-old male patient had been admitted to the Mandaqui Hospital with a diagnosis of lobar pneumonia, pleural effusion, and right lung atelectasis. Treatment consisted of antibiotics and physiotherapy sessions, using a technique described in the literature as Insufflation Technique to Reverse Atelectasis (ITRA, which consists of a thoracic block of healthy lung tissue, leaving only the atelectasis area free, associated with the use of invasive or noninvasive mechanical ventilation with positive airway pressure for reversal of atelectasis. Two physiotherapy sessions were conducted daily. The sessions lasted 20 minutes and were fractionated into four series of five minutes each. Each series bilateral thoracic block was performed for 20 seconds with a pause lasting for the same time. Associated with the thoracic block, a continuous positive airways pressure was used using a facial mask and 7 cm H2O PEEP provided via CPAP. Conclusion. ITRA technique was effective in reversing atelectasis in this patient.

  12. Vascular Endothelium and Hypovolemic Shock. (United States)

    Gulati, Anil


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

  13. Modified Blalock clamp: a single-hand autostatic device for pulmonary vessel occlusion during lung cancer resection


    Petrella, Francesco; Solli, Piergiorgio; Borri, Alessandro; Spaggiari, Lorenzo


    Vascular clamping during lung cancer resection may be difficult in patients with short vessels or large neoplasms preventing adequate and safe exposure. In addition, the physiological vicinity of some vessels to rigid structures like the bronchi may interfere with ideal clamp positioning even in ordinary procedures. We have modified the original Blalock clamp to facilitate the control of pulmonary vessels and physiologically compress the vessel walls, thereby allowing optimal vascular resecti...

  14. Multiple cystic lung disease

    Directory of Open Access Journals (Sweden)

    Flavia Angélica Ferreira Francisco


    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.

  15. Conformal Nets II: Conformal Blocks (United States)

    Bartels, Arthur; Douglas, Christopher L.; Henriques, André


    Conformal nets provide a mathematical formalism for conformal field theory. Associated to a conformal net with finite index, we give a construction of the `bundle of conformal blocks', a representation of the mapping class groupoid of closed topological surfaces into the category of finite-dimensional projective Hilbert spaces. We also construct infinite-dimensional spaces of conformal blocks for topological surfaces with smooth boundary. We prove that the conformal blocks satisfy a factorization formula for gluing surfaces along circles, and an analogous formula for gluing surfaces along intervals. We use this interval factorization property to give a new proof of the modularity of the category of representations of a conformal net.

  16. Azelnidipine inhibits Msx2-dependent osteogenic differentiation and matrix mineralization of vascular smooth muscle cells. (United States)

    Shimizu, Takehisa; Tanaka, Toru; Iso, Tatsuya; Kawai-Kowase, Keiko; Kurabayashi, Masahiko


    Vascular calcification is an active and regulated process that is similar to bone formation. While calcium channel blockers (CCBs) have been shown to improve outcomes in atherosclerotic vascular disease, it remains unknown whether CCBs have an effect on the process of vascular calcification. Here we investigated whether CCBs inhibit osteogenic differentiation and matrix mineralization of vascular smooth muscle cells induced by Msx2, a key factor of vascular calcification. Human aortic smooth muscle cells (HASMCs) were transduced with adenovirus expressing MSX2 and were treated with 3 distinct CCBs. Azelnidipine, a dihydropyridine subclass of CCBs, significantly decreased alkaline phosphatase (ALP) activity of Msx2-overexpressed HASMCs, whereas verapamil and diltiazem had no effect. Furthermore, azelnidipine, but not verapamil and diltiazem, significantly decreased matrix mineralization of Msx2-overexpressing HASMCs. Azelnidipine significantly attenuated the induction of ALP gene expression by Msx2, a key transcription factor in osteogenesis, while it did not reduce enzymatic activity of ALP. Furthermore, azelnidipine inhibited the ability of Msx2 to activate the ALP gene, but had no effect on Notch-induced Msx2 expression. Given that L-type calcium channels are equally blocked by these CCBs, our results suggest that azelnidipine inhibits the Msx2-dependent process of vascular calcification by mechanisms other than inhibition of calcium channel activity.

  17. Molecular features of secondary vascular tissue regeneration after bark girdling in Populus. (United States)

    Zhang, Jing; Gao, Ge; Chen, Jia-Jia; Taylor, Gail; Cui, Ke-Ming; He, Xin-Qiang


    Regeneration is a common strategy for plants to repair damage to their tissue after attacks from other organisms or physical assaults. However, how differentiating cells acquire regenerative competence and rebuild the pattern of new tissues remains largely unknown. Using anatomical observation and microarray analysis, we investigated the morphological process and molecular features of secondary vascular tissue regeneration after bark girdling in trees. After bark girdling, new phloem and cambium regenerate from differentiating xylem cells and rebuild secondary vascular tissue pattern within 1 month. Differentiating xylem cells acquire regenerative competence through epigenetic regulation and cell cycle re-entry. The xylem developmental program was blocked, whereas the phloem or cambium program was activated, resulting in the secondary vascular tissue pattern re-establishment. Phytohormones play important roles in vascular tissue regeneration. We propose a model describing the molecular features of secondary vascular tissue regeneration after bark girdling in trees. It provides information for understanding mechanisms of tissue regeneration and pattern formation of the secondary vascular tissues in plants.

  18. [Sex steroids and vascular risk]. (United States)

    Rozenbaum, H


    The chemical diversity of estrogen and progestogen components of oral contraceptive (OC) products, their use alone or in combination, and the diversity of treatment regimens and doses account for the majority of contradictions in the immense literature on vascular and metabolic side effects of these hormones. OCs are exclusively composed of synthetic hormones. All OCs impose metabolic modifications on the organism and especially on the hepatic parenchyma due to delayed hepatic degradation. Certain factors increase the risk of vascular accidents associated with OC use: metabolic changes affecting coagulation, lipids, glucides, and arterial hypertension, immunologic phenomena, smoking, and obesity. As a whole, OCs affect coagulation by elevating factors 7 and 10, decreasing antithrombin iii (in high doses), and decreasing plasma fibrinolytic activity. synthetic estrogens cause an elevation of HDL cholesterol, a slight elevation of phospholipids, and a dose-dependent elevation of triglycerides and their VLDL fraction. As a group, progestogens tend to decrease the HDL fraction of cholesterol. Norethindrone is incapable of opposing the hypertriglyceridemic action of synthtic estrogens, while norgestrel partially opposes it. Lipid modifications provoked by combined OCs are a function of the nature and dosage of the components. Among hemodynamic modifications, synthetic estrogens cause elevations in renin substrate, plasma renin activity, angiotensin 2 and aldosterone. Synthetic progestogens may have various effects depending on type and dose, but they do not appear sufficient to cause hypertension unless other factors linked to individual predispositions are present. Microdoses of progestogens alone do not affect the renin-angiotensin-aldosterone system. Studies have also been conducted on the effect of OCs on cardiac function and on the vascular walls. Prospective studies suggest a relative risk of 3 for venous thromboembolic accidents among OC users, while

  19. Multimodal imaging of lung cancer and its microenvironment (Conference Presentation) (United States)

    Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.


    Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.

  20. Immune surveillance of the lung by migrating tissue monocytes (United States)

    Rodero, Mathieu P; Poupel, Lucie; Loyher, Pierre-Louis; Hamon, Pauline; Licata, Fabrice; Pessel, Charlotte; Hume, David A; Combadière, Christophe; Boissonnas, Alexandre


    Monocytes are phagocytic effector cells in the blood and precursors of resident and inflammatory tissue macrophages. The aim of the current study was to analyse and compare their contribution to innate immune surveillance of the lung in the steady state with macrophage and dendritic cells (DC). ECFP and EGFP transgenic reporters based upon Csf1r and Cx3cr1 distinguish monocytes from resident mononuclear phagocytes. We used these transgenes to study the migratory properties of monocytes and macrophages by functional imaging on explanted lungs. Migratory monocytes were found to be either patrolling within large vessels of the lung or locating at the interface between lung capillaries and alveoli. This spatial organisation gives to monocytes the property to capture fluorescent particles derived from both vascular and airway routes. We conclude that monocytes participate in steady-state surveillance of the lung, in a way that is complementary to resident macrophages and DC, without differentiating into macrophages. DOI: PMID:26167653

  1. Protective effects of mastic oil from Pistacia lentiscus variation chia against experimental growth of lewis lung carcinoma. (United States)

    Magkouta, Sophia; Stathopoulos, Georgios T; Psallidas, Ioannis; Papapetropoulos, Andreas; Kolisis, Fragiskos N; Roussos, Charis; Loutrari, Heleni


    Mastic oil from Pistacia lentiscus variation chia, a traditionally used dietary flavoring agent with medicinal properties, has been shown to exert in vitro antitumor activities, but no study has addressed in vivo efficacy and mechanisms of action. Presently, we demonstrated that treatment of immunocompetent mice with mastic oil (45 mg/kg body weight, intraperitoneally, 3 times a wk for approximately 3 wk) significantly inhibited tumor growth (56.4% +/- 5.7 maximum reduction in tumor volumes) without toxicity. Analysis of tumors by immunohistochemistry and ELISA indicated that this effect is associated with increased apoptosis, reduced neovascularization, and inhibition of chemokine expression. Likewise mastic oil reduced vascular endothelial growth factor and chemokine release by Lewis lung carcinoma (LLC) cells. Furthermore, mastic oil administration decreased small guanosine triphosphatases (GTPases) Ras, RhoA and nuclear factor-kappa-B-dependent reporter gene expression in vivo and in vitro, indicating a mechanistic link between mastic oil activities and blocking of relevant signaling and transcription pathways. A dose-response comparison with perillyl alcohol and alpha-pinene, two of its components, revealed a higher efficacy of mastic oil, pointing to a beneficial collective interaction among its ingredients. Conclusively, our results provide novel in vivo evidence of mastic oil inhibitory effects on tumor growth and set a rational basis for its future application in cancer prevention.

  2. MarineMineralsProgramBlocks (United States)

    Bureau of Ocean Energy Management, Department of the Interior — This data set contains OCS block outlines and delineated polygons in ESRI ArcGIS shape file format for the BOEM Gulf of Mexico Region that contain sediment resources...

  3. Hawaii Census 2000 Block Groups (United States)

    U.S. Environmental Protection Agency — This data layer represents Census 2000 demographic data derived from the PL94-171 redistricting files and SF3. Census geographic entities include blocks, blockgroups...

  4. Left bundle-branch block

    DEFF Research Database (Denmark)

    Risum, Niels; Strauss, David; Sogaard, Peter;


    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...

  5. Multi-block and path modelling procedures

    DEFF Research Database (Denmark)

    Høskuldsson, Agnar


    The author has developed a unified theory of path and multi-block modelling of data. The data blocks are arranged in a directional path. Each data block can lead to one or more data blocks. It is assumed that there is given a collection of input data blocks. Each of them is supposed to describe one...

  6. Vascular Stem Cells in Vascular Remodeling and Diseases

    Directory of Open Access Journals (Sweden)

    Anna Meiliana


    Full Text Available BACKGROUND: Blood vessels are a source of stem and progenitor cells, which likely contribute to a variety of vascular processes and diseases. Emerging concepts in this field could influence therapeutic approaches to diseases of blood vessels such as atherosclerosis. CONTENT: Vascular Stem Cells (VSCs field is only beginning to emerge, and thus, many issues regarding VSCs’s identity and function remain poorly understood. In fact, even after decades of intensive research, Mesenchymal Stem Cells (MSC, which is suggested to be VSCs, is still having many outstanding issues of its own. And, on top of this, likewise decades-long intensive pericyte research has not been able resolve the identity issue. While favors Adventitial Progenitor Cells (APCs over pericytes as the likely VSC candidate, it should be pointed out that currently the opposite view (i.e., pericytes as VSCs is more prevalent, and many excellent reviews, including a recent one, have discussed this issue extensively. SUMMARY: It has been postulated that, within the vasculature, APCs could differentiate into pericytes (CD34- CD31- CD140b+ SMA-, endothelial cells (CD34+ CD31+ CD140b- SMA-, and smooth muscle cells (SMCs (CD34- CD31- CD140b- SMA+; and during tissue expansion or repair, APCs could also differentiate into tissue-specific cell types (e.g., muscle and fat Thus, in vitro, APCs fulfill all criteria for being VSCs. Meanwhile, in vivo evidence is still limited and will require further investigation. KEYWORDS: vascular stem cells, VSC, mesenchymal stem cells, MSC, endothelial progenitor cells, EPC, adventitial progenitor cells, APC.

  7. Advances in target therapy in lung cancer

    Directory of Open Access Journals (Sweden)

    Jean-Paul Sculier


    Full Text Available Herein, we have reviewed and analysed recent literature, published in 2013 and early 2014, in the context of pre-existing data. Considered target therapies were tyrosine kinase inhibitors of active epidermal growth factor receptor mutations (e.g. erlotinib, gefinitib and afatinib, anaplastic lymphoma kinase rearrangements (e.g. crizotinib or angiogenesis (drugs under development, or monoclonal antibodies against vascular endothelial growth factor (e.g. bevacizumab or epidermal growth factor receptors (e.g. cetuximab. The therapeutic project has to consider tyrosine kinase inhibitors in the case of nonsmall cell lung cancer with active epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangement. However, these drugs should not be used in the absence of the targeted genetic abnormalities.

  8. Progression and metastasis of lung cancer. (United States)

    Popper, Helmut H


    Metastasis in lung cancer is a multifaceted process. In this review, we will dissect the process in several isolated steps such as angiogenesis, hypoxia, circulation, and establishment of a metastatic focus. In reality, several of these processes overlap and occur even simultaneously, but such a presentation would be unreadable. Metastasis requires cell migration toward higher oxygen tension, which is based on changing the structure of the cell (epithelial-mesenchymal transition), orientation within the stroma and stroma interaction, and communication with the immune system to avoid attack. Once in the blood stream, cells have to survive trapping by the coagulation system, to survive shear stress in small blood vessels, and to find the right location for extravasation. Once outside in the metastatic locus, tumor cells have to learn the communication with the "foreign" stroma cells to establish vascular supply and again express molecules, which induce immune tolerance.

  9. Bosutinib Therapy Ameliorates Lung Inflammation and Fibrosis in Experimental Silicosis (United States)

    Carneiro, Priscila J.; Clevelario, Amanda L.; Padilha, Gisele A.; Silva, Johnatas D.; Kitoko, Jamil Z.; Olsen, Priscilla C.; Capelozzi, Vera L.; Rocco, Patricia R. M.; Cruz, Fernanda F.


    Silicosis is an occupational lung disease for which no effective therapy exists. We hypothesized that bosutinib, a tyrosine kinase inhibitor, might ameliorate inflammatory responses, attenuate pulmonary fibrosis, and thus improve lung function in experimental silicosis. For this purpose, we investigated the potential efficacy of bosutinib in the treatment of experimental silicosis induced in C57BL/6 mice by intratracheal administration of silica particles. After 15 days, once disease was established, animals were randomly assigned to receive DMSO or bosutinib (1 mg/kg/dose in 0.1 mL 1% DMSO) by oral gavage, twice daily for 14 days. On day 30, lung mechanics and morphometry, total and differential cell count in alveolar septa and granuloma, levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, transforming growth factor (TGF)-β, and vascular endothelial growth factor in lung homogenate, M1 and M2 macrophages, total leukocytes, and T cells in BALF, lymph nodes, and thymus, and collagen fiber content in alveolar septa and granuloma were analyzed. In a separate in vitro experiment, RAW264.7 macrophages were exposed to silica particles in the presence or absence of bosutinib. After 24 h, gene expressions of arginase-1, IL-10, IL-12, inducible nitric oxide synthase (iNOS), metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, and caspase-3 were evaluated. In vivo, in silicotic animals, bosutinib, compared to DMSO, decreased: (1) fraction area of collapsed alveoli, (2) size and number of granulomas, and mononuclear cell granuloma infiltration; (3) IL-1β, TNF-α, IFN-γ, and TGF-β levels in lung homogenates, (4) collagen fiber content in lung parenchyma, and (5) viscoelastic pressure and static lung elastance. Bosutinib also reduced M1 cell counts while increasing M2 macrophage population in both lung parenchyma and granulomas. Total leukocyte, regulatory T, CD4+, and CD8+ cell counts in the lung-draining lymph


    Institute of Scientific and Technical Information of China (English)

    Guojun Liu


    Nanostructure fabrication from block copolymers in my group normally involves polymer design, synthesis, selfassembly, selective domain crosslinking, and sometimes selective domain removal. Preparation of thin films with nanochannels was used to illustrate the strategy we took. In this particular case, a linear triblock copolymer polyisopreneblock-poly(2-cinnamoylethyl methacrylate)-block-poly(t-butyl acrylate), PI-b-PCEMA-b-PtBA, was used. Films, 25 to50μm thick, were prepared from casting on glass slides a toluene solution of PI-b-PCEMA-b-PtBA and PtBA homopolymer,hPtBA, where hPtBA is shorter than the PtBA block. At the hPtBA mass fraction of 20% relative to the triblock or the total PtBA (hPtBA and PtBA block) volume fraction of 0.44, hPtBA and PtBA formed a seemingly continuous phase in the matrix of PCEMA and PI. Such a block segregation pattern was locked in by photocrosslinking the PCEMA domain. Nanochannels were formed by extracting out hPtBA with solvent. Alternatively, larger channels were obtained from extracting out hPtBA and hydrolyzing the t-butyl groups of the PtBA block. Such membranes were not liquid permeable but had gas permeability constants ~6 orders of magnitude higher than that of low-density polyethylene films.

  11. The aging lung

    Directory of Open Access Journals (Sweden)

    Lowery EM


    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

  12. Interventional Analgesic Management of Lung Cancer Pain (United States)

    Hochberg, Uri; Elgueta, Maria Francisca; Perez, Jordi


    Lung cancer is one of the four most prevalent cancers worldwide. Comprehensive patient care includes not only adherence to clinical guidelines to control and when possible cure the disease but also appropriate symptom control. Pain is one of the most prevalent symptoms in patients diagnosed with lung cancer; it can arise from local invasion of chest structures or metastatic disease invading bones, nerves, or other anatomical structures potentially painful. Pain can also be a consequence of therapeutic approaches like surgery, chemotherapy, or radiotherapy. Conventional medical management of cancer pain includes prescription of opioids and coadjuvants at doses sufficient to control the symptoms without causing severe drug effects. When an adequate pharmacological medical management fails to provide satisfactory analgesia or when it causes limiting side effects, interventional cancer pain techniques may be considered. Interventional pain management is devoted to the use of invasive techniques such as joint injections, nerve blocks and/or neurolysis, neuromodulation, and cement augmentation techniques to provide diagnosis and treatment of pain syndromes resistant to conventional medical management. Advantages of interventional approaches include better analgesic outcomes without experiencing drug-related side effects and potential for opioid reduction thus avoiding central side effects. This review will describe various pain syndromes frequently described in lung cancer patients and those interventional techniques potentially indicated for those cases. PMID:28261561

  13. Hypersensitivity of lung vessels to catecholamines in systemic hypertension. (United States)

    Guazzi, M D; Alimento, M; Fiorentini, C; Pepi, M; Polese, A


    Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper-reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over-reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure.

  14. Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia (United States)

    Nogueira-Silva, Cristina; Carvalho-Dias, Emanuel; Piairo, Paulina; Nunes, Susana; Baptista, Maria J; Moura, Rute S; Correia-Pinto, Jorge


    Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT1) and type 2 (AT2) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT2-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT2 receptor is presented as a putative antenatal therapy for CDH. PMID:22113494

  15. Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Tamás Dolinay

    Full Text Available BACKGROUND: Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/mitogen activated protein kinase kinase-3 and c-Jun-NH(2-terminal kinase-1 in ventilator-induced lung injury and investigate novel independent mechanisms contributing to lung injury during mechanical ventilation. METHODOLOGY AND PRINCIPLE FINDINGS: C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 (mkk-3(-/- or c-Jun-NH(2-terminal kinase-1 (jnk1(-/- were ventilated, and lung injury parameters were assessed. We demonstrate that mkk3(-/- or jnk1(-/- mice displayed significantly reduced inflammatory lung injury and apoptosis relative to wild-type mice. Since jnk1(-/- mice were highly resistant to ventilator-induced lung injury, we performed comprehensive gene expression profiling of ventilated wild-type or jnk1(-/- mice to identify novel candidate genes which may play critical roles in the pathogenesis of ventilator-induced lung injury. Microarray analysis revealed many novel genes differentially expressed by ventilation including matrix metalloproteinase-8 (MMP8 and GADD45alpha. Functional characterization of MMP8 revealed that mmp8(-/- mice were sensitized to ventilator-induced lung injury with increased lung vascular permeability. CONCLUSIONS: We demonstrate that mitogen-activated protein kinase pathways mediate inflammatory lung injury during ventilator-induced lung injury. C-Jun-NH(2-terminal kinase was also involved in alveolo-capillary leakage and edema formation, whereas MMP8 inhibited alveolo-capillary protein leakage.

  16. Traversing and labeling interconnected vascular tree structures from 3D medical images (United States)

    O'Dell, Walter G.; Govindarajan, Sindhuja Tirumalai; Salgia, Ankit; Hegde, Satyanarayan; Prabhakaran, Sreekala; Finol, Ender A.; White, R. James


    Purpose: Detailed characterization of pulmonary vascular anatomy has important applications for the diagnosis and management of a variety of vascular diseases. Prior efforts have emphasized using vessel segmentation to gather information on the number or branches, number of bifurcations, and branch length and volume, but accurate traversal of the vessel tree to identify and repair erroneous interconnections between adjacent branches and neighboring tree structures has not been carefully considered. In this study, we endeavor to develop and implement a successful approach to distinguishing and characterizing individual vascular trees from among a complex intermingling of trees. Methods: We developed strategies and parameters in which the algorithm identifies and repairs false branch inter-tree and intra-tree connections to traverse complicated vessel trees. A series of two-dimensional (2D) virtual datasets with a variety of interconnections were constructed for development, testing, and validation. To demonstrate the approach, a series of real 3D computed tomography (CT) lung datasets were obtained, including that of an anthropomorphic chest phantom; an adult human chest CT; a pediatric patient chest CT; and a micro-CT of an excised rat lung preparation. Results: Our method was correct in all 2D virtual test datasets. For each real 3D CT dataset, the resulting simulated vessel tree structures faithfully depicted the vessel tree structures that were originally extracted from the corresponding lung CT scans. Conclusion: We have developed a comprehensive strategy for traversing and labeling interconnected vascular trees and successfully implemented its application to pulmonary vessels observed using 3D CT images of the chest.

  17. Unilateral hyperlucency of the lung: a systematic approach to accurate radiographic interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Hyung Jun; Oh, Yu Whan; Choi, Eun Jung; Seo, Bo Kyung; Cho, Kyu Ran; Kang, Eun Young; Kim, Jung Hyuk [Korea University College of Medicine, Seoul (Korea, Republic of)


    The radiographic appearance of a unilateral hyperlucent lung is related to various conditions, the accurate radiographic interpretation of which requires a structured approach as well as an awareness of the spectrum of these entities. Firstly, it is important to determine whether a hyperlucent hemithorax is associated with artifacts resulting from rotation of the patient, grid cutoff, or the heel effect. The second step is to determine whether or not a hyperlucent lung is abnormal. Lung that is in fact normal may appear hyperlucent because of diffusely increased opacity of the opposite hemithorax. Thirdly, thoracic wall and soft tissue abnormalities such as mastectomy of Poland syndrome may cause hyperinflation. Lastly, abnormalities of lung parenchyma may result in hyperlucency. Lung abnormalities and be divided into two groups: a) obstructive or compensatory hyperinflation; and b) reduced vascular perfusion of the lung due to congenital or acquired vascular abnormalities. In this article, we describe and illustrate the imaging spectrum of these causes and outline a structured approach to accurate radiographic interpretation.

  18. Skin delivery by block copolymer nanoparticles (block copolymer micelles). (United States)

    Laredj-Bourezg, Faiza; Bolzinger, Marie-Alexandrine; Pelletier, Jocelyne; Valour, Jean-Pierre; Rovère, Marie-Rose; Smatti, Batoule; Chevalier, Yves


    Block copolymer nanoparticles often referred to as "block copolymer micelles" have been assessed as carriers for skin delivery of hydrophobic drugs. Such carriers are based on organic biocompatible and biodegradable materials loaded with hydrophobic drugs: poly(lactide)-block-poly(ethylene glycol) copolymer (PLA-b-PEG) nanoparticles that have a solid hydrophobic core made of glassy poly(d,l-lactide), and poly(caprolactone)-block-poly(ethylene glycol) copolymer (PCL-b-PEG) nanoparticles having a liquid core of polycaprolactone. In vitro skin absorption of all-trans retinol showed a large accumulation of retinol in stratum corneum from both block copolymer nanoparticles, higher by a factor 20 than Polysorbate 80 surfactant micelles and by a factor 80 than oil solution. Additionally, skin absorption from PLA-b-PEG nanoparticles was higher by one order of magnitude than PCL-b-PEG, although their sizes (65nm) and external surface (water-swollen PEG layer) were identical as revealed by detailed structural characterizations. Fluorescence microscopy of histological skin sections provided a non-destructive picture of the storage of Nile Red inside stratum corneum, epidermis and dermis. Though particle cores had a different physical states (solid or liquid as measured by (1)H NMR), the ability of nanoparticles for solubilization of the drug assessed from their Hildebrand solubility parameters appeared the parameter of best relevance regarding skin absorption.


    Sepehr, Reyhaneh; Audi, Said H; Maleki, Sepideh; Staniszewski, Kevin; Eis, Annie L; Konduri, Girija G; Ranji, Mahsa


    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

  20. Effects of vascular targeting photodynamic therapy on lymphatic tumor metastasis (United States)

    Fateye, B.; He, C.; Chen, B.


    Vascular targeting photodynamic therapy (vPDT) is currently in clinical trial for prostate cancer (PCa) treatment. In order to study the effect of vPDT on tumor metastasis, GFP-PC3 or PC-3 xenografts were treated with verteporfin (BPD) PDT. Vascular function was assessed by ultrasound imaging; lymph node and lung metastasis were assessed by fluorescence imaging. vPDT significantly reduced tumor blood flow within 30minutes to 2 hours of treatment. Sub-curative treatment resulted in re-perfusion within 2 weeks of treatment and increased lymph node metastasis. With curative doses, no metastasis was observed. In order to identify cellular or matrix factors and cytokines implicated, conditioned medium from BPD PDTtreated endothelial cells was incubated with PC3 cells in vitro. Tumor cell proliferation and migration was assessed. By immunoblotting, we evaluated the change in mediators of intracellular signaling or that may determine changes in tumor phenotype. Low sub-curative dose (200ng/ml BPD) of endothelial cells was associated with ~15% greater migration in PC3 cells when compared with control. This dose was also associated with sustained activation of Akt at Ser 473, an upstream effector in the Akt/ mTOR pathway that has been correlated with Gleason scores in PCa and with survival and metastasis in vitro and in vivo. In conclusion, the study implicates efficacy of PDT of endothelial cells as an important determinant of its consequences on adjacent tumor proliferation and metastasis.

  1. Immunotherapy for Lung Cancers

    Directory of Open Access Journals (Sweden)

    Ming-Yi Ho


    Full Text Available Lung cancer is the leading cause of cancer-related deaths worldwide. Although treatment methods in surgery, irradiation, and chemotherapy have improved, prognosis remains unsatisfactory and developing new therapeutic strategies is still an urgent demand. Immunotherapy is a novel therapeutic approach wherein activated immune cells can specifically kill tumor cells by recognition of tumor-associated antigens without damage to normal cells. Several lung cancer vaccines have demonstrated prolonged survival time in phase II and phase III trials, and several clinical trials are under investigation. However, many clinical trials involving cancer vaccination with defined tumor antigens work in only a small number of patients. Cancer immunotherapy is not completely effective in eradicating tumor cells because tumor cells escape from host immune scrutiny. Understanding of the mechanism of immune evasion regulated by tumor cells is required for the development of more effective immunotherapeutic approaches against lung cancer. This paper discusses the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer.

  2. Lung Cancer Statistics. (United States)

    Torre, Lindsey A; Siegel, Rebecca L; Jemal, Ahmedin


    Lung cancer is the leading cause of cancer death among both men and women in the United States. It is also the leading cause of cancer death among men and the second leading cause of cancer death among women worldwide. Lung cancer rates and trends vary substantially by sex, age, race/ethnicity, socioeconomic status, and geography because of differences in historical smoking patterns. Lung cancer mortality rates in the United States are highest among males, blacks, people of lower socioeconomic status, and in the mid-South (e.g., Kentucky, Mississippi, Arkansas, and Tennessee). Globally, rates are highest in countries where smoking uptake began earliest, such as those in North America and Europe. Although rates are now decreasing in most of these countries (e.g., United States, United Kingdom, Australia), especially in men, they are increasing in countries where smoking uptake occurred later. Low- and middle-income countries now account for more than 50% of lung cancer deaths each year. This chapter reviews lung cancer incidence and mortality patterns in the United States and globally.

  3. Lung cancer screening: Update

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)


    Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

  4. Inhalational Lung Disease

    Directory of Open Access Journals (Sweden)

    S Kowsarian


    Full Text Available Inhalational lung diseases are among the most important occupational diseases. Pneumoconiosis refers to a group of lung diseases result from inhalation of usually inorganic dusts such as silicon dioxide, asbestos, coal, etc., and their deposition in the lungs. The resultant pulmonary disorders depend on the susceptibility of lungs; size, concentration, solubility and fibrogenic properties of the inhaled particles; and duration of exposure. Radiographic manifestations of pneumoconiosis become apparent several years after exposure to the particles. However, for certain types of dusts, e.g., silicone dioxide crystal and beryllium, heavy exposure within a short period can cause an acute disease. Pulmonary involvement in asbestosis is usually in the lower lobes. On the contrary, in silicosis and coal worker pneumoconiosis, the upper lobes are involved predominantly. For imaging evaluation of pneumoconiosis, high-resolution computed tomography (CT is superior to conventional chest x-ray. Magnetic resonance imaging (MRI and positron emission tomography (PET scan are helpful in those with suspected tumoral lesions. In this essay, we reviewed the imaging aspects of inhalational lung disease.

  5. Vascular dementia: Facts and controversies

    Directory of Open Access Journals (Sweden)

    Pavlović Aleksandra


    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

  6. VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung. (United States)

    Healy, A M; Morgenthau, L; Zhu, X; Farber, H W; Cardoso, W V


    We used whole lung cultures as a model to study blood vessel formation in vitro and to examine the role that epithelial-mesenchymal interactions play during embryonic pulmonary vascular development. Mouse lungs were isolated at embryonic day 11.5 (E11.5) and cultured for up to 4 days prior to blood vessel analysis. Platelet endothelial cell adhesion molecule-1 (PECAM/CD31) and thrombomodulin (TM/CD141) immunolocalization demonstrate that vascular development occurs in lung cultures. The vascular structures identified in lung cultures first appear as a loosely associated plexus of capillary-like structures that with time surround the airways. To investigate the potential role of vascular endothelial cell growth factor (VEGF) during pulmonary neovascularization, we immunolocalized VEGF in embryonic lungs. Our data demonstrate that VEGF is uniformly present in the airway epithelium and the subepithelial matrix of E11.5 lungs. At later time points, E13.5 and E15.5, VEGF is no longer detected in the proximal airways, but is restricted to the branching tips of airways in the distal lung. RT-PCR analysis reveals that VEGF(164) is the predominant isoform expressed in lung cultures. Grafting heparin-bound VEGF(164) beads onto lung explants locally stimulates a marked neovascular response within 48 hr in culture. Semi-quantitative RT-PCR reveals an 18% increase in PECAM mRNA in VEGF(164)-treated whole lung cultures as compared with untreated cultures. The restricted temporal and spatial expression of VEGF suggests that matrix-associated VEGF links airway branching with blood vessel formation by stimulating neovascularization at the leading edge of branching airways.

  7. Lipoxin A4 inhibits immune cell binding to salivary epithelium and vascular endothelium. (United States)

    Chinthamani, Sreedevi; Odusanwo, Olutayo; Mondal, Nandini; Nelson, Joel; Neelamegham, Sriram; Baker, Olga J


    Lipoxins are formed by leukocytes during cell-cell interactions with epithelial or endothelial cells. Native lipoxin A(4) (LXA(4)) binds to the G protein-coupled lipoxin receptors formyl peptide receptor 2 (FPR2)/ALX and CysLT1. Furthermore, LXA(4) inhibits recruitment of neutrophils, by attenuating chemotaxis, adhesion, and transmigration across vascular endothelial cells. LXA(4) thus appears to serve as an endogenous "stop signal" for immune cell-mediated tissue injury (Serhan CN; Annu Rev Immunol 25: 101-137, 2007). The role of LXA(4) has not been addressed in salivary epithelium, and little is known about its effects on vascular endothelium. Here, we determined that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) receptor activation in vascular endothelium and salivary epithelium upregulated the expression of adhesion molecules that facilitates the binding of immune cells. We hypothesize that the activation of the ALX/FPR2 and/or CysLT1 receptors by LXA(4) decreases this cytokine-mediated upregulation of cell adhesion molecules that enhance lymphocyte binding to both the vascular endothelium and salivary epithelium. In agreement with this hypothesis, we observed that nanomolar concentrations of LXA(4) blocked IL-1β- and TNF-α-mediated upregulation of E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). Binding of Jurkat cells to stimulated HUVECs was abrogated by LXA(4). Furthermore, LXA(4) preincubation with human submandibular gland cell line (HSG) also blocked TNF-α-mediated upregulation of vascular cell adhesion molecule-1 (VCAM-1) in these cells, and it reduced lymphocyte adhesion. These findings suggest that ALX/FPR2 and/or CysLT1 receptor activation in endothelial and epithelial cells blocks cytokine-induced adhesion molecule expression and consequent binding of lymphocytes, a critical event in the pathogenesis of Sjögren's syndrome (SS).

  8. [Vascular compression of the duodenum]. (United States)

    Acosta, B; Guachalla, G; Martínez, C; Felce, S; Ledezma, G


    The acute vascular compression of the duodenum is a well-recognized clinical entity, characterized by recurrent vomiting, abdominal distention, weight loss, post prandial distress. The cause of compression is considered to be effect produced as a result of the angle formed by the superior mesenteric vessels and sometimes by one of its first two branches, and vertebrae and paravertebral muscles, when the angle between superior mesenteric vessels and the aorta it's lower than 18 degrees we can saw this syndrome. The duodenojejunostomy is the best treatment, as well as in our patient.

  9. Vascular comorbidities in multiple sclerosis

    DEFF Research Database (Denmark)

    Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils


    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...... 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...

  10. Optimal Backward Perturbation Analysis for the Block Skew Circulant Linear Systems with Skew Circulant Blocks

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang


    Full Text Available We first give the block style spectral decomposition of arbitrary block skew circulant matrix with skew circulant blocks. Secondly, we obtain the singular value of block skew circulant matrix with skew circulant blocks as well. Finally, based on the block style spectral decomposition, we deal with the optimal backward perturbation analysis for the block skew circulant linear system with skew circulant blocks.

  11. Vascular endothelial growth factor enhances macrophage clearance of apoptotic cells (United States)

    Dalal, Samay; Horstmann, Sarah A.; Richens, Tiffany R.; Tanaka, Takeshi; Doe, Jenna M.; Boe, Darren M.; Voelkel, Norbert F.; Taraseviciene-Stewart, Laimute; Janssen, William J.; Lee, Chun G.; Elias, Jack A.; Bratton, Donna; Tuder, Rubin M.; Henson, Peter M.; Vandivier, R. William


    Efficient clearance of apoptotic cells from the lung by alveolar macrophages is important for the maintenance of tissue structure and function. Lung tissue from humans with emphysema contains increased numbers of apoptotic cells and decreased levels of vascular endothelial growth factor (VEGF). Mice treated with VEGF receptor inhibitors have increased numbers of apoptotic cells and develop emphysema. We hypothesized that VEGF regulates apoptotic cell clearance by alveolar macrophages (AM) via its interaction with VEGF receptor 1 (VEGF R1). Our data show that the uptake of apoptotic cells by murine AMs and human monocyte-derived macrophages is inhibited by depletion of VEGF and that VEGF activates Rac1. Antibody blockade or pharmacological inhibition of VEGF R1 activity also decreased apoptotic cell uptake ex vivo. Conversely, overexpression of VEGF significantly enhanced apoptotic cell uptake by AMs in vivo. These results indicate that VEGF serves a positive regulatory role via its interaction with VEGF R1 to activate Rac1 and enhance AM apoptotic cell clearance. PMID:22307908

  12. Lung cancer - non-small cell (United States)

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

  13. Aerosolized 3-bromopyruvate inhibits lung tumorigenesis without causing liver toxicity. (United States)

    Zhang, Qi; Pan, Jing; North, Paula E; Yang, Shoua; Lubet, Ronald A; Wang, Yian; You, Ming


    3-Bromopyruvate, an alkylating agent and a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. However, the chemopreventive effect of 3-bromopyruvate in lung tumorigenesis has not been tested. In this study, we investigated the chemopreventive activity of 3-bromopyruvate in a mouse lung tumor model. Benzo(a)pyrene was used to induce lung tumors, and 3-bromopyruvate was administered by oral gavage to female A/J mice. We found that 3-bromopyruvate significantly decreased tumor multiplicity and tumor load by 58% and 83%, respectively, at a dose of 20 mg/kg body weight by gavage. Due to the known liver toxicity of 3-bromopyruvate in animal models given large doses of 3-bromopyruvate, confirmed in this study, we decided to test the chemopreventive activity of aerosolized 3-bromopyruvate in the same lung tumor model. As expected, aerosolized 3-bromopyruvate similarly significantly decreased tumor multiplicity and tumor load by 49% and 80%, respectively, at a dose of 10 mg/mL by inhalation. Interestingly, the efficacy of aerosolized 3-bromopyruvate did not accompany any liver toxicity indicating that it is a safer route of administering this compound. Treatment with 3-bromopyruvate increased immunohistochemical staining for cleaved caspase-3, suggesting that the lung tumor inhibitory effects of 3-bromopyruvate were through induction of apoptosis. 3-Bromopyruvate also dissociated hexokinase II from mitochondria, reduced hexokinase activity, and blocked energy metabolism in cancer cells, finally triggered cancer cell death and induced apoptosis through caspase-3, and PARP in human lung cancer cell line. The ability of 3-bromopyruvate to inhibit mouse lung tumorigenesis, in part through induction of apoptosis, merits further investigation of this compound as a chemopreventive agent for human lung cancer.

  14. MicroRNA-181b regulates NF-κB-mediated vascular inflammation. (United States)

    Sun, Xinghui; Icli, Basak; Wara, Akm Khyrul; Belkin, Nathan; He, Shaolin; Kobzik, Lester; Hunninghake, Gary M; Vera, Miguel Pinilla; Blackwell, Timothy S; Baron, Rebecca M; Feinberg, Mark W


    EC activation and dysfunction have been linked to a variety of vascular inflammatory disease states. The function of microRNAs (miRNAs) in vascular EC activation and inflammation remains poorly understood. Herein, we report that microRNA-181b (miR-181b) serves as a potent regulator of downstream NF-κB signaling in the vascular endothelium by targeting importin-α3, a protein that is required for nuclear translocation of NF-κB. Overexpression of miR-181b inhibited importin-α3 expression and an enriched set of NF-κB-responsive genes such as adhesion molecules VCAM-1 and E-selectin in ECs in vitro and in vivo. In addition, treatment of mice with proinflammatory stimuli reduced miR-181b expression. Rescue of miR-181b levels by systemic administration of miR-181b "mimics" reduced downstream NF-κB signaling and leukocyte influx in the vascular endothelium and decreased lung injury and mortality in endotoxemic mice. In contrast, miR-181b inhibition exacerbated endotoxin-induced NF-κB activity, leukocyte influx, and lung injury. Finally, we observed that critically ill patients with sepsis had reduced levels of miR-181b compared with control intensive care unit (ICU) subjects. Collectively, these findings demonstrate that miR-181b regulates NF-κB-mediated EC activation and vascular inflammation in response to proinflammatory stimuli and that rescue of miR-181b expression could provide a new target for antiinflammatory therapy and critical illness.

  15. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine


    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  16. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan;


    Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage......, 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...

  17. Quantifying single microvessel permeability in isolated blood-perfused rat lung preparation. (United States)

    Kandasamy, Kathirvel; Parthasarathi, Kaushik


    The isolated blood-perfused lung preparation is widely used to visualize and define signaling in single microvessels. By coupling this preparation with real time imaging, it becomes feasible to determine permeability changes in individual pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse them with autologous blood. Then, we outline steps to infuse fluorophores or agents via a microcatheter into a small lung region. Using these procedures described, we determined permeability increases in rat lung microvessels in response to infusions of bacterial lipopolysaccharide. The data revealed that lipopolysaccharide increased fluid leak across both venular and capillary microvessel segments. Thus, this method makes it possible to compare permeability responses among vascular segments and thus, define any heterogeneity in the response. While commonly used methods to define lung permeability require postprocessing of lung tissue samples, the use of real time imaging obviates this requirement as evident from the present method. Thus, the isolated lung preparation combined with real time imaging offers several advantages over traditional methods to determine lung microvascular permeability, yet is a straightforward method to develop and implement.

  18. A Peptide to Reduce Pulmonary Edema in a Rat Model of Lung Transplantation (United States)

    Finsterwalder, Richard; Friedl, Heinz P.; Rauscher, Sabine; Gröger, Marion; Kocher, Alfred; Wagner, Christine; Wagner, Stephan N.; Fischer, Gottfried; Schultz, Marcus J.; Wiedemann, Dominik; Petzelbauer, Peter


    Background Despite significant advances in organ preservation, surgical techniques and perioperative care, primary graft dysfunction is a serious medical problem in transplantation medicine in general and a specific problem in patients undergoing lung transplantation. As a result, patients develop lung edema, causing reduced tissue oxygenation capacity, reduced lung compliance and increased requirements for mechanical ventilatory support. Yet, there is no effective strategy available to protect the grafted organ from stress reactions induced by ischemia/reperfusion and by the surgical procedure itself. Methods We assessed the effect of a cingulin-derived peptide, XIB13 or a random peptide in an established rat model of allogeneic lung transplantation. Donor lungs and recipients received therapeutic peptide at the time of transplantation and outcome was analyzed 100min and 28 days post grafting. Results XIB13 improved blood oxygenation and reduced vascular leak 100min post grafting. Even after 28 days, lung edema was significantly reduced by XIB13 and lungs had reduced fibrotic or necrotic zones. Moreover, the induction of an allogeneic T cell response was delayed indicating a reduced antigen exchange between the donor and the host. Conclusions In summary, we provide a new tool to strengthen endothelial barrier function thereby improving outcomes in lung transplantation. PMID:26536466

  19. A Peptide to Reduce Pulmonary Edema in a Rat Model of Lung Transplantation.

    Directory of Open Access Journals (Sweden)

    Klaudia Schossleitner

    Full Text Available Despite significant advances in organ preservation, surgical techniques and perioperative care, primary graft dysfunction is a serious medical problem in transplantation medicine in general and a specific problem in patients undergoing lung transplantation. As a result, patients develop lung edema, causing reduced tissue oxygenation capacity, reduced lung compliance and increased requirements for mechanical ventilatory support. Yet, there is no effective strategy available to protect the grafted organ from stress reactions induced by ischemia/reperfusion and by the surgical procedure itself.We assessed the effect of a cingulin-derived peptide, XIB13 or a random peptide in an established rat model of allogeneic lung transplantation. Donor lungs and recipients received therapeutic peptide at the time of transplantation and outcome was analyzed 100min and 28 days post grafting.XIB13 improved blood oxygenation and reduced vascular leak 100min post grafting. Even after 28 days, lung edema was significantly reduced by XIB13 and lungs had reduced fibrotic or necrotic zones. Moreover, the induction of an allogeneic T cell response was delayed indicating a reduced antigen exchange between the donor and the host.In summary, we provide a new tool to strengthen endothelial barrier function thereby improving outcomes in lung transplantation.

  20. Extraordinary Vessels Needling for Vascular Dementia

    Institute of Scientific and Technical Information of China (English)

    YU Jin; LAI Xin-sheng; HUANG Qiu-tang; XIAO Yuan-chun


    Purpose To observe the clinical efficacy of extraordinary vessels needling in treating vascular dementia. Method 39 cases vascular dementia were treated by acupoints selected from the eight extraordinary meridians and the time needling techniques such as eight methods of spiritual turtle, in accordance with time period and pattern identifition. Results 2 cases were cured, 30 cases improved and 7 cases failed; the total effective rate was 82.1%. Conclusion Extraordinary vessels needling has positive effects in treating vascular dementia.

  1. The importance of phrenic nerve preservation and its effect on long-term postoperative lung function after pneumonectomy

    DEFF Research Database (Denmark)

    Kocher, Gregor J; Lysgaard, Jannie; Blichfeldt-Eckhardt, Morten Rune


    , decided to investigate the effect of temporary ipsilateral cervical phrenic nerve block on dynamic lung volumes in mid- to long-term pneumonectomy patients. METHODS: We investigated 14 patients after a median of 9 years post pneumonectomy (range: 1-15 years). Lung function testing (spirometry......) and fluoroscopic and/or sonographic assessment of diaphragmatic motion on the pneumonectomy side were performed before and after ultrasonographic-guided ipsilateral cervical phrenic nerve block by infiltration with lidocaine. RESULTS: Ipsilateral phrenic nerve block was successfully achieved in 12 patients (86......%). In the remaining 2 patients, diaphragmatic motion was already paradoxical before the nerve block. We found no significant difference on dynamic lung function values (FEV1 'before' 1.39 ± 0.44 vs FEV1 'after' 1.38 ± 0.40; P = 0.81). CONCLUSIONS: Induction of a temporary diaphragmatic palsy did not significantly...

  2. Sac-0601 prevents retinal vascular leakage in a mouse model of diabetic retinopathy. (United States)

    Maharjan, Sony; Lee, Sujin; Agrawal, Vijayendra; Choi, Hyun-Jung; Maeng, Yong-Sun; Kim, Kyeojin; Kim, Nam-Jung; Suh, Young-Ger; Kwon, Young-Guen


    Endothelium integrity is important for the normal functioning of vessels, the disruption of which can lead to disease. The blood-retinal barrier required for normal retinal function is compromised in diabetic retinopathy, causing retinal vascular leakage. Previously, we demonstrated the ability of Sac-0601[((2R,3S)-3-acetoxy-6-((3S,10R,13R,17R)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yloxy)-3,6-dihydro-2H-pyran-2-yl)methyl acetate], a pseudo-sugar derivative of cholesterol, to increase survival of retinal endothelial cells. In the present study, we evaluated the ability of Sac-0601 to prevent retinal vascular leakages in vitro and in vivo. Sac-0601 treatment blocked VEGF-induced formation of actin stress fibers and stabilized the cortical actin ring in retinal endothelial cells. It also inhibited degradation of occludin, an important tight junction protein, and blocked VEGF-induced disruption of its linear pattern at the cell border. The [(14)C] sucrose permeability assay demonstrated that Sac-0601 was able to prevent VEGF-induced retinal endothelial permeability. The compound inhibited the vascular leakage in retina of mice intravitreally injected with VEGF. And it also significantly reduced the leakage in retina of diabetic retinopathy mice model. Taken together, our findings suggest the potential therapeutic usefulness of Sac-0601 for retinal vascular permeability diseases.

  3. Interstitial lung disease

    Institute of Scientific and Technical Information of China (English)


    970328 Expression FGF-b and C-myc in mouse lungtissue affected by hypoxia OUYANG Nengtai(欧阳能太), et al. Guangzhou Respir Instit,Guangzhou, 510120, Chin J Tuberc Respir Dis 1997; 20(1): 22-24. Objective: To study FGF’S roles in the reconstruc-tion of vascular walls owing to chronic hypoxia. Meth-

  4. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury.

    Directory of Open Access Journals (Sweden)

    Srabani Mitra

    Full Text Available Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1 induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury.

  5. National Lung Screening Trial (NLST) (United States)

    The National Lung Screening Trial (NLST), a research study sponsored by the National Cancer Institute that used low-dose helical CT scans or chest X-ray to screen men and women at risk for lung cancer.

  6. Drugs Approved for Lung Cancer (United States)

    ... Ask about Your Treatment Research Drugs Approved for Lung Cancer This page lists cancer drugs approved by the ... listed here. Drugs Approved for Non-Small Cell Lung Cancer Abitrexate (Methotrexate) Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation) ...

  7. Lung Cancer Rates by State (United States)

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English Español (Spanish) Recommend ... incidence data are currently available. Rates of Getting Lung Cancer by State The number of people who get ...

  8. What Are Lung Function Tests? (United States)

    ... include tests that measure lung size and air flow, such as spirometry and lung volume tests. Other tests measure how well gases such as oxygen get in and out of your blood. These tests include pulse oximetry and arterial blood ...

  9. 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)


    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.)

  10. Robust lung identification in MSCT via controlled flooding and shape constraints: dealing with anatomical and pathological specificity (United States)

    Fetita, Catalin; Tarando, Sebastian; Brillet, Pierre-Yves; Grenier, Philippe A.


    Correct segmentation and labeling of lungs in thorax MSCT is a requirement in pulmonary/respiratory disease analysis as a basis for further processing or direct quantitative measures: lung texture classification, respiratory functional simulations, intrapulmonary vascular remodeling evaluation, detection of pleural effusion or subpleural opacities, are only few clinical applications related to this requirement. Whereas lung segmentation appears trivial for normal anatomo-pathological conditions, the presence of disease may complicate this task for fully-automated algorithms. The challenges come either from regional changes of lung texture opacity or from complex anatomic configurations (e.g., thin septum between lungs making difficult proper lung separation). They make difficult or even impossible the use of classic algorithms based on adaptive thresholding, 3-D connected component analysis and shape regularization. The objective of this work is to provide a robust segmentation approach of the pulmonary field, with individualized labeling of the lungs, able to overcome the mentioned limitations. The proposed approach relies on 3-D mathematical morphology and exploits the concept of controlled relief flooding (to identify contrasted lung areas) together with patient-specific shape properties for peripheral dense tissue detection. Tested on a database of 40 MSCT of pathological lungs, the proposed approach showed correct identification of lung areas with high sensitivity and specificity in locating peripheral dense opacities.

  11. Tumor vascular disruption using various radiation types

    Directory of Open Access Journals (Sweden)

    JJ Bevelacqua


    Full Text Available The feasibility of disrupting a tumor’s vascular structure with various radiation types and radionuclides is investigated. Calculated absorbed dose profiles for photons and 4He ions suggest that low-energy beta-gamma and alpha emitting radionuclides can deposit sufficient absorbed dose to disrupt a tumor’s vascular structure while minimizing the dose outside the blood vessel. Candidate radionuclides uniformly distributed in microspheres are theoretically investigated with respect to their vascular disruption potential and to offer an alternative to 90Y microsphere therapy. Requisite activities of candidate low-energy beta-gamma and alpha emitting radionuclides to facilitate vascular disruption are calculated.

  12. Vascular nursing in Greece: luxury or necessity? (United States)

    Georgakarakos, Efstratios; Bitza, Christina; Papanas, Nikolaos; Matsagkas, Miltiadis; Lazarides, Miltos K


    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.

  13. NADH/NADPH Oxidase and Vascular Function. (United States)

    Griendling, K K; Ushio-Fukai, M


    The vascular NADH/NADPH oxidase has been shown to be the major source of superoxide in the vessel wall. Recent work has provided insight into its structure and activity in vascular cells. This enzyme is involved in both vascular smooth muscle hypertrophy and in some forms of impaired endothelium-dependent relaxation. Because oxidative stress in general participates in the pathogenesis of hypertension and atherosclerosis, the enzymes that produce reactive oxygen species may be important determinants of the course of vascular disease. (Trends Cardiovasc Med 1997;7:301-307). © 1997, Elsevier Science Inc.

  14. Proatherogenic pathways leading to vascular calcification

    Energy Technology Data Exchange (ETDEWEB)

    Mazzini, Michael J. [Department of Cardiology, Boston University Medical Center, Boston, MA (United States); Schulze, P. Christian [Department of Medicine, Boston University Medical Center, Boston, MA (United States)]. E-mail:


    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.

  15. Vascular anomalies: differential diagnosis and mimickers. (United States)

    Garzon, Maria C; Weitz, Nicole; Powell, Julie


    Vascular anomalies are very common in children and encompass a wide spectrum of diseases. Many vascular anomalies can be mistaken for infantile hemangioma (IH). In addition, there is a variety of rare disorders including benign and malignant tumors that may mimic IH and other types of vascular anomalies. Understanding the clinical features, natural history, and typical clinical course of different types of vascular anomalies is essential in order to make the correct diagnosis and guide management. Radiologic imaging plays an important role in establishing the diagnosis; and when the diagnosis remains in doubt, a biopsy performed by a surgical specialist with expertise may prove to be lifesaving.

  16. Bronchoscopic lung volume reduction

    Directory of Open Access Journals (Sweden)

    M. I. Polkey


    Full Text Available Surgical lung volume reduction can improve exercise performance and forced expiratory volume in one second in patients with emphysema. However, the procedure is associated with a 5% mortality rate and a nonresponse rate of 25%. Accordingly, interest has focused on alternative ways of reducing lung volume. Two principle approaches are used: collapse of the diseased area using blockers placed endobronchially and the creation of extrapulmonary pathways. Preliminary data from the former approach suggest that it can be successful and that the magnitude of success is related to reduction in dynamic hyperinflation.

  17. Poverty and lung health. (United States)

    Rusen, I D; Squire, S Bertel; Billo, Nils E


    The International Union Against Tuberculosis and Lung Disease (The Union) held its 40th World Conference on Lung Health in Cancun, Mexico, between 3 and 7 December 2009. It was attended by over 2000 delegates from 104 countries around the world. The conference featured four stimulating plenary sessions and an extensive selection of scientific symposia. A total of 1125 abstracts were also presented from five broad categories: clinical trials and TB basic science, clinical research for treatment and care, epidemiology, education, advocacy and social issues, and policy and program implementation. In addition, the conference was preceded by a series of well-attended postgraduate courses and workshops.

  18. Ultrasound-guided bilateral continuous sciatic nerve blocks with stimulating catheters for postoperative pain relief after bilateral lower limb amputations*.

    NARCIS (Netherlands)

    Geffen, G.J. van; Scheuer, M.; Müller, A.; Garderniers, J.; Gielen, M.J.M.


    The performance of continuous bilateral sciatic nerve blocks under ultrasonographic control using stimulating catheters is described in a 4-year-old child with VACTERL syndrome. Ultrasound showed an abnormal vascular and nerve supply to the lower limbs. The use of ultrasound guidance made successful

  19. The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease. (United States)

    Karmouty-Quintana, Harry; Zhong, Hongyan; Acero, Luis; Weng, Tingting; Melicoff, Ernestina; West, James D; Hemnes, Anna; Grenz, Almut; Eltzschig, Holger K; Blackwell, Timothy S; Xia, Yang; Johnston, Richard A; Zeng, Dewan; Belardinelli, Luiz; Blackburn, Michael R


    Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A(2B)R) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A(2B)R or treatment with the A(2B)R antagonist GS-6201. Results demonstrated that GS-6201 treatment or genetic removal of the A(2B)R attenuated vascular remodeling and hypertension in our model. Furthermore, direct A(2B)R activation on vascular cells promoted interleukin-6 and endothelin-1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A(2B)R antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease.

  20. 表皮生长因子受体和血管内皮细胞生长因子受体之外肺癌靶向治疗新进展%Targeted therapies for lung cancer beyond anti-epidermal growth factor receptors and anti-vascular endothelial cell growth factor receptors: exploring a new frontier

    Institute of Scientific and Technical Information of China (English)

    虞永峰; 陆舜


    目前肺癌的生物靶向治疗已进入临床治疗阶段,以吉非替尼、厄洛替尼和西妥昔单抗为代表的抗表皮生长因子受体(epidermal growth factor receptor, EGFR)通路的药物和以贝伐单抗为代表的抗血管内皮细胞生长因子受体(vascular endothelial cell growth factor receptor, VEGFR)通路的药物已成功地应用于肺癌临床治疗.然而,肺癌分子生物学机制十分复杂,以EGFR和VEGFR信号通路为靶点的治疗存在局限和不足.近年来,肺癌新的分子生物靶点逐渐受到关注,例如棘皮动物微管相关蛋白4/间变淋巴瘤激酶(echinoderm microtubule-associated protein-like 4/anaplastic lymphoma kinase, EML4-ALK)融合基因、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)、胰岛素样生长因子Ⅰ型受体(insulin-like growth factor type Ⅰ receptor, IGF-1R)和间质上皮转变因子(mesenchymal-epithelial transition factor, c-MET)等.本文对上述分子生物学标志物在肺癌治疗中的作用及其相关临床研究进展进行综述.