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Sample records for inhibits alveolar development

  1. Alveolar development and disease.

    Science.gov (United States)

    Whitsett, Jeffrey A; Weaver, Timothy E

    2015-07-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis.

  2. Effects of phosphodiesterase 4 inhibition on alveolarization and hyperoxia toxicity in newborn rats.

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    Céline Méhats

    Full Text Available BACKGROUND: Prolonged neonatal exposure to hyperoxia is associated with high mortality, leukocyte influx in airspaces, and impaired alveolarization. Inhibitors of type 4 phosphodiesterases are potent anti-inflammatory drugs now proposed for lung disorders. The current study was undertaken to determine the effects of the prototypal phosphodiesterase-4 inhibitor rolipram on alveolar development and on hyperoxia-induced lung injury. METHODOLOGY/FINDINGS: Rat pups were placed under hyperoxia (FiO2>95% or room air from birth, and received rolipram or its diluent daily until sacrifice. Mortality rate, weight gain and parameters of lung morphometry were recorded on day 10. Differential cell count and cytokine levels in bronchoalveolar lavage and cytokine mRNA levels in whole lung were recorded on day 6. Rolipram diminished weight gain either under air or hyperoxia. Hyperoxia induced huge mortality rate reaching 70% at day 10, which was prevented by rolipram. Leukocyte influx in bronchoalveolar lavage under hyperoxia was significantly diminished by rolipram. Hyperoxia increased transcript and protein levels of IL-6, MCP1, and osteopontin; rolipram inhibited the increase of these proteins. Alveolarization was impaired by hyperoxia and was not restored by rolipram. Under room air, rolipram-treated pups had significant decrease of Radial Alveolar Count. CONCLUSIONS: Although inhibition of phosphodiesterases 4 prevented mortality and lung inflammation induced by hyperoxia, it had no effect on alveolarization impairment, which might be accounted for by the aggressiveness of the model. The less complex structure of immature lungs of rolipram-treated pups as compared with diluent-treated pups under room air may be explained by the profound effect of PDE4 inhibition on weight gain that interfered with normal alveolarization.

  3. Bmp2 and Bmp4 accelerate alveolar bone development.

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    Ou, Mingming; Zhao, Yibing; Zhang, Fangming; Huang, Xiaofeng

    2015-06-01

    Alveolar bone remodeling is a continuous process that takes place during development and in response to various physiological and pathological stimuli. However, detailed knowledge regarding the underlying mechanisms involved in alveolar bone development is still lacking. This study aims at improving our understanding of alveolar bone formation and the role of bone morphogenetic proteins (Bmps) in this process. Mice at embryonic (E) day 13.5 to postnatal (PN) day 15.5 were selected to observe the process of alveolar bone development. Alveolar bone development was found to be morphologically observable at E14.5. Molar teeth isolated from mice at PN7.5 were pretreated with Bmp2, Bmp4, Noggin, or BSA, and grafted subcutaneously into mice. The subcutaneously implanted tooth germs formed alveolar bone indicating the role of the dental follicle in alveolar bone development. Alveolar bone formation was increased after pretreatment with Bmp2 and Bmp4, but not with Noggin. Gene expression levels in dental follicle cells from murine molars were also determined by real-time RT-PCR. The expression levels of Runx2, Bsp, and Ocn were significantly higher in dental follicle cells cultured with Bmp2 or Bmp4, and significantly lower in those cultured with Noggin when compared with that of the BSA controls. Our results suggest that the dental follicle participates in alveolar bone formation and Bmp2/4 appears to accelerate alveolar bone development.

  4. Cigarette Smoke Extract Inhibits the Proliferation of Alveolar Epithelial Cells and Augments the Expression of P21WAF1

    Institute of Scientific and Technical Information of China (English)

    Zongxian JIAO; Qilin AO; Xiaona GE; Mi XIONG

    2008-01-01

    Cigarette smoking is intimately related with the development of chronic obstructive pulmonary diseases, and alveolar epithelium is a major target for the exposure of cigarette smoke ex- tract. In order to investigate the effect of cigarette smoke extract on the proliferation of alveolar epithelial cell type Ⅱand its relationship with P21WAF1, the alveolar epithelial type Ⅱ cell line (A549) cells were chosen as surrogate cells to represent alveolar epithelial type Ⅱ cells. MTT assay was used to detect cell viability after interfered with different concentrations of cigarette smoke ex-tract. It was observed cigarette smoke extract inhibited the growth of A549 cells in a dose- and time-dependent manner. The morphological changes, involving the condensation and margination of nuclear chromatin, even karyorrhexis, were observed by both Hoechst staining and electronic mi-croscopy. Flow cytometry analysis demonstrated the increased cell percentages in G1 and subG1phases after the cells were incubated with cigarette smoke extract. The expression of p21WAF1 protein and mRNA was also significantly increased as detected by the methods of Western blot or reverse transcription-polymerase chain reaction respectively. In conclusion, cigarette smoke extract inhibits the proliferation of alveolar epithelial cell type Ⅱ and blocks them in G1/S phase. The intracellular accumulation of P21WAF1 may be one of the mechanisms which contribute to cigarette smoke ex-tract-induced inhibition of cell proliferation.

  5. Dehydroepiandrosterone inhibits the spontaneous release of superoxide radical by alveolar macrophages in vitro in asbestosis

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    Rom, W.N.; Harkin, T. (New York Univ. Medical Center, New York (United States))

    1991-08-01

    Asbestosis is characterized by an alveolar macrophage alveolitis with injury and fibrosis of the lower respiratory tract. Alveolar macrophages recovered by bronchoalveolar lavage spontaneously release exaggerated amounts of oxidants including superoxide anion and hydrogen peroxide that may mediate alveolar epithelial cell injury. Dehydroepiandrosterone (DHEA) is a normally occurring adrenal androgen that inhibits glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose phosphate shunt necessary for NADPH generation and superoxide anion formation. In this regard, the authors hypothesized that DHEA may reduce asbestos-induced oxidant release. DHEA added in vitro to alveolar macrophages lavaged from 11 nonsmoking asbestos workers significantly reduced superoxide anion release. DHEA is an antioxidant and potential anticarcinogenic agent that may have a therapeutic role in reducing the increased oxidant burden in asbestos-induced alveolitis of the lower respiratory tract.

  6. Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

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    Weber, Nina C.; van der Sluijs, Koen; Hackl, Florian; Hotz, Lorenz; Dahan, Albert; Hollmann, Markus W.; Berger, Marc M.

    2014-01-01

    We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (IV) bolus injection had no effect. The aim of the present study was to characterize whether continuous IV infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of IV S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered IV over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by IV lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by IV S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by IV S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of IV S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport. PMID:25386677

  7. Pirfenidone inhibits p38-mediated generation of procoagulant microparticles by human alveolar epithelial cells.

    Science.gov (United States)

    Neri, Tommaso; Lombardi, Stefania; Faìta, Francesca; Petrini, Silvia; Balìa, Cristina; Scalise, Valentina; Pedrinelli, Roberto; Paggiaro, Pierluigi; Celi, Alessandro

    2016-08-01

    Pirfenidone is a drug recently approved for idiopathic pulmonary fibrosis but its mechanisms of action are partially unknown. We have previously demonstrated that the airways of patients with idiopathic pulmonary fibrosis contain procoagulant microparticles that activate coagulation factor X to its active form, Xa, a proteinase that signals fibroblast growth and differentiation, thus potentially contributing to the pathogenesis of the disease. We also reported that in vitro exposure of human alveolar cells to H2O2 causes microparticle generation. Since p38 activation is involved in microparticle generation in some cell models and p38 inhibition is one of the mechanisms of action of pirfenidone, we investigated the hypothesis that H2O2-induced generation of microparticles by alveolar cells is dependent on p38 phosphorylation and is inhibited by pirfenidone. H2O2 stimulation of alveolar cells caused p38 phosphorylation that was inhibited by pirfenidone. The drug also inhibited H2O2 induced microparticle generation as assessed by two independent methods (solid phase thrombin generation and flow cytometry). The shedding of microparticle-bound tissue factor activity was also inhibited by pirfenidone. Inhibition of p38-mediated generation of procoagulant microparticle is a previously unrecognized mechanism of action of the antifibrotic drug, pirfenidone.

  8. Ketamine Inhibits Lung Fluid Clearance through Reducing Alveolar Sodium Transport

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    Yong Cui

    2011-01-01

    Full Text Available Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobes ex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker, fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride-sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+ currents (ENaC activity in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema.

  9. Short Communication: HIV Controller T Cells Effectively Inhibit Viral Replication in Alveolar Macrophages.

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    Walker-Sperling, Victoria E; Merlo, Christian A; Buckheit, Robert W; Lambert, Allison; Tarwater, Patrick; Kirk, Greg D; Drummond, M Bradley; Blankson, Joel N

    Macrophages are targets of HIV-1 infection, and control of viral replication within these cells may be an important component of a T-cell-based vaccine. Although several studies have analyzed the ability of CD8(+) T cells to inhibit viral replication in monocyte-derived macrophages, the effect of T cells on HIV-1-infected tissue macrophages is less clear. We demonstrate here that both CD4(+) and CD8(+) T-cell effectors from HIV controllers are capable of suppressing viral replication in bronchoalveolar lavage-derived alveolar macrophages. These findings have implications for HIV-1 vaccine and eradication strategies.

  10. Angiotensin-(1-7)/Mas Signaling Inhibits Lipopolysaccharide-Induced ADAM17 Shedding Activity and Apoptosis in Alveolar Epithelial Cells.

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    Ma, Xinhua; Xu, Daomiao; Ai, Yuhang; Zhao, Shuangping; Zhang, Lina; Ming, Guangfeng; Liu, Zhiyong

    2016-01-01

    A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, is the pivotal shedding enzyme mediating acute lung inflammation. On the other hand, angiotensin (Ang)-(1-7)/Mas signaling has been shown to improve acute respiratory distress syndrome and protect alveolar epithelial cells from apoptosis. In this study, we explored the effect of Ang-(1-7)/Mas signaling on the expression and activity of ADAM17 and assessed its impact on apoptosis in lipopolysaccharide (LPS)-treated human alveolar epithelial cells. LPS markedly induced the shedding activity of ADAM17 in alveolar epithelial cells, which was blocked by selective c-Jun N-terminal kinase (JNK) inhibitor SP600125. Ang-(1-7) concentration-dependently inhibited LPS-induced ADAM17 shedding activity, which was abolished by selective Mas blocker A779 and Mas shRNA. LPS and Ang-(1-7) showed no significant effect on the expression of ADAM17. Overexpression of ADAM17 synergized with LPS on increasing the shedding activity of ADAM17 and apoptosis in alveolar epithelial cells, counteracting the inhibitory effects of Ang-(1-7). In addition, LPS significantly increased the JNK activity in alveolar epithelial cells; Ang-(1-7) concentration-dependently inhibited LPS-induced JNK activity, which was abolished by A779 and Mas shRNA. In conclusion, this study suggests that Ang-(1-7)/Mas signaling inhibits LPS-induced alveolar epithelial cell apoptosis by inhibiting LPS-induced shedding activity of ADAM17, likely by a JNK-dependent mechanism. © 2015 S. Karger AG, Basel.

  11. Inhibition of HIV-1 replication in alveolar macrophages by adenovirus gene transfer vectors.

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    Rice, Joshua; Connor, Ruth; Worgall, Stefan; Moore, John P; Leopold, Philip L; Kaner, Robert J; Crystal, Ronald G

    2002-08-01

    To assess the hypothesis that infection of alveolar macrophages (AM) with adenovirus (Ad) gene transfer vectors might prevent subsequent human immunodeficiency virus (HIV)-1 replication in AM, AM isolated from normal volunteers were infected with increasing doses of first generation (E1(-)) Ad vectors, followed 72 h later by infection with HIV-1(JRFL), an R5/M-tropic strain that preferentially uses the CCR5 coreceptor. As a measure of HIV-1 replication, p24 Ag was quantified by enzyme-linked imunosorbent assay in supernatants on Days 4 to 14 after HIV-1infection. Pretreatment of the AM with an Ad vector resulted in a dose- and time-dependent suppression of subsequent HIV-1 replication. The Ad vector inhibition of HIV-1 replication was independent of the transgene in the Ad vector expression cassette and E4 genes in the Ad backbone. Moreover, it did not appear to be secondary to a soluble factor released by the AM, nor was it overridden by the concomitant transfer of the CCR5 or CXCR4 receptors to the AM before HIV-1 infection. These observations have implications regarding pulmonary host responses associated with HIV-1 infection, as well as possibly uncovering new therapeutic strategies against HIV-1 infection.

  12. Adenosine deaminase acting on RNA-1 (ADAR1 inhibits HIV-1 replication in human alveolar macrophages.

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    Michael D Weiden

    Full Text Available While exploring the effects of aerosol IFN-γ treatment in HIV-1/tuberculosis co-infected patients, we observed A to G mutations in HIV-1 envelope sequences derived from bronchoalveolar lavage (BAL of aerosol IFN-γ-treated patients and induction of adenosine deaminase acting on RNA 1 (ADAR1 in the BAL cells. IFN-γ induced ADAR1 expression in monocyte-derived macrophages (MDM but not T cells. ADAR1 siRNA knockdown induced HIV-1 expression in BAL cells of four HIV-1 infected patients on antiretroviral therapy. Similar results were obtained in MDM that were HIV-1 infected in vitro. Over-expression of ADAR1 in transformed macrophages inhibited HIV-1 viral replication but not viral transcription measured by nuclear run-on, suggesting that ADAR1 acts post-transcriptionally. The A to G hyper-mutation pattern observed in ADAR1 over-expressing cells in vitro was similar to that found in the lungs of HIV-1 infected patients treated with aerosol IFN-γ suggesting the model accurately represented alveolar macrophages. Together, these results indicate that ADAR1 restricts HIV-1 replication post-transcriptionally in macrophages harboring HIV-1 provirus. ADAR1 may therefore contribute to viral latency in macrophages.

  13. Surface iron inhibits quartz-induced cytotoxic and inflammatory responses in alveolar macrophages.

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    Ghiazza, Mara; Scherbart, Agnes M; Fenoglio, Ivana; Grendene, Francesca; Turci, Francesco; Martra, Gianmario; Albrecht, Catrin; Schins, Roel P F; Fubini, Bice

    2011-01-14

    The mechanism of enhancement/inhibition of quartz toxicity induced by iron is still unclear. Here the amount of iron on a fibrogenic quartz (Qz) was increased by wet impregnation (Fe(NO(3))(3) 0.67 and 6.7 wt %). X-ray diffraction (XRD), XRF diffuse reflectance, UV-vis, and infrared (IR) spectroscopies revealed dispersed ferric ions, and hematite aggregates at the higher loading. Surface features relevant to pathogenicity and cell responses were compared not only to the original quartz but also to reference quartz DQ12. Surface charge (ζ-potential) was more negative on the original and low-loaded specimen than on the high-loaded one. DQ12 had a less negative ζ-potential than Qz, ascribed to the absence of aluminium present in Qz (1.7 wt %). All quartz specimens were able to generate HO(•) radicals, iron-loaded samples being more reactive than original quartz. Iron deposition inhibited the rupture of a C-H bond. All quartzes were phagocytized by alveolar macrophages (AMΦ cell line NR8383) to the same extent, irrespective of their surface state. Conversely, iron loading increased AMΦ viability (evaluated by cytotoxicity and induction of apoptosis). Qz was found to be much less cytotoxic than DQ12. The induction of oxidative stress and inflammatory responses (evaluated by HO-1 mRNA expression and TNF-α mRNA and protein expression) revealed a reduction in inflammogenicity upon iron loading and a more inflammogenic potency of DQ12 ascribed to undissociated SiOH interacting via H-bonding with cell membrane components. The results suggest that besides aluminium also iron at the quartz surface may have an inhibitory effect on adverse health responses.

  14. Chloroquine inhibits Rhodococcus equi replication in murine and foal alveolar macrophages by iron-starvation.

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    Gressler, Leticia T; Bordin, Angela I; McQueen, Cole M; Cohen, Noah D; de Vargas, Agueda Castagna

    2016-05-30

    Rhodococcus equi preferentially infects macrophages causing pyogranulomatous pneumonia in young foals. Both the vapA and rhbC genes are up-regulated in an iron (Fe)-deprived environment, such as that found within macrophages. Chloroquine (CQ) is a drug widely used against malaria that suppresses the intracellular availability of Fe in eukaryotic cells. The main objective of this study was to evaluate the ability of CQ to inhibit replication of virulent R. equi within murine (J774A.1) and foal alveolar macrophages (AMs) and to verify whether the mechanism of inhibition could be Fe-deprivation-dependent. CQ effect on R. equi extracellular survival and toxicity to J774A.1 were evaluated. R. equi survival within J774A.1 and foal AMs was evaluated under CQ (10 and 20μM), bovine saturated transferrin (bHTF), and bovine unsaturated transferrin (bATF) exposure. To explore the action mechanism of CQ, the superoxide anion production, the lysozyme activity, as well as the relative mRNA expression of vapA and rhbC were examined. CQ at≤20μM had no effect on R. equi extracellular multiplication and J774A.1 viability. Exposure to CQ significantly and markedly reduced survival of R. equi within J774A.1 and foal AMs. Treatment with bHTF did not reverse CQ effect on R. equi. Exposure to CQ did not affected superoxide anion production or lysozyme activity, however vapA and rhbC expression was significantly increased. Our results reinforce the hypothesis that intracellular availability of Fe is required for R. equi survival, and our initial hypothesis that CQ can limit replication of R. equi in J774A.1 and foal AMs, most likely by Fe starvation. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Low pH Environmental Stress Inhibits LPS and LTA-Stimulated Proinflammatory Cytokine Production in Rat Alveolar Macrophages

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    Stanley F. Fernandez

    2013-01-01

    Full Text Available Gastric aspiration increases the risks for developing secondary bacterial pneumonia. Cytokine elaboration through pathogen recognition receptors (PRRs is an important mechanism in initiating innate immune host response. Effects of low pH stress, a critical component of aspiration pathogenesis, on the PRR pathways were examined, specifically toll-like receptor-2 (TLR2 and TLR4, using isolated rat alveolar macrophages (aMØs. We assessed the ability of aMØs after brief exposure to acidified saline to elaborate proinflammatory cytokines in response to lipopolysaccharide (LPS and lipoteichoic acid (LTA stimulation, known ligands of TLR4 and TLR2, respectively. Low pH stress reduced LPS- and LTA-mediated cytokine release (CINC-1, MIP-2, TNF-, MCP-1, and IFN-. LPS and LTA increased intracellular Ca2+ concentrations while Ca2+ chelation by BAPTA decreased LPS- and LTA-mediated cytokine responses. BAPTA blocked the effects of low pH stress on most of LPS-stimulated cytokines but not of LTA-stimulated responses. In vivo mouse model demonstrates suppressed E. coli and S. pneumoniae clearance following acid aspiration. In conclusion, low pH stress inhibits antibacterial cytokine response of aMØs due to impaired TLR2 (MyD88 pathway and TLR4 signaling (MyD88 and TRIF pathways. The role of Ca2+ in low pH stress-induced signaling is complex but appears to be distinct between LPS- and LTA-mediated responses.

  16. Interaction of the European genotype porcine reproductive and respiratory syndrome virus (PRRSV with sialoadhesin (CD169/Siglec-1 inhibits alveolar macrophage phagocytosis

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    De Baere Miet I

    2012-05-01

    Full Text Available Abstract Porcine reproductive and respiratory syndrome virus (PRRSV is an arterivirus that shows a restricted in vivo tropism for subsets of porcine macrophages, with alveolar macrophages being major target cells. The virus is associated with respiratory problems in pigs of all ages and is commonly isolated on farms with porcine respiratory disease complex (PRDC. Due to virus-induced macrophage death early in infection, PRRSV hampers the innate defence against pathogens in the lungs. In addition, the virus might also directly affect the antimicrobial functions of macrophages. This study examined whether interaction of European genotype PRRSV with primary alveolar macrophages (PAM affects their phagocytic capacity. Inoculation of macrophages with both subtype I PRRSV (LV and subtype III PRRSV (Lena showed that the virus inhibits PAM phagocytosis. Similar results were obtained using inactivated PRRSV (LV, showing that initial interaction of the virion with the cell is sufficient to reduce phagocytosis, and that no productive infection is required. When macrophages were incubated with sialoadhesin- (Sn or CD163-specific antibodies, two entry mediators of the virus, only Sn-specific antibodies downregulated the phagocytic capacity of PAM, indicating that interaction with Sn, but not CD163, mediates the inhibitory effect of PRRSV on phagocytosis. In conclusion, this study shows that European genotype PRRSV inhibits PAM phagocytosis in vitro, through the interaction with its internalization receptor Sn. If similar events occur in vivo, this interaction may be important in the development of PRDC, as often seen in the field.

  17. Development and characterization of a rabbit alveolar bone nonhealing defect model.

    NARCIS (Netherlands)

    Young, S.; Bashoura, A.G.; Borden, T.; Baggett, L.S.; Jansen, J.A.; Wong, M.; Mikos, A.G.

    2008-01-01

    The aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty-four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 1

  18. Knockdown of flotillin-2 inhibits lung surfactant secretion by alveolar type Ⅱ cells

    Institute of Scientific and Technical Information of China (English)

    Narendranath Reddy Chintagari; Deming Gou; Lin Liu

    2008-01-01

    @@ Dear Editor, Lung surfactant is stored in lamellar bodies and exocytosed following fusion of the lamellar bodies with the plasma membrane of alveolar type Ⅱ (AT2) cells [1].A number of proteins have been shown to be involved in surfactant secretion including SNAREs,NSF,α-SNAP and annexin A2 [2,3].Lipid rafts enriched in SNAREs are crucial for surfactant secretion [4].

  19. Boric acid inhibits alveolar bone loss in rats by affecting RANKL and osteoprotegerin expression.

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    Sağlam, M; Hatipoğlu, M; Köseoğlu, S; Esen, H H; Kelebek, S

    2014-08-01

    The goal of the present study was to evaluate the effects of systemic boric acid on the levels of expression of RANKL and osteoprotegerin (OPG) and on histopathologic and histometric changes in a rat periodontitis model. Twenty-four Wistar rats were divided into three groups of eight animals each: nonligated (NL); ligature only (LO); and ligature plus treatment with boric acid (BA) (3 mg/kg per day for 11 d). A 4/0 silk suture was placed in a subgingival position around the mandibular right first molars; after 11 d the rats were killed, and alveolar bone loss in the first molars was histometrically determined. Periodontal tissues were examined histopathologically to assess the differences among the study groups. RANKL and OPG were detected immunohistochemically. Alveolar bone loss was significantly higher in the LO group than in the BA and NL groups (p boric acid may reduce alveolar bone loss by affecting the RANKL/OPG balance in periodontal disease in rats. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Alveolar flows of the developing lungs:from embryonic to early childhood airways

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    Tenenbaum-Katan, Janna; Hofemeier, Philipp; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josue

    2014-11-01

    At the onset of life in utero the respiratory system is simply a liquid-filled duct. With our first breath, alveoli are filled with air and become a significant port of entry for airborne particles. As such, alveolar lining is nearly fully functional at birth, though lung development continues during childhood as structural changes increase alveolar surface area to optimize ventilation. We hypothesize that such fluid dynamical changes potentially affect two phenomena occurring within alveoli: (i) flow patterns in airspaces at distinct stages of both in- and ex-utero life and (ii) fate of inhaled particles ex-utero. To investigate these phenomena, we combine experimental and numerical approaches where (i) microfluidic in vitro devices mimic liquid flows across the epithelium of fetal airspaces, and (ii) computational simulations are employed to examine particle transport and deposition in the deep alveolated regions of infants' lungs. Our approaches capture anatomically-inspired geometries based on morphometrical data, as well as physiological flows, including the convective-diffusive nature of submicron particle transport in alveolar regions.Overall, we investigate respiratory flows in alveolar regions of developing lungs, from early embryonic stages to late childhood

  1. Alveolar Echinococcus species from Vulpes corsac in Hulunbeier, Inner Mongolia, China, and differential development of the metacestodes in experimental rodents.

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    Tang, Chong-Ti; Wang, Yan-Hai; Peng, Wen-Feng; Tang, Liang; Chen, Dong

    2006-08-01

    Adults of alveolar Echinococcus species with different uterine structures were collected from Vulpes corsac in the Hulunbeier Pasture of Northeastern China in 2001. They were Echinococcus multilocularis Leuckart, 1863 (type No. 3, similar to E. m. multilocularis), with vaselike uterus; Echinococcus cf. sibiricensis Rausch et Schiller, 1954 (type No. 1), with pyriform uterus; and Echinococcus sp. (type No. 2) with spherical uterus at segment top. The metacestode development in rodents also differed among those 3 parasites. In the case of E. multilocularis (type No. 3), many germinal cells grew on the inner surface of early cysts, most of which metastasized into host tissue to form brood vesicles or from the germinal cell layer on the inner surface of the vesicle wall. Cells also had an appearance of proliferating by means of alveolar buds from alveolar tissue that developed outward to form new alveolar foci. In Echinococcus cf. sibiricensis (type No. 1), the formation of alveolar vesicles was due to the metastasizing of germinal tissue into host tissue; protoscoleces grew in the center of alveolar vesicles. In type No. 2 (Echinococcus sp.), the formation of the alveolar vesicle was by multiplication of germinal cell layers on the inner surface of alveolar cysts; protoscoleces grew from the germinal cell layer and mesh in the vesicles. On the basis of uterine structure and on differences in development of metacestodes in experimental rodents, we propose that the 3 types of Echinococcus represent 3 independent species: E. multilocularis, Echinococcus sibiricensis, and Echinococcus sp. (type No. 2-as yet under study).

  2. The effect of activated alveolar macrophages on experimental lung emphysema development. III. Morphological analysis of the lung tissue and alveolar macrophages in situ.

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    Sulkowski, S; Nowak, H F; Sulkowska, M; Sobaniec-Lotowska, M; Andrzejewska, A; Sulik, M; Dziecioł, J; Famulski, W; Poczopko, B

    1995-01-01

    Morphological (in light and transmission electron microscope) as well as morphometrical analysis of the lungs was performed on experimental, papain-induced lung emphysema. Development of emphysematous changes was studied seven days after a single intratracheal instillation of papain solution. The effect of alveolar macrophages (AM) activation by BCG-vaccine on changes in pulmonary tissue was analyzed. In the rats given BCG the number of AM increased and demonstrated enhanced activity. Increase in reticulin fibre density in places of AM cumulation, particularly in BCG+papain-treated rats was observed. The lungs of animals treated with BCG+papain showed enhancing of emphysema comparing with the papain-treated rats. Development of emphysematous changes, especially in BCG+papain-treated rats coexisted with cumulation of activated alveolar macrophages and collagen fibres as well as type II alveolar epithelial cells proliferation. Our data support the inflammatory-repair hypothesis of emphysema pathogenesis and indicate that AM regulate collagen production in the lung. Type II alveolar epithelial cells seem be important in lung injury and repair.

  3. Alveolar progenitor and stem cells in lung development, renewal and cancer.

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    Desai, Tushar J; Brownfield, Douglas G; Krasnow, Mark A

    2014-03-13

    Alveoli are gas-exchange sacs lined by squamous alveolar type (AT) 1 cells and cuboidal, surfactant-secreting AT2 cells. Classical studies suggested that AT1 arise from AT2 cells, but recent studies propose other sources. Here we use molecular markers, lineage tracing and clonal analysis to map alveolar progenitors throughout the mouse lifespan. We show that, during development, AT1 and AT2 cells arise directly from a bipotent progenitor, whereas after birth new AT1 cells derive from rare, self-renewing, long-lived, mature AT2 cells that produce slowly expanding clonal foci of alveolar renewal. This stem-cell function is broadly activated by AT1 injury, and AT2 self-renewal is selectively induced by EGFR (epidermal growth factor receptor) ligands in vitro and oncogenic Kras(G12D) in vivo, efficiently generating multifocal, clonal adenomas. Thus, there is a switch after birth, when AT2 cells function as stem cells that contribute to alveolar renewal, repair and cancer. We propose that local signals regulate AT2 stem-cell activity: a signal transduced by EGFR-KRAS controls self-renewal and is hijacked during oncogenesis, whereas another signal controls reprogramming to AT1 fate.

  4. CBX7 deficiency plays a positive role in dentin and alveolar bone development.

    Science.gov (United States)

    Zhou, Zhixuan; Yin, Ying; Jiang, Fei; Niu, Yuming; Wan, Shujian; Chen, Ning; Shen, Ming

    2016-08-01

    To clarify the role of CBX7 deficiency in dentin and alveolar bone development, the dental and mandibular phenotypes of homozygous CBX7-knockout (CBX7(-/-)) mice were compared with their wild-type (WT) counterparts at 3 weeks age. In contrast to WT littermates, dental volume and dentin sialoprotein-positive area were significantly increased, whereas the area ratio of predentin to dentin was decreased markedly in CBX7(-/-) mice. Mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive area, osteoblast number and activity, protein expression and mRNA level of Runt-related transcription factor 2 (Runx2), alkaline phosphatase, osteocalcin, osteopontin and bone morphogenetic protein 2 (BMP2) were all remarkably increased, while osteoclast number and activity, and mRNA expression ratio of NF-κB ligand (RANKL) to osteoprotegerin (opg) were all decreased significantly in the alveolar bone of CBX7(-/-) mice compared with their WT counterparts. Moreover, proliferating cell nuclear antigen (PCNA)-positive cells were found more in Hertwig' s epithelial root sheath of CBX7(-/-) mice, and their protein level of cyclin E1, cyclin-dependent kinase 2 (CDK2) were correspondingly increased in contrast to WT mice. Taken together, these results of this study suggest that CBX7 deficiency plays a positive role in dentin and alveolar bone formation.

  5. Development of a lung slice preparation for recording ion channel activity in alveolar epithelial type I cells

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    Crandall Edward D

    2005-04-01

    Full Text Available Abstract Background Lung fluid balance in the healthy lung is dependent upon finely regulated vectorial transport of ions across the alveolar epithelium. Classically, the cellular locus of the major ion transport processes has been widely accepted to be the alveolar type II cell. Although evidence is now emerging to suggest that the alveolar type I cell might significantly contribute to the overall ion and fluid homeostasis of the lung, direct assessment of functional ion channels in type I cells has remained elusive. Methods Here we describe a development of a lung slice preparation that has allowed positive identification of alveolar type I cells within an intact and viable alveolar epithelium using living cell immunohistochemistry. Results This technique has allowed, for the first time, single ion channels of identified alveolar type I cells to be recorded using the cell-attached configuration of the patch-clamp technique. Conclusion This exciting new development should facilitate the ascription of function to alveolar type I cells and allow us to integrate this cell type into the general model of alveolar ion and fluid balance in health and disease.

  6. Inhibition of tumor necrosis factor-α reduces alveolar septal cell apoptosis in passive smoking rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Cheng; CAI Shan; CHEN Ping; CHEN Jian-bo; WU Jie; WU Shang-jie; ZHOU Rui

    2008-01-01

    Background Recent studies have revealed that lung cell apoptosis plays an important role in pathogenesis of cigarette-induced chronic obstructive pulmonary disease (COPD).Tumor necrosis factor alpha(TNF-α)is one of the most important cytokines which are involved in COPD.This study aimed at investigating the jnfluence of its inhibitor,recombinant human necrosis factor-alpha receptor Ⅱ:IgG Fc fusion protein(rhTNFR:Fc)on alveolar septal cell apoptosis in passive smoking rats.Methods Forty-eight rats were randomly divided into a normal control group,a passive smoking group,an rhTNFR:Fc intervention group and a sham intervention group.The passive smoking rats were treated by exposure to cigarette smoking daily for 80 days.Afcer smoking for one month the rhTNFR:Fc Intervention group was treated with rhTNFR:Fc by subcutaneous injection,the sham intervention group injected subcutaneousIv with a neutral preparation(normal saline 0.1 ml,manicol 0.8 ml,cane sugar 0.2 mg,Tris 0.024 mg as a control.Lung function was determined and the levels of TNF-α in serum and broncho-alveolar lavage fluid(BALF)were measured with enzyme-linked immunosorbnent assay (ELISA).Lung tissue sections stained by hematoxylin and eosin(HE)were observed for study of morphological alternations.Mean linear intercept(MLI)and mean alveolar numbers(MAN)were measured and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)method was carried out to determine the percentage of positive cells and distribution of apoptotic cells.Results Increased MLI and decreased MAN were found in the passive smoking group compared with both the normal control group and the rhTNFR:Fc intervention group(P<0.05).Forced expiratory volume in 0.3 second(FEV0.3)/forced vital capacity(FVC)and peak expiratory flow(PEF)were lower in the passive smoking group than that in the normal control group(P<0.05).Compared with the sham intervention group,FEV0.3/FVC and PEF increased in the rhTNFR:Fc intervention

  7. Autocatalytic nitration of prostaglandin endoperoxide synthase-2 by nitrite inhibits prostanoid formation in rat alveolar macrophages.

    Science.gov (United States)

    Schildknecht, Stefan; Karreman, Christiaan; Daiber, Andreas; Zhao, Cheng; Hamacher, Jürg; Perlman, David; Jung, Birgit; van der Loo, Bernd; O'Connor, Peter; Leist, Marcel; Ullrich, Volker; Bachschmid, Markus Michael

    2012-11-15

    Prostaglandin endoperoxide H(2) synthase (PGHS) is a well-known target for peroxynitrite-mediated nitration. In several experimental macrophage models, however, the relatively late onset of nitration failed to coincide with the early peak of endogenous peroxynitrite formation. In the present work, we aimed to identify an alternative, peroxynitrite-independent mechanism, responsible for the observed nitration and inactivation of PGHS-2 in an inflammatory cell model. In primary rat alveolar macrophages stimulated with lipopolysaccharide (LPS), PGHS-2 activity was suppressed after 12 h, although the prostaglandin endoperoxide H(2) synthase (PGHS-2) protein was still present. This coincided with a nitration of the enzyme. Coincubation with a nitric oxide synthase-2 (NOS-2) inhibitor preserved PGHS-2 nitration and at the same time restored thromboxane A(2) (TxA(2)) synthesis in the cells. Formation of reactive oxygen species (ROS) was maximal at 4 h and then returned to baseline levels. Nitrite (NO(2)(-)) production occurred later than ROS generation. This rendered generation of peroxynitrite and the nitration of PGHS-2 unlikely. We found that the nitrating agent was formed from NO(2)(-), independent from superoxide ((•)O(2)(-)). Purified PGHS-2 treated with NO(2)(-) was selectively nitrated on the active site Tyr(371), as identified by mass spectrometry (MS). Exposure to peroxynitrite resulted in the nitration not only of Tyr(371), but also of other tyrosines (Tyr). The data presented here point to an autocatalytic nitration of PGHS-2 by NO(2)(-), catalyzed by the enzyme's endogenous peroxidase activity and indicate a potential involvement of this mechanism in the termination of prostanoid formation under inflammatory conditions.

  8. The H2S-generating enzymes cystathionine β-synthase and cystathionine γ-lyase play a role in vascular development during normal lung alveolarization.

    Science.gov (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

    2015-10-01

    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. Copyright © 2015 the American Physiological Society.

  9. Late appearance of a type I alveolar epithelial cell marker during fetal rat lung development.

    Science.gov (United States)

    Danto, S I; Zabski, S M; Crandall, E D

    1994-10-01

    Recent studies in fetal lung using immunological and molecular probes have revealed type I and type II cell phenotypic markers in primordial lung epithelial cells prior to the morphogenesis of these cell types. We have recently developed monoclonal antibodies specific for adult type I cells. To evaluate further the temporal appearance of the type I cell phenotype during alveolar epithelial cell ontogeny, we analyzed fetal lung development using one of our monoclonal antibodies (mAb VIII B2). The epitope recognized by mAb VIII B2 first appears in the canalicular stage of fetal lung development, at approx. embryonic day 19 (E19), in occasional, faintly stained tubules. Staining with this type I cell probe becomes more intense and more widespread with increasing gestational age, during which time the pattern of staining changes. Initially, all cells of the distal epithelial tubules are uniformly labelled along their apical and basolateral surfaces. As morphological differentiation of the alveolar epithelium proceeds, type I cell immunoreactivity appears to become restricted to the apical surface of the primitive type I cells in a pattern approaching that seen in the mature lung. We concurrently analyzed developing fetal lung with an antiserum to surfactant apoprotein-A (alpha-SP-A). Consistent with the findings of others, labeling of SP-A was first detectable in scattered cuboidal cells at E18. Careful examination of the double-labeled specimens suggested that some cells were reactive with both the VIII B2 and SP-A antibodies, particularly at E20. Confocal microscopic analysis of such sections from E20 lung confirmed this impression. Three populations of cells were detected: cells labeled only with alpha-SP-A, cells labeled only with mAb VIII B2, and a smaller subset of cells labeled by both.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. [Alveolar hemorrhage].

    Science.gov (United States)

    Parrot, A; Fartoukh, M; Cadranel, J

    2015-04-01

    Alveolar hemorrhage occurs relatively rarely and is a therapeutic emergency because it can quickly lead to acute respiratory failure, which can be fatal. Hemoptysis associated with anemia and pulmonary infiltrates suggest the diagnosis of alveolar hemorrhage, but may be absent in one third of cases including patients in respiratory distress. The diagnosis of alveolar hemorrhage is based on the findings of a bronchoalveolar lavage. The causes are numerous. It is important to identify alveolar hemorrhage due to sepsis, then separate an autoimmune cause (vasculitis associated with antineutrophil cytoplasmic antibody, connective tissue disease and Goodpasture's syndrome) with the search for autoantibodies and biopsies from readily accessible organs, from a non-immune cause, performing echocardiography. Lung biopsy should be necessary only in exceptional cases. If the hemorrhage has an immune cause, treatment with steroids and cyclophosphamide may be started. The indications for treatment with rituximab are beginning to be established (forms that are not severe and refractory forms). The benefit of plasma exchange is unquestionable in Goodpasture's syndrome. In patients with an immune disease that can lead to an alveolar hemorrhage, removing any source of infection is the first priority. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  11. Research progress on alveolar bone development%牙槽骨发生的研究进展

    Institute of Scientific and Technical Information of China (English)

    欧明明; 黄晓峰; 韩培彦

    2014-01-01

    Absorption and loss of alveolar bone are some of the main reasons of tooth loss. Therefore, clinics must understand how to reconstruct alveolar bone. To date, treatment strategies to rescue or regenerate the alveolar bone are limited. The process of developing biological alveolar bone formation in the early stage may help to understand the mechanism of bone regeneration and benefit clinical treatment. Alveolar bone is partially derived from dental follicle cells. Many growth factors and transcription factors are involved in the development of alveolar bone. In this review, the relationship between alveolar bone formation and many factors will be discussed in detail. This review also highlights recent advances in understanding alveolar bone development with and without varying factors.%牙槽骨再生是牙周组织疾病治疗的根本。牙槽骨发生属于膜内成骨,成骨细胞来源于多潜能神经嵴牙囊间质细胞,伴随着牙体的发生而发生。牙胚由成釉器、牙乳头和牙囊组成,而牙囊则形成牙骨质、牙周膜和牙槽骨。骨形态发生蛋白(BMP)可启动、促进和调节骨的发生、发育、生长、重塑和修复。核心结合因子1可使牙囊间质细胞向成骨细胞分化,对膜内成骨和软骨内成骨有控制作用。成纤维细胞生长因子通过调控骨干细胞复制,成骨细胞分化和程序性死亡,各种细胞及相关因子的表达来控制骨形成。WNT在BMP的刺激下促进成骨细胞分化,增强BMP诱导下的Ⅰ型胶原、特殊骨基质蛋白和骨钙蛋白表达。声音刺猬蛋白、转化生长因子β和肌节同源盒蛋白2在牙槽骨和牙骨质中表达强烈,其基因突变可致牙槽骨丧失。本文就牙槽骨发生与牙囊间的关系以及参与牙槽骨发生的细胞因子等研究进展作一综述。

  12. Characterization, anticancer drug susceptibility and atRA-induced growth inhibition of a novel cell line (HUMEMS) established from pleural effusion of alveolar rhabdomyosarcoma of breast tissue.

    Science.gov (United States)

    Ohi, Satoshi

    2007-05-01

    We recently established a cell line derived from pleural effusion from a 13-year-old girl with primary alveolar rhabdomyosarcoma (RMS with a chromosomal translocation t[2;13]) in the breast tissue. The cell line was designated as HUMEMS. Cases of primary alveolar RMS swelling in the breast are extremely rare (about 0.2% of all RMSs). Therefore, the HUMEMS cell line is an important material for studying therapeutics for malignant tumors in children. The HUMEMS cell line we isolated consisted of two morphological subtypes. One type (SSN cells) is small in size and has a single nucleus. Another (LMN cells) is large in size and has two or more nuclei. Both SSN cells and LMN cells were immunohistochemically positive for desmin and slightly positive for myoglobin. Our data suggested LMN cells are well-differentiated SSN cells. Moreover, in some of the LMN cells, rapid cell contractions (1-5 times/10 sec) were observed. We investigated the anticancer drug susceptibility of the HUMEMS cell line with an oxygen electrode apparatus (Daikin, DOX-10, JPN) and effect of all-trans-retinoic acid (atRA) to the cell line. The atRA-treatment inhibited proliferation of the HUMEMS cells.

  13. Parathyroid hormone-related protein is not required for normal ductal or alveolar development in the post-natal mammary gland.

    Directory of Open Access Journals (Sweden)

    Kata Boras-Granic

    Full Text Available PTHrP is necessary for the formation of the embryonic mammary gland and, in its absence, the embryonic mammary bud fails to form the neonatal duct system. In addition, PTHrP is produced by the breast during lactation and contributes to the regulation of maternal calcium homeostasis during milk production. In this study, we examined the role of PTHrP during post-natal mammary development. Using a PTHrP-lacZ transgenic mouse, we surveyed the expression of PTHrP in the developing post-natal mouse mammary gland. We found that PTHrP expression is restricted to the basal cells of the gland during pubertal development and becomes expressed in milk secreting alveolar cells during pregnancy and lactation. Based on the previous findings that overexpression of PTHrP in cap and myoepithelial cells inhibited ductal elongation during puberty, we predicted that ablation of native PTHrP expression in the post-natal gland would result in accelerated ductal development. To address this hypothesis, we generated two conditional models of PTHrP-deficiency specifically targeted to the postnatal mammary gland. We used the MMTV-Cre transgene to ablate the floxed PTHrP gene in both luminal and myoepithelial cells and a tetracycline-regulated K14-tTA;tetO-Cre transgene to target PTHrP expression in just myoepithelial and cap cells. In both models of PTHrP ablation, we found that mammary development proceeds normally despite the absence of PTHrP. We conclude that PTHrP signaling is not required for normal ductal or alveolar development.

  14. Parathyroid hormone-related protein is not required for normal ductal or alveolar development in the post-natal mammary gland.

    Science.gov (United States)

    Boras-Granic, Kata; VanHouten, Joshua; Hiremath, Minoti; Wysolmerski, John

    2011-01-01

    PTHrP is necessary for the formation of the embryonic mammary gland and, in its absence, the embryonic mammary bud fails to form the neonatal duct system. In addition, PTHrP is produced by the breast during lactation and contributes to the regulation of maternal calcium homeostasis during milk production. In this study, we examined the role of PTHrP during post-natal mammary development. Using a PTHrP-lacZ transgenic mouse, we surveyed the expression of PTHrP in the developing post-natal mouse mammary gland. We found that PTHrP expression is restricted to the basal cells of the gland during pubertal development and becomes expressed in milk secreting alveolar cells during pregnancy and lactation. Based on the previous findings that overexpression of PTHrP in cap and myoepithelial cells inhibited ductal elongation during puberty, we predicted that ablation of native PTHrP expression in the post-natal gland would result in accelerated ductal development. To address this hypothesis, we generated two conditional models of PTHrP-deficiency specifically targeted to the postnatal mammary gland. We used the MMTV-Cre transgene to ablate the floxed PTHrP gene in both luminal and myoepithelial cells and a tetracycline-regulated K14-tTA;tetO-Cre transgene to target PTHrP expression in just myoepithelial and cap cells. In both models of PTHrP ablation, we found that mammary development proceeds normally despite the absence of PTHrP. We conclude that PTHrP signaling is not required for normal ductal or alveolar development.

  15. TNF-α mediated increase of HIF-1α inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI).

    Science.gov (United States)

    Tang, Mengjie; Tian, Yihao; Li, Doulin; Lv, Jiawei; Li, Qun; Kuang, Changchun; Hu, Pengchao; Wang, Ying; Wang, Jing; Su, Ke; Wei, Lei

    2014-01-01

    Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function and increased pulmonary vascular permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated with all types of modulations of cytoskeleton rearrangement-dependent cellular morphology and function, such as adhesion, shrinkage, and permeability. The present studies were conducted to investigate the effects and mechanisms by which tumor necrosis factor-alpha (TNF-α) increases the tight junction permeability in lung tissue associated with acute lung inflammation. After incubating A549 cells for 24 hours with different concentrations (0-100 ng/mL) of TNF-α, 0.1 to 8 ng/mL TNF-α exhibited no significant effect on cell viability compared with the 0 ng/mL TNF-α group (control group). However, 10 ng/mL and 100 ng/mL TNF-α dramatically inhibited the viability of A549 cells compared with the control group (*pTNF-α for 24 hours displayed significantly increased cell permeability (*pinhibition of VASP expression increased the cell permeability (*pTNF-α in lung tissues and serum significantly increased at one hour, and the value reached a peak at four hours. Moreover, the Evans Blue absorption value of the mouse lung tissues reached a peak at four hours. The HIF-1α protein expression level in mouse lung tissues increased significantly at four hours and eight hours (**pTNF-α to inhibit VASP expression and to modulate the acute pulmonary inflammation process, and these molecules play an important role in the impairment of the alveolar-capillary barrier.

  16. N-Acetyl-L-cysteine and pyrrolidine dithiocarbamate inhibited nuclear factor-кB activation in alveolar macrophages by different mechanisms

    Institute of Scientific and Technical Information of China (English)

    Ya-qing LI; Zhen-xiang ZHANG; Yong-jian XU; Wang NI; Shi-xin CHEN; Zhao YANG; Dan MA

    2006-01-01

    Aim:To study the effects of N-acetyl-L-cysteine(NAC)and pyrrolidine dithiocarbamate(PDTC)on the phosphorylation of IκB kinase(IKK)β,IKKα,and IκBa in alveolar macrophages(AM),and to explore the pharmacological mechanisms of NAC and PDTC as inhibitors of NF-κB activation.Methods:AM were collected from bronchoalveolar lavage fluid from the patients with chronic obstructive pulmonary disease.The AM were incubated for 1.5h with NAC and PDTC,and then stimulated for 90 min by either tumor necrosis factor(TNF)-α or interleukin(IL)-1.Western blotting was used to detect the protein phosphorylation levels of IKKβ,IKKα,and IκBα.NF-κB activity was analyzed by using an electrophoretic mobility shift assay.Resuits:NAC inhibited the phosphorylation of IKKβ,IKKα,and IκBα induced by TNF-α,but had no effect on the phosphorylation of IKKβ,IKKα and IκBα induced by IL-1.PDTC did not inhibit the phosphorylation of IκBα induced by TNF-α or IL-1.Similarly,NAC inhibited the activation of NF-κB induced by TNF-α,but had no effect on the activation of NF-κB induced by IL-1.PDTC significantly inhibited the activation of NF-κB induced by TNF-α and IL-1.The electrophoretic mobility shift assay also showed that PDTC and NAC do not directly inhibit NF-κB DNA binding activity in vitro.Conclusion:PDTC prevents the degradation of IκBα via the ubiquitylation-proteasome proteolytic pathway.NAC can inhibit the processes upstream of IKK activation induced by TNF-α,which results in the decline of NF-κB activity.

  17. The effect of activated alveolar macrophages on experimental lung emphysema development. II. The study of fibroblast and alveolar macrophage co-culture.

    Science.gov (United States)

    Sulkowska, M; Wołczyński, S; Sulkowski, S; Sobaniec-Lotowska, M; Chyczewski, L; Sulik, M; Kulikowski, M; Dziecioł, J; Berger, W

    1995-01-01

    The cell-cell interaction between fibroblasts and alveolar macrophages was examined using a co-culture system. Alveolar macrophages (AM) were harvested from the bronchoalveolar lavages (BAL) of rats with papain induced lung emphysema. The BCG-vaccine was applied as a macrophage mobilizing and activating agent. The morphological examinations carried out in scanning electron microscope (SEM) as well as the evaluation of the uptake of 3H-thymidine did not show any significant differences between respective co-cultures of fibroblasts and AM isolated both from the lungs of control and experimental animals (treated with BCG or papain, and BCG+papain). However, significant growth were noted in 3H-thymidine uptake between fibroblast cultures done with or without cells isolated from the lungs. The results obtained suggest that AM can promote fibroblast proliferation during the progression of experimental lung emphysema.

  18. Mitochondrial dysfunction contributes to alveolar developmental arrest in hyperoxia-exposed mice.

    Science.gov (United States)

    Ratner, Veniamin; Starkov, Anatoly; Matsiukevich, Dzmitry; Polin, Richard A; Ten, Vadim S

    2009-05-01

    This study investigated whether mitochondrial dysfunction contributes to alveolar developmental arrest in a mouse model of bronchopulmonary dysplasia (BPD). To induce BPD, 3-day-old mice were exposed to 75% O2. Mice were studied at two time points of hyperoxia (72 h or 2 wk) and after 3 weeks of recovery in room air (RA). A separate cohort of mice was exposed to pyridaben, a complex-I (C-I) inhibitor, for 72 hours or 2 weeks. Alveolarization was quantified by radial alveolar count and mean linear intercept methods. Pulmonary mitochondrial function was defined by respiration rates, ATP-production rate, and C-I activity. At 72 hours, hyperoxic mice demonstrated significant inhibition of C-I activity, reduced respiration and ATP production rates, and significantly decreased radial alveolar count compared with controls. Exposure to pyridaben for 72 hours, as expected, caused significant inhibition of C-I and ADP-phosphorylating respiration. Similar to hyperoxic littermates, these pyridaben-exposed mice exhibited significantly delayed alveolarization compared with controls. At 2 weeks of exposure to hyperoxia or pyridaben, mitochondrial respiration was inhibited and associated with alveolar developmental arrest. However, after 3 weeks of recovery from hyperoxia or 2 weeks after 72 hours of exposure to pyridaben alveolarization significantly improved. In addition, there was marked normalization of C-I and mitochondrial respiration. The degree of hyperoxia-induced pulmonary simplification and recovery strongly (r(2) = 0.76) correlated with C-I activity in lung mitochondria. Thus, the arrest of alveolar development induced by either hyperoxia or direct inhibition of mitochondrial oxidative phosphorylation indicates that bioenergetic failure to maintain normal alveolar development is one of the fundamental mechanisms responsible for BPD.

  19. Pulmonary alveolar microlithiasis

    Directory of Open Access Journals (Sweden)

    Surender Kashyap

    2013-01-01

    Full Text Available Pulmonary alveolar microlithiasis (PAM is a rare, chronic lung disease with bilateral intra-alveolar calcium and phosphate deposition throughout the lung parenchyma with predominance to lower and midzone. Although, etiology and pathogenesis of PAM is not fully understood, the mutation in SLC34A2 gene that encodes a sodium-phosphate co-transporter in alveolar type II cells resulting in the accumulation and forming of microliths rich in calcium phosphate (due to impaired clearance are considered to be the cause of the disease. Chest radiograph and high-resolution CT of thorax are nearly pathognomonic for diagnosing PAM. HRCT demonstrates diffuse micronodules showing slight perilobular predominance resulting in calcification of interlobular septa. Patients with PAM are asymptomatic till development of hypoxemia and cor-pulmonale. No therapy has been proven to be beneficial except lung transplantation.

  20. Alveolar Macrophage Polarisation in Lung Cancer

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    Saleh A. Almatroodi

    2014-01-01

    Full Text Available The role of alveolar macrophages in lung cancer is multifaceted and conflicting. Alveolar macrophage secretion of proinflammatory cytokines has been found to enhance antitumour functions, cytostasis (inhibition of tumour growth, and cytotoxicity (macrophage-mediated killing. In contrast, protumour functions of alveolar macrophages in lung cancer have also been indicated. Inhibition of antitumour function via secretion of the anti-inflammatory cytokine IL-10 as well as reduced secretion of proinflammatory cytokines and reduction of mannose receptor expression on alveolar macrophages may contribute to lung cancer progression and metastasis. Alveolar macrophages have also been found to contribute to angiogenesis and tumour growth via the secretion of IL-8 and VEGF. This paper reviews the evidence for a dual role of alveolar macrophages in lung cancer progression.

  1. Activation of phosphatase and tensin homolog on chromosome 10 mediates the inhibition of FcgammaR phagocytosis by prostaglandin E2 in alveolar macrophages.

    Science.gov (United States)

    Canetti, Claudio; Serezani, Carlos H; Atrasz, Rachelle G; White, Eric S; Aronoff, David M; Peters-Golden, Marc

    2007-12-15

    PGE2 has important inhibitory effects on the macrophage host defense functions of phagocytosis and killing, yet the molecular mechanisms involved remain to be fully elucidated. PGE2 causes an elevation of cAMP in alveolar macrophages (AMs), which in turn activates the cAMP effector targets, protein kinase A and the exchange protein activated by cAMP (Epac)-1. We now report that FcgammaR-induced PI3K/Akt and ERK-1/2 activation are inhibited by PGE2 in AMs. By specifically inhibiting the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in AMs, we attenuated the inhibitory effects of both PGE2 and a specific Epac-1 agonist (8-pCPT-2'-O-Me-cAMP) on FcgammaR-mediated phagocytosis and Akt/ERK-1/2 activation; PTEN inhibition also decreased PGE2-induced suppression of bacterial killing by AMs. Moreover, PGE2 and the Epac-1 agonist induced an increase in PTEN lipid phosphatase activity, and this was associated with decreased tyrosine phosphorylation on PTEN-a mechanism known to regulate PTEN activity. Using a pharmacological approach, we demonstrated a role for Src homology 2-containing protein tyrosine phosphatase-1 in the PGE2-induced tyrosine dephosphorylation of PTEN. Collectively, these data reveal that PGE2, via Epac-1 activation, enhances SHP-1 activity, resulting in increased PTEN activity. We suggest that this mechanism contributes to the ability of PGE2 to inhibit PI3K-dependent innate immune signaling in primary macrophages.

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

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    Mansoor A Syed

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

  3. Effect of two models of intrauterine growth restriction on alveolarization in rat lungs: morphometric and gene expression analysis.

    Directory of Open Access Journals (Sweden)

    Elodie Zana-Taieb

    Full Text Available Intrauterine growth restriction (IUGR in preterm infants increases the risk of bronchopulmonary dysplasia, characterized by arrested alveolarization. We evaluated the impact of two different rat models (nitric oxide synthase inhibition or protein deprivation of IUGR on alveolarization, before, during, and at the end of this postnatal process. We studied IUGR rat pups of dams fed either a low protein (LPD or a normal diet throughout gestation and pups of dams treated by continuous infusion of Nω-nitro-L-arginine methyl ester (L-NAME or its diluent on the last four days of gestation. Morphometric parameters, alveolar surface (Svap, mean linear intercept (MLI and radial alveolar count (RAC and transcriptomic analysis were determined with special focus on genes involved in alveolarization. IUGR pups regained normal weight at day 21 in the two treated groups. In the LPD group, Svap, MLI and RAC were not different from those of controls at day 4, but were significantly decreased at day 21, indicating alveolarization arrest. In the L-NAME group, Svap and RAC were significantly decreased and MLI was increased at day 4 with complete correction at day 21. In the L-NAME model, several factors involved in alveolarization, VEGF, VEGF-R1 and -R2, MMP14, MMP16, FGFR3 and 4, FGF18 and 7, were significantly decreased at day 4 and/or day 10, while the various factors studied were not modified in the LPD group. These results demonstrate that only maternal protein deprivation leads to sustained impairment of alveolarization in rat pups, whereas L-NAME impairs lung development before alveolarization. Known growth factors involved in lung development do not seem to be involved in LPD-induced alveolarization disorders, raising the question of a possible programming of altered alveolarization.

  4. Early activation of the alveolar macrophage is critical to the development of lung ischemia-reperfusion injury.

    NARCIS (Netherlands)

    Naidu, BV; Krishnadasan, B; Farivar, AS; Woolley, SM; Thomas, R; Rooijen, van N.; Verrier, ED; Mulligan, MS

    2003-01-01

    .006) and marked reductions in bronchoalveolar lavage fluid leukocyte accumulation. Alveolar macrophage-depleted animals also demonstrated marked reductions of the elaboration of multiple proinflammatory chemokines and cytokines in the lavage effluent and nuclear transcription factors in lung homoge

  5. ROCK inhibition prevents early mouse embryo development.

    Science.gov (United States)

    Duan, Xing; Chen, Kun-Lin; Zhang, Yu; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2014-08-01

    ROCK is a Rho-GTPase effector that is important for actin assembly and is involved in various cellular functions, including cell contraction, migration, motility, and tumor cell invasion. In this study, we investigated ROCK expression and function during early mouse embryo development. Inhibiting ROCK by Y-27632 treatment at the zygote stage resulted in first cleavage failure, and most embryos failed to develop to the 8-cell stage. When adding Y-27632 at the 8-cell stage, embryos failed to undergo compaction and could not develop into blastocysts. In addition, fluorescence staining intensity analysis indicated that actin expression at blastomere membranes was significantly reduced. After ROCK inhibition, two or more nuclei were observed in a cell, which indicated possible cytokinesis failure. Moreover, after ROCK inhibition with Y-27632, the phosphorylation levels of LIMK1/2, a downstream molecule of ROCK, were decreased at blastomere membranes. Thus, our results showed conserved roles for ROCK in this mammalian embryo model and indicated that a ROCK-LIMK1/2-actin pathway might regulate cleavage and blastocyst formation during early mouse embryo development.

  6. Effect of cigarette smoke extract on P-glycoprotein function in primary cultured and newly developed alveolar epithelial cells.

    Science.gov (United States)

    Takano, Mikihisa; Naka, Ryosuke; Sasaki, Yoshihiro; Nishimoto, Saori; Yumoto, Ryoko

    2016-12-01

    The effect of cigarette smoke extract (CSE) on P-glycoprotein (P-gp) function in the distal lung is unclear. In this study, we first examined the expression and function of P-gp and the effect of CSE in rat primary cultured alveolar epithelial cells. The expression of P-gp protein was observed in type I-like cells, but not in type II cells. In type I-like cells, rhodamine 123 (Rho123) accumulation was enhanced by various P-gp inhibitors such as verapamil and cyclosporine A. In addition, the expression of P-gp mRNAs, mdr1a and mdr1b, as well as P-gp activity increased along with the transdifferentiation. When type I-like cells were co-incubated with CSE, P-gp activity was suppressed. Next, we attempted to clarify the effect of CSE on P-gp function in human-derived cultured alveolar epithelial cells. For this purpose, we isolated an A549 clone (A549/P-gp) expressing P-gp, because P-gp expression in native A549 cells was negligible. In A549/P-gp cells, P-gp was functionally expressed, and the inhibitory effect of CSE on P-gp was observed. These results suggested that smoking would directly suppress P-gp activity, and that A549/P-gp cell line should be a useful model to further study the effect of xenobiotics on P-gp function in the alveolar epithelial cells.

  7. Lung alveolar epithelium and interstitial lung disease.

    Science.gov (United States)

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

    2009-01-01

    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.

  8. Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat.

    Science.gov (United States)

    Deng, Haijing; Xu, Hong; Zhang, Xianghong; Sun, Yue; Wang, Ruimin; Brann, Darrell; Yang, Fang

    2016-03-01

    The epithelial-mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties.

  9. Alveolar hypoventilation treated with medroxyprogesterone.

    OpenAIRE

    Milerad, J.; Lagercrantz, H; Löfgren, O.

    1985-01-01

    Two children aged 1 and 20 months developed alveolar hypoventilation syndrome. They suffered severe apnoeic episodes and periodically required assisted ventilation. Their ventilatory response to carbon dioxide was lower than that of normal children and the transcutaneous oxygen tension during sleep was well below the normal range. Treatment with medroxyprogesterone acetate resulted in an improved response to carbon dioxide, and assisted ventilation was no longer needed. Oxygen and carbon diox...

  10. The role of synthetic biomaterials in resorptive alveolar bone regeneration

    OpenAIRE

    2007-01-01

    The alveolar bone tissue resorption defect has a significant role in dentistry. Because of the bone tissue deficit developed by alveolar resorption, the use of synthetic material CP/PLGA (calcium-phosphate/polylactide-co-gliycolide) composite was introduced. Investigations were performed on rats with artificially produced resorption of the mandibular bone. The results show that the best effect on alveolar bone were attained by using nano-composite implants. The effect of the nanocomposite was...

  11. Pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    B. Crestani

    2011-06-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic “crazy paving” pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy or anti-GM-CSF antibodies (rituximab and plasmapheresis are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

  12. 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

    2011-06-01

    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

  13. 香烟烟雾提取物抑制肺泡上皮细胞的增殖并诱导其凋亡%Cigarette smoke extract inhibits the proliferation of alveolar epithelial cells and induces apoptosis

    Institute of Scientific and Technical Information of China (English)

    焦宗宪; 敖启林; 熊密

    2006-01-01

    in morphology, and the appearance of DNA fragmentation and annexin V-FITC/propidium iodide (PI) staining assay at molecular level. It was found that CSE treatment resulted in the upregulation of Fas/APO-1 receptor and activation of caspase-3. CSE also initiated accumulation of intracellular reactive oxygen species, which was detected by laser confocal microscopy. Taken together, CSE could inhibit the cell growth and induce apoptosis of A549 cells through Fas receptor pathway.Oxidative stress caused by CSE may be the radical factor leading to apoptosis as well as cell growth inhibition in alveolar epithelial cells.

  14. . Psychological predictors of inhibition development in educational environments

    Directory of Open Access Journals (Sweden)

    Symanyuk, Elvira E.

    2016-09-01

    Full Text Available This article examines psychological predictors of inhibition in educational environments as well as various aspects of pedagogical communication, including facilitation, which is aimed at enhancing educational effectiveness and developing students by means of using a particular communication style and the teacher’s personality. The need to study inhibition (the deterioration of teacher-children interactions; the negation of a student’s individuality; the inability to understand and accept students’ viewpoints; teacher-provoked conflicts; and emotional callousness is substantiated. The essence of psychological predictors as independent variables, changes in which lead to changes in other dependent variables, allowing the prediction of inhibition development, is explained. The research objective was to identify psychological predictors of the development of inhibition in pedagogical communication. An empirical study was conducted using standardized techniques for diagnosing communicative attitudes (V. Boyko, developing general communicative tolerance (V. Boyko, identifying aggressiveness (A. Asinger, identifying the level of empathy (V. Boyko, and identifying the degree of pedagogical inhibition (L. Polosova. The sample contained 375 teachers from Yekaterinburg educational institutions, with participant selection made using stratified sampling. The teacher’s personality features (a negative communicative attitude, low communicative tolerance and empathy, and higher levels of aggression were shown to be key predictors of inhibition, which itself was found to depend on the length of teaching experience. At the beginning of one’s professional teaching career, the level of inhibition is minimal. However, the level of inhibition reaches its maximum level after 5-10 years of teaching, and after 20 years, there is a sharp decrease in the level of inhibition. The conclusion of this study stresses the importance of developing strategies to

  15. Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema.

    Science.gov (United States)

    Solymosi, Esther A; Kaestle-Gembardt, Stefanie M; Vadász, István; Wang, Liming; Neye, Nils; Chupin, Cécile Julie Adrienne; Rozowsky, Simon; Ruehl, Ramona; Tabuchi, Arata; Schulz, Holger; Kapus, Andras; Morty, Rory E; Kuebler, Wolfgang M

    2013-06-18

    Alveolar fluid clearance driven by active epithelial Na(+) and secondary Cl(-) absorption counteracts edema formation in the intact lung. Recently, we showed that impairment of alveolar fluid clearance because of inhibition of epithelial Na(+) channels (ENaCs) promotes cardiogenic lung edema. Concomitantly, we observed a reversal of alveolar fluid clearance, suggesting that reversed transepithelial ion transport may promote lung edema by driving active alveolar fluid secretion. We, therefore, hypothesized that alveolar ion and fluid secretion may constitute a pathomechanism in lung edema and aimed to identify underlying molecular pathways. In isolated perfused lungs, alveolar fluid clearance and secretion were determined by a double-indicator dilution technique. Transepithelial Cl(-) secretion and alveolar Cl(-) influx were quantified by radionuclide tracing and alveolar Cl(-) imaging, respectively. Elevated hydrostatic pressure induced ouabain-sensitive alveolar fluid secretion that coincided with transepithelial Cl(-) secretion and alveolar Cl(-) influx. Inhibition of either cystic fibrosis transmembrane conductance regulator (CFTR) or Na(+)-K(+)-Cl(-) cotransporters (NKCC) blocked alveolar fluid secretion, and lungs of CFTR(-/-) mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride reproduced alveolar fluid and Cl(-) secretion that were again CFTR-, NKCC-, and Na(+)-K(+)-ATPase-dependent. Our findings show a reversal of transepithelial Cl(-) and fluid flux from absorptive to secretory mode at hydrostatic stress. Alveolar Cl(-) and fluid secretion are triggered by ENaC inhibition and mediated by NKCC and CFTR. Our results characterize an innovative mechanism of cardiogenic edema formation and identify NKCC1 as a unique therapeutic target in cardiogenic lung edema.

  16. Cultured alveolar epithelial cells from septic rats mimic in vivo septic lung.

    Directory of Open Access Journals (Sweden)

    Taylor S Cohen

    Full Text Available Sepsis results in the formation of pulmonary edema by increasing in epithelial permeability. Therefore we hypothesized that alveolar epithelial cells isolated from septic animals develop tight junctions with different protein composition and reduced barrier function relative to alveolar epithelial cells from healthy animals. Male rats (200-300 g were sacrificed 24 hours after cecal ligation and double puncture (2CLP or sham surgery. Alveolar epithelial cells were isolated and plated on fibronectin-coated flexible membranes or permeable, non-flexible transwell substrates. After a 5 day culture period, cells were either lysed for western analysis of tight junction protein expressin (claudin 3, 4, 5, 7, 8, and 18, occludin, ZO-1, and JAM-A and MAPk (JNK, ERK, an p38 signaling activation, or barrier function was examined by measuring transepithelial resistance (TER or the flux of two molecular tracers (5 and 20 A. Inhibitors of JNK (SP600125, 20 microM and ERK (U0126, 10 microM were used to determine the role of these pathways in sepsis induced epithelial barrier dysfunction. Expression of claudin 4, claudin 18, and occludin was significantly lower, and activation of JNK and ERK signaling pathways was significantly increased in 2CLP monolayers, relative to sham monolayers. Transepithelial resistance of the 2CLP monolayers was reduced significantly compared to sham (769 and 1234 ohm-cm(2, respectively, however no significant difference in the flux of either tracer was observed. Inhibition of ERK, not JNK, significantly increased TER and expression of claudin 4 in 2CLP monolayers, and prevented significant differences in claudin 18 expression between 2CLP and sham monolayers. We conclude that alveolar epithelial cells isolated from septic animals form confluent monolayers with impaired barrier function compared to healthy monolayers, and inhibition of ERK signaling partially reverses differences between these monolayers. This model provides a unique

  17. Recent advances in alveolar biology: evolution and function of alveolar proteins.

    Science.gov (United States)

    Orgeig, Sandra; Hiemstra, Pieter S; Veldhuizen, Edwin J A; Casals, Cristina; Clark, Howard W; Haczku, Angela; Knudsen, Lars; Possmayer, Fred

    2010-08-31

    This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two groups of surfactant proteins - the small molecular weight hydrophobic SPs, SP-B and -C, that regulate interfacial adsorption of the lipids, and the large hydrophilic SPs, SP-A and -D, which are surfactant collectins capable of inhibiting foreign pathogens. Further aiding pulmonary host defence are non-surfactant collectins and antimicrobial peptides that are expressed across the biological kingdoms. Linking to the first symposium session, which emphasised molecular structure and biophysical function of surfactant lipids and proteins, this review begins with a discussion of the role of temperature and hydrostatic pressure in shaping the evolution of SP-C in mammals. Transitioning to the role of the alveolus in innate host defence we discuss the structure, function and regulation of antimicrobial peptides, the defensins and cathelicidins. We describe the recent discovery of novel avian collectins and provide evidence for their role in preventing influenza infection. This is followed by discussions of the roles of SP-A and SP-D in mediating host defence at the alveolar surface and in mediating inflammation and the allergic response of the airways. Finally we discuss the use of animal models of lung disease including knockouts to develop an understanding of the role of these proteins in initiating and/or perpetuating disease with the aim of developing new therapeutic strategies.

  18. Bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.

    Science.gov (United States)

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin; Metcalf, Jordan Patrick

    2012-12-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness.

  19. [Dento-alveolar injuries].

    Science.gov (United States)

    Voorsmit, R A; Kuijpers-Jagtman, A M

    1992-11-01

    Most dento-alveolar traumas can be managed by the dentist-general practitioner. Still, there are some specific injuries which should be treated by dental specialists. Some specific guidelines are given for the combined surgical-orthodontic treatment of fracture of the coronal part of the root, intrusive luxation, abnormal position of the permanent tooth due to traumatic displacement of the deciduous tooth, ankylosis and tooth loss.

  20. Proteinosis alveolar pulmonar

    Directory of Open Access Journals (Sweden)

    Concepción Sánchez Infante

    2011-12-01

    Full Text Available La proteinosis alveolar pulmonar es una enfermedad respiratoria crónica, caracterizada por alteración en el metabolismo del surfactante, lo que determina su acumulación anormal en el espacio alveolar. Es una enfermedad extremadamente rara. Se han reportado solamente 500 casos en la literatura. Se describió por primera vez en 1958. Se presenta un caso de proteinosis alveolar pulmonar en un lactante de 2 meses, con desnutrición proteico energética, que ingresa por dificultad respiratoria e hipoxemia, y, con imágenes radiológicas de tipo retículo-nodulillar, en vidrio deslustrado, en el cual se plantea inicialmente el diagnóstico de bronconeumonía. Ante la evolución desfavorable y no respuesta al tratamiento, se realizó un estudio para descartar enfermedades pulmonares crónicas. El paciente fallece y se confirma el diagnóstico por anatomía patológica. Se realiza una revisión del tema.

  1. Alveolar proteinosis associated with aluminium dust inhalation.

    Science.gov (United States)

    Chew, R; Nigam, S; Sivakumaran, P

    2016-08-01

    Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Legionella pneumophila infection induces programmed cell death, caspase activation, and release of high-mobility group box 1 protein in A549 alveolar epithelial cells: inhibition by methyl prednisolone

    Directory of Open Access Journals (Sweden)

    Koide Michio

    2008-05-01

    Full Text Available Abstract Background Legionella pneumophila pneumonia often exacerbates acute lung injury (ALI and acute respiratory distress syndrome (ARDS. Apoptosis of alveolar epithelial cells is considered to play an important role in the pathogenesis of ALI and ARDS. In this study, we investigated the precise mechanism by which A549 alveolar epithelial cells induced by L. pneumophila undergo apoptosis. We also studied the effect of methyl prednisolone on apoptosis in these cells. Methods Nuclear deoxyribonucleic acid (DNA fragmentation and caspase activation in L. pneumophila-infected A549 alveolar epithelial cells were assessed using the terminal deoxyribonucleotidyl transferase-mediated triphosphate (dUTP-biotin nick end labeling method (TUNEL method and colorimetric caspase activity assays. The virulent L. pneumophila strain AA100jm and the avirulent dotO mutant were used and compared in this study. In addition, we investigated whether methyl prednisolone has any influence on nuclear DNA fragmentation and caspase activation in A549 alveolar epithelial cells infected with L. pneumophila. Results The virulent strain of L. pneumophila grew within A549 alveolar epithelial cells and induced subsequent cell death in a dose-dependent manner. The avirulent strain dotO mutant showed no such effect. The virulent strains of L. pneumophila induced DNA fragmentation (shown by TUNEL staining and activation of caspases 3, 8, 9, and 1 in A549 cells, while the avirulent strain did not. High-mobility group box 1 (HMGB1 protein was released from A549 cells infected with virulent Legionella. Methyl prednisolone (53.4 μM did not influence the intracellular growth of L. pneumophila within alveolar epithelial cells, but affected DNA fragmentation and caspase activation of infected A549 cells. Conclusion Infection of A549 alveolar epithelial cells with L. pneumophila caused programmed cell death, activation of various caspases, and release of HMGB1. The dot/icm system, a

  3. Alveolar cleft closure with iliac bone graft: A case report.

    Directory of Open Access Journals (Sweden)

    Tichvy Tammama

    2017-04-01

    Conclusion: The timing of alveolar bone grafting usually associated with the state of the developing of dentition. Post operative management is important to get a good result, and to prevent any complications.

  4. Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development.

    Science.gov (United States)

    Chung, Il-Hyuk; Yamaza, Takayoshi; Zhao, Hu; Choung, Pill-Hoon; Shi, Songtao; Chai, Yang

    2009-04-01

    The vertebrate neural crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory cranial neural crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-beta signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.

  5. Alveolar bone grafting

    Directory of Open Access Journals (Sweden)

    Lilja Jan

    2009-10-01

    Full Text Available In patients with cleft lip and palate, bone grafting in the mixed dentition in the residual alveolar cleft has become a well-established procedure. The main advantages can be summarised as follows: stabilisation of the maxillary arch; facilitation of eruption of the canine and sometimes facilitation of the lateral incisor eruption; providing bony support to the teeth adjacent to the cleft; raising the alar base of the nose; facilitation of closure of an oro-nasal fistula; making it possible to insert a titanium fixture in the grafted site and to obtain favourable periodontal conditions of the teeth within and adjacent to the cleft. The timing of the ABG surgery take into consideration not only eruption of the canine but also that of the lateral incisor, if present. The best time for bone grafting surgery is when a thin shell of bone still covers the soon erupting lateral incisor or canine tooth close to the cleft.

  6. Inhibition of auxin movement from the shoot into the root inhibits lateral root development in Arabidopsis

    Science.gov (United States)

    Reed, R. C.; Brady, S. R.; Muday, G. K.

    1998-01-01

    In roots two distinct polar movements of auxin have been reported that may control different developmental and growth events. To test the hypothesis that auxin derived from the shoot and transported toward the root controls lateral root development, the two polarities of auxin transport were uncoupled in Arabidopsis. Local application of the auxin-transport inhibitor naphthylphthalamic acid (NPA) at the root-shoot junction decreased the number and density of lateral roots and reduced the free indoleacetic acid (IAA) levels in the root and [3H]IAA transport into the root. Application of NPA to the basal half of or at several positions along the root only reduced lateral root density in regions that were in contact with NPA or in regions apical to the site of application. Lateral root development was restored by application of IAA apical to NPA application. Lateral root development in Arabidopsis roots was also inhibited by excision of the shoot or dark growth and this inhibition was reversible by IAA. Together, these results are consistent with auxin transport from the shoot into the root controlling lateral root development.

  7. Nitric oxide prevents alveolar senescence and emphysema in a mouse model.

    Directory of Open Access Journals (Sweden)

    Amanda E Boe

    Full Text Available Nω-nitro-L-arginine methyl ester (L-NAME treatment induces arteriosclerosis and vascular senescence. Here, we report that the systemic inhibition of nitric oxide (NO production by L-NAME causes pulmonary emphysema. L-NAME-treated lungs exhibited both the structural (alveolar tissue destruction and functional (increased compliance and reduced elastance characteristics of emphysema development. Furthermore, we found that L-NAME-induced emphysema could be attenuated through both genetic deficiency and pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1. Because PAI-1 is an important contributor to the development of senescence both in vitro and in vivo, we investigated whether L-NAME-induced senescence led to the observed emphysematous changes. We found that L-NAME treatment was associated with molecular and cellular evidence of premature senescence in mice, and that PAI-1 inhibition attenuated these increases. These findings indicate that NO serves to protect and defend lung tissue from physiological aging.

  8. The role of synthetic biomaterials in resorptive alveolar bone regeneration

    Directory of Open Access Journals (Sweden)

    Kaličanin Biljana M.

    2007-01-01

    Full Text Available The alveolar bone tissue resorption defect has a significant role in dentistry. Because of the bone tissue deficit developed by alveolar resorption, the use of synthetic material CP/PLGA (calcium-phosphate/polylactide-co-gliycolide composite was introduced. Investigations were performed on rats with artificially produced resorption of the mandibular bone. The results show that the best effect on alveolar bone were attained by using nano-composite implants. The effect of the nanocomposite was ascertained by determining the calcium and phosphate content, as a basis of the hydroxyapatite structure. The results show that synthetic CP/PLGA nanocomposite alleviate the rehabilitation of weakened alveolar bone. Due to its osteoconductive effect, CP/PLGA can be the material of choice for bone substitution in the future.

  9. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona

    2010-01-01

    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release...... accumulated in type II alveolar epithelial cells, lacking CFTR. P. aeruginosa organisms were rarely present in inflamed alveoli. CONCLUSIONS: Chronic inflammation and remodeling is present in alveolar tissues of the CF lung and needs to be addressed by anti-inflammatory therapies....

  10. FGFR4 signaling couples to Bim and not Bmf to discriminate subsets of alveolar rhabdomyosarcoma cells.

    Science.gov (United States)

    Wachtel, Marco; Rakic, Jelena; Okoniewski, Michal; Bode, Peter; Niggli, Felix; Schäfer, Beat W

    2014-10-01

    Biological heterogeneity represents a major obstacle for cancer treatment. Therefore, characterization of treatment-relevant tumor heterogeneity is necessary to develop more effective therapies in the future. Here, we uncovered population heterogeneity among PAX/FOXO1-positive alveolar rhabdomyosarcoma by characterizing prosurvival networks initiated by FGFR4 signaling. We found that FGFR4 signaling rescues only subgroups of alveolar rhabdomyosarcoma cells from apoptosis induced by compounds targeting the IGF1R-PI3K-mTOR pathway. Differences in both proapoptotic machinery and FGFR4-activated signaling are involved in the different behavior of the phenotypes. Proapoptotic stress induced by the kinase inhibitors is sensed by Bim/Bad in rescue cells and by Bmf in nonrescue cells. Anti-apoptotic ERK1/2 signaling downstream of FGFR4 is long-lasting in rescue and short-termed in most non-rescue cells. Gene expression analysis detected signatures specific for these two groups also in biopsy samples. The different cell phenotypes are present in different ratios in alveolar rhabdomyosarcoma tumors and can be identified by AP2β expression levels. Hence, inhibiting FGFR signaling might represent an important strategy to enhance efficacy of current RMS treatments.

  11. Neutrophil-induced injury of rat pulmonary alveolar epithelial cells.

    Science.gov (United States)

    Simon, R H; DeHart, P D; Todd, R F

    1986-11-01

    The damage to pulmonary alveolar epithelial cells that occurs in many inflammatory conditions is thought to be caused in part by phagocytic neutrophils. To investigate this process, we exposed monolayers of purified rat alveolar epithelial cells to stimulated human neutrophils and measured cytotoxicity using a 51Cr-release assay. We found that stimulated neutrophils killed epithelial cells by a process that did not require neutrophil-generated reactive oxygen metabolites. Pretreatment of neutrophils with an antibody (anti-Mo1) that reduced neutrophil adherence to epithelial cells limited killing. Although a variety of serine protease inhibitors partially inhibited cytotoxicity, we found that neutrophil cytoplasts, neutrophil lysates, neutrophil-conditioned medium, purified azurophilic or specific granule contents, and purified human neutrophil elastase did not duplicate the injury. We conclude that stimulated neutrophils can kill alveolar epithelial cells in an oxygen metabolite-independent manner. Tight adherence of stimulated neutrophils to epithelial cell monolayers appears to promote epithelial cell killing.

  12. The importance of surfactant on the development of neonatal pulmonary diseases Síndrome da angustia respiratória aguda e proteinose alveolar congênita

    Directory of Open Access Journals (Sweden)

    Priscila Pinheiro Ribeiro Lyra

    2007-01-01

    Full Text Available Pulmonary surfactant is a substance composed of a lipoprotein complex that is essential to pulmonary function. Pulmonary surfactant proteins play an important role in the structure, function, and metabolism of surfactant; 4 specific surfactant proteins have been identified: surfactant proteins-A, surfactant proteins-B, surfactant proteins-C, and surfactant proteins-D. Clinical, epidemiological, and biochemical evidence suggests that the etiology of respiratory distress syndrome is multifactorial with a significant genetic component. There are reports about polymorphisms and mutations on the surfactant protein genes, especially surfactant proteins-B, that may be associated with respiratory distress syndrome, acute respiratory distress syndrome, and congenital alveolar proteinosis. Individual differences regarding respiratory distress syndrome and acute respiratory distress syndrome as well as patient response to therapy might reflect phenotypic diversity due to genetic variation, in part. The study of the differences between the allelic variants of the surfactant protein genes can contribute to the understanding of individual susceptibility to the development of several pulmonary diseases. The identification of the polymorphisms and mutations that are indeed important for the pathogenesis of the diseases related to surfactant protein dysfunction, leading to the possibility of genotyping individuals at increased risk, constitutes a new research field. In the future, findings in these endeavors may enable more effective genetic counseling as well as the development of prophylactic and therapeutic strategies that would provide a real impact on the management of newborns with respiratory distress syndrome and other pulmonary diseases.O surfactante pulmonar é uma substância composta por um complexo lipoprotéico essencial para a função pulmonar normal. As proteínas do surfactante têm importante papel na estrutura, função e metabolismo do

  13. [Development of a peristaltic inhibition model in mice].

    Science.gov (United States)

    Cui, S; Li, Y; Li, Y; Han, C

    2000-11-01

    Diphenoxylate was administered to mice at the dose of 5 mg/kg BW for the development of peristaltic inhibition model for formulating the examination procedure of health foods. An ink solution containing 5% charcoal was then administered 30 minutes later. The length of ink progradation of the small intestine of mice was calculated 25 minutes after the administration of ink. The results in this model was stable and reliable, and it was recommended to use this model to verify the function of health foods.

  14. Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS.

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    Wenli Yang

    Full Text Available The hepatopulmonary syndrome (HPS develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2 play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL. We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064 induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.

  15. Oxidative Stress, Cell Death, and Other Damage to Alveolar Epithelial Cells Induced by Cigarette Smoke

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    Nagai A

    2003-09-01

    Full Text Available Abstract Cigarette smoking is a major risk factor in the development of various lung diseases, including pulmonary emphysema, pulmonary fibrosis, and lung cancer. The mechanisms of these diseases include alterations in alveolar epithelial cells, which are essential in the maintenance of normal alveolar architecture and function. Following cigarette smoking, alterations in alveolar epithelial cells induce an increase in epithelial permeability, a decrease in surfactant production, the inappropriate production of inflammatory cytokines and growth factors, and an increased risk of lung cancer. However, the most deleterious effect of cigarette smoke on alveolar epithelial cells is cell death, i.e., either apoptosis or necrosis depending on the magnitude of cigarette smoke exposure. Cell death induced by cigarette smoke exposure can largely be accounted for by an enhancement in oxidative stress. In fact, cigarette smoke contains and generates many reactive oxygen species that damage alveolar epithelial cells. Whether apoptosis and/or necrosis in alveolar epithelial cells is enhanced in healthy cigarette smokers is presently unclear. However, recent evidence indicates that the apoptosis of alveolar epithelial cells and alveolar endothelial cells is involved in the pathogenesis of pulmonary emphysema, an important cigarette smoke-induced lung disease characterized by the loss of alveolar structures. This review will discuss oxidative stress, cell death, and other damage to alveolar epithelial cells induced by cigarette smoke.

  16. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    Science.gov (United States)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  17. Role of ICAM-1 in the aggregation and adhesion of human alveolar macrophages in response to TNF-α and INF-γ

    Directory of Open Access Journals (Sweden)

    Masahiro Sasaki

    2001-01-01

    Full Text Available Intracellular adhesion molecule-1 (ICAM-1-mediated cell-cell adhesion is thought to play an important role at sites of inflammation. Recent evidence suggests that ICAM-1 surface expression on alveolar macrophages is increased in pulmonary sarcoidosis and that inflammatory granuloma formation is characterized by the aggregation of macrophages. The present study shows that ICAM-1 expression is significantly elevated on alveolar macrophages from patients with sarcoidosis in response to tumor necrosis factor-α (TNF-α and interferon- γ (INF-γ compared with healthy controls. Aggregation and adhesion were significantly increased in alveolar macrophages treated with TNF-α and INF-γ, and significantly inhibited in those pretreated with a monoclonal antibody to ICAM-1. Similarly, aggregation and adhesion were inhibited in macrophages treated with heparin, which then exhibited a wide range of biological activities relevant to inflammation. These results suggested that the surface expression of ICAM-1 on alveolar macrophages in response to TNF-α and INF-γ is important in mediating aggregation and adhesion. Additionally, heparin may be useful for developing novel therapeutic agents for fibrotic lung disease.

  18. Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments

    Science.gov (United States)

    Lewis, Katherine Jean Reeder

    The alveolar epithelium consists of two cell phenotypes, elongated alveolar type I cells (AT1) and rounded alveolar type II cells (ATII), and exists in a complex three-dimensional environment as a polarized cell layer attached to a thin basement membrane and enclosing a roughly spherical lumen. Closely surrounding the alveolar cysts are capillary endothelial cells as well as interstitial pulmonary fibroblasts. Many factors are thought to influence alveolar epithelial cell differentiation during lung development and wound repair, including physical and biochemical signals from the extracellular matrix (ECM), and paracrine signals from the surrounding mesenchyme. In particular, disrupted signaling between the alveolar epithelium and local fibroblasts has been implicated in the progression of several pulmonary diseases. However, given the complexity of alveolar tissue architecture and the multitude of signaling pathways involved, designing appropriate experimental platforms for this biological system has been difficult. In order to isolate key factors regulating cellular behavior, the researcher ideally should have control over biophysical properties of the ECM, as well as the ability to organize multiple cell types within the scaffold. This thesis aimed to develop a 3D synthetic hydrogel platform to control alveolar epithelial cyst formation, which could then be used to explore how extracellular cues influence cell behavior in a tissue-relevant cellular arrangement. To accomplish this, a poly(ethylene glycol) (PEG) hydrogel network containing enzymatically-degradable crosslinks and bioadhesive pendant peptides was employed as a base material for encapsulating primary alveolar epithelial cells. First, an array of microwells of various cross-sectional shapes was photopatterned into a PEG gel containing photo-labile crosslinks, and primary ATII cells were seeded into the wells to examine the role of geometric confinement on differentiation and multicellular arrangement

  19. An Optimised Human Cell Culture Model for Alveolar Epithelial Transport

    Science.gov (United States)

    Birch, Nigel P.; Suresh, Vinod

    2016-01-01

    Robust and reproducible in vitro models are required for investigating the pathways involved in fluid homeostasis in the human alveolar epithelium. We performed functional and phenotypic characterisation of ion transport in the human pulmonary epithelial cell lines NCI-H441 and A549 to determine their similarity to primary human alveolar type II cells. NCI-H441 cells exhibited high expression of junctional proteins ZO-1, and E-cadherin, seal-forming claudin-3, -4, -5 and Na+-K+-ATPase while A549 cells exhibited high expression of pore-forming claudin-2. Consistent with this phenotype NCI-H441, but not A549, cells formed a functional barrier with active ion transport characterised by higher electrical resistance (529 ± 178 Ω cm2 vs 28 ± 4 Ω cm2), lower paracellular permeability ((176 ± 42) ×10−8 cm/s vs (738 ± 190) ×10−8 cm/s) and higher transepithelial potential difference (11.9 ± 4 mV vs 0 mV). Phenotypic and functional properties of NCI-H441 cells were tuned by varying cell seeding density and supplement concentrations. The cells formed a polarised monolayer typical of in vivo epithelium at seeding densities of 100,000 cells per 12-well insert while higher densities resulted in multiple cell layers. Dexamethasone and insulin-transferrin-selenium supplements were required for the development of high levels of electrical resistance, potential difference and expression of claudin-3 and Na+-K+-ATPase. Treatment of NCI-H441 cells with inhibitors and agonists of sodium and chloride channels indicated sodium absorption through ENaC under baseline and forskolin-stimulated conditions. Chloride transport was not sensitive to inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) under either condition. Channels inhibited by 5-nitro-1-(3-phenylpropylamino) benzoic acid (NPPB) contributed to chloride secretion following forskolin stimulation, but not at baseline. These data precisely define experimental conditions for the application of NCI

  20. Partial pulmonary embolization disrupts alveolarization in fetal sheep

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    Hooper Stuart B

    2010-04-01

    Full Text Available Abstract Background Although bronchopulmonary dysplasia is closely associated with an arrest of alveolar development and pulmonary capillary dysplasia, it is unknown whether these two features are causally related. To investigate the relationship between pulmonary capillaries and alveolar formation, we partially embolized the pulmonary capillary bed. Methods Partial pulmonary embolization (PPE was induced in chronically catheterized fetal sheep by injection of microspheres into the left pulmonary artery for 1 day (1d PPE; 115d gestational age; GA or 5 days (5d PPE; 110-115d GA. Control fetuses received vehicle injections. Lung morphology, secondary septal crests, elastin, collagen, myofibroblast, PECAM1 and HIF1α abundance and localization were determined histologically. VEGF-A, Flk-1, PDGF-A and PDGF-Rα mRNA levels were measured using real-time PCR. Results At 130d GA (term ~147d, in embolized regions of the lung the percentage of lung occupied by tissue was increased from 29 ± 1% in controls to 35 ± 1% in 1d PPE and 44 ± 1% in 5d PPE fetuses (p VEGF and Flk-1, although a small increase in PDGF-Rα expression at 116d GA, from 1.00 ± 0.12 in control fetuses to 1.61 ± 0.18 in 5d PPE fetuses may account for impaired differentiation of alveolar myofibroblasts and alveolar development. Conclusions PPE impairs alveolarization without adverse systemic effects and is a novel model for investigating the role of pulmonary capillaries and alveolar myofibroblasts in alveolar formation.

  1. Inhibition of Haemonchus contortus larval development by fungal lectins.

    Science.gov (United States)

    Heim, Christian; Hertzberg, Hubertus; Butschi, Alex; Bleuler-Martinez, Silvia; Aebi, Markus; Deplazes, Peter; Künzler, Markus; Štefanić, Saša

    2015-08-19

    Lectins are carbohydrate-binding proteins that are involved in fundamental intra- and extracellular biological processes. They occur ubiquitously in nature and are especially abundant in plants and fungi. It has been well established that certain higher fungi produce lectins in their fruiting bodies and/or sclerotia as a part of their natural resistance against free-living fungivorous nematodes and other pests. Despite relatively high diversity of the glycan structures in nature, many of the glycans targeted by fungal lectins are conserved among organisms of the same taxon and sometimes even among different taxa. Such conservation of glycans between free-living and parasitic nematodes is providing us with a useful tool for discovery of novel chemotherapeutic and vaccine targets. In our study, a subset of fungal lectins emanating from toxicity screens on Caenorhabditis elegans was tested for their potential to inhibit larval development of Haemonchus contortus. The effect of Coprinopsis cinerea lectins - CCL2, CGL2, CGL3; Aleuria aurantia lectin - AAL; Marasmius oreades agglutinin - MOA; and Laccaria bicolor lectin - Lb-Tec2, on cultivated Haemonchus contortus larval stages was investigated using a larval development test (LDT). To validate the results of the toxicity assay and determine lectin binding capacity to the nematode digestive tract, biotinylated versions of lectins were fed to pre-infective larval stages of H. contortus and visualized by fluorescent microscopy. Lectin histochemistry on fixed adult worms was performed to investigate the presence and localisation of lectin binding sites in the disease-relevant developmental stage. Using an improved larval development test we found that four of the six tested lectins: AAL, CCL2, MOA and CGL2, exhibited a dose-dependent toxicity in LDT, as measured by the number of larvae developing to the L3 stage. In the case of AAL, CGL2 and MOA lectin, doses as low as 5 μg/ml caused >95 % inhibition of larval

  2. Pulmonary alveolar microlithiasis with calcified pleural plaques

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    Malhotra Balbir

    2010-01-01

    Full Text Available Pulmonary alveolar microlithiasis (PAM is a rare disease. Herein we report a case of pulmonary alveolar microlithiasis who was suspected to have the disease on chest X-ray and was confirmed on high resolution CT and transbronchial lung biopsy. These investigations showed characteristic features of pulmonary alveolar microlithiasis with diffuse interstitial pulmonary fibrosis.

  3. Beta-adrenoceptor stimulation of alveolar fluid clearance is increased in rats with heart failure.

    Science.gov (United States)

    Maron, Michael B; Luther, Daniel J; Pilati, Charles F; Ohanyan, Vahagn; Li, Tianbo; Koshy, Shyny; Horne, Walter I; Meszaros, J Gary; Walro, Jon M; Folkesson, Hans G

    2009-09-01

    The alveolar epithelium plays a critical role in resolving pulmonary edema. We thus hypothesized that its function might be upregulated in rats with heart failure, a condition that severely challenges the lung's ability to maintain fluid balance. Heart failure was induced by left coronary artery ligation. Echocardiographic and cardiovascular hemodynamics confirmed its development at 16 wk postligation. At that time, alveolar fluid clearance was measured by an increase in protein concentration over 1 h of a 5% albumin solution instilled into the lungs. Baseline alveolar fluid clearance was similar in heart failure and age-matched control rats. Terbutaline was added to the instillate to determine whether heart failure rats responded to beta-adrenoceptor stimulation. Alveolar fluid clearance in heart failure rats was increased by 194% after terbutaline stimulation compared with a 153% increase by terbutaline in control rats. To determine the mechanisms responsible for this accelerated alveolar fluid clearance, we measured ion transporter expression (ENaC, Na-K- ATPase, CFTR). No significant upregulation was observed for these ion transporters in the heart failure rats. Lung morphology showed significant alveolar epithelial type II cell hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell hyperplasia is the likely explanation for the increased terbutaline-stimulated alveolar fluid clearance in heart failure rats. These data provide evidence for previously unrecognized mechanisms that can protect against or hasten resolution of alveolar edema in heart failure.

  4. 鼠哺乳期二(噁)英暴露对子代牙槽骨生长发育的影响%Effects of lactational dioxin exposure to development of alveolar bone in SD rat offspring

    Institute of Scientific and Technical Information of China (English)

    耿华欧; 章锦才; 胡彬; 王京滨

    2008-01-01

    目的 研究鼠哺乳期二(噁)英类物质2,3,7,8-四氯二苯对二(噁)英暴露对大鼠仔鼠牙槽骨生长发育的影响.方法 60天龄2,3,7,8-四氯二苯对二(噁)英暴露组和对照组仔大鼠被处死,将其带有磨牙的上颌骨行树脂包埋,制备硬组织磨片并在荧光显微镜下观察,对两实验组牙槽骨的组织形态、荧光标记情况及组织形态计量学参数进行比较.结果 与对照组相比,二(噁)英暴露组牙槽骨骨小梁结构较为疏松,荧光标记较紊乱.实验组与对照组骨小梁宽度分别为(52.5±5.2)μm及(59.4±6.6)μm,二者差异有统计学意义(P<0.05);骨小梁数目分别为(3.27±0.23)mm-1及(3.75±0.29)mm-1,差异有统计学意义(P<0.01);骨小梁分离度分别为(217.3±37.6)μm及(177.6±33.8)μm,差异有统计学意义(P<0.05);矿化沉积率分别为(0.68±0.08)μm/d及(0.95±0.12)μm/d,差异亦有统计学意义(P<0.05).结论 二(噁)英类物质哺乳期暴露显著降低了大鼠仔鼠牙槽骨的质、量,并影响其空间构型.%Objective To study the influence of lactational dioxin exposure(2,3,7,8-tetrachlorodibenzo-p-dixon,TCDD)on development of alveolar bone in SD rat offspring.Methods The rats of TCDD exposure group and control group were sacrificed and the alveolar bone with molars of PD60 rats in the two groups were embedded in resin.The sections were observed by fluorescent microscope.The alveolar bone formation was evaluated by histological examination,tetracycline fluorescence marker and quantitative histomorphometry.The indices of quantitative histomorphometry were compaired.Resuits The trabecular structure of abeolar bone was looser in TCDD exposure group than in the control group.The tetracycline fluorescence markers were more disorganized in TCDD group.The indices of quantitative histomorphometry of alveolar bone between two groups showed significantly difierent. Conclusions Lactational 2,3,7,8-TCDD exposure decreased the quality and quantity of

  5. True Fibroma of Alveolar Mucosa

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    Shankargouda Patil

    2014-01-01

    Full Text Available Benign fibrous overgrowths are often found in the oral cavity, almost always being reactive/irritational in nature. However, benign mesenchymal neoplasms of the fibroblasts are extremely uncommon. Here we report a case of “True Fibroma of Alveolar Mucosa” for its rarity.

  6. Temporal dynamics of the developing lung transcriptome in three common inbred strains of laboratory mice reveals multiple stages of postnatal alveolar development

    OpenAIRE

    Beauchemin, Kyle J.; Julie M. Wells; Kho, Alvin T.; Philip, Vivek M.; Kamir, Daniela; Kohane, Isaac S; Graber, Joel H.; Bult, Carol J.

    2016-01-01

    To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns w...

  7. Is alveolar cleft reconstruction still controversial? (Review of literature

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    Sameh A. Seifeldin

    2016-01-01

    Full Text Available Cleft lip and palate (CL/P is a frequent congenital malformation that manifests in several varieties including unilateral or bilateral and complete or incomplete. Alveolar cleft reconstruction remains controversial with regard to timing, graft materials, surgical techniques, and methods of evaluation. Many studies have been conducted addressing these points to develop an acceptable universal protocol for managing CL/P. The primary goal of alveolar cleft reconstruction in CL/P patients is to provide a bony bridge at the cleft site that allows maxillary arch continuity, oronasal fistula repair, eruption of the permanent dentition into the newly formed bone, enhances nasal symmetry through providing alar base support, orthodontic movement and placement of osseointegrated implants when indicated. Other goals include improving speech, improvement of periodontal conditions, establishing better oral hygiene, and limiting growth disturbances. In order to rehabilitate oral function in CL/P patients alveolar bone grafting is necessary. Secondary bone grafting is the most widely accepted method for treating alveolar clefts. Autogenous bone graft is the primary source for reconstructing alveolar cleft defects and is currently the preferred grafting material.

  8. Megalin mediates transepithelial albumin clearance from the alveolar space of intact rabbit lungs.

    Science.gov (United States)

    Buchäckert, Yasmin; Rummel, Sebastian; Vohwinkel, Christine U; Gabrielli, Nieves M; Grzesik, Benno A; Mayer, Konstantin; Herold, Susanne; Morty, Rory E; Seeger, Werner; Vadász, István

    2012-10-15

    The alveolo-capillary barrier is effectively impermeable to large solutes such as proteins. A hallmark of acute lung injury/acute respiratory distress syndrome is the accumulation of protein-rich oedema fluid in the distal airspaces. Excess protein must be cleared from the alveolar space for recovery; however, the mechanisms of protein clearance remain incompletely understood. In intact rabbit lungs 29.8 ± 2.2% of the radio-labelled alveolar albumin was transported to the vascular compartment at 37°C within 120 min, as assessed by real-time measurement of 125I-albumin clearance from the alveolar space. At 4°C or 22°C significantly lower albumin clearance (3.7 ± 0.4 or 16.2 ± 1.1%, respectively) was observed. Deposition of a 1000-fold molar excess of unlabelled albumin into the alveolar space or inhibition of cytoskeletal rearrangement or clathrin-dependent endocytosis largely inhibited the transport of 125I-albumin to the vasculature, while administration of unlabelled albumin to the vascular space had no effect on albumin clearance. Furthermore, albumin uptake capacity was measured as about 0.37 mg ml−1 in cultured rat lung epithelial monolayers, further highlighting the (patho)physiological relevance of active alveolar epithelial protein transport. Moreover, gene silencing and pharmacological inhibition of the multi-ligand receptor megalin resulted in significantly decreased albumin binding and uptake in monolayers of primary alveolar type II and type I-like and cultured lung epithelial cells. Our data indicate that clearance of albumin from the distal air spaces is facilitated by an active, high-capacity, megalin-mediated transport process across the alveolar epithelium. Further understanding of this mechanism is of clinical importance, since an inability to clear excess protein from the alveolar space is associated with poor outcome in patients with acute lung injury/acute respiratory distress syndrome.

  9. A contemporary perspective on techniques for the clinical assessment of alveolar bone

    Energy Technology Data Exchange (ETDEWEB)

    Hausmann, E. (State Univ. of New York, Buffalo (USA))

    1990-03-01

    Radiographic techniques, traditional ones as well as newer ones under development, for clinically assessing alveolar bone are critically assessed. Traditional intraoral radiography is reexamined, in particular with regard to the accuracy with which the alveolar crest is seen. Evidence is presented for a more accurate representation of the alveolar crest on bitewings rather than periapical films. Application in periodontics of newer radiographic techniques, subtraction radiography, and single and dual photon aborptiometry presently under clinical development are discussed in regard to their potential and limitations. Similarly, radiopharmaceuticals to evaluate the metabolic status of alveolar bone are discussed as well as the potential for using analyses of gingival crevice fluid as a window for assessment of alveolar crest metabolism. 46 references.

  10. Impact of alginate-producing Pseudomonas aeruginosa on alveolar macrophage apoptotic cell clearance.

    Science.gov (United States)

    McCaslin, Charles A; Petrusca, Daniela N; Poirier, Christophe; Serban, Karina A; Anderson, Gregory G; Petrache, Irina

    2015-01-01

    Pseudomonas aeruginosa infection is a hallmark of lung disease in cystic fibrosis. Acute infection with P. aeruginosa profoundly inhibits alveolar macrophage clearance of apoptotic cells (efferocytosis) via direct effect of virulence factors. During chronic infection, P. aeruginosa evades host defense by decreased virulence, which includes the production or, in the case of mucoidy, overproduction of alginate. The impact of alginate on innate immunity, in particular on macrophage clearance of apoptotic cells is not known. We hypothesized that P. aeruginosa strains that exhibit reduced virulence impair macrophage clearance of apoptotic cells and we investigated if the polysaccharide alginate produced by mucoid P. aeruginosa is sufficient to inhibit alveolar macrophage efferocytosis. Rat alveolar or human peripheral blood monocyte (THP-1)-derived macrophage cell lines were exposed in vitro to exogenous alginate or to wild type or alginate-overproducing mucoid P. aeruginosa prior to challenge with apoptotic human Jurkat T-lymphocytes. The importance of LPS contamination and that of structural integrity of alginate polymers was tested using alginate of different purities and alginate lyase, respectively. Alginate inhibited alveolar macrophage efferocytosis in a dose- and time-dependent manner. This effect was augmented but not exclusively attributed to lipopolysaccharide (LPS) present in alginates. Alginate-producing P. aeruginosa inhibited macrophage efferocytosis by more than 50%. A mannuronic-specific alginate lyase did not restore efferocytosis inhibited by exogenous guluronic-rich marine alginate, but had a marked beneficial effect on efferocytosis of alveolar macrophages exposed to mucoid P. aeruginosa. Despite decreased virulence, mucoid P. aeruginosa may contribute to chronic airway inflammation through significant inhibition of alveolar clearance of apoptotic cells and debris. The mechanism by which mucoid bacteria inhibit efferocytosis may involve alginate

  11. A Latent Variables Examination of Processing Speed, Response Inhibition, and Working Memory during Typical Development

    Science.gov (United States)

    McAuley, Tara; White, Desiree A.

    2011-01-01

    This study addressed three related aims: (a) to replicate and extend previous work regarding the nonunitary nature of processing speed, response inhibition, and working memory during development; (b) to quantify the rate at which processing speed, response inhibition, and working memory develop and the extent to which the development of these…

  12. Reversible transdifferentiation of alveolar epithelial cells.

    Science.gov (United States)

    Danto, S I; Shannon, J M; Borok, Z; Zabski, S M; Crandall, E D

    1995-05-01

    Alveolar epithelial type II (AT2) cells have been thought to be the progenitors of terminally differentiated type I (AT1) cells in the adult animal in vivo. In this study, we used an AT1 cell-specific monoclonal antibody (mAb VIII B2) to investigate expression of the AT1 cell phenotype accompanying reversible changes in expression of the AT2 cell phenotype. AT2 cells were isolated and cultured either on attached collagen gels or on gels detached 1 or 4 days after plating and maintained thereafter as floating gels. Monolayers on both attached and floating gels were harvested on days 4 and 8 and analyzed by electron microscopy for changes in morphology and binding of mAb VIII B2. Results indicate that: (1) alveolar epithelial cells (AEC) on attached gels develop characteristics of the AT1 cell phenotype, (2) AEC on gels detached on day 1 maintain features of the AT2 cell phenotype (and do not react with mAb VIII B2), and (3) the expression of AT1 cell phenotypic traits seen by day 4 on attached gels is reversed after detachment. We conclude that commitment to the AT1 and AT2 cell lineages requires continuous regulatory input to maintain the differentiated states, and that transdifferentiation between AT2 and AT1 cells may be reversible.

  13. PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma.

    Science.gov (United States)

    Marshall, Amy D; van der Ent, Martijn A; Grosveld, Gerard C

    2012-10-01

    We and others have identified FGFR4 as a direct transcriptional target of the alveolar rhabdomyosarcoma (ARMS) specific fusion protein, PAX3-FOXO1. We hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector of PAX3-FOXO1, contributing to PAX3-FOXO1 tumorigenic phenotypes. However, we demonstrate that enhanced expression of FGFR4 does not contribute to inhibited differentiation, enhanced proliferation, or transformation downstream of PAX3-FOXO1 in primary mouse myoblasts. Therefore we were unable to identify any contribution of up regulation of wild type FGFR4 to PAX3-FOXO1 driven tumorigenesis. Conversely, a constitutively active mutant of FGFR4 can enhance primary myoblast proliferation and transformation, indicating activating mutations of FGFR4 could contribute to the development and progression of ARMS. We sequenced the FGFR4 mRNA from five ARMS cell lines and identified no somatic mutations, nor any association with any human single nucleotide polymorphism within the FGFR4 coding region.

  14. [Persistent dento-alveolar pain disorder (PDAP)].

    Science.gov (United States)

    Warnsinck, C J; Koutris, M; Shemesh, H; Lobbezoo, F

    2015-02-01

    Dento-alveolar pain is common in the orofacial area. Persistent dento-alveolar pain could be experienced without an identifiable etiology with poor response to existing treatments. Confusion about the diagnosis and classification of persistent dento-alveolar pain (PDAP) disorders could explain the difficulties in treatment and unfavorable prognosis. Recently, initial steps were made to improve the taxonomy and diagnostic criteria for PDAP in order to improve clinical research and care.

  15. Hydrogen sulfide donor regulates alveolar epithelial cell apoptosis in rats with acute lung injury

    Institute of Scientific and Technical Information of China (English)

    LIU Wen-li; LIU Zhi-wei; LI Tian-shui; WANG Cong; ZHAO Bin

    2013-01-01

    Background Acute lung injury (ALl) is a common syndrome associated with high morbidity and mortality in emergency medicine.Cell apoptosis plays a key role in the pathogenesis of ALl.Hydrogen sulfide (H2S) plays a protective role during acute lung injury.We designed this study to examine the role of H2S in the lung alveolar epithelial cell apoptosis in rats with ALl.Methods Sixty-nine male Sprague Dawley rats were used.ALl was induced by intra-tail vein injection of oleic acid (OA).NaHS solution was injected intraperitonally 30 minutes before OA injection as the NaHS pretreatment group.Single sodium hydrosulfide pretreatment group and control group were designed.Index of quantitative assessment (IQA),wet/dry weight (W/D) ratio and the percentage of polymorphonuclear leukocyte (PMN) cells in the bronchoalveolar lavage fluid (BALF) were determined.H2S level in lung tissue was measured by a sensitive sulphur electrode.Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Fas protein was measured by immunohistochemical staining.Results The level of endogenous H2S in lung tissue decreased with the development of ALl induced by OA injection.Apoptosis and Fas protein in alveolar epithelial cells increased in the ALl of rats but NaHS lessened apoptosis and Fas protein expression in alveolar epithelial cells of rats with ALl.Conclusion Endogenous H2S protects rats from oleic acid-induced ALl,probably by inhibiting cell apoptosis.

  16. The role of probiotic on alveolar bone resorption

    Directory of Open Access Journals (Sweden)

    Desi Sandra Sari

    2011-09-01

    Full Text Available Background: Probiotics are microbes derived from the group of lactic acid bacteria that work to maintain the health of hosts. Probiotics can also be used to improve oral health. Periodontal disease is usually marked with gingival inflammation and alveolar bone resorption. Gram negative anaerobic bacteria that play important role in human periodontal disease are Porphyromonas gingivalis. (P. gingivalis. P. gingivalis is a virulent bacteria in vivo or in vitro, and mostly found in subgingival plaque of periodontitis patients. Purpose: This study is aimed to know the role of probiotics to inhibit the resorption of alveolar bone induced with P. gingivalis. Methods: This study used male wistar rats divided into 4 groups. Group I was control group (without treatment; group II was induced with P. gingivalis ATCC 33277 for 5 days; group III was induced with P. gingivalis ATCC 33277 and also injected with probiotics (Lactobacillus casei ATCC 4224 for 5 days simultaneously; and group IV was induced with P. gingivalis ATCC 33277 for 5 days and also injected by probiotics (Lactobacillus casei ATCC 4224 in the next 5 days. After that, the samples were decapitated, taken their alveolar bone, and then were examined by immunohistochemistry to observe osteoclast activity in alveolar bone resorption by using tartrate-resistant acid phosphatase (TRAP expression. All data were then analyzed statistically. Results: It is known that there were significant differences of TRAP expression among all those treatment groups (p < 0.05. Conclusion: It then can be concluded that probiotics can decrease osteoclast activity in periodontal tissue of wistar rats, so it can inhibit alveolar bone resorption.Latar belakang: Probiotik adalah mikroba dari golongan bakteri asam laktat yang bekerja mempertahankan kesehatan host dan probiotik dapat digunakan untuk meningkatkan kesehatan rongga mulut. Penyakit periodontal ditandai dengan adanya keradangan pada gingiva dan resobsi tulang

  17. EP4 inhibition attenuates the development of diabetic and non-diabetic experimental kidney disease.

    Science.gov (United States)

    Thieme, Karina; Majumder, Syamantak; Brijmohan, Angela S; Batchu, Sri N; Bowskill, Bridgit B; Alghamdi, Tamadher A; Advani, Suzanne L; Kabir, M Golam; Liu, Youan; Advani, Andrew

    2017-06-13

    The therapeutic targeting of prostanoid subtype receptors may slow the development of chronic kidney disease (CKD) through mechanisms that are distinct from those of upstream COX inhibition. Here, employing multiple experimental models of CKD, we studied the effects of inhibition of the EP4 receptor, one of four receptor subtypes for the prostanoid prostaglandin E2. In streptozotocin-diabetic endothelial nitric oxide synthase knockout mice, EP4 inhibition attenuated the development of albuminuria, whereas the COX inhibitor indomethacin did not. In Type 2 diabetic db/db mice, EP4 inhibition lowered albuminuria to a level comparable with that of the ACE inhibitor captopril. However, unlike captopril, EP4 inhibition had no effect on blood pressure or hyperfiltration although it did attenuate mesangial matrix accumulation. Indicating a glucose-independent mechanism of action, EP4 inhibition also attenuated proteinuria development and glomerular scarring in non-diabetic rats subjected to surgical renal mass ablation. Finally, in vitro, EP4 inhibition prevented transforming growth factor-ß1 induced dedifferentiation of glomerular podocytes. In rodent models of diabetic and non-diabetic CKD, EP4 inhibition attenuated renal injury through mechanisms that were distinct from either broadspectrum COX inhibition or "standard of care" renin angiotensin system blockade. EP4 inhibition may represent a viable repurposing opportunity for the treatment of CKD.

  18. Behavioral Inhibition as a Risk Factor for the Development of Childhood Anxiety Disorders: A Longitudinal Study

    OpenAIRE

    Muris, Peter; Brakel, Anna; Arntz, Arnoud; Schouten, Erik

    2010-01-01

    textabstractThis longitudinal study examined the additive and interactive effects of behavioral inhibition and a wide range of other vulnerability factors in the development of anxiety problems in youths. A sample of 261 children, aged 5 to 8 years, 124 behaviorally inhibited and 137 control children, were followed during a 3-year period. Assessments took place on three occasions to measure children's level of behavioral inhibition, anxiety disorder symptoms, other psychopathological symptoms...

  19. Pulmonary alveolar proteinosis in a cat

    NARCIS (Netherlands)

    Szatmári, Viktor; Teske, Erik; Nikkels, Peter G J; Griese, Matthias; de Jong, Pim A; Grinwis, Guy; Theegarten, Dirk; Veraa, Stefanie; van Steenbeek, Frank G; Drent, Marjolein; Bonella, Francesco

    2015-01-01

    BACKGROUND: Pulmonary alveolar proteinosis is an extremely rare lung disease in animals and humans. It is characterized by the deposition of a large amount of phospholipoproteinaceous material in the alveoli. There are several possible etiologies, both congenital and acquired. Alveolar macrophages

  20. Pulmonary alveolar proteinosis in a cat

    NARCIS (Netherlands)

    Szatmári, Viktor; Teske, Erik; Nikkels, Peter G J; Griese, Matthias; de Jong, Pim A; Grinwis, Guy; Theegarten, Dirk; Veraa, Stefanie; van Steenbeek, Frank G; Drent, Marjolein; Bonella, Francesco

    2015-01-01

    BACKGROUND: Pulmonary alveolar proteinosis is an extremely rare lung disease in animals and humans. It is characterized by the deposition of a large amount of phospholipoproteinaceous material in the alveoli. There are several possible etiologies, both congenital and acquired. Alveolar macrophages p

  1. Intracranial alveolar echinococcosis: CT and MRI

    Energy Technology Data Exchange (ETDEWEB)

    Bensaid, A.H. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Dietemann, J.L. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Filippi de la Palavesa, M.M. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Klinkert, A. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Kastler, B. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Gangi, A. (Dept. of Radiology B, Univ. Hospital, Strasbourg (France)); Jacquet, G. (Dept. of Neurosurgery, Univ. Hospital, Besancon (France)); Cattin, F. (Dept. of Radiology, Univ. Hospital, Besancon (France))

    1994-05-01

    Intracranial alveolar echinococcosis is uncommon. We report a patient with right frontal lobe and palpebral lesions secondary to a primary hepatic focus with secondary lesion in the lung. The intracranial and palpebral cystic masses were totally removed and both proved to be alveolar hydatid cysts. An unusual feature in this case is CT and MRI demonstration of dural and bony extension. (orig.)

  2. Pulmonary alveolar microlithiasis in children

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, H. [Center of Diagnostic Radiology, Frankfurt Univ. (Germany); Loercher, U. [Center of Diagnostic Radiology, Frankfurt Univ. (Germany); Kitz, R. [Center of Pediatrics, Frankfurt Univ. (Germany); Zielen, S. [Center of Pediatrics, Frankfurt Univ. (Germany); Ahrens, P. [Center of Pediatrics, Frankfurt Univ. (Germany); Koenig, R. [Inst. of Human Genetics, Frankfurt Univ. (Germany)

    1996-01-01

    Two asymptomatic Turkish sibs are presented, a 4-year-old boy and his 7-year-old sister, with pulmonary alveolar microlithiasis (PAM) confirmed by transbronchial lung biopsy and bronchoalveolar lavage. Chest radiographs and high resolution CT demonstrated wide-spread intra-alveolar calcifications in both lungs. The lesions were sharply defined and less than 1 mm in diameter. CT documented a high concentration of microliths along the bronchovascular bundles, the intralobular fissue and the (sub)pleural lung parenchyma. The combination of bronchoalveolar lavage and roentgenographic appearance in high resolution CT are characteristic and pathognomonic, and can confirm the diagnosis. The more severe changes in the elder sib and the radiographic controls suggest that the pulmonary disease may be progressive in our patients. The described family of consanguineous, unaffected parents with two affected and one healthy child confirmed the autosomal recessive inheritance of PAM (McKusick 265100). In addition, the affected girl had autosomal recessive Waardenburg-anophthalmia syndrome (McKusick 206920), raising the question of whether this is a chance occurrence or possibly a contiguous gene syndrome. (orig.)

  3. High CO2 levels impair alveolar epithelial function independently of pH.

    Directory of Open Access Journals (Sweden)

    Arturo Briva

    Full Text Available BACKGROUND: In patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2 is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells. Signaling pathways sensitive to changes in CO2 levels were described in plants and neuronal mammalian cells. However, it has not been fully elucidated whether non-neuronal cells sense and respond to CO2. The Na,K-ATPase consumes approximately 40% of the cellular metabolism to maintain cell homeostasis. Our study examines the effects of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar fluid reabsorption which is a marker of alveolar epithelial function. PRINCIPAL FINDINGS: We found that short-term increases in pCO2 impaired alveolar fluid reabsorption in rats. Also, we provide evidence that non-excitable, alveolar epithelial cells sense and respond to high levels of CO2, independently of extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via activation of PKCzeta which phosphorylates the Na,K-ATPase, causing it to endocytose from the plasma membrane into intracellular pools. CONCLUSIONS: Our data suggest that alveolar epithelial cells, through which CO2 is eliminated in mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar epithelial function, independently of pH, which is relevant in patients with lung diseases and altered alveolar gas exchange.

  4. Behavioral Inhibition as a Risk Factor for the Development of Childhood Anxiety Disorders: A Longitudinal Study

    NARCIS (Netherlands)

    P.E.H.M. Muris (Peter); A.M.L. van Brakel (Anna); A. Arntz (Arnoud); E. Schouten (Erik)

    2011-01-01

    textabstractThis longitudinal study examined the additive and interactive effects of behavioral inhibition and a wide range of other vulnerability factors in the development of anxiety problems in youths. A sample of 261 children, aged 5 to 8 years, 124 behaviorally inhibited and 137 control childre

  5. Learning-Inhibiting Problems Experienced by Middle School Teachers: Implications for Staff Development

    OpenAIRE

    Dillard, Patricia Hutcherson

    2000-01-01

    Learning-Inhibiting Problems Experienced by Middle School Teachers: Implications for Staff Development Patricia H. Dillard (ABSTRACT) This study sought to determine if there were statistically significant differences between years of teaching experience and education relative to learning-inhibiting problems in the classroom. These differences were measured by responses on surveys, classroom observations, review of summative teacher appraisal instruments and focus group...

  6. Skoog Primary Periosteoplasty versus Secondary Alveolar Bone Grafting in Unilateral Cleft Lip and Alveolus: Long-Term Effects on Alveolar Bone Formation and Maxillary Growth.

    Science.gov (United States)

    Jabbari, Fatima; Hakelius, Malin M; Thor, Andreas L I; Reiser, Erika A; Skoog, Valdemar T; Nowinski, Daniel J

    2017-01-01

    Clefts involving the alveolus are treated using one of two strategies: primary periosteoplasty at the time of lip repair or secondary alveolar bone grafting at mixed dentition. Most teams favor secondary alveolar bone grafting because of its high success rate, and concerns have been raised that primary periosteoplasty may interfere with maxillary growth. However, primary periosteoplasty may obviate the need for future bone grafting and is still practiced in some centers. Few studies compare the long-term outcomes of these two strategies. Fifty-seven consecutive patients born with unilateral cleft lip and alveolus were studied retrospectively. All patients underwent primary lip repair using Skoog's method; 28 patients underwent primary periosteoplasty at the time of lip repair and the remaining 29 underwent secondary alveolar bone grafting at mixed dentition. Occlusal radiographs obtained at ages 10 and 16 years were analyzed for alveolar bone height. Cephalometric analysis assessed growth at ages 5, 10, and 18 years. Seventeen of 28 patients treated using primary periosteoplasty required later secondary bone grafting, and the bone height at age 16 years was lower in the primary periosteoplasty group (p < 0.0001). There was a more pronounced decrease in maxillary protrusion from ages 5 to 10 years in the primary periosteoplasty group (p < 0.03). However, at age 18 there was no significant difference in maxillary growth between the two groups. Primary periosteoplasty did not seem to inhibit long-term maxillary growth but was ineffective as a method of reconstructing the alveolar cleft. Therapeutic, III.

  7. Testing alternative hypotheses regarding the association between behavioral inhibition and language development in toddlerhood.

    Science.gov (United States)

    Smith Watts, Ashley K; Patel, Deepika; Corley, Robin P; Friedman, Naomi P; Hewitt, John K; Robinson, JoAnn L; Rhee, Soo H

    2014-01-01

    Studies have reported an inverse association between language development and behavioral inhibition or shyness across childhood, but the direction of this association remains unclear. This study tested alternative hypotheses regarding this association in a large sample of toddlers. Data on behavioral inhibition and expressive and receptive language abilities were collected from 816 twins at ages 14, 20, and 24 months. Growth and regression models were fit to the data to assess the longitudinal associations between behavioral inhibition and language development from 14 to 24 months. Overall, there were significant associations between behavioral inhibition and expressive language, and minimal associations with receptive language, indicating that the association is better explained by reticence to respond rather than deficient language development. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.

  8. Identification of porcine alveolar macrophage glycoproteins involved in infection of porcine respiratory and reproductive syndrome virus.

    NARCIS (Netherlands)

    Wissink, E.H.J.; Wijk, van H.A.R.; Pol, J.M.A.; Godeke, G.J.; Rijn, van P.A.; Rottier, P.J.M.; Meulenberg, J.J.M.

    2003-01-01

    The aim of this study was to identify the receptor(s) for PRRSV on porcine alveolar macrophages (PAMs) by producing monoclonal antibodies (MAbs) against these cells. Hybridoma supernatants were selected for their ability to block PRRSV infection. Four MAbs, 1-8D2, 9.4C7, 9.9F2, and 3-3H2 inhibited i

  9. Cigarette smoke exposure aggravates air space enlargement and alveolar cell apoptosis in Smad3 knockout mice.

    Science.gov (United States)

    Farkas, Laszlo; Farkas, Daniela; Warburton, David; Gauldie, Jack; Shi, Wei; Stampfli, Martin R; Voelkel, Norbert F; Kolb, Martin

    2011-10-01

    The concept of genetic susceptibility factors predisposing cigarette smokers to develop emphysema stems from the clinical observation that only a fraction of smokers develop clinically significant chronic obstructive pulmonary disease. We investigated whether Smad3 knockout mice, which develop spontaneous air space enlargement after birth because of a defect in transforming growth factor-β (TGF-β) signaling, develop enhanced alveolar cell apoptosis and air space enlargement following cigarette smoke exposure. We investigated Smad3(-/-) and Smad3(+/+) mice at different adult ages and determined air space enlargement, alveolar cell proliferation, and apoptosis. Furthermore, laser-capture microdissection and real-time PCR were used to measure compartment-specific gene expression. We then compared the effects of cigarette smoke exposure on Smad3(-/-) and littermate controls. Smad3 knockout resulted in the development of air space enlargement in the adult mouse and was associated with decreased alveolar VEGF levels and activity and increased alveolar cell apoptosis. Cigarette smoke exposure aggravated air space enlargement and alveolar cell apoptosis. We also found increased Smad2 protein expression and phosphorylation, which was enhanced following cigarette smoke exposure, in Smad3-knockout animals. Double immunofluorescence analysis revealed that endothelial apoptosis started before epithelial apoptosis. Our data indicate that balanced TGF-β signaling is not only important for regulation of extracellular matrix turnover, but also for alveolar cell homeostasis. Impaired signaling via the Smad3 pathway results in alveolar cell apoptosis and alveolar destruction, likely via increased Smad2 and reduced VEGF expression and might represent a predisposition for accelerated development of emphysema due to cigarette smoke exposure.

  10. Gastric metastasis from an alveolar soft part sarcoma in a child: case report and review of the literature.

    Science.gov (United States)

    Williams, Paul W; Brown, Kathryn B; Westmoreland, Tamarah; Herrington, Betty; Sawaya, David E; Rezeanu, Luminita; Nowicki, Michael J

    2014-04-01

    The authors report a child with alveolar soft part sarcoma who developed significant anemia due to gastrointestinal blood loss. Evaluation revealed the source of bleeding as a gastric metastasis, which was successfully removed. A brief review of gastrointestinal involvement by alveolar soft part sarcoma is discussed.

  11. Modification of matrix metalloproteinase activities from alveolar macrophages during chronic coal mine dust exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Oberson, D.; Wastiaux, A.; Lefevre, J.P.; Sebastien, P.; Lafuma, C. [Centre National de la Recherche Scientifique (UA-CNRS), Creteil (France). Lab. de Biochimie du Tissu Conjunctif

    1994-12-31

    Macrophage derived products have been implicated in pneumoconiosis induced by chronic coal dust inhalation. To assess the role of macrophages during chronic inflammatory processes in relation to pneumoconiosis, their capacity to secrete matrix metalloproteinase (MMP) activities was studied. Two groups of rats were exposed to 100 or 200 mg m{sup -3}, 6 h per day, 5 days per week and sacrified at 9, 28 and 78 days of exposure, and 6 months following the end of exposure. A total of 92 kDa proform and 88 kDa active form collagenase type IV (gelatinase) were investigated in macrophage culture medium (MEM), macrophage extracts (MACs) and bronchoalveolar fluid (BAL). In parallel, net gelatinase and interstitial collagenase activities were evaluated by degradation of radiolabelled specific substrates. Pneumoconiotic lessons developed during the late dust exposure and the recovery phase and were associated with macrophage alveolitis. Results showed that chronic coal dust inhalation induced the increase of total gelatinase activities secreted into the MEM and the BAL. The net gelatinase and collagenase activities were increased in parallel in MEM whereas they appeared inhibited when secreted in the BAL whatever the dust exposure time. These results suggest that chronic coal mine dust exposure is capable of inducing chronic alveolar MACs activation in regard to their persistent highly increased capacity to degrade in situ extracelluar matrix components, namely collagen types IV or V. Such a deregulation associated with the acute inhibition process towards MMPs in the alveolar space, allowed the authors to propose a role of MMPs during pneumoconiosis. 17 refs., 5 figs., 1 tab.

  12. Tyrosine Kinase Inhibition: An Approach to Drug Development

    Science.gov (United States)

    Levitzki, Alexander; Gazit, Aviv

    1995-03-01

    Protein tyrosine kinases (PTKs) regulate cell proliferation, cell differentiation, and signaling processes in the cells of the immune system. Uncontrolled signaling from receptor tyrosine kinases and intracellular tyrosine kinases can lead to inflammatory responses and to diseases such as cancer, atherosclerosis, and psoriasis. Thus, inhibitors that block the activity of tyrosine kinases and the signaling pathways they activate may provide a useful basis for drug development. This article summarizes recent progress in the development of PTK inhibitors and demonstrates their potential use in the treatment of disease.

  13. Retinoid induction of alveolar regeneration: from mice to man?

    Science.gov (United States)

    Hind, M; Gilthorpe, A; Stinchcombe, S; Maden, M

    2009-05-01

    The use of retinoids to induce human lung regeneration is under investigation in a number of studies in patients with chronic obstructive pulmonary disease (COPD). Retinoic acid (RA) has complex pleiotropic functions during vertebrate patterning and development and can induce regeneration in a number of different organ systems. Studies of retinoid signalling during lung development might provide a molecular basis to explain pharmacological induction of alveolar regeneration in adult models of lung disease. In this review the role of endogenous RA signalling during alveologenesis is explored and data suggesting that a number of exogenous retinoids can induce regeneration in the adult lung are discussed. Current controversies in this area are highlighted and a hypothesis of lung regeneration is put forward. Understanding the cellular and molecular mechanisms of induction of regeneration will be central for effective translation into patients with lung disease and may reveal novel insights into the pathogenesis of alveolar disease and senescence.

  14. Primary Pulmonary Plasmacytoma with Diffuse Alveolar Consolidation: A Case Report

    Directory of Open Access Journals (Sweden)

    Zohreh Mohammad Taheri

    2010-01-01

    Full Text Available Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy.

  15. Identification of an Autophagy Defect in Smokers’ Alveolar Macrophages1

    OpenAIRE

    2010-01-01

    Alveolar macrophages are essential for clearing bacteria from the alveolar surface and preventing microbial-induced infections. It is well documented that smokers have an increased incidence of infections, in particular lung infections. Alveolar macrophages accumulate in smokers’ lungs but they have a functional immune deficit. In this study, we identify for the first time an autophagy defect in smokers’ alveolar macrophages. Smokers’ alveolar macrophages accumulate both autophagosomes and p6...

  16. Consideraciones anatomicas del conducto alveolar inferior

    National Research Council Canada - National Science Library

    Ortiz, Yudy Patricia; Camargo Canon, Oscar Andres; Ruge Jimenez, Omar Yamid

    2009-01-01

    ..., las distancias del agujero mentoniano al borde basal y la cresta alveolar. Se hicieron cortes en la rama y el cuerpo, para determinar las relaciones con estructuras anatomicas proximas. Resultados...

  17. Tracheal compression delays alveolar collapse during deep diving in marine mammals.

    Science.gov (United States)

    Bostrom, Brian L; Fahlman, Andreas; Jones, David R

    2008-05-31

    Marine mammals have very compliant alveoli and stiff upper airways; an adaptation that allows air to move from the alveoli into the upper airways, during breath-hold diving. Alveolar collapse is thought occur between 30 and 100 m and studies that have attempted to estimate gas exchange at depth have used the simplifying assumption that gas exchange ceases abruptly at the alveolar collapse depth. Here we develop a mathematical model that uses compliance values for the alveoli and upper airspaces, estimated from the literature, to predict volumes of the respiratory system at depth. Any compressibility of the upper airways decreases the volume to contain alveolar air yielding lung collapse pressures 2x that calculated assuming an incompressible upper airway. A simple relationship with alveolar volume was used to predict relative pulmonary shunt at depth. The results from our model agree with empirical data on gas absorption at depth as well as the degree of tracheal compression in forced and free diving mammals.

  18. Evolución en el tratamiento de la atrofia alveolar

    Directory of Open Access Journals (Sweden)

    Oscar García-Roco Pérez

    2002-08-01

    Full Text Available Con el objetivo de describir la evolución del tratamiento de la atrofia alveolar se realiza una revisión bibliográfica actualizada de 25 referencias, se destacan las vestibuloplastias, injertos óseos, biomateriales, implantes endóseos, regeneración ósea guiada y la distracción ósea, que corrigen o compensan la atrofia alveolar con sus indicaciones, ventajas y desventajas.An updated literature review of 25 references was made to describe the development in the treatment of dental alveolar atrophy. Some procedures that correct or compensate alveolar atrophies such as vestibuloplasty, bone grafting, biomaterials, endo-bone implants, guided bone regeneration and bone distraction. Their indications, advantages and disadvantages are set forth.

  19. Cadmium inhibits neurogenesis in zebrafish embryonic brain development

    Energy Technology Data Exchange (ETDEWEB)

    Chow, Elly Suk Hen [Division of Biology, California Institute of Technology, 1200 California Boulevard, Pasadena, CA 91125 (United States); Hui, Michelle Nga Yu; Lin Chunchi [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China); Cheng Shukhan [Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong (China)], E-mail: bhcheng@cityu.edu.hk

    2008-05-01

    Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected by cadmium. We observe prominent reductions in the expression of several proneuronal genes including ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated neurons and glia in the facial sensory ganglia as indicated by decreased zn-12 expression. Also, a lower transcription level of neurogenic genes, ngn1 and neuroD, is observed in neurons. Our data suggest that cadmium-induced neurotoxicity can be caused by impaired neurogenesis, resulting in markedly reduced neuronal differentiation and axonogenesis.

  20. New developments in atherosclerosis: clinical potential of PCSK9 inhibition

    Directory of Open Access Journals (Sweden)

    Giunzioni I

    2015-08-01

    Full Text Available Ilaria Giunzioni, Hagai Tavori Knight Cardiovascular Institute, Center for Preventive Cardiology, Oregon Health and Science University, Portland, OR, USA Abstract: Pro-protein convertase subtilisin/kexin type 9 (PCSK9 is a secreted 692-amino acid protein that binds surface low-density lipoprotein (LDL receptor (LDLR and targets it toward lysosomal degradation. As a consequence, the number of LDLRs at the cell surface is decreased, and LDL-cholesterol (LDL-C clearance is reduced, a phenomenon that is magnified by gain-of-function mutations of PCSK9. In contrast, loss-of-function mutations of PCSK9 result in increased surface LDLR and improved LDL-C clearance. This provides the rationale for targeting PCSK9 in hypercholesterolemic subjects as a means to lower LDL-C levels. Monoclonal antibodies (mAbs against PCSK9 that block its interaction with the LDLR have been developed in the past decade. Two companies have recently received the approval for their anti-PCSK9 mAbs by the US Food and Drug Administration (FDA and the European Medicines Agency (EMA Regeneron/Sanofi, with alirocumab (commercial name – PRALUENT® and, Amgen with evolocumab (commercial name – Repatha™. The introduction of anti-PCSK9 mAbs will provide an alternative therapeutic strategy to address many of the unmet needs of current lipid-lowering therapies, such as inability to achieve goal LDL-C level, or intolerance and aversion to statins. This review will focus on the kinetics of PCSK9, pharmacokinetics and pharmacodynamics of anti-PCSK9 mAbs, and recent data linking PCSK9 and anti-PCSK9 mAbs to cardiovascular events. Moreover, it will highlight the unanswered questions that still need to be addressed in order to understand the physiologic function, kinetics, and dynamics of PCSK9. Keywords: PCSK9, LDLR, monoclonal antibodies, pharmacokinetics, cardiovascular risk

  1. New developments in atherosclerosis: clinical potential of PCSK9 inhibition

    Science.gov (United States)

    Giunzioni, Ilaria; Tavori, Hagai

    2015-01-01

    Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a secreted 692-amino acid protein that binds surface low-density lipoprotein (LDL) receptor (LDLR) and targets it toward lysosomal degradation. As a consequence, the number of LDLRs at the cell surface is decreased, and LDL-cholesterol (LDL-C) clearance is reduced, a phenomenon that is magnified by gain-of-function mutations of PCSK9. In contrast, loss-of-function mutations of PCSK9 result in increased surface LDLR and improved LDL-C clearance. This provides the rationale for targeting PCSK9 in hypercholesterolemic subjects as a means to lower LDL-C levels. Monoclonal antibodies (mAbs) against PCSK9 that block its interaction with the LDLR have been developed in the past decade. Two companies have recently received the approval for their anti-PCSK9 mAbs by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Regeneron/Sanofi, with alirocumab (commercial name – PRALUENT®) and, Amgen with evolocumab (commercial name – Repatha™). The introduction of anti-PCSK9 mAbs will provide an alternative therapeutic strategy to address many of the unmet needs of current lipid-lowering therapies, such as inability to achieve goal LDL-C level, or intolerance and aversion to statins. This review will focus on the kinetics of PCSK9, pharmacokinetics and pharmacodynamics of anti-PCSK9 mAbs, and recent data linking PCSK9 and anti-PCSK9 mAbs to cardiovascular events. Moreover, it will highlight the unanswered questions that still need to be addressed in order to understand the physiologic function, kinetics, and dynamics of PCSK9. PMID:26345307

  2. Behavioral Inhibition as a Risk Factor for the Development of Childhood Anxiety Disorders: A Longitudinal Study.

    Science.gov (United States)

    Muris, Peter; van Brakel, Anna M L; Arntz, Arnoud; Schouten, Erik

    2011-04-01

    This longitudinal study examined the additive and interactive effects of behavioral inhibition and a wide range of other vulnerability factors in the development of anxiety problems in youths. A sample of 261 children, aged 5 to 8 years, 124 behaviorally inhibited and 137 control children, were followed during a 3-year period. Assessments took place on three occasions to measure children's level of behavioral inhibition, anxiety disorder symptoms, other psychopathological symptoms, and a number of other vulnerability factors such as insecure attachment, negative parenting styles, adverse life events, and parental anxiety. Results obtained with Structural Equation Modeling indicated that behavioral inhibition primarily acted as a specific risk factor for the development of social anxiety symptoms. Furthermore, the longitudinal model showed additive as well as interactive effects for various vulnerability factors on the development of anxiety symptoms. That is, main effects of anxious rearing and parental trait anxiety were found, whereas behavioral inhibition and attachment had an interactive effect on anxiety symptomatology. Moreover, behavioral inhibition itself was also influenced by some of the vulnerability factors. These results provide support for dynamic, multifactorial models for the etiology of child anxiety problems.

  3. Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling.

    Science.gov (United States)

    Brown, Kari; Filuta, Alyssa; Ludwig, Marie-Gabrielle; Seuwen, Klaus; Jaros, Julian; Vidal, Solange; Arora, Kavisha; Naren, Anjaparavanda P; Kandasamy, Kathirvel; Parthasarathi, Kaushik; Offermanns, Stefan; Mason, Robert J; Miller, William E; Whitsett, Jeffrey A; Bridges, James P

    2017-06-02

    Pulmonary function is dependent upon the precise regulation of alveolar surfactant. Alterations in pulmonary surfactant concentrations or function impair ventilation and cause tissue injury. Identification of the molecular pathways that sense and regulate endogenous alveolar surfactant concentrations, coupled with the ability to pharmacologically modulate them both positively and negatively, would be a major therapeutic advance for patients with acute and chronic lung diseases caused by disruption of surfactant homeostasis. The orphan adhesion GPCR GPR116 (also known as Adgrf5) is a critical regulator of alveolar surfactant concentrations. Here, we show that human and mouse GPR116 control surfactant secretion and reuptake in alveolar type II (AT2) cells by regulating guanine nucleotide-binding domain α q and 11 (Gq/11) signaling. Synthetic peptides derived from the ectodomain of GPR116 activated Gq/11-dependent inositol phosphate conversion, calcium mobilization, and cortical F-actin stabilization to inhibit surfactant secretion. AT2 cell-specific deletion of Gnaq and Gna11 phenocopied the accumulation of surfactant observed in Gpr116-/- mice. These data provide proof of concept that GPR116 is a plausible therapeutic target to modulate endogenous alveolar surfactant pools to treat pulmonary diseases associated with surfactant dysfunction.

  4. Myricetin Prevents Alveolar Bone Loss in an Experimental Ovariectomized Mouse Model of Periodontitis.

    Science.gov (United States)

    Huang, Jialiang; Wu, Chuanlong; Tian, Bo; Zhou, Xiao; Ma, Nian; Qian, Yufen

    2016-03-22

    Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX) mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS) control (sham) OVX + ligature + PBS (vehicle), and OVX + ligature + low or high (2 or 5 mg∙kg(-1)∙day(-1), respectively) doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p.) every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

  5. Myricetin Prevents Alveolar Bone Loss in an Experimental Ovariectomized Mouse Model of Periodontitis

    Directory of Open Access Journals (Sweden)

    Jialiang Huang

    2016-03-01

    Full Text Available Periodontitis is a common chronic inflammatory disease, which leads to alveolar bone resorption. Healthy and functional alveolar bone, which can support the teeth and enable their movement, is very important for orthodontic treatment. Myricetin inhibited osteoclastogenesis by suppressing the expression of some genes, signaling pathways, and cytokines. This study aimed to investigate the effects of myricetin on alveolar bone loss in an ovariectomized (OVX mouse model of periodontitis as well as in vitro osteoclast formation and bone resorption. Twenty-four healthy eight-week-old C57BL/J6 female mice were assigned randomly to four groups: phosphate-buffered saline (PBS control (sham OVX + ligature + PBS (vehicle, and OVX + ligature + low or high (2 or 5 mg∙kg−1∙day−1, respectively doses of myricetin. Myricetin or PBS was injected intraperitoneally (i.p. every other day for 30 days. The maxillae were collected and subjected to further examination, including micro-computed tomography (micro-CT, hematoxylin and eosin (H&E staining, and tartrate-resistant acid phosphatase (TRAP staining; a resorption pit assay was also performed in vitro to evaluate the effects of myricetin on receptor activator of nuclear factor κ-B ligand (RANKL-induced osteoclastogenesis. Myricetin, at both high and low doses, prevented alveolar bone resorption and increased alveolar crest height in the mouse model and inhibited osteoclast formation and bone resorption in vitro. However, myricetin was more effective at high dose than at low dose. Our study demonstrated that myricetin had a positive effect on alveolar bone resorption in an OVX mouse model of periodontitis and, therefore, may be a potential agent for the treatment of periodontitis and osteoporosis.

  6. Behavioral Inhibition and Risk for Developing Social Anxiety Disorder: A Meta-Analytic Study

    Science.gov (United States)

    Clauss, Jacqueline A.; Blackford, Jennifer Urbano

    2012-01-01

    Objective: Behavioral inhibition (BI) has been associated with increased risk for developing social anxiety disorder (SAD); however, the degree of risk associated with BI has yet to be systematically examined and quantified. The goal of the present study was to quantify the association between childhood BI and risk for developing SAD. Method: A…

  7. New perspectives on self-control development: Highlighting the role of intentional inhibition

    NARCIS (Netherlands)

    Schel, M.; Scheres, A.P.J.; Crone, E.A.M.

    2014-01-01

    The ability to exert self-control over one׳s thoughts and actions is crucial for successful functioning in daily life. To date, self-control development has been primarily studied from the perspective of externally driven inhibition. In this review, we introduce a new perspective on the development

  8. CDA-2, a urinary preparation, inhibits lung cancer development through the suppression of NF-kappaB activation in myeloid cell.

    Directory of Open Access Journals (Sweden)

    Xuan Wang

    Full Text Available CDA-2 (cell differentiation agent 2, a urinary preparation, has potent anti- proliferative and pro-apoptotic properties in cancer cells. However, the mechanisms of tumor inhibitory action of CDA-2 are far from clear, and especially there was no report on lung cancer. Here we demonstrate that CDA-2 and its main component phenylacetylglutamine (PG reduce the metastatic lung tumor growth, and increases survival time after inoculation with Lewis lung carcinoma (LLC cells in a dose-dependent manner in C57BL6 mice. Proliferative program analysis in cancer cells revealed a fundamental impact of CDA-2 and PG on proliferation and apoptosis, including Bcl-2, Bcl-XL, cIAP1, Survivin, PCNA, Ki-67 proteins and TUNEL assays. CDA-2 and PG significantly reduced NF-κB DNA-binding activity in lung cancer cells and in alveolar macrophages of tumor bearing mice and especially decreased the release of inflammatory factors including TNFα, IL-6, and KC. Furthermore, CDA-2 and PG decrease the expressions of TLR2, TLR6, and CD14, but not TLR1, TLR3, TLR4, and TLR9 in bone-marrow-derived macrophages (BMDM of mice stimulated by LLC-conditioned medium (LLC-CM. Over-expressing TLR2 in BMDM prevented CDA-2 and PG from inhibiting NF-κB activation, as well as induction of TNFα and IL-6. TLR2:TLR6 complexes mediate the effect of NF-κB inactivation by CDA-2. In conclusion, CDA-2 potently inhibits lung tumor development by reduction of the inflammation in lung through suppression of NF-κB activation in myeloid cells, associating with modulation of TLR2 signaling.

  9. [Cleft lip, alveolar and palate sequelae. Proposal of new alveolar score by the Alveolar Cleft Score (ACS) classification].

    Science.gov (United States)

    Molé, C; Simon, E

    2015-06-01

    The management of cleft lip, alveolar and palate sequelae remains problematic today. To optimize it, we tried to establish a new clinical index for diagnostic and prognostic purposes. Seven tissue indicators, that we consider to be important in the management of alveolar sequelae, are listed by assigning them individual scores. The final score, obtained by adding together the individual scores, can take a low, high or maximum value. We propose a new classification (ACS: Alveolar Cleft Score) that guides the therapeutic team to a prognosis approach, in terms of the recommended surgical and prosthetic reconstruction, the type of medical care required, and the preventive and supportive therapy to establish. Current studies are often only based on a standard radiological evaluation of the alveolar bone height at the cleft site. However, the gingival, the osseous and the cellular areas bordering the alveolar cleft sequelae induce many clinical parameters, which should be reflected in the morphological diagnosis, to better direct the surgical indications and the future prosthetic requirements, and to best maintain successful long term aesthetic and functional results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. Alveolar epithelial type II cell: defender of the alveolus revisited

    Directory of Open Access Journals (Sweden)

    Fehrenbach Heinz

    2001-01-01

    Full Text Available Abstract In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2 cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today.

  11. Metabolic shift in lung alveolar cell mitochondria following acrolein exposure.

    Science.gov (United States)

    Agarwal, Amit R; Yin, Fei; Cadenas, Enrique

    2013-11-15

    Acrolein, an α,β unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A2 activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.

  12. Perawatan Ortodontik Gigi Anterior Berjejal dengan Tulang Alveolar yang Tipis

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    Miesje K. Purwanegara

    2015-09-01

    Full Text Available Anterior teeth movement in orthodontic treatment is limited to labiolingual direction by very thin alveolar bone. An uncontrolled anterior tooth movement to labiolingual direction can cause alveolar bone perforation at its root segment. This case report is to remind us that alveolar bone thickness limits orthodontc tooth movement. A case of crowded anterior teeth with thin alveolar bone in malocclusion I is reported. This case is treated using adgewise orthodontic appliance. Protraction of anterior teeth is anticipated due to thin alveolar bone on the anterior surface. The conclusion is although the alveolar bone surrounding the crowded anterior teeth is thin, by controlling the movement the teeth reposition is allowed.

  13. Orthopantomographic study of the alveolar bone level on periodontal disease

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ki Sik; You, Dong Soo [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1972-11-15

    The author had measured the alveolar bone level of periodontal disease on 50 cases of orthopantomogram to detect the degree of alveolar bone resorption of both sexes of Korean. The results were obtained as follows; 1. Alveolar bone resorption of mesial and distal portion was similar in same patient. 2. The order of alveolar bone resorption was mandibular anterior region, posterior region, canine and premolar region of both jaws. 3. The degree of alveolar bone destruction was severe in shorter root length than longer one. 4. The degree of alveolar bone resorption was severe in fourth decades.

  14. Momordica charantia trypsin inhibitor Ⅱ inhibits growth and development of Helicoverpa armigera

    Institute of Scientific and Technical Information of China (English)

    Manasi Alok Telang; Prashant Pyati; Mohini Sainani; Vidya Shrikant Gupta; Ashok Prabhakar Giri

    2009-01-01

    Bitter gourd (Momordica charantia L.) seeds contain several squash-type serine proteinase inhibitors (PIs),which inhibit the digestive proteinases of the polyphagous insect pest Helicoverpa armigera.In the present work isolation of a DNA sequence encoding the mature peptide of a trypsin inhibitor McTI-Ⅱ,its cloning and expression as a recombinant protein using Pichia pastoris have been reported.Recombinant McTI-Ⅱinhibited bovine trypsin at 1:1 molar ratio,as expected,but did not inhibit chymotrypsin or elastase.McTI-Ⅱalso strongly inhibited trypsin-like proteinases (81% inhibition) as well as the total proteolytic activity of digestive proteinases (70% inhibition) from the midgut of H.armigera larvae.The insect larvae fed with McTI-Ⅱ-incorporated artificial diet suffered over 70% reduction in the average larval weight after 12 days of feeding.Moreover,ingestion of McTI-Ⅱresulted in 23% mortality in the larval population.The strong antimetabolic activity of McTI-Ⅱtoward H.armigera indicates its probable use in developing insect tolerance in susceptible plants.

  15. X-ray radiation and development inhibition of Helicoverpa armigera Hübner (Lepidoptera: Noctuidae)

    Science.gov (United States)

    Kim, Junheon; Jung, Soon-Oh; Jang, Sin Ae; Kim, Jeongmin; Park, Chung Gyoo

    2015-10-01

    Effect of X-ray radiation on the development inhibition was evaluated for all stages of the life cycle of Helicoverpa armigera to determine a radiation dose for potential quarantine treatment against the insect. ED99 values for inhibition of hatching, pupation, and adult emergence from irradiated eggs were 413, 210, and 154 Gy, respectively. ED99 values for inhibition of pupation and adult emergence from irradiated larvae were 221 and 167 Gy, respectively. Pupa was the most tolerant to X-ray radiation. ED99 value for inhibition of adult emergence from irradiated pupae was as high as 2310 Gy, whereas that for inhibition of F1 egg hatching was only 66 Gy. ED99 value for inhibition of hatching of F1 eggs which were laid by irradiated adults was estimated to 194 Gy. X-ray irradiation against H. armigera is recommended as an alternative method to methyl bromide fumigation for phytosanitary treatments during quarantine. X-ray radiation dose of 200 Gy is proposed as a potential quarantine treatment dose for H. armigera eggs and larvae.

  16. Alveolar rhabdomyosarcoma in children with histomorphological review

    Directory of Open Access Journals (Sweden)

    S. K. Nema

    2014-04-01

    Full Text Available Rhabdomyosarcomas (RMS are aggressive malignant neoplasm of mesenchymal origin, related to skeletal muscle lineage. These are the most common soft tissue tumors in children. The diagnosis is made by microscopic analysis and ancillary techniques like immunohistochemistry, electron microscopy, cytogenetics and molecular biology. We encountered a case of a 03 years old child who presented with a tender, reddish, soft swelling over cheek for three weeks. The FNAC was reported as a small round cell tumor, Probably Primitive Neuroectodermal Tumor (PNET. The biopsy of tumor revealed a small round cell tumor with an alveolar pattern. Tumor giant cells were absent and mitotic figures were infrequent. Hence, differentials of alveolar rhabdomyosarcoma and PNET were rendered. Immunohistochemistry (IHC demonstrated desmin positivity. Thus, a final diagnosis of alveolar rhabdomyosarcoma was offered. [Int J Res Med Sci 2014; 2(2.000: 775-778

  17. Lateralization Technique and Inferior Alveolar Nerve Transposition

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    Angélica Castro Pimentel

    2016-01-01

    Full Text Available Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics.

  18. Lateralization Technique and Inferior Alveolar Nerve Transposition

    Science.gov (United States)

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  19. The development of adolescents' internalizing behavior: longitudinal effects of maternal sensitivity and child inhibition.

    Science.gov (United States)

    van der Voort, Anja; Linting, Mariëlle; Juffer, Femmie; Bakermans-Kranenburg, Marian J; Schoenmaker, Christie; van Ijzendoorn, Marinus H

    2014-04-01

    Internalizing symptoms such as withdrawn and anxious-depressed behavior are common in adolescence. This prospective longitudinal study helps to gain insight into the development of internalizing behavior, focusing on the role of early parent-child interaction while ruling out genetic similarity as a confounder. More specifically, the central question addressed in this study was whether parental sensitivity and child inhibited temperament predict children's withdrawn and anxious-depressed behavior in middle childhood and adolescence. We followed 160 early-adopted children (53 % girls) from infancy to adolescence. Structural equation modeling was used to test relationships both prospectively and concurrently. The results revealed that more sensitive parenting in infancy and middle childhood predicted less inhibited behavior in adolescence, which in turn predicted fewer internalizing problems in adolescence. The findings suggest that maternal sensitivity lowers adolescents' inhibited behavior and decreases the risk for adolescents' internalizing problem behavior indirectly through lower levels of inhibition. Supporting sensitive parenting in the years before adolescence may protect children from developing inhibited behavior and internalizing behavior problems in adolescence.

  20. Development of response activation and inhibition in a selective stop-signal task

    NARCIS (Netherlands)

    van de Laar, M.C.; van den Wildenberg, W.P.M.; van Boxtel, G.J.M.; van der Molen, M.W.

    2014-01-01

    To gain more insight into the development of action control, the current brain potential study examined response selection, activation, and selective inhibition during choice- and stop-signal processing in three age groups (8-, 12-, and 21-year-olds). Results revealed that age groups differed in the

  1. PERIPUBERTAL DEHP EXPOSURE INHIBITS ANDROGEN-DEPENDENT DEVELOPMENT IN SPRAGUE-DAWLEY RATS

    Science.gov (United States)

    Peripubertal DEHP exposure inhibits androgen-dependent development in Sprague-Dawley rats.N.C. Noriega, J. Furr, C. Lambright, V.S. Wilson and L.E. Gray.noriega.nigel@epa.govUS EPA, MD-72 RTD, NHEERL, ORD, RTP, NC 27711The plasticizer Di (2-ethylhe...

  2. Social-Emotional Inhibition of Return in Children with Autism Spectrum Disorder versus Typical Development

    Science.gov (United States)

    Antezana, Ligia; Mosner, Maya G.; Troiani, Vanessa; Yerys, Benjamin E.

    2016-01-01

    In typical development there is a bias to orient visual attention to social information. Children with ASD do not reliably demonstrate this bias, and the role of attention orienting has not been well studied. We examined attention orienting via the inhibition of return (IOR) mechanism in a spatial cueing task using social-emotional cues; we…

  3. Retrospective Assessment of Behavioral Inhibition in Infants and Toddlers: Development of a Parent Report Questionnaire

    Science.gov (United States)

    Gensthaler, A.; Mohler, E.; Resch, F.; Paulus, F.; Schwenck, C.; Freitag, C. M.; Goth, K.

    2013-01-01

    A behaviorally inhibited temperament in early childhood has been identified as a potential risk factor for anxiety disorders in children and adolescents. The purpose of our investigation was the development and evaluation of the factor structure, reliability and validity of the first retrospective parent report measure to assess behavioral…

  4. Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3

    Institute of Scientific and Technical Information of China (English)

    Ji-Hui Yu; Li Long; Zhi-Xiao Luo; Lin-Man Li; Jie-Ru You

    2016-01-01

    Objective: To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells. Methods: Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3. Results: MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS-induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin-1β. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages. Conclusions: MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies.

  5. Conditional deletion of epithelial IKKβ impairs alveolar formation through apoptosis and decreased VEGF expression during early mouse lung morphogenesis

    Directory of Open Access Journals (Sweden)

    Li Changgong

    2011-10-01

    Full Text Available Abstract Background Alveolar septation marks the beginning of the transition from the saccular to alveolar stage of lung development. Inflammation can disrupt this process and permanently impair alveolar formation resulting in alveolar hypoplasia as seen in bronchopulmonary dysplasia in preterm newborns. NF-κB is a transcription factor central to multiple inflammatory and developmental pathways including dorsal-ventral patterning in fruit flies; limb, mammary and submandibular gland development in mice; and branching morphogenesis in chick lungs. We have previously shown that epithelial overexpression of NF-κB accelerates lung maturity using transgenic mice. The purpose of this study was to test our hypothesis that targeted deletion of NF-κB signaling in lung epithelium would impair alveolar formation. Methods We generated double transgenic mice with lung epithelium-specific deletion of IKKβ, a known activating kinase upstream of NF-κB, using a cre-loxP transgenic recombination strategy. Lungs of resulting progeny were analyzed at embryonic and early postnatal stages to determine specific effects on lung histology, and mRNA and protein expression of relevant lung morphoreulatory genes. Lastly, results measuring expression of the angiogenic factor, VEGF, were confirmed in vitro using a siRNA-knockdown strategy in cultured mouse lung epithelial cells. Results Our results showed that IKKβ deletion in the lung epithelium transiently decreased alveolar type I and type II cells and myofibroblasts and delayed alveolar formation. These effects were mediated through increased alveolar type II cell apoptosis and decreased epithelial VEGF expression. Conclusions These results suggest that epithelial NF-κB plays a critical role in early alveolar development possibly through regulation of VEGF.

  6. Assessment of cytochrome p450 enzyme inhibition and inactivation in drug discovery and development.

    Science.gov (United States)

    Nettleton, David O; Einolf, Heidi J

    2011-01-01

    Evaluation of the potential of a drug candidate to inhibit or inactivate cytochrome P450 (CYP) enzymes remains an important part of pharmaceutical drug Discovery and Development programs. CYP enzymes are considered to be one of the most important enzyme families involved in the metabolic clearance of the vast majority of prescribed drugs. Clinical drug-drug interactions (DDI) involving inhibition or time-dependent inactivation of these enzymes can result in dangerous side effects resulting from reduced clearance/increased exposure of the drug being affected (the 'victim' drug). In this regard, pharmaceutical companies have become quite vigilant in mitigating CYP inhibition/inactivation liabilities of drug candidates early in Discovery including continued risk assessment throughout Development. In this review, common strategies and decision making processes for the assessment of DDI risk in the different stages of pharmaceutical development are discussed. In addition, in vitro study designs, analysis, and interpretation of CYP inhibition and inactivation data are described in stage appropriate context. The in vitro tools and knowledge available now enable the Discovery Chemist to place the potential CYP DDI liability of a drug candidate into perspective and to aid in the optimization of chemical drug design to further mitigate this risk.

  7. Effect of terbutaline on alveolar liquid clearance after oleic acid-induced lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    TAO Jun; YANG Tian-de; LI Hong; DU Zhi-yong

    2006-01-01

    Objective: To investigate whether terbutaline affects alveolar liquid clearance after oleic acid-induced lung injury in rats.Methods: Forty healthy Wistar rats ( weighing 250-280 g) were randomly divided into five groups ( n = 8 in each group): the normal control group ( control group),oleic acid injury group ( injury group), terbutaline-treated group (terbutaline group ), terbutaline plus amiloridetreated group (terbutaline + amiloride group ) and terbutaline plus ouabain-treated group (terbutaline + ouabain group). Acute lung injury model was induced by intravenous oleic acid (0. 25 mi/kg body weight). 24 hours later, 1.5 μCi 125I-labeled 5% albumin solution (5 ml/kg body weight) was dripped into the lungs through trachea.The alveolar liquid clearance rate, extravascular lung water content, and arterial blood gas were measured 1 hour thereafter.Results: At 24 hours after infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia,with the alveolar liquid clearance rate decreased by 49.2 % and the extravascular lung water content elevated by 47.9%. Compared with the rats in the injury group,terbutaline (10-4 mol/L ) significantly increased the alveolar liquid clearance rate, decreased the extravascular lung water content and improved hypoxemia. The effect of terbutaline was partly blocked by amiloride and ouabain,which were inhibitors of sodium transport. Terbutaline increased the alveolar liquid clearance rate by 63.7 %, and amiloride and ouabain reduced the alveolar liquid clearance rate by 54.7% and 56.8%, respectively.Conclusions: Terbutaline can accelerate alveolar liquid clearance through increasing sodium transport to attenuate pulmonary edema, thus improving gas exchange,which may have therapeutical effect on pulmonary edema after acute lung injury.

  8. Mac-1 deficiency induces respiratory failure by affecting type I alveolar epithelial cells.

    Science.gov (United States)

    Wang, J; Ci, Y B; Liu, C L; Sun, H M

    2017-08-31

    As a β2 integrin family member, Mac-1 plays an important role in the inflammatory response. Inflammation and lung injury are closely associated, but the involvement of Mac-1 in the occurrence and development of such pathologies remains poorly understood. We aimed to investigate the relationship between Mac-1 deficiency and respiratory failure in Mac-1 knockout {Mac-1(-/-)} mice, using C57BL/6J mice as a control. The newborn survival rate of Mac-1(-/-) mice was calculated, and mouse lung tissue was treated with hematoxylin and eosin and subjected to immunofluorescent staining. Moreover, western blotting and immunohistochemistry were used to detect the expression of molecules specific to type I and type II alveolar epithelial cells, as well as alveolar surfactant proteins secreted by the latter. Survival of Mac-1(-/-) pups was significantly lower than that of newborn C57BL/6J mice. In a float test, lung tissues from C57BL/6J mice were buoyant, whereas those of Mac-1(-/-) mice were not. Compared with C57BL/6J mice, expression of proSP-C {specific to type II alveolar epithelial cells} and alveolar surfactant proteins in Mac-1(-/-) mice was not significantly different, implying that type II cell function was unaltered. However, western blotting revealed expression of T1α, Aqp5, and Snx5 {type I alveolar epithelial cell markers} in Mac-1(-/-) mice to be significantly decreased {P Mac-1 may play an important role in respiratory failure. Its absence leads to this condition not by influencing type II alveolar epithelial cells or their secreted surfactant proteins, but rather by reducing type I alveolar cell numbers.

  9. Zanthoxylum piperitum reversed alveolar bone loss of periodontitis via regulation of bone remodeling-related factors.

    Science.gov (United States)

    Kim, Mi Hye; Lee, Hye Ji; Park, Jung-Chul; Hong, Jongki; Yang, Woong Mo

    2017-01-04

    Zanthoxylum piperitum (ZP) has been used to prevent toothache in East Asia. In this study, we investigated the effects of ZP on periodontitis along with alveolar bone loss. Twenty-eight male Sprague-Dawley rats were assigned into 4 groups; non-ligated (NOR), ligated and treated vehicle (CTR), ligated and treated 1mg/mL ZP (ZP1), and ligated and treated 100mg/mL ZP (ZP100). Sterilized 3-0 nylon ligature was placed into the subgingival sulcus around the both sides of mandibular first molar. After topical application of 1 and 100mg/mL ZP for 2 weeks, mandibles was removed for histology. In addition, SaOS-2 osteoblast cells were treated 1, 10 and 100μg/mL ZP for 24h to analyze the expressions of alveolar bone-related markers. Several alveolar bone resorption pits, which indicate cementum demineralization were decreased by ZP treatment. Topical ZP treatment inhibited periodontitis-induced alveolar bone loss. In addition, there were significant reduction of osteoclastic activities following topical ZP treatment in periodontium. The expression of RANKL was decreased in SaOS-2 osteoblast cells by treating ZP, while that of OPG was increased. ZP treatment increased the expressions of Runx2 and Osterix in SaOS-2 cells. In summary, ZP treatment inhibited alveolar bone loss as well as maintained the integrity of periodontal structures via regulation of bone remodeling. ZP may be a therapeutic target for treating periodontitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. 小鼠牙槽骨发育过程中与牙胚之间距离变化的初步研究%A preliminary study of the change of distance between the alveolar bone and tooth germ of the developing mice

    Institute of Scientific and Technical Information of China (English)

    欧明明; 黄晓峰

    2015-01-01

    目的:观察胚胎期及出生后小鼠牙胚与牙槽骨之间距离变化,为研究小鼠牙槽骨发育提供形态学基础。方法将实验用小鼠分成两组:I 组包括胚胎期(E15.5、E16.5、E17.5、E18.5)小鼠头部行组织学处理后冠状面切片,II组包括出生后(PN1.5、PN3.5、PN5.5、PN7.5、PN10.5、PN15.5和 PN30.5)小鼠单侧上颌骨组织学处理后行失状面切片,分别测量牙胚与牙槽骨之间距离后进行比较。结果小鼠出生前牙胚根尖1/3区域与周围骨质之间距离宽度呈递减趋势,而出生后则呈递增趋势;出生后近中牙尖区域此宽度随着牙胚的发育整体呈递减趋势。结论在牙周组织的发育过程中,牙囊细胞起到关键性的作用,它和牙源性上皮相互协作形成牙槽骨,这就导致了牙胚和牙槽骨之间距离随着牙胚的发育而发生着变化。%Objective To provide the morphological basis for alveolar bone development,we observed the change of distance between the tooth germ and alveolar bone of mice. Methods After histological processing,the head of embryonic mice(E15. 5,E16. 5,E17. 5 ,E18. 5 and PN0. 5)were made into sagittal sections and the post natal ones(PN1. 5,PN3. 5,PN5. 5,PN7. 5,PN10. 5,PN15. 5 and PN30. 5)were made into coronal sections. Results The distance between the apical 1 / 3 of root and alveolar bone is a descending tendency of embryos,but it is an in-crease trend of post natal ones. The distance between the mesial cusp and alveolar bone has a descending tendency. Conclusion During the de-velopment of periodontal tissue,dental follicle cells played a critical role. The alveolar bone developed form dental follicle cells. Dental follicle cells interacted with odontogenic epithelial cells result in the difference of distance between tooth germ and alveolar bone.

  11. Iatrogenic injury to the inferior alveolar nerve

    DEFF Research Database (Denmark)

    Hillerup, Søren

    2008-01-01

    The purpose of this prospective, non-randomised, descriptive study is to characterise the neurosensory deficit and associated neurogenic discomfort in 52 patients with iatrogenic injury to the inferior alveolar nerve (IAN). All patients were examined and followed up according to a protocol assess...

  12. Intending to forget: the development of cognitive inhibition in directed forgetting.

    Science.gov (United States)

    Harnishfeger, K K; Pope, R S

    1996-07-01

    The thesis of this research is that children's cognitive inhibition increases in efficiency with age over the middle childhood years, and this increasing efficiency contributes to developmental improvements in memory performance. To explore this thesis, the development of efficient retrieval inhibition, defined as the suppression of activation and retrieval paths to information stored in long-term memory, was investigated. In Experiment 1, first, third, and fifth graders and adults participated in a directed-forgetting experiment. Using a blocked-cuing procedure, subjects were given a "forget" or "remember" cue halfway through an unrelated free-recall list. At recall, subjects were asked either to remember all the words (even the ones they had been instructed to forget) or to remember only to-be-remembered words. The results suggested that the ability to intentionally inhibit the maintenance and recall of irrelevant information improves gradually over the elementary school years, but is not fully mature by fifth grade. Children were less able than adults to inhibit the to-be-forgotten words, and they were less able to withhold production of remembered to-be-forgotten words than were adults. Experiment 2 replicated the development effects found in the first experiment and demonstrated that the developmental differences in performance were due to differences in mnemonic processing rather than differences in the ability to understand the instructions of the tasks.

  13. Chloride transport-driven alveolar fluid secretion is a major contributor to cardiogenic lung edema

    OpenAIRE

    Solymosi, Esther A.; Kaestle-Gembardt, Stefanie M.; Vadász, István; Wang, Liming; Neye, Nils; Chupin, Cécile Julie Adrienne; Rozowsky, Simon; Ruehl, Ramona; Tabuchi, Arata; Schulz, Holger; Kapus, Andras; Morty, Rory E.; Kuebler, Wolfgang M.

    2013-01-01

    This study describes a novel mechanism for the formation of cardiogenic lung edema, a potentially fatal complication of left heart disease that was previously attributed to passive fluid filtration across an intact alveolo-capillary barrier. Instead, we demonstrate that a major part of cardiogenic edema results from active epithelial secretion of Cl− and secondary fluid flux into the alveolar space. Transepithelial Cl− secretion is triggered by inhibition of epithelial Na+ uptake and mediated...

  14. Inferior Alveolar Nerve Injury in Trauma-Induced Mandible Fractures.

    Science.gov (United States)

    Tay, Andrew Ban Guan; Lai, Juen Bin; Lye, Kok Weng; Wong, Wai Yee; Nadkarni, Nivedita V; Li, Wenyun; Bautista, Dianne

    2015-07-01

    This prospective observational cohort study sought to determine the prevalence of inferior alveolar nerve (IAN) injury after mandibular fractures before and after treatment and to elucidate factors associated with the incidence of post-treatment IAN injury and time to normalization of sensation. Consenting patients with mandibular fractures (excluding dentoalveolar, pathologic, previous fractures, or mandibular surgery) were prospectively evaluated for subjective neurosensory disturbance (NSD) and underwent neurosensory testing before treatment and then 1 week, 1.5, 3, 6, and 12 months after treatment. Eighty patients (men, 83.8%; mean age, 30.0 yr; standard deviation, 12.6 yr) with 123 mandibular sides (43 bilateral) were studied. Injury etiology included assault (33.8%), falls (31.3%), motor vehicle accidents (25.0%), and sports injuries (6.3%). Half the fractures (49.6%) involved the IAN-bearing posterior mandible; all condylar fractures (13.0%) had no NSD. Treatment included open reduction and internal fixation (ORIF; 74.8%), closed reduction and fixation (22.0%), or no treatment (3.3%). Overall prevalence of IAN injury was 33.7% (95% confidence interval [CI], 24.8-42.6) before treatment and 53.8% (95% CI, 46.0-61.6) after treatment. In the IAN-bearing mandible, the prevalence was 56.2% (95% CI, 43.2-69.2) before treatment and 72.9% (95% CI, 63.0-82.7) after treatment. In contrast, this prevalence in the non-IAN-bearing mandible was 12.6% (95% CI, 4.1-21.1) before treatment and 31.6% (95% CI, 20.0-43.3) after treatment. Factors associated with the development of post-treatment IAN injury included fracture site and gap distance (a 1-mm increase was associated with a 27% increase in odds of post-treatment sensory alteration). Time to normalization after treatment was associated with type of treatment (ORIF inhibited normalization) and fracture site (IAN-bearing sites took longer to normalize). IAN injury was 4 times more likely in IAN-bearing posterior mandibular

  15. Gastric Helicobacter Infection Inhibits Development of Oral Tolerance to Food Antigens in Mice

    Science.gov (United States)

    Matysiak-Budnik, Tamara; van Niel, Guillaume; Mégraud, Francis; Mayo, Kathryn; Bevilacqua, Claudia; Gaboriau-Routhiau, Valérie; Moreau, Marie-Christiane; Heyman, Martine

    2003-01-01

    The increase in the transcellular passage of intact antigens across the digestive epithelium infected with Helicobacter pylori may interfere with the regulation of mucosal immune responses. The aim of this work was to study the capacity of Helicobacter infection to inhibit the development of oral tolerance or to promote allergic sensitization and the capacity of a gastro-protective agent, rebamipide, to interfere with these processes in mice. Oral tolerance to ovalbumin (OVA) was studied in 48 C3H/He 4-week-old mice divided into four groups: (i) OVA-sensitized mice; (ii) OVA-“tolerized” mice (that is, mice that were rendered immunologically tolerant); (iii) H. felis-infected, OVA-tolerized mice; (iv) and H. felis-infected, OVA-tolerized, rebamipide-treated mice. Oral sensitization to hen egg lysozyme (HEL) was studied in 48 mice divided into four groups: (i) controls; (ii) HEL-sensitized mice; (iii) H. felis-infected, HEL-sensitized mice; and (iv) H. felis-infected, HEL-sensitized, rebamipide-treated mice. Specific anti-OVA or anti-HEL immunoglobulin E (IgE) and IgG1/IgG2a serum titers were measured by enzyme-linked immunosorbent assay. Additionally, the capacity of rebamipide to interfere with antigen presentation and T-cell activation in vitro, as well as absorption of rebamipide across the epithelial monolayer, was tested. H. felis infection led to the inhibition of oral tolerance to OVA, but rebamipide prevented this inhibitive effect of H. felis. H. felis infection did not enhance the sensitization to HEL, but rebamipide inhibited the development of this sensitization. Moreover, rebamipide inhibited in a dose-dependent manner antigen presentation and T-cell activation in vitro and was shown to be able to cross the epithelium at a concentration capable of inducing this inhibitory effect. We conclude that H. felis can inhibit the development of oral tolerance to OVA in mice and that this inhibition is prevented by rebamipide. PMID:12933867

  16. Loss of p120 catenin aggravates alveolar edema of ventilation induced lung injury

    Institute of Scientific and Technical Information of China (English)

    DAI Chen-yang; DAI Guo-feng; SUN Yu; WANG Yue-lan

    2013-01-01

    Background p120 catenin (p120ctn) is an adheren junction protein that regulates barrier function,but its role has not been explored in alveolar edema induced by ventilation.We measured stretch-induced cell gap formation in MLE 12 cells due to the loss of p120.We hypothesized that alveolar permeability was increased by high lung inflation associated with alveolar epithelia cell tight junctions being destroyed,which resulted from the loss of p120.Methods Cultured MLE12 cells were subjected to being stretched or un-stretched (control) and some cells were pretreated with pp2 (c-src inhibitor).After the end of stretching for 0,1,2,and 4 hours,the cells were lysed,and p120 expression and c-src activation was determined by Western blotting analysis.In vivo,SD rats were taken to different tidal volumes (Vt 7 ml/kg or 40 ml/kg,PEEP=0,respiratory rate 30-40 betas/min) for 0,1,2,and 4 hour and some were pretreated with pp2,and alveolar edema was calculated.Rerults It was found that p120 expression was reduced and c-src activation increased in a time-dependent and strain-dependent manner due to cyclic-stretch of the alveolar epithelial cells.These changes could be reversed by inhibition of c-src.We obtained similar changes in rats when they were subjected to large tidal volumes and the alveolar edema increased more than in rats in the low Vt group.Pretreated the rats with inhibition of c-src had less pulmonary edema induced by the high tidal volume ventilation.Conclusions Cyclic stretch MLE 12 cells induced the loss of p120 and may be the same reason by high tidal volume ventilation in rats can aggravate alveolar edema.Maintenance of p120 expression may be a novel therapeutic strategy for the prevention and treatment of ventilation induced lung injury (VILI).

  17. Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and induces necrosis in alveolar macrophages.

    Science.gov (United States)

    Assis, Patricia A; Espíndola, Milena S; Paula-Silva, Francisco W G; Rios, Wendy M; Pereira, Priscilla A T; Leão, Sylvia C; Silva, Célio L; Faccioli, Lúcia H

    2014-05-19

    Phospholipases C (PLCs) are virulence factors found in several bacteria. In Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE2, an essential factor in cell membrane protection. Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. The isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE2 production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE2 inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE2 production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells. Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE2 production.

  18. Effect of odanacatib on root resorption and alveolar bone metabolism during orthodontic tooth movement.

    Science.gov (United States)

    Wei, X X; Chu, J P; Zou, Y Z; Ru, N; Cui, S X; Bai, Y X

    2015-12-22

    The aim of this study was to investigate the effect of local administration of odanacatib (ODN) on orthodontic root resorption and the status of alveolar bone metabolism in rat molars. All specimens were scanned using microcomputed tomography and then the raw images were reconstructed. The total volume of the root resorption craters of the 60 g-NS (normal saline) group was higher than in the 60 g-ODN group and the control group. In the 60 g-NS group, the bone volume fraction values of alveolar bone were significantly decreased compared with the other 2 groups. There were no significant differences in the bone volume fraction values of the tibiae among the 3 groups. The results of tartrate-resistant acid phosphatase-positive (TRAP+) numbers showed that there was no difference between the 60 g-NS group and the 60 g-ODN group. The expression of cathepsin K was decreased significantly in the 60 g-ODN group. These results indicate that ODN reduces orthodontics-induced external root resorption and increases alveolar bone metabolism. This may be because ODN inhibits the activity of odontoclasts, but maintains the quantity of odontoclasts and enhances bone formation. ODN promotes local alveolar bone metabolism, but does not affect systemic bone metabolism.

  19. Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair

    Science.gov (United States)

    Kumar, Varsha Suresh; Zhang, Wei; Rehman, Jalees; Malik, Asrar B.

    2015-01-01

    The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa–induced lung injury, we identified a population of stem cell antigen (Sca)-1–expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1–expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C+Sca-1+ cells expressed Wnt signaling pathway genes, and inhibiting Wnt/β-catenin signaling prevented the regenerative function of Sp-C+Sca-1+ cells in vitro. Thus, P. aeruginosa–mediated lung injury induces the generation of a Sca-1+ subset of type II cells. The progenitor phenotype of the Sp-C+Sca-1+ cells that mediates alveolar epithelial repair might involve Wnt signaling. PMID:25474582

  20. Pattern classification of response inhibition in ADHD: toward the development of neurobiological markers for ADHD.

    Science.gov (United States)

    Hart, Heledd; Chantiluke, Kaylita; Cubillo, Ana I; Smith, Anna B; Simmons, Andrew; Brammer, Michael J; Marquand, Andre F; Rubia, Katya

    2014-07-01

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern classification to task-based functional magnetic resonance imaging (fMRI) of inhibition, to accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and thirty age-matched healthy boys underwent fMRI while performing a Stop task. fMRI data were analyzed with Gaussian process classifiers (GPC), a machine learning approach, to predict individual ADHD diagnosis based on task-based activation patterns. Traditional univariate case-control analyses were also performed to replicate previous findings in a relatively large dataset. The pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. The regions of the discriminative network most predictive of controls included later developing lateral prefrontal, striatal, and temporo-parietal areas that mediate inhibition, while regions most predictive of ADHD were in earlier developing ventromedial fronto-limbic regions, which furthermore correlated with symptom severity. Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral prefrontal, striatal, and temporo-parietal regions that overlapped with areas predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We show that significant individual classification of ADHD patients of 77% can be achieved using whole brain pattern analysis of task-based fMRI inhibition data, suggesting that multivariate pattern recognition analyses of inhibition networks can provide objective diagnostic neuroimaging biomarkers of ADHD. Copyright © 2013 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

  1. Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

    Science.gov (United States)

    Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

    2010-01-01

    Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

  2. Matricaria chamomilla extract inhibits both development of morphine dependence and expression of abstinence syndrome in rats.

    Science.gov (United States)

    Gomaa, Adel; Hashem, Tahia; Mohamed, Mahmoud; Ashry, Esraa

    2003-05-01

    The effect of Matricaria chamomilla (M. chamomilla) on the development of morphine dependence and expression of abstinence was investigated in rats. The frequencies of withdrawal behavioral signs (paw tremor, rearing, teeth chattering, body shakes, ptosis, diarrhea, and urination) and weight loss induced by naloxone challenge were demonstrated in morphine-dependent rats receiving M. chamomilla extract or saline. The withdrawal behavioral manifestations and weight loss were inhibited significantly by chronic co-administration of M. chamomilla extract with morphine. Administration of a single dose of M. chamomilla before the naloxone challenge in morphine-dependent animals abolished the withdrawal behavioral manifestations. The dramatic increase of plasma cAMP induced by naloxone-precipitated abstinence was prevented by chronic co-administration of M. chamomilla extract with morphine. These results suggest that M. chamomilla extract inhibits the development of morphine dependence and expression of abstinence syndrome.

  3. The beta-lactam antibiotic, ceftriaxone, inhibits the development of opioid-induced hyperalgesia in mice.

    Science.gov (United States)

    Chen, Zhijun; He, Ying; Wang, Zaijie Jim

    2012-02-16

    The glutamate transporter GLT-1 is primarily responsible for glutamate clearance in the spinal cord. beta-Lactam antibiotics have been shown to attenuate neuropathic pain behaviors by promoting GLT-1 expression and function in the CNS. The present study tested the hypothesis that ceftriaxone, a prototype beta-lactam antibiotic, can prevent the development of opioid-induced hyperalgesia (OIH) in mice. Repeated morphine administration produced mechanical allodynia and thermal hyperalgesia, signs of OIH, and reduced spinal GLT-1 expression in mice. Ceftriaxone (200mg/kg/d, i.p., for 7 d) inhibited OIH. Correlating with the behavioral effects, ceftriaxone reversed downregulation of GLT-1 expression that was induced by OIH. These results suggest that ceftriaxone inhibited the development of OIH by up-regulating spinal GLT-1 expression.

  4. Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response

    Science.gov (United States)

    Roberts, Lydia M; Ledvina, Hannah E; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P; Sempowski, Gregory D; Frelinger, Jeffrey A

    2015-01-01

    Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c.DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data. PMID:26029367

  5. Inferior Alveolar Nerve Injuries Following Implant Placement - Importance of Early Diagnosis and Treatment: a Systematic Review

    Directory of Open Access Journals (Sweden)

    Ilana Shavit

    2014-12-01

    Full Text Available Objectives: The purpose of this article is to systematically review diagnostic procedures and risk factors associated with inferior alveolar nerve injury following implant placement, to identify the time interval between inferior alveolar nerve injury and its diagnosis after surgical dental implant placement and compare between outcomes of early and delayed diagnosis and treatment given based on case series recorded throughout a period of 10 years. Material and Methods: We performed literature investigation through MEDLINE (PubMed electronic database and manual search through dental journals to find articles concerning inferior alveolar nerve injury following implant placement. The search was restricted to English language articles published during the last 10 years, from December 2004 to March 2014. Results: In total, we found 33 articles related to the topic, of which 27 were excluded due to incompatibility with established inclusion criteria. Six articles were eventually chosen to be suitable. The studies presented diagnostic methods of inferior alveolar nerve sensory deficit, and we carried out an assessment of the proportion of patients diagnosed within different time intervals from the time the injury occurred. Conclusions: Various diagnostic methods have been developed throughout the years for dealing with 1 quite frequent complication in the implantology field - inferior alveolar nerve injury. Concurrently, the importance of early diagnosis and treatment was proved repeatedly. According to the results of the data analysis, a relatively high percentage of the practitioners successfully accomplished this target and achieved good treatment outcomes.

  6. 蓝玉簪颗粒抑制脂多糖诱导大鼠肺泡巨噬细胞TNF-α产生及相关机制研究%Gentiana veitchiorum particles inhibited LPS induced pulmonary alveolar macrophages(AM)TNF-α production and the underlying mechanism

    Institute of Scientific and Technical Information of China (English)

    侯颖; 曹蔚; 李涛; 刘水冰; 张晓楠; 李旭波; 田琼; 尤福生

    2011-01-01

    AIM: To investigate the effect of Gentiana veitchiorum particles on the expression of TNF-α in pulmonary alveolar macrophages (AM) which induced by LPS, to explain the mechanism about anti-inflammatory action of Gentiana veitchiorum particles. METHODS: Purification of rat AM, TNF-α level in AM culture supematant was detected by ELISA. Western blot method for detecting the expression of TNF-α and pERK in the AM. While application of ERK antagonist (PD98059) in rat AM and the expression of TNFα was observed by Western blot. RESULTS: Gentiana veitchiorum particles can reduce the LPS induced AM TNF-α increase in dose dependent manner. Gentiana veitchiorum particles (100 mg/L) can significantly reduce the LPS induc ed pERK and TNF-α protein expression in AM. compared with LPS stimulation group, we found that ERK inhibitor ( PD98059 30 mol/L), Gentiana veitchiorum particles intervention and Gentiana veitchiorum particles + PD98059 groups' TNF-α expression were significantly reduced in rat AM. CONCLUSION: Gentiana veitchiorum particles can inhibit the LPS induced pulmonary AM TNF-α expression, one of the possible mechanism is to inhibit the extracailular signal transduction pathway.%目的:探讨蓝玉簪颗粒对脂多糖(LPS)诱导大鼠肺泡巨噬细胞(AM)内TNF-α表达及可能作用机制.方法:分离纯化AM,应用ELISA法检测蓝玉簪颗粒对LPS诱导的大鼠AM培养上清中的TNF-α水平的影响,应用Western blot方法检测大鼠AM内TNF-α及pERK蛋白表达水平,同时应用ERK拮抗剂(PD98059)观察AM内TNF-α蛋白表达.结果:蓝玉簪颗粒可剂量依赖的降低由于LPS刺激导致的AM培养上清内TNF-α含量升高;蓝玉簪(100 mg/L)颗粒可显著降低由于LPS刺激导致的AM细胞内pERK及TNF-α蛋白表达升高;ERK特异性抑制剂(PD98059 30 mol/L)及蓝玉簪颗粒干预,蓝玉簪颗粒+PD98059干预后,我们发现与LPS刺激组相比,大鼠AM中TNF-α表达显著降低.结论:蓝玉

  7. Aberrant Proliferation of Differentiating Alveolar Cells Induces Hyperplasia in Resting Mammary Glands of SV40-TAg Transgenic Mice

    OpenAIRE

    Quante, Timo; Wegwitz, Florian; Abe, Julia; Rossi, Alessandra; Deppert, Wolfgang; Bohn, Wolfgang

    2014-01-01

    WAP-T1 transgenic mice express SV40-TAg under control of the whey acidic protein (WAP) promoter, which directs activity of this strong viral oncogene to luminal cells of the mammary gland. Resting uniparous WAP-T1 glands develop hyperplasia composed of TAg positive cells prior to appearance of advanced tumor stages. We show that cells in hyperplasia display markers of alveolar differentiation, suggesting that TAg targets differentiating cells of the alveolar compartment. The glands show signi...

  8. Aberrant proliferation of differentiating alveolar cells induces hyperplasia in resting mammary glands of SV40-TAg transgenic mice

    OpenAIRE

    Wolfgang eBohn; Timo eQuante

    2014-01-01

    WAP-T1 transgenic mice express SV40-TAg under control of the WAP promoter (Whey Acidic Protein) which directs activity of this strong viral oncogene to luminal cells of the mammary gland. Resting uniparous WAP-T1 glands develop hyperplasia composed of TAg positive cells prior to appearance of advanced tumor stages. We show that cells in hyperplasia display markers of alveolar differentiation, suggesting that TAg targets differentiating cells of the alveolar compartment. The glands show signif...

  9. Asbestos fibres and man made mineral fibres: induction and release of tumour necrosis factor-alpha from rat alveolar macrophages.

    OpenAIRE

    Ljungman, A G; Lindahl, M.; Tagesson, C

    1994-01-01

    OBJECTIVES--Mounting evidence suggests that asbestos fibres can stimulate alveolar macrophages to generate the potent inflammatory and fibrogenic mediator, tumour necrosis factor-alpha (TNF-alpha), and that this may play an important part in the onset and development of airway inflammation and lung fibrosis due to asbestos fibre inhalation. Little is known, however, about the ability of other mineral fibres to initiate formation and release of TNF-alpha by alveolar macrophages. Therefore the ...

  10. Enhanced rifampicin delivery to alveolar macrophages by solid lipid nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Chuan Junlan [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Li Yanzhen [Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery Technology and Pharmacokinetics (China); Yang Likai; Sun Xun [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China); Zhang Qiang [Peking University, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences (China); Gong Tao, E-mail: gongtaoy@126.com; Zhang Zhirong, E-mail: zrzzl@vip.sina.com [West China School of Pharmacy, Sichuan University, Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (China)

    2013-05-15

    The present study aimed at developing a drug delivery system targeting the densest site of tuberculosis infection, the alveolar macrophages (AMs). Rifampicin (RFP)-loaded solid lipid nanoparticles (RFP-SLNs) with an average size of 829.6 {+-} 16.1 nm were prepared by a modified lipid film hydration method. The cytotoxicity of RFP-SLNs to AMs and alveolar epithelial type II cells (AECs) was examined using MTT assays. The viability of AMs and AECs was above 80 % after treatment with RFP-SLNs, which showed low toxicity to both AMs and AECs. Confocal Laser Scanning Microscopy was employed to observe the interaction between RFP-SLNs and both AMs and AECs. After incubating the cells with RFP-SLNs for 2 h, the fluorescent intensity in AMs was more and remained longer (from 0.5 to 12 h) when compared with that in AECs (from 0.5 to 8 h). In vitro uptake characteristics of RFP-SLNs in AMs and AECs were also investigated by detection of intracellular RFP by High performance liquid chromatography. Results showed that RFP-SLNs delivered markedly higher RFP into AMs (691.7 ng/mg in cultured AMs, 662.6 ng/mg in primary AMs) than that into AECs (319.2 ng/mg in cultured AECs, 287.2 ng/mg in primary AECs). Subsequently, in vivo delivery efficiency and the selectivity of RFP-SLNs were further verified in Sprague-Dawley rats. Under pulmonary administration of RFP-SLNs, the amount of RFP in AMs was significantly higher than that in AECs at each time point. Our results demonstrated that solid lipid nanoparticles are a promising strategy for the delivery of rifampicin to alveolar macrophages selectively.

  11. Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice.

    Science.gov (United States)

    Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Miyaura, Chisato; Inada, Masaki

    2015-01-01

    Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo.

  12. White matter correlates of cognitive inhibition during development: a diffusion tensor imaging study.

    Science.gov (United States)

    Treit, S; Chen, Z; Rasmussen, C; Beaulieu, C

    2014-09-12

    Inhibitory control and cognitive flexibility are two key executive functions that develop in childhood and adolescence, increasing one's capacity to respond dynamically to changing external demands and refrain from impulsive behaviors. These gains evolve in concert with significant brain development. Magnetic resonance imaging studies have identified numerous frontal and cingulate cortical areas associated with performance on inhibition tasks, but less is known about the involvement of the underlying anatomical connectivity, namely white matter. Here we used diffusion tensor imaging (DTI) to examine correlations between a DTI-derived parameter, fractional anisotropy (FA) of white matter, and performance on the NEPSY-II Inhibition test (Naming, Inhibition and Switching conditions) in 49 healthy children aged 5-16years (20 females; 29 males). First, whole brain voxel-based analysis revealed several clusters in the frontal projections of the corpus callosum, where higher FA was associated with worse inhibitory performance, as well as several clusters in posterior brain regions and one in the brainstem where higher FA was associated with better cognitive flexibility (in the Switching task), suggesting a dichotomous relationship between FA and these two aspects of cognitive control. Tractography through these clusters identified several white matter tracts, which were then manual traced in native space. Pearson's correlations confirmed associations between higher FA of frontal projections of the corpus callosum with poorer inhibitory performance (independent of age), though associations with Switching were not significant. Post-hoc evaluation suggested that FA of orbital and anterior frontal projections of the corpus callosum also mediated performance differences across conditions, which may reflect differences in self-monitoring or strategy use. These findings suggest a link between the development of inhibition and cognitive control with that of the underlying white

  13. New regenerative treatment for tooth and periodontal bone defect associated with posttraumatic alveolar bone crush fracture.

    Science.gov (United States)

    Kiyokawa, Kensuke; Kiyokawa, Munekatsu; Takagi, Mikako; Rikimaru, Hideaki; Fukaya, Takuji

    2009-05-01

    We developed a new regenerative treatment of tooth and periodontal defect and tooth dislocation associated with posttraumatic alveolar bone crush fracture in the region of the maxillary anterior teeth. Using this method, dislocated teeth are first extracted and crushed alveolar bone is debrided. The dislocated teeth are then reimplanted, and cancellous iliac bone (bone marrow) is grafted to the area surrounding the teeth to regenerate periodontal bone. Tooth reimplantation was completely successful in 2 cases, and periodontal bone regenerated to a sufficient height with the iliac bone graft. Compared with the general method of treatment with a prosthesis (bridge), when using this method to treat cases such as these, there is no sacrifice of healthy teeth adjacent to the defect, and sufficient esthetic and functional recovery is possible. It is thought that this method could be applied as a new treatment of alveolar bone fracture in the future.

  14. Periodontal plastic surgery for management of cleft alveolar ridge: a case report.

    Science.gov (United States)

    Agrawal, Amit A; Yeltiwar, Ramreddy K

    2012-02-01

    Cleft lips, alveoli, and palates are the most common congenital malformations of the head and neck region, all of which often can be managed successfully when presented at a young age. It is a common belief that clefts in the alveolar ridge should be treated with the help of bone grafting materials. This could be the best option when the cleft is to be treated in early age, when the patient is still developing and has high regenerative potential. However, in adults, the literature supports the fact that bone grafting in alveolar clefts has a higher chance for failure. The present case report exemplifies a periodontal plastic surgical procedure involving a combination of connective tissue and free gingival grafting to restore the form and function of a cleft alveolar ridge in an adult patient.

  15. Development of response inhibition in the context of relevant versus irrelevant emotions.

    Science.gov (United States)

    Schel, Margot A; Crone, Eveline A

    2013-01-01

    The present study examined the influence of relevant and irrelevant emotions on response inhibition from childhood to early adulthood. Ninety-four participants between 6 and 25 years of age performed two go/nogo tasks with emotional faces (neutral, happy, and fearful) as stimuli. In one go/nogo task emotion formed a relevant dimension of the task and in the other go/nogo task emotion was irrelevant and participants had to respond to the color of the faces instead. A special feature of the latter task, in which emotion was irrelevant, was the inclusion of free choice trials, in which participants could freely decide between acting and inhibiting. Results showed a linear increase in response inhibition performance with increasing age both in relevant and irrelevant affective contexts. Relevant emotions had a pronounced influence on performance across age, whereas irrelevant emotions did not. Overall, participants made more false alarms on trials with fearful faces than happy faces, and happy faces were associated with better performance on go trials (higher percentage correct and faster RTs) than fearful faces. The latter effect was stronger for young children in terms of accuracy. Finally, during the free choice trials participants did not base their decisions on affective context, confirming that irrelevant emotions do not have a strong impact on inhibition. Together, these findings suggest that across development relevant affective context has a larger influence on response inhibition than irrelevant affective context. When emotions are relevant, a context of positive emotions is associated with better performance compared to a context with negative emotions, especially in young children.

  16. Development of response inhibition in the context of relevant versus irrelevant emotions

    Directory of Open Access Journals (Sweden)

    Margot A Schel

    2013-07-01

    Full Text Available The present study examined the influence of relevant and irrelevant emotions on response inhibition from childhood to early adulthood. Ninety-four participants between 6 and 25 years of age performed two go/nogo tasks with emotional faces (neutral, happy, and fearful as stimuli. In one go/nogo task emotion formed a relevant dimension of the task and in the other go/nogo task emotion was irrelevant and participants had to respond to the color of the faces instead. A special feature of the latter task, in which emotion was irrelevant, was the inclusion of free choice trials, in which participants could freely decide between acting and inhibiting. Results showed a linear increase in response inhibition performance with increasing age both in relevant and irrelevant affective contexts. Relevant emotions had a pronounced influence on performance across age, whereas irrelevant emotions did not. Overall, participants made more false alarms on trials with fearful faces than happy faces, and happy faces were associated with better performance on go trials (higher percentage correct and faster RTs than fearful faces. The latter effect was stronger for young children in terms of accuracy. Finally, during the free choice trials participants did not base their decisions on affective context, confirming that irrelevant emotions do not have a strong impact on inhibition. Together, these findings suggest that across development relevant affective context has a larger influence on response inhibition than irrelevant affective context. When emotions are relevant, a context of positive emotions is associated with better performance compared to a context with negative emotions, especially in young children.

  17. In vitro inhibition of pigmentation and fiber development in colored cotton

    Institute of Scientific and Technical Information of China (English)

    Shu-na YUAN; Waqas MALIK; Shui-jin HUA; Noreen BIBI; Xue-de WANG

    2012-01-01

    Colored cotton has naturally pigmented fibers.The mechanism of pigmentation in cotton fiber is not well documented.This experiment was conducted to study the effects cf respiratory chain inhibitors,i.e.,rotenone and thiourea,on pigmentation and fiber development in colored cotton.After 1 d post-anthesis,ovaries were harvested and developing ovules were cultured on the liquid medium containing different concentrations of rotenone and thiourea for 30 d.The results demonstrate that both respiratory inhibitors reduced fiber length and ovule development under ovule culture conditions,and the inhibition efficiency of rotenone was much higher than that of thiourea.Rotenone and thiourea also showed significant effects on fiber pigment (color) development in colored cotton.In green cotton fiber,rotenone advanced fiber pigment development by 7 d at 200 μmol/L,while thiourea inhibited fiber pigmentation at all treatment levels (400,600,800,1000,and 2000 μmol/L).Both respiratory inhibitors,however,had no significant effects on pigmentation of brown cotton fibers.The activities of cytochrome c oxidase (COX) and polyphenol oxidase (PPO) decreased significantly with increasing levels of both respiratory inhibitors.It is suggested that both respiratory inhibitors have important roles in deciphering the mechanism of pigmentation and fiber development in colored cotton.

  18. Clinical indications for digital imaging in dento-alveolar trauma. Part 1: traumatic injuries.

    Science.gov (United States)

    Cohenca, Nestor; Simon, James H; Roges, Ramon; Morag, Yoav; Malfaz, Jose Maria

    2007-04-01

    Traumatized teeth present a clinical challenge with regard to their diagnosis, treatment plan, and prognosis. Recent developments in imaging systems have enabled clinicians to visualize structural changes effectively. Computed tomography, magnetic resonance imaging and cone beam computed tomography are among the most commonly used systems for dental and maxillofacial surgery. The purpose of this review is to describe the advantages and disadvantages of each technique and the clinical application for dento-alveolar trauma. Three clinical cases are described to illustrate the potential use of the NewTom 3G for diagnosis and treatment plan of dento-alveolar traumatic injuries.

  19. Inhibition of larval development of the marine copepod Acartia tonsa by four synthetic musk substances

    DEFF Research Database (Denmark)

    Wollenberger, Leah; Breitholtz, M.; Kusk, Kresten Ole

    2003-01-01

    ketone) and 2.5 mg/l (Tonalide(TM)). Since, the synthetic musks strongly inhibited larval development in A. tonsa at low nominal concentrations, they should be considered as very toxic. The larval development test with A. tonsa is able to provide important aquatic toxicity data for the evaluation...... of synthetic musks, for which there is little published ecotoxicological information available regarding Crustacea. It is suggested that subchronic and chronic copepod toxicity tests should be used more frequently for risk assessment of environmental pollutants. (C) 2002 Elsevier Science B.V. All rights...

  20. Inhibition of apoptosis in early tooth development alters tooth shape and size.

    Science.gov (United States)

    Kim, J-Y; Cha, Y-G; Cho, S-W; Kim, E-J; Lee, M-J; Lee, J-M; Cai, J; Ohshima, H; Jung, H-S

    2006-06-01

    Apoptosis plays important roles in various stages of organogenesis. In this study, we hypothesized that apoptosis would play an important role in tooth morphogenesis. We examined the role of apoptosis in early tooth development by using a caspase inhibitor, z-VAD-fmk, concomitant with in vitro organ culture and tooth germ transplantation into the kidney capsule. Inhibition of apoptosis at the early cap stage did not disrupt the cell proliferation level when compared with controls. However, the macroscopic morphology of mice molar teeth exhibited dramatic alterations after the inhibition of apoptosis. Crown height was reduced, and mesiodistal diameter was increased in a concentration-dependent manner with z-VAD-fmk treatment. Overall, apoptosis in the enamel knot would be necessary for the proper formation of molar teeth, including appropriate shape and size.

  1. Pelvic alveolar rhabdomyosarcoma in a young adult

    Directory of Open Access Journals (Sweden)

    David Reisner, MD

    2014-01-01

    Full Text Available Rhabdomyosarcomas are soft-tissue tumors, rare in adults. Accounting for nearly 5% of childhood cancers, they represent less than 0.03% of adult malignancies (1, 2. Three different subtypes of rhabdomyosarcoma have been described (embryonal, alveolar and pleomorphic, making up approximately 50%, 30%, and 20% of the cases, respectively (3. Although the definitive diagnosis is made pathologically, some distinguishing features among these subtypes, and between rhabdomyosarcomas and other soft-tissue tumors, can be suggested on MRI and CT. We present an interesting case of a 20-year-old female with a locally aggressive pelvic alveolar rhabdomyosarcoma. While the prognosis has improved with newer treatment techniques, overall survival rates remain poor. Our case study presents typical features of a rare disease, which can often present a diagnostic dilemma for clinicians.

  2. Dephasing and diffusion on the alveolar surface

    Science.gov (United States)

    Buschle, L. R.; Kurz, F. T.; Kampf, T.; Wagner, W. L.; Duerr, J.; Stiller, W.; Konietzke, P.; Wünnemann, F.; Mall, M. A.; Wielpütz, M. O.; Schlemmer, H. P.; Ziener, C. H.

    2017-02-01

    We propose a surface model of spin dephasing in lung tissue that includes both susceptibility and diffusion effects to provide a closed-form solution of the Bloch-Torrey equation on the alveolar surface. The nonlocal susceptibility effects of the model are validated against numerical simulations of spin dephasing in a realistic lung tissue geometry acquired from synchotron-based μ CT data sets of mouse lung tissue, and against simulations in the well-known Wigner-Seitz model geometry. The free induction decay is obtained in dependence on microscopic tissue parameters and agrees very well with in vivo lung measurements at 1.5 Tesla to allow a quantification of the local mean alveolar radius. Our results are therefore potentially relevant for the clinical diagnosis and therapy of pulmonary diseases.

  3. Silver Nanoparticles in Alveolar Bone Surgery Devices

    Directory of Open Access Journals (Sweden)

    Stefano Sivolella

    2012-01-01

    Full Text Available Silver (Ag ions have well-known antimicrobial properties and have been applied as nanostrategies in many medical and surgical fields, including dentistry. The use of silver nanoparticles (Ag NPs may be an option for reducing bacterial adhesion to dental implant surfaces and preventing biofilm formation, containing the risk of peri-implant infections. Modifying the structure or surface of bone grafts and membranes with Ag NPs may also prevent the risk of contamination and infection that are common when alveolar bone augmentation techniques are used. On the other hand, Ag NPs have revealed some toxic effects on cells in vitro and in vivo in animal studies. In this setting, the aim of the present paper is to summarize the principle behind Ag NP-based devices and their clinical applications in alveolar bone and dental implant surgery.

  4. [Alveolar haemorrhage following a cannabis water pipe].

    Science.gov (United States)

    Moatemri, Z; Zaibi, H; Dabboussi, S; Mhamedi, S; Aichaouia, C; Khadhraoui, M; Cheikh, R

    2016-10-01

    Respiratory toxicity of cannabis is well-known today particularly with the new consumption patterns. We report the case of a 25-year-old man admitted for haemoptysis, with unfavourable outcome and acute respiratory failure. Various explorations concluded to acute respiratory distress syndrome secondary to diffuse alveolar haemorrhage. Etiological assessment was initially negative. Outcome was favourable during hospitalization, authorizing the discharge of our patient. Two days later, alveolar haemorrhage recur, with positive toxicological tests for cannabis and the patient admits smoking cannabis by plastic "bang". We illustrate, through this case, the severity of respiratory complications caused by new methods of using cannabis, particularly with plastic 'bang', hence the need to insist of the importance of supported withdrawal and to inform young people how these techniques are serious.ssss. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Development of fluorescent Plasmodium falciparum for in vitro growth inhibition assays

    Directory of Open Access Journals (Sweden)

    Crabb Brendan S

    2010-06-01

    Full Text Available Abstract Background Plasmodium falciparum in vitro growth inhibition assays are widely used to evaluate and quantify the functional activity of acquired and vaccine-induced antibodies and the anti-malarial activity of known drugs and novel compounds. However, several constraints have limited the use of these assays in large-scale population studies, vaccine trials and compound screening for drug discovery and development. Methods The D10 P. falciparum line was transfected to express green fluorescent protein (GFP. In vitro growth inhibition assays were performed over one or two cycles of P. falciparum asexual replication using inhibitory polyclonal antibodies raised in rabbits, an inhibitory monoclonal antibody, human serum samples, and anti-malarials. Parasitaemia was evaluated by microscopy and flow cytometry. Results Transfected parasites expressed GFP throughout all asexual stages and were clearly detectable by flow cytometry and fluorescence microscopy. Measurement of parasite growth inhibition was the same when determined by detection of GFP fluorescence or staining with ethidium bromide. There was no difference in the inhibitory activity of samples when tested against the transfected parasites compared to the parental line. The level of fluorescence of GFP-expressing parasites increased throughout the course of asexual development. Among ring-stages, GFP-fluorescent parasites were readily separated from uninfected erythrocytes by flow cytometry, whereas this was less clear using ethidium bromide staining. Inhibition by serum and antibody samples was consistently higher when tested over two cycles of growth compared to one, and when using a 1 in 10 sample dilution compared to 1 in 20, but there was no difference detected when using a different starting parasitaemia to set-up growth assays. Flow cytometry based measurements of parasitaemia proved more reproducible than microscopy counts. Conclusions Flow cytometry based assays using GFP

  6. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

    Science.gov (United States)

    Cheng, Michelle; Ho, Samantha; Yoo, Jun Hwan; Tran, Deanna Hoang-Yen; Bakirtzi, Kyriaki; Su, Bowei; Tran, Diana Hoang-Ngoc; Kubota, Yuzu; Ichikawa, Ryan; Koon, Hon Wai

    2015-01-01

    Background Cathelicidin (LL-37 in humans and mCRAMP in mice) represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT) of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-β1-induced EMT of colon cancer cells. Media conditioned by the human colonic CCD-18Co fibroblasts promoted human colon cancer HT-29 cell proliferation. Cathelicidin pretreatment inhibited colon cancer cell proliferation mediated by media conditioned by human colonic CCD-18Co fibroblasts. Cathelicidin disrupted tubulin distribution in colonic fibroblasts. Disruption of tubulin in fibroblasts reduced fibroblast-supported colon cancer cell proliferation. Conclusion Cathelicidin effectively inhibits colon cancer development by interfering with EMT and fibroblast

  7. Phagocytic properties of lung alveolar wall cells

    Directory of Open Access Journals (Sweden)

    Tanaka,Akisuke

    1974-04-01

    Full Text Available For the purpose to define the mechanism of heavy metal intoxication by inhalation, morphologic observations were made on rat lungs after nasal instillation of iron colloid particles of positive and negative electric charges. Histochemical observation was also made on the liver and spleen of these animals. The instilled iron colloid particles reach the alveolar cavity easily, as can be seen in the tissue sections stained by Prussian blue reaction. Alveolar macrophages do take up them avidly both of positive and negative charges, though much less the positive particles than negative ones. In contrast, the alveolar epithelial cells take up solely positive particles by phagocytosis but not negative ones. Electron microscope observation revealed that the positive particles are ingested by Type I epithelial cells by pinocytosis and by Type II cells by phagocytosis as well. Then the iron colloid particles are transferred into the basement membrane by exocytosis. Travelling through the basement membrane they are again taken up by capillary endothelial cells by phagocytosis. Some particles were found in the intercellular clefts of capillary endothelial cells but not any iron colloid particles in the intercellular spaces of epithelial cells and in the capillary lumen. However, the liver and spleen tissues of the animals given iron colloid showed a strong positive iron reaction. On the basis of these observations, the mechanism of acute intoxication by inhaling heavy metal dusts like lead fume is discussed from the view point of selective uptake of alveolar epithelial and capillary endothelial cells for the particles of the positive electric cha'rge.

  8. Bis-enoxacin blocks rat alveolar bone resorption from experimental periodontitis.

    Directory of Open Access Journals (Sweden)

    Mercedes F Rivera

    Full Text Available Periodontal diseases are multifactorial, caused by polymicrobial subgingival pathogens, including Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Chronic periodontal infection results in inflammation, destruction of connective tissues, periodontal ligament, and alveolar bone resorption, and ultimately tooth loss. Enoxacin and a bisphosphonate derivative of enoxacin (bis-enoxacin inhibit osteoclast formation and bone resorption and also contain antibiotic properties. Our study proposes that enoxacin and/or bis-enoxacin may be useful in reducing alveolar bone resorption and possibly bacterial colonization. Rats were infected with 10(9 cells of polymicrobial inoculum consisting of P. gingivalis, T. denticola, and T. forsythia, as an oral lavage every other week for twelve weeks. Daily subcutaneous injections of enoxacin (5 mg/kg/day, bis-enoxacin (5, 25 mg/kg/day, alendronate (1, 10 mg/kg/day, or doxycycline (5 mg/day were administered after 6 weeks of polymicrobial infection. Periodontal disease parameters, including bacterial colonization/infection, immune response, inflammation, alveolar bone resorption, and systemic spread, were assessed post-euthanasia. All three periodontal pathogens colonized the rat oral cavity during polymicrobial infection. Polymicrobial infection induced an increase in total alveolar bone resorption, intrabony defects, and gingival inflammation. Treatment with bis-enoxacin significantly decreased alveolar bone resorption more effectively than either alendronate or doxycycline. Histologic examination revealed that treatment with bis-enoxacin and enoxacin reduced gingival inflammation and decreased apical migration of junctional epithelium. These data support the hypothesis that bis-enoxacin and enoxacin may be useful for the treatment of periodontal disease.

  9. Management of maxillary alveolar process fractures

    Directory of Open Access Journals (Sweden)

    Shukhrat Boymuradov

    2011-04-01

    Full Text Available Incidence of maxillofacial traumas is reported steadily increasing, maxillary fractures being extremely severe. Maxillary alveolar process (AP and front teeth are traumatized more frequently than any other parts of the maxilla. Deprivation of teeth and AP post-traumatic flaw as well as loss of alveolar height not only create a cosmetic defect but also complicate subsequent prosthetics of the patients. The work was initiated to assess efficacy of “CollapAn L” in comparison with a combination of “Osteon”, an osteoplastic material, and “Colla Guide” resorbable membrane in prevention of AP post-traumatic flaws and deformities. 60 patients aged from 16 to 47 with the comminuted fractures of maxillary AP emergently hospitalized were examined and treated. The findings showed that Combination of “Osteon” and “Colla Guide” resorbable membrane is the one to increase efficacy of the treatment, facilitating preservation of and alveolar crest height and shape. In addition, preservation of bone tissue mineralization helps avoid risk of the bone wound inflammatory morbidity.

  10. Endogenous histamine inhibits the development of morphine-induced conditioned place preference

    Institute of Scientific and Technical Information of China (English)

    Ying-xia GONG; Min LV; Yong-ping ZHU; Yuan-yuan ZHU; Er-qing WEI; Hong SHI; Qun-li ZENG; Zhong CHEN

    2007-01-01

    Aim:The conditioned place preference (CPP) paradigm was used to investigate the effects of endogenous histamine on the processes leading to morphine-induced reward-seeking behavior in Sprague-Dawley rats. Methods: The model of CPP was used to assess the rewarding effect of morphine. The levels of histamine,glutamate, γ-aminobutyric acid (GABA), dopamine (DA) and 3, 4-dihydroxyphenyl-acetic acid (DOPAC) in rat brains were measured with high-performance liquid chromatography. Immunohistochemistry technique was used to observe the morphological changes of neurons. Results: Intraperitoneal injection of mor-phine (2, 5 or 10 mg/kg) induced the development of CPP in a dose-dependent manner. In addition, morphine administrations (10 mg/kg) decreased the hista-mine content and reduced the number and size of histaminergic neurons in the tuberomammillary nucleus (TM), as well as markedly increasing the DOPAC/DA ratios in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Intra-peritoneal injection of histidine (50, 100 or 200 mg/kg) dose-dependently inhibited the development of morphine-induced CPP. Bilateral lesions of the TM, which decreased the histamine levels in the VTA and NAc, potentiated the development of CPP induced by morphine (1 mg/kg, a dose that produced no appreciable effect when given alone) and increased the DOPAC/DA ratios in the VTA and NAc, but did not change the glutamate or GABA levels in these nuclei. Histidine reversed the effects of the TM lesions. Conclusion: These results indicate that endog-enous histamine plays a role in inhibiting the development of morphine-induced reward-seeking behavior, and the inhibition may involve the modulation of dopa-minergic activity.

  11. Inhibition of larval development of the marine copepod Acartia tonsa by four synthetic musk substances.

    Science.gov (United States)

    Wollenberger, Leah; Breitholtz, Magnus; Ole Kusk, Kresten; Bengtsson, Bengt Erik

    2003-04-15

    A nitro musk (musk ketone) and three polycyclic musks (Tonalide, Galaxolide and Celestolide) were tested for acute and subchronic effects on a marine crustacean, the calanoid copepod Acartia tonsa. Sublethal effects on A. tonsa larvae were investigated with a rapid and cost effective bioassay, which is based on the easily detectable morphological change from the last nauplius to the first copepodite stage during copepod larval development. The inhibition of larval development after 5 days exposure was a very sensitive endpoint, with 5-d-EC(50)-values as low as 0.026 mg/l (Tonalide), 0.059 mg/l (Galaxolide), 0.066 mg/l (musk ketone) and 0.160 mg/l (Celestolide), respectively. These values were generally more than one order of magnitude below the 48-h-LC(50)-values found for adults, which were 0.47 mg/l (Galaxolide), 0.71 mg/l (Celestolide), 1.32 mg/l (musk ketone) and 2.5 mg/l (Tonalide). Since the synthetic musks strongly inhibited larval development in A. tonsa at low nominal concentrations, they should be considered as very toxic. The larval development test with A. tonsa is able to provide important aquatic toxicity data for the evaluation of synthetic musks, for which there is little published ecotoxicological information available regarding Crustacea. It is suggested that subchronic and chronic copepod toxicity tests should be used more frequently for risk assessment of environmental pollutants.

  12. Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation.

    Science.gov (United States)

    Wettstein, Guillaume; Bellaye, Pierre-Simon; Kolb, Martin; Hammann, Arlette; Crestani, Bruno; Soler, Paul; Marchal-Somme, Joëlle; Hazoume, Adonis; Gauldie, Jack; Gunther, Andreas; Micheau, Olivier; Gleave, Martin; Camus, Philippe; Garrido, Carmen; Bonniaud, Philippe

    2013-04-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation. Transition of epithelial/mesothelial cells into myofibroblasts [epithelial-to-mesenchymal transition (EMT)] occurs under the influence of transforming growth factor (TGF)-β1, with Snail being a major transcription factor. We study here the role of the heat-shock protein HSP27 in fibrogenesis and EMT. In vitro, we have up- and down-modulated HSP27 expression in mesothelial and epithelial cell lines and studied the expression of different EMT markers induced by TGF-β1. In vivo, we inhibited HSP27 with the antisense oligonucleotide OGX-427 (in phase II clinical trials as anticancer agent) in our rat subpleural/pulmonary fibrosis models. We demonstrate that HSP27 is strongly expressed during the fibrotic process in patients with IPF and in different in vivo models. We showed that HSP27 binds to and stabilizes Snail and consequently induces EMT. Conversely, HSP27 knockdown leads to Snail proteasomal degradation, thus inhibiting TGF-β1-induced EMT. Inhibition of HSP27 with OGX-427 efficiently blocks EMT and fibrosis development. Controls in vivo were an empty adenovirus that did not induce fibrosis and a control antisense oligonucleotide. The present work opens the possibility of a new therapeutic use for HSP27 inhibitors against IPF, for which there is no conclusively effective treatment.

  13. N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung Development In Vivo and In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengchang Liao

    2016-01-01

    Full Text Available Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR’s expression and role in fetal lung development. Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801’s influence on intrauterine hypoxia-induced retardation of fetal lung development was tested in vivo, and NMDA’s direct effect on fetal lung development was observed using fetal lung organ culture in vitro. Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damage in vivo. In vitro experiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression. Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

  14. Recrutamento alveolar em pacientes no pós-operatório imediato de cirurgia cardíaca Alveolar recruitment in patients in the immediate postoperative period of cardiac surgery

    Directory of Open Access Journals (Sweden)

    Cauê Padovani

    2011-03-01

    Full Text Available Complicações pulmonares no pós-operatório de cirurgia cardíaca são frequentes, destacando-se a atelectasia e a hipoxemia. As manobras de recrutamento alveolar contribuem significativamente para a prevenção e o tratamento destas complicações. Desta forma, este estudo buscou agrupar e atualizar os conhecimentos relacionados à utilização das manobras de recrutamento alveolar no pós-operatório imediato de cirurgia cardíaca. Observou-se a eficácia do recrutamento alveolar por meio de diferentes técnicas específicas e a necessidade do desenvolvimento de novas pesquisas.Lung complications during postoperative period of cardiac surgery are frequently, highlighting atelectasis and hypoxemia. Alveolar recruitment maneuvers have an important role in the prevention and treatment of these complications. Thus, this study reviewed and updated the alveolar recruitment maneuvers performance in the immediate postoperative period of cardiac surgery. We noted the efficacy of alveolar recruitment through different specific techniques and the need for development of new studies.

  15. "Play Skills" for Shy Children: Development of a "Social Skills Facilitated Play" Early Intervention Program for Extremely Inhibited Preschoolers

    Science.gov (United States)

    Coplan, Robert J.; Schneider, Barry H.; Matheson, Adrienne; Graham, Allison

    2010-01-01

    The aim of the present study was to develop and provide a preliminary evaluation of a social-skills-based early intervention program specifically designed to assist extremely inhibited preschoolers. Participants were a sample of n = 522 extremely inhibited preschool-aged children, who were randomly assigned to either the "Social Skills…

  16. Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes

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    Rafael L. Simões

    2013-01-01

    Full Text Available Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3–30 μM elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS and nitric oxide (NO generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF-κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes.

  17. Proinflammatory responses of heme in alveolar macrophages: repercussion in lung hemorrhagic episodes.

    Science.gov (United States)

    Simões, Rafael L; Arruda, Maria Augusta; Canetti, Cláudio; Serezani, Carlos H; Fierro, Iolanda M; Barja-Fidalgo, Christina

    2013-01-01

    Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM) being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3-30 μM) elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS) and nitric oxide (NO) generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF- κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes.

  18. Integrin alpha(3)-subunit expression modulates alveolar epithelial cell monolayer formation.

    Science.gov (United States)

    Lubman, R L; Zhang, X L; Zheng, J; Ocampo, L; Lopez, M Z; Veeraraghavan, S; Zabski, S M; Danto, S I; Borok, Z

    2000-07-01

    We investigated expression of the alpha(3)-integrin subunit by rat alveolar epithelial cells (AECs) grown in primary culture as well as the effects of monoclonal antibodies with blocking activity against the alpha(3)-integrin subunit on AEC monolayer formation. alpha(3)-Integrin subunit mRNA and protein were detectable in AECs on day 1 and increased with time in culture. alpha(3)- and beta(1)-integrin subunits coprecipitated in immunoprecipitation experiments with alpha(3)- and beta(1)-subunit-specific antibodies, consistent with their association as the alpha(3)beta(1)-integrin receptor at the cell membrane. Treatment with blocking anti-alpha(3) monoclonal antibody from day 0 delayed development of transepithelial resistance, reduced transepithelial resistance through day 5 compared with that in untreated AECs, and resulted in large subconfluent patches in monolayers viewed by scanning electron microscopy on day 3. These data indicate that alpha(3)- and beta(1)-integrin subunits are expressed in AEC monolayers where they form the heterodimeric alpha(3)beta(1)-integrin receptor at the cell membrane. Blockade of the alpha(3)-integrin subunit inhibits formation of confluent AEC monolayers. We conclude that the alpha(3)-integrin subunit modulates formation of AEC monolayers by virtue of the key role of the alpha(3)beta(1)-integrin receptor in AEC adhesion.

  19. Hydrogen sulfide inhibits development of atherosclerosis through up-regulating protein S-nitrosylation.

    Science.gov (United States)

    Lin, Yan; Chen, Yulong; Zhu, Ninghong; Zhao, Sihai; Fan, Jianglin; Liu, Enqi

    2016-10-01

    Hydrogen sulfide (H2S) is an important gaseous signaling molecule that serves many important regulatory roles in physiological and pathophysiological conditions. H2S exerts an anti-atherosclerotic effect through mediating the biological functions of nitric oxide (NO). However, its mechanism of action is unclear. The purpose of this study is to explore the effect mechanism of H2S on the development of atherosclerosis with regard to protein S-nitrosylation. A total of 45 male apoE(-/-) mice were randomly divided into three groups. Atherosclerosis was induced by Western diet (21% fat and 0.15% cholesterol) with/without administration of a H2S donor (NaHS) or an endogenous cystathionine γ-lyase inhibitor (d, l-propargylglycine) for 12 weeks. After 12 weeks, plasma lipid and plasma NO levels were measured. Aortic gross lesion area and histopathological features of aortic lesion were determined. Additionally, the level of S-nitrosylated proteins in vascular smooth muscle cells (VSMCs) was detected using immunofluorescence in aorta. Rat VSMCs were performed in an in vitro experiment. Inducible nitric oxide synthase (iNOS) protein expression, NO generation, protein S-nitrosylation, and cell proliferation and migration were measured. We found that H2S significantly reduced the aortic atherosclerotic lesion area (P=0.006) and inhibited lipid and macrophage accumulation (P=0.004, P=0.002) and VSMC proliferation (P=0.019) in apoE(-/-) mice. H2S could up-regulate levels of plasma NO and protein S-nitrosylation in aorta VSMCs. However, d, l- propargylglycine had the opposite effect, increasing the lesion area and the content of lipids and macrophages in the lesions of apoE(-/-) mice and down-regulating plasma NO levels and protein S-nitrosylation in aorta VSMCs. In vitro experiments, H2S could significantly reverse the reduction of iNOS expression and NO generation induced by oxidized low-density lipoprotein in VSMCs. Moreover, H2S could increase the protein S

  20. Delta-Notch signaling and lateral inhibition in zebrafish spinal cord development

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    Givan Lee Anne

    2001-07-01

    Full Text Available Abstract Background Vertebrate neural development requires precise coordination of cell proliferation and cell specification to guide orderly transition of mitotically active precursor cells into different types of post-mitotic neurons and glia. Lateral inhibition, mediated by the Delta-Notch signaling pathway, may provide a mechanism to regulate proliferation and specification in the vertebrate nervous system. We examined delta and notch gene expression in zebrafish embryos and tested the role of lateral inhibition in spinal cord patterning by ablating cells and genetically disrupting Delta-Notch signaling. Results Zebrafish embryos express multiple delta and notch genes throughout the developing nervous system. All or most proliferative precursors appeared to express notch genes whereas subsets of precursors and post-mitotic neurons expressed delta genes. When we ablated identified primary motor neurons soon after they were born, they were replaced, indicating that specified neurons laterally inhibit neighboring precursors. Mutation of a delta gene caused precursor cells of the trunk neural tube to cease dividing prematurely and develop as neurons. Additionally, mutant embryos had excess early specified neurons, with fates appropriate for their normal positions within the neural tube, and a concomitant deficit of late specified cells. Conclusions Our results are consistent with the idea that zebrafish Delta proteins, expressed by newly specified neurons, promote Notch activity in neighboring precursors. This signaling is required to maintain a proliferative precursor population and generate late-born neurons and glia. Thus, Delta-Notch signaling may diversify vertebrate neural cell fates by coordinating cell cycle control and cell specification.

  1. Inferior alveolar nerve injuries associated with mandibular fractures.

    Science.gov (United States)

    Bede, Salwan Yousif Hanna; Ismael, Waleed Khaleel; Al-Assaf, Dhuha A; Omer, Saad Salem

    2012-11-01

    The study evaluates the incidence of inferior alveolar nerve injuries in mandibular fractures, the duration of their recovery, and the factors associated with them. Fifty-two patients with mandibular fractures involving the ramus, angle, and body regions were included in this study; the inferior alveolar nerve was examined for neurological deficit posttraumatically using sharp/blunt differentiation method, and during the follow-up period the progression of neural recovery was assessed. The incidence of neural injury of the inferior alveolar nerve was 42.3%, comminuted and displaced linear fractures were associated with higher incidence of inferior alveolar nerve injury and prolonged recovery time, and recovery of inferior alveolar nerve function occurred in 91%.Fractures of the mandible involving the ramus, angle, and body regions, and comminuted and displaced linear fractures are factors that increase the incidence of inferior alveolar nerve injuries. Missile injuries can be considered as another risk factor.

  2. PERFORATION OF INFERIOR ALVEOLAR NERVE BY MAXILLARY ARTERY. Perforation of inferior alveolar nerve by maxillary artery

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    Prakash B Billakanti

    2016-03-01

    Full Text Available La fosa infratemporal es un área anatómica clínicamente importante para la administración de agentes anestésicos locales en odontología y cirugía maxilofacial. Fueron estudiadas variaciones en la anatomía del nervio alveolar inferior y la arteria maxilar en la disección infratemporal. Durante la disección rutinaria de la cabeza en el cadáver de un varón adulto, fue observada una variación excepcional en el origen del nervio alveolar inferior y su relación con las estructuras circundantes. El nervio alveolar inferior se originaba en el nervio mandibular por dos raíces y la primera parte de la arteria maxilar estaba incorporada entre ambas. El origen embriológico de esta variación y sus implicaciones clínicas es debatido. Dado que la arteria maxilar transcurría entre las dos raíces del nervio alveolar inferior, y el nervio estaba fijado entre el foramen oval y el foramen mandibular, el atrapamiento vásculo-nervioso pudo causar entume-cimiento o dolor de cabeza e interferir con la inyección de anestésicos locales en la fosa infratemporal.  Variaciones anatómicas en esta región deben ser tenidas en cuenta, especialmente en casos de tratamiento fallido de neuralgia del trigémino. Infratemporal fossa is clinically important anatomical area for the delivery of local anesthetic agents in dentistry and maxillofacial surgery. Variations in the anatomy of the inferior alveolar nerve and maxillary artery were studied in infratemporal dissection. During routine dissection of the head in an adult male cadaver an unusual variation in the origin of the inferior alveolar nerve and its relationship with the surrounding structures was observed. The inferior alveolar nerve originated from the mandibular nerve by two roots and the first part of the maxillary artery was incorporated between them. An embryologic origin of this variation and its clinical implications is discussed. Because the maxillary artery runs between the two roots of

  3. Recent advances in alveolar biology: some new looks at the alveolar interface.

    Science.gov (United States)

    Possmayer, Fred; Hall, Stephen B; Haller, Thomas; Petersen, Nils O; Zuo, Yi Y; Bernardino de la Serna, Jorge; Postle, Anthony D; Veldhuizen, Ruud A W; Orgeig, Sandra

    2010-08-31

    This article examines the manner in which some new methodologies and novel concepts have contributed to our understanding of how pulmonary surfactant reduces alveolar surface tension. Investigations utilizing small angle X-ray diffraction, inverted interface fluorescence microscopy, time of flight-secondary ion mass spectroscopy, atomic force microscopy, two-photon fluorescence microscopy and electrospray mass spectroscopy are highlighted and a new model of ventilation-induced acute lung injury described. This contribution attempts to emphasize how these new approaches have resulted in a fuller appreciation of events presumably occurring at the alveolar interface. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  4. FGF signaling pathway in the developing chick lung: expression and inhibition studies.

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    Rute S Moura

    Full Text Available BACKGROUND: Fibroblast growth factors (FGF are essential key players during embryonic development. Through their specific cognate receptors (FGFR they activate intracellular cascades, finely regulated by modulators such as Sprouty. Several FGF ligands (FGF1, 2, 7, 9, 10 and 18 signaling through the four known FGFRs, have been implicated in lung morphogenesis. Although much is known about mammalian lung, so far, the avian model has not been explored for lung studies. METHODOLOGY/PRINCIPAL FINDINGS: In this study we provide the first description of fgf10, fgfr1-4 and spry2 expression patterns in early stages of chick lung development by in situ hybridization and observe that they are expressed similarly to their mammalian counterparts. Furthermore, aiming to determine a role for FGF signaling in chick lung development, in vitro FGFR inhibition studies were performed. Lung explants treated with an FGF receptor antagonist (SU5402 presented an impairment of secondary branch formation after 48 h of culture; moreover, abnormal lung growth with a cystic appearance of secondary bronchi and reduction of the mesenchymal tissue was observed. Branching and morphometric analysis of lung explants confirmed that FGFR inhibition impaired branching morphogenesis and induced a significant reduction of the mesenchyme. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that FGFRs are essential for the epithelial-mesenchymal interactions that determine epithelial branching and mesenchymal growth and validate the avian embryo as a good model for pulmonary studies, namely to explore the FGF pathway as a therapeutic target.

  5. NaoXinTong Inhibits the Development of Diabetic Retinopathy in db/db Mice

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    Mengyang Liu

    2015-01-01

    Full Text Available Buchang NaoXinTong capsule (NXT is a Chinese Materia Medica standardized product extracted from 16 Chinese traditional medical herbs and widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. Formation of microaneurysms plays an important role in the development of diabetic retinopathy. In this study, we investigated if  NXT can protect diabetic mice against the development of diabetic retinopathy. The db/db mice (~6 weeks old, a diabetic animal model, were divided into two groups and fed normal chow or plus NXT for 14 weeks. During the treatment, fasting blood glucose levels were monthly determined. After treatment, retinas were collected to determine retinal thickness, accumulation of carbohydrate macromolecules, and caspase-3 (CAS-3 expression. Our results demonstrate that administration of NXT decreased fasting blood glucose levels. Associated with the decreased glucose levels, NXT blocked the diabetes-induced shrink of multiple layers, such as photoreceptor layer and outer nuclear/plexiform layers, in the retina. NXT also inhibited the diabetes-induced expression of CAS-3 protein and mRNA, MMP-2/9 and TNFα mRNA, accumulation of carbohydrate macromolecules, and formation of acellular capillaries in the retina. Taken together, our study shows that NXT can inhibit the development of diabetic retinopathy and suggests a new potential application of NXT in clinic.

  6. Inhibition of Ageratina adenophora on Spore Germination and Gametophyte Development of Macrothelypteris torresiana

    Institute of Scientific and Technical Information of China (English)

    Kai-Mei Zhang; Lei Shi; Chuang-Dao Jiang; Zhen-Yu Li

    2008-01-01

    Allalopathy of Ageratina adenophora plays an important role in its invasion. However, we have little knowledge of its allelpathic effects on ferns. In Petri dish bioassays, the inhibitory potential of aqueous leachates from roots, stems and leaves of A. adenophora was studied on the spore germination and gametophyte development of Macrothelypteris torresiana. All leachates Inhibited the spore germination and growth of the first rhizoid of M. torresiana and inhibitory effects Increased with increasing leachate concentrations. Root leachates proved most inhibitory. Gametophyte rhizoids of M. torresiana treated with stem and leaf leachates ofA. adenophora were erect, which was similar to those of the control. However, gametophyte rhizoids of M. torresiana treated with root leachates of A. adenophora were erect, but also curving or swollen. Moreover, curving and swollen rhizoids Increased with Increasing concentrations. As time went by, rhizoids treated with root leachates were not so curved and the swelling almost disappeared. Possible causes are discussed in the present study. The increasing concentrations of leaf leachates also delayed the stages of gametophyte development. With the treatment of root leachates, the delay was more obvious. Thus A. adenophora inhibited the spore germination and gametophyte development of M. torresiana and the root leachates were most inhibitory.

  7. Anatomy of Mandibular Vital Structures. Part I: Mandibular Canal and Inferior Alveolar Neurovascular Bundle in Relation with Dental Implantology

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    Hom-Lay Wang

    Full Text Available Objectives: It is critical to determine the location and configuration of the mandibular canal and related vital structures during the implant treatment. The purpose of the present study was to review the literature concerning the mandibular canal and inferior alveolar neurovascular bundle anatomical variations related to the implant surgery.Material and Methods: Literature was selected through the search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were mandibular canal, inferior alveolar nerve, and inferior alveolar neurovascular bundle. The search was restricted to English language articles, published from 1973 to November 2009. Additionally, a manual search in the major anatomy, dental implant, prosthetic and periodontal journals and books were performed.Results: In total, 46 literature sources were obtained and morphological aspects and variations of the anatomy related to implant treatment in posterior mandible were presented as two entities: intraosseous mandibular canal and associated inferior alveolar neurovascular bundle.Conclusions: A review of morphological aspects and variations of the anatomy related to mandibular canal and mandibular vital structures are very important especially in implant therapy since inferior alveolar neurovascular bundle exists in different locations and possesses many variations. Individual, gender, age, race, assessing technique used and degree of edentulous alveolar bone atrophy largely influence these variations. It suggests that osteotomies in implant dentistry should not be developed in the posterior mandible until the position of the mandibular canal is established.

  8. Complications in the treatment with alveolar extraosseous distractors. Literature review

    OpenAIRE

    Rodriguez Grandjean, Alfredo; Reininger, David; López Quiles, Juan

    2015-01-01

    Background To review the literature that analyses the types and frequency of complications associated with the use of extraosseous alveolar distraction from 2007 to 2013. Material and Methods Review of the literature in PubMed, using these keywords; alveolar ridge, alveolar distraction osteogenesis, complication, literature review. Inclusion criteria were: articles published between 2007 and 2013 that included the distraction protocol, the complications encountered and the time when they occu...

  9. 17{beta}-Estradiol inhibits chondrogenesis in the skull development of zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Fushimi, Shigeko, E-mail: fushimi@med.kawasaki-m.ac.jp [Department of Public Health, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Wada, Naoyuki, E-mail: wada@med.kawasaki-m.ac.jp [Department of Molecular and Developmental Biology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Nohno, Tsutomu, E-mail: nohno@bcc.kawasaki-m.ac.jp [Department of Molecular and Developmental Biology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Tomita, Masafumi, E-mail: toxicology@med.kawasaki-m.ac.jp [Department of Medical Toxicology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan); Saijoh, Kiyofumi, E-mail: saijohk@med.kanazawa-u.ac.jp [Department of Hygiene, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa 920-8564 (Japan); Sunami, Shigeo, E-mail: ssunami@med.kawasaki-m.ac.jp [Department of Clinical Nutrition, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki 701-0193 (Japan); Katsuyama, Hironobu, E-mail: katsu@med.kawasaki-m.ac.jp [Department of Public Health, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192 (Japan)

    2009-12-13

    17{beta}-Estradiol (E2) plays important roles in the development and differentiation of the gonad and central nervous systems, but little is known regarding the effects of exogenous E2 on chondrogenesis in skeletal development. In the present study, we found that treatment with E2 1-5 days post-fertilization (dpf) at concentrations above 1.5 x 10{sup -5} M increased the mortality rate in zebrafish embryos. Morphological analysis showed that treatment with E2 1-5 dpf caused abnormal cartilage formation in a dose-dependent manner at concentrations above 5 x 10{sup -6} M. E2 1-5 dpf at 1.5 x 10{sup -5} M caused defects of the ethmoid plate, parallel cleft of the trabecular cartilage, and hypoplasia of Meckel's cartilage and the ceratohyal cartilage. The sensitivity of embryos to E2 depended on the developmental stage. In early chondrogenesis (1-2 dpf), the embryos were highly sensitive to E2, leading to hypoplasia of the cartilage. In situ hybridization studies showed that expression levels of patched1 (ptc1) and patched2 (ptc2) receptor mRNAs were markedly decreased by exposure to 2 x 10{sup -5} M E2 1-2 dpf. However, the expression levels of sonic hedgehog (shh) and tiggywinkle hedgehog (twhh) mRNAs were constant in the E2-treated embryos. In addition, the estrogen receptor antagonist ICI 182,780 did not completely abolish the effects of E2, suggesting that E2 may not inhibit chondrogenesis through its nuclear estrogen receptor. These results suggest that exposure to exogenous E2 possibly inhibits chondrogenesis via inhibition of the hedgehog (Hh) signal transduction system.

  10. Novel bioceramic-reinforced hydrogel for alveolar bone regeneration.

    Science.gov (United States)

    Iviglia, Giorgio; Cassinelli, Clara; Torre, Elisa; Baino, Francesco; Morra, Marco; Vitale-Brovarone, Chiara

    2016-10-15

    The osseointegration of dental implants and their consequent long-term success is guaranteed by the presence, in the extraction site, of healthy and sufficient alveolar bone. Bone deficiencies may be the result of extraction traumas, periodontal disease and infection. In these cases, placement of titanium implants is contraindicated until a vertical bone augmentation is obtained. This goal is achieved using bone graft materials, which should simulate extracellular matrix (ECM), in order to promote osteoblast proliferation and fill the void, maintaining the space without collapsing until the new bone is formed. In this work, we design, develop and characterize a novel, moldable chitosan-pectin hydrogel reinforced by biphasic calcium phosphate particles with size in the range of 100-300μm. The polysaccharide nature of the hydrogel mimics the ECM of natural bone, and the ceramic particles promote high osteoblast proliferation, assessed by Scanning Electron Microscopy analysis. Swelling properties allow significant adsorption of water solution (up to 200% of solution content) so that the bone defect space can be filled by the material in an in vivo scenario. The incorporation of ceramic particles makes the material stable at different pH and increases the compressive elastic modulus, toughness and ultimate tensile strength. Furthermore, cell studies with SAOS-2 human osteoblastic cell line show high cell proliferation and adhesion already after 72h, and the presence of ceramic particles increases the expression of alkaline phosphatase activity after 1week. These results suggest a great potential of the developed moldable biomaterials for the regeneration of the alveolar bone. The positive fate of a surgical procedure involving the insertion of a titanium screw still depends on the quality and quantity of alveolar bone which is present in the extraction site. Available materials are basically hard scaffold materials with un-predictable behavior in different condition

  11. Quantifying second generation ethanol inhibition: Design of Experiments approach and kinetic model development.

    Science.gov (United States)

    Schneiderman, Steven J; Johnson, Roger W; Menkhaus, Todd J; Gilcrease, Patrick C

    2015-03-01

    While softwoods represent a potential feedstock for second generation ethanol production, compounds present in their hydrolysates can inhibit fermentation. In this study, a novel Design of Experiments (DoE) approach was used to identify significant inhibitory effects on Saccharomyces cerevisiae D5A for the purpose of guiding kinetic model development. Although acetic acid, furfural and 5-hydroxymethyl furfural (HMF) were present at potentially inhibitory levels, initial factorial experiments only identified ethanol as a significant rate inhibitor. It was hypothesized that high ethanol levels masked the effects of other inhibitors, and a subsequent factorial design without ethanol found significant effects for all other compounds. When these non-ethanol effects were accounted for in the kinetic model, R¯(2) was significantly improved over an ethanol-inhibition only model (R¯(2)=0.80 vs. 0.76). In conclusion, when ethanol masking effects are removed, DoE is a valuable tool to identify significant non-ethanol inhibitors and guide kinetic model development.

  12. Inhibition of growth and development of root border cells in wheat by Al.

    Science.gov (United States)

    Zhu, Mu-Yuan; Ahn, Sung-Ju; Matsumoto, Hideaki

    2003-03-01

    The production and development of border cells vary with genotype, and they are released in wheat at an earlier stage of root development than other species studied so far. No significant difference was observed in the maximum number of border cells between Al-tolerant (Atlas 66) and Al-sensitive (Scout 66) cultivars in the absence of Al treatment. Al seriously inhibited the production and release of border cells, resulting in clumping of border cells in Scout 66, but less clustering in Atlas 66. The number of border cells released from roots treated with Al is significantly less than that from roots grown without Al treatment. Al treatment induced the death of detached border cells in vitro and they were killed by a 20-h treatment with 25 micro m Al. No significant difference in survival percentage of detached border cells was observed between Atlas 66 and Scout 66, regardless of the presence or absence of Al. The removal of border cells from root tips of both Atlas 66 and Scout 66 enhanced the Al-induced inhibition of root elongation concomitant with increased Al accumulation in the root. These results suggest that border cells adhered to the root tips play a potential role in the protection of root from Al injury in wheat.

  13. MLKL inhibition attenuates hypoxia-ischemia induced neuronal damage in developing brain.

    Science.gov (United States)

    Qu, Yi; Shi, Jing; Tang, Ying; Zhao, Fengyan; Li, Shiping; Meng, Junjie; Tang, Jun; Lin, Xuemei; Peng, Xiaodong; Mu, Dezhi

    2016-05-01

    Mixed lineage kinase domain-like protein (MLKL) is a critical molecule mediating cell necroptosis. However, its role in brain injury remains obscure. We first investigated the functions and mechanisms of MLKL in mediating neuronal damage in developing brain after hypoxia-ischemia. Neuronal necroptosis was induced by oxygen-glucose deprivation (OGD) plus caspase inhibitor zVAD treatment (OGD/zVAD). We found that two important necroptosis related proteins, receptor-interacting protein 1 and 3 (RIP1, RIP3) were upregulated. Furthermore, the interaction of RIP1-RIP3 with MLKL increased. Inhibition of MLKL through siRNA diminished RIP1-RIP3-MLKL interaction and attenuated neuronal death induced by OGD/zVAD. The translocation of oligomerized MLKL to the neuronal membrane leading to the injury of cellular membrane is the possible new mechanism of neuronal necroptosis. Animal experiment with neonatal rats further proved that MLKL inhibition attenuated brain damage induced by hypoxia-ischemia. These findings suggest that MLKL is a target to attenuate brain damage in developing brain.

  14. PERFORATION OF INFERIOR ALVEOLAR NERVE BY MAXILLARY ARTERY. LA PERFORACION DEL NERVIO ALVEOLAR INFERIOR POR LA ARTERIA MAXILAR

    OpenAIRE

    Vanishree S Nayak; Ramachandra Bhat K; Prakash Billakanti Babu

    2011-01-01

    Infratemporal fossa is clinically important anatomical area for the delivery of local anesthetic agents in dentistry and maxillofacial surgery. Variations in the anatomy of the inferior alveolar nerve and maxillary artery were studied in infratemporal dissection. During routine dissection of the head in an adult male cadaver an unusual variation in the origin of the inferior alveolar nerve and its relationship with the surrounding structures was observed. The inferior alveolar nerve originate...

  15. The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Bryan D. Johnston

    2015-01-01

    Full Text Available In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed.

  16. The Ovariectomized Rat as a Model for Studying Alveolar Bone Loss in Postmenopausal Women

    Science.gov (United States)

    Johnston, Bryan D.; Ward, Wendy E.

    2015-01-01

    In postmenopausal women, reduced bone mineral density at the hip and spine is associated with an increased risk of tooth loss, possibly due to a loss of alveolar bone. In turn, having fewer natural teeth may lead to compromised food choices resulting in a poor diet that can contribute to chronic disease risk. The tight link between alveolar bone preservation, tooth retention, better nutritional status, and reduced risk of developing a chronic disease begins with the mitigation of postmenopausal bone loss. The ovariectomized rat, a widely used preclinical model for studying postmenopausal bone loss that mimics deterioration of bone tissue in the hip and spine, can also be used to study mineral and structural changes in alveolar bone to develop drug and/or dietary strategies aimed at tooth retention. This review discusses key findings from studies investigating mandible health and alveolar bone in the ovariectomized rat model. Considerations to maximize the benefits of this model are also included. These include the measurement techniques used, the age at ovariectomy, the duration that a rat is studied after ovariectomy and habitual diet consumed. PMID:26060817

  17. Cathelicidin suppresses colon cancer development by inhibition of cancer associated fibroblasts

    Directory of Open Access Journals (Sweden)

    Cheng M

    2014-12-01

    Full Text Available Michelle Cheng,1,* Samantha Ho,1,* Jun Hwan Yoo,1,2,* Deanna Hoang-Yen Tran,1,* Kyriaki Bakirtzi,1 Bowei Su,1 Diana Hoang-Ngoc Tran,1 Yuzu Kubota,1 Ryan Ichikawa,1 Hon Wai Koon1 1Center for Inflammatory Bowel Diseases, Division of Digestive Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; 2Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Republic of Korea *These authors share co-first authorship Background: Cathelicidin (LL-37 in humans and mCRAMP in mice represents a family of endogenous antimicrobial and anti-inflammatory peptides. Cancer-associated fibroblasts can promote the proliferation of colon cancer cells and growth of colon cancer tumors. Methods: We examined the role of cathelicidin in the development of colon cancer, using subcutaneous human HT-29 colon-cancer-cell-derived tumor model in nude mice and azoxymethane- and dextran sulfate-mediated colon cancer model in C57BL/6 mice. We also determined the indirect antitumoral mechanism of cathelicidin via the inhibition of epithelial–mesenchymal transition (EMT of colon cancer cells and fibroblast-supported colon cancer cell proliferation. Results: Intravenous administration of cathelicidin expressing adeno-associated virus significantly reduced the size of tumors, tumor-derived collagen expression, and tumor-derived fibroblast expression in HT-29-derived subcutaneous tumors in nude mice. Enema administration of the mouse cathelicidin peptide significantly reduced the size and number of colonic tumors in azoxymethane- and dextran sulfate-treated mice without inducing apoptosis in tumors and the adjacent normal colonic tissues. Cathelicidin inhibited the collagen expression and vimentin-positive fibroblast expression in colonic tumors. Cathelicidin did not directly affect HT-29 cell viability, but did significantly reduce tumor growth factor-ß1-induced EMT of colon cancer cells. Media conditioned by the

  18. Development of a New Class of Drugs To Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers

    Science.gov (United States)

    2016-10-01

    endocrine targeting therapies designed to block AR activity that re- emerges during castration. However, despite a growing armamentarium of drugs ...AWARD NUMBERS: W81XWH-14-1-0518 TITLE: Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration- Resistant...DATES COVERED 30Sep2015 - 29Sep2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0518 Development of a New Class of Drugs To Inhibit All

  19. GABAB Receptor Antagonist CGP46381 Inhibits Form-Deprivation Myopia Development in Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Zhen-Ying Cheng

    2015-01-01

    Full Text Available The aim was to investigate the effects of the GABAB receptor antagonist, CGP46381, on form-deprivation myopia (FDM in guinea pigs. Twenty-four guinea pigs had monocular visual deprivation induced using a diffuser for 11 days (day 14 to 25. The deprived eyes were treated with daily subconjunctival injections (100 μl of either 2% CGP46381, 0.2% CGP46381, or saline or received no injection. The fellow eyes were left untreated. Another six animals received no treatment. At the start and end of the treatment period, ocular refractions were measured using retinoscopy and vitreous chamber depth (VCD and axial length (AL using A-scan ultrasound. All of the deprived eyes developed relative myopia (treated versus untreated eyes, P0.05. Subconjunctival injections of CGP46381 inhibit FDM development in guinea pigs in a dose-dependent manner.

  20. 牙弓/牙槽骨弓的塑形矫治——基于牙弓形态发育不良的儿童错(拾)畸形诊断与阻断治疗%Dental alveolar bone and dental arch remodeling in children: orthodontic diagnosis and treatments based on individual child arch development

    Institute of Scientific and Technical Information of China (English)

    李小兵

    2016-01-01

    The etiology of malocclusions basically involves both congenital and environmental factors. Malocclusion is the result of the abnormal development of the orofacial complex (including tooth, dental alveolar bone, upper and lower jaws). Early orthodontic interceptive treatments involve the elimination of all congenital and environmental factors that contribute to the malformation of the orofacial complex, as well as interrupt the deviated development of the orofacial complex and the occlusion. Early orthodontic interceptive treatments mainly aim to use children's growth potential to correct abnormal develop-ments of occlusions and orthodontically treat malocclusions more efficiently. The early orthodontic interceptive treatments include correcting the child's bad oral habits, training the abnormal functioned para-oral muscles, maintaining the normal eruptions of succeeding permanent teeth, applying interceptive treatments to the mal-developed teeth, and employing functional orthopedic treatments for abnormal growths of the upper and lower jaws. In orthodontics, correcting mal-positioned teeth is called orthodontic treatment, while rectifying the abnormal relationships of the upper and lower jaws is called functional orthopedic treatment. However, no clear definition is available as regards to the early orthodontic interceptive treatment of malocclusions caused by the deviated development of the dental alveolar bone. This new theory of "early dental alveolar bone and dental arch remodeling technique" was proposed by Professor Li Xiaobing of the Department of Pediatric Dentistry, Faculty of Pediatric Dentistry and Orthodontics in West China Hospital of Stomatology through his clinical analyses and investigation of his early orthodontic interceptive treatments. He defined the early orthodontic corrections of abnormal growth of dental alveolar bone as "remodel". The "early dental alveolar bone and dental arch remodeling theory and technique" is proved useful in

  1. Segment distraction to reduce a wide alveolar cleft before alveolar bone grafting.

    NARCIS (Netherlands)

    Binger, T.; Katsaros, C.; Rucker, M.; Spitzer, W.J.

    2003-01-01

    OBJECTIVE: To demonstrate a method for reduction of wide alveolar clefts prior to bone grafting. This method aims to facilitate bone grafting and achieve adequate soft tissue coverage of the graft with attached gingiva. CASE REPORT: Treatment of a patient with bilateral cleft lip and palate with a s

  2. Recent advances in alveolar biology: Evolution and function of alveolar proteins

    NARCIS (Netherlands)

    Orgeig, S.; Hiemstra, P.S.; Veldhuizen, E.J.A.; Casals, C.; Clark, H.W.; Hackzu, A.; Knudsen, L.; Possmayer, F.

    2010-01-01

    This review is focused on the evolution and function of alveolar proteins. The lung faces physical and environmental challenges, due to changing pressures/volumes and foreign pathogens, respectively. The pulmonary surfactant system is integral in protecting the lung from these challenges via two gro

  3. 3D-CT evaluation of secondary alveolar bone grafts in alveolar clefts

    Energy Technology Data Exchange (ETDEWEB)

    Naitoh, Hiroshi; Nishimura, Yoshihiko [Kyoto Univ. (Japan). Graduate School of Medicine; Yamawaki, Yoshiroh [Kyoto Katsura Hospital (Japan); Morimoto, Naoki [Kobe City General Hospital (Japan)

    2002-07-01

    From 1994 to 2000, we treated 116 patients with cleft alveolus by secondary alveolar bone grafts, and 48 of them were evaluated morphologically with 3D-CT. The frequency of successful bony bridging was significantly higher in the group whose grafts were completely enveloped (including the anterior alveolar ridge) with a mucoperiosteal flap. The frequency was also significantly higher in the group who underwent bone grafts at the age of 13 or less, and canine eruptions did not influence the ratio. Some cases showed such an improved growth pattern of grafted bone that the shape of the affected maxilla resembled that of the normal side, after long-term follow-up observations. The growth increment was remarkable in anterior maxillary height. Orthodontic management guides the canine or incisor into the reconstructed area of the previous cleft. We surmise that the new occlusal position puts pressure on the grafted bone and promotes further osteogenesis. These findings show that it is important to produce sufficient bony bridge to guide the canine or incisor, not the volume of grafted bone, in secondary alveolar bone grafts. Long-term follow-up observation, after more than 2-3 years, is also necessary to evaluate secondary alveolar bone grafts. (author)

  4. 右美托咪啶对异氟醚抑制切皮时患者体动反应的肺泡气最低有效浓度的影响%Effect of dexmedetomidine on minimum alveolar concentration of isoflurane required to inhibit the body movement during skin incision

    Institute of Scientific and Technical Information of China (English)

    冀翔宇; 王世端; 刘英志; 周赞宫; 朱德璋

    2011-01-01

    Objective To investigate the effect of dexmedetomidine on minimum alveolar concentration (MAC) of isoflurane required to inhibit the body movement during skin incision. Methods Forty-eight ASA Ⅰ or Ⅱ patients aged 40-60 yr with body mass index of 22-27 kg/m2 undergoing elective upper abdominal surgery under general anesthesia were randomly divided into 3 groups: control group (group C, n = 15);low dose dexmedetomidine group (group D1, n = 17) and high dose dexmedetomidine group (group D2, n = 16). The patients were unpremedicated. Dexmedetomidine 0.4 and 0.8 μg/kg in normal saline (NS) 15 ml was infused over 15 min before induction of anesthesia in D1 and D2 groups respectively. Anesthesia was induced with fentanyl-propofol-succinylcholine. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained with isoflurane. MAC of isoflurane was determined by up-and-down technique. The initial end-tidal isofiurane concentration was set at 1.0%, 0.8% and 0.6% in C, D1 and D2 groups respectively. Each time the end-tidal isoflurane concentration was increased/decreased by 0.2%. Skin incision was made after 15 min of equilibration, when the twitch height returned to more than 90% of its control value. Movement of body and limbs including swallowing and coughing were carefully looked for when skin incision was made. MAC of isoflurane was the mean of end-tidal concentration of isoflurane of each crossover pair, and 95 % CI was calculated. Results MAC of isoflurane was significantly decreased in D1 and D2 groups as compared with group C and in group D2 as compared with group D1( P < 0.05 or 0.01 ). Conclusion Dexmedetomidine can significantly decrease MAC of isoflurane required to inhibit the body movement during skin incision in a dose-dependent manner.%目的 探讨右美托咪啶对异氟醚抑制切皮时患者体动反应的肺泡气最低有效浓度(MAC)的影响.方法 择期全身麻醉下行上腹部手术患者,年龄40~60

  5. DMPD: Silica binding and toxicity in alveolar macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18226603 Silica binding and toxicity in alveolar macrophages. Hamilton RF Jr, Thaku...l) Show Silica binding and toxicity in alveolar macrophages. PubmedID 18226603 Title Silica binding and toxicity in alveolar

  6. Autophagy facilitates multidrug resistance development through inhibition of apoptosis in breast cancer cells.

    Science.gov (United States)

    Sun, W L; Lan, D; Gan, T Q; Cai, Z W

    2015-01-01

    Acquired multidrug resistance (MDR) is the main mechanism of chemotherapeutic drugs resistance. Nevertheless, the mechanisms of MDR are complex and still not very clear. Recently, including our previous study, several studies have revealed that macroautophagy (here referred to as autophagy) induced by anti-cancer drugs in breast cancer cells may facilitate the development of resistance to epirubicin (EPI), paclitaxel (PTX), tamoxifen or herceptin. Whereas there are a few studies on the relationship between autophagy and MDR, especially the studies designed directly employing induced resistant breast cancer cells. Based on previous study, we explored the relationship between autophagy and MDR. The results showed that induced EPI-resistant MCF-7er and SK-BR-3er cells were simultaneously resistant to PTX and vinorelbine (NVB), which demonstrated that the cells obtained MDR phenotype. Furthermore, PTX and NVB could also induce autophagy in MCF-7er and SK-BR-3er cells, and the induced autophagy protected the cells from apoptosis, which facilitated the development of resistance to PTX and NVB. Thus, autophagy promoted the development of MDR in breast cancer cells through inhibition of apoptosis. In addition, we found that P-glycoprotein (Pgp) was overexpressed in MCF-7er and SK-Br-3er cells. And we preliminarily investigated the relationship between autophagy and P-glycoprotein (Pgp). The results showed that the expression of the protein did not obviously change despite the inhibition of autophagy. Therefore, the role of Pgp in the development of MDR might be independent of autophahy. Also this finding implies that autophagy might be a target to overcome MDR in breast cancer cells, and clinical use autophagy inhibitors might be one of the important strategies for overcoming MDR in breast cancer therapy. Autophagy, apoptosis, multidrug resistance, breast cancer, chemotherapy.

  7. Decompression of inferior alveolar nerve: case report.

    Science.gov (United States)

    Marques, Tiago Miguel Santos; Gomes, Joana Marques

    2011-01-01

    Paresthesia as a result of mechanical trauma is one of the most frequent sensory disturbances of the inferior alveolar nerve. This case report describes surgical treatment for paresthesia caused by a compressive phenomenon within the mandibular canal. The cause of the compression, a broken instrument left in the patient's mouth during previous endodontic therapy, was identified during routine radiography and computed tomography. Once the foreign object was removed by surgery, the paresthesia resolved quickly. This case highlights the potential for an iatrogenic mechanical cause of paresthesia.

  8. YC-1 potentiates cAMP-induced CREB activation and nitric oxide production in alveolar macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan (China); Tang, Ming-Chi [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Kuo, Liang-Mou [Department of General Surgery, Chang Gung Memorial Hospital at Chia-Yi, Taiwan (China); Chang, Wen-De; Chung, Pei-Jen; Chang, Ya-Wen; Fang, Yao-Ching [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China)

    2012-04-15

    Alveolar macrophages play significant roles in the pathogenesis of several inflammatory lung diseases. Increases in exhaled nitric oxide (NO) are well documented to reflect disease severity in the airway. In this study, we investigated the effect of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), a known activator of soluble guanylyl cyclase, on prostaglandin (PG)E{sub 1} (a stable PGE{sub 2} analogue) and forskolin (a adenylate cyclase activator) induced NO production and inducible NO synthase (iNOS) expression in rat alveolar macrophages (NR8383). YC-1 did not directly cause NO production or iNOS expression, but drastically potentiated PGE{sub 1}- or forskolin-induced NO production and iNOS expression in NR8383 alveolar macrophages. Combination treatment with YC-1 and PGE{sub 1} significantly increased phosphorylation of the cAMP response element-binding protein (CREB), but not nuclear factor (NF)-κB activation. The combined effect on NO production, iNOS expression, and CREB phosphorylation was reversed by a protein kinase (PK)A inhibitor (H89), suggesting that the potentiating functions were mediated through a cAMP/PKA signaling pathway. Consistent with this, cAMP analogues, but not the cGMP analogue, caused NO release, iNOS expression, and CREB activation. YC-1 treatment induced an increase in PGE{sub 1}-induced cAMP formation, which occurred through the inhibition of cAMP-specific phosphodiesterase (PDE) activity. Furthermore, the combination of rolipram (an inhibitor of PDE4), but not milronone (an inhibitor of PDE3), and PGE{sub 1} also triggered NO production and iNOS expression. In summary, YC-1 potentiates PGE{sub 1}-induced NO production and iNOS expression in alveolar macrophages through inhibition of cAMP PDE activity and activation of the cAMP/PKA/CREB signaling pathway. Highlights: ► YC-1 potentiated PGE1-induced iNOS expression in alveolar macrophages. ► The combination of YC-1 and PGE1 increased CREB but not NFκB activation.

  9. Development of a thyroperoxidase inhibition assay for high-throughput screening.

    Science.gov (United States)

    Paul, Katie B; Hedge, Joan M; Rotroff, Daniel M; Hornung, Michael W; Crofton, Kevin M; Simmons, Steven O

    2014-03-17

    High-throughput screening (HTPS) assays to detect inhibitors of thyroperoxidase (TPO), the enzymatic catalyst for thyroid hormone (TH) synthesis, are not currently available. Herein, we describe the development of a HTPS TPO inhibition assay. Rat thyroid microsomes and a fluorescent peroxidase substrate, Amplex UltraRed (AUR), were employed in an end-point assay for comparison to the existing kinetic guaiacol (GUA) oxidation assay. Following optimization of assay metrics, including Z', dynamic range, and activity, using methimazole (MMI), the assay was tested with a 21-chemical training set. The potency of MMI-induced TPO inhibition was greater with AUR compared to GUA. The dynamic range and Z' score with MMI were as follows: 127-fold and 0.62 for the GUA assay, 18-fold and 0.86 for the 96-well AUR assay, and 11.5-fold and 0.93 for the 384-well AUR assay. The 384-well AUR assay drastically reduced animal use, requiring one-tenth of the rat thyroid microsomal protein needed for the GUA 96-well format assay. Fourteen chemicals inhibited TPO, with a relative potency ranking of MMI > ethylene thiourea > 6-propylthiouracil > 2,2',4,4'-tetrahydroxy-benzophenone > 2-mercaptobenzothiazole > 3-amino-1,2,4-triazole > genistein > 4-propoxyphenol > sulfamethazine > daidzein > 4-nonylphenol > triclosan > iopanoic acid > resorcinol. These data demonstrate the capacity of this assay to detect diverse TPO inhibitors. Seven chemicals acted as negatives: 2-hydroxy-4-methoxybenzophenone, dibutylphthalate, diethylhexylphthalate, diethylphthalate, 3,5-dimethylpyrazole-1-methanol, methyl 2-methyl-benzoate, and sodium perchlorate. This assay could be used to screen large numbers of chemicals as an integral component of a tiered TH-disruptor screening approach.

  10. Nostril Base Augmentation Effect of Alveolar Bone Graft

    Directory of Open Access Journals (Sweden)

    Woojin Lee

    2013-09-01

    Full Text Available Background The aims of alveolar bone grafting are closure of the fistula, stabilization ofthe maxillary arch, support for the roots of the teeth adjacent to the cleft on each side.We observed nostril base augmentation in patients with alveolar clefts after alveolar bonegrafting. The purpose of this study was to evaluate the nostril base augmentation effect ofsecondary alveolar bone grafting in patients with unilateral alveolar cleft.Methods Records of 15 children with alveolar clefts who underwent secondary alveolar bonegrafting with autogenous iliac cancellous bone between March of 2011 and May of 2012 werereviewed. Preoperative and postoperative worm’s-eye view photographs and reconstructedthree-dimensional computed tomography (CT scans were used for photogrammetry. Thedepression of the nostril base and thickness of the philtrum on the cleft side were measuredin comparison to the normal side. The depression of the cleft side pyriform aperture wasmeasured in comparison to the normal side on reconstructed three-dimensional CT.Results Significant changes were seen in the nostril base (P=0.005, the philtrum length(P=0.013, and the angle (P=0.006. The CT measurements showed significant changes in thepyriform aperture (P<0.001 and the angle (P<0.001.Conclusions An alveolar bone graft not only fills the gap in the alveolar process but alsoaugments the nostril base after surgery. In this study, only an alveolar bone graft was performedto prevent bias from other procedures. Nostril base augmentation can be achieved byperforming alveolar bone grafts in children, in whom invasive methods are not advised.

  11. Nostril Base Augmentation Effect of Alveolar Bone Graft

    Directory of Open Access Journals (Sweden)

    Woojin Lee

    2013-09-01

    Full Text Available BackgroundThe aims of alveolar bone grafting are closure of the fistula, stabilization of the maxillary arch, support for the roots of the teeth adjacent to the cleft on each side. We observed nostril base augmentation in patients with alveolar clefts after alveolar bone grafting. The purpose of this study was to evaluate the nostril base augmentation effect of secondary alveolar bone grafting in patients with unilateral alveolar cleft.MethodsRecords of 15 children with alveolar clefts who underwent secondary alveolar bone grafting with autogenous iliac cancellous bone between March of 2011 and May of 2012 were reviewed. Preoperative and postoperative worm's-eye view photographs and reconstructed three-dimensional computed tomography (CT scans were used for photogrammetry. The depression of the nostril base and thickness of the philtrum on the cleft side were measured in comparison to the normal side. The depression of the cleft side pyriform aperture was measured in comparison to the normal side on reconstructed three-dimensional CT.ResultsSignificant changes were seen in the nostril base (P=0.005, the philtrum length (P=0.013, and the angle (P=0.006. The CT measurements showed significant changes in the pyriform aperture (P<0.001 and the angle (P<0.001.ConclusionsAn alveolar bone graft not only fills the gap in the alveolar process but also augments the nostril base after surgery. In this study, only an alveolar bone graft was performed to prevent bias from other procedures. Nostril base augmentation can be achieved by performing alveolar bone grafts in children, in whom invasive methods are not advised.

  12. Molecular basis for the inhibition of Drosophila eye development by Antennapedia.

    Science.gov (United States)

    Plaza, S; Prince, F; Jaeger, J; Kloter, U; Flister, S; Benassayag, C; Cribbs, D; Gehring, W J

    2001-02-15

    Hox genes encoding homeodomain transcriptional regulators are known to specify the body plan of multicellular organisms and are able to induce body plan transformations when misexpressed. These findings led to the hypothesis that duplication events and misexpression of Hox genes during evolution have been necessary for generating the observed morphological diversity found in metazoans. It is known that overexpressing Antennapedia (Antp) in the head induces antenna-to-leg as well as head-to-thorax transformation and eye reduction. At present, little is known about the exact molecular mechanism causing these phenotypes. The aim of this study is to understand the basis of inhibition of eye development. We demonstrate that Antp represses the activity of the eye regulatory cascade. By ectopic expression, we show that Antp antagonizes the activity of the eye selector gene eyeless. Using both in vitro and in vivo experiments, we demonstrate that this inhibitory mechanism involves direct protein-protein interactions between the DNA-binding domains of EY and ANTP, resulting in mutual inhibition.

  13. Increased shear stress inhibits angiogenesis in veins and not arteries during vascular development.

    Science.gov (United States)

    Chouinard-Pelletier, Guillaume; Jahnsen, Espen D; Jones, Elizabeth A V

    2013-01-01

    Vascular development is believed to occur first by vasculogenesis followed by angiogenesis. Though angiogenesis is the formation of new vessels, we found that vascular density actually decreases during this second stage. The onset of the decrease coincided with the entry of erythroblasts into circulation. We therefore measured the level of shear stress at various developmental stages and found that it was inversely proportional to vascular density. To investigate whether shear stress was inhibitory to angiogenesis, we altered shear stress levels either by preventing erythroblasts from entering circulation ("low" shear stress) or by injection of a starch solution to increase the blood plasma viscosity ("high" shear stress). By time-lapse microscopy, we show that reverse intussusception (merging of two vessels) is inversely proportional to the level of shear stress. We also found that angiogenesis (both sprouting and splitting) was inversely proportional to shear stress levels. These effects were specific to the arterial or venous plexus however, such that the effect on reverse intussusception was present only in the arterial plexus and the effect on sprouting only in the venous plexus. We cultured embryos under altered shear stress in the presence of either DAPT, a Notch inhibitor, or DMH1, an inhibitor of the bone morphogenetic protein (BMP) pathway. DAPT treatment phenocopied the inhibition of erythroblast circulation ("low" shear stress) and the effect of DAPT treatment could be partially rescued by injection of starch. Inhibition of the BMP signaling prevented the reduction in vascular density that was observed when starch was injected to increase shear stress levels.

  14. Inhibition of peripubertal sheep mammary gland development by cysteamine through reducing progesterone and growth factor production.

    Science.gov (United States)

    Zhao, Yong; Feng, Yanni; Zhang, Hongfu; Kou, Xin; Li, Lan; Liu, Xinqi; Zhang, Pengfei; Cui, Liantao; Chu, Meiqiang; Shen, Wei; Min, Lingjiang

    2017-02-01

    Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets. Most interestingly, it inhibited mammary gland development after 2 or 5 months of treatment by reducing the organ index and the number of mammary gland ducts. Plasma growth hormone and estradiol remained unchanged; however, plasma progesterone levels and the protein level of HSD3β1 in sheep ovaries were decreased by cysteamine. In addition to steroid hormones, growth factors produced in the mammary glands also play crucial roles in mammary gland development. Results showed that protein levels of HGF, GHR, and IGF1R were decreased after 5 months of cysteamine treatment. These findings together suggest that progesterone and local growth factors in mammary glands might be involved in cysteamine initiated inhibition of pubertal ovine mammary gland development. Furthermore, it may lead to a reduction in fertility. Therefore, cysteamine should be used with great caution until its actions have been further investigated and its limitations overcome.

  15. Taenia taeniaeformis: inhibition of metacestode development in the rat by gossypol.

    Science.gov (United States)

    Rikihisa, Y; Lin, Y C

    1986-04-01

    The effect of gossypol, a polyphenolic compound, on developing Taenia taeniaeformis larvae in the rat liver was examined. Five groups of rats were used. In group 1, subcutaneous injection of gossypol at 10 mg/kg was started 5 days prior to administration of tapeworm eggs. In group 2, gossypol injections were started 5 days after administration of eggs. Groups 3 and 4 were infected and noninfected rats, respectively, which received the vehicle (10% ethyl alcohol in 0.85% NaCl) only. Group 5 rats were noninfected but received gossypol. From each group, 5 rats were killed on days 7, 12, and 22 of infection, respectively. The number and size of larvae and the size of the livers were much less in rats gossypol injected 5 days before infection than those in the vehicle-treated group. Administration of gossypol 5 days after infection resulted in less inhibition. The size and the thickness of the fibrous capsule around larvae of the gossypol-treated rats were much smaller than those of the control-infected group. The actively developing larvae excrete or secrete a sulfated glycosaminoglycan which is specifically stained with alcian blue. There was much more alcian blue-positive substance around the larvae and the capsule of the control-infected liver compared to the gossypol-treated infected animal. The percentage body weight of the spleen was significantly greater in the gossypol-treated rats in both infected and noninfected groups. These results suggest that gossypol may directly inhibit tapeworm larval development or that elimination of the tapeworm may be resulted from gossypol-induced stimulation of host cell-mediated immunity.

  16. Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study

    Directory of Open Access Journals (Sweden)

    S Matsubara

    2010-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism, and it plays an important role in cell proliferation and antioxidant regulation within cells in various organs. Although marked cell proliferation and oxidant/antioxidant metabolism occur in lung alveolar epithelial cells, definite data has been lacking as to whether cytochemically detectable G6PD is present in alveolar epithelial cells. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of the present study was to investigate the subcellular localization of G6PD in alveolar cells in the rat lung using a newly- developed enzyme-cytochemistry (copper-ferrocyanide method. Type I cells and stromal endothelia and fibroblasts showed no activities. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of type II alveolar epithelial cells. The cytochemical controls ensured specific detection of enzyme activity. This enzyme may play a role in airway defense by delivering substances for cell proliferation and antioxidant forces, thus maintaining the airway architecture.

  17. Pulmonary Alveolar Microlithiasis - Clinico-Radiological dissociation - A case report with Radiological review.

    Science.gov (United States)

    Khaladkar, Sanjay Mhalasakant; Kondapavuluri, Sushen Kumar; Kamal, Anubhav; Kalra, Raghav; Kuber, Rajesh

    2016-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare chronic lung disease characterized by deposition of intra alveolar calcium and phosphate in bilateral lung parenchyma with predominance in lower and mid zones. Etiology and pathogenesis is not fully understood. However, mutation in SLC34A2 gene that encodes a sodium phosphate co-transporter in alveolar type-II cells resulting in formation and accumulation of microliths rich in calcium phosphate due to impaired clearance is considered the cause of disease. Patients with PAM are asymptomatic till development of hypoxemia and cor pulmonale. It remains static, while in some it progresses to pulmonary fibrosis, respiratory failure and cor pulmonale. We report a case of 44 year old male patient presenting with progressive shortness of breath on exertion for one year in duration with dry cough, more since last six months. Chest radiograph showed dense micronodular opacities giving classical sandstorm appearance. High resolution computed tomography (HRCT) showed microcalcification, subpleural cystic changes and calcified pleura. Lung biopsy showed calcospherites within alveolar spaces.

  18. Lipopolysaccharide disrupts the directional persistence of alveolar myofibroblast migration through EGF receptor.

    Science.gov (United States)

    Li, Huiping; Yuan, Xiaobing; Tang, Jun; Zhang, Yongjun

    2012-03-15

    Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased alveolar number and increased airspace size. Formation of alveoli involves a process known as secondary septation triggered by myofibroblasts. This study investigated the underlying mechanisms of altered lung morphogenesis in a rat model of BPD induced by intra-amniotic injection of lipopolysaccharide (LPS). Results showed that LPS disrupted alveolar morphology and led to abnormal localization of myofibroblasts in the lung of newborn rats, mostly in primary septa with few in secondary septa. To identify potential mechanisms, in vitro experiments were carried out to observe the migration behavior of myofibroblasts. The migration speed of lung myofibroblasts increased with LPS treatment, whereas the directional persistence decreased. We found that LPS induced activation of EGFR and overexpression of its ligand, TGF-α in myofibroblasts. AG1478, an EGFR inhibitor, abrogated the enhanced locomotivity of myofibroblasts by LPS and also increased the directional persistence of myofibroblast migration. Myofibroblasts showed a high asymmetry of phospho-EGFR localization, which was absent after LPS treatment. Application of rhTGF-α to myofibroblasts decreased the directional persistence. Our findings indicated that asymmetry of phospho-EGFR localization in myofibroblasts was important for cell migration and its directional persistence. We speculate that LPS exposure disrupts the asymmetric localization of phospho-EGFR, leading to decreased stability of cell polarity and final abnormal location of myofibroblasts in vivo, which is critical to secondary septation and may contribute to the arrested alveolar development in BPD.

  19. The immune toxicity of titanium dioxide on primary pulmonary alveolar macrophages relies on their surface area and crystal structure.

    Science.gov (United States)

    Liu, Ran; Yin, Li-hong; Pu, Yue-pu; Li, Yun-hui; Zhang, Xiao-qiang; Liang, Ge-yu; Li, Xiao-bo; Zhang, Juan; Li, Yan-fen; Zhang, Xue-yan

    2010-12-01

    Surface properties are critical to assess effects of titanium dioxide (TiO2) primary nanoparticles on the immune function of pulmonary alveolar macrophage (PAMs). In this study the immune toxicity of TiO2 primary nanoparticles on PAMs relies on their surface area and crystal structure were determined. The primary PAMs of rats exposed to different sizes and crystal structure of TiO2 particles at different dosages for 24 hrs were evaluated for cytokines, phagocytosis, chemotaxis and surface molecules expression. Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) level of PAMs significantly increased when exposed to TiO2 primary particles and there were significant association with the exposure total surface area and crystal structure of TiO2 particles in the former. TiO2 particles showed significant inhibiting effects on phagocytotic ability, chemotactic ability, Fc receptors and MHC-II molecular expression of macrophages compared with control. Exposure dosage and crystal structure of TiO2 particles play effects on phagocytotic ability and chemotactic ability of PAMs. These results suggested that TiO2 nanoparticles could induce the release of inflammatory mediators, initiate the inflammation development and inhibit the immune function of PAMs associated with non-specific immunity and specific immunity relies on surface area and crystal structure. NO activity might be a candidate marker indicating the TiO2 exposure burden and cell damage in PAMs.

  20. Tongue-Palate Contact of Perceptually Acceptable Alveolar Stops

    Science.gov (United States)

    Lee, Alice; Gibbon, Fiona E.; O'Donovan, Cliona

    2013-01-01

    Increased tongue-palate contact for perceptually acceptable alveolar stops has been observed in children with speech sound disorders (SSD). This is a retrospective study that further investigated this issue by using quantitative measures to compare the target alveolar stops /t/, /d/ and /n/ produced in words by nine children with SSD (20 tokens of…

  1. Estrogen regulates pulmonary alveolar formation, loss, and regeneration in mice.

    Science.gov (United States)

    Massaro, Donald; Massaro, Gloria Decarlo

    2004-12-01

    Lung tissue elastic recoil and the dimension and number of pulmonary gas-exchange units (alveoli) are major determinants of gas-exchange function. Loss of gas-exchange function accelerates after menopause in the healthy aged and is progressively lost in individuals with chronic obstructive pulmonary disease (COPD). The latter, a disease of midlife and later, though more common in men than in women, is a disease to which women smokers and never smokers may be more susceptible than men; it is characterized by diminished lung tissue elastic recoil and presently irremediable alveolar loss. Ovariectomy in sexually immature rats diminishes the formation of alveoli, and estrogen prevents the diminution. In the present work, we found that estrogen receptor-alpha and estrogen receptor-beta, the only recognized mammalian estrogen receptors, are required for the formation of a full complement of alveoli in female mice. However, only the absence of estrogen receptor-beta diminishes lung elastic tissue recoil. Furthermore, ovariectomy in adult mice results, within 3 wk, in loss of alveoli and of alveolar surface area without a change of lung volume. Estrogen replacement, after alveolar loss, induces alveolar regeneration, reversing the architectural effects of ovariectomy. These studies 1) reveal estrogen receptors regulate alveolar size and number in a nonredundant manner, 2) show estrogen is required for maintenance of already formed alveoli and induces alveolar regeneration after their loss in adult ovariectomized mice, and 3) offer the possibility estrogen can slow alveolar loss and induce alveolar regeneration in women with COPD.

  2. Perawatan Pulpa Gigi Sulung Disertai Abses Dento Alveolar

    OpenAIRE

    2008-01-01

    Abses dento alveolar adalah kumputan pus yang berada pada tulang alveolar sekitar apeks gigi akibat kematian pulpa. Matinya pulpa dapat disebabkan bakteri, trauma, iritasi mekanis, termis maupun kimiawi. Pengaruh bakteri merupakan penyebab kerusakan jaringan pulpa yang terbesar. Perluasan infeksi ke dalam jaringan periapikal dapat melalui foramen apikalke jaringan periodontal sehingga terjadi inflarnasi. Bila virulensi bakteri meningkat disertai rendahnya pertahanan tubuh penderita dapat ...

  3. Alveolar ridge augmentation by osteoinductive materials in goats

    DEFF Research Database (Denmark)

    Pinholt, E M; Haanaes, H R; Roervik, M

    1992-01-01

    The purpose of the present study was to determine whether alveolar ridge augmentation could be induced in goats. In 12 male goats allogenic, demineralized, and lyophilized dentin or bone was implanted subperiosteally on the buccal sides of the natural edentulous regions of the alveolar process of...

  4. Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal transition in alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Araki Hiromasa

    2007-04-01

    Full Text Available Abstract Background Proteinase-activated receptors (PARs; PAR1–4 that can be activated by serine proteinases such as thrombin and neutrophil catepsin G are known to contribute to the pathogenesis of various pulmonary diseases including fibrosis. Among these PARs, especially PAR4, a newly identified subtype, is highly expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in the formation of fibrotic response in the lung, through alveolar epithelial-mesenchymal transition (EMT which contributes to the increase in myofibroblast population. Methods EMT was assessed by measuring the changes in each specific cell markers, E-cadherin for epithelial cell, α-smooth muscle actin (α-SMA for myofibroblast, using primary cultured mouse alveolar epithelial cells and human lung carcinoma-derived alveolar epithelial cell line (A549 cells. Results Stimulation of PAR with thrombin (1 U/ml or a synthetic PAR4 agonist peptide (AYPGKF-NH2, 100 μM for 72 h induced morphological changes from cobblestone-like structure to elongated shape in primary cultured alveolar epithelial cells and A549 cells. In immunocytochemical analyses of these cells, such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased α-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor growth factor-β (TGF-β. Western blot analyses of PAR4-stimulated A549 cells also showed similar changes in expression of these EMT-related marker proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal growth factor receptor (EGFR kinase and Src. PAR4-mediated morphological changes in primary cultured alveolar epithelial cells were reduced in the presence of these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or tyrosine phosphorylated Src level in A549 cells, and the former response being inhibited by Src inhibitor. Conclusion PAR4 stimulation of alveolar epithelial cells induced epithelial

  5. Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.

    Science.gov (United States)

    Checa, Marco; Hagood, James S; Velazquez-Cruz, Rafael; Ruiz, Victor; García-De-Alba, Carolina; Rangel-Escareño, Claudia; Urrea, Francisco; Becerril, Carina; Montaño, Martha; García-Trejo, Semiramis; Cisneros Lira, José; Aquino-Gálvez, Arnoldo; Pardo, Annie; Selman, Moisés

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease of unknown etiology. A growing body of evidence indicates that it may result from an aberrant activation of alveolar epithelium, which induces the expansion of the fibroblast population, their differentiation to myofibroblasts and the excessive accumulation of extracellular matrix. The mechanisms that activate the alveolar epithelium are unknown, but several studies indicate that smoking is the main environmental risk factor for the development of IPF. In this study we explored the effect of cigarette smoke on the gene expression profile and signaling pathways in alveolar epithelial cells. Lung epithelial cell line from human (A549), was exposed to cigarette smoke extract (CSE) for 1, 3, and 5 weeks at 1, 5 and 10% and gene expression was evaluated by complete transcriptome microarrays. Signaling networks were analyzed with the Ingenuity Pathway Analysis software. At 5 weeks of exposure, alveolar epithelial cells acquired a fibroblast-like phenotype. At this time, gene expression profile revealed a significant increase of more than 1000 genes and deregulation of canonical signaling pathways such as TGF-β and Wnt. Several profibrotic genes involved in EMT were over-expressed, and incomplete EMT was observed in these cells, and corroborated in mouse (MLE-12) and rat (RLE-6TN) epithelial cells. The secretion of activated TGF-β1 increased in cells exposed to cigarette smoke, which decreased when the integrin alpha v gene was silenced. These findings suggest that the exposure of alveolar epithelial cells to CSE induces the expression and release of a variety of profibrotic genes, and the activation of TGF-β1, which may explain at least partially, the increased risk of developing IPF in smokers.

  6. Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Marco Checa

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive and lethal disease of unknown etiology. A growing body of evidence indicates that it may result from an aberrant activation of alveolar epithelium, which induces the expansion of the fibroblast population, their differentiation to myofibroblasts and the excessive accumulation of extracellular matrix. The mechanisms that activate the alveolar epithelium are unknown, but several studies indicate that smoking is the main environmental risk factor for the development of IPF. In this study we explored the effect of cigarette smoke on the gene expression profile and signaling pathways in alveolar epithelial cells. Lung epithelial cell line from human (A549, was exposed to cigarette smoke extract (CSE for 1, 3, and 5 weeks at 1, 5 and 10% and gene expression was evaluated by complete transcriptome microarrays. Signaling networks were analyzed with the Ingenuity Pathway Analysis software. At 5 weeks of exposure, alveolar epithelial cells acquired a fibroblast-like phenotype. At this time, gene expression profile revealed a significant increase of more than 1000 genes and deregulation of canonical signaling pathways such as TGF-β and Wnt. Several profibrotic genes involved in EMT were over-expressed, and incomplete EMT was observed in these cells, and corroborated in mouse (MLE-12 and rat (RLE-6TN epithelial cells. The secretion of activated TGF-β1 increased in cells exposed to cigarette smoke, which decreased when the integrin alpha v gene was silenced. These findings suggest that the exposure of alveolar epithelial cells to CSE induces the expression and release of a variety of profibrotic genes, and the activation of TGF-β1, which may explain at least partially, the increased risk of developing IPF in smokers.

  7. Neonatal peripheral immune challenge activates microglia and inhibits neurogenesis in the developing murine hippocampus.

    Science.gov (United States)

    Smith, Peter L P; Hagberg, Henrik; Naylor, Andrew S; Mallard, Carina

    2014-01-01

    The early postnatal period represents an important window in rodent hippocampal development with peak hilar neurogenesis and widespread microgliogenesis occurring in the first week of life. Inflammation occurring during this period may negatively influence development, potentially facilitating or increasing susceptibility to later-life pathology. We administered the Gram-negative bacterial coat protein lipopolysaccharide (LPS) systemically at postnatal day 5 (1 mg/kg i.p.) and assessed potential effects on microgliogenesis, inflammation and neurogenesis in the developing hippocampus. LPS administration led to an acute but transient increase in absolute number and density of ionized calcium-binding adaptor molecule 1-immunoreactive microglia, a change attributable to increased proliferation of central nervous system-resident microglia/microglial precursor cells but not infiltration of peripheral monocyte-derived macrophages. qRT-PCR analysis of hippocampal gene expression showed these LPS-mediated changes to be associated with persistent dysregulation of genes associated with both M1 and M2 microglial phenotypes, indicating prolonged alteration in hippocampal inflammatory status. Further, analysis of progenitor cell regulation in the hippocampal subgranular zone revealed a transient inhibition of the neuronal differentiation pathway up to 2 weeks after LPS administration, a change occurring specifically through effects on type 3 neural progenitor cells and independently of altered cell proliferation or survival of newly born cells. Together, our results show that systemic inflammation occurring during the early neonatal period is sufficient to alter inflammatory status and dysregulate the ongoing process of neurogenesis in the developing hippocampal germinal niche.

  8. Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A

    Science.gov (United States)

    Yi, Quan-Yong; Deng, Gang; Chen, Nan; Bai, Zhi-Sha; Yuan, Jian-Shu; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun

    2016-01-01

    Previous studies have shown that metformin, an AMP-activated protein kinase activator widely prescribed for type 2 diabetes, is especially beneficial in cases of diabetic retinopathy (DR) with undetermined mechanisms. Here, we used a streptozotocin-induced diabetes model in mice to study the effects of metformin on the development of DR. We found that 10 weeks after STZ treatment, DR was induced in STZ-treated mice, regardless treatment of metformin. However, metformin alleviated the DR, seemingly through attenuating the retina neovascularization. The total vascular endothelial cell growth factor A (VEGF-A) in eyes was not altered by metformin, but the phosphorylation of the VEGF receptor 2 (VEGFR2) was decreased, which inhibited VEGF signaling. Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2. These findings are critical for generating novel medicine for DR treatment.

  9. Influences of Fucoxanthin on Alveolar Bone Resorption in Induced Periodontitis in Rat Molars.

    Science.gov (United States)

    Kose, Oguz; Arabaci, Taner; Yemenoglu, Hatice; Kara, Adem; Ozkanlar, Seckin; Kayis, Sevki; Duymus, Zeynep Yesil

    2016-03-30

    The aim of this study was to evaluate the effects of systemic fucoxanthin treatment on alveolar bone resorption in rats with periodontitis. Thirty rats were divided into control, experimental periodontitis (EP), and experimental periodontitis-fucoxanthin (EP-FUCO) groups. Periodontitis was induced by ligature for four weeks. After removal of the ligature, the rats in the EP-FUCO group were treated with a single dose of fucoxanthin (200 mg/kg bw) per day for 28 consecutive days. At the end of the study, all of the rats were euthanized and intracardiac blood and mandible tissue samples were obtained for biochemical, immunohistochemical, and histometric analyses. Fucoxanthin treatment resulted in a slight decrease in tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels and a significant decrease in oxidative stress index. It was observed that fucoxanthin caused a significant reduction in receptor activator of nuclear factor kappa-β ligand (RANKL) levels and a statistically non-significant elevation in osteoprotegerin and bone-alkaline phosphatase levels. There were no significant differences in alveolar bone loss levels between the EP and EP-FUCO groups. This experimental study revealed that fucoxanthin provides a limited reduction in alveolar bone resorption in rats with periodontitis. One of the mechanisms underlying the mentioned limited effect might be related to the ability of fucoxanthin to inhibit oxidative stress-related RANKL-mediated osteoclastogenesis.

  10. Identification of an autophagy defect in smokers' alveolar macrophages.

    Science.gov (United States)

    Monick, Martha M; Powers, Linda S; Walters, Katherine; Lovan, Nina; Zhang, Michael; Gerke, Alicia; Hansdottir, Sif; Hunninghake, Gary W

    2010-11-01

    Alveolar macrophages are essential for clearing bacteria from the alveolar surface and preventing microbe-induced infections. It is well documented that smokers have an increased incidence of infections, in particular lung infections. Alveolar macrophages accumulate in smokers' lungs, but they have a functional immune deficit. In this study, we identify an autophagy defect in smokers' alveolar macrophages. Smokers' alveolar macrophages accumulate both autophagosomes and p62, a marker of autophagic flux. The decrease in the process of autophagy leads to impaired protein aggregate clearance, dysfunctional mitochondria, and defective delivery of bacteria to lysosomes. This study identifies the autophagy pathway as a potential target for interventions designed to decrease infection rates in smokers and possibly in individuals with high environmental particulate exposure.

  11. T-cell-expressed proprotein convertase FURIN inhibits DMBA/TPA-induced skin cancer development

    Science.gov (United States)

    Vähätupa, Maria; Aittomäki, Saara; Martinez Cordova, Zuzet; May, Ulrike; Prince, Stuart; Uusitalo-Järvinen, Hannele; Pesu, Marko

    2016-01-01

    ABSTRACT Proprotein convertases (PCSK) have a critical role in the body homeostasis as enzymes responsible for processing precursor proteins into their mature forms. FURIN, the first characterized member of the mammalian PCSK family, is overexpressed in multiple malignancies and the inhibition of its activity has been considered potential cancer treatment. FURIN has also an important function in the adaptive immunity, since its deficiency in T cells causes an impaired peripheral immune tolerance and accelerates immune responses. We addressed whether deleting FURIN from the immune cells would strengthen anticancer responses by subjecting mouse strains lacking FURIN from either T cells or macrophages and granulocytes to the DMBA/TPA two-stage skin carcinogenesis protocol. Unexpectedly, deficiency of FURIN in T cells resulted in enhanced and accelerated development of tumors, whereas FURIN deletion in macrophages and granulocytes had no effect. The epidermises of T-cell-specific FURIN deficient mice were significantly thicker with more proliferating Ki67+ cells. In contrast, there were no differences in the numbers of the T cells. The flow cytometric analyses of T-cell populations in skin draining lymph nodes showed that FURIN T-cell KO mice have an inherent upregulation of early activation marker CD69 as well as more CD4+CD25+Foxp3+ positive T regulatory cells. In the early phase of tumor promotion, T cells from the T-cell-specific FURIN knockout animals produced more interferon gamma, whereas at later stage the production of Th2- and Th17-type cytokines was more prominent than in wild-type controls. In conclusion, while PCSK inhibitors are promising therapeutics in cancer treatment, our results show that inhibiting FURIN specifically in T cells may promote squamous skin cancer development.

  12. Rituximab therapy in pulmonary alveolar proteinosis improves alveolar macrophage lipid homeostasis

    Directory of Open Access Journals (Sweden)

    Malur Anagha

    2012-06-01

    Full Text Available Abstract Rationale Pulmonary Alveolar Proteinosis (PAP patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ and the PPARγ-regulated ATP binding cassette (ABC lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL fluid, and 7/9 patients completing the trial demonstrated clinical improvement as measured by arterial blood oxygenation. Objectives This study sought to determine whether rituximab therapy would restore lipid metabolism in PAP alveolar macrophages. Methods BAL samples were collected from patients pre- and 6-months post-rituximab infusion for evaluation of mRNA and lipid changes. Results Mean PPARγ and ABCG1 mRNA expression increased 2.8 and 5.3-fold respectively (p ≤ 0.05 after treatment. Lysosomal phospholipase A2 (LPLA2 (a key enzyme in surfactant degradation mRNA expression was severely deficient in PAP patients pre-treatment but increased 2.8-fold post-treatment. In supplemental animal studies, LPLA2 deficiency was verified in GM-CSF KO mice but was not present in macrophage-specific PPARγ KO mice compared to wild-type controls. Oil Red O intensity of PAP alveolar macrophages decreased after treatment, indicating reduced intracellular lipid while extracellular free cholesterol increased in BAL fluid. Furthermore, total protein and Surfactant protein A were significantly decreased in the BAL fluid post therapy. Conclusions Reduction in GM

  13. Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages

    Directory of Open Access Journals (Sweden)

    Liao Chung-Ping

    2010-04-01

    Full Text Available Abstract Background Pneumocystis pneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance of Pneumocystis organisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased in Pneumocystis infected hosts. To understand how Pneumocystis inactivates alveolar macrophages, Affymetrix GeneChip® RG-U34A DNA microarrays were used to study the difference in global gene expression in alveolar macrophages from uninfected and Pneumocystis carinii-infected Sprague-Dawley rats. Results Analyses of genes that were affected by Pneumocystis infection showed that many functions in the cells were affected. Antigen presentation, cell-mediated immune response, humoral immune response, and inflammatory response were most severely affected, followed by cellular movement, immune cell trafficking, immunological disease, cell-to-cell signaling and interaction, cell death, organ injury and abnormality, cell signaling, infectious disease, small molecular biochemistry, antimicrobial response, and free radical scavenging. Since rats must be immunosuppressed in order to develop Pneumocystis infection, alveolar macrophages from four rats of the same sex and age that were treated with dexamethasone for the entire eight weeks of the study period were also examined. With a filter of false-discovery rate less than 0.1 and fold change greater than 1.5, 200 genes were found to be up-regulated, and 144 genes were down-regulated by dexamethasone treatment. During Pneumocystis pneumonia, 115 genes were found to be up- and 137 were down-regulated with the same filtering criteria. The top ten genes up-regulated by Pneumocystis infection were Cxcl10, Spp1, S100A9, Rsad2, S100A8, Nos2, RT1-Bb, Lcn2, RT1-Db1, and Srgn with fold changes ranging between 12.33 and 5.34; and the top ten down-regulated ones were Lgals1, Psat1, Tbc1d23, Gsta1, Car5b, Xrcc5, Pdlim1, Alcam

  14. VNAR single-domain antibodies specific for BAFF inhibit B cell development by molecular mimicry.

    Science.gov (United States)

    Häsler, Julien; Flajnik, Martin F; Williams, Gareth; Walsh, Frank S; Rutkowski, J Lynn

    2016-07-01

    B cell-activating factor (BAFF) plays a dominant role in the B cell homeostasis. However, excessive BAFF promotes the development of autoreactive B-cells and several antibodies have been developed to block its activity. Bispecific antibodies with added functionality represent the next wave of biologics that may be more effective in the treatment of complex autoimmune disease. The single variable domain from the immunoglobulin new antigen receptor (VNAR) is one of the smallest antibody recognition units that could be combined with monospecific antibodies to develop bispecific agents. We isolated a panel of BAFF-binding VNARs with low nM potency from a semi-synthetic phage display library and examined their functional activity. The anti-BAFF VNARs blocked the binding of BAFF to all three of its receptors (BR3, TACI and BCMA) and the presence of the conserved DXL receptor motif found in the CDR3 regions suggests molecular mimicry as the mechanism of antagonism. One clone was formatted as an Fc fusion for functional testing and it was found to inhibit both mouse and human BAFF with equal potency ex vivo in a splenocyte proliferation assay. In mice, subchronic administration reduced the number of immature and transitional intermediates B cells and mature B cell subsets. These results indicate that VNAR single domain antibodies function as selective B-cell inhibitors and offer an alternative molecular format for targeting B-cell disorders.

  15. Development of a murine mycobacterial growth inhibition assay for evaluating vaccines against Mycobacterium tuberculosis.

    Science.gov (United States)

    Parra, Marcela; Yang, Amy L; Lim, JaeHyun; Kolibab, Kristopher; Derrick, Steven; Cadieux, Nathalie; Perera, Liyanage P; Jacobs, William R; Brennan, Michael; Morris, Sheldon L

    2009-07-01

    The development and characterization of new tuberculosis (TB) vaccines has been impeded by the lack of reproducible and reliable in vitro assays for measuring vaccine activity. In this study, we developed a murine in vitro mycobacterial growth inhibition assay for evaluating TB vaccines that directly assesses the capacity of immune splenocytes to control the growth of Mycobacterium tuberculosis within infected macrophages. Using this in vitro assay, protective immune responses induced by immunization with five different types of TB vaccine preparations (Mycobacterium bovis BCG, an attenuated M. tuberculosis mutant strain, a DNA vaccine, a modified vaccinia virus strain Ankara [MVA] construct expressing four TB antigens, and a TB fusion protein formulated in adjuvant) can be detected. Importantly, the levels of vaccine-induced mycobacterial growth-inhibitory responses seen in vitro after 1 week of coculture correlated with the protective immune responses detected in vivo at 28 days postchallenge in a mouse model of pulmonary tuberculosis. In addition, similar patterns of cytokine expression were evoked at day 7 of the in vitro culture by immune splenocytes taken from animals immunized with the different TB vaccines. Among the consistently upregulated cytokines detected in the immune cocultures are gamma interferon, growth differentiation factor 15, interleukin-21 (IL-21), IL-27, and tumor necrosis factor alpha. Overall, we have developed an in vitro functional assay that may be useful for screening and comparing new TB vaccine preparations, investigating vaccine-induced protective mechanisms, and assessing manufacturing issues, including product potency and stability.

  16. dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development.

    Science.gov (United States)

    Guan, Zhen; Wang, Xiuwei; Dong, Yanting; Xu, Lin; Zhu, Zhiqiang; Wang, Jianhua; Zhang, Ting; Niu, Bo

    2015-02-03

    Exposure to environmental toxic chemicals in utero during the neural tube development period can cause developmental disorders. To evaluate the disruption of neural tube development programming, the murine neural tube defects (NTDs) model was induced by interrupting folate metabolism using methotrexate in our previous study. The present study aimed to examine the effects of dNTP deficiency induced by hydroxyurea (HU), a specific ribonucleotide reductase (RNR) inhibitor, during murine neural tube development. Pregnant C57BL/6J mice were intraperitoneally injected with various doses of HU on gestation day (GD) 7.5, and the embryos were checked on GD 11.5. RNR activity and deoxynucleoside triphosphate (dNTP) levels were measured in the optimal dose. Additionally, DNA damage was examined by comet analysis and terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling (TUNEL) assay. Cellular behaviors in NTDs embryos were evaluated with phosphorylation of histone H3 (PH-3) and caspase-3 using immunohistochemistry and western blot analysis. The results showed that NTDs were observed mostly with HU treatment at an optimal dose of 225 mg/kg b/w. RNR activity was inhibited and dNTP levels were decreased in HU-treated embryos with NTDs. Additionally, increased DNA damage, decreased proliferation, and increased caspase-3 were significant in NTDs embryos compared to the controls. Results indicated that HU induced murine NTDs model by disturbing dNTP metabolism and further led to the abnormal cell balance between proliferation and apoptosis.

  17. Alveolar Ridge Conservation by Early Bone Formation After Tooth Extraction in Rabbits. A Histomorphological Study

    Science.gov (United States)

    Cantín, Mario; Olate, Sergio; Fuentes, Ramón; Vásquez, Bélgica

    2016-01-01

    SUMMARY Alveolar ridge volume loss is an irreversible process. To prevent this physiological event, which typically result in significant local anatomical changes in both the horizontal and the vertical dimension, some strategies are indicated to minimize the loss of ridge volume that typically follows tooth extraction. The purpose of this study was to evaluate if three different bone grafts could promote new bone formation in the alveolar socket following tooth extraction for the alveolar ridge conservation. First mandibular molars of male adults rabbits were extracted and the extraction sockets were randomly treated with three different bone grafts, one xenograft and two alloplastic grafts, and a group that received no treatment (blood clot). The extraction sockets of selected rabbits from each group were evaluated at 4, 6, or 8-week post-extraction. The results indicated that the extraction sockets treated with alloplastic graft (biphasic calcium phosphate) exhibited lamellar bone formation (6.5%) as early as four weeks after the extraction was performed. Moreover, the degree of new bone formation was significantly higher (P<0.05) in the extraction sockets treated with biphasic calcium phosphate at 8-week post-extraction than that in the other study groups. In this study, we demonstrated that the proposed animal model is useful to evaluate the bone formation after tooth extraction and the alveolar ridge conservation is feasible. The new bone formation and alveolar ridge preservation with bone graft after extraction of molar teeth, could result in the maintenance of sufficient bone volume to place an implant in an ideal restorative position without the need for ancillary implant site development procedures. PMID:27840551

  18. NF-kappaB regulatory mechanisms in alveolar macrophages from patients with acute respiratory distress syndrome.

    Science.gov (United States)

    Moine, P; McIntyre, R; Schwartz, M D; Kaneko, D; Shenkar, R; Le Tulzo, Y; Moore, E E; Abraham, E

    2000-02-01

    Activation of the nuclear regulatory factor NF-kappaB occurs in the lungs of patients with the acute respiratory distress syndrome (ARDS) and may contribute to the increased expression of immunoregulatory cytokines and other proinflammatory mediators in this setting. Because of the important role that NF-kappaB activation appears to play in the development of acute lung injury, we examined cytoplasmic and nuclear NF-kapppaB counterregulatory mechanisms, involving IkappaB proteins, in alveolar macrophages obtained from 7 control patients without lung injury and 11 patients with established ARDS. Cytoplasmic levels of the NF-kappaB subunits p50, p65, and c-Rel were significantly decreased in alveolar macrophages from patients with ARDS, consistent with enhanced migration of liberated NF-kappaB dimers from the cytoplasm to the nucleus. Cytoplasmic and nuclear levels of IkappaBalpha were not significantly altered in alveolar macrophages from patients with established ARDS, compared with controls. In contrast, nuclear levels of Bcl-3 were significantly decreased in patients with ARDS compared with controls (P = 0.02). No IkappaBgamma, IkappaBbeta, or p105 proteins were detected in the cytoplasm of alveolar macrophages from control patients or patients with ARDS. The presence of activated NF-kappaB in alveolar macrophages from patients with established ARDS implies the presence of an ongoing stimulus for NF-kappaB activation. In this setting, appropriate counterregulatory mechanisms to normalize nuclear levels of NF-kappaB and to suppress NF-kappaB-mediated transcription, such as increased cytoplasmic and nuclear IkappaBalpha levels or decreased Bcl-3 levels, appeared to be induced. Nevertheless, even though counterregulatory mechanisms to NF-kappaB activation are activated in lung macrophages of patients with ARDS, NF-kappaB remains activated. These results suggest that fundamental abnormalities in transcriptional mechanisms involving NF-kappaB and important in the

  19. RNA interference-mediated silencing of SOCS-1 via lentiviral vector promotes apoptosis of alveolar epithelial cells in vitro.

    Science.gov (United States)

    Qian, Yan-Rong; Zhang, Qiu-Rui; Cheng, Ting; Wan, Huan-Ying; Zhou, Min

    2012-02-01

    Suppressor of cytokine signaling-1 (SOCS1) is a protein that negatively regulates cytokine and growth factor signaling. However, little is known regarding the precise role it plays in idiopathic pulmonary fibrosis. The aim of the present study was to construct a recombinant lentiviral vector for RNA interference targeting the SOCS1 gene and to detect the expression in human alveolar epithelial cells. A lentiviral vector-mediated RNA interference method was used to establish a SOCS1-negative cell line of alveolar origin (A549). Three pairs of complementary small hairpin RNA (shRNA) oligonucleotides targeting the SOCS1 gene were designed, synthesized and inserted into the pPll3.7 vector. Packaged lentivirus particles were obtained after 48 h, and the supernatant was used to transfect the human alveolar epithelial cell line A549. The expression of the SOCS1 protein was detected by Western blotting. MTT assay was used to detect the cell proliferation of alveolar epithelial cells with SOCS1 knockdown. The recombinant plasmids were confirmed by sequencing. The lentivirus-containing supernatant effectively infected the A549 cell line, and the expression of SOCS1 protein was inhibited, which was confirmed by Western blotting in the target cells. MTT assay indicated the inhibition effect for cell proliferation of A549 cells in the SOCS1-RNA interference group, compared to the control group with no interference-mediated silencing of the SOCS1 gene. A lentiviral vector for RNA interference targeting the SOCS1 gene was successfully constructed, and cell survival tests showed that knockdown of the SOCS1 gene promotes the apoptosis of alveolar cells.

  20. Alveolar ventilation in children during flexible bronchoscopy.

    Science.gov (United States)

    Sadot, Efraim; Gut, Guy; Sivan, Yakov

    2016-11-01

    Hypoxia and hypercarbia complicate flexible bronchoscopy (FB). Unlike oxygenation by pulse-oximetry, alveolar ventilation is not routinely monitored during FB. The aim of this study was to investigate ventilation in children undergoing FB by measuring carbon-dioxide (CO2 ) levels using the transcutaneous technique. Children admitted for FB were recruited. In addition to routine monitoring, transcutaneous CO2 (TcCO2 ) levels were recorded. All were sedated using the same protocol. Ninety-five children were studied. There was no association between peak TcCO2 or rise in TcCO2 and age, weight percentile, bronchoscope size, or diagnosis. Median baseline TcCO2 was 36 mmHg (IQR 32,40), median peak TcCO2 was 51 mmHg (IQR 43,62) with median TcCO2 rise of 17 mmHg (IQR 6.5,23.7). A rise of 15 mmHg or higher was recorded in 55% (n = 52) patients. Children requiring total propofol dose over 3.5 mg/kg had a significantly higher TcCO2 peak of 57.6 mmHg (IQR 47.8,66.7) compared to 47.1 mmHg (IQR 40,57) (P = 0.004) and a higher rise in TcCO2 22.5 mmHg (IQR 17,33.9) compared to 13.6 mmHg (6,22) (P = 0.001). Results were not affected by intranasal midazolam and broncho-alveolar lavage. No complications were reported. Non clinically significant (i.e., not lower than 90%) brief drops in oxygen saturation were observed. A large proportion of children undergoing FB have significant alveolar hypoventilation indicated by a rise in TcCO2 . Monitoring ventilation with TcCO2 is feasible and should be added during FB particularly in cases that are expected to require large amounts of sedation and patients susceptible to complications from respiratory acidosis. Pediatr Pulmonol. 2016;51:1177-1182. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Does small-perimeter fencing inhibit mule deer or pronghorn use of water developments?

    Science.gov (United States)

    Larsen, R.T.; Bissonette, J.A.; Flinders, J.T.; Robinson, A.C.

    2011-01-01

    Wildlife water development can be an important habitat management strategy in western North America for many species, including both pronghorn (Antilocapra americana) and mule deer (Odocoileus hemionus). In many areas, water developments are fenced (often with small-perimeter fencing) to exclude domestic livestock and feral horses. Small-perimeter exclosures could limit wild ungulate use of fenced water sources, as exclosures present a barrier pronghorn and mule deer must negotiate to gain access to fenced drinking water. To evaluate the hypothesis that exclosures limit wild ungulate access to water sources, we compared use (photo counts) of fenced versus unfenced water sources for both pronghorn and mule deer between June and October 2002-2008 in western Utah. We used model selection to identify an adequate distribution and best approximating model. We selected a zero-inflated negative binomial distribution for both pronghorn and mule deer photo counts. Both pronghorn and mule deer photo counts were positively associated with sampling time and average daily maximum temperature in top models. A fence effect was present in top models for both pronghorn and mule deer, but mule deer response to small-perimeter fencing was much more pronounced than pronghorn response. For mule deer, we estimated that presence of a fence around water developments reduced photo counts by a factor of 0.25. We suggest eliminating fencing of water developments whenever possible or fencing a big enough area around water sources to avoid inhibiting mule deer. More generally, our results provide additional evidence that water development design and placement influence wildlife use. Failure to account for species-specific preferences will limit effectiveness of management actions and could compromise research results. Copyright ?? 2011 The Wildlife Society.

  2. Liver transplantation for alveolar echinococcosis in an endemic region.

    Science.gov (United States)

    Aydinli, Bulent; Ozturk, Gurkan; Arslan, Sukru; Kantarci, Mecit; Tan, Onder; Ahıskalioglu, Ali; Özden, Kemalettin; Colak, Abdurrahim

    2015-08-01

    Alveolar echinococcosis (AE) is a chronic disease caused by ingestion of the eggs of the parasitic cestode Echinococcosis multilocularis (EM). In severe cases, liver transplantation (LT) may represent the only possibility of survival and cure. Patients undergoing LT associated with hepatic AE at our institution between April 2011 and October 2014 were investigated retrospectively. The clinical findings of the 27 patients who participated in the study were noted. Kaplan-Meier and chi-square tests were used to investigate the effect of these characteristics on survival and mortality. Living donor LT was performed on 20 patients (74.1%), and deceased donor LT was performed on 7 patients (25.9%). Hilar invasion was the most common indication (14 patients, 51.9%) for transplantation. The patient follow-up was 16.1 ± 11.4 months, and the overall survival rate was 77.8%. Primary nonfunction developed only in 2 patients in the posttransplantation period. Six patients died during monitoring, the most common cause of death being sepsis (3 patients). The relationship between the mortality rate of the patients and the invasion of the bile duct and/or portal vein by alveolar lesions was found to be statistically significant (P = 0.024 and P = 0.043, respectively). According to PNM staging, when the AE disease exceeds the resectability limits, the only alternative for the treatment of the disease is LT. However, different from LT due to cirrhosis, it is extremely difficult to perform a transplantation for AE disease because of the invasive characteristics of it. In order to decrease the difficulty of the operation and the postoperative mortality, the intracystic abscess and cholangitis which occur because of AE must be treated via medical and percutaneous methods before transplantation.

  3. The Minimum Alveolar Concentration of Sevoflurane for Respiratory Depression

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    V. V. Likhvantsev

    2011-01-01

    Full Text Available Objective: to provide a rationale for a need to introduce the new constant — the minimum alveolar concentration for respiratory depression (MACrespiratory depression and to determine its value. Subjects and methods. Forty-three patients aged 20— 45 years, who had normal weight and ASA physical status I—II, were examined. All the patients underwent induction of sevorane anesthesia without narcotic analgesics, nitrous oxide, and myorelaxants. A laryngeal mask was installed after MAClm was achieved. Sevorane concentrations were increased on a vaporizer, by changing Etanesth at a rate of 0.2 vol% per min until Etanesthresp;ratory depression was achieved. Results. A rationale was provided for a need to introduce the new inhalation anesthesia constant MACrespiratory depression that is, in accordance with the MAC conception, regarded as the inhalation anesthetic concentration that necessitates assisted ventilation in 50% of the patients. MACrespiratory depression was 1.8 MAC. This is essentially more than both MAC and 1.3 MAC, the anesthetic concentration at which any operation can be performed in 90% of patients. At the same time, the derived value of 3.7 vol% is somewhat below MACbarr (4.07 vol%, which means that anesthesia with sevorane only under spontaneous respiration will be inadequate in few patients or its performance will be associated with the risk of hypoxia. Conclusion. The authors’ successively developed concept of anesthesia with preserved spontaneous respiration necessitates the introduction of the new inhalation anesthesia constant MACrespiratory depression. Its value is 3.7% vol% for sevoflurane. Key words: induction of anesthesia, minimum alveolar concentration, spontaneous respiration, inhalation anesthesia.

  4. A computational approach to understand in vitro alveolar morphogenesis.

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    Sean H J Kim

    Full Text Available Primary human alveolar type II (AT II epithelial cells maintained in Matrigel cultures form alveolar-like cysts (ALCs using a cytogenesis mechanism that is different from that of other studied epithelial cell types: neither proliferation nor death is involved. During ALC formation, AT II cells engage simultaneously in fundamentally different, but not fully characterized activities. Mechanisms enabling these activities and the roles they play during different process stages are virtually unknown. Identifying, characterizing, and understanding the activities and mechanisms are essential to achieving deeper insight into this fundamental feature of morphogenesis. That deeper insight is needed to answer important questions. When and how does an AT cell choose to switch from one activity to another? Why does it choose one action rather than another? We report obtaining plausible answers using a rigorous, multi-attribute modeling and simulation approach that leveraged earlier efforts by using new, agent and object-oriented capabilities. We discovered a set of cell-level operating principles that enabled in silico cells to self-organize and generate systemic cystogenesis phenomena that are quantitatively indistinguishable from those observed in vitro. Success required that the cell components be quasi-autonomous. As simulation time advances, each in silico cell autonomously updates its environment information to reclassify its condition. It then uses the axiomatic operating principles to execute just one action for each possible condition. The quasi-autonomous actions of individual in silico cells were sufficient for developing stable cyst-like structures. The results strengthen in silico to in vitro mappings at three levels: mechanisms, behaviors, and operating principles, thereby achieving a degree of validation and enabling answering the questions posed. We suggest that the in silico operating principles presented may have a biological counterpart

  5. Three metabolites from an entomopathogenic bacterium, Xenorhabdus nematophila, inhibit larval development of Spodoptera exigua (Lepidoptera: Noctuidae) by inhibiting a digestive enzyme, phospholipase A2

    Institute of Scientific and Technical Information of China (English)

    Jaehyun Kim; Yonggyun Kim

    2011-01-01

    An entomopathogenic bacterium, Xenorhabdus nematophila, has been known to induce significant immunosuppression of target insects by inhibiting immune-associated phospholipase A2 (PLA2), which subsequently shuts down biosynthesis of eicosanoids that are critical in immune mediation in insects. Some metabolites originated from the bacterial culture broth have been identified and include benzylideneacetone, proline-tyrosine and acetylated phenylalanine-glycine-valine, which are known to inhibit enzyme activity of PLA2 extracted from hemocyte and fat body. This study tested their effects on digestive PLA2 of the beet armyworm, Spodoptera exigua. Young larvae fed different concentrations of the three metabolites resulted in significant adverse effects on larval development even at doses below 100 μg/mL. In particular, they induced significant reduction in digestive efficiency of ingested food. All three metabolites significantly inhibited catalytic activity of digestive PLA2 extracted from midgut lumen of the fifth instar larvae at a low micromolar range. These results suggest that the inhibitory activities of the three bacterial metabolites on digestive PLA2 of S. exigua midgut may explain some of their oral toxic effects.

  6. Hemorragia alveolar associada a nefrite lúpica Alveolar hemorrhage associated with lupus nephritis

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    Ricardo Henrique de Oliveira Braga Teixeira

    2003-12-01

    Full Text Available Hemorragia alveolar, como causa de insuficiência respiratória, é pouco freqüente, com diversas etiologias possíveis. Entre elas, o lúpus eritematoso sistêmico, que se apresenta geralmente como síndrome pulmão-rim, possui alta morbimortalidade. Acredita-se que a patogênese da microangiopatia, tanto renal como pulmonar, esteja associada ao depósito de imunocomplexos, que ativariam as vias de apoptose celular. Relatam-se dois casos de pacientes com nefrite lúpica que evoluíram com hemorragia alveolar associada à insuficiência respiratória necessitando de ventilação mecânica com evoluções totalmente distintas frente às terapias farmacológicas. O achado de anticorpos antimembrana basal em um dos casos evidencia a multiplicidade de mecanismos fisiopatológicos possivelmente envolvidos, que poderiam justificar as respostas heterogêneas frente aos tratamentos disponíveis.Alveolar hemorrhage leading to respiratory failure is uncommon. Various etiologies have been reported, including systemic lupus erythematosus, which generally presents as pulmonary-renal syndrome. It is believed that the pathogenesis of microangiopathy is related to deposits of immune complexes that lead to activation of cellular apoptosis. The authors report two cases of alveolar hemorrhage and respiratory failure, both requiring mechanical ventilation. The two cases had opposite outcomes after pharmacological therapy. The presence of anti-glomerular basement membrane antibodies in one of the cases demonstrates the multiplicity of physiopathological mechanisms that may be involved. This multiplicity of mechanisms provides a possible explanation for the heterogeneous responses to the available treatments.

  7. [A case of central alveolar hypoventilation syndrome associated with cerebral infarction].

    Science.gov (United States)

    Yamada, A; Kamoda, M; Ikezoe, K; Tsukaguchi, M; Katanaka, J; Deguchi, K; Miki, H; Takeuchi, H

    1993-03-01

    Central alveolar hypoventilation syndrome (CAH), or Ondine's curse, is a very rare disease characterized by dysfunction of respiratory center in the brain stem. Here, we report a case of CAH associated with cerebral infarction. A 59-year-old man developed right facial sensory deficit at age 56. Then, the facial sensory deficit spread to the left side and dysarthria and dysphagia also developed. Since age 58, he often developed respiratory failure and consciousness disturbance. Arterial blood gas analysis revealed alveolar hypoventilation and respiratory acidosis. Disorders of peripheral organs such as lung, airway, thorax and neuromuscular diseases were ruled out. Brain MRI showed cerebral infarction in the brain stem. We diagnosed him as CAH associated with brain stem infarction.

  8. Diffuse alveolar hemorrhage due to ketorolac tromethamine.

    Science.gov (United States)

    Marak, Creticus P; Alappan, Narendrakumar; Shim, Chang; Guddati, Achuta K

    2013-01-01

    Drug-induced lung disease (DILD) is a common but frequently missed diagnosis. Therefore, a high index of clinical suspicion and familiarity with the clinical syndromes associated with DILD are important in making the diagnosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the mostly commonly used classes of medications. NSAIDs are safe when used at prescribed doses. Side effects from use of NSAIDs are not uncommon and can affect almost every organ system in the body. NSAIDs are notorious for causing pulmonary toxicity, the common ones being bronchospasm and hypersensitivity reactions. Diffuse alveolar hemorrhage (DAH) secondary to NSAIDs is uncommon. Here, we report a case of DAH secondary to the use of ketorolac tromethamine.

  9. Imaging features of alveolar soft part sarcoma

    Institute of Scientific and Technical Information of China (English)

    Teng Jin; Ping Zhang Co-first author; Xiaoming Li

    2015-01-01

    Objective The aim of this study was to analyze the imaging features of alveolar soft part sarcoma (ASPS). Methods The imaging features of 11 cases with ASPS were retrospectively analyzed. Results ASPS mainly exhibited an isointense or slightly high signal intensity on T1-weighted imaging (T1WI), and a mixed high signal on T2-weighted imaging (T2WI). ASPS was partial, with rich tortuous flow voids, or “line-like” low signal septa. The essence of the mass was heterogeneous enhancement. The 1H-MRS showed a slight choline peak at 3.2 ppm. Conclusion The wel-circumscribed mass and blood voids, combined with “line-like” low signals play a significant role in diagnosis. The choline peak and the other signs may be auxiliary diagnoses.

  10. Vestibuloplasty after secondary alveolar bone grafting.

    Science.gov (United States)

    Iino, M; Fukuda, M; Murakami, K; Horiuchi, T; Niitsu, K; Seto, K

    2001-11-01

    This paper introduces a surgical technique for vestibuloplasty after secondary alveolar bone grafting of patients with cleft lip and palate (CLP). This paper also reports on the patients who underwent this modified vestibuloplasty. The vestibuloplasty technique described in this paper consists of: (1) reduction of submucosal scar tissue of the upper lip, (2) V-Y plasty of the superficial mucosa, (3) placement of horizontal mattress sutures between nostril floor skin and freed marginal mucosa, (4) application of artificial skin to cover the exposed periosteal surface, and (5) use of a removable retention splint. This surgical procedure appears to be very useful for patients with CLP. The technique enables the surgeon to obtain an adequate sulcus depth around the graft area. In addition, this technique releases the mucosal scar contraction and improves the shape and mobility of the upper lip.

  11. [Clinical aspect of diffuse alveolar hemorrhage syndrome].

    Science.gov (United States)

    Ishida, Kazuo; Seki, Reiko; Inoue, Takeo; Iwamoto, Tokuzen; Hoshino, Makoto; Nakagawa, Takemasa

    2003-12-01

    Thirteen cases of diffuse alveolar hemorrhage (DAH) were encountered in our Hospital between January 1996 and October 2001. Eight patients were men and five were women, their mean age being 59.5 +/- 19.2 years (range, 18-88 years). Three patients had systemic lupus erythematosus (SLE), three (23%) had polyarteritis nodosa (including microscopic PN), one (7.7%) had allergic granulomatous angitis, one (7.7%) had Goodpasture syndrome, one (7.7%) had MPO-ANCA-associated vasculitis, one (7.7%) had Behçet's disease, one (7.7%) had chronic heart failure caused by mitral stenosis, one (7.7%) had chronic renal failure (etiology unknown), and the last had no particular disorder. Nine episodes (69%) had occurred as complications of primary diseases, four (31%) as the first symptoms of underlying diseases. Prognosis was poor in the former cases but in the latter, the prognosis was relatively favorable.

  12. Pseudomonas aeruginosa lipopolysaccharide inhibits Candida albicans hyphae formation and alters gene expression during biofilm development.

    Science.gov (United States)

    Bandara, H M H N; K Cheung, B P; Watt, R M; Jin, L J; Samaranayake, L P

    2013-02-01

    Elucidation of bacterial and fungal interactions in multispecies biofilms will have major impacts on understanding the pathophysiology of infections. The objectives of this study were to (i) evaluate the effect of Pseudomonas aeruginosa lipopolysaccharide (LPS) on Candida albicans hyphal development and transcriptional regulation, (ii) investigate protein expression during biofilm formation, and (iii) propose likely molecular mechanisms for these interactions. The effect of LPS on C. albicans biofilms was assessed by XTT-reduction and growth curve assays, light microscopy, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). Changes in candidal hypha-specific genes (HSGs) and transcription factor EFG1 expression were assessed by real-time polymerase chain reaction and two-dimensional gel electrophoresis, respectively. Proteome changes were examined by mass spectrometry. Both metabolic activities and growth rates of LPS-treated C. albicans biofilms were significantly lower (P GDH1), CaO19.11135(PGK1), CaO19.9877(HNT1) by P. aeruginosa LPS. Our data imply that bacterial LPS inhibit C. albicans biofilm formation and hyphal development. The P. aeruginosa LPS likely target glycolysis-associated mechanisms during candidal filamentation.

  13. Arbuscular mycorrhiza enhance the rate of litter decomposition while inhibiting soil microbial community development.

    Science.gov (United States)

    Gui, Heng; Hyde, Kevin; Xu, Jianchu; Mortimer, Peter

    2017-02-08

    Although there is a growing amount of evidence that arbuscular mycorrhizal fungi (AMF) influence the decomposition process, the extent of their involvement remains unclear. Therefore, given this knowledge gap, our aim was to test how AMF influence the soil decomposer communities. Dual compartment microcosms, where AMF (Glomus mosseae) were either allowed access (AM+) to or excluded (AM-) from forest soil compartments containing litterbags (leaf litter from Calophyllum polyanthum) were used. The experiment ran for six months, with destructive harvests at 0, 90, 120, 150, and 180 days. For each harvest we measured AMF colonization, soil nutrients, litter mass loss, and microbial biomass (using phospholipid fatty acid analysis (PLFA)). AMF significantly enhanced litter decomposition in the first 5 months, whilst delaying the development of total microbial biomass (represented by total PLFA) from T150 to T180. A significant decline in soil available N was observed through the course of the experiment for both treatments. This study shows that AMF have the capacity to interact with soil microbial communities and inhibit the development of fungal and bacterial groups in the soil at the later stage of the litter decomposition (180 days), whilst enhancing the rates of decomposition.

  14. Imaging Therapeutic PARP Inhibition In Vivo through Bioorthogonally Developed Companion Imaging Agents

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    Thomas Reiner

    2012-03-01

    Full Text Available A number of small-molecule poly (ADP-ribose polymerase (PARP inhibitors are currently undergoing advanced clinical trials. Determining the distribution and target inhibitory activity of these drugs in individual subjects, however, has proven problematic. Here, we used a PARP agent for positron emission tomography-computed tomography (PET-CT imaging (18F-BO, which we developed based on the Olaparib scaffold using rapid bioorthogonal conjugation chemistries. We show that the bioorthogonal 18F modification of the parent molecule is simple, highly efficient, and well tolerated, resulting in a half maximal inhibitory concentration (IC50 of 17.9 ± 1.1 nM. Intravital imaging showed ubiquitous distribution of the drug and uptake into cancer cells, with ultimate localization within the nucleus, all of which were inhibitable. Whole-body PET-CT imaging showed tumoral uptake of the drug, which decreased significantly, after a daily dose of Olaparib. Standard 18F-fludeoxyglucose imaging, however, failed to detect such therapy-induced changes. This research represents a step toward developing a more generic approach for the rapid codevelopment of companion imaging agents based on small-molecule therapeutic inhibitors.

  15. Arbuscular mycorrhiza enhance the rate of litter decomposition while inhibiting soil microbial community development

    Science.gov (United States)

    Gui, Heng; Hyde, Kevin; Xu, Jianchu; Mortimer, Peter

    2017-01-01

    Although there is a growing amount of evidence that arbuscular mycorrhizal fungi (AMF) influence the decomposition process, the extent of their involvement remains unclear. Therefore, given this knowledge gap, our aim was to test how AMF influence the soil decomposer communities. Dual compartment microcosms, where AMF (Glomus mosseae) were either allowed access (AM+) to or excluded (AM−) from forest soil compartments containing litterbags (leaf litter from Calophyllum polyanthum) were used. The experiment ran for six months, with destructive harvests at 0, 90, 120, 150, and 180 days. For each harvest we measured AMF colonization, soil nutrients, litter mass loss, and microbial biomass (using phospholipid fatty acid analysis (PLFA)). AMF significantly enhanced litter decomposition in the first 5 months, whilst delaying the development of total microbial biomass (represented by total PLFA) from T150 to T180. A significant decline in soil available N was observed through the course of the experiment for both treatments. This study shows that AMF have the capacity to interact with soil microbial communities and inhibit the development of fungal and bacterial groups in the soil at the later stage of the litter decomposition (180 days), whilst enhancing the rates of decomposition. PMID:28176855

  16. Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice

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    De Clercq Erik

    2003-12-01

    Full Text Available Abstract Background Viral replication as well as an immunopathological component are assumed to be involved in the development of coxsackie B virus (CBV-induced myocarditis. We observed that mycophenolic acid (MPA, the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF, inhibits coxsackie B3 virus (CBV3 replication in primary Human myocardial fibroblasts. We therefore studied whether MMF, which is thus endowed with a direct antiviral as well as immunosuppressive effect, may prevent CBV-induced myocarditis in a murine model. Results Four week old C3H-mice were infected with CBV3 and received twice daily, for 7 consecutive days (from one day before to 5 days post-virus inoculation treatment with MMF via oral gavage. Treatment with MMF resulted in a significant reduction in the development of CBV-induced myocarditis as assessed by morphometric analysis, i.e. 78% reduction when MMF was administered at 300 mg/kg/day (p Conclusion The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model.

  17. [Clinicopathological diagnosis of diffuse alveolar hemorrhage].

    Science.gov (United States)

    Fang, F; Li, Y M; Hu, S T; Wang, H T; Liu, D G; Wang, C

    2016-01-12

    To improve knowledge about the clinical and pathological features of diffuse alveolar hemorrhage (DAH). Six cases DAH with intact clinical and pathological data were retrospectively analyzed during the period from May 1999 to May 2015 in Beijing Hospital. There were altogether 2 males and 4 females, with age ranging from 32 to 68 years (mean 58.8 years). Specimens were obtained by autopsy (3 cases), open lung biopsy (2 cases) and renal biopsy (2 cases), including 1 case of open lung biopsy in 2003, renal biopsy in 2012. Clinically, the patients presented with cough, shortness of breath and dyspnea, including 5 cases of hemoptysis, 4 cases of fever, 3 cases of skin and mucosa bleeding, 2 cases of gross hematuria, 2 cases of microscopic hematuria, 3 cases of renal functional impairment. A total of 5 cases had different levels of elevated erythrocyte sedimentation rate and C-reactive protein, 6 cases had moderate anemia, hypoxemia, diffuse infiltrates with alveolar filling in chest CT. Serum antineutrophil cytoplasmic antibody was positive in 3 cases, anti-glomerular basement membrane antibody was present in 1 case. Pathological diagnosis: 2 cases of Granulomatosis with polyangiitis (GPA), 2 cases of Microscopic polyangiitis (MPA), 1 case of Goodpasture syndrome, 1 case of pulmonary veno-occlusive disease (PVOD). 3 cases died; 2 cases were discharged; 1 case received symptomatic treatment, follow-up after discharge. The mainly clinical characteristics of DAH are varied degree of dyspnea, anemia, hypoxemia, and extensive ground-glass opacification or consolidation in image, with or without haemoptysis; diffuse acute or chronic pulmonary hemorrhage in lung tissue is the main pathological feature.

  18. [Distraction osteogenesis of deficient alveolar bone prior to dental rehabilitation].

    Science.gov (United States)

    Shilo, D; Emodi, O; Aizenbud, D; Rachmiel, A

    2015-07-01

    Implant supported rehabilitation has become very common in treatment plans nowadays, yet many patients lack the vertical and horizontal bone dimensions required for endosseous implant insertion. Distraction osteogenesis is a technique in which bone is generated by progressive elongation of two bone fragments following an osteotomy or corticotomy. Distraction osteogenesis of the alveolar ridge as a treatment modality in implant dentistry is a very useful technique that allows for adequate bone formation suitable for implant insertion. Alveolar distraction can be unidirectional, bidirectional, multidirectional or horizontal. Alveolar distraction osteogenesis can be performed by using intraosseous distraction devices, intraosseous distraction implants or by extraosseous devices which are the most prevalent today. Distraction osteogenesis has many advantages such as gradual lengthening of the bone with no need for an autogenous bone graft and lack of the associated donor site morbidity as well as distraction of the surrounding soft tissue together with the transported bone. One of the major challenges when using alveolar distraction osteogenesis is controlling the vector of distraction, this problem should be further addressed in future researches. We describe different methods for alveolar distraction osteogenesis, including the surgical procedure, latency period, lengthening and consolidation period. We also discuss the advantages, disadvantages and complications of the method. In this manuscript a case of mandibular alveolar deficiency following mandibular fracture and loss of teeth and the alveolar bone is presented. This patient was treated by alveolar distraction osteogenesis with excellent results. This patient was later rehabilitated . using endosseous implants as demonstrated by radiographs. Alveolar distraction osteogenesis provides a method to regain both hard tissue and soft tissue without additional grafting and is an efficient modality in cases of medium

  19. Endotoxin induced peritonitis elicits monocyte immigration into the lung: implications on alveolar space inflammatory responsiveness

    Directory of Open Access Journals (Sweden)

    Welte Tobias

    2006-02-01

    Full Text Available Abstract Background Acute peritonitis developing in response to gram-negative bacterial infection is known to act as a trigger for the development of acute lung injury which is often complicated by the development of nosocomial pneumonia. We hypothesized that endotoxin-induced peritonitis provokes recruitment of monocytes into the lungs, which amplifies lung inflammatory responses to a second hit intra-alveolar challenge with endotoxin. Methods Serum and lavage cytokines as well as bronchoalveolar lavage fluid cells were analyzed at different time points after intraperitoneal or intratracheal application of LPS. Results We observed that mice challenged with intraperitoneal endotoxin developed rapidly increasing serum and bronchoalveolar lavage fluid (BALF cytokine and chemokine levels (TNFα, MIP-2, CCL2 and a nearly two-fold expansion of the alveolar macrophage population by 96 h, but this was not associated with the development of neutrophilic alveolitis. In contrast, expansion of the alveolar macrophage pool was not observed in CCR2-deficient mice and in wild-type mice systemically pretreated with the anti-CD18 antibody GAME-46. An intentional two-fold expansion of alveolar macrophage numbers by intratracheal CCL2 following intraperitoneal endotoxin did not exacerbate the development of acute lung inflammation in response to intratracheal endotoxin compared to mice challenged only with intratracheal endotoxin. Conclusion These data, taken together, show that intraperitoneal endotoxin triggers a CCR2-dependent de novo recruitment of monocytes into the lungs of mice but this does not result in an accentuation of neutrophilic lung inflammation. This finding represents a previously unrecognized novel inflammatory component of lung inflammation that results from endotoxin-induced peritonitis.

  20. Inhibition of Hyaluronic Acid Synthesis Suppresses Angiogenesis in Developing Endometriotic Lesions.

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    Carla N Olivares

    Full Text Available The development and long-term survival of endometriotic lesions is crucially dependent on an adequate vascularization. Hyaluronic acid (HA through its receptor CD44 has been described to be involved in the process of angiogenesis.To study the effect of HA synthesis inhibition using non-toxic doses of 4-methylumbelliferone (4-MU on endometriosis-related angiogenesis.The cytotoxicity of different in vitro doses of 4-MU on endothelial cells was firstly tested by means of a lactate dehydrogenase assay. The anti-angiogenic action of non-cytotoxic doses of 4-MU was then assessed by a rat aortic ring assay. In addition, endometriotic lesions were induced in dorsal skinfold chambers of female BALB/c mice, which were daily treated with an intraperitoneal injection of 0.9% NaCl (vehicle group; n = 6, 20 mg/kg 4-MU (n = 8 or 80 mg/kg 4-MU (n = 7 throughout an observation period of 14 days. The effect of 4-MU on their vascularization, survival and growth were studied by intravital fluorescence microscopy, histology and immunohistochemistry.Non-cytotoxic doses of 4-MU effectively inhibited vascular sprout formation in the rat aortic ring assay. Endometriotic lesions in dorsal skinfold chambers of 4-MU-treated mice dose-dependently exhibited a significantly smaller vascularized area and lower functional microvessel density when compared to vehicle-treated controls. Histological analyses revealed a downregulation of HA expression in 4-MU-treated lesions. This was associated with a reduced density of CD31-positive microvessels within the lesions. In contrast, numbers of PCNA-positive proliferating and cleaved caspase-3-positive apoptotic cells did not differ between 4-MU-treated and control lesions.The present study demonstrates for the first time that targeting the synthesis of HA suppresses angiogenesis in developing endometriotic lesions. Further studies have to clarify now whether in the future this anti-angiogenic effect can be used beneficially for the

  1. Fractura da cortical alveolar resultante da exodontia de dentes anquilosados

    OpenAIRE

    2010-01-01

    Monografia apresentada à Universidade Fernando Pessoa para obtenção do grau Licenciado em Medicina Dentária A anquilose dento-alveolar constitui uma condição patológica que consiste na fusão anatómica entre o cemento radicular e o osso alveolar propriamente dito, podendo ocorrer durante qualquer etapa do processo eruptivo. Os factores etiológicos da anquilose dento-alveolar ainda não estão totalmente esclarecidos, existindo diversas teorias que pretendem explicar o fenómeno. O objectivo...

  2. Aryl hydrocarbon receptor inhibition promotes hematolymphoid development from human pluripotent stem cells.

    Science.gov (United States)

    Angelos, Mathew G; Ruh, Paige N; Webber, Beau R; Blum, Robert H; Ryan, Caitlin D; Bendzick, Laura; Shim, Seonhui; Yingst, Ashley M; Tufa, Dejene M; Verneris, Michael R; Kaufman, Dan S

    2017-06-29

    The aryl hydrocarbon receptor (AHR) plays an important physiological role in hematopoiesis. AHR is highly expressed in hematopoietic stem and progenitor cells (HSPCs) and inhibition of AHR results in a marked expansion of human umbilical cord blood-derived HSPCs following cytokine stimulation. It is unknown whether AHR also contributes earlier in human hematopoietic development. To model hematopoiesis, human embryonic stem cells (hESCs) were allowed to differentiate in defined conditions in the presence of the AHR antagonist StemReginin-1 (SR-1) or the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We demonstrate a significant increase in CD34(+)CD31(+) hematoendothelial cells in SR-1-treated hESCs, as well as a twofold expansion of CD34(+)CD45(+) hematopoietic progenitor cells. Hematopoietic progenitor cells were also significantly increased by SR-1 as quantified by standard hematopoietic colony-forming assays. Using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-engineered hESC-RUNX1c-tdTomato reporter cell line with AHR deletion, we further demonstrate a marked enhancement of hematopoietic differentiation relative to wild-type hESCs. We also evaluated whether AHR antagonism could promote innate lymphoid cell differentiation from hESCs. SR-1 increased conventional natural killer (cNK) cell differentiation, whereas TCDD treatment blocked cNK development and supported group 3 innate lymphoid cell (ILC3) differentiation. Collectively, these results demonstrate that AHR regulates early human hematolymphoid cell development and may be targeted to enhance production of specific cell populations derived from human pluripotent stem cells. © 2017 by The American Society of Hematology.

  3. Adolescent development of inhibition as a function of SES and gender: Converging evidence from behavior and fMRI.

    Science.gov (United States)

    Spielberg, Jeffrey M; Galarce, Ezequiel M; Ladouceur, Cecile D; McMakin, Dana L; Olino, Thomas M; Forbes, Erika E; Silk, Jennifer S; Ryan, Neal D; Dahl, Ronald E

    2015-08-01

    The ability to adaptively inhibit responses to tempting/distracting stimuli in the pursuit of goals is an essential set of skills necessary for adult competence and wellbeing. These inhibitory capacities develop throughout childhood, with growing evidence of important maturational changes occurring in adolescence. There also has been intense interest in the role of social adversity on the development of executive function, including inhibitory control. We hypothesized that the onset of adolescence could be a time of particular opportunity/vulnerability in the development of inhibition due to the large degree of maturational changes in neural systems involved in regulatory control. We investigated this hypothesis in a longitudinal study of adolescents by examining the impact of socioeconomic status (SES) on the maturation of inhibition and concurrent brain function. Furthermore, we examined gender as a potential moderator of this relationship, given evidence of gender-specificity in the developmental pathways of inhibition as well as sex differences in adolescent development. Results reveal that lower SES is associated with worse behavioral inhibition over time and a concurrent increase in anterior cingulate (ACC) activation, but only in girls. We also found that lower SES girls exhibited decreased ACC ↔ dorsolateral prefrontal cortex (dlPFC) coupling over time. Our findings suggest that female adolescents with lower SES appear to develop less efficient inhibitory processing in dlPFC, requiring greater and relatively unsuccessful compensatory recruitment of ACC. In summary, the present study provides a novel window into the neural mechanisms by which the influence of SES on inhibition may be transmitted during adolescence.

  4. Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development

    Directory of Open Access Journals (Sweden)

    Tonya R. Ellis

    2016-09-01

    Full Text Available Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodeling, cell-signaling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN is an inexpensive, broad-spectrum inhibitor of metalloproteinases that functions by chelating the catalytic zinc ion, however its use in vivo has been limited due to suspected off-target effects. PhN is very similar in structure to phenanthrene (PhE, a well-studied poly aromatic hydrocarbon (PAH known to cause toxicity in aquatic animals by activating the aryl hydrocarbon receptor (AhR. We show that zebrafish are more sensitive to PhN than PhE, and that PhN causes a superset of the effects caused by PhE. Morpholino knock-down of the AhR rescues the effects of PhN that are shared with PhE, suggesting these are due to PAH toxicity. The effects of PhN that are not shared with PhE (specifically disruption of neural crest development and angiogenesis involve processes known to depend on metalloproteinase activity. Furthermore these PhN-specific effects are not rescued by AhR knock-down, suggesting that these are bona fide effects of metalloproteinase inhibition, and that PhN can be used as a broad spectrum metalloproteinase inhibitor for studies with zebrafish in vivo.

  5. Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development

    Science.gov (United States)

    Ellis, Tonya R.; Crawford, Bryan D.

    2016-01-01

    Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodeling, cell-signaling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN) is an inexpensive, broad-spectrum inhibitor of metalloproteinases that functions by chelating the catalytic zinc ion, however its use in vivo has been limited due to suspected off-target effects. PhN is very similar in structure to phenanthrene (PhE), a well-studied poly aromatic hydrocarbon (PAH) known to cause toxicity in aquatic animals by activating the aryl hydrocarbon receptor (AhR). We show that zebrafish are more sensitive to PhN than PhE, and that PhN causes a superset of the effects caused by PhE. Morpholino knock-down of the AhR rescues the effects of PhN that are shared with PhE, suggesting these are due to PAH toxicity. The effects of PhN that are not shared with PhE (specifically disruption of neural crest development and angiogenesis) involve processes known to depend on metalloproteinase activity. Furthermore these PhN-specific effects are not rescued by AhR knock-down, suggesting that these are bona fide effects of metalloproteinase inhibition, and that PhN can be used as a broad spectrum metalloproteinase inhibitor for studies with zebrafish in vivo. PMID:27618022

  6. Development of urease based amperometric biosensors for the inhibitive determination of Hg (II).

    Science.gov (United States)

    Domínguez-Renedo, O; Alonso-Lomillo, M A; Ferreira-Gonçalves, L; Arcos-Martínez, M J

    2009-10-15

    Enzymatic amperometric procedures for measurement of Hg (II), based on the inhibitive action of this metal on urease enzyme activity, were developed. Screen-printed carbon electrodes (SPCEs) and gold nanoparticles modified screen-printed carbon electrodes (AuNPs/SPCEs) were used as supports for the cross-linking inmobilization of the enzyme urease. The amperometric response of urea was affected by the presence of Hg (II) ions which caused a decreasing in the current intensity. The optimum working conditions were found using experimental design methodology. Under these conditions, repeatability and reproducibility for both types of biosensors were determined, reaching values below 6% in terms of residual standard deviation. The detection limit obtained for Hg (II) was 4.2x10(-6)M for urease/SPCE biosensor and 5.6x10(-8)M for urease/AuNPs/SPCE biosensor. Analysis of the possible effect of the presence of foreign ions in the solution was performed. The method was applied to determine levels of Hg (II) in spiked human plasma samples.

  7. Ursolic acid inhibits the development of nonalcoholic fatty liver disease by attenuating endoplasmic reticulum stress.

    Science.gov (United States)

    Li, Jian-Shuang; Wang, Wen-Jun; Sun, Yu; Zhang, Yu-Hao; Zheng, Ling

    2015-05-01

    Ursolic acid (UA) is a natural pentacyclic triterpenoid compound, which is enriched with many herbs and plants, such as apple, cranberry and olive. UA performs multiple biological activities including anti-oxidation, anti-inflammation, anti-cancer and hepatoprotection. However, the exact mechanism underlying the hepatoprotective activity of UA remains unclear. In this study, the effects of UA on the development of nonalcoholic fatty liver disease (NAFLD) were investigated. In vivo, UA treatment (0.14%, w/w) significantly decreased the liver weight, serum levels of ALT/AST and hepatic steatosis in db/db mice (a type 2 diabetic mouse model). In vitro, UA treatment (10-30 μg ml(-1)) significantly decreased palmitic acid induced intracellular lipid accumulation in L02 cells. Our results suggested that the beneficial effects of UA on NAFLD may be due to its ability to increase lipid β-oxidation and to inhibit the hepatic endoplasmic reticulum (ER) stress. Together, UA may be further considered as a natural compound for NAFLD treatment.

  8. CXCR2 inhibition enhances sulindac-mediated suppression of colon cancer development.

    Science.gov (United States)

    Lee, Yong Suk; Choi, Dongwon; Kim, Nam Yoon; Yang, Sara; Jung, Eunson; Hong, Mingu; Yang, Dongyun; Lenz, Heinz-Josef; Hong, Young-Kwon

    2014-07-01

    Small chemical compound sulindac has been approved as a preventive approach against colon cancer for its effectiveness in treatment of precancerous adenoma. Due to its severe toxicities in the cardiovascular, gastrointestinal and renal systems, however, a combination of low-dose sulindac with other chemopreventive agents has been sought after as an alternative therapeutic strategy that could increase its effectiveness, while minimizing its adverse effects. To identify the promising alternative approach, we investigated the therapeutic potential of targeting the interleukin (IL)-8/CXCR2 pathway in colon cancer treatment using both loss-of-function (CXCR2 knockout) and gain-of-function (IL-8 overexpression) mouse models, as the IL-8/CXCR2 pathway has been shown to be activated in intestinal tumors of both human and experimental animals. We found that deletion of CXCR2 gene and ectopic expression of IL-8 suppresses and enhances, respectively, intestinal tumor development caused by a mutation in the APC gene. Moreover, a single copy deletion of CXCR2 gene resulted in abrogation of COX-2 and Gro-α upregulation in intestinal tumors caused by the APC mutation. Moreover, a single copy (heterozygote) deletion of CXCR2 gene was sufficient to synergize with a low-dose sulindac treatment in suppressing APCmin-induced intestinal polyposis. Together, our study provides a therapeutic justification of combined inhibition of CXCR2 and sulindac treatment in colon cancer prevention.

  9. Development of inhibition as a function of the presence of a supernatural agent.

    Science.gov (United States)

    King, Ashley C

    2011-01-01

    In this study the author examined the developmental differences in inhibition and cognition of 4-8-year-old children as a function of the suggested presence of a supernatural agent. Previous evolutionarily-relevant research has suggested that humans are naturally primed to think in terms of supernatural agents and that, given the correct context, individuals readily accept novel supernatural entities and alter their behavior accordingly. All children in this study played 4 games designed to assess their present level of inhibitory and cognitive development. Children in the experimental condition were also introduced to an invisible Princess Alice and were told that she was watching during the games. Following these measures, all children engaged in a resistance-to-temptation task. Results revealed that cognitively advanced children were more likely to express belief in Princess Alice than were less cognitively advanced children. This research provides support that cognitive maturity, rather than immaturity, may be necessary for children to express belief in novel supernatural agents.

  10. Alveolar macrophages play a key role in cockroach-induced allergic inflammation via TNF-α pathway.

    Directory of Open Access Journals (Sweden)

    Joo Young Kim

    Full Text Available The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF-α. We determined whether the serine protease in German cockroach extract (GCE enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR, inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model.

  11. ROLE OF POLYAMINES IN INHIBITION OF ETHYLENE BIOSYNTHESIS AND THEIR EFFECTS ON RICE ANTHER CULTURE DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Iswari S. Dewi

    2016-10-01

    Full Text Available The polyamines such as putrescine, spermidine, and spermine were reported to increase green plant regeneration in rice anther culture. Low response of anther culture of rice sub-species indica may be improved with the addition of putrescine in the culture media. Four experiments were conducted to study the role of polyamines in inhibition of ethylene biosynthesis and their effects on rice anther culture development. Anthers of two subspecies of rice, indica (IR64, Krowal, Jatiluhur and japonica (Taipei 309 were cultured onto media supplemented with putrescine (N6P and without putrescine (N6. Youngpanicles containing the anthers at mid-to-late nucleate microspores were cold pretreated at 5 + 2°C and incubated in the dark for 8 days before the anthers were cultured. Resultsshowed that medium without putrescine produced an earlier senescence of indica rice anther than that of japonica. The addition of 10-3 M putrescine into the culture media inhibited ethylene biosynthesis as anther senescence delayed, increased the three polyamines contents, and decreased the ACC content as well as ACC oxydase activity in anther-derived calli. In the anther and anther-derived calli of subspecies indica, the totalpolyamines content was lower (10.14 nM g-1 anther and 8.48 nM g-1 calli than that of subspecies japonica (12.61 nM g-1 anther and 10.16 nM g-1 calli, whereas the ethylene production was higher (32.31 nM g-1 anther and 2.48 nM g-1 calli than the japonica (31.68 nM g-1 anther and 1.76 nM g-1 calli. This study suggests that application of 10-3 M putrescine in anther culture of rice subspecies indica improves androgenesis by inhibitingearly senescence of cultured anthers and enhancing embryo or callus formation from microspores.

  12. Alveolar ridge augmentation in rats by combined hydroxylapatite and osteoinductive material

    DEFF Research Database (Denmark)

    Pinholt, E M; Bang, G; Haanaes, H R

    1991-01-01

    , lyophilized dentin or bone and implanted subperiosteally for alveolar ridge augmentation purposes and heterotopically in the abdominal muscles in rats. Light microscopic evaluation revealed that HA was surrounded by fibrous connective tissue containing foreign body giant cells and it had neither......The purpose of this study was to examine if increased bony ingrowth developed when hydroxylapatite was implanted together with an osteoinductive substrate. Dense hydroxylapatite granules (HA) (Calcitite, Calcitek, San Diego, CA, USA) were mixed with equal volumes of allogenic, demineralized...

  13. Kinetics of Interaction and Fate of Pasteurella hemolytica in Bovine Alveolar Macrophages

    OpenAIRE

    Maheswaran, S K; Berggren, K. A.; Simonson, R. R.; Ward, G E; Muscoplat, C C

    1980-01-01

    To study the role of pulmonary alveolar macrophages (PAMs) in phagocytizing Pasteurella hemolytica, we developed an in vitro cultivation method for preparing them. This procedure provided an adherent monolayer of PAMs which were nonspecific esterase-positive and phagocytized latex beads. The phagocytosis and fate of P. hemolytica (biotype A, serotype 1) by PAMs in suspension were studied. The kinetics of phagocytosis were determined by quantitatively measuring the uptake of 24-h [3H]thymidine...

  14. Autoimmune pulmonary alveolar proteinosis co-existing with breast cancer: a case report

    OpenAIRE

    Sawai, Toyomitsu; Umeyama, Yasuhiro; Yoshioka, Sumako; Matsuo, Nobuko; Suyama, Naofumi; Kohno, Shigeru

    2014-01-01

    Introduction. Pulmonary alveolar proteinosis is a rare pulmonary disease characterized by excessive alveolar accumulation of surfactant due to defective alveolar clearance by macrophages. There are only a few published case reports of pulmonary alveolar proteinosis occurring in association with solid cancers. To the best of our knowledge, there are no previously reported cases of pulmonary alveolar proteinosis associated with breast cancer. Case presentation. A 48-year-old Asian woman, a nons...

  15. Clinical case of the course of congenital alveolar-capillary dysplasia of the lungs at a newborn

    Directory of Open Access Journals (Sweden)

    Gavrilova E.S.

    2016-06-01

    Full Text Available The article describes a clinical case of a child with an alveolar-capillary dysplasia of the lungs — a rare cause of pulmonary hypertension at a newborn. This pathology is of particular interest from a clinical point of view as it rarely occurs in the clinical practice of a neonatologist. It should be noted that the prenatal diagnosis of this disease is of significant difficulty. The authors found it necessary to highlight the cause of development, the clinical presentation and the methods of diagnostics of alveolar-capillary dysplasia of the lungs.

  16. Prevention of Alveolar Osteitis After Third Molar Surgery ...

    African Journals Online (AJOL)

    2017-05-16

    May 16, 2017 ... of alveolar osteitis after third molar surgery: Comparative study of the effect of warm saline ... recovery after dental extractions as evidenced by reports across the ... routine use after oral surgical procedures not to be common.

  17. Alveolar proteinosis in Behçet's disease

    Directory of Open Access Journals (Sweden)

    Tetikkurt Cuneyt

    2010-08-01

    Full Text Available Abstract A 51-year-old man with Behçet's disease complained of fever, dry cough and dyspnea during exertion. Chest CT showed ground glass opacities with interstitial septal thickening in both lungs. Bronchoalveolar lavage (BAL revealed amorphous and lipoproteinaceous material that was periodic acid-Schiff (PAS stain positive. Transbronchial biopsy specimen demonstrated PAS positive alveolar eosinophilic material consistent with pulmonary alveolar proteinosis. Serum anti-granulocyte-macrophage colony stimulating factor (GM-CSF antibody was negative. Recent studies have reported anti-GMCSF not present in the the serum of patients with secondary pulmonary alveolar proteinosis (PAP but they have not reported so in patients with idiopathic PAP. We report a case of alveolar proteinosis in the setting of Behçet's disease with spontaneous remission.

  18. Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD

    NARCIS (Netherlands)

    Hart, H.; Chantiluke, K.; Cubillo, A.I.; Smith, A.B.; Simmons, A.; Brammer, M.J.; Marquand, A.F.; Rubia, K.

    2014-01-01

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern

  19. Zingerone suppresses angiogenesis via inhibition of matrix metalloproteinases during tumor development

    Science.gov (United States)

    Kim, Ja-Eun; Park, Chan; Jeong, Joo-Won

    2016-01-01

    Angiogenesis is an essential step for tumor survival and progression, and the inhibition of angiogenesis is a good strategy for tumor therapeutics. In this study, we investigated the therapeutic effect of zingerone in a mouse tumor model. Zingerone suppressed tumor progression and tumor angiogenesis. Moreover, we found that zingerone inhibited the angiogenic activities of endothelial cells by both direct and indirect means. A mechanistic study showed that the activities of MMP-2 and MMP-9 in tumor cells were decreased by treatment with zingerone. Interestingly, zingerone-mediated inhibition of MMP-2 and MMP-9 was involved in the JNK pathway. In conclusion, zingerone showed strong anti-angiogenic activity via the inhibition of MMP-2 and MMP-9 during tumor progression, suggesting that zingerone may be a potential therapeutic drug for human cancers. PMID:27323807

  20. Exogenous hydrogen sulfide (H2S protects alveolar growth in experimental O2-induced neonatal lung injury.

    Directory of Open Access Journals (Sweden)

    Arul Vadivel

    Full Text Available BACKGROUND: Bronchopulmonary dysplasia (BPD, the chronic lung disease of prematurity, remains a major health problem. BPD is characterized by impaired alveolar development and complicated by pulmonary hypertension (PHT. Currently there is no specific treatment for BPD. Hydrogen sulfide (H2S, carbon monoxide and nitric oxide (NO, belong to a class of endogenously synthesized gaseous molecules referred to as gasotransmitters. While inhaled NO is already used for the treatment of neonatal PHT and currently tested for the prevention of BPD, H2S has until recently been regarded exclusively as a toxic gas. Recent evidence suggests that endogenous H2S exerts beneficial biological effects, including cytoprotection and vasodilatation. We hypothesized that H2S preserves normal alveolar development and prevents PHT in experimental BPD. METHODS: We took advantage of a recently described slow-releasing H2S donor, GYY4137 (morpholin-4-ium-4-methoxyphenyl(morpholino phosphinodithioate to study its lung protective potential in vitro and in vivo. RESULTS: In vitro, GYY4137 promoted capillary-like network formation, viability and reduced reactive oxygen species in hyperoxia-exposed human pulmonary artery endothelial cells. GYY4137 also protected mitochondrial function in alveolar epithelial cells. In vivo, GYY4137 preserved and restored normal alveolar growth in rat pups exposed from birth for 2 weeks to hyperoxia. GYY4137 also attenuated PHT as determined by improved pulmonary arterial acceleration time on echo-Doppler, pulmonary artery remodeling and right ventricular hypertrophy. GYY4137 also prevented pulmonary artery smooth muscle cell proliferation. CONCLUSIONS: H2S protects from impaired alveolar growth and PHT in experimental O2-induced lung injury. H2S warrants further investigation as a new therapeutic target for alveolar damage and PHT.

  1. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2009-06-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  2. Impact of the Oral Commensal Flora on Alveolar Bone Homeostasis

    OpenAIRE

    Irie, K; Novince, C.M.; Darveau, R. P.

    2014-01-01

    Homeostasis of healthy periodontal tissues is affected by innate and adaptive immunosurveillance mechanisms in response to the normal oral flora. Recent comparisons of germ-free (GF) and normal specific-pathogen-free (SPF) mice have revealed the impact of host immunosurveillance mechanisms in response to the normal oral flora on alveolar bone height. Prior reports that alveolar bone height is significantly less in normal SPF mice compared with their age- and strain-matched GF counterparts sug...

  3. Modified Dento - Alveolar Distraction Osteogenesis Technique for Rapid Canine Retraction

    Directory of Open Access Journals (Sweden)

    Sameer Patil

    2012-01-01

    Full Text Available Distraction Osteogenesis claims to reduce the duration of treatment as well aid in conservation of anchorage. With the introduction of Dento- alveolar distraction retraction of canine can now be done in about 2-3 weeks with minimal loss of anchorage and little/no root resorption. However, surgical procedure required for dento-alveolar distraction can cause significant swelling and post operative discomfort. Our small modification in the surgical procedure drastically reduces the discomfort and improves patient compliance.

  4. Modified Dento - Alveolar Distraction Osteogenesis Technique for Rapid Canine Retraction

    OpenAIRE

    Sameer Patil; Sharadindu Kotrashetti; Sumit Yadev; Ketan Vhora

    2012-01-01

    Distraction Osteogenesis claims to reduce the duration of treatment as well aid in conservation of anchorage. With the introduction of Dento- alveolar distraction retraction of canine can now be done in about 2-3 weeks with minimal loss of anchorage and little/no root resorption. However, surgical procedure required for dento-alveolar distraction can cause significant swelling and post operative discomfort. Our small modification in the surgical procedure drastically reduces the discomfort an...

  5. Alveolar lymphangioma in infants: report of two cases.

    LENUS (Irish Health Repository)

    FitzGerald, Kirsten

    2012-02-01

    The alveolar lymphangioma is a benign but relatively rare condition found only in the oral cavities of black infants. Dentists practising in Ireland may be unaware of this condition due to its racial specificity. This paper presents two case reports of multiple alveolar lymphangiomas found in black infants in a children\\'s hospital in Ireland. The epidemiology, aetiology, clinical presentation, histology, and management options are discussed. The photographs should aid the practitioner in recognising these lesions.

  6. Dynamic thermal performance of alveolar brick construction system

    Energy Technology Data Exchange (ETDEWEB)

    Gracia, A. de; Castell, A.; Medrano, M. [GREA Innovacio Concurrent, Edifici CREA, Universitat de Lleida, Pere de Cabrera s/n, 25001 Lleida (Spain); Cabeza, L.F., E-mail: lcabeza@diei.udl.ca [GREA Innovacio Concurrent, Edifici CREA, Universitat de Lleida, Pere de Cabrera s/n, 25001 Lleida (Spain)

    2011-07-15

    Highlights: {yields} Even though U-value does not measure thermal inertia, it is the commonly used parameter. {yields} The thermal performance analysis of buildings must include the evaluation of transient parameters. {yields} Transient parameters of alveolar brick constructive system show good agreement with its low energy consumption. -- Abstract: Alveolar bricks are being introduced in building sector due to the simplicity of their construction system and to the elimination of the insulation material. Nevertheless, it is not clear if this new system is energetically efficient and which is its thermal behaviour. This paper presents an experimental and theoretical study to evaluate the thermal behaviour of the alveolar brick construction system, compared with a traditional Mediterranean brick system with insulation. The experimental study consists of measuring the thermal performance of four real house-like cubicles. The thermal transmittance in steady-state, also known as U-value, is calculated theoretically and experimentally for each cubicle, presenting the insulated cubicles as the best construction system, with differences around 45% in comparison to the alveolar one. On the other hand, experimental results show significantly smaller differences on the energy consumption between the alveolar and insulated construction systems during summer period (around 13% higher for the alveolar cubicle). These values demonstrate the high thermal efficiency of the alveolar system. In addition, the lack of agreement between the measured energy consumption and the calculated U-values, guides the authors to analyze the thermal inertia of the different building components. Therefore, several transient parameters, extracted from the heat transfer matrix and from experimental data, are also evaluated. It can be concluded that the alveolar brick construction system presents higher thermal inertia than the insulated one, justifying the low measured energy consumption.

  7. Neutrophil-induced injury of rat pulmonary alveolar epithelial cells.

    OpenAIRE

    Simon, R H; DeHart, P D; Todd, R F

    1986-01-01

    The damage to pulmonary alveolar epithelial cells that occurs in many inflammatory conditions is thought to be caused in part by phagocytic neutrophils. To investigate this process, we exposed monolayers of purified rat alveolar epithelial cells to stimulated human neutrophils and measured cytotoxicity using a 51Cr-release assay. We found that stimulated neutrophils killed epithelial cells by a process that did not require neutrophil-generated reactive oxygen metabolites. Pretreatment of neut...

  8. Anaesthetic management of bilateral alveolar proteinosis for bronchopulmonary lavage.

    Directory of Open Access Journals (Sweden)

    Dixit R

    1998-01-01

    Full Text Available The most hazardous manifestation of pulmonary alveolar proteinosis is progressive hypoxia for which bronchopulmonary lavage (BPL is the single most effective treatment. Unfortunately this procedure under general anesthesia itself increases the risk of hypoxia due to the need for one lung ventilation. It was therefore considered interesting to report the successful anaesthetic management of a patient with pulmonary alveolar proteinosis for Bronchopulmonary lavage.

  9. Horizontal alveolar bone loss: A periodontal orphan

    Directory of Open Access Journals (Sweden)

    Jayakumar A

    2010-01-01

    Full Text Available Background: Attempts to successfully regenerate lost alveolar bone have always been a clinician′s dream. Angular defects, at least, have a fairer chance, but the same cannot be said about horizontal bone loss. The purpose of the present study was to evaluate the prevalence of horizontal alveolar bone loss and vertical bone defects in periodontal patients; and later, to correlate it with the treatment modalities available in the literature for horizontal and vertical bone defects. Materials and Methods: The study was conducted in two parts. Part I was the radiographic evaluation of 150 orthopantomographs (OPGs (of patients diagnosed with chronic periodontitis and seeking periodontal care, which were digitized and read using the AutoCAD 2006 software. All the periodontitis-affected teeth were categorized as teeth with vertical defects (if the defect angle was ≤45° and defect depth was ≥3 mm or as having horizontal bone loss. Part II of the study comprised search of the literature on treatment modalities for horizontal and vertical bone loss in four selected periodontal journals. Results: Out of the 150 OPGs studied, 54 (36% OPGs showed one or more vertical defects. Totally, 3,371 teeth were studied, out of which horizontal bone loss was found in 3,107 (92.2% teeth, and vertical defects were found only in 264 (7.8% of the teeth, which was statistically significant (P<.001. Search of the selected journals revealed 477 papers have addressed the treatment modalities for vertical and horizontal types of bone loss specifically. Out of the 477 papers, 461 (96.3% have addressed vertical bone loss, and 18 (3.7% have addressed treatment options for horizontal bone loss. Two papers have addressed both types of bone loss and are included in both categories. Conclusion: Horizontal bone loss is more prevalent than vertical bone loss but has been sidelined by researchers as very few papers have been published on the subject of regenerative treatment

  10. Infection-related mental and inferior alveolar nerve paresthesia: literature review and presentation of two cases.

    Science.gov (United States)

    Morse, D R

    1997-07-01

    A review of the literature on infection-related mental and inferior alveolar nerve paresthesia is given. This is followed by 2 case reports. The first case is of a mandibular left second molar in which a chloropercha overfill puff occurred in the vicinity of the inferior alveolar canal. The tooth remained asymptomatic until 2 and 1/2 yr later, when the periapical lesion enlarged and swelling, pain, and paresthesia developed. The paresthesia resolved 2 weeks following periapical surgery. The second case is of a mandibular right first premolar in which paresthesia began 1 day after the initial endodontic treatment. The intracanal medication was formocresol on a cotton pellet that was squeezed dry. The paresthesia was treated by irrigation, antibiotics, and dexamethasone. The paresthesia lasted 7 weeks, and when it resolved the root canal was filled with gutta-percha/eucapercha. Almost 9 months later, the tooth remained asymptomatic.

  11. MicroRNAs: Potential Biomarkers and Therapeutic Targets for Alveolar Bone Loss in Periodontal Disease

    Directory of Open Access Journals (Sweden)

    Tadayoshi Kagiya

    2016-08-01

    Full Text Available Periodontal disease is an inflammatory disease caused by bacterial infection of tooth-supporting structures, which results in the destruction of alveolar bone. Osteoclasts play a central role in bone destruction. Osteoclasts are tartrate-resistant acid phosphatase (TRAP-positive multinucleated giant cells derived from hematopoietic stem cells. Recently, we and other researchers revealed that microRNAs are involved in osteoclast differentiation. MicroRNAs are novel, single-stranded, non-coding, small (20–22 nucleotides RNAs that act in a sequence-specific manner to regulate gene expression at the post-transcriptional level through cleavage or translational repression of their target mRNAs. They regulate various biological activities such as cellular differentiation, apoptosis, cancer development, and inflammatory responses. In this review, the roles of microRNAs in osteoclast differentiation and function during alveolar bone destruction in periodontal disease are described.

  12. Decoronation of an ankylosed tooth for preservation of alveolar bone prior to implant placement.

    Science.gov (United States)

    Filippi, A; Pohl, Y; von Arx, T

    2001-04-01

    A 12-year-old patient sustained avulsions of both permanent maxillary central incisors. Subsequently, both teeth developed replacement resorption. The left incisor was extracted alio loco. The right incisor was treated by decoronation (removal of crown and pulp, but preservation of the root substance). Comparison of both sites demonstrated complete preservation of the height and width of the alveolar bone at the decoronation site, whereas the tooth extraction site showed considerable bone loss. In addition, some vertical bone apposition was found on top of the decoronated root. Decoronation is a simple and safe surgical procedure for preservation of alveolar bone prior to implant placement. It must be considered as a treatment option for teeth affected by replacement resorption if tooth transplantation is not feasible.

  13. MicroRNA-146a inhibits glioma development by targeting Notch1.

    Science.gov (United States)

    Mei, Jie; Bachoo, Robert; Zhang, Chun-Li

    2011-09-01

    Dysregulated epidermal growth factor receptor (EGFR) signaling through either genomic amplification or dominant-active mutation (EGFR(vIII)), in combination with the dual inactivation of INK4A/ARF and PTEN, is a leading cause of gliomagenesis. Our global expression analysis for microRNAs revealed that EGFR activation induces miR-146a expression, which is further potentiated by inactivation of PTEN. Unexpectedly, overexpression of miR-146a attenuates the proliferation, migration, and tumorigenic potential of Ink4a/Arf(-/-) Pten(-/-) Egfr(vIII) murine astrocytes. Its ectopic expression also inhibits the glioma development of a human glioblastoma cell line in an orthotopic xenograft model. Such an inhibitory function of miR-146a on gliomas is largely through downregulation of Notch1, which plays a key role in neural stem cell maintenance and is a direct target of miR-146a. Accordingly, miR-146a modulates neural stem cell proliferation and differentiation and reduces the formation and migration of glioma stem-like cells. Conversely, knockdown of miR-146a by microRNA sponge upregulates Notch1 and promotes tumorigenesis of malignant astrocytes. These findings indicate that, in response to oncogenic cues, miR-146a is induced as a negative-feedback mechanism to restrict tumor growth by repressing Notch1. Our results provide novel insights into the signaling pathways that link neural stem cells to gliomagenesis and may lead to new strategies for treating brain tumors.

  14. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

    Science.gov (United States)

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F.; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  15. Lung vasculitis and alveolar hemorrhage: pathology.

    Science.gov (United States)

    Fishbein, Gregory A; Fishbein, Michael C

    2011-06-01

    Pulmonary vasculitides are a diverse group of limited and systemic disorders associated with inflammation of pulmonary vessels and parenchyma. These diseases often have distinctive clinical, serological, and histopathological features-extrapulmonary sites of involvement, circulating autoantibodies, predispositions for small or large vessels, and others. Some have characteristic inflammatory lesions; others are characterized by the absence of such lesions. Frequently pathological findings overlap, rendering classification, and diagnosis a challenge. The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel diseases constitute the major pulmonary vasculitides. These include Wegener granulomatosis (WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Less frequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Behçet syndrome, and connective tissue diseases may involve pulmonary vessels, but these entities are better associated with extrapulmonary disease. Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonary vasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA and WG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Schönlein purpura, and systemic lupus erythematosus. Less commonly, DAH may be secondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemic disease, DAH may be idiopathic-referred to as isolated pulmonary capillaritis (IPC) or idiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis.

  16. Treatment with AICAR inhibits blastocyst development, trophectoderm differentiation and tight junction formation and function in mice.

    Science.gov (United States)

    Calder, Michele D; Edwards, Nicole A; Betts, Dean H; Watson, Andrew J

    2017-09-13

    What is the impact of adenosine monophosphate-activated protein kinase (AMPK) activation on blastocyst formation, gene expression, and tight junction formation and function? AMPK activity must be tightly controlled for normal preimplantation development and blastocyst formation to occur. AMPK isoforms are detectable in oocytes, cumulus cells and preimplantation embryos. Cultured embryos are subject to many stresses that can activate AMPK. Two primary experiments were carried out to determine the effect of AICAR treatment on embryo development and maintenance of the blastocoel cavity. Embryos were recovered from superovulated mice. First, 2-cell embryos were treated with a concentration series (0-2000 μM) of AICAR for 48 h until blastocyst formation would normally occur. In the second experiment, expanded mouse blastocysts were treated for 9 h with 1000 μM AICAR. Outcomes measured included development to the blastocyst stage, cell number, blastocyst volume, AMPK phosphorylation, Cdx2 and blastocyst formation gene family expression (mRNAs and protein measured using quantitative RT-PCR, immunoblotting, immunofluorescence), tight junction function (FITC dextran dye uptake assay), and blastocyst ATP levels. The reversibility of AICAR treatment was assessed using Compound C (CC), a well-known inhibitor of AMPK, alone or in combination with AICAR. Prolonged treatment with AICAR from the 2-cell stage onward decreases blastocyst formation, reduces total cell number, embryo diameter, leads to loss of trophectoderm cell contacts and membrane zona occludens-1 staining, and increased nuclear condensation. Treatment with CC alone inhibited blastocyst development only at concentrations that are higher than normally used. AICAR treated embryos displayed altered mRNA and protein levels of blastocyst formation genes. Treatment of blastocysts with AICAR for 9 h induced blastocyst collapse, altered blastocyst formation gene expression, increased tight junction permeability and

  17. Inhibitory effects of French pine bark extract, Pycnogenol®, on alveolar bone resorption and on the osteoclast differentiation.

    Science.gov (United States)

    Sugimoto, Hideki; Watanabe, Kiyoko; Toyama, Toshizo; Takahashi, Shun-suke; Sugiyama, Shuta; Lee, Masaichi-Chang-il; Hamada, Nobushiro

    2015-02-01

    Pycnogenol(®) (PYC) is a standardized bark extract from French maritime pine (Pinus pinaster Aiton). We examined the inhibitory effects of PYC on alveolar bone resorption, which is a characteristic feature of periodontitis, induced by Porphyromonas gingivalis (P. gingivalis) and osteoclast differentiation. In rat periodontitis model, rats were divided into four groups: group A served as the non-infected control, group B was infected orally with P. gingivalis ATCC 33277, group C was administered PYC in the diet (0.025%: w/w), and group D was infected with P. gingivalis and administered PYC. Administration of PYC along with P. gingivalis infection significantly reduced alveolar bone resorption. Treatment of P. gingivalis with 1 µg/ml PYC reduced the number of viable bacterial cells. Addition of PYC to epithelial cells inhibited adhesion and invasion by P. gingivalis. The effect of PYC on osteoclast formation was confirmed by tartrate-resistant acid phosphatase staining. PYC treatment significantly inhibited osteoclast formation. Addition of PYC (1-100 µg/ml) to purified osteoclasts culture induced cell apoptosis. These results suggest that PYC may prevent alveolar bone resorption through its antibacterial activity against P. gingivalis and by suppressing osteoclastogenesis. Therefore, PYC may be useful as a therapeutic and preventative agent for bone diseases such as periodontitis.

  18. Killing of Klebsiella pneumoniae by human alveolar macrophages.

    Science.gov (United States)

    Hickman-Davis, Judy M; O'Reilly, Philip; Davis, Ian C; Peti-Peterdi, Janos; Davis, Glenda; Young, K Randall; Devlin, Robert B; Matalon, Sadis

    2002-05-01

    We investigated putative mechanisms by which human surfactant protein A (SP-A) effects killing of Klebsiella pneumoniae by human alveolar macrophages (AMs) isolated from bronchoalveolar lavagates of patients with transplanted lungs. Coincubation of AMs with human SP-A (25 microg/ml) and Klebsiella resulted in a 68% decrease in total colony forming units by 120 min compared with AMs infected with Klebsiella in the absence of SP-A, and this SP-A-mediated effect was abolished by preincubation with N(G)-monomethyl-L-arginine. Incubation of transplant AMs with SP-A increased intracellular Ca(2+) concentration ([Ca(2+)](i)) by 70% and nitrite and nitrate (NO(x)) production by 45% (from 0.24 +/- 0.02 to 1.3 +/- 0.21 nmol small middle dot 10(6) AMs(-1).h(-1)). Preincubation with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester inhibited the increase in [Ca(2+)](i) and abrogated the SP-A-mediated Klebsiella phagocytosis and killing. In contrast, incubation of AMs from normal volunteers with SP-A decreased both [Ca(2+)](i) and NO(x) production and did not result in killing of Klebsiella. Significant killing of Klebsiella was also seen in a cell-free system by sustained production of peroxynitrite (>1 microM/min) at pH 5 but not at pH 7.4. These findings indicate that SP-A mediates pathogen killing by AMs from transplant lungs by stimulating phagocytosis and production of reactive oxygen-nitrogen intermediates.

  19. Identification of Goodpasture antigens in human alveolar basement membrane.

    Science.gov (United States)

    Yoshioka, K; Iseki, T; Okada, M; Morimoto, Y; Eryu, N; Maki, S

    1988-01-01

    Goodpasture (GP) antigens, protein components reactive with human autoantibodies against glomerular basement membrane (GBM), were identified in human alveolar basement membrane (ABM) using an enzyme-linked immunoassay (ELISA), Western blotting and immunoprecipitation. All six anti-GBM antisera studied, three obtained from patients with glomerulonephritis and pulmonary haemorrhages (i.e. GP syndrome), and three from patients with glomerulonephritis alone, distinctively reacted with collagenase-digested (CD) ABM. Very cationic 22-28 kD and 40-48 kD components were detected by blot analysis combined with two-dimensional gel electrophoresis. These proteins showed some similarities to GP antigens in human GBM with respect to the monomer-dimer composition and charge distribution. Inhibition ELISA revealed that the binding of anti-GBM antisera to CDGBM decreased when they were pre-incubated with CDABM, suggesting that the anti-GBM antisera recognized the same epitope(s) on the GBM and ABM. Heterogeneity of the GP antigens in human ABM was demonstrated by blotting; monomeric antigens were absent or at low levels in the CDABM of three out of 10 normal individuals. In immunoprecipitation, anti-GBM antisera from patients with and without pulmonary haemorrhage showed different reactivities with CDABM. The former antisera precipitated both monomeric and dimeric components, but the latter did not. The observations of variation in monomer-dimer composition of ABM, and the different binding of anti-GBM antisera to it may explain why only some patients with anti-GBM nephritis have lung involvement. Images Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:2466590

  20. Latent inhibition in the developing rat: an examination of context-specific effects.

    Science.gov (United States)

    Yap, Carol S L; Richardson, Rick

    2005-07-01

    Latent inhibition (LI) refers to the reduction in conditioned responding when the conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor-shock pairings markedly reduced conditioned freezing in 25-day-old rats; however, this LI effect was observed only if odor preexposure and odor-shock pairings occurred in the same context (i.e., LI was context-specific at this age). The results of Experiment 1b showed that 18-day-olds also exhibited LI, but this effect was not context-specific at this age. In Experiment 2, rats were preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days of age. These rats exhibited context-specific latent inhibition, suggesting that 18-day-old rats encoded the preexposure context. In Experiment 3, all parameters were identical to Experiment 2, with the exception that odor-shock pairings were given at approximately PN18 and testing occurred at approximately PN25. These rats exhibited latent inhibition at test, but this effect was not context-specific. The results of this study suggest that (a) PN18 rats can exhibit latent inhibition, and (b) the expression of context-specific latent inhibition depends on the age at which conditioning occurs.

  1. Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms.

    Science.gov (United States)

    Bridge, Katherine; Revill, Charlotte; Macrae, Fraser; Bailey, Marc; Yuldasheva, Nadira; Wheatcroft, Stephen; Butlin, Roger; Foster, Richard; Scott, D Julian; Gils, Ann; Ariens, Robert

    2017-01-01

    Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression.

  2. Coffee and its waste repel gravid Aedes albopictus females and inhibit the development of their embryos.

    Science.gov (United States)

    Satho, Tomomitsu; Dieng, Hamady; Ahmad, Muhammad Hishamuddin Itam; Ellias, Salbiah Binti; Hassan, Ahmad Abu; Abang, Fatimah; Ghani, Idris Abd; Miake, Fumio; Ahmad, Hamdan; Fukumitsu, Yuki; Zuharah, Wan Fatma; Majid, Abdul Hafiz Ab; Kassim, Nur Faeza Abu; Hashim, Nur Aida; Ajibola, Olaide Olawunmi; Al-Khayyat, Fatima Abdulla; Nolasco-Hipolito, Cirilo

    2015-05-14

    Dengue is a prevalent arboviral disease and the development of insecticide resistance among its vectors impedes endeavors to control it. Coffee is drunk by millions of people daily worldwide, which is associated with the discarding of large amounts of waste. Coffee and its waste contain large amounts of chemicals many of which are highly toxic and none of which have a history of resistance in mosquitoes. Once in solution, coffee is brownish in colour, resembling leaf infusion, which is highly attractive to gravid mosquitoes. To anticipate the environmental issues related to the increasing popularity of coffee as a drink, and also to combat insecticide resistance, we explored the deterrence potentials of coffee leachates against the ovipositing and embryonic stages of the dengue vector, Aedes albopictus. In a series of choice, no-choice, and embryo toxicity bioassays, we examined changes in the ovipositional behaviours and larval eclosion of Ae. albopictus in response to coffee extracts at different concentrations. Oviposition responses were extremely low when ovicups holding highly concentrated extract (HCE) of coffee were the only oviposition sites. Gravid females retained increased numbers of mature eggs until 5 days post-blood feeding. When provided an opportunity to oviposit in cups containing coffee extracts and with water, egg deposition occurred at lower rates in those containing coffee, and HCE cups were far less attractive to females than those containing water only. Females that successfully developed in a coffee environment preferentially oviposited in such cups when in competition with preferred oviposition sites (water cups), but this trait did not continue into the fourth generation. Larval eclosion occurred at lower rates among eggs that matured in a coffee environment, especially among those that were maintained on HCE-moistened substrates. The observations of the present study indicate a pronounced vulnerability of Ae. albopictus to the presence

  3. An ultra fast detection method reveals strain-induced Ca(2+) entry via TRPV2 in alveolar type II cells.

    Science.gov (United States)

    Fois, Giorgio; Wittekindt, Oliver; Zheng, Xing; Felder, Erika Tatiana; Miklavc, Pika; Frick, Manfred; Dietl, Paul; Felder, Edward

    2012-09-01

    A commonly used technique to investigate strain-induced responses of adherent cells is culturing them on an elastic membrane and globally stretching the membrane. However, it is virtually impossible to acquire microscopic images immediately after the stretch with this method. Using a newly developed technique, we recorded the strain-induced increase of the cytoplasmic Ca(2+) concentration ([Ca(2+)](c)) in rat primary alveolar type II (ATII) cells at an acquisition rate of 30ms and without any temporal delay. We can show that the onset of the mechanically induced rise in [Ca(2+)](c) was very fast (<30 ms), and Ca(2+) entry was immediately abrogated when the stimulus was withdrawn. This points at a direct mechanical activation of an ion channel. RT-PCR revealed high expression of TRPV2 in ATII cells, and silencing TRPV2, as well as blocking TRPV channels with ruthenium red, significantly reduced the strain-induced Ca(2+) response. Moreover, the usually homogenous pattern of the strain-induced [Ca(2+)](c) increase was converted into a point-like response after both treatments. Also interfering with actin/myosin and integrin binding inhibited the strain-induced increase of [Ca(2)](c). We conclude that TRPV2 participates in strain-induced Ca(2+) entry in ATII cells and suggest a direct mechanical activation of the channel that depends on FAs and actin/myosin. Furthermore, our results underline the importance of cell strain systems that allow high temporal resolution.

  4. Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila

    Directory of Open Access Journals (Sweden)

    Ilaria Drago

    2016-09-01

    Full Text Available The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn—a brain region critical for olfactory memory formation—causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism.

  5. Inorganic lead may inhibit neurite development in cultured rat hippocampal neurons through hyperphosphorylation.

    Science.gov (United States)

    Kern, M; Audesirk, G

    1995-09-01

    Inorganic lead inhibits neurite initiation in cultured rat hippocampal neurons at concentrations as low as 100 nM. Conflicting reports suggest that Pb2+ may stimulate or inhibit protein kinase C, adenylyl cyclase, phosphodiesterase, and calmodulin, or increase intracellular free Ca2+ concentrations. Therefore, Pb2+ may alter the activities of Ca2+/calmodulin-dependent protein kinase (CaM kinase) or protein kinases C or A. We cultured rat hippocampal neurons in 100 nM PbCI2 alone or in combination with kinase or calmodulin inhibitors. Inhibiting protein kinase C with calphostin C exacerbated the inhibition of neurite initiation caused by PbCI2, but inhibiting protein kinase A with KT5720, CaM kinase with KN62, or calmodulin with calmidazolium completely reversed the effects of PbCI2. These results indicate that Pb2+ may inhibit neurite initiation by inappropriately stimulating protein phosphorylation by CaM kinase or cyclic AMP-dependent protein kinase (PKA), possibly by stimulating calmodulin. This hypothesis is supported by findings that other treatments that should increase protein phosphorylation (okadaic acid, a protein phosphatase inhibitor, and Sp-cAMPS, a PKA activator) also reduced neurite initiation. Whole-cell intracellular free Ca2+ ion concentrations were not significantly altered by 100 nM PbCI2 at 4, 12, 24, or 48 hr. Therefore, the hypothesized stimulatory effects of Pb2+ exposure on calmodulin, CaM kinase, or PKA are probably not caused by increases in whole-cell intracellular free Ca2+, but may be attributable either to intracellular Pb2+ or to localized increases in [Ca2+]in that are not reflected in whole-cell measurements.

  6. Dissolution of beryllium in artificial lung alveolar macrophage phagolysosomal fluid.

    Science.gov (United States)

    Stefaniak, Aleksandr B; Virji, M Abbas; Day, Gregory A

    2011-05-01

    Dissolution of a lung burden of poorly soluble beryllium particles is hypothesized to be necessary for development of chronic beryllium lung disease (CBD) in humans. As such, particle dissolution rate must be sufficient to activate the lung immune response and dissolution lifetime sufficient to maintain chronic inflammation for months to years to support development of disease. The purpose of this research was to investigate the hypothesis that poorly soluble beryllium compounds release ions via dissolution in lung fluid. Dissolution kinetics of 17 poorly soluble particulate beryllium materials that span extraction through ceramics machining (ores, hydroxide, metal, copper-beryllium [CuBe] fume, oxides) and three CuBe alloy reference materials (chips, solid block) were measured over 31 d using artificial lung alveolar macrophage phagolysosomal fluid (pH 4.5). Differences in beryllium-containing particle physicochemical properties translated into differences in dissolution rates and lifetimes in artificial phagolysosomal fluid. Among all materials, dissolution rate constant values ranged from 10(-5) to 10(-10)gcm(-2)d(-1) and half-times ranged from tens to thousands of days. The presence of magnesium trisilicate in some beryllium oxide materials may have slowed dissolution rates. Materials associated with elevated prevalence of CBD had faster beryllium dissolution rates [10(-7)-10(-8)gcm(-2)d(-1)] than materials not associated with elevated prevalence (p<0.05).

  7. Distracción osteogénica alveolar como método de aumento del reborde alveolar Alveolar osteogenic distraction as method to increase the alveolar ridge

    Directory of Open Access Journals (Sweden)

    Denia Morales Navarro

    2011-03-01

    Full Text Available La distracción osteogénica alveolar, como proceso biológico de neoformación de hueso alveolar, nos motivó a la realización de la presente revisión bibliográfica, con el objetivo enfatizar en el análisis de las variables: antecedentes históricos en Cuba, clasificación de los distractores, fases de la distracción (latencia, distracción y consolidación, indicaciones, contraindicaciones, ventajas, desventajas y complicaciones. Se realizó una revisión bibliográfica mediante la consulta de bases de datos de los sistemas referativos, como MEDLINE y PubMed con la utilización de descriptores "alveolar distraction" y "osteogenic distraction". Se consultaron las fuentes bibliográficas publicadas fundamentalmente en los últimos 5 años, lo que reveló que esta técnica es una excelente alternativa para la formación de huesos y tejidos blandos en zonas de atrofia alveolar, que consta de tres etapas: latencia, distracción y consolidación; un método previsible y con bajas tasas de reabsorción ósea en comparación con otras técnicas de aumento del reborde alveolar. Tiene su principal indicación en la terapia de implantes al proveer volumen óseo. Debemos individualizar cada caso y usar el método más adecuado según las características clínicas y personales del paciente. Una adecuada selección de los casos y una mejor comprensión de la técnica son los puntales para lograr exitosos resultados mediante la distracción osteogénica alveolar. En Cuba se ha aplicado poco la distracción alveolar, por lo que ha sido necesario ampliar los estudios sobre esta temática.The alveolar osteogenic distraction, as a biological process of alveolar bone neoformation, motivates us to make the bibliographic review whose objective was to emphasize in analysis the following variables: historical backgrounds in Cuba, distraction classification, distraction phases (latency, distraction and consolidation, indications, contraindications, advantages

  8. Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection.

    Science.gov (United States)

    Madeira, Mila F M; Queiroz-Junior, Celso M; Montero-Melendez, Trinidad; Werneck, Silvia M C; Corrêa, Jôice D; Soriani, Frederico M; Garlet, Gustavo P; Souza, Daniele G; Teixeira, Mauro M; Silva, Tarcilia A; Perretti, Mauro

    2016-12-01

    Alveolar bone loss is a result of an aggressive form of periodontal disease (PD) associated with Aggregatibacter actinomycetemcomitans (Aa) infection. PD is often observed with other systemic inflammatory conditions, including arthritis. Melanocortin peptides activate specific receptors to exert antiarthritic properties, avoiding excessing inflammation and modulating macrophage function. Recent work has indicated that melanocortin can control osteoclast development and function, but whether such protection takes place in infection-induced alveolar bone loss has not been investigated. The purpose of this study was to evaluate the role of melanocortin in Aa-induced PD. Mice were orally infected with Aa and treated with the melanocortin analog DTrp(8)-γMSH or vehicle daily for 30 d. Then, periodontal tissue was collected and analyzed. Aa-infected mice treated with DTrp(8)-γMSH presented decreased alveolar bone loss and a lower degree of neutrophil infiltration in the periodontium than vehicle-treated animals; these actions were associated with reduced periodontal levels of TNF-α, IFN-γ, and IL-17A. In vitro experiments with cells differentiated into osteoclasts showed that osteoclast formation and resorptive activity were attenuated after treatment with DTrp(8)-γMSH. Thus, melanocortin agonism could represent an innovative way to tame overexuberant inflammation and, at the same time, preserve bone physiology, as seen after Aa infection.-Madeira, M. F. M., Queiroz-Junior, C. M., Montero-Melendez, T., Werneck, S. M. C., Corrêa, J. D., Soriani, F. M., Garlet, G. P., Souza, D. G., Teixeira, M. M., Silva, T. A., Perretti, M. Melanocortin agonism as a viable strategy to control alveolar bone loss induced by oral infection. © FASEB.

  9. Diminished Alveolar Microvascular Reserves in Type 2 Diabetes Reflect Systemic Microangiopathy

    Science.gov (United States)

    Chance, William W.; Rhee, Chanhaeng; Yilmaz, Cuneyt; Dane, D. Merrill; Pruneda, M. Lourdes; Raskin, Philip; Hsia, Connie C.W.

    2008-01-01

    OBJECTIVE—Alveolar microvascular function is moderately impaired in type 1 diabetes, as manifested by restriction of lung volume and diffusing capacity (DLCO). We examined whether similar impairment develops in type 2 diabetes and defined the physiologic sources of impairment as well as the relationships to glycemia and systemic microangiopathy. RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted at a university-affiliated diabetes treatment center and outpatient diabetes clinic, involving 69 nonsmoking type 2 diabetic patients without overt cardiopulmonary disease. Lung volume, pulmonary blood flow (Q̇), DLCO, membrane diffusing capacity (measured from nitric oxide uptake [DLNO]), and pulmonary capillary blood volume (VC) were determined at rest and exercise for comparison with those in 45 healthy nonsmokers as well as with normal reference values. RESULTS—In type 2 diabetic patients, peak levels of oxygen uptake, Q̇ and DLCO, DLNO, and VC at exercise were 10–25% lower compared with those in control subjects. In nonobese patients (BMI DLNO, and VC were fully explained by the lower lung volume and peak Q̇, but these factors did not fully explain the impairment in obese patients (BMI >30 kg/m2). The slope of the increase in VC with respect to Q̇ was reduced ∼20% in patients regardless of BMI, consistent with impaired alveolar-capillary recruitment. Functional impairment was directly related to A1C level, retinopathy, neuropathy, and microalbuminuria in a sex-specific manner. CONCLUSIONS—Alveolar microvascular reserves are reduced in type 2 diabetes, reflecting restriction of lung volume, alveolar perfusion, and capillary recruitment. This reduction correlates with glycemic control and extrapulmonary microangiopathy and is aggravated by obesity. PMID:18492945

  10. Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats

    Institute of Scientific and Technical Information of China (English)

    WANG Zong-yu; WU Sheng-nan; ZHU Zhao-zhong; YANG Ba-xian; ZHU Xi

    2013-01-01

    Background Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation,but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response,anticoagulant inhibition,fibrinolytic supression and fibrin deposition.We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces,it could block the procoagulant tendency,lessen depletion of coagulation factors,and even influence the inflammatory response.We also assessed the effects of different administration regimens of heparin.Methods Male Wistar rats were given inhaled heparin starting 30 minutes before (prophylactic heparin) or 2 hours after (therapeutic heparin) intravenous lipopolysaccharide (LPS) was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS.Thrombin-antithrombin complexes,activated protein C,tissue type and urokinase type plasminogen activators (t-PNu-PA),plasminogen activator inhibitor-1 (PAl-1),tumor necrosis factor-α,interleukin-6 in bronchoalveolar lavage,and lung tissue myeloperoxidase activity,and histology score were measured at three time-points.PAI-1/(t-PA + u-PA) was calculated based on the before-mentioned parameters.Statistical analysis was made using one-way analysis of variance (ANOVA) with post hoc test or Student's t test in the case of heterogeneity of variance.Results An alveolar procoagulant reaction,depressed fibrinolysis,and inflammatory response occurred in endotoxemia-induced lung injury.Local prophylactic application of heparin attenuated coagulation and early inflammation,promoted fibrinolysis,and reduced the histology score.Therapeutic application of heparin had similar,but weaker effects.Conclusions Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response,promote flbrinolysis,and alleviate pulmonary pathology in endotoxemia

  11. Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD

    NARCIS (Netherlands)

    Hart, H.; Chantiluke, K.; Cubillo, A.I.; Smith, A.B.; Simmons, A.; Brammer, M.J.; Marquand, A.F.; Rubia, K.

    2014-01-01

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern clas

  12. 9-cis -carotene Inhibits Atherosclerosis Development in Female LDLR-/- Mice

    Directory of Open Access Journals (Sweden)

    Noa Zolberg Relevy

    2015-02-01

    Full Text Available Background: Several epidemiological studies have shown that diets rich in carotenoids are associated with a reduced risk of cardiovascular disease. However, administration of synthetic all-trans -carotene was reported to have no effect on cardiovascular disease. We previously showed that the 9-cis -carotene-rich powder of the alga Dunaliella bardawil inhibits atherogenesis and reduces plasma non-HDL cholesterol levels in mice. Context and purpose of this study: We sought to study whether isolated 9-cis -carotene inhibits atherogenesis in a murine model of atherosclerosis. Results: Twelve-week-old female LDL receptor knockout mice (LDLR-/- were pretreated for 2 weeks with regular chow diet fortified with the alga Dunaliella powder, 9-cis β-carotene isomer, all-trans β-carotene isomer, or 9-cis retinoic acid, followed by 10 weeks of a high-fat diet with the same fortifications. In contrast to Dunaliella, 9-cis β-carotene did not inhibit the high fat dietinduced elevation of plasma cholesterol. In addition, diet fortification with Dunaliella powder, β-carotene isomers, or 9-cis retinoic acid did not change the plasma retinol or retinoic acid levels.Nevertheless, 9-cis β-carotene significantly inhibited atherogenesis compared to the control mice (39% reduction. Conclusions: The results suggest that 9-cis β-carotene should be considered as an antiatherogenic agent in the human diet

  13. Estimation of the number of alveolar capillaries by the Euler number (Euler-Poincaré characteristic).

    Science.gov (United States)

    Willführ, Alper; Brandenberger, Christina; Piatkowski, Tanja; Grothausmann, Roman; Nyengaard, Jens Randel; Ochs, Matthias; Mühlfeld, Christian

    2015-12-01

    The lung parenchyma provides a maximal surface area of blood-containing capillaries that are in close contact with a large surface area of the air-containing alveoli. Volume and surface area of capillaries are the classic stereological parameters to characterize the alveolar capillary network (ACN) and have provided essential structure-function information of the lung. When loss (rarefaction) or gain (angiogenesis) of capillaries occurs, these parameters may not be sufficient to provide mechanistic insight. Therefore, it would be desirable to estimate the number of capillaries, as it contains more distinct and mechanistically oriented information. Here, we present a new stereological method to estimate the number of capillary loops in the ACN. One advantage of this method is that it is independent of the shape, size, or distribution of the capillaries. We used consecutive, 1 μm-thick sections from epoxy resin-embedded material as a physical disector. The Euler-Poincaré characteristic of capillary networks can be estimated by counting the easily recognizable topological constellations of "islands," "bridges," and "holes." The total number of capillary loops in the ACN can then be calculated from the Euler-Poincaré characteristic. With the use of the established estimator of alveolar number, it is possible to obtain the mean number of capillary loops per alveolus. In conclusion, estimation of alveolar capillaries by design-based stereology is an efficient and unbiased method to characterize the ACN and may be particularly useful for studies on emphysema, pulmonary hypertension, or lung development.

  14. Receptor-mediated endocytosis of macromolecules and strategy to enhance their transport in alveolar epithelial cells.

    Science.gov (United States)

    Takano, Mikihisa; Kawami, Masashi; Aoki, Ayako; Yumoto, Ryoko

    2015-05-01

    Pulmonary delivery is an attractive administration route for therapeutic proteins and peptides. In this context, endocytosis/transcytosis at the distal lung epithelial barrier is an important process in the pulmonary absorption of therapeutic macromolecules. The alveolar epithelium is comprised of type I and type II cells. Understanding the transport mechanisms in these cells is essential for the development of efficient pulmonary delivery systems of therapeutic macromolecules. Endocytic pathways for albumin and insulin in alveolar epithelial cells and possible receptors for the endocytosis are discussed. Strategies to enhance the endocytosis and pulmonary absorption of macromolecules are also discussed, by focusing on the effects of cationic poly(amino acid)s. Although the surface area occupied by type II cells in alveoli is much smaller than that covered by type I cells, type II cells may significantly contribute to the endocytosis/transcytosis of macromolecules such as albumin. Identification of the receptors involved in the cellular uptake of each macromolecule is prerequisite for the understanding and regulation of its transport into and across alveolar epithelial cells. Establishment of novel in-vitro culture cell models of type I and type II cells would be a great help for the future advance of this research field.

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

    Science.gov (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

    2016-02-01

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

  16. Bone Replacement Materials and Techniques Used for Achieving Vertical Alveolar Bone Augmentation

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh

    2015-05-01

    Full Text Available Alveolar bone augmentation in vertical dimension remains the holy grail of periodontal tissue engineering. Successful dental implant placement for restoration of edentulous sites depends on the quality and quantity of alveolar bone available in all spatial dimensions. There are several surgical techniques used alone or in combination with natural or synthetic graft materials to achieve vertical alveolar bone augmentation. While continuously improving surgical techniques combined with the use of auto- or allografts provide the most predictable clinical outcomes, their success often depends on the status of recipient tissues. The morbidity associated with donor sites for auto-grafts makes these techniques less appealing to both patients and clinicians. New developments in material sciences offer a range of synthetic replacements for natural grafts to address the shortcoming of a second surgical site and relatively high resorption rates. This narrative review focuses on existing techniques, natural tissues and synthetic biomaterials commonly used to achieve vertical bone height gain in order to successfully restore edentulous ridges with implant-supported prostheses.

  17. Alveolar Rhabdomyosarcoma in a 69-Year-Old Woman Receiving Glucagon-Like Peptide-2 Therapy

    Directory of Open Access Journals (Sweden)

    Laura E. Zyczynski

    2015-01-01

    Full Text Available A 69-year-old woman was diagnosed with alveolar rhabdomyosarcoma (ARMS of the nasopharynx. She has a history of catastrophic thromboembolic event in the abdomen that caused short-gut syndrome and dependence on total parenteral nutrition (TPN twelve hours per day. She was treated for short-gut syndrome with teduglutide, a glucagon-like peptide-2 (GLP-2 analog, which led to reduction of TPN requirements. However, a few months later, she developed metastatic alveolar rhabdomyosarcoma. Though a causative relationship is unlikely between the peptide and ARMS due to the brief time course between teduglutide therapy and sarcoma diagnosis, neoplastic growth may have been accelerated by the GLP-2 analog, causing release of IGF-1. The transmembrane receptor for IGF-1 is frequently overexpressed in ARMS and is implicated in cell proliferation and metastatic behavior. This case describes a rare incidence of metastatic alveolar rhabdomyosarcoma in a sexagenarian and possibly the first case reported associated with the use of teduglutide. Teduglutide was discontinued due to a potential theoretical risk of acceleration of sarcoma growth, and the patient’s rhabdomyosarcoma is in remission following sarcoma chemotherapy.

  18. Osteocytic Sclerostin Expression in Alveolar Bone in Rats With Diabetes Mellitus and Ligature-Induced Periodontitis.

    Science.gov (United States)

    Kim, Ji-Hye; Lee, Dong-Eun; Woo, Gye-Hyeong; Cha, Jeong-Heon; Bak, Eun-Jung; Yoo, Yun-Jung

    2015-08-01

    Osteocytic sclerostin inhibits bone formation, and its expression is stimulated by tumor necrosis factor (TNF)-α. This study investigates sclerostin and TNF-α expression in rats with diabetes mellitus (DM) and periodontitis. Rats were divided into control (C), periodontitis (P), and DM + periodontitis (DP) groups. After induction of DM by streptozotocin, periodontitis was induced by ligature. At day 0 (control) and at days 3 and 20 after induction of periodontitis, alveolar bone, osteoclasts, osteoid area, and TNF-α and sclerostin expression were evaluated. The distance between the cemento-enamel junction and the alveolar bone crest of the DP group was longer than that of the P group at day 20 after induction of periodontitis, but the number of osteoclasts was not different. Osteoid area decreased in both the P and DP groups by day 3, but whereas sustained osteoid suppression was observed in the DP group at day 20, osteoid formation was increased in the P group. The number of sclerostin-positive osteocytes increased in both groups at day 3, but the increased number of sclerostin-positive osteocytes was maintained only in the DP group through day 20. The number of TNF-α-positive cells increased more in the DP group than in the P group. Enhanced alveolar bone loss, suppressed bone formation, and prevalent TNF-α expression were characteristic of the DP group compared with the P group. Suppressed bone formation in the DP group was observed simultaneously with increased sclerostin and TNF-α expression. These results suggest that upregulated osteocytic sclerostin expression in periodontitis accompanied by DM may play a role in suppressed bone formation.

  19. A functional connection between pRB and transforming growth factor beta in growth inhibition and mammary gland development.

    Science.gov (United States)

    Francis, Sarah M; Bergsied, Jacqueline; Isaac, Christian E; Coschi, Courtney H; Martens, Alison L; Hojilla, Carlo V; Chakrabarti, Subrata; Dimattia, Gabriel E; Khoka, Rama; Wang, Jean Y J; Dick, Frederick A

    2009-08-01

    Transforming growth factor beta (TGF-beta) is a crucial mediator of breast development, and loss of TGF-beta-induced growth arrest is a hallmark of breast cancer. TGF-beta has been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-beta cytostatic signaling, pRB is thought to be dispensable for mammary development. Using gene-targeted mice carrying subtle missense changes in pRB (Rb1(DeltaL) and Rb1(NF)), we have discovered that pRB plays a critical role in mammary gland development. In particular, Rb1 mutant female mice have hyperplastic mammary epithelium and defects in nursing due to insensitivity to TGF-beta growth inhibition. In contrast with previous studies that highlighted the inhibition of cyclin/CDK activity by TGF-beta signaling, our experiments revealed that active transcriptional repression of E2F target genes by pRB downstream of CDKs is also a key component of TGF-beta cytostatic signaling. Taken together, our work demonstrates a unique functional connection between pRB and TGF-beta in growth control and mammary gland development.

  20. On the evolution of the pulmonary alveolar lipofibroblast.

    Science.gov (United States)

    Torday, John S; Rehan, Virender K

    2016-01-15

    The pulmonary alveolar lipofibroblast was first reported in 1970. Since then its development, structure, function and molecular characteristics have been determined. Its capacity to actively absorb, store and 'traffic' neutral lipid for protection of the alveolus against oxidant injury, and for the active supply of substrate for lung surfactant phospholipid production have offered the opportunity to identify a number of specialized functions of these strategically placed cells. Namely, Parathyroid Hormone-related Protein (PTHrP) signaling, expression of Adipocyte Differentiation Related Protein, leptin, peroxisome proliferator activator receptor gamma, and the prostaglandin E2 receptor EP2- which are all stretch-regulated, explaining how and why surfactant production is 'on-demand' in service to ventilation-perfusion matching. Because of the central role of the lipofibroblast in vertebrate lung physiologic evolution, it is a Rosetta Stone for understanding how and why the lung evolved in adaptation to terrestrial life, beginning with the duplication of the PTHrP Receptor some 300 mya. Moreover, such detailed knowledge of the workings of the lipofibroblast have provided insight to the etiology and effective treatment of Bronchopulmonary Dysplasia based on physiologic principles rather than on pharmacology.

  1. Mesodermal Pten inactivation leads to alveolar capillary dysplasia- like phenotype.

    Science.gov (United States)

    Tiozzo, Caterina; Carraro, Gianni; Al Alam, Denise; Baptista, Sheryl; Danopoulos, Soula; Li, Aimin; Lavarreda-Pearce, Maria; Li, Changgong; De Langhe, Stijn; Chan, Belinda; Borok, Zea; Bellusci, Saverio; Minoo, Parviz

    2012-11-01

    Alveolar capillary dysplasia (ACD) is a congenital, lethal disorder of the pulmonary vasculature. Phosphatase and tensin homologue deleted from chromosome 10 (Pten) encodes a lipid phosphatase controlling key cellular functions, including stem/progenitor cell proliferation and differentiation; however, the role of PTEN in mesodermal lung cell lineage formation remains unexamined. To determine the role of mesodermal PTEN in the ontogeny of various mesenchymal cell lineages during lung development, we specifically deleted Pten in early embryonic lung mesenchyme in mice. Pups lacking Pten died at birth, with evidence of failure in blood oxygenation. Analysis at the cellular level showed defects in angioblast differentiation to endothelial cells and an accompanying accumulation of the angioblast cell population that was associated with disorganized capillary beds. We also found decreased expression of Forkhead box protein F1 (Foxf1), a gene associated with the ACD human phenotype. Analysis of human samples for ACD revealed a significant decrease in PTEN and increased activated protein kinase B (AKT). These studies demonstrate that mesodermal PTEN has a key role in controlling the amplification of angioblasts as well as their differentiation into endothelial cells, thereby directing the establishment of a functional gas exchange interface. Additionally, these mice could serve as a murine model of ACD.

  2. HES6 enhances the motility of alveolar rhabdomyosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wickramasinghe, Caroline M [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); MRC Laboratory of Molecular Biology, Addenbrooke' s Hospital Cambridge, CB2 0QH (United Kingdom); Domaschenz, Renae [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN (United Kingdom); Amagase, Yoko [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women' s College of Liberal Arts, Kodo, Kyotanabe, Kyoto 610-0395 (Japan); Williamson, Daniel [Molecular Cytogenetics, The Institute of Cancer Research, Sutton SM2 5NG (United Kingdom); Northern Institute for Cancer Research, Paul O' Gorman Building, Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH (United Kingdom); Missiaglia, Edoardo; Shipley, Janet [Molecular Cytogenetics, The Institute of Cancer Research, Sutton SM2 5NG (United Kingdom); Murai, Kasumi [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom); Jones, Philip H, E-mail: phj20@cam.ac.uk [MRC Cancer Cell Unit, Hutchison-MRC Research centre, Addenbrooke' s Hospital Cambridge, CB2 0XZ (United Kingdom)

    2013-01-01

    Absract: HES6, a member of the hairy-enhancer-of-split family of transcription factors, plays multiple roles in myogenesis. It is a direct target of the myogenic transcription factor MyoD and has been shown to regulate the formation of the myotome in development, myoblast cell cycle exit and the organization of the actin cytoskeleton during terminal differentiation. Here we investigate the expression and function of HES6 in rhabdomyosarcoma, a soft tissue tumor which expresses myogenic genes but fails to differentiate into muscle. We show that HES6 is expressed at high levels in the subset of alveolar rhabdomyosarcomas expressing PAX/FOXO1 fusion genes (ARMSp). Knockdown of HES6 mRNA in the ARMSp cell line RH30 reduces proliferation and cell motility. This phenotype is rescued by expression of mouse Hes6 which is insensitive to HES6 siRNA. Furthermore, expression microarray analysis indicates that the HES6 knockdown is associated with a decrease in the levels of Transgelin, (TAGLN), a regulator of the actin cytoskeleton. Knockdown of TAGLN decreases cell motility, whilst TAGLN overexpression rescues the motility defect resulting from HES6 knockdown. These findings indicate HES6 contributes to the pathogenesis of ARMSp by enhancing both proliferation and cell motility.

  3. Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release.

    Science.gov (United States)

    Leikauf, G D; Fink, S P; Miller, M L; Lockey, J E; Driscoll, K E

    1995-01-01

    Refractory ceramic fiber has been developed for industrial processes requiring materials with high thermal and mechanical stability. To evaluate the biological activity of this fiber, rat alveolar macrophages were exposed for < or = 24 h to 0-1,000 micrograms/ml of refractory ceramic fiber, crocidolite asbestos, silica (fibrogenic particles), or titanium dioxide (a nonfibrogenic particle), and eicosanoid, tumor necrosis factor-alpha (TNF), and lactate dehydrogenase release were measured. Particle dimensions were determined by electron microscopy. Radioactivity coeluting with leukotriene B4 (LTB4) and immunoreactive LTB4 and TNF release increased after refractory ceramic fiber and were similar in magnitude after asbestos but less than after silica. For example, the total [3H]eicosanoid release increased 3.9-fold after refractory ceramic fiber, 4.6-fold after asbestos, and 8.7-fold after silica. Refractory ceramic fiber and asbestos also have similar particle dimensions (diameter, length, and surface area). Inasmuch as macrophage-derived LTB4 and TNF are potent mediators in inflammatory events, including migration and activation of neutrophils, these findings suggest that refractory ceramic fiber can activate macrophages in vitro to release mediators relevant to in vivo findings of inflammation and fibrotic lung disease in laboratory animals.

  4. Executive functions in early childhood: interrelations and structural development of inhibition, set-shifting and working memory

    Directory of Open Access Journals (Sweden)

    Paolo Stievano

    2013-04-01

    Full Text Available The aim of the present study is to examine the interrelations of executive function (EF tasks with general cognitive ability and linguistic level in preschool children. The analyses of the correlation between EF sub-domains, particularly inhibition and set-shifting, have been studied to comprehend the ontogenesis of EFs. Task analysis has allowed us to identify which EF sub-domains are prevalent in each task, with particular attention to inhibition and set-shifting definitions. The sample was composed of 40 typically developing children from 48 to 69 months old (M=58 months, SD=5.02; 28 boys and 12 girls. The results give some insight into the development of executive functions, their utility in clinical assessment and indication.

  5. Alveolar targeting of aerosol pentamidine. Toward a rational delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Simonds, A.K.; Newman, S.P.; Johnson, M.A.; Talaee, N.; Lee, C.A.; Clarke, S.W. (Royal Free Hospital, London (England))

    1990-04-01

    Nebulizer systems that deposit a high proportion of aerosolized pentamidine on large airways are likely to be associated with marked adverse side effects, which may lead to premature cessation of treatment. We have measured alveolar deposition and large airway-related side effects (e.g., cough, breathlessness, and effect on pulmonary function) after aerosolization of 150 mg pentamidine isethionate labeled with {sup 99m}Tc-Sn-colloid. Nine patients with AIDS were studied using three nebulizer systems producing different droplet size profiles: the Acorn System 22, Respirgard II, and Respirgard II with the inspiratory baffle removed. Alveolar deposition was greatest and side effects least with the nebulizer producing the smallest droplet size profile (Respirgard II), whereas large airway-related side effects were prominent and alveolar deposition lowest with the nebulizer producing the largest droplet size (Acorn System 22). Values for alveolar deposition and adverse airway effects were intermediate using the Respirgard with inspiratory baffle removed, thus indicating the importance of the baffle valve in determining droplet size. Addition of a similar baffle valve to the Acorn System 22 produced a marked improvement in droplet size profile. Selection of a nebulizer that produces an optimal droplet size range offers the advantage of enhancing alveolar targeting of aerosolized pentamidine while reducing large airway-related side effects.

  6. Composition of alveolar liquid in the foetal lamb.

    Science.gov (United States)

    Adamson, T M; Boyd, R D; Platt, H S; Strang, L B

    1969-09-01

    1. Experiments were performed on foetal lambs at gestations between 125 days and term. The foetus was exteriorized at Caesarean section with the umbilical cord and placental attachment maintained intact. Samples of liquid from the alveolar parts of the lung were withdrawn through a tracheal cannula and samples of lung lymph, plasma and amniotic liquid were also obtained. Measurements were made of total osmolality, concentrations of electrolytes and urea, pH and P(CO2). Titrations were carried out with N/10 HCl and N/10 NaOH. The water content of the liquids was estimated and concentrations expressed per kg H(2)O.2. In alveolar liquid [H(+)], [K(+)] and [Cl(-)] were higher and [Ca(2+)], [phosphates] and [HCO(3) (-)] were lower than in plasma or lymph. In amniotic liquid osmolality [Na(+)], [Cl(-)] and [Ca(2+)] were lower and [phosphates] higher than in plasma or lymph. Alveolar liquid/plasma ratios of [HCO(3) (-)], [Ca(2+)], [Cl(-)] and [K(+)] differed from ultra filtrate/plasma ratios of these ions.3. Titration curves demonstrated a very small amount of buffering in alveolar liquid at its in vivo pH of 6.27 mostly due to HCO(3) (-) at an average concentration of 2.8 mM/kg H(2)O.4. It is concluded that foetal alveolar liquid is not an ultrafiltrate of plasma nor a mixture of amniotic liquid and plasma ultrafiltrate, but a special material elaborated by the foetal lung.

  7. Depressant effects of ambroxol and erdosteine on cytokine synthesis, granule enzyme release, and free radical production in rat alveolar macrophages activated by lipopolysaccharide.

    Science.gov (United States)

    Jang, Yoon Young; Song, Jin Ho; Shin, Yong Kyoo; Han, Eun Sook; Lee, Chung Soo

    2003-04-01

    The present study examined the effects of ambroxol and erdosteine, bronchial expectorants, on the cytokine synthesis, granule enzyme release, and free radical production in rat alveolar macrophages activated by lipopolysaccharide. Ambroxol and erdosteine significantly decreased the production of tumour necrosis factors-alpha, interleukin-1beta, and interleukin-6 in alveolar macrophages activated by lipopolysaccharide. These drugs significantly reduced the production of superoxide anion, hydrogen peroxide, and nitric oxide and the release of acid phosphatase and lysozyme in lipopolysaccharide-activated macrophages. Ambroxol and erdosteine showed no scavenging effect on superoxide anion and hydrogen peroxide, whereas both drugs effectively decomposed nitric oxide. The results show that ambroxol and erdosteine may inhibit the responses, including cytokine synthesis and free radical production, in rat alveolar macrophages activated by lipopolysaccharide. Unlike the production of reactive oxygen species, the inhibitory effect of ambroxol and erdosteine on the production of nitric oxide in lipopolysaccharide-activated alveolar macrophages may be accomplished by a scavenging action on the species and inhibition of the respiratory burst.

  8. Thyrocytes responding to IFN-gamma are essential for development of lymphocytic spontaneous autoimmune thyroiditis and inhibition of thyrocyte hyperplasia.

    Science.gov (United States)

    Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

    2006-01-15

    IFN-gamma promotes the development of lymphocytic spontaneous autoimmune thyroiditis (L-SAT) in NOD.H-2h4 mice and inhibits the development of thyrocyte hyperplasia and proliferation (TEC H/P). The precise mechanisms by which IFN-gamma promotes L-SAT and inhibits TEC H/P are unknown. To determine whether responsiveness of lymphocytes or thyrocytes to IFN-gamma is important for the development of these lesions, IFN-gammaR-/- mice, which develop TEC H/P similar to IFN-gamma-/- mice, were used as recipients for adoptive cell transfer. Wild-type (WT) splenocytes or bone marrow induced L-SAT and inhibited TEC H/P in IFN-gamma-/-, but not IFN-gammaR-/- recipients. IFN-gammaR-/- recipients of WT cells developed severe TEC H/P, but did not develop L-SAT, suggesting that thyrocytes responding to IFN-gamma are important for inhibition of TEC H/P. Unexpectedly, IFN-gammaR-/- splenocytes or bone marrow did not induce L-SAT in IFN-gamma-/- or WT mice even though IFN-gammaR-/- lymphocyte donors produced as much IFN-gamma as lymphocytes from WT donors, and thyrocytes could respond to IFN-gamma. Real-time PCR indicated that recipients of IFN-gammaR-/- bone marrow expressed less mRNA for IFN-gamma-inducible chemokines compared with recipients of WT bone marrow. This might limit the migration of IFN-gammaR-/- lymphocytes to thyroids. Few IFN-gammaR-/- lymphocytes infiltrated thyroids even in the presence of WT lymphocytes, suggesting that lymphocytes unable to respond to IFN-gamma are not induced to migrate to thyroids. These results suggest that thyrocytes must be able to respond to IFN-gamma for the development of L-SAT and inhibition of TEC H/P, and lymphocytes must be able to respond to IFN-gamma to induce L-SAT.

  9. Response Inhibition and Academic Abilities in Typically Developing Children with Attention-Deficit-Hyperactivity Disorder-Combined Subtype

    OpenAIRE

    2010-01-01

    Research in Attention-Deficit/Hyperactivity Disorder (ADHD) generally utilizes clinical samples or children with comorbid psychiatric diagnoses. Findings indicated that children with ADHD experience academic underachievement and poor performance on measures of response inhibition (RI). Less is known, about the neuropsychological profile of typically developing children with ADHD. The aim of the current study was twofold: (1) determine if academic skills and RI were impaired in typically devel...

  10. Administration of Danhong Injection to diabetic db/db mice inhibits the development of diabetic retinopathy and nephropathy.

    Science.gov (United States)

    Liu, Mengyang; Pan, Quan; Chen, Yuanli; Yang, Xiaoxiao; Zhao, Buchang; Jia, Lifu; Zhu, Yan; Zhang, Boli; Gao, Xiumei; Li, Xiaoju; Han, Jihong; Duan, Yajun

    2015-06-10

    Danhong Injection (DHI), a Chinese medicine for treatment of patients with coronary heart disease, inhibits primary abdominal aortic aneurysms in apoE deficient (apoE(-/-)) mice. Formation of microaneurysms plays an important role in the development of diabetic retinopathy and nephropathy. It remains unknown if DHI can reduce these diabetic complications. In this study, diabetic db/db mice in two groups were injected with saline and DHI, respectively, for 14 weeks. Blood and tissue samples were collected to determine serum glucose, lipids and tissue structure. DHI reduced diabetes-induced body weight gain, serum cholesterol and glucose levels. In retinas, DHI blocked the shrink of whole retina and retinal sub-layers by inhibiting expression of caspase 3, matrix metalloproteinase 2 (MMP-2) and MMP-9, accumulation of carbohydrate macromolecules and formation of acellular capillaries. DHI improved renal functions by inhibiting mesangial matrix expansion, expression of vascular endothelial growth factor A, fibronectin and advanced glycation end products in kidneys. Mechanistically, DHI induced expression of glucokinase, AMPKα/phosphorylated AMPKα, insulin receptor substrate 1, fibroblast growth factor 21 and peroxisome proliferator-activated γ. Expression of genes responsible for energy expenditure was also activated by DHI. Therefore, DHI inhibits diabetic retinopathy and nephropathy by ameliorating glucose metabolism and demonstrates a potential application in clinics.

  11. In vitro actinomycete biofilm development and inhibition by the polyene antibiotic, nystatin, on IUD copper surfaces.

    Science.gov (United States)

    Shanmughapriya, Santhanam; Francis, Arumugam Lency; Kavitha, Senthil; Natarajaseenivasan, Kalimuthusamy

    2012-01-01

    The presence of intrauterine contraceptive devices (IUDs) gives a solid surface for attachment and an ideal niche for biofilm to form and flourish. Pelvic actinomycosis is often associated with the use of IUDs. Treatment of IUD-associated pelvic actinomycosis requires the immediate removal of the IUD. Therefore, this article presents in vitro evidence to support the use of novel antibiotics in the treatment of actinomycete biofilms. Twenty one clinical actinomycetes isolates from endocervical swabs of IUD wearers were assessed for their biofilm forming ability. An in vitro biofilm model with three isolates, Streptomyces strain A4, Nocardia strain C15 and Nocardia strain C17 was subjected to treatment with nystatin. Inhibition of biofilm formation by nystatin was found to be concentration dependent, with MBIC50 values in the range 0.08-0.16 mg ml(-1). Furthermore, at a concentration of 0.16 mg ml(-1), nystatin inhibited the twitching motility of the isolates, providing evidence for a possible mechanism of biofilm inhibition.

  12. Effective inhibition of lytic development of bacteriophages λ, P1 and T4 by starvation of their host, Escherichia coli

    Directory of Open Access Journals (Sweden)

    Węgrzyn Alicja

    2007-02-01

    Full Text Available Abstract Background Bacteriophage infections of bacterial cultures cause serious problems in genetic engineering and biotechnology. They are dangerous not only because of direct effects on the currently infected cultures, i.e. their devastation, but also due to a high probability of spreading the phage progeny throughout a whole laboratory or plant, which causes a real danger for further cultivations. Therefore, a simple method for quick inhibition of phage development after detection of bacterial culture infection should be very useful. Results Here, we demonstrate that depletion of a carbon source from the culture medium, which provokes starvation of bacterial cells, results in rapid inhibition of lytic development of three Escherichia coli phages, λ, P1 and T4. Since the effect was similar for three different phages, it seems that it may be a general phenomenon. Moreover, similar effects were observed in flask cultures and in chemostats. Conclusion Bacteriophage lytic development can be inhibited efficiently by carbon source limitation in bacterial cultures. Thus, if bacteriophage contamination is detected, starvation procedures may be recommended to alleviate deleterious effects of phage infection on the culture. We believe that this strategy, in combination with the use of automated and sensitive bacteriophage biosensors, may be employed in the fermentation laboratory practice to control phage outbreaks in bioprocesses more effectively.

  13. Alveolar-filling growth pattern of sarcomatoid malignant pleural mesothelioma.

    Science.gov (United States)

    Hayakawa, Takamitsu; Tajima, Shogo; Takanashi, Yusuke; Takahashi, Tsuyoshi; Neyatani, Hiroshi; Funai, Kazuhito

    2016-09-01

    A case of sarcomatoid malignant pleural mesothelioma showing extremely rare growth pattern is described. A 63-year-old man presented to our hospital with left pleural effusion. A computed tomography (CT) scan of the chest showed diffusely thickened left visceral and parietal pleura associated with intermingled pulmonary infiltrative shadowing. Biopsy of the pleura under general anaesthesia confirmed the diagnosis of sarcomatoid malignant pleural mesothelioma. The patient underwent left extra-pleural pneumonectomy. Histopathologically, the sarcomatoid spindle tumour cells changed their morphology to polygonal cells in the pulmonary parenchyma and grew upwards, filling the alveolar space without the destruction of its septa, showing an alveolar-filling growth pattern. The current report indicates a case of sarcomatoid pleural mesothelioma that shows an alveolar-filling growth pattern, despite having not been thoroughly categorized in the World Health Organization (WHO) classification.

  14. Alveolar process reconstruction after tooth extraction by orthodontic indications

    Directory of Open Access Journals (Sweden)

    Kovalev М.О.

    2013-09-01

    Full Text Available The objective of the study is to determine indications for alveolar bone reconstruction after tooth extraction according to orthodontic indications. Material and methods. 62 patients (first maturity level with dental arch asymmetry due to loss of a premolar on one side of the mouth were examined and treated. Frontal-diagonal coefficient of the dental arch was used to determine the correlation between tooth size and dental arch parameters. Results. It has been demonstrated that changes of the alveolar ridge following the extraction of the first premolars in patients of the experimental group were less significant as compared with the controls. Conclusion. It is reasonable to apply this method simultaneously with the removal of a tooth for orthodontic indications or when the alveolar ridge in the post-extraction socket leaves insufficient bone volume.

  15. Alveolar rhabdomyosarcoma involving the mandibular ramus and its surrounding tissues

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Gwangju (Korea, Republic of)

    2004-06-15

    Rhabdomyosarcoma, when it occurs in the head and neck, is primarily found in children. Alveolar rhabdomyosarcoma is rarely seen in the oral lesion, comparing to the embryonal and the pleomorphic variants. This is a report of a case of alveolar rhabdomyosarcoma in the mandible in a ten-year old girl who complained of a non-painful swelling on the right cheek. The right lower 1st molar was mobile. Her radiographs revealed an extensive radiolucency with somewhat irregular border on the right mandibular ramus. The right mandibular 1st and 2nd molars lost their lamina dura and were floating. CT images revealed smooth-outlined soft tissue mass occupying the pterygomandibular space, the infratemporal space, and the masseteric muscle with thinning and perforation of the right mandibular angle and ramus. Histopathological and immunohistochemical findings established the final diagnosis of alveolar rhabdomyosarcoma.

  16. Electronic thermography for the assessment of inferior alveolar nerve deficit.

    Science.gov (United States)

    Gratt, B M; Shetty, V; Saiar, M; Sickles, E A

    1995-08-01

    Neurosensory deficit is one of the major complications encountered in oral and maxillofacial surgery. OBJECTIVES. To determine the efficacy of electronic thermography in objectively assessing neurosensory deficits of the inferior alveolar nerve. STUDY DESIGN. Three studies were conducted measuring skin temperature over the chin region of the face at 0.1 degree C accuracy. RESULTS. (1) Thermal symmetry of the chin region in normal subjects (delta T = 0.2 degree C, SD = 0.02 degree C); (2) Induction of transient thermal asymmetry by local anesthetic injection (delta T = +0.4 degree C, SD = 0.2 degree C); (3) nine subjects with neurologic alterations of the inferior alveolar nerve (delta T = +0.5 degree C, SD = 0.2 degree C). Statistically significant differences were found between control group and experimental groups at p alveolar nerve injury or by pharmacologic nerve block.

  17. Traumatic neuroma of the inferior alveolar nerve: a case report.

    Science.gov (United States)

    Arribas-García, Ignacio; Alcalá-Galiano, Andrea; Gutiérrez, Ramón; Montalvo-Moreno, Juan José

    2008-03-01

    Traumatic neuromas are rare entities which characteristically arise subsequently to surgery and are usually accompanied by pain, typically neuralgic. We present an unusual case of an intraosseous traumatic neuroma of the inferior alveolar nerve following tooth extraction. A 56-year-old man consulted for paresthesias and hyperesthesia in the left mandibular region following extraction of the left mandibular third molar (#38). The panoramic radiograph revealed a radiolucent lesion in the inferior alveolar nerve canal, and CT demonstrated the existence of a mass within the canal, producing widening of the same. Nerve-sparing excisional biopsy was performed. Histopathology and immunohistochemistry were consistent with traumatic neuroma of the left inferior alveolar nerve. After 3 years of follow-up, the patient is asymptomatic and there are no signs of recurrence.

  18. Role of cytoskeleton in cytokine production from lung alveolar epithelial cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Cytokines are involved in both host defense and inflammatory lung injury. Recent work from our laboratory and others has demonstrated that in addition to classical immune cells, lung alveolar epithelial cells (or pneumocytes) can also produce cytokines in response to various stimuli. This new knowledge has advanced our view of the host defense system in the lung. The regulatory mechanisms of cytokine production have been studied in great detail at various cellular and molecular levels, but the mechanisms of intracellular cytokine transport are largely unknown. Our recent studies suggest that the cytoskeleton could play an important role in mediating intracellular cytokine trafficking. This could be an important regulatory step for cytokine production. For example, lipopolyssacharide (LPS) induced tumor necrosis factor-α (TNF-α) from rat pneumocytes, which was further enhanced by a microfilament-disrupting agent. LPS also induced macrophage inflammatory protein-2(MIP-2), a chemokine for neutrophil recruitment and activation, from rat pneumocytes. This effect was enhanced by microtubule-disrupting agents. We speculate that both microfilaments and microtubules are involved in regulating cytokine transportation in pneumocytes through different mechanisms. Further investigation in on going in my laboratory. From a clinical perspective, if we understand the mechanisms regulating cytokine production and release from lung alveolar epithelial cells, we may be able to enhance or inhibit release of crucial cytokines depending on the clinical situation.

  19. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor.

    Science.gov (United States)

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C; Kim, Kevin K

    2014-04-15

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.

  20. Vascularization of the gray whale palate (Cetacea, Mysticeti, Eschrichtius robustus): soft tissue evidence for an alveolar source of blood to baleen.

    Science.gov (United States)

    Ekdale, Eric G; Deméré, Thomas A; Berta, Annalisa

    2015-04-01

    The origin of baleen in mysticetes heralded a major transition during cetacean evolution. Extant mysticetes are edentulous in adulthood, but rudimentary teeth develop in utero within open maxillary and mandibular alveolar grooves. The teeth are resorbed prenatally and the alveolar grooves close as baleen germ develops. Arteries supplying blood to highly vascularized epithelial tissue from which baleen develops pass through lateral nutrient foramina in the area of the embryonic alveolar grooves and rudimentary teeth. Those vessels are hypothesized to be branches of the superior alveolar artery, but branches of the greater palatine arteries may play a role in the baleen vascularization. Through a combination of latex injection, CT, and traditional dissection of the palate of a neonatal gray whale (Eschrichtius robustus), we confirm that the baleen receives blood from vessels within the superior alveolar canal via the lateral foramina. The greater palatine artery is restricted to its own passage with no connections to the baleen. This study has implications for the presence of baleen in extinct taxa by identifying the vessels and bony canals that supply blood to the epithelium from which baleen develops. The results indicate that the lateral foramina in edentulous mysticete fossils are bony correlates for the presence of baleen, and the results can be used to help identify bony canals and foramina that have been used to reconstruct baleen in extinct mysticetes that retained teeth in adulthood. Further comparisons are made with mammals that also possess oral keratin structures, including ruminants, ornithorhynchid monotremes, and sirenians.

  1. 双维控制牙槽骨牵张器的成骨效应%A bidirectional alveolar bone distraction device for osteogenesis of alveolar bone

    Institute of Scientific and Technical Information of China (English)

    黄代营; 聂二民; 孙明; 黎炽彬

    2011-01-01

    背景:牵张成骨增高牙槽嵴在基础研究及临床已有很多成功报道,双维控制垂直牙槽骨牵张器可有效防止单向直线牵张器行牙槽骨牵张发生轴向移位.目的:研制双维控制的牙槽骨牵张器,并通过动物实验观察其成骨效应.方法:选择杂种犬4只,拔除一侧下颌前磨牙形成萎缩牙槽骨模型.1个月后行骨切开放置双维牵张器,7 d后垂直牵张 (1 mm/d,共5 d).完成垂直牵张后,利用双维牵张器颊向控制功能将移动骨块颊向牵出(大约2.4 mm),固定2个月后行大体观察及组织学检查.结果与结论:4只犬中2只黏膜伤口愈合良好,2只黏膜出现裂开,行二次缝合后愈合,牵张器固位良好,未出现松动、脱落.牵张骨块向垂直向及颊向的位移量满足实验目的要求,牙槽骨垂直向高度平均增加(5.0±0.2) mm,颊向宽度平均增加(2.4±0.3) mm.大体观察及组织学检查均证实牵张成骨的骨块新骨形成良好.说明双维控制垂直牙槽骨牵张器能较好的控制移动骨块垂直或颊向的移动方向,并且新骨形成良好.%BACKGROUND: Alveolar bone augmentation using a unidirectional dist raction device may lead to axial displacement. Abidirectional distraction device can control the vertical and buccal-lingual directions. But studies regarding this have been rarelyreported.OBJECTIVE: To develop a bidirectional alveolar bone distraction device and to investigate its effects on osteogenic effectsthrough an animal experiment.METHODS: Four adult mongrel dogs were established into models of alveolar bone atrophy by extraction of unilateral mandiblepremolars. After 1 month, alveolar bone was cut open and a bilateral distraction device was placed. Seven days later, thedistraction was started at a rate of 1 mm/day for 5 days. At last, buccal-lingual direction distraction (approximately 2.4 mm) wastaken for once, followed by a consolidation period of 2 months. Subsequently, gross observation and

  2. In vitro dose-dependent inhibition of the intracellular spontaneous calcium oscillations in developing hippocampal neurons by ketamine.

    Directory of Open Access Journals (Sweden)

    Lining Huang

    Full Text Available Spatial and temporal abnormalities in the frequency and amplitude of the cytosolic calcium oscillations can impact the normal physiological functions of neuronal cells. Recent studies have shown that ketamine can affect the growth and development and even induce the apoptotic death of neurons. This study used isolated developing hippocampal neurons as its study subjects to observe the effect of ketamine on the intracellular calcium oscillations in developing hippocampal neurons and to further explore its underlying mechanism using Fluo-4-loaded laser scanning confocal microscopy. Using a semi-quantitative method to analyze the spontaneous calcium oscillatory activities, a typical type of calcium oscillation was observed in developing hippocampal neurons. In addition, the administration of NMDA (N-Methyl-D-aspartate at a concentration of 100 µM increased the calcium oscillation amplitude. The administration of MK801 at a concentration of 40 µM inhibited the amplitude and frequency of the calcium oscillations. Our results demonstrated that an increase in the ketamine concentration, starting from 30 µM, gradually decreased the neuronal calcium oscillation amplitude. The inhibition of the calcium oscillation frequency by 300 µM ketamine was statistically significant, and the neuronal calcium oscillations were completely eliminated with the administration of 3,000 µM Ketamine. The administration of 100, 300, and 1,000 µM NMDA to the 1 mM ketamine-pretreated hippocampal neurons restored the frequency and amplitude of the calcium oscillations in a dose-dependent manner. In fact, a concentration of 1,000 µM NMDA completely reversed the decrease in the calcium oscillation frequency and amplitude that was induced by 1 mM ketamine. This study revealed that ketamine can inhibit the frequency and amplitude of the calcium oscillations in developing hippocampal neurons though the NMDAR (NMDA receptor in a dose-dependent manner, which might highlight a

  3. Anaesthesia for serial whole-lung lavage in a patient with severe pulmonary alveolar proteinosis: a case report

    Directory of Open Access Journals (Sweden)

    Webb Stephen T

    2008-11-01

    Full Text Available Abstract Introduction Pulmonary alveolar proteinosis is a rare condition that requires treatment by whole-lung lavage. We report a case of severe pulmonary alveolar proteinosis and discuss a safe and effective strategy for the anaesthetic management of patients undergoing this complex procedure. Case presentation A 34-year-old Caucasian man was diagnosed with severe pulmonary alveolar proteinosis. He developed severe respiratory failure and subsequently underwent serial whole-lung lavage. Our anaesthetic technique included the use of pre-oxygenation, complete lung separation with a left-sided double-lumen endotracheal tube, one-lung ventilation with positive end-expiratory pressure, appropriate ventilatory monitoring, cautious use of positional manoeuvres and single-lumen endotracheal tube exchange for short-term postoperative ventilation. Conclusion Patients with pulmonary alveolar proteinosis may present with severe respiratory failure and require urgent whole-lung lavage. We have described a safe and effective strategy for anaesthesia for whole-lung lavage. We recommend our anaesthetic technique for patients undergoing this complex and uncommon procedure.

  4. Single-stage implantation in the atrophic alveolar ridge of the mandible with the Norian skeletal repair system.

    Science.gov (United States)

    Hölzle, Frank; Bauer, Florian; Kesting, Marco R; Mücke, Thomas; Deppe, Herbert; Wolff, Klaus-Dietrich; Swaid, Sami

    2011-10-01

    Dental implants have played a part in rehabilitation of the jaws for more than 40 years, but in some cases they alone are inadequate because of extreme alveolar resorption. Correction may necessitate a two-stage procedure with additional interventions. We have made a preliminary study of the use of the Norian skeletal repair system (SRS), a carbonated calcium phosphate bone cement used to augment the alveolar ridge as a single-stage procedure, with the placement of implants. Ten edentulous patients with insufficient vertical bone in the interforaminal area were treated. After a horizontal osteotomy and crestal mobilisation of the alveolar ridge, implants were placed through the crestal part and fixed in the basal part of the mandible. Norian SRS was used to fill the gap created. The prostheses were inserted 3 months later. Forty implants were inserted. The follow up period was 60 months, and no fractures or dislocations developed. One of the implants was lost and there was one wound dehiscence, but no surgical intervention or revision was necessary. Radiographs showed good consolidation of the bony structure in all cases. We have described a reliable, single-stage procedure for augmentation and implantation in a highly atrophic alveolar crest. A 98% survival is comparable with those of other techniques. Further clinical trials are necessary to replicate these promising results.

  5. Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus

    Directory of Open Access Journals (Sweden)

    Kosmider Beata

    2012-06-01

    oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29 levels. Conclusions Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.

  6. Reconstruction of alveolar defects in patients with cleft lip and palate - 111 consecutive patients

    DEFF Research Database (Denmark)

    Andersen, Kristian

    2012-01-01

    Reconstruction of alveolar defects in patients with cleft lip and palate - 111 consecutive patients......Reconstruction of alveolar defects in patients with cleft lip and palate - 111 consecutive patients...

  7. Dietary proanthocyanidins inhibit UV radiation-induced skin tumor development through functional activation of the immune system.

    Science.gov (United States)

    Katiyar, Santosh K

    2016-06-01

    The incidence of skin cancer is equivalent to the incidence of malignancies in all other organs combined. The main risk factor for this disease is overexposure of the skin to solar ultraviolet (UV) radiation. UV irradiation induces inflammation, oxidative stress, DNA damage, and suppression of the immune system in the skin, which together contribute to carcinogenesis. The use of dietary phytochemicals shows great promise as a complementary and alternative strategy for skin cancer prevention. Grape seed proanthocyanidins (GSPs) have been tested extensively for their anti-skin cancer effect using in vivo animal models. Supplementation of an AIN76A control diet with GSPs (0.2 and 0.5%, w/w) significantly inhibits UV radiation-induced skin tumor development as well as malignant transformation of papillomas to carcinoma in mice. The inhibition of UVB-induced skin tumor development by GSPs is mediated through interrelated mechanisms of action including: (i) inhibition of inflammation, (ii) rapid repair of damaged DNA, and (iii) stimulation of immune system. Additionally, the chemopreventive effects of GSPs involve DNA repair-dependent functional activation of antigen-presenting cells and stimulation of CD8(+) effector T cells. These effects of GSPs could be useful in attenuation of the adverse effects of UV radiation and may have health benefits in humans. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Enzyme inhibition as a key target for the development of novel metal-based anti-cancer therapeutics.

    Science.gov (United States)

    Griffith, Darren; Parker, James P; Marmion, Celine J

    2010-06-01

    Historically, DNA has been the target for many metal-based anti-cancer drugs, but drawbacks of prevailing therapies have stimulated the search for new molecular targets which may present unique opportunities for therapeutic exploitation. Enzyme inhibition has recently been identified as an alternative and significant target. The pursuit of novel metallodrug candidates that selectively target enzymes is now the subject of intense investigation in medicinal bioinorganic chemistry and chemical biology. In the field of drug design, it is recognised by many that exploiting the structural and chemical diversity of metal ions for the identification of potential hit and lead candidates can dramatically increase the number of possible drug candidates that may be added to the already abundant armoury of chemotherapeutic agents. This review will focus on recent key advancements in enzyme inhibition as a key target for the development of novel metal-based anti-cancer therapeutics. The enormous clinical success of classical platinum drugs, amongst others, coupled with the wealth of knowledge accumulated in recent years on enzyme structure and function, has undoubtedly been the impetus behind the development of new metallodrug candidates with enzyme inhibitory properties. Recent trends in this field will be reviewed with a particular emphasis on metal complexes that inhibit protein and lipid kinases, matrix metalloproteases, telomerases, topoisomerases, glutathione-S-transferases, and histone deacetylases.

  9. Thermal behavior of premises equipped with different alveolar structures

    Directory of Open Access Journals (Sweden)

    Lajimi Nour

    2015-01-01

    Full Text Available This paper presents a numerical study of local thermal behavior. Vertical walls are equipped with alveolar structure and/or simple glazing in East, South and West frontages. Local temperature is assumed to be variable with time or imposed at set point temperature. Results principally show that the simple glazing number has a sensitive effect on convection heat transfer and interior air temperature. They also show that the diode effect is more sensitive in winter. The effect of alveolar structure and simple glazing on the power heating in case with set point temperature is also brought out.

  10. From alveolar diffuse atrophy to aggressive periodontitis: a brief history.

    Science.gov (United States)

    Guzeldemir, Esra; Toygar, Hilal Uslu

    2006-01-01

    Technologic advances in mechanics, electronics, physics, chemistry, and computer science have contributed to advances in dental medicine. Periodontology is not only a clinical science but is also directly related to the basic sciences. Research is conducted in laboratories rather than in clinics now. During the last century, aggressive periodontitis has received attention from numerous researchers because of its multifactorial features. This paper explores the long scientific journey of aggressive periodontitis, beginning with its first definition as alveolar diffuse atrophy. Perhaps in the future, "alveolar diffuse atrophy" will be referred to by another name or term. However, this journey will never end.

  11. Alveolar hemorrhage as the initial presentation of systemic lupus erythematosus.

    Science.gov (United States)

    de Holanda, Bruna A; Barreto, Isabela G Menna; de Araujo, Isadora S Gomes; de Araujo, Daniel B

    2016-01-01

    Alveolar hemorrhage (AH) is a rare syndrome that can often occur in autoimmune diseases, blood clotting disorders, infection or by acute inhalation injury, presenting rapid evolution and high mortality, especially with late diagnosis and treatment. Among the autoimmune diseases, there are reported cases in patients with primary antiphospholipid syndrome (PAPS), vasculitis and systemic lupus erythematosus (SLE). An early diagnosis is an essential tool in the successful management of this complication, requiring aggressive treatment based on vigorous immunosuppression and broad-spectrum antibiotic. We describe here a case of alveolar hemorrhage associated with glomerulonephritis as the open presentation in a patient with SLE.

  12. Alveolar ridge rehabilitation to increase full denture retention and stability

    Directory of Open Access Journals (Sweden)

    Mefina Kuntjoro

    2010-12-01

    Full Text Available Background: Atrophic mandibular alveolar ridge generally complicates prostetic restoration expecially full denture. Low residual alveolar ridge and basal seat can cause unstable denture, permanent ulcer, pain, neuralgia, and mastication difficulty. Pre-proshetic surgery is needed to improve denture retention and stability. Augmentation is a major surgery to increase vertical height of the atrophic mandible while vestibuloplasty is aimed to increase the denture bearing area. Purpose: The augmentation and vestibuloplasty was aimed to provide stability and retentive denture atrophic mandibular alveolar ridge. Case: A 65 years old woman patient complained about uncomfortable denture. Clinical evaluate showed flat ridge in the anterior mandible, flabby tissue and candidiasis, while residual ridge height was classified into class IV. Case management: Augmentation using autograph was conducted as the mandible vertical height is less than 15 mm. Autograph was used to achieve better bone quantity and quality. Separated alveolar ridge was conducted from left to right canine region and was elevated 0.5 mm from the previous position to get new ridge in the anterior region. The separated alveolar ridge was fixated by using T-plate and ligature wire. Three months after augmentation fixation appliances was removed vestibuloplasty was performed to increase denture bearing area that can make a stable and retentive denture. Conclusion: Augmentation and vestibuloplasty can improve flat ridge to become prominent.Latar belakang: Ridge mandibula yang atrofi pada umumnya mempersulit pembuatan restorasi prostetik terutama gigi tiruan lengkap (GTL. Residual alveolar ridge dan basal seat yang rendah menyebabkan gigi tiruan menjadi tidak stabil, menimbulkan ulser permanen, nyeri, neuralgia, dan kesulitan mengunyah. Tujuan: Augmentasi dan vestibuloplasti pada ridge mandibula yang atrofi dilakukan untuk menciptakan gigi tiruan yang stabil dan retentive. Kasus: Pasien wanita

  13. Alveolar hemorrhage as the initial presentation of systemic lupus erythematosus

    Science.gov (United States)

    de Holanda, Bruna A.; Barreto, Isabela G. Menna; de Araujo, Isadora S. Gomes

    2016-01-01

    Alveolar hemorrhage (AH) is a rare syndrome that can often occur in autoimmune diseases, blood clotting disorders, infection or by acute inhalation injury, presenting rapid evolution and high mortality, especially with late diagnosis and treatment. Among the autoimmune diseases, there are reported cases in patients with primary antiphospholipid syndrome (PAPS), vasculitis and systemic lupus erythematosus (SLE). An early diagnosis is an essential tool in the successful management of this complication, requiring aggressive treatment based on vigorous immunosuppression and broad-spectrum antibiotic. We describe here a case of alveolar hemorrhage associated with glomerulonephritis as the open presentation in a patient with SLE. PMID:27994272

  14. Development and evaluation of a monoclonal antibody-based inhibition ELISA for the quantification of chymosin in solution.

    Science.gov (United States)

    Rolet-Répécaud, O; Arnould, C; Dupont, D; Gavoye, S; Beuvier, E; Achilleos, C

    2015-05-20

    Chymosin is the major enzyme of natural rennet, traditionally used in cheese making for its high milk-clotting activity. For technical reasons, an accurate characterization of rennet should include its total clotting activity and also its enzymatic composition. Monoclonal antibodies specific to chymosin were obtained from mice immunized with purified bovine chymosin, and an inhibition enzyme-linked immunosorbent assay (ELISA) was developed for the quantification of chymosin in solution. No cross-reactivity was observed with other milk-clotting enzymes commonly used in cheese making. The limit of detection and limit of quantification were 125 and 400 ng/mL, respectively. The values of precision within and among runs were 7.23 and 7.39%, respectively, and satisfying recovery, from 92 to 119%, was found for spiked samples. The inhibition ELISA was successfully applied to commercial rennets, and the results were consistent with those obtained using the standard chromatographic method (IDF 110: A, 1987).

  15. Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells.

    Science.gov (United States)

    Kang, Soo-Young; Seeram, Navindra P; Nair, Muraleedharan G; Bourquin, Leslie D

    2003-05-08

    Anthocyanins, which are bioactive phytochemicals, are widely distributed in plants and especially enriched in tart cherries. Based on previous observations that tart cherry anthocyanins and their respective aglycone, cyanidin, can inhibit cyclooxygenase enzymes, we conducted experiments to test the potential of anthocyanins to inhibit intestinal tumor development in Apc(Min) mice and growth of human colon cancer cell lines. Mice consuming the cherry diet, anthocyanins, or cyanidin had significantly fewer and smaller cecal adenomas than mice consuming the control diet or sulindac. Colonic tumor numbers and volume were not significantly influenced by treatment. Anthocyanins and cyanidin also reduced cell growth of human colon cancer cell lines HT 29 and HCT 116. The IC(50) of anthocyanins and cyanidin was 780 and 63 microM for HT 29 cells, respectively and 285 and 85 microM for HCT 116 cells, respectively. These results suggest that tart cherry anthocyanins and cyanidin may reduce the risk of colon cancer.

  16. Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Huixian [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Shi, Zhenqi [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Qiao, Ping [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Department of Pharmacology, Norman Bethune Medical College, Jilin University, Changchun, Jilin 130021 (China); Li, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); McCoy, Erin M. [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Mao, Ping [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China); Xu, Hui [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Feng, Xu [Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Wang, Shunqing, E-mail: shqwang_cn@yahoo.com [Department of Hematology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180 (China)

    2013-11-01

    Highlights: •IL-3 treatment of bone marrow cells generates a population of hematopoietic cells. •IL-3-dependent hematopoietic cells are capable of differentiating into osteoclasts. •Osteoclasts derived from IL-3-dependent hematopoietic cells are functional. •IL-3 promotes the development of osteoclast progenitors. •IL-3 inhibits the osteoclastogenic process. -- Abstract: Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the

  17. Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

    Directory of Open Access Journals (Sweden)

    Hiroshi Kondo

    2015-01-01

    Full Text Available Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated an in vitro system to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12 were further analyzed. Under serum-free culture conditions, surfactant protein C (SPC, an ATII marker, was upregulated in both H12 and B7. Aquaporin 5 (AQP5, an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited, SPC and thyroid transcription factor-1 (TTF-1 expression levels were enhanced. After treatment with dexamethasone (DEX, 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP, 3-isobutyl-1-methylxanthine (IBMX, and keratinocyte growth factor (KGF, surfactant protein B and TTF-1 expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

  18. Effect of P2X7 receptor knockout on AQP-5 expression of type I alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Georg Ebeling

    Full Text Available P2X7 receptors, ATP-gated cation channels, are specifically expressed in alveolar epithelial cells. The pathophysiological function of this lung cell type, except a recently reported putative involvement in surfactant secretion, is unknown. In addition, P2X7 receptor-deficient mice show reduced inflammation and lung fibrosis after exposure with bleomycin. To elucidate the role of the P2X7 receptor in alveolar epithelial type I cells we characterized the pulmonary phenotype of P2X7 receptor knockout mice by using immunohistochemistry, western blot analysis and real-time RT PCR. No pathomorphological signs of fibrosis were found. Results revealed, however, a remarkable loss of aquaporin-5 protein and mRNA in young knockout animals. Additional in vitro experiments with bleomycin treated precision cut lung slices showed a greater sensitivity of the P2X7 receptor knockout mice in terms of aquaporin-5 reduction as wild type animals. Finally, P2X7 receptor function was examined by using the alveolar epithelial cell lines E10 and MLE-12 for stimulation experiments with bleomycin. The in vitro activation of P2X7 receptor was connected with an increase of aquaporin-5, whereas the inhibition of the receptor with oxidized ATP resulted in down regulation of aquaporin-5. The early loss of aquaporin-5 which can be found in different pulmonary fibrosis models does not implicate a specific pathogenetic role during fibrogenesis.

  19. Development of Small Molecules that Specifically Inhibit the D-loop Activity of RAD51.

    Science.gov (United States)

    Lv, Wei; Budke, Brian; Pawlowski, Michal; Connell, Philip P; Kozikowski, Alan P

    2016-05-26

    RAD51 is the central protein in homologous recombination (HR) DNA repair and represents a therapeutic target in oncology. Herein we report a novel class of RAD51 inhibitors that were identified by high throughput screening. In contrast to many previously reported RAD51 inhibitors, our lead compound 1 is capable of blocking RAD51-mediated D-loop formation (IC50 21.3 ± 7.8 μM) at concentrations that do not influence RAD51 binding to ssDNA. In human cells, 1 inhibits HR (IC50 13.1 ± 1.6 μM) without blocking RAD51's ability to assemble into subnuclear foci at sites of DNA damage. We determined that the active constituent of 1 is actually an oxidized derivative (termed RI(dl)-1 or 8) of the original screening compound. Our SAR campaign also yielded RI(dl)-2 (hereafter termed 9h), which effectively blocks RAD51's D-loop activity in biochemical systems (IC50 11.1 ± 1.3 μM) and inhibits HR activity in human cells (IC50 3.0 ± 1.8 μM).

  20. Vinegar Treatment Prevents the Development of Murine Experimental Colitis via Inhibition of Inflammation and Apoptosis.

    Science.gov (United States)

    Shen, Fengge; Feng, Jiaxuan; Wang, Xinhui; Qi, Zhimin; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Wang, Chao; Liu, Mingyuan; Liu, Bo; Yu, Lu

    2016-02-10

    This study investigated the preventive effects of vinegar and acetic acid (the active component of vinegar) on ulcerative colitis (UC) in mice. Vinegar (5% v/v) or acetic acid (0.3% w/v) treatment significantly reduced the disease activity index and histopathological scores, attenuated body weight loss, and shortened the colon length in a murine experimental colitis model induced by dextran sulfate sodium (DSS). Further mechanistic analysis showed that vinegar inhibited inflammation through suppressing Th1 and Th17 responses, the NLRP3 inflammasome, and MAPK signaling activation. Vinegar also inhibited endoplasmic reticulum (ER) stress-mediated apoptosis in the colitis mouse model. Surprisingly, pretreatment with vinegar for 28 days before DSS induction increased levels of the commensal lactic acid-producing or acetic acid-producing bacteria, including Lactobacillus, Bifidobacteria, and Enterococcus faecalis, whereas decreased Escherichia coli levels were found in the feces of mice. These results suggest that vinegar supplementation might provide a new dietary strategy for the prevention of UC.

  1. Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss

    Institute of Scientific and Technical Information of China (English)

    Ujjal K Bhawal; Nobushiro Hamada; Ikuo Nasu; Hirohisa Arakawa; Koh Shibutani; Hye-Jin Lee; Kazumune Arikawa; Michiharu Shimosaka; Masatoshi Suzuki; Toshizo Toyama; Takenori Sato; Ryota Kawamata; Chieko Taguchi

    2015-01-01

    Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride (NaF) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin (IL)-1b, matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL (receptor activator of nuclear factor kB ligand) and macrophage colony-stimulating factor (M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells (NFAT) c1 was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.

  2. Serial bronchoscopic lung lavage in pulmonary alveolar proteinosis under local anesthesia

    Directory of Open Access Journals (Sweden)

    K Rennis Davis

    2015-01-01

    Full Text Available Pulmonary alveolar proteinosis (PAP is a rare disease, characterized by alveolar accumulation of surfactant composed of proteins and lipids due to defective surfactant clearance by alveolar macrophages. Mainstay of treatment is whole lung lavage, which requires general anesthesia. Herein, we report a case of primary PAP, successfully treated with serial bronchoscopic lung lavages under local anesthesia.

  3. The effect of synthetic inducers of systemic resistance in inhibiting grey mold development on geranium and poinsettia

    Directory of Open Access Journals (Sweden)

    Jolanta Floryszak-Wieczorek

    2013-12-01

    Full Text Available Several chemical activators of resistance were tested to evaluate their efficiency in restricting development caused by Botryotinia fuckeliana (Botrytis cinerea on geranium and poinsettia leaves. The used signal pathway inducers of salicylic acid, such as DL-â-aminobutyric acid (BABA, g-aminobutyric acid (GABA and benzothiadiazole (BTH, at the applied rates markedly inhibited the development of grey mould in the both plant species. The mentioned inducers showed no toxic or restricting effect on the fungus growth and development under in vitro conditions. Only methyl jasmonate (Me-JA, a potential activator of independent signal transduction pathway, at the applied quantities (O,1-1,0 mg·ml-1, noticeably enhanced the disease spot development probably through stimulation of ethylene synthesis in plant. Me-JA added to medium with B.cinerea showed a strong antifungal action, whereas ethylene significantly stimulated mycelium growth in the in vitro cultures.

  4. Inhibition of misleading heuristics as a core mechanism for typical cognitive development: evidence from behavioural and brain-imaging studies.

    Science.gov (United States)

    Borst, Grégoire; Aïte, Ania; Houdé, Olivier

    2015-04-01

    Cognitive development is generally conceived as incremental with knowledge of increasing complexity acquired throughout childhood and adolescence. However, several studies have now demonstrated not only that infants possess complex cognitive abilities but also that older children, adolescents, and adults tend to make systematic errors even in simple logical reasoning tasks. Therefore, one of the main issues for any theory of typical cognitive development is to provide an explanation of why at some age and in some contexts children, adolescents, and adults do not express a knowledge or cognitive principle that they already acquired when they were younger. In this review, we present convergent behavioural and neurocognitive evidence that cognitive development is more similar to a non-linear dynamic system than to a linear, stage-like system. In this theoretical framework, errors can emerge in problems similar to the ones infants or young children were succeeding when older children, adolescents, and adults rely on a misleading heuristic rather than on the correct logical algorithm to solve such problems. And the core mechanism for overcoming these errors is inhibitory control (i.e. the ability to inhibit the misleading heuristics). Therefore, typical cognitive development relies not only on the ability to acquire knowledge of incremental complexity but also to inhibit previously acquired knowledge.

  5. Inhibition of Rac controls NPM-ALK-dependent lymphoma development and dissemination.

    Science.gov (United States)

    Colomba, A; Giuriato, S; Dejean, E; Thornber, K; Delsol, G; Tronchère, H; Meggetto, F; Payrastre, B; Gaits-Iacovoni, F

    2011-06-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM-ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM-ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM-ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas.

  6. ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease

    Science.gov (United States)

    AbdAlla, Said; Langer, Andreas; Fu, Xuebin; Quitterer, Ursula

    2013-01-01

    Increased generation of reactive oxygen species (ROS) is a significant pathological feature in the brains of patients with Alzheimer’s disease (AD). Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta) aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE) level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP), and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration. PMID:23959119

  7. Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis development in LDL-receptor deficient mice.

    Science.gov (United States)

    Kritikou, Eva; van Puijvelde, Gijs H M; van der Heijden, Thomas; van Santbrink, Peter J; Swart, Maarten; Schaftenaar, Frank H; Kröner, Mara J; Kuiper, Johan; Bot, Ilze

    2016-11-24

    Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation in the damaged vessels, LPA can act as a potent activator for various types of immune cells through its specific membrane receptors LPA1/3. LPA elicits chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic plaque progression. In this study we aimed to inhibit LPA signaling by means of LPA1/3 antagonism using the small molecule Ki16425. We show that LPA1/3 inhibition significantly impaired atherosclerosis progression. Treatment with Ki16425 also resulted in reduced CCL2 production and secretion, which led to less monocyte and neutrophil infiltration. Furthermore, we provide evidence that LPA1/3 blockade enhanced the percentage of non-inflammatory, Ly6C(low) monocytes and CD4(+) CD25(+) FoxP3(+) T-regulatory cells. Finally, we demonstrate that LPA1/3 antagonism mildly reduced plasma LDL cholesterol levels. Therefore, pharmacological inhibition of LPA1/3 receptors may prove a promising approach to diminish atherosclerosis development.

  8. ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Ursula Quitterer

    2013-08-01

    Full Text Available Increased generation of reactive oxygen species (ROS is a significant pathological feature in the brains of patients with Alzheimer’s disease (AD. Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP, and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration.

  9. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats

    Institute of Scientific and Technical Information of China (English)

    陶军; 杨天德; 陈祥瑞; 黄河

    2004-01-01

    Objective:Impaired active fluid transport of alveolar epithelium may involve in the pathogenesis and resolution of alveolar edema. Thc objective of this study was to explore the changes in alveolar epithelial liquid clearance during lung edema following acute lung injury induced by oleic acid. Methods:Forty-eight Wistar rats were randomly divided into six groups, I.e. , injured, amiloride, ouabain, amiloride plus ouabain and terbutaline groups. Twenty- four hours after the induction of acute lung injury by intravenous oleic acid (0.25 ml/kg), 5% albumin solution with 1.5 μCi 125Ⅰ-labeled albumin (5 ml/kg) was delivered into both lungs via trachea. Alveolar liquid clearance (ALC), extravascular lung water ( EVLW ) content and arterial blood gases were measured one hour thereafter.Results: At 24 h after the infusion of oleic acid, the rats developed pulmonary edema and severe hypoxemia, with EVLW increased by 47.9% and ALC decreased by 49.2%. Addition of either 2 × 10-3 M amiloride or 5 × 10-4 M ouabain to the instillation further reduced ALC and increased EVLW. ALC increased by approximately 63.7% and EVLW decreased by 46.9% with improved hypoxemia in the Terbutaline (10-4 M) group, compared those in injured rats. A significant negative correlation was found between the increment of EVLW and the reduction of ALC. Onclusions:Active fluid transport of alveolar epithelium might play a role in the pathogenesis of lung edema in acute lung injury.

  10. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus.

    Science.gov (United States)

    Qian, Zhaohui; Travanty, Emily A; Oko, Lauren; Edeen, Karen; Berglund, Andrew; Wang, Jieru; Ito, Yoko; Holmes, Kathryn V; Mason, Robert J

    2013-06-01

    Severe acute respiratory syndrome (SARS)-coronavirus (CoV) produces a devastating primary viral pneumonia with diffuse alveolar damage and a marked increase in circulating cytokines. One of the major cell types to be infected is the alveolar type II cell. However, the innate immune response of primary human alveolar epithelial cells infected with SARS-CoV has not been defined. Our objectives included developing a culture system permissive for SARS-CoV infection in primary human type II cells and defining their innate immune response. Culturing primary human alveolar type II cells at an air-liquid interface (A/L) improved their differentiation and greatly increased their susceptibility to infection, allowing us to define their primary interferon and chemokine responses. Viral antigens were detected in the cytoplasm of infected type II cells, electron micrographs demonstrated secretory vesicles filled with virions, virus RNA concentrations increased with time, and infectious virions were released by exocytosis from the apical surface of polarized type II cells. A marked increase was evident in the mRNA concentrations of interferon-β and interferon-λ (IL-29) and in a large number of proinflammatory cytokines and chemokines. A surprising finding involved the variability of expression of angiotensin-converting enzyme-2, the SARS-CoV receptor, in type II cells from different donors. In conclusion, the cultivation of alveolar type II cells at an air-liquid interface provides primary cultures in which to study the pulmonary innate immune responses to infection with SARS-CoV, and to explore possible therapeutic approaches to modulating these innate immune responses.

  11. Hemorragia alveolar como complicación del uso de trombolíticos Alveolar hemorrhage as a complication of thrombolytic therapy

    Directory of Open Access Journals (Sweden)

    Alejandra González

    2011-12-01

    Full Text Available La trombolisis se usa como estrategia de reperfusión coronaria en el infarto agudo de miocardio. El sangrado es su principal complicación; la mayoría ocurre en los sitios de accesos venosos y es leve, pero también pueden presentarse hemorragia gastrointestinal, retroperitoneal, genitourinaria, pulmonar y a nivel del sistema nervioso central, episodios estos generalmente de mayor gravedad y a veces fatales. Se describe aquí el caso de un paciente que recibió terapia trombolítica con estreptoquinasa como tratamiento por un infarto de miocardio, y que posteriormente desarrolló insuficiencia respiratoria aguda, infiltrados pulmonares bilaterales, caída del hematocrito y aumento de la difusión de monóxido de carbono, cuadro compatible con diagnóstico de hemorragia alveolar.Coronary thrombolysis is used as a strategy for coronary reperfusion for acute myocardial infarction. Bleeding is the main complication described. Although most of these events occur at sites of vascular access and are mild, in some cases gastrointestinal, retroperitoneal, genitourinary, lung and central nervous system bleeding may occur. These episodes are usually serious and sometimes fatal. The following report describes the case of a patient who received thrombolytic therapy with streptokinase as a treatment for myocardial infarction. Subsequently he developed acute respiratory failure, bilateral pulmonary infiltrates and fall of hematocrit compatible with diagnosis of alveolar hemorrhage.

  12. Endodontic-related inferior alveolar nerve and mental foramen paresthesia.

    Science.gov (United States)

    Morse, D R

    1997-10-01

    Paresthesia is a condition that involves perverted sensations of pain, touch, or temperature. It has a variety of possible causes. This article presents a literature review and case reports of endodontically related inferior alveolar nerve and mental foramen paresthesia. Nondrug prevention methods and the dental uses of dexamethasone are also discussed.

  13. Pulmonary alveolar proteinosis in an indium-processing worker

    Institute of Scientific and Technical Information of China (English)

    XIAO Yong-long; CAI Hou-rong; WANG Yi-hua; MENG Fan-qing; ZHANG De-ping

    2010-01-01

    @@ With the increasing number of workers engaged in liquid-crystal displays (LCD) manufacturer, lung diseases related to this occupational exposure are attracting more attention.Herein we report a case of interstitial lung disease in a LCD processing worker, which was pathologically confirmed as pulmonary alveolar proteinosis (PAP).

  14. Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins

    NARCIS (Netherlands)

    Szafranski, P.; Gambin, T.; Dharmadhikari, A.V.; Akdemir, K.C.; Jhangiani, S.N.; Schuette, J.; Godiwala, N.; Yatsenko, S.A.; Sebastian, J.; Madan-Khetarpal, S.; Surti, U.; Abellar, R.G.; Bateman, D.A.; Wilson, A.L.; Markham, M.H.; Slamon, J.; Santos-Simarro, F.; Palomares, M.; Nevado, J.; Lapunzina, P.; Chung, B.H.; Wong, W.L.; Chu, Y.W.; Mok, G.T.; Kerem, E.; Reiter, J.; Ambalavanan, N.; Anderson, S.A.; Kelly, D.R.; Shieh, J.; Rosenthal, T.C.; Scheible, K.; Steiner, L.; Iqbal, M.A.; McKinnon, M.L.; Hamilton, S.J.; Schlade-Bartusiak, K.; English, D.; Hendson, G.; Roeder, E.R.; DeNapoli, T.S.; Littlejohn, R.O.; Wolff, D.J.; Wagner, C.L.; Yeung, A.; Francis, D.; Fiorino, E.K.; Edelman, M.; Fox, J.; Hayes, D.A.; Janssens, S.; Baere, E. De; Menten, B.; Loccufier, A.; Vanwalleghem, L.; Moerman, P.; Sznajer, Y.; Lay, A.S.; Kussmann, J.L.; Chawla, J.; Payton, D.J.; Phillips, G.E.; Brosens, E.; Tibboel, D.; Klein, A.; Maystadt, I.; Fisher, R.; Sebire, N.; Male, A.; Chopra, M.; Pinner, J.; Malcolm, G.; Peters, G.; Arbuckle, S.; Lees, M.; Mead, Z.; Quarrell, O.; Sayers, R.; Owens, M.; Shaw-Smith, C.; Lioy, J.; McKay, E.; Leeuw, N. de; Feenstra, I.; Spruijt, L.; Elmslie, F.; Thiruchelvam, T.; Bacino, C.A.; Langston, C.; Lupski, J.R.; Sen, P.; Popek, E.; Stankiewicz, P.

    2016-01-01

    Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC0108

  15. Granulocyte macrophage colony stimulating factor therapy for pulmonary alveolar proteinosis.

    Science.gov (United States)

    Shende, Ruchira P; Sampat, Bhavin K; Prabhudesai, Pralhad; Kulkarni, Satish

    2013-03-01

    We report a case of 58 year old female diagnosed with Pulmonary Alveolar Proteinosis (PAP) with recurrence of PAP after 5 repeated whole lung lavage, responding to subcutaneous injections of Granulocyte Macrophage Colony Stimulating Factor therapy (GM-CSF). Thus indicating that GM-CSF therapy is a promising alternative in those requiring repeated whole lung lavage

  16. Complications in alveolar distraction osteogenesis of the atrophic mandible.

    NARCIS (Netherlands)

    Perdijk, F.B.; Meijer, G.J.; Strijen, P.J.; Koole, R.

    2007-01-01

    To improve the starting point for placement of dental implants, 45 patients suffering from atrophied edentulous mandibles, with a vertical height varying between 7.3 and 15.8mm, were treated by alveolar vertical distraction osteogenesis (VDO). The mean follow-up period was 3 years, ranging from 1 to

  17. Complications in alveolar distraction osteogenesis of the atrophic mandible

    NARCIS (Netherlands)

    Perdijk, F. B. T.; van Strijen, P. J.; Meijer, G.

    2007-01-01

    To improve the starting point for placement of dental implants, 45 patients suffering from atrophied edentulous mandibles, with a vertical height varying between 7.3 and 15.8 turn, were treated by alveolar vertical distraction osteogenesis (VDO). The mean follow-up period was 3 years, ranging from 1

  18. Classification of Alveolar Bone Destruction Patterns on Maxillary ...

    African Journals Online (AJOL)

    2017-09-14

    Sep 14, 2017 ... The aim of this research was to classify alveolar bone defects in the ... 669 maxillary molars of 243 patients with periodontal bone loss were investigated on four aspects ...... about one-third (35.2%) of all defects.[28,29] Our ...

  19. Remodeling dynamics in the alveolar process in skeletally mature dogs.

    Science.gov (United States)

    Huja, Sarandeep S; Fernandez, Soledad A; Hill, Kara J; Li, Yan

    2006-12-01

    Bone turnover rates can be altered by metabolic and mechanical demands. Due to the difference in the pattern of loading, we hypothesized that there are differences in bone remodeling rates between the maxillary and mandibular alveolar processes. Furthermore, in a canine model, the alveolar process of teeth that lack contact (e.g., second premolars) would have a different turnover rate than bone supporting teeth with functional contact (e.g., first molars). Six skeletally mature male dogs were given a pair of calcein labels. After sacrifice, specimens representing the anterior and posterior locations of both jaws were prepared for examination by histomorphometric methods to evaluate the bone volume/total volume (BV/TV; %), bone volume (mm2), mineral apposition rate (MAR; microm/day), and bone formation rate (BFR; %/year) in the alveolar process. There were no significant differences (P>0.05) in the BV/TV within the jaws. The bone volume within the alveolar process of the mandible was 2.8-fold greater than in the maxilla. The MAR was not significantly different between the jaws and anteroposterior locations. However, the BFR was significantly (Parchitecture.

  20. An unusual delayed complication of inferior alveolar nerve block.

    Science.gov (United States)

    Smyth, Joanna; Marley, John

    2010-01-01

    Systemic and localised complications after administration of local anaesthetic for dental procedures are well recognised. We present two cases of patients with trismus and sensory deficit that arose during resolution of trismus as a delayed complication of inferior alveolar nerve block.

  1. Hyperpolarized Xe MR imaging of alveolar gas uptake in humans.

    Directory of Open Access Journals (Sweden)

    Zackary I Cleveland

    Full Text Available BACKGROUND: One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange. METHODS AND PRINCIPAL FINDINGS: Here we exploit the solubility, high magnetic resonance (MR signal intensity, and large chemical shift of hyperpolarized (HP (129Xe to probe the regional uptake of alveolar gases by directly imaging HP (129Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP (129Xe magnetization is rapidly replenished by diffusive exchange with alveolar (129Xe. The dissolved HP (129Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs. CONCLUSIONS: The features observed in dissolved-phase (129Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios, higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP (129Xe imaging reports on pulmonary function at a fundamental level.

  2. Alveolar Ridge Split Technique Using Piezosurgery with Specially Designed Tips

    Science.gov (United States)

    Moro, Alessandro; Foresta, Enrico; Falchi, Marco; De Angelis, Paolo; D'Amato, Giuseppe; Pelo, Sandro

    2017-01-01

    The treatment of patients with atrophic ridge who need prosthetic rehabilitation is a common problem in oral and maxillofacial surgery. Among the various techniques introduced for the expansion of alveolar ridges with a horizontal bone deficit is the alveolar ridge split technique. The aim of this article is to give a description of some new tips that have been specifically designed for the treatment of atrophic ridges with transversal bone deficit. A two-step piezosurgical split technique is also described, based on specific osteotomies of the vestibular cortex and the use of a mandibular ramus graft as interpositional graft. A total of 15 patients were treated with the proposed new tips by our department. All the expanded areas were successful in providing an adequate width and height to insert implants according to the prosthetic plan and the proposed tips allowed obtaining the most from the alveolar ridge split technique and piezosurgery. These tips have made alveolar ridge split technique simple, safe, and effective for the treatment of horizontal and vertical bone defects. Furthermore the proposed piezosurgical split technique allows obtaining horizontal and vertical bone augmentation.

  3. Alveolar Ridge Split Technique Using Piezosurgery with Specially Designed Tips

    Directory of Open Access Journals (Sweden)

    Alessandro Moro

    2017-01-01

    Full Text Available The treatment of patients with atrophic ridge who need prosthetic rehabilitation is a common problem in oral and maxillofacial surgery. Among the various techniques introduced for the expansion of alveolar ridges with a horizontal bone deficit is the alveolar ridge split technique. The aim of this article is to give a description of some new tips that have been specifically designed for the treatment of atrophic ridges with transversal bone deficit. A two-step piezosurgical split technique is also described, based on specific osteotomies of the vestibular cortex and the use of a mandibular ramus graft as interpositional graft. A total of 15 patients were treated with the proposed new tips by our department. All the expanded areas were successful in providing an adequate width and height to insert implants according to the prosthetic plan and the proposed tips allowed obtaining the most from the alveolar ridge split technique and piezosurgery. These tips have made alveolar ridge split technique simple, safe, and effective for the treatment of horizontal and vertical bone defects. Furthermore the proposed piezosurgical split technique allows obtaining horizontal and vertical bone augmentation.

  4. Alveolar echinococcosis localized in the liver, lung and brain

    Institute of Scientific and Technical Information of China (English)

    Seyit Mehmet Kayacan; Kutigin Turkmen; Fatih Yakar; Kerim Guier; Sezai Vatansever; Suleyman Temiz; Bora Uslu; Dilek Kayacan; Vakur Akkaya; Osman Erk; Büent Saka; Aytac Karadag

    2008-01-01

    @@ Echinococcosis is a parasitic disease caused by the larval forms of echinococci. It has two main forms as the unilocular cystic form that is more commonly seen and caused by E. granulosus and the alveolar form that is rarely seen and caused by E.

  5. Green tea polyphenol blocks h(2)o(2)-induced interleukin-8 production from human alveolar epithelial cells.

    Science.gov (United States)

    Matsuoka, Katsunari; Isowa, Noritaka; Yoshimura, Takashi; Liu, Mingyao; Wada, Hiromi

    2002-06-07

    Reactive oxygen species (ROS) play crucial roles in ischemia-reperfusion (IR) injury of lung transplants. Reactive oxygen species may stimulate the production of neutrophil chemotactic factors such as interleukin-8 (IL-8), from alveolar epithelial cells, causing recruitment and activation of neutrophils in the reperfused tissue. Green tea polyphenol has potent anti-oxidative activities and anti-inflammatory effects by decreasing cytokine production. In the present study, we found that green tea polyphenol significantly inhibited IL-8 production induced by hydrogen peroxide (H(2)O(2)) in human lung alveolar epithelial cells (A549 line). It has been shown that mitogen activated protein kinases, such as Jun N-terminal kinase (JNK), p38 and p44/42, could mediate IL-8 production from a variety of cell types. We further investigated the effect of green tea polyphenol on these protein kinases, and demonstrated that H(2)O(2)-induced phosphorylation of JNK and p38 but not p44/42 was inhibited by green tea polyphenol in A549 cells. We speculate that green tea polyphenol may inhibit H(2)O(2)-induced IL-8 production from A549 cells through inactivation of JNK and p38.

  6. Hyperoxia increases the elastic modulus of alveolar epithelial cells through Rho kinase.

    Science.gov (United States)

    Wilhelm, Kristina R; Roan, Esra; Ghosh, Manik C; Parthasarathi, Kaushik; Waters, Christopher M

    2014-02-01

    Patients with acute lung injury are administered high concentrations of oxygen during mechanical ventilation, and while both hyperoxia and mechanical ventilation are necessary, each can independently cause additional injury. However, the precise mechanisms that lead to injury are not well understood. We hypothesized that alveolar epithelial cells may be more susceptible to injury caused by mechanical ventilation because hyperoxia causes cells to be stiffer due to increased filamentous actin (f-actin) formation via the GTPase RhoA and its effecter Rho kinase (ROCK). We examined cytoskeletal structures in cultured murine lung alveolar epithelial cells (MLE-12) under normoxic and hyperoxic (48 h) conditions. We also measured cell elasticity (E) using an atomic force microscope in the indenter mode. Hyperoxia caused increased f-actin stress fibers and bundle formation, an increase in g- and f-actin, an increase in nuclear area and a decrease in nuclear height, and cells became stiffer (higher E). Treatment with an inhibitor (Y-27632) of ROCK significantly decreased E and prevented the cytoskeletal changes, while it did not influence the nuclear height and area. Pre-exposure of cells to hyperoxia promoted detachment when cells were subsequently stretched cyclically, but the ROCK inhibitor prevented this effect. Hyperoxia caused thickening of vinculin focal adhesion plaques, and inhibition of ROCK reduced the formation of distinct focal adhesion plaques. Phosphorylation of focal adhesion kinase was significantly reduced by both hyperoxia and treatment with Y-27632. Hyperoxia caused increased cell stiffness and promoted cell detachment during stretch. These effects were ameliorated by inhibition of ROCK.

  7. Modulation of t1alpha expression with alveolar epithelial cell phenotype in vitro.

    Science.gov (United States)

    Borok, Z; Danto, S I; Lubman, R L; Cao, Y; Williams, M C; Crandall, E D

    1998-07-01

    T1alpha is a recently identified gene expressed in the adult rat lung by alveolar type I (AT1) epithelial cells but not by alveolar type II (AT2) epithelial cells. We evaluated the effects of modulating alveolar epithelial cell (AEC) phenotype in vitro on T1alpha expression using either soluble factors or changes in cell shape to influence phenotype. For studies on the effects of soluble factors on T1alpha expression, rat AT2 cells were grown on polycarbonate filters in serum-free medium (MDSF) or in MDSF supplemented with either bovine serum (BS, 10%), rat serum (RS, 5%), or keratinocyte growth factor (KGF, 10 ng/ml) from either day 0 or day 4 through day 8 in culture. For studies on the effects of cell shape on T1alpha expression, AT2 cells were plated on thick collagen gels in MDSF supplemented with BS. Gels were detached on either day 1 (DG1) or day 4 (DG4) or were left attached until day 8. RNA and protein were harvested at intervals between days 1 and 8 in culture, and T1alpha expression was quantified by Northern and Western blotting, respectively. Expression of T1alpha progressively increases in AEC grown in MDSF +/- BS between day 1 and day 8 in culture, consistent with transition toward an AT1 cell phenotype. Exposure to RS or KGF from day 0 prevents the increase in T1alpha expression on day 8, whereas addition of either factor from day 4 through day 8 reverses the increase. AEC cultured on attached gels express high levels of T1alpha on days 4 and 8. T1alpha expression is markedly inhibited in both DG1 and DG4 cultures, consistent with both inhibition and reversal of the transition toward the AT1 cell phenotype. These results demonstrate that both soluble factors and alterations in cell shape modulate T1alpha expression in parallel with AEC phenotype and provide further support for the concept that transdifferentiation between AT2 and AT1 cell phenotypes is at least partially reversible.

  8. Detection of chromosomal regions showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Bortoluzzi Stefania

    2004-06-01

    Full Text Available Abstract Background Rhabdomyosarcoma is a relatively common tumour of the soft tissue, probably due to regulatory disruption of growth and differentiation of skeletal muscle stem cells. Identification of genes differentially expressed in normal skeletal muscle and in rhabdomyosarcoma may help in understanding mechanisms of tumour development, in discovering diagnostic and prognostic markers and in identifying novel targets for drug therapy. Results A Perl-code web client was developed to automatically obtain genome map positions of large sets of genes. The software, based on automatic search on Human Genome Browser by sequence alignment, only requires availability of a single transcribed sequence for each gene. In this way, we obtained tissue-specific chromosomal maps of genes expressed in rhabdomyosarcoma or skeletal muscle. Subsequently, Perl software was developed to calculate gene density along chromosomes, by using a sliding window. Thirty-three chromosomal regions harbouring genes mostly expressed in rhabdomyosarcoma were identified. Similarly, 48 chromosomal regions were detected including genes possibly related to function of differentiated skeletal muscle, but silenced in rhabdomyosarcoma. Conclusion In this study we developed a method and the associated software for the comparative analysis of genomic expression in tissues and we identified chromosomal segments showing differential gene expression in human skeletal muscle and in alveolar rhabdomyosarcoma, appearing as candidate regions for harbouring genes involved in origin of alveolar rhabdomyosarcoma representing possible targets for drug treatment and/or development of tumor markers.

  9. Characterizing the lung tissue mechanical properties using a micromechanical model of alveolar sac

    Science.gov (United States)

    Karami, Elham; Seify, Behzad; Moghadas, Hadi; Sabsalinejad, Masoomeh; Lee, Ting-Yim; Samani, Abbas

    2017-03-01

    According to statistics, lung disease is among the leading causes of death worldwide. As such, many research groups are developing powerful tools for understanding, diagnosis and treatment of various lung diseases. Recently, biomechanical modeling has emerged as an effective tool for better understanding of human physiology, disease diagnosis and computer assisted medical intervention. Mechanical properties of lung tissue are important requirements for methods developed for lung disease diagnosis and medical intervention. As such, the main objective of this study is to develop an effective tool for estimating the mechanical properties of normal and pathological lung parenchyma tissue based on its microstructure. For this purpose, a micromechanical model of the lung tissue was developed using finite element (FE) method, and the model was demonstrated to have application in estimating the mechanical properties of lung alveolar wall. The proposed model was developed by assembling truncated octahedron tissue units resembling the alveoli. A compression test was simulated using finite element method on the created geometry and the hyper-elastic parameters of the alveoli wall were calculated using reported alveolar wall stress-strain data and an inverse optimization framework. Preliminary results indicate that the proposed model can be potentially used to reconstruct microstructural images of lung tissue using macro-scale tissue response for normal and different pathological conditions. Such images can be used for effective diagnosis of lung diseases such as Chronic Obstructive Pulmonary Disease (COPD).

  10. Preventive treatment of alveolar pulmonary edema of cardiogenic origin

    Institute of Scientific and Technical Information of China (English)

    Gideon Charach; Michael Shochat; Alexander Rabinovich; Oded Ayzenberg; Jacob George; Lior Charach; Pavel Rabinovich

    2012-01-01

    Objective To evaluate the efficacy of preventive treatment (PT) on alveolar pulmonary edema (APE) of cardiogenic origin using a monitor based on principles of internal thoracic impedance (ITI) measurements. Methods We conducted blinded clinical trials on patients with ST-elevation myocardial infarction (STEMI) and monitored whether the condition would progress to APE. ITI was measured noninvasively by the Edema Guard Monitor (EGM, model RS-207) every 30 min. The measurement threshold for the diagnosis of APE was fixed at > 12% decrease in ITI from baseline as described in our methodology. The patients were divided into one group that received standard treatment after the appearance of clinical signs of APE without considering the prediction of APE by EGM devise (Group 1), and another group of asymptomatic patients in whom development of APE was predicted by using only EGM measurements (Group 2). The latter participants' PT consisted of furosemide, intravenous nitroglycerine and supplemental oxygen. Results One-hundred and fifty patients with acute STEMI were enrolled into this study. Group 1 included 100 patients (53% males, age 64.1 ± 12.6 years). Treatment was started after the clinical appearance of overt signs of APE. Group 2 included 50 patients (54% males, age 65.2 ± 11.9 years) who received PT based on EGM measurements. Group 2 had significantly fewer cases of APE (n = 4, 8%) than Group 1 (n = 100, 100%) (P > 0.001). While APE was lethal in six (6%) Group 1 patients, PT resulted in prompt resolution of APE in all four (8%) Group 2 patients. Conclusion ITI is a useful modality for early diagnosis and PT of pulmonary edema of cardiogenic origin.

  11. Environmentally relevant concentrations of ammonium perchlorate inhibit thyroid function and alter sex ratios in developing Xenopus laevis.

    Science.gov (United States)

    Goleman, Wanda L; Carr, James A; Anderson, Todd A

    2002-03-01

    Embryos and larvae of the South African frog Xenopus laevis were exposed to ammonium perchlorate (AP) or control medium for 70 d. The dosage levels (59 ppb, 14,140 ppb) bracketed a range of perchlorate concentrations measured in surface waters at the Longhorn Army Ammunition Plant (LHAAP) in Karnack, Texas, USA. The experiment also included a 28-d nontreatment recovery period to assess the reversibility of AP effects. There were no significant effects of AP on mortality or hatching success. There were no effects of AP on developmental abnormalities such as bent/asymmetric tails or edema. Ammonium perchlorate inhibited forelimb emergence, the percentage of animals completing tail resorption, and hindlimb development during the 70-d exposure period. Only the upper AP concentration reduced whole-body thyroxine content, whereas both concentrations caused significant hypertrophy of the thyroid follicular epithelium. Both concentrations of AP caused a skewed sex ratio, significantly reducing the percentage of males at metamorphosis. The effects of AP on metamorphosis and thyroid function were reversed during the 28-d nontreatment recovery period. We conclude that AP inhibits thyroid activity and alters gonadal differentiation in developing X. laevis. These effects were observed at concentrations at or below concentrations reported in surface waters contaminated with ammonium perchlorate, suggesting that this contaminant may pose a threat to normal development and growth in natural amphibian populations.

  12. L—type calcium channel blockers inhibit the development but not the expression of sensitization to morphine in mice

    Institute of Scientific and Technical Information of China (English)

    ZhanQ; ZhenJW

    2002-01-01

    The relationship between opioid actions and L-type calcium channel blockers has been well documented.However,there is no report relevant to L-type calcium channel blockers and morphinesensitization,which is suggested to be an analog of behaviors that are the characteristics of drug addiction.Here the effects of three L-type calcium channel blockers,nimodipine,nifedipine and verapamil,on morphine-induced locomotor activity,the development and the expression of sensitization to morphine were studied systematically.The results showed that both nimodipine and verapamil attenuated,while nifedipine had only a tendency to decrease morphine-induced locomotor activity.All the three drugs inhibited the development of sensitization to morphine.However,none of them showed any effects on the expression of morphine sensitization.These results indicate that blocking L-tpye calcium channel attenuates the locomotor stimulating effects of morphine and inhibits the development but not the expression of morphine-sensitization.

  13. Membranous nephropathy, antitubular basement membrane antibodies and alveolar hemorrhage in a diabetic child.

    Science.gov (United States)

    Gallego, N; Olivares, F; Mampaso, F; Gonzalo, A; Barrio, R; Estepa, R; Ortuño, J

    1990-01-01

    We describe an 8-year-old boy who was diagnosed as having diabetes mellitus at the age of 3 months. During the follow-up the diabetes was uncontrolled, and he presented nephrotic syndrome with renal function impairment, a renal biopsy showing a membranous nephropathy. Subsequently he had episodes of anemia and dyspnea, due to alveolar hemorrhage, and he also developed Fanconi's syndrome. A later renal biopsy showed membranous glomerulonephritis and interstitial nephritis. The presence of antitubular basement membrane antibodies was noted but antialveolar basement membrane antibodies were not detected. We do not believe that this unusual clinical picture was a coincidence, and we speculate about a possible explanation.

  14. Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

    Science.gov (United States)

    Yoshida, Masahiro; Yamakawa, Hideaki; Yabe, Masami; Ishikawa, Takeo; Takagi, Masamichi; Matsumoto, Kei; Hamaguchi, Akihiko; Ogura, Makoto; Kuwano, Kazuyoshi

    2015-01-01

    We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

  15. Intracellular pathogens within alveolar macrophages in a patient with HIV infection: diagnostic challenge

    Directory of Open Access Journals (Sweden)

    Takashi Shinha

    2015-03-01

    Full Text Available In HIV-infected individuals, macrophages, the key defense effector cells, manifest defective activity in their interactions with a wide variety of opportunistic pathogens, including fungi and protozoa. Understanding the morphological characteristics of intracellular opportunistic pathogens in addition to their pathogenesis is of critical importance to provide optimal therapy, thereby decreasing morbidity and mortality in HIV-infected patients. We herein present a case of disseminated histoplasmosis confused with disseminated visceral leishmaniasis in an HIV-infected individual from Guyana who developed intracellular organisms within alveolar macrophages

  16. Alveolar bone grafting with simultaneous cleft lip rhinoplasty.

    Science.gov (United States)

    Kim, Young-Eun; Han, Jihyeon; Baek, Rong-Min; Kim, Baek-Kyu

    2016-11-01

    Optimal timing for cleft lip rhinoplasty is controversial. Definitive rhinoplasty is deferred until facial skeletal growth is completed. Intermediate rhinoplasty is performed after stabilization of the grafted alveolar bone, because the grafted bone tends to be absorbed over several months postoperatively, distorting the nasal profile. Here, we report our experience with simultaneous rhinoplasty during alveolar bone grafting for indicated patients, describe our surgical technique that ensures long-term bone graft survival, and report graft take rates and nasal profile changes. This retrospective chart review included a total of 54 patients; 44 underwent alveolar bone grafting only, and 10 underwent simultaneous cleft lip rhinoplasty. All surgeries were conducted with a judicious mucosal incision for tensionless wound closure. Bone graft take was evaluated with dental radiographs by the Bergland classification. Further, nasal aesthetic outcome was evaluated with medical photographs, based on nostril height and width and alar base width. In total, 96.3% of clefts showed graft success with Type I (66.7%) or Type II (27.8%) classifications; only 3.7% of clefts showed unfavorable results classified as Type III, and no clefts showed Type IV failure. The nasal shape was flatter with a decreased nostril height and increased nostril width after alveolar bone grafting, while nostril height was increased and nostril width was decreased in patients who underwent simultaneous rhinoplasty. With surgical techniques ensuring alveolar bone graft survival, simultaneous cleft lip rhinoplasty can result in nasal aesthetic improvement for patients with severe nasal deformities, decreasing the number of operations. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Hard tissue augmentation for alveolar defects before implant placement

    Directory of Open Access Journals (Sweden)

    Mutia Rochmawati

    2017-08-01

    Full Text Available Background. Often when planning implant therapy, there is a need to augment or  replace  bone  that  has  been  lost. The alveolar defects may occur as a result of tooth loss due to extraction, advanced periodontal diseases or trauma, long term use of removable appliances, dehiscence and fenestration defects, developmental defects/clefts, congenitally missing teeth and odontogenic cysts and tumors. Insufficient bone volume can be brought about by hard tissue augmentation. This techniques have led to increased predictability in reconstruction of alveolar ridge defects and functional implant placement. Purpose. To describe the methods of hard tissue augmentation which can be done with block grafts (autografts and allografts, particulate grafts (cortical and cancellous, xenografts, or synthetic materials. Review. The reconstruction of a normal alveolar housing, in height and width, is imperative to achieve a harmonious balance between biology, function, and aesthetics. Depending on the size and morphology of the defect, horizontal or vertical, various augmentation procedures can be used. Soft tissue management is a critical aspect of hard tissue augmentation procedures. Incisions, reflection, and manipulation should be designed to optimize blood supply and wound closure. The design and management of mucoperiosteal flaps must consider the increased dimensions of the ridge after augmentation as well as esthetics and approximation of the wound margins. The surgical procedure needs to be executed with utmost care to preserve the maximum vascularity to the flap and minimize tissue injury. Conclusion. Alveolar ridge defects can be classified by using Seibert’s classification or HVC System. The treatment of alveolar ridge defect before implant placement can be done with hard tissue augmentation.

  18. Alveolar bone measurement precision for phosphor-plate images

    Science.gov (United States)

    HILDEBOLT, CHARLES F.; COUTURE, REX; GARCIA, NATHALIA M.; DIXON, DEBRA; SHANNON, WILLIAM DOUGLAS; LANGENWALTER, ERIC; CIVITELLI, ROBERTO

    2009-01-01

    Objectives To demonstrate methods for determining measurement precision and to determine the precision of alveolar-bone measurements made with a vacuum-coupled, positioning device and phosphor-plate images. Study design Subjects were rigidly attached to the x-ray tube by means of a vacuum coupling device and custom, cross-arch, bite plates. Original and repeat radiographs (taken within minutes of each other) were obtained of the mandibular posterior teeth of 51 subjects, and cementoenamel-junction-alveolar-crest (CEJ-AC) distances were measured on both sets of images. In addition, x-ray-transmission (radiodensity) and alveolar-crest-height differences were determined by subtracting one image from the other. Image subtractions and measurements were performed twice. Based on duplicate measurements, the root-mean-square standard deviation (precision) and least-significant change (LSC) were calculated. LSC is the magnitude of change in a measurement needed to indicate that a true biological change has occurred. Results The LSCs were 4% for x-ray transmission, 0.49 mm for CEJ-AC distance, and 0.06 mm for crest-height 0.06 mm. Conclusion The LSCs for our CEJ-AC and x-ray transmission measurements are similar to what has been reported. The LSC for alveolar-crest height (determined with image subtraction) was less than 0.1 mm. Compared with findings from previous studies, this represents a highly precise measurement of alveolar crest height. The methods demonstrated for calculating LSC can be used by investigators to determine how large changes in radiographic measurements need to be before the changes can be considered (with 95% confidence) true biological changes and not noise (that is, equipment/observer error). PMID:19716499

  19. Delays in GABAergic interneuron development and behavioral inhibition after prenatal stress

    National Research Council Canada - National Science Library

    Lussier, Stephanie J; Stevens, Hanna E

    2016-01-01

    .... Prenatal stress delays GABAergic progenitor migration, but the significance of these early developmental disruptions for the continued development of GABAergic cells in the juvenile brain is unclear...

  20. Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats

    Directory of Open Access Journals (Sweden)

    Takagi Tomohisa

    2012-09-01

    Full Text Available Abstract Background The pathogenesis of inflammatory bowel disease (IBD is complex, and an effective therapeutic strategy has yet to be established. Recently, carbon monoxide (CO has been reported to be capable of reducing inflammation by multiple mechanisms. In this study, we evaluated the role of colonic CO insufflation in acute colitis induced by trinitrobenzene sulfonic acid (TNBS in rats. Methods Acute colitis was induced with TNBS in male Wistar rats. Following TNBS administration, the animals were treated daily with 200 ppm of intrarectal CO gas. The distal colon was removed to evaluate various parameters of inflammation, including thiobarbituric acid (TBA-reactive substances, tissue-associated myeloperoxidase (MPO activity, and the expression of cytokine-induced neutrophil chemoattractant (CINC-1 in colonic mucosa 7 days after TNBS administration. Results The administration of TNBS induced ulceration with surrounding edematous swelling in the colon. In rats treated with CO gas, the colonic ulcer area was smaller than that of air-treated rats 7 days after TNBS administration. The wet colon weight was significantly increased in the TNBS-induced colitis group, which was markedly abrogated by colonic insufflation with CO gas. The increase of MPO activity, TBA-reactive substances, and CINC-1 expression in colonic mucosa were also significantly inhibited by colonic insufflation with CO gas. Conclusions Colonic insufflation with CO gas significantly ameliorated TNBS-induced colitis in rats. Clinical application of CO gas to improve colonic inflammatory conditions such as IBD might be useful.

  1. Development of an inhibitive assay using commercial Electrophorus electricus acetylcholinesterase for heavy metal detection.

    Science.gov (United States)

    Shukor, M Y; Tham, L G; Halmi, M I E; Khalid, I; Begum, Ghousia; Syed, M A

    2013-09-01

    Near-real-ime assay is anassay method that the whole process from sampling until results could be obtained in approximately Iess than one hour. The ElIman assay for acetyl cholinesterase (AChE) has near real-time potential due to its simplicity and fast assay time. The commercial acetylcholinesterase from Electrophorus electricus is well known for its uses in insecticides detection. A lesser known fact is AChE is also sensitive to heavy metals. A near real-time inhibitive assay for heavy metals using AChE from this source showed promising results. Several heavy metals such as copper, silver and mercury could be etected with IC50 values of1.212, 0.1185 and 0.097 mg I-1, respectively. The Limits of Detection (LOD) for copper, silver and mercury were 0.01, 0.015 and 0.01 mg I-1, respectively. TheLimits of quantitation (LOQ) or copper, silver and mercury were 0.196, 0.112 and 0.025 mg I-1, respectively. The LOQvalues for copper, silver and mercury were well below the maximum permissible limit for these metal ions as outlined by Malaysian Department of Environment. A polluted location demonstrated near real-time applicability of the assay with variation oftemporal levels of heavy metals detected. The results show that AChE from Electrophorus electricus has the potential to be used as a near real-time biomonitoring tool for heavy

  2. Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction

    Science.gov (United States)

    Lin, Jie; Zhang, Lei; Zhang, Mingming; Hu, Jianqiang; Wang, Tingting; Duan, Yu; Man, Wanrong; Wu, Bin; Feng, Jiaxu; Sun, Lei; Li, Congye; Zhang, Rongqing; Wang, Haichang; Sun, Dongdong

    2016-01-01

    Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function. Mst1 overexpression deceased CMECs autophagy as evidenced by decreased LC3 expression and enhanced protein aggregation when subjected to high glucose culture. Mst1 knockout improved cardiac microvessel integrity and enhanced cardiac functions in diabetic mice. Mst1 knockdown up-regulated autophagy as indicated by more typical autophagosomes and increased LC3 expression in CMECs subjected to high glucose cultures. Mst1 knockdown also promoted autophagic flux in the presence of bafilomycin A1. Mst1 overexpression increased CMECs apoptosis, whereas Mst1 knockout decreased CMECs apoptosis. Sirt1 knockout abolished the effects of Mst1 overexpression in cardiac microvascular injury and cardiac dysfunction. In conclusion, Mst1 knockout preserved cardiac microvessel integrity and improved cardiac functions in diabetic mice. Mst1 decreased sirt1 activity, inhibited autophagy and enhanced apoptosis in CMECs, thus participating in the pathogenesis of diabetic coronary microvascular dysfunction. PMID:27680548

  3. Niacin attenuates the production of pro-inflammatory cytokines in LPS-induced mouse alveolar macrophages by HCA2 dependent mechanisms.

    Science.gov (United States)

    Zhou, Ershun; Li, Yimeng; Yao, Minjun; Wei, Zhengkai; Fu, Yunhe; Yang, Zhengtao

    2014-11-01

    Niacin has been reported to have potent anti-inflammatory effects in LPS-induced acute lung injury. However, the molecular mechanism of niacin has not been fully understood. The aim of the present study was to investigate the effects of niacin on the production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in LPS-induced mouse alveolar macrophages and explore its underlying mechanism. Mouse alveolar macrophages were incubated in the presence or absence of various concentrations of niacin (1, 10, 100 μmol/l) 1h before LPS (1 μg/ml) challenge. The results showed that niacin reduced the levels of TNF-α, IL-6 and IL-1β in LPS-challenged alveolar macrophages. Furthermore, NF-κB activation was inhibited by niacin through blocking the phosphorylation of NF-κB p65 and IκBα. In addition, silencing HCA2 abrogated the effect of niacin on the production of pro-inflammatory cytokines. These findings suggested that niacin attenuated the LPS-induced pro-inflammatory cytokines possibly mediated by HCA2 in LPS-challenged alveolar macrophages.

  4. The influence of cryopreservation on a benzimidazole-resistant isolate of Haemonchus contortus conditioned for inhibited development.

    Science.gov (United States)

    Hendrikx, W M; Boersema, J H; Eysker, M

    1988-01-01

    Larvae of a fenbendazole (FBZ)-selected, benzimidazole-resistant strain of Haemonchus contortus were conditioned for inhibited development during 7 weeks at 15 degrees C. Sheep raised nearly worm-free were infected with nonfrozen larvae (L3). Larvae from the same batch were exsheathed and cryopreserved over liquid nitrogen for 1 year, and another group of sheep was infected with the same dose of these L3 larvae after thawing. Egg hatch assays for all sheep were done between 21 and 30 days post infection (p.i.). Fenbendazole susceptibility was tested by treating 50% of each group of sheep on day 30 p.i. Worm counts of all sheep were done on day 38 p.i. The exsheathment time of the designated frozen L3 larvae at 15 degrees C exceeded the usual time span at room temperature. Of the frozen L3 larvae, 60% was motile after thawing. The mean LC50 values (micrograms tiabendazole/ml) and the mean percentage of efficacy after FBZ treatment against total worm burden, adults and early L4 larvae of nonfrozen and frozen H. contortus were not significantly different. The mean percentages of take (infectivity) for nonfrozen and frozen doses were 35.3% and 5.9%, respectively (P less than 0.001). In nontreated sheep, the mean percentages of inhibition for nonfrozen and frozen doses were 91.9%, and 54.2%, respectively (P less than 0.01). The exsheathment time seems to be temperature-dependent. The induction of inhibited development of L3 larvae during 7 weeks was as effective as during 5 weeks at 15 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Danhong injection inhibits the development of atherosclerosis in both Apoe⁻/⁻ and Ldlr⁻/⁻ mice.

    Science.gov (United States)

    Chen, Yuanli; Liu, Mengyang; Zhao, Tao; Zhao, Buchang; Jia, Lifu; Zhu, Yan; Zhang, Boli; Gao, Xiumei; Li, Guangliang; Li, Xiaoju; Xiang, Rong; Han, Jihong; Duan, Yajun

    2014-05-01

    Danhong injection (DHI), a certificated Chinese medical product made from radix salviae miltiorrhizae and flos carthami, is prescribed to patients with coronary heart disease in China. To investigate if DHI can inhibit atherosclerosis, apolipoprotein E-deficient (Apoe⁻/⁻) or low-density lipoprotein receptor-deficient (Ldlr⁻/⁻) mice on high-fat diet were divided into 2 groups and received daily intraperitoneal injection of saline and DHI, respectively, for 16 or 20 weeks. After the treatment, mouse aortas were collected to determine lesions, expression of adenosine triphosphate-binding cassette transporter A1 and tumor necrosis factor-α (TNF-α), and macrophage accumulation. Additionally, serum lipid profiles and expression of hepatic HMG-CoA reductase messenger RNA and low-density lipoprotein receptor protein were determined. We observed that DHI inhibited lesions in both Apoe⁻/⁻ and Ldlr⁻/⁻ mice. Associated with the decreased lesions, the aortic adenosine triphosphate-binding cassette transporter A1 expression was increased, whereas the macrophage accumulation was decreased in male Apoe⁻/⁻ mice and both male and female Ldlr⁻/⁻ mice. Although DHI reduced HMG-CoA reductase messenger RNA expression in both female Apoe⁻/⁻ and Ldlr⁻/⁻ mice, it decreased low-density lipoprotein cholesterol levels only in female Apoe⁻/⁻ mice. In addition to attenuation of lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 in macrophages, and human C-reactive protein in hepatocytes, respectively, at the transcriptional level in vitro, DHI also reduced TNF-α protein expression in aortic root of both Apoe⁻/⁻ and Ldlr⁻/⁻ mice, suggesting the importance of the anti-inflammatory properties of DHI in the inhibition of lesion development. Taken together, our study demonstrates that DHI inhibits atherosclerosis in both Apoe⁻/⁻ and Ldlr⁻/⁻ mice with various mechanisms, including anti-inflammation. The inhibition of atherosclerosis

  6. Distracción osteogénica alveolar como método de aumento del reborde alveolar

    Directory of Open Access Journals (Sweden)

    Denia Morales Navarro

    2011-03-01

    Full Text Available La distracción osteogénica alveolar, como proceso biológico de neoformación de hueso alveolar, nos motivó a la realización de la presente revisión bibliográfica, con el objetivo enfatizar en el análisis de las variables: antecedentes históricos en Cuba, clasificación de los distractores, fases de la distracción (latencia, distracción y consolidación, indicaciones, contraindicaciones, ventajas, desventajas y complicaciones. Se realizó una revisión bibliográfica mediante la consulta de bases de datos de los sistemas referativos, como MEDLINE y PubMed con la utilización de descriptores "alveolar distraction" y "osteogenic distraction". Se consultaron las fuentes bibliográficas publicadas fundamentalmente en los últimos 5 años, lo que reveló que esta técnica es una excelente alternativa para la formación de huesos y tejidos blandos en zonas de atrofia alveolar, que consta de tres etapas: latencia, distracción y consolidación; un método previsible y con bajas tasas de reabsorción ósea en comparación con otras técnicas de aumento del reborde alveolar. Tiene su principal indicación en la terapia de implantes al proveer volumen óseo. Debemos individualizar cada caso y usar el método más adecuado según las características clínicas y personales del paciente. Una adecuada selección de los casos y una mejor comprensión de la técnica son los puntales para lograr exitosos resultados mediante la distracción osteogénica alveolar. En Cuba se ha aplicado poco la distracción alveolar, por lo que ha sido necesario ampliar los estudios sobre esta temática.

  7. Ovine progressive pneumonia virus capsid antigen as found in CD163- and CD172a-positive alveolar macrophages of persistently infected sheep.

    Science.gov (United States)

    Herrmann-Hoesing, L M; Noh, S M; Snekvik, K R; White, S N; Schneider, D A; Truscott, T; Knowles, D P

    2010-05-01

    In situ detection of ovine progressive pneumonia virus (OPPV) and the phenotypic identification of the cells that harbor OPPV have not been described for the OPPV-affected tissues, which include lung, mammary gland, synovial membranes of the carpal joint, and choroid plexus of the brain. In this study, the authors first developed a single enzyme-based automated immunohistochemical (IHC) analysis for detection of OPPV capsid antigen (CA) on OPPV-affected tissues, using 2 anti-CAEV CA monoclonal antibodies, 5A1 and 10A1, and 2 enzyme-based IHC systems. Out of 10 naturally and persistently OPPV-infected ewes, OPPV CA was detected in intercellular regions of the carpal synovial membrane of 1 ewe, in cells resembling alveolar macrophages and pulmonary interstitial macrophages in lung tissue of 3 ewes, and in mammary alveolar cells of 1 ewe. Furthermore, dual enzyme-based automated IHC analyses revealed that OPPV CA was predominantly detected in CD172a- or CD163-positive alveolar macrophages of the lungs and mammary gland. That anti-inflammatory (CD163) and downregulatory (CD172a) types of alveolar macrophage harbor OPPV CA leads to the possibility that during persistent infection with OPPV, the host alveolar macrophage might serve to limit inflammation while OPPV persists undetected by the host adaptive immune response in the lung and mammary gland.

  8. Production of Fibronectin by the Human Alveolar Macrophage: Mechanism for the Recruitment of Fibroblasts to Sites of Tissue Injury in Interstitial Lung Diseases

    Science.gov (United States)

    Rennard, Stephen I.; Hunninghake, Gary W.; Bitterman, Peter B.; Crystal, Ronald G.

    1981-11-01

    Because cells of the mononuclear phagocyte system are known to produce fibronectin and because alveolar macrophages are activated in many interstitial lung diseases, the present study was designed to evaluate a role for the alveolar macrophage as a source of the increased levels of fibronectin found in the lower respiratory tract in interstitial lung diseases and to determine if such fibronectin might contribute to the development of the fibrosis found in these disorders by being a chemoattractant for human lung fibroblasts. Production of fibronectin by human alveolar macrophages obtained by bronchoalveolar lavage and maintained in short-term culture in serum-free conditions was demonstrated; de novo synthesis was confirmed by the incorporation of [14C]proline. This fibronectin had a monomer molecular weight of 220,000 and was antigenically similar to plasma fibronectin. Macrophages from patients with idiopathic pulmonary fibrosis produced fibronectin at a rate 20 times higher than did normal macrophages; macrophages from patients with pulmonary sarcoidosis produced fibronectin at 10 times the normal rate. Macrophages from 6 of 10 patients with various other interstitial disorders produced fibronectin at rates greater than the rate of highest normal control. Human alveolar macrophage fibronectin was chemotactic for human lung fibroblasts, suggesting a functional role for this fibronectin in the derangement of the alveolar structures that is characteristic of these disorders.

  9. MAPK-Mediated YAP Activation Controls Mechanical-Tension-Induced Pulmonary Alveolar Regeneration

    Directory of Open Access Journals (Sweden)

    Zhe Liu

    2016-08-01

    Full Text Available The pulmonary alveolar epithelium undergoes extensive regeneration in response to lung injuries, including lung resection. In recent years, our understanding of cell lineage relationships in the pulmonary alveolar epithelium has improved significantly. However, the molecular and cellular mechanisms that regulate pneumonectomy (PNX-induced alveolar regeneration remain largely unknown. In this study, we demonstrate that mechanical-tension-induced YAP activation in alveolar stem cells plays a major role in promoting post-PNX alveolar regeneration. Our results indicate that JNK and p38 MAPK signaling is critical for mediating actin-cytoskeleton-remodeling-induced nuclear YAP expression in alveolar stem cells. Moreover, we show that Cdc42-controlled actin remodeling is required for the activation of JNK, p38, and YAP in post-PNX lungs. Our findings together establish that the Cdc42/F-actin/MAPK/YAP signaling cascade is essential for promoting alveolar regeneration in response to mechanical tension in the lung.

  10. CCR5 Blockade Suppresses Melanoma Development Through Inhibition of IL-6-Stat3 Pathway via Upregulation of SOCS3.

    Science.gov (United States)

    Tang, Qiu; Jiang, Jun; Liu, Jian

    2015-12-01

    In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, we found that chemokine receptor 5 (CCR5) neutralization resulted in reduced melanoma tumor size, decreased percentage of CD11b+ Gr-1(+) myeloid-derived suppressor cells (MDSCs), and increased proportion of cluster of differentiation (CD)3+ T cells in tumor tissues. Suppressive activity of MDSCs on CD4+ T cells and CD8+ T cell proliferation is significantly inhibited by anti-CCR5 antibody. CCR5 blockade also suppresses interleukin (IL)-6 induction, which in turn deactivates signal transducer and activator of transcription 3 (Stat3) in tumors. Furthermore, the suppressed B16 tumor growth induced by CCR5 blockade is abolished with additional administration of recombinant IL-6. CCR5 blockade also induces suppressor of cytokine signaling 3 (SOCS3) upregulations, and anti-CCR5 antibody fails to suppress expression of phospho-Stat3 (p-Stat3), matrix metallopeptidase 9 (MMP9), and IL-6 in cells transfected with SOCS3 short-interfering RNA (SiRNA). All these data suggest that CCR5 blockade suppresses melanoma development through inhibition of IL-6-Stat3 pathway via upregulation of SOCS3.

  11. Ghrelin inhibits the development of acute pancreatitis and nuclear factor kappaB activation in pancreas and liver.

    Science.gov (United States)

    Zhou, Xiaolei; Xue, Chengrui

    2009-10-01

    To investigate the influence of ghrelin on the development of severe acute pancreatitis (SAP) and the expression of nuclear factor kappaB (NF-kappaB) p65 in the pancreas and liver. Severe acute pancreatitis was induced in rat by sodium taurocholate injection in the pancreaticobiliary duct. Ghrelin was administrated twice at the dose 10 or 20 nmol/kg per injection, respectively. Then, serum amylase activity; serum tumor necrosis factor alpha, interleukin 1beta, and interleukin 6 concentrations; and morphological signs of pancreatitis and hepatic damage were measured. Meanwhile, determination of pancreatic and hepatic NF-kappaB p65 expression was performed by Western blotting and immunohistochemistry. The serumal parameters increased, and morphological damages were observed in the pancreas and liver in SAP rats. Nuclear factor kappaB p65 expression was significantly higher in the pancreas and liver than sham-operated rats (P pancreas and liver. Ghrelin inhibits the development of acute pancreatitis induced by sodium taurocholate. It exerts the therapeutic effects through inhibiting NF-kappaB expression, thereby blocks the inflammatory signal transduction pathway and reduces the release of inflammatory media and cytokines.

  12. Characteristic aspects of alveolar proteinosis diagnosis Aspectos característicos do diagnóstico da proteinose alveolar

    Directory of Open Access Journals (Sweden)

    Thiago Prudente Bártholo

    2012-02-01

    Full Text Available Alveolar proteinosis is an uncommon pulmonary disease characterized by an accumulation of surfactant in terminal airway and alveoli, thereby impairing gas exchange and engendering respiratory insufficiency in some cases. Three clinically and etiologically distinct forms of pulmonary alveolar proteinosis are recognized: congenital, secondary and idiopathic, the latter corresponding to 90% of the cases. In this case report we present a young male patient that was diagnosed with alveolar proteinosis. Computed tomography of the thorax, bronchoscopy and transbronchial biopsy were performed. The histopathologic aspect was characteristic. The patient was discharged in good health conditions and remains asymptomatic to date.Proteinose alveolar é uma doença pulmonar incomum caracterizada pelo acúmulo de surfactante nas vias aéreas terminais e nos alvéolos, alterando a troca gasosa e, em alguns casos, promovendo insuficiência respiratória. Três formas clínicas e etiologicamente distintas de proteinose alveolar são reconhecidas: congênitas, secundárias e idiopáticas (mais de 90% dos casos são de etiologia idiopática. Neste relato, apresentamos um homem jovem que foi diagnosticado com proteinose pulmonar. Tomografia computadorizada de tórax, broncoscopia e biópsia transbrônquica foram realizadas. O aspecto histopatológico foi característico. O paciente teve alta, com boas condições de saúde, e encontra-se assintomático nos dias de hoje.

  13. Painful neuropathy caused by compression of the inferior alveolar nerve by focal osteosclerotic lesion of the mandible: A case report.

    Science.gov (United States)

    Debevc, David; Hitij, Tomaž; Kansky, Andrej

    2017-01-01

    Osteosclerotic lesions are a common finding on dental radiographs. They are considered developmental variants of a normal bone architecture and they usually do not need any treatment. The purpose of this article is to present a rare case of osteosclerotic lesion of the mandible causing trigeminal neuropathy by compression of the alveolar nerve. The pain started with dental hypersensitivity of the mandibular right first molar. Later on, signs of irreversible molar tooth pulpitis developed. Endodontic therapy and apicoectomy did not resolve the pain, which later intensified, and painful neuropathy localized to inferior alveolar nerve developed; therefore, surgical decompression was indicated. Treating a dental patient with neuralgic pain is always a challenge, especially if there is no obvious source or reason for this type of pain. A clear evaluation and treatment protocol are important to minimize the patient's morbidity and avoid unnecessary overtreatment.

  14. Curcumin inhibits development and cell adhesion in Dictyostelium discoideum: Implications for YakA signaling and GST enzyme function

    Energy Technology Data Exchange (ETDEWEB)

    Garige, Mamatha; Walters, Eric, E-mail: ewalters@howard.edu

    2015-11-13

    The molecular basis for nutraceutical properties of the polyphenol curcumin (Curcuma longa, Turmeric) is complex, affecting multiple factors that regulate cell signaling and homeostasis. Here, we report the effect of curcumin on cellular and developmental mechanisms in the eukaryotic model, Dictyostelium discoideum. Dictyostelium proliferation was inhibited in the presence of curcumin, which also suppressed the prestarvation marker, discoidin I, members of the yakA-mediated developmental signaling pathway, and expression of the extracellular matrix/cell adhesion proteins (DdCAD and csA). This resulted in delayed chemotaxis, adhesion, and development of the organism. In contrast to the inhibitory effects on developmental genes, curcumin induced gstA gene expression, overall GST activity, and generated production of reactive oxygen species. These studies expand our knowledge of developmental and biochemical signaling influenced by curcumin, and lends greater consideration of GST enzyme function in eukaryotic cell signaling, development, and differentiation.

  15. The angiotensin receptor blocker, Losartan, inhibits mammary tumor development and progression to invasive carcinoma

    Science.gov (United States)

    Coulson, Rhiannon; Liew, Seng H.; Connelly, Angela A.; Yee, Nicholas S.; Deb, Siddhartha; Kumar, Beena; Vargas, Ana C.; O’Toole, Sandra A.; Parslow, Adam C.; Poh, Ashleigh; Putoczki, Tracy; Morrow, Riley J.; Alorro, Mariah; Lazarus, Kyren A.; Yeap, Evie F.W.; Walton, Kelly L.; Harrison, Craig A.; Hannan, Natalie J.; George, Amee J.; Clyne, Colin D.; Ernst, Matthias; Allen, Andrew M.; Chand, Ashwini L.

    2017-01-01

    Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2−ve tumors correlating with poor prognosis. However, there is no evidence, so far, of the functional contribution of AT1R to breast tumorigenesis. We explored the potential therapeutic benefit of ARB in a carcinogen-induced mouse model of breast cancer and clarified the mechanisms associated with its success. Mammary tumors were induced with 7,12-dimethylbenz[α]antracene (DMBA) and medroxyprogesterone acetate (MPA) in female wild type mice and the effects of the ARB, Losartan treatment assessed in a preventative setting (n = 15 per group). Tumor histopathology was characterised by immunohistochemistry, real-time qPCR to detect gene expression signatures, and tumor cytokine levels measured with quantitative bioplex assays. AT1R was detected with radiolabelled ligand binding assays in fresh frozen tumor samples. We showed that therapeutic inhibition of AT1R, with Losartan, resulted in a significant reduction in tumor burden; and no mammary tumor incidence in 20% of animals. We observed a significant reduction in tumor progression from DCIS to invasive cancer with Losartan treatment. This was associated with reduced tumor cell proliferation and a significant reduction in IL-6, pSTAT3 and TNFα levels. Analysis of tumor immune cell infiltrates, however, demonstrated no significant differences in the recruitment of lymphocytes or tumour

  16. Inhibition of polyamine oxidase activity affects tumor development during the maize-Ustilago maydis interaction.

    Science.gov (United States)

    Jasso-Robles, Francisco Ignacio; Jiménez-Bremont, Juan Francisco; Becerra-Flora, Alicia; Juárez-Montiel, Margarita; Gonzalez, María Elisa; Pieckenstain, Fernando Luis; García de la Cruz, Ramón Fernando; Rodríguez-Kessler, Margarita

    2016-05-01

    Ustilago maydis is a biotrophic plant pathogenic fungus that leads to tumor development in the aerial tissues of its host, Zea mays. These tumors are the result of cell hypertrophy and hyperplasia, and are accompanied by the reprograming of primary and secondary metabolism of infected plants. Up to now, little is known regarding key plant actors and their role in tumor development during the interaction with U. maydis. Polyamines are small aliphatic amines that regulate plant growth, development and stress responses. In a previous study, we found substantial increases of polyamine levels in tumors. In the present work, we describe the maize polyamine oxidase (PAO) gene family, its contribution to hydrogen peroxide (H2O2) production and its possible role in tumor development induced by U. maydis. Histochemical analysis revealed that chlorotic lesions and maize tumors induced by U. maydis accumulate H2O2 to significant levels. Maize plants inoculated with U. maydis and treated with the PAO inhibitor 1,8-diaminooctane exhibit a notable reduction of H2O2 accumulation in infected tissues and a significant drop in PAO activity. This treatment also reduced disease symptoms in infected plants. Finally, among six maize PAO genes only the ZmPAO1, which encodes an extracellular enzyme, is up-regulated in tumors. Our data suggest that H2O2 produced through PA catabolism by ZmPAO1 plays an important role in tumor development during the maize-U. maydis interaction.

  17. A method for measuring post-extraction alveolar dimensional changes with volumetric computed tomography.

    Science.gov (United States)

    Bontá, Hernán; Galli, Federico G; Caride, Facundo; Carranza, Nelson

    2012-01-01

    The aim of this study is to present a predictable method for evaluating dimensional changes in the alveolar ridge through cone beam computed tomography (CT). Twenty subjects with single-rooted tooth extraction indication were selected for this preliminary report, which is part of a larger ongoing investigation. After extraction, two CT scans were performed; the first within 24 hours post-extraction (TC1) and the second 6 months (TC2) later. A radiographic guide with a radiopaque element placed along the tooth axis was developed to locate the same plane of reference in two different CT scans. For each patient, backtrack analysis was performed in order to establish the reproducibility error of a predetermined point in space between two CT scans. Briefly, an anatomical landmark was selected and its coordinates to the radiopaque marker were recorded. One week later, the coordinates were followed backwards in the same CT scan to obtain the position where the reference point should be located. A similar process was carried out between two different CT scans taken 6 months apart. The distance between the anatomical reference and the obtained point of position was calculated to establish the accuracy of the method. Additionally, a novel method for evaluating dimensional changes of the alveolus after tooth extraction is presented. The backtrack analysis determined an average within-examiner discrepancy between both measurements from the same CT scan of 0.19 mm. SD +/- 0.05. With the method presented herein, a reference point in a CT scan can be accurately backtracked and located in a second CT scan taken six months later. Taken together they open the possibility of calculating dimensional changes that occur in the alveolar ridge over time, such as post-extraction alveolar resorption, or the bone volume gained after different augmentation procedures.

  18. Deficits in lung alveolarization and function after systemic maternal inflammation and neonatal hyperoxia exposure.

    Science.gov (United States)

    Velten, Markus; Heyob, Kathryn M; Rogers, Lynette K; Welty, Stephen E

    2010-05-01

    Systemic maternal inflammation contributes to preterm birth and is associated with development of bronchopulmonary dysplasia (BPD). Infants with BPD exhibit decreased alveolarization, diffuse interstitial fibrosis with thickened alveolar septa, and impaired pulmonary function. We tested the hypothesis that systemic prenatal LPS administration to pregnant mice followed by postnatal hyperoxia exposure is associated with prolonged alterations in pulmonary structure and function after return to room air (RA) that are more severe than hyperoxia exposure alone. Timed-pregnant C3H/HeN mice were dosed with LPS (80 microg/kg) or saline on gestation day 16. Newborn pups were exposed to RA or 85% O2 for 14 days and then to RA for an additional 14 days. Data were collected and analyzed on postnatal days 14 and 28. The combination of prenatal LPS and postnatal hyperoxia exposure generated a phenotype with more inflammation (measured as no. of macrophages per high-power field) than either insult alone at day 28. The combined exposures were associated with a diffuse fibrotic response [measured as hydroxyproline content (microg)] but did not induce a more severe developmental arrest than hyperoxia alone. Pulmonary function tests indicated that hyperoxia, independent of maternal exposure, induced compliance decreases on day 14 that did not persist after RA recovery. Either treatment alone or combined induced an increase in resistance on day 14, but the increase persisted on day 28 only in pups receiving the combined treatment. In conclusion, the combination of systemic maternal inflammation and neonatal hyperoxia induced a prolonged phenotype of arrested alveolarization, diffuse fibrosis, and impaired lung mechanics that mimics human BPD. This new model should be useful in designing studies of specific mechanisms and interventions that could ultimately be utilized to define therapies to prevent BPD in premature infants.

  19. Deficits in lung alveolarization and function after systemic maternal inflammation and neonatal hyperoxia exposure

    Science.gov (United States)

    Heyob, Kathryn M.; Rogers, Lynette K.; Welty, Stephen E.

    2010-01-01

    Systemic maternal inflammation contributes to preterm birth and is associated with development of bronchopulmonary dysplasia (BPD). Infants with BPD exhibit decreased alveolarization, diffuse interstitial fibrosis with thickened alveolar septa, and impaired pulmonary function. We tested the hypothesis that systemic prenatal LPS administration to pregnant mice followed by postnatal hyperoxia exposure is associated with prolonged alterations in pulmonary structure and function after return to room air (RA) that are more severe than hyperoxia exposure alone. Timed-pregnant C3H/HeN mice were dosed with LPS (80 μg/kg) or saline on gestation day 16. Newborn pups were exposed to RA or 85% O2 for 14 days and then to RA for an additional 14 days. Data were collected and analyzed on postnatal days 14 and 28. The combination of prenatal LPS and postnatal hyperoxia exposure generated a phenotype with more inflammation (measured as no. of macrophages per high-power field) than either insult alone at day 28. The combined exposures were associated with a diffuse fibrotic response [measured as hydroxyproline content (μg)] but did not induce a more severe developmental arrest than hyperoxia alone. Pulmonary function tests indicated that hyperoxia, independent of maternal exposure, induced compliance decreases on day 14 that did not persist after RA recovery. Either treatment alone or combined induced an increase in resistance on day 14, but the increase persisted on day 28 only in pups receiving the combined treatment. In conclusion, the combination of systemic maternal inflammation and neonatal hyperoxia induced a prolonged phenotype of arrested alveolarization, diffuse fibrosis, and impaired lung mechanics that mimics human BPD. This new model should be useful in designing studies of specific mechanisms and interventions that could ultimately be utilized to define therapies to prevent BPD in premature infants. PMID:20223995

  20. Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter.

    Science.gov (United States)

    Granillo, Olivia M; Brahmajothi, Mulugu V; Li, Sheng; Whorton, A Richard; Mason, S Nicholas; McMahon, Timothy J; Auten, Richard L

    2008-07-01

    Nitric oxide (NO) effects are often mediated via S-nitrosothiol (SNO) formation; SNO uptake has recently been shown to be mediated in some cell types via system L-type amino acid transporters (LAT-1, 2). Inhaled NO therapy may exert some biological effects via SNO formation. We therefore sought to determine if pulmonary epithelial SNO uptake depended on LAT or peptide transporter 2 (PEPT2). Both LAT-1 and PEPT2 proteins were detected by immunoblot and immunocytochemistry in L2 cells and rat lung. We tested SNO uptake through the transporters by exposing rat alveolar epithelial cells (L2 and type II) to RSNOs: S-nitrosoglutathione, S-nitrosocysteinylglycine (SNO-Cys-Gly), S-nitrosocysteine (CSNO), and to NO donor diethylamine NONOate (DEA-NONOate). SNO was detected in cell lysates by ozone chemiluminescence. NO uptake was detected by fluorescence in alveolar epithelial cells loaded with 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) diacetate cultured in submersion and exposed to RSNOs and DEA NONOate. Addition of L-Cys but not D-Cys to RSNOs or DEA NONOate increased SNO and DAF-FM signal that was inhibited by coincubation with LAT competitors. Incubation of cells with PEPT2 substrate SNO-Cys-Gly showed no increase in SNO or DAF-FM signal unless incubated with L-Cys. This was unaffected by PEPT2 inhibition. We conclude that RSNOs (thionitrites, S-nitrosothiols) and NO enter alveolar epithelial cells predominantly by S-nitrosation of L-Cys, which is then imported through LAT.

  1. Genetic pharmacotherapy as an early CNS drug development strategy: testing glutaminase inhibition for schizophrenia treatment in adult mice

    Directory of Open Access Journals (Sweden)

    Susana eMingote

    2016-01-01

    Full Text Available Genetic pharmacotherapy is an early drug development strategy for the identification of novel CNS targets in mouse models prior to the development of specific ligands. Here for the first time, we have implemented this strategy to address the potential therapeutic value of a glutamate-based pharmacotherapy for schizophrenia involving inhibition of the glutamate recycling enzyme phosphate-activated glutaminase. Mice constitutively heterozygous for GLS1, the gene encoding glutaminase, manifest a schizophrenia resilience phenotype, a key dimension of which is an attenuated locomotor response to propsychotic amphetamine challenge. If resilience is due to glutaminase deficiency in adulthood, then glutaminase inhibitors should have therapeutic potential. However, this has been difficult to test given the dearth of neuroactive glutaminase inhibitors. So, we used genetic pharmacotherapy to test the therapeutic potential of glutaminase inhibition. We specifically asked whether adult induction of GLS1 heterozygosity would attenuate amphetamine responsiveness. We generated conditional floxGLS1 mice and crossed them with global CAG ERT2 cre/+ mice to produce GLS1 iHET mice, susceptible to tamoxifen induction of GLS1 heterozygosity. One month after tamoxifen treatment of adult GLS1 iHET mice, we found a 50% reduction in GLS1 allelic abundance and glutaminase mRNA levels in the brain. While GLS1 iHET mice showed some recombination prior to tamoxifen, there was no impact on mRNA levels. We then asked whether induction of GLS heterozygosity would attenuate the locomotor response to propsychotic amphetamine challenge. Before tamoxifen, control and GLS1 iHET mice did not differ in their response to amphetamine. One month after tamoxifen treatment, amphetamine-induced hyperlocomotion was blocked in GLS1 iHET mice. The block was largely maintained after 5 months. Thus, a genetically induced glutaminase reduction — mimicking pharmacological inhibition — strongly

  2. Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

    Science.gov (United States)

    Stadelmann, Britta; Rufener, Reto; Aeschbacher, Denise; Spiliotis, Markus; Gottstein, Bruno; Hemphill, Andrew

    2016-03-01

    The metacestode (larval) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV), comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

  3. Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis.

    Directory of Open Access Journals (Sweden)

    Britta Stadelmann

    2016-03-01

    Full Text Available The metacestode (larval stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE, a very severe and in many cases incurable disease. To date, benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options. Benzimidazoles inhibit metacestode proliferation, but do not act parasiticidal. Thus, benzimidazoles have to be taken a lifelong, can cause adverse side effects such as hepatotoxicity, and are ineffective in some patients. We here describe a newly developed screening cascade for the evaluation of the in vitro efficacy of new compounds that includes assessment of parasiticidal activity. The Malaria Box from Medicines for Malaria Venture (MMV, comprised of 400 commercially available chemicals that show in vitro activity against Plasmodium falciparum, was repurposed. Primary screening was carried out at 10 μM by employing the previously described PGI assay, and resulted in the identification of 24 compounds that caused physical damage in metacestodes. Seven out of these 24 drugs were also active at 1 μM. Dose-response assays revealed that only 2 compounds, namely MMV665807 and MMV665794, exhibited an EC50 value below 5 μM. Assessments using human foreskin fibroblasts and Reuber rat hepatoma cells showed that the salicylanilide MMV665807 was less toxic for these two mammalian cell lines than for metacestodes. The parasiticidal activity of MMV665807 was then confirmed using isolated germinal layer cell cultures as well as metacestode vesicles by employing viability assays, and its effect on metacestodes was morphologically evaluated by electron microscopy. However, both oral and intraperitoneal application of MMV665807 to mice experimentally infected with E. multilocularis metacestodes did not result in any reduction of the parasite load.

  4. Lithium Impairs Kidney Development and Inhibits Glycogen Synthase Kinase-3β in Collecting Duct Principal Cells

    DEFF Research Database (Denmark)

    Kjærsgaard, Gitte; Madsen, Kirsten; Marcussen, Niels

    on serine9 (pGSK-3β)and subsequent epithelial to mesenchymal dedifferentiation (EMT). GSK-3β immunoreactive protein was associated with collecting ducts in developing and adult human and rat kidney. Total GSK-3β protein abundance was stable in medulla while it decreased in cortex in the postnatal period...

  5. Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis.

    Science.gov (United States)

    Bhattarai, Govinda; Poudel, Sher Bahadur; Kook, Sung-Ho; Lee, Jeong-Chae

    2016-01-01

    Resveratrol is an antioxidant and anti-inflammatory polyphenol. Periodontitis is induced by oral pathogens, where a systemic inflammatory response accompanied by oxidative stress is the major event initiating disease. We investigated how resveratrol modulates cellular responses and the mechanisms related to this modulation in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (hGFs). We also explored whether resveratrol protects rats against alveolar bone loss in an experimental periodontitis model. Periodontitis was induced around the first upper molar of the rats by applying ligature infused with LPS. Stimulating hGFs with 5μg/ml LPS augmented the expression of cyclooxygenase-2, matrix metalloproteinase (MMP)-2, MMP-9, and Toll-like receptor-4. LPS treatment also stimulated the production of reactive oxygen species (ROS) and the phosphorylation of several protein kinases in the cells. However, the expression of heme oxygenase-1 (HO-1) and nuclear factor-E2 related factor 2 (Nrf2) was inhibited by the addition of LPS. Resveratrol treatment almost completely inhibited all of these changes in LPS-stimulated cells. Specifically, resveratrol alone augmented HO-1 induction via Nrf2-mediated signaling. Histological and micro-CT analyses revealed that administration of resveratrol (5mg/kg body weight) improved ligature/LPS-mediated alveolar bone loss in rats. Resveratrol also attenuated the production of inflammation-related proteins, the formation of osteoclasts, and the production of circulating ROS in periodontitis rats. Furthermore, resveratrol suppressed LPS-mediated decreases in HO-1 and Nrf2 levels in the inflamed periodontal tissues. Collectively, our findings suggest that resveratrol protects rats from periodontitic tissue damage by inhibiting inflammatory responses and by stimulating antioxidant defense systems. The aims of this study were to investigate how resveratrol modulates cellular responses and the mechanisms related to this modulation in

  6. Strong inhibition of replicative DNA synthesis in the developing rat cerebral cortex and glioma cells by roscovitine.

    Science.gov (United States)

    Yakisich, Juan Sebastian; Vita, Marina Fernanda; Siden, Ake; Tasat, Deborah Ruth; Cruz, Mabel

    2010-06-01

    The effects of the cyclin-dependent kinase inhibitors roscovitine and olomoucine on DNA synthesis rate during normal rat brain development were studied by using short time (90 min) incubation. Both purine analogues at 100 microM concentration decreased the DNA synthesis of rat cerebral cortex in an age-dependent manner. The maximum inhibitory effect (approximately 90% for roscovitine, approximately 60% for olomoucine) occurred in rats of 2-13 days postnatal age. In adult rats (> 60 days postnatal age), the effect of both purine analogues was low. Roscovitine even at 200 microM concentration did not inhibit the fraction of DNA synthesis insensitive to hydroxyurea (unscheduled DNA synthesis (UDS)). In addition, in the RG2 rat glioma model, roscovitine produced a strong inhibition of DNA synthesis in glioma cells when compared to adult normal tissue. Since in adult rat brain more than 60% of DNA synthesis is related to DNA repair, usually measured as UDS, our results indicate that roscovitine strongly blocks ongoing DNA synthesis connected with replicative processes.

  7. Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70

    Science.gov (United States)

    Warzecha, Zygmunt; Dembinski, Artur; Ceranowicz, Piotr; Konturek, Stanislaw J; Dembinski, Marcin; Pawlik, Wieslaw W; Tomaszewska, Romana; Stachura, Jerzy; Kusnierz-Cabala, Beata; Naskalski, Jerzy W; Konturek, Peter C

    2005-01-01

    AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process. METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg). RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1β. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis. CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70. PMID:16273606

  8. Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70

    Institute of Scientific and Technical Information of China (English)

    Zygmunt Warzecha; Jerzy W Naskalski; Peter C Konturek; Artur Dembinski; Piotr Ceranowicz; Stanislaw J Konturek; Marcin Dembinski; Wieslaw W Pawlik; Romana Tomaszewska; Jerzy Stachura; Beata Kusnierz-Cabala

    2005-01-01

    AIM: To determine whether ischemic preconditioning (IP)affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process.METHODS: In male Wistar rats, IP was performed by damping of celiac artery (twice for 5 min at 5-min intervals).Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg).RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1β.Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis.Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis.CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.

  9. Inhibition of nodule development by multicopy promoters of Rhizobium meliloti nif/fix genes

    Institute of Scientific and Technical Information of China (English)

    吴桐; 朱家璧; 俞冠翘; 沈善炯

    1995-01-01

    Using luc gene as a reporter to study the activation of Rhizobium meliloti nif/fix genes in thedevelopment of symbiosis,the authors observed that nodule development and nitrogen fixation were inhibitedby both multicopy promoters of nifHDK and fixABCX.The phenotype of R.meliloti containing multicopynif/fix promoters appeared exactly like that of nifA mutant.Using lacZ as a reporter,the authors got the same re-sults.By contrast,the rhizobia containing low-copy promoters of nif/fix genes were normal fornodule development and nitrogen fixation.These results substantiate the evidence that the product of nifAgene not only acts as a transcriptional activator of nif/fix genes,but also plays an important role in thedevelopment of root nodules.

  10. The selective vitamin D receptor agonist, elocalcitol, reduces endometriosis development in a mouse model by inhibiting peritoneal inflammation.

    Science.gov (United States)

    Mariani, Margherita; Viganò, Paola; Gentilini, Davide; Camisa, Barbara; Caporizzo, Elvira; Di Lucia, Pietro; Monno, Antonella; Candiani, Massimo; Somigliana, Edgardo; Panina-Bordignon, Paola

    2012-07-01

    Endometriosis, which is characterized by the growth of endometrial tissue at ectopic locations as well as vascular development and inflammation, is still an unmet clinical need since an optimal drug that allows for both pain and infertility management does not exist. Since both the eutopic and the ectopic endometrium express the vitamin D receptor (VDR), and VDR agonists are endowed with anti-proliferative and anti-inflammatory properties, we evaluated the effect of elocalcitol, a VDR agonist with low calcaemic liability, in a mouse model of experimentally induced endometriosis. Endometriosis was induced by injection of syngeneic endometrial tissue fragments into adult Balb/c female mice. After having confirmed by immunohistochemistry that endometriotic lesions developing in mice expressed VDR, the mice were administered with elocalcitol (100 μg/kg) or vehicle orally, once a day, for various durations of time. In this model, elocalcitol was able to reduce total lesion weight up to 70% upon treatment for 1 week before and 2 weeks after disease induction. Interestingly, a therapeutic effect was also observed on already established lesions. Elocalcitol was shown to reduce the capacity of mouse endometrial cells to adhere to collagen. In addition in treated mice, a decreased state of peritoneal inflammation was demonstrated by the inhibition of macrophage recruitment and inflammatory cytokine secretion. The VDR agonist elocalcitol inhibits lesion development in a validated mouse model of endometriosis, and exerts a protective effect on both the implantation and organization of transferred endometrial tissue. These preliminary data in mice provide a sound rationale for further testing in primate models and eventually in humans.

  11. Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis.

    Science.gov (United States)

    Hoffman, Ewelina; Patel, Aateka; Ball, Doug; Klapwijk, Jan; Millar, Val; Kumar, Abhinav; Martin, Abigail; Mahendran, Rhamiya; Dailey, Lea Ann; Forbes, Ben; Hutter, Victoria

    2017-05-24

    Progress to the clinic may be delayed or prevented when vacuolated or "foamy" alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Cell health, morphology and lipid content were comparable (p content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.

  12. Inhibition of Rho at different stages of thymocyte development gives different perspectives on Rho function.

    Science.gov (United States)

    Cleverley, S; Henning, S; Cantrell, D

    1999-06-17

    Development of thymocytes can be staged according to the levels of expression of the cell-surface markers CD4, CD8, CD44, CD25 and CD2. Thymocyte development is regulated by a complex signalling network [1], one component of which is the GTPase Rho. The bacterial enzyme C3 transferase from Clostridium botulinum selectively ADP-ribosylates Rho in its effector-binding domain and thereby abolishes its biological function [2,3]. To explore the function of Rho in thymocyte development, we previously used the proximal promoter of the gene encoding the Src-family kinase p56lck to make transgenic mice that selectively express C3 transferase in the thymus [4,6]. In these mice, which lack Rho function from the earliest thymocyte stages, thymocyte numbers are reduced by approximately 50- to 100-fold. Here, we describe transgenic mice that express C3 transferase under the control of the locus control region (LCR) of the CD2 gene; this regulatory element drives expression at a later stage of thymocyte development than the lck proximal promoter [7]. In these mice, thymocyte numbers were also reduced by 50- to 100-fold, but unlike the lck-C3 mice, in which the reduction predominantly results from defects in cell survival of CD25(+) thymocyte progenitors, the CD2-C3 transgenic mice had a pre-T-cell differentiation block at the CD25(+) stage after rearrangement of the T-cell receptor (TCR) beta chains. Analysis of CD2-C3 mice demonstrated that Rho acts as an intracellular switch for TCR beta selection, the critical thymic-differentiation checkpoint. These results show that Rho-mediated survival signals for CD25(+) pre-T cells are generated by the extracellular signals that act on earlier thymocyte precursors and also that temporal cell-type-specific elimination of Rho can reveal different functions of this GTPase in vivo.

  13. The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap.

    Science.gov (United States)

    Lavado, Alfonso; Ware, Michelle; Paré, Joshua; Cao, Xinwei

    2014-11-01

    The corpus callosum connects cerebral hemispheres and is the largest axon tract in the mammalian brain. Callosal malformations are among the most common congenital brain anomalies and are associated with a wide range of neuropsychological deficits. Crossing of the midline by callosal axons relies on a proper midline environment that harbors guidepost cells emitting guidance cues to instruct callosal axon navigation. Little is known about what controls the formation of the midline environment. We find that two components of the Hippo pathway, the tumor suppressor Nf2 (Merlin) and the transcriptional coactivator Yap (Yap1), regulate guidepost development and expression of the guidance cue Slit2 in mouse. During normal brain development, Nf2 suppresses Yap activity in neural progenitor cells to promote guidepost cell differentiation and prevent ectopic Slit2 expression. Loss of Nf2 causes malformation of midline guideposts and Slit2 upregulation, resulting in callosal agenesis. Slit2 heterozygosity and Yap deletion both restore callosal formation in Nf2 mutants. Furthermore, selectively elevating Yap activity in midline neural progenitors is sufficient to disrupt guidepost formation, upregulate Slit2 and prevent midline crossing. The Hippo pathway is known for its role in controlling organ growth and tumorigenesis. Our study identifies a novel role of this pathway in axon guidance. Moreover, by linking axon pathfinding and neural progenitor behaviors, our results provide an example of the intricate coordination between growth and wiring during brain development.

  14. Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism

    Directory of Open Access Journals (Sweden)

    Jackson Lauren R

    2012-03-01

    Full Text Available Abstract Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P

  15. Reactivity of alveolar epithelial cells in primary culture with type I cell monoclonal antibodies.

    Science.gov (United States)

    Danto, S I; Zabski, S M; Crandall, E D

    1992-03-01

    An understanding of the process of alveolar epithelial cell growth and differentiation requires the ability to trace and analyze the phenotypic transitions that the cells undergo. This analysis demands specific phenotypic probes to type II and, especially, type I pneumocytes. To this end, monoclonal antibodies have been generated to type I alveolar epithelial cells using an approach designed to enhance production of lung-specific clones from a crude lung membrane preparation. The monoclonal antibodies were screened by a combination of enzyme-linked immunosorbent assay and immunohistochemical techniques, with the determination of type I cell specificity resting primarily on immunoelectron microscopic localization. Two of these new markers of the type I pneumocyte phenotype (II F1 and VIII B2) were used to analyze primary cultures of type II cells growing on standard tissue culture plastic and on a variety of substrata reported to affect the morphology of these cells in culture. On tissue culture plastic, the antibodies fail to react with early (days 1 to 3) type II cell cultures. The cells become progressively more reactive with time in culture to a plateau of approximately 6 times background by day 8, with a maximum rate of increase between days 3 and 5. This finding is consistent with the hypothesis that type II cells in primary culture undergo at least partial differentiation into type I cells. Type II cells grown on laminin, which reportedly delays the loss of type II cell appearance, and on fibronectin, which has been reported to facilitate cell spreading and loss of type II cell features, develop the type I cell markers during cultivation in vitro with kinetics similar to those on uncoated tissue culture plastic. Cells on type I collagen and on tissue culture-treated Nuclepore filters, which have been reported to support monolayers with type I cell-like morphology, also increase their expression of the II F1 and VIII B2 epitopes around days 3 to 5. Taken

  16. Experimental alveolitis in rats: microbiological, acute phase response and histometric characterization of delayed alveolar healing.

    Science.gov (United States)

    Rodrigues, Moacyr Tadeu Vicente; Cardoso, Camila Lopes; Carvalho, Paulo Sérgio Perri de; Cestari, Tânia Mary; Feres, Magda; Garlet, Gustavo Pompermaier; Ferreira, Osny

    2011-01-01

    The pathogenesis of alveolitis is not well known and therefore experimental situations that mimic some features of this disease should be developed. In this study, the evolution of the experimentally induced infection in rat sockets is characterized, which leads to clinical signs of suppurative alveolitis with remarkable wound healing disturbs. Non-infected (Group I) and experimentally infected sockets in Rattus novergicus (Group II) were histometrically evaluated regarding the kinetics of alveolar healing. In addition, the characterization of the present bacteria in inoculation material and the serum levels of C-reactive protein (CRP) were performed. The detected species were Capnocytophaga ochracea, Fusobacterium nucleatum ss nucleatum, Prevotella melaninogenica, Streptococcus anginosus, Treponema socranskii and Streptococcus sanguis. All experimentally infected rats developed suppurative alveolitis, showing higher levels of CRP in comparison to those non-infected ones. Furthermore, infected rats presented a significant delayed wound healing as measured by the histometric analysis (higher persistent polymorphonuclear infiltrate and lower density of newly formed bone). These findings indicate that rat sockets with experimentally induced infection produced higher levels of serum CRP, showing the potential of disseminated infection and a disturb in the alveolar repair process in an interesting experimental model for alveolitis studies.

  17. Experimental alveolitis in rats: microbiological, acute phase response and histometric characterization of delayed alveolar healing

    Directory of Open Access Journals (Sweden)

    Moacyr Tadeu Vicente Rodrigues

    2011-06-01

    Full Text Available The pathogenesis of alveolitis is not well known and therefore experimental situations that mimic some features of this disease should be developed. OBJECTIVE: In this study, the evolution of the experimentally induced infection in rat sockets is characterized, which leads to clinical signs of suppurative alveolitis with remarkable wound healing disturbs. MATERIAL AND METHODS: Non-infected (Group I and experimentally infected sockets in Rattus novergicus (Group II were histometrically evaluated regarding the kinetics of alveolar healing. In addition, the characterization of the present bacteria in inoculation material and the serum levels of C-reactive protein (CRP were performed. The detected species were Capnocytophaga ochracea, Fusobacterium nucleatum ss nucleatum, Prevotella melaninogenica, Streptococcus anginosus, Treponema socranskii and Streptococcus sanguis. RESULTS: All experimentally infected rats developed suppurative alveolitis, showing higher levels of CRP in comparison to those non-infected ones. Furthermore, infected rats presented a significant delayed wound healing as measured by the histometric analysis (higher persistent polymorphonuclear infiltrate and lower density of newly formed bone. CONCLUSION: These findings indicate that rat sockets with experimentally induced infection produced higher levels of serum CRP, showing the potential of disseminated infection and a disturb in the alveolar repair process in an interesting experimental model for alveolitis studies.

  18. Three-dimensional microstructure of human alveolar trabecular bone: a micro-computed tomography study

    Science.gov (United States)

    2017-01-01

    Purpose The microstructural characteristics of trabecular bone were identified using micro-computed tomography (micro-CT), in order to develop a potential strategy for implant surface improvement to facilitate osseointegration. Methods Alveolar bone specimens from the cadavers of 30 humans were scanned by high-resolution micro-CT and reconstructed. Volumes of interest chosen within the jaw were classified according to Hounsfield units into 4 bone quality categories. Several structural parameters were measured and statistically analyzed. Results Alveolar bone specimens with D1 bone quality had significantly higher values for all structural parameters than the other bone quality categories, except for trabecular thickness (Tb.Th). The percentage of bone volume, trabecular separation (Tb.Sp), and trabecular number (Tb.N) varied significantly among bone quality categories. Tb.Sp varied markedly across the bone quality categories (D1: 0.59±0.22 mm, D4: 1.20±0.48 mm), whereas Tb.Th had similar values (D1: 0.30±0.08 mm, D4: 0.22±0.05 mm). Conclusions Bone quality depended on Tb.Sp and number—that is, endosteal space architecture—rather than bone surface and Tb.Th. Regardless of bone quality, Tb.Th showed little variation. These factors should be taken into account when developing individualized implant surface topographies. PMID:28261521

  19. SPC-Cre-ERT2 transgenic mouse for temporal gene deletion in alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Yao-Song Gui

    Full Text Available Although several Cre-loxP-based gene knockout mouse models have been generated for the study of gene function in alveolar epithelia in the lung, their applications are still limited. In this study, we developed a SPC-Cre-ER(T2 mouse model, in which a tamoxifen-inducible Cre recombinase (Cre-ER(T2 is under the control of the human surfactant protein C (SPC promoter. The specificity and efficiency of Cre-ER(T2 activity was first evaluated by crossing SPC-Cre-ER(T2 mouse with ROSA26R mouse, a β-galactosidase reporter strain. We found that Cre-ER(T2 was expressed in 30.7% type II alveolar epithelial cells of SPC-Cre-ER(T2/ROSA26R mouse lung tissues in the presence of tamoxifen. We then tested the tamoxifen-inducible recombinase activity of Cre-ER(T2 in a mouse strain bearing TSC1 conditional knockout alleles (TSC1(fx/fx. TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ER(T2/TSC1(fx/fx mice. Therefore this SPC-Cre-ER(T2 mouse model may be a valuable tool to investigate functions of genes in lung development, physiology and disease.

  20. The contrast between alveolar and velar stops with typical speech data: acoustic and articulatory analyses.

    Science.gov (United States)

    Melo, Roberta Michelon; Mota, Helena Bolli; Berti, Larissa Cristina

    2017-06-08

    This study used acoustic and articulatory analyses to characterize the contrast between alveolar and velar stops with typical speech data, comparing the parameters (acoustic and articulatory) of adults and children with typical speech development. The sample consisted of 20 adults and 15 children with typical speech development. The analyzed corpus was organized through five repetitions of each target-word (/'kap ə/, /'tapə/, /'galo/ e /'daɾə/). These words were inserted into a carrier phrase and the participant was asked to name them spontaneously. Simultaneous audio and video data were recorded (tongue ultrasound images). The data was submitted to acoustic analyses (voice onset time; spectral peak and burst spectral moments; vowel/consonant transition and relative duration measures) and articulatory analyses (proportion of significant axes of the anterior and posterior tongue regions and description of tongue curves). Acoustic and articulatory parameters were effective to indicate the contrast between alveolar and velar stops, mainly in the adult group. Both speech analyses showed statistically significant differences between the two groups. The acoustic and articulatory parameters provided signals to characterize the phonic contrast of speech. One of the main findings in the comparison between adult and child speech was evidence of articulatory refinement/maturation even after the period of segment acquisition.

  1. SPC-Cre-ERT2 transgenic mouse for temporal gene deletion in alveolar epithelial cells.

    Science.gov (United States)

    Gui, Yao-Song; Wang, Lianmei; Tian, Xinlun; Feng, Ruie; Ma, Aiping; Cai, Baiqiang; Zhang, Hongbing; Xu, Kai-Feng

    2012-01-01

    Although several Cre-loxP-based gene knockout mouse models have been generated for the study of gene function in alveolar epithelia in the lung, their applications are still limited. In this study, we developed a SPC-Cre-ER(T2) mouse model, in which a tamoxifen-inducible Cre recombinase (Cre-ER(T2)) is under the control of the human surfactant protein C (SPC) promoter. The specificity and efficiency of Cre-ER(T2) activity was first evaluated by crossing SPC-Cre-ER(T2) mouse with ROSA26R mouse, a β-galactosidase reporter strain. We found that Cre-ER(T2) was expressed in 30.7% type II alveolar epithelial cells of SPC-Cre-ER(T2)/ROSA26R mouse lung tissues in the presence of tamoxifen. We then tested the tamoxifen-inducible recombinase activity of Cre-ER(T2) in a mouse strain bearing TSC1 conditional knockout alleles (TSC1(fx/fx)). TSC1 deletion was detected in the lungs of tamoxifen treated SPC-Cre-ER(T2)/TSC1(fx/fx) mice. Therefore this SPC-Cre-ER(T2) mouse model may be a valuable tool to investigate functions of genes in lung development, physiology and disease.

  2. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    Science.gov (United States)

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician.

  3. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    Science.gov (United States)

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician. PMID:27471408

  4. Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of collagen-induced arthritis

    Institute of Scientific and Technical Information of China (English)

    Xue Yuan; Lee Ann Garrett-Sinha; Debanjan Sarkar; Shuying Yang

    2014-01-01

    IFT20 is the smallest member of the intraflagellar transport protein (IFT) complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20flox/flox (IFT20f/f) mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis (CIA). We found that both Lck-Cre/IFT20f/f and CD4-Cre/IFT20f/f mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4-and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20f/f mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20f/f mice compared to Lck-Cre/IFT201/1 littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20f/f mice had only mild effects on the development of T cells and CIA. The expression of IL-1b, IL-6 and TGF-b1 were significantly downregulated in the paw of Lck-Cre/IFT20f/f mice, but just slight decreased in CD4-Cre/IFT20f/f mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

  5. Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

    Directory of Open Access Journals (Sweden)

    Gintaras Juodzbalys

    2011-01-01

    Full Text Available Objectives: The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement.Material and Methods: Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies.Results: In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement.Conclusions: The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management.

  6. An automatic early stage alveolar-bone-resorption evaluation method on digital dental panoramic radiographs

    Science.gov (United States)

    Zhang, Min; Katsumata, Akitoshi; Muramatsu, Chisako; Hara, Takeshi; Suzuki, Hiroki; Fujita, Hiroshi

    2014-03-01

    Periodontal disease is a kind of typical dental diseases, which affects many adults. The presence of alveolar bone resorption, which can be observed from dental panoramic radiographs, is one of the most important signs of the progression of periodontal disease. Automatically evaluating alveolar-bone resorption is of important clinic meaning in dental radiology. The purpose of this study was to propose a novel system for automated alveolar-bone-resorption evaluation from digital dental panoramic radiographs for the first time. The proposed system enables visualization and quantitative evaluation of alveolar bone resorption degree surrounding the teeth. It has the following procedures: (1) pre-processing for a test image; (2) detection of tooth root apices with Gabor filter and curve fitting for the root apex line; (3) detection of features related with alveolar bone by using image phase congruency map and template matching and curving fitting for the alveolar line; (4) detection of occlusion line with selected Gabor filter; (5) finally, evaluation of the quantitative alveolar-bone-resorption degree in the area surrounding teeth by simply computing the average ratio of the height of the alveolar bone and the height of the teeth. The proposed scheme was applied to 30 patient cases of digital panoramic radiographs, with alveolar bone resorption of different stages. Our initial trial on these test cases indicates that the quantitative evaluation results are correlated with the alveolar-boneresorption degree, although the performance still needs further improvement. Therefore it has potential clinical practicability.

  7. Blue-Green Algae Inhibit the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice.

    Science.gov (United States)

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Wegner, Casey J; Park, Young-Ki; Balunas, Marcy; Lee, Ji-Young

    2015-12-01

    Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE(-/-)) mice, a well-established mouse model of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks. Plasma total cholesterol (TC) and triglycerides (TG) were measured, and livers were analyzed for histology and gene expression. Morphometric analysis for lesions and immunohistochemical analysis for CD68 were conducted in the aorta and the aortic root. NO supplementation significantly decreased plasma TC and TG, and liver TC, compared to control and SP groups. In the livers of NO-fed mice, less lipid droplets were present with a concomitant decrease in fatty acid synthase protein levels than the other groups. There was a significant increase in hepatic low-density lipoprotein receptor protein levels in SP-supplemented mice than in control and NO groups. Quantification of aortic lesions by en face analysis demonstrated that both NO and SP decreased aortic lesion development to a similar degree compared with control. While lesions in the aortic root were not significantly different between groups, the CD68-stained area in the aortic root was significantly lowered in BGA-fed mice than controls. In conclusion, both NO and SP supplementation decreased the development of atherosclerotic lesions, suggesting that they may be used as a natural product for atheroprotection.

  8. Bruxism elicited by inferior alveolar nerve injury: a case report.

    Science.gov (United States)

    Melis, Marcello; Coiana, Carlo; Secci, Simona

    2012-02-01

    The aim of this case report is to describe the history of a patient who received an injury to the right inferior alveolar nerve after placement of a dental implant, with bruxism noted afterward. The symptoms were managed by the use of an occlusal appliance worn at night and occasionally during the day, associated with increased awareness of parafunction during the day to reduce muscle pain and fatigue. Paresthesia of the teeth, gingiva, and lower lip persisted but were reduced during appliance use.

  9. Alveolar ridge augmentation in rats by Bio-Oss

    DEFF Research Database (Denmark)

    Pinholt, E M; Bang, G; Haanaes, H R

    1991-01-01

    The purpose of the study was to examine if Bio-Oss initiated osteoinduction or osteoconduction when implanted into rats. Sintered and unsintered granules of the anorganic bovine bone Bio-Oss was implanted subperiosteally for alveolar ridge augmentation purposes and heterotopically in the abdominal...... muscles of rats. Light microscopic evaluation revealed no osteoinduction or osteoconduction in connection with sintered or unsintered Bio-Oss. A foreign body reaction was observed around both forms....

  10. Alveolar bone loss: mechanisms, potential therapeutic targets, and interventions.

    Science.gov (United States)

    Intini, G; Katsuragi, Y; Kirkwood, K L; Yang, S

    2014-05-01

    This article reviews recent research into mechanisms underlying bone resorption and highlights avenues of investigation that may generate new therapies to combat alveolar bone loss in periodontitis. Several proteins, signaling pathways, stem cells, and dietary supplements are discussed as they relate to periodontal bone loss and regeneration. RGS12 is a crucial protein that mediates osteoclastogenesis and bone destruction, and a potential therapeutic target. RGS12 likely regulates osteoclast differentiation through regulating calcium influx to control the calcium oscillation-NFATc1 pathway. A working model for RGS10 and RGS12 in the regulation of Ca(2+) oscillations during osteoclast differentiation is proposed. Initiation of inflammation depends on host cell-microbe interactions, including the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Oral p38 inhibitors reduced lipopolysaccharide (LPS)-induced bone destruction in a rat periodontitis model but showed unsatisfactory safety profiles. The p38 substrate MK2 is a more specific therapeutic target with potentially superior tolerability. Furthermore, MKP-1 shows anti-inflammatory activity, reducing inflammatory cytokine biosynthesis and bone resorption. Multipotent skeletal stem cell (SSC) populations exist within the bone marrow and periosteum of long bones. These bone-marrow-derived SSCs and periosteum-derived SSCs have shown therapeutic potential in several applications, including bone and periodontal regeneration. The existence of craniofacial bone-specific SSCs is suggested based on existing studies. The effects of calcium, vitamin D, and soy isoflavone supplementation on alveolar and skeletal bone loss in post-menopausal women were investigated. Supplementation resulted in stabilization of forearm bone mass density and a reduced rate of alveolar bone loss over 1 yr, compared with placebo. Periodontal attachment levels were also well-maintained and alveolar bone loss suppressed during 24 wk of

  11. Thermal behavior of premises equipped with different alveolar structures

    OpenAIRE

    Lajimi Nour; Boukadida Noureddine

    2015-01-01

    This paper presents a numerical study of local thermal behavior. Vertical walls are equipped with alveolar structure and/or simple glazing in East, South and West frontages. Local temperature is assumed to be variable with time or imposed at set point temperature. Results principally show that the simple glazing number has a sensitive effect on convection heat transfer and interior air temperature. They also show that the diode effect is more sensitive in w...

  12. Coronectomy - A viable alternative to prevent inferior alveolar nerve injury

    Directory of Open Access Journals (Sweden)

    Alok Sagtani

    2015-12-01

    Full Text Available Background and Objectives: Coronectomy is a relatively new method to prevent the risk of Inferior Alveolar Nerve (IAN injury during removal of lower third molars with limited scientific literature among Nepalese patients. Thus, a study was designed to evaluate coronectomy regarding its use, outcomes and complications.Materials and Methods: A descriptive study was conducted from December 2012 to December 2013 among patients attending Department of Oral and Maxillofacial Surgery, College of Dental Sciences, BP Koirala Institute of Health Sciences, Dharan, Nepal for removal of mandibular third molars. After reviewing the radiograph for proximity of third molar to the IAN, coronectomy was advised. A written informed consent was obtained from the patients and coronectomy was performed. Patients were recalled after one week. The outcome measures in the follow-up visit were primary healing, pain, infection, dry socket, root exposure and IAN injury. The prevalence of IAN proximity of lower third molars and incidence of complications were calculated.Results: A total 300 mandibular third molars were extracted in 278 patients during the study period. Out of 300 impacted mandibular third molar, 41 (13.7% showed close proximity to inferior alveolar nerve . The incidence of complications and failed procedure was 7.4% among the patients who underwent coronectomy. During the follow up visit, persistent pain and root exposure was reported while other complications like inferior alveolar nerve injury, dry socket and infection was not experienced by the study patients.Conclusion: With a success rate of 92.6% among the 41 patients, coronectomy is a viable alternative to conventional total extraction for mandibular third molars who have a higher risk for damage to the inferior alveolar nerve.JCMS Nepal. 2015;11(3:1-5.

  13. Inhibition of planar cell polarity extends neural growth during regeneration, homeostasis, and development.

    Science.gov (United States)

    Beane, Wendy S; Tseng, Ai-Sun; Morokuma, Junji; Lemire, Joan M; Levin, Michael

    2012-08-10

    The ability to stop producing or replacing cells at the appropriate time is essential, as uncontrolled growth can lead to loss of function and even cancer. Tightly regulated mechanisms coordinate the growth of stem cell progeny with the patterning needs of the host organism. Despite the importance of proper termination during regeneration, cell turnover, and embryonic development, very little is known about how tissues determine when patterning is complete during these processes. Using planarian flatworms, we show that the planar cell polarity (PCP) pathway is required to stop the growth of neural tissue. Although traditionally studied as regulators of tissue polarity, we found that loss of the PCP genes Vangl2, DAAM1, and ROCK by RNA interference (individually or together) resulted in supernumerary eyes and excess optical neurons in intact planarians, while regenerating planarians had continued hyperplasia throughout the nervous system long after controls ceased new growth. This failure to terminate growth suggests that neural tissues use PCP as a readout of patterning, highlighting a potential role for intact PCP as a signal to stem and progenitor cells to halt neuronal growth when patterning is finished. Moreover, we found this mechanism to be conserved in vertebrates. Loss of Vangl2 during normal development, as well as during Xenopus tadpole tail regeneration, also leads to the production of excess neural tissue. This evolutionarily conserved function of PCP represents a tractable new approach for controlling the growth of nerves.

  14. New chemical method of viral inactivation for vaccine development based on membrane fusion inhibition.

    Science.gov (United States)

    Stauffer, Fausto; De Miranda, Joari; Schechter, Marcos C; Queiroz, Fernando A; Santos, Nathalia O; Alves, Ada M B; Da Poian, Andrea T

    2007-11-14

    Membrane fusion is an essential step in the entry of enveloped viruses into their host cells. This process is triggered by conformational changes in viral surface glycoproteins. We have demonstrated previously that modification of vesicular stomatitis virus (VSV) with diethylpyrocarbonate (DEPC) abolished the conformational changes on VSV glycoprotein and the fusion reaction induced by the virus. Moreover, we observed that viral treatment with DEPC inactivates the virus, preserving the conformational integrity of its surface proteins. In the present work, we evaluated the potential use of DEPC as a viral inactivating chemical agent for the development of useful vaccines. Pathogenicity and viral replication in Balb/c mice were abolished by viral treatment with 0.5mM DEPC. In addition, antibodies elicited in mice after intraperitoneal immunization with DEPC-inactivated V