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Sample records for alveolar epithelial repair

  1. Complementary roles of KCa3.1 channels and β1-integrin during alveolar epithelial repair.

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    Girault, Alban; Chebli, Jasmine; Privé, Anik; Trinh, Nguyen Thu Ngan; Maillé, Emilie; Grygorczyk, Ryszard; Brochiero, Emmanuelle

    2015-09-04

    Extensive alveolar epithelial injury and remodelling is a common feature of acute lung injury and acute respiratory distress syndrome (ARDS) and it has been established that epithelial regeneration, and secondary lung oedema resorption, is crucial for ARDS resolution. Much evidence indicates that K(+) channels are regulating epithelial repair processes; however, involvement of the KCa3.1 channels in alveolar repair has never been investigated before. Wound-healing assays demonstrated that the repair rates were increased in primary rat alveolar cell monolayers grown on a fibronectin matrix compared to non-coated supports, whereas an anti-β1-integrin antibody reduced it. KCa3.1 inhibition/silencing impaired the fibronectin-stimulated wound-healing rates, as well as cell migration and proliferation, but had no effect in the absence of coating. We then evaluated a putative relationship between KCa3.1 channel and the migratory machinery protein β1-integrin, which is activated by fibronectin. Co-immunoprecipitation and immunofluorescence experiments indicated a link between the two proteins and revealed their cellular co-distribution. In addition, we demonstrated that KCa3.1 channel and β1-integrin membrane expressions were increased on a fibronectin matrix. We also showed increased intracellular calcium concentrations as well as enhanced expression of TRPC4, a voltage-independent calcium channel belonging to the large TRP channel family, on a fibronectin matrix. Finally, wound-healing assays showed additive effects of KCa3.1 and TRPC4 inhibitors on alveolar epithelial repair. Taken together, our data demonstrate for the first time complementary roles of KCa3.1 and TRPC4 channels with extracellular matrix and β1-integrin in the regulation of alveolar repair processes.

  2. The Milieu of Damaged Alveolar Epithelial Type 2 Cells Stimulates Alveolar Wound Repair by Endogenous and Exogenous Progenitors

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    Buckley, Susan; Shi, Wei; Carraro, Gianni; Sedrakyan, Sargis; Da Sacco, Stefano; Driscoll, Barbara A.; Perin, Laura; De Filippo, Roger E.

    2011-01-01

    Alveolar epithelial integrity is dependent upon the alveolar milieu, yet the milieu of the damaged alveolar epithelial cell type 2 (AEC2) has been little studied. Characterization of its components may offer the potential for ex vivo manipulation of stem cells to optimize their therapeutic potential. We examined the cytokine profile of AEC2 damage milieu, hypothesizing that it would promote endogenous epithelial repair while recruiting cells from other locations and instructing their engraftment and differentiation. Bronchoalveolar lavage and lung extract from hyperoxic rats represented AEC2 in vivo damage milieu, and medium from a scratch-damaged AEC2 monolayer represented in vitro damage. CINC-2 and ICAM, the major cytokines detected by proteomic cytokine array in AEC2 damage milieu, were chemoattractive to normoxic AECs and expedited in vitro wound healing, which was blocked by their respective neutralizing antibodies. The AEC2 damage milieu was also chemotactic for exogenous uncommitted human amniotic fluid stem cells (hAFSCs), increasing migration greater than 20-fold. hAFSCs attached within an in vitro AEC2 wound and expedited wound repair by contributing cytokines migration inhibitory factor and plasminogen activator inhibitor 1 to the AEC2 damage milieu, which promoted wound healing. The AEC2 damage milieu also promoted differentiation of a subpopulation of hAFSCs to express SPC, TTF-1, and ABCA3, phenotypic markers of distal alveolar epithelium. Thus, the microenvironment created by AEC2 damage not only promotes autocrine repair but also can attract uncommitted stem cells, which further augment healing through cytokine secretion and differentiation. PMID:21700959

  3. Simulation of lung alveolar epithelial wound healing in vitro.

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    Kim, Sean H J; Matthay, Michael A; Mostov, Keith; Hunt, C Anthony

    2010-08-06

    The mechanisms that enable and regulate alveolar type II (AT II) epithelial cell wound healing in vitro and in vivo remain largely unknown and need further elucidation. We used an in silico AT II cell-mimetic analogue to explore and better understand plausible wound healing mechanisms for two conditions: cyst repair in three-dimensional cultures and monolayer wound healing. Starting with the analogue that validated for key features of AT II cystogenesis in vitro, we devised an additional cell rearrangement action enabling cyst repair. Monolayer repair was enabled by providing 'cells' a control mechanism to switch automatically to a repair mode in the presence of a distress signal. In cyst wound simulations, the revised analogue closed wounds by adhering to essentially the same axioms available for alveolar-like cystogenesis. In silico cell proliferation was not needed. The analogue recovered within a few simulation cycles but required a longer recovery time for larger or multiple wounds. In simulated monolayer wound repair, diffusive factor-mediated 'cell' migration led to repair patterns comparable to those of in vitro cultures exposed to different growth factors. Simulations predicted directional cell locomotion to be critical for successful in vitro wound repair. We anticipate that with further use and refinement, the methods used will develop as a rigorous, extensible means of unravelling mechanisms of lung alveolar repair and regeneration.

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

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    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

  5. Modulation of epithelial sodium channel in human alveolar epithelial ...

    African Journals Online (AJOL)

    Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway. Bi-Huan Cheng, Li-Wei Pan, Sheng-Rong Zhang, Bin-Yu Ying, Ben-Ji Wang, Guo-Liang Lin, Shi-Fang Ding ...

  6. Modulation of epithelial sodium channel in human alveolar epithelial ...

    African Journals Online (AJOL)

    Modulation of epithelial sodium channel in human alveolar epithelial cells by lipoxin A4 through AhR-cAMP-dependent pathway. Bi-Huan Cheng1,2, Li-Wei Pan2, Sheng-Rong Zhang3, Bin-Yu Ying2, Ben-Ji. Wang2, Guo-Liang Lin2 and Shi-Fang Ding1*. 1Department of Critical Care Medicine, Qilu Hospital of Shandong ...

  7. The axonal guidance cue semaphorin 3C contributes to alveolar growth and repair.

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    Arul Vadivel

    Full Text Available Lung diseases characterized by alveolar damage such as bronchopulmonary dysplasia (BPD in premature infants and emphysema lack efficient treatments. Understanding the mechanisms contributing to normal and impaired alveolar growth and repair may identify new therapeutic targets for these lung diseases. Axonal guidance cues are molecules that guide the outgrowth of axons. Amongst these axonal guidance cues, members of the Semaphorin family, in particular Semaphorin 3C (Sema3C, contribute to early lung branching morphogenesis. The role of Sema3C during alveolar growth and repair is unknown. We hypothesized that Sema3C promotes alveolar development and repair. In vivo Sema3C knock down using intranasal siRNA during the postnatal stage of alveolar development in rats caused significant air space enlargement reminiscent of BPD. Sema3C knock down was associated with increased TLR3 expression and lung inflammatory cells influx. In a model of O2-induced arrested alveolar growth in newborn rats mimicking BPD, air space enlargement was associated with decreased lung Sema3C mRNA expression. In vitro, Sema3C treatment preserved alveolar epithelial cell viability in hyperoxia and accelerated alveolar epithelial cell wound healing. Sema3C preserved lung microvascular endothelial cell vascular network formation in vitro under hyperoxic conditions. In vivo, Sema3C treatment of hyperoxic rats decreased lung neutrophil influx and preserved alveolar and lung vascular growth. Sema3C also preserved lung plexinA2 and Sema3C expression, alveolar epithelial cell proliferation and decreased lung apoptosis. In conclusion, the axonal guidance cue Sema3C promotes normal alveolar growth and may be worthwhile further investigating as a potential therapeutic target for lung repair.

  8. [Clinical research on repairing alveolar cleft with osteoinduction active material].

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    She, Xiao-ming; Zhang, Qian; Tian, Kun; Yang, Li; Xiong, Gui-fa

    2010-08-01

    To study the feasibility and authenticity of repairing alveolar defects in alveolar cleft patients with osteoinduction active material (OAM) in clinic. Twenty-seven cases of alveolar defect chosen from clinic were divided into two groups (test group and control group). For test group (12 cases), OAM was transplanted to repair the alveolar cleft. For control group (15 cases), autogenous ilium cancellous bone were transplanted into the defect region to repair alveolar cleft. At 6 months after operation, CT and three-dimensional reconstruction were used to observe alveolar appearance, and the effect and clinical success rate of recover alveolar cleft by using different repair material were compared. In the 27 cases, all the maxillary continuity was restored except two of test group and two of control group. There was no significant difference between test group and control group regarding the clinical success rate of the alveolar cleft repair (P = 1.000). OAM was used to repair the alveolar cleft that can result in new bone formations and the burgeon of canines from the bone grafted areas. There is no significant difference between OAM and autogenous ilium cancellous bone regarding the effect of the alveolar cleft repair.

  9. Contemporary Approaches in the Repair of Alveolar Clefts

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    Ufuk Tatli

    2014-08-01

    Full Text Available Cleft lip and palate is one of the most common craniofacial anomalies. The repair of the alveolar clefts is an important part of the treatment for patients with cleft lip and palate. The treatment concepts of alveolar bone grafting are still controversial. The corresponding controversial issues are; timing of alveolar bone grafting, graft materials, and timing of the orthodontic expansion. In the present article, aforementioned controversial issues and contemporary treatment modalities of the maxillary alveolar clefts were reviewed in the light of current literature. In conclusion, the most suitable time for alveolar bone grafting is mixed dentition period. Grafting procedure may be performed in the early or late phases of this period depending on some clinical features. Adjunct orthodontic expansion procedures should be performed before and/or after grafting depending on the patient's current features. [Archives Medical Review Journal 2014; 23(4.000: 563-574

  10. Decreased CXCL12 is associated with impaired alveolar epithelial cell migration and poor lung healing after lung resection.

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    Kanter, Jacob A; Sun, Haiying; Chiu, Stephen; DeCamp, Malcolm M; Sporn, Peter H S; Sznajder, Jacob I; Bharat, Ankit

    2015-10-01

    Prolonged air leak (PAL) is an important cause of morbidity and mortality after lung resection, but its pathogenesis has not been elucidated. Migration of alveolar type II epithelial cells is essential for lung wound repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on alveolar epithelial cell migration and lung wound healing. CXCL12 in the pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay. Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound closure, cell migration, and proliferation assays. Western blot was used to analyze Rac1 and cofilin. Pleural CXCL12 was decreased in patients with PAL (1,389 ± 192 vs 3,270 ± 247 pg/mL; P alveolar epithelial cell migration by binding to its receptor CXCR4 and may have a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is associated with Rac1 and cofilin activation. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 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.

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

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    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

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

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

    2016-02-01

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

  14. Ontogeny of pulmonary alveolar epithelial markers of differentiation.

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    Joyce-Brady, M F; Brody, J S

    1990-02-01

    We studied differentiation of the pulmonary epithelium in the periphery of fetal rat lung in vivo and in vitro by comparing the ontogeny of cell-surface glycoconjugates with that of surfactant phospholipids. Apical surface binding of the lectin Maclura pomifera agglutinin (MPA) and expression of a 200-kDa MPA-binding glycoprotein (MPA-gp200) was evident at 20 days gestation in type 2 cells, but did not correlate with ultrastructural features of type 2 cell differentiation. Epithelial cells isolated from peripheral lung of 18-day gestation fetal rats displayed hormone-sensitive surfactant synthesis prior to the hormone-insensitive expression of MPA-gp200. Expression of MPA-gp200 occurred in association with the appearance of many new apical surface proteins suggesting a hormone-independent process of polar membrane differentiation. Thus membrane and secretory differentiation are discordant and can be dissociated. In vivo binding of Ricinus communis 1 agglutinin (RCA1), an apical marker of the differentiated alveolar type 1 cell occurred in undifferentiated peripheral lung epithelial cells as early as 18 days gestation, disappeared from differentiating type 2 cells and appeared in differentiated type 1 cells. Both undifferentiated fetal epithelial cells at 18 days gestation and fully differentiated type 1 cells express multiple glycoproteins with terminal beta-linked galactose residues which bind RCA1. Some of these RCA1-binding glycoproteins appear to be similar. These observations suggest that alveolar epithelial type 1 cells may derive directly from undifferentiated peripheral lung epithelial cells as well as from fully differentiated type 2 cells. In addition, terminal differentiation of fetal lung peripheral epithelium into type 1 and type 2 cells may involve repression as well as induction of differentiation-related genes.

  15. Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling.

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    Ito, Yoko; Correll, Kelly; Schiel, John A; Finigan, Jay H; Prekeris, Rytis; Mason, Robert J

    2014-07-01

    There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. Copyright © 2014 the American Physiological Society.

  16. DNA repair in human bronchial epithelial cells

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    Fornace, A.J. Jr.; Lechner, J.F.; Grafstrom, R.C.; Harris, C.C.

    1982-01-01

    The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

  17. Spatiotemporal dynamics of actin remodeling and endomembrane trafficking in alveolar epithelial type I cell wound healing.

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    Godin, Lindsay M; Vergen, Jorge; Prakash, Y S; Pagano, Richard E; Hubmayr, Rolf D

    2011-04-01

    Alveolar epithelial type I cell (ATI) wounding is prevalent in ventilator-injured lungs and likely contributes to pathogenesis of "barotrauma" and "biotrauma." In experimental models most wounded alveolar cells repair plasma membrane (PM) defects and survive insults. Considering the force balance between edge energy at the PM wound margins and adhesive interactions of the lipid bilayer with the underlying cytoskeleton (CSK), we tested the hypothesis that subcortical actin depolymerization is a key facilitator of PM repair. Using real-time fluorescence imaging of primary rat ATI transfected with a live cell actin-green fluorescent protein construct (Lifeact-GFP) and loaded with N-rhodamine phosphatidylethanolamine (PE), we examined the spatial and temporal coordination between cytoskeletal remodeling and PM repair following micropuncture. Membrane integrity was inferred from the fluorescence intensity profiles of the cytosolic label calcein AM. Wounding led to rapid depolymerization of the actin CSK near the wound site, concurrent with accumulation of endomembrane-derived N-rhodamine PE. Both responses were sustained until PM integrity was reestablished, which typically occurs between ∼10 and 40 s after micropuncture. Only thereafter did the actin CSK near the wound begin to repolymerize, while the rate of endomembrane lipid accumulation decreased. Between 60 and 90 s after successful PM repair, after translocation of the actin nucleation factor cortactin, a dense actin fiber network formed. In cells that did not survive micropuncture injury, actin remodeling did not occur. These novel results highlight the importance of actin remodeling in ATI cell repair and suggest molecular targets for modulating the repair process.

  18. Alveolocapillary model system to study alveolar re-epithelialization

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    Willems, Coen H.M.P.; Zimmermann, Luc J.I.; Sanders, Patricia J.L.T.; Wagendorp, Margot; Kloosterboer, Nico [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands); Cohen Tervaert, Jan Willem [Division of Clinical and Experimental Immunology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht (Netherlands); Duimel, Hans J.Q.; Verheyen, Fons K.C.P. [Electron Microscopy Unit, Department of Molecular Cell Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Iwaarden, J. Freek van, E-mail: f.vaniwaarden@maastrichtuniversity.nl [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands)

    2013-01-01

    In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process. -- Highlights: ► Model system for vital imaging and high throughput screening. ► Microvascular endothelium influences re-epithelialization. ► A549 cells form protrusions through membrane to contact HPMEC. ► A549 cells and HPMECs form heterocellular tight-, gap- and adherens-junctions.

  19. Ultrastructural Study of Alveolar Epithelial Type II Cells by High-Frequency Oscillatory Ventilation

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    Xiaofei Qin

    2013-01-01

    Full Text Available Alveolar epithelial type II cells (AECIIs containing lamellar bodies (LBs are alveolar epithelial stem cells that have important functions in the repair of lung structure and function after lung injury. The ultrastructural changes in AECIIs after high-frequency oscillatory ventilation (HFOV with a high lung volume strategy or conventional ventilation were evaluated in a newborn piglet model with acute lung injury (ALI. After ALI with saline lavage, newborn piglets were randomly assigned into five study groups (three piglets in each group, namely, control (no mechanical ventilation, conventional ventilation for 24 h, conventional ventilation for 48 h, HFOV for 24 h, and HFOV for 48 h. The lower tissues of the right lung were obtained to observe the AECII ultrastructure. AECIIs with reduced numbers of microvilli, decreased LBs electron density, and vacuole-like LBs deformity were commonly observed in all five groups. Compared with conventional ventilation groups, the decrease in numbers of microvilli and LBs electron density, as well as LBs with vacuole-like appearance and polymorphic deformity, was less severe in HFOV with high lung volume strategy groups. AECIIs were injured during mechanical ventilation. HFOV with a high lung volume strategy resulted in less AECII damage than conventional ventilation.

  20. Lipoxin A4 promotes lung epithelial repair whilst inhibiting fibroblast proliferation

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    Shengxing Zheng

    2016-10-01

    Full Text Available Therapy that promotes epithelial repair whilst protecting against fibroproliferation is critical for restoring lung function in acute and chronic respiratory diseases. Primary human alveolar type II cells were used to model the effects of lipoxin A4 in vitro upon wound repair, proliferation, apoptosis and transdifferention. Effects of lipoxin A4 upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also assessed. Lipoxin A4 promoted type II cell wound repair and proliferation, blocked the negative effects of soluble Fas ligand/tumour necrosis factor α upon cell proliferation, viability and apoptosis, and augmented the epithelial cell proliferative response to bronchoaveolar lavage fluid (BALF from acute respiratory distress syndrome (ARDS. In contrast, Lipoxin A4 reduced fibroblast proliferation, collagen production and myofibroblast differentiation induced by transforming growth factor β and BALF from ARDS. The effects of Lipoxin A4 were phosphatidylinositol 3′-kinase dependent and mediated via the lipoxin A4 receptor. Lipoxin A4 appears to promote alveolar epithelial repair by stimulating epitheial cell wound repair, proliferation, reducing apoptosis and promoting trans-differentiation of alveolar type II cells into type I cells. Lipoxin A4 reduces fibroblast proliferation, collagen production and myofibroblast differentiation. These data suggest that targeting lipoxin actions may be a therapeutic strategy for treating the resolution phase of ARDS.

  1. Protein Expression Profile of Rat Type Two Alveolar Epithelial Cells During Hyperoxic Stress and Recovery

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    Bhargava, Maneesh

    Rationale: In rodent model systems, the sequential changes in lung morphology resulting from hyperoxic injury are well characterized, and are similar to changes in human acute respiratory distress syndrome (ARDS). In the injured lung, alveolar type two (AT2) epithelial cells play a critical role restoring the normal alveolar structure. Thus characterizing the changes in AT2 cells will provide insights into the mechanisms underpinning the recovery from lung injury. Methods: We applied an unbiased systems level proteomics approach to elucidate molecular mechanisms contributing to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from rat lungs at predetermined intervals during hyperoxic injury and recovery. Protein expression profiles were determined by using iTRAQRTM with tandem mass spectrometry. Results: Of 959 distinct proteins identified, 183 significantly changed in abundance during the injury-recovery cycle. Gene Ontology enrichment analysis identified cell cycle, cell differentiation, cell metabolism, ion homeostasis, programmed cell death, ubiquitination, and cell migration to be significantly enriched by these proteins. Gene Set Enrichment Analysis of data acquired during lung repair revealed differential expression of gene sets that control multicellular organismal development, systems development, organ development, and chemical homeostasis. More detailed analysis identified activity in two regulatory pathways, JNK and miR 374. A Short Time-series Expression Miner (STEM) algorithm identified protein clusters with coherent changes during injury and repair. Conclusion: Coherent changes occur in the AT2 cell proteome in response to hyperoxic stress. These findings offer guidance regarding the specific molecular mechanisms governing repair of the injured lung.

  2. Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing.

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    Crosby, Lynn M; Luellen, Charlean; Zhang, Zhihong; Tague, Larry L; Sinclair, Scott E; Waters, Christopher M

    2011-10-01

    After acute lung injury, repair of the alveolar epithelium occurs on a substrate undergoing cyclic mechanical deformation. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. We examined epithelial repair during cyclic stretch (CS) in a scratch-wound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caused significant intercellular gap formation compared with static cells. Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier.

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

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    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

  4. Reduced Frizzled Receptor 4 Expression Prevents WNT/β-Catenin-driven Alveolar Lung Repair in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Skronska-Wasek, Wioletta; Mutze, Kathrin; Baarsma, Hoeke A; Bracke, Ken R; Alsafadi, Hani N; Lehmann, Mareike; Costa, Rita; Stornaiuolo, Mariano; Novellino, Ettore; Brusselle, Guy G; Wagner, Darcy E; Yildirim, Ali Ö; Königshoff, Melanie

    2017-07-15

    Chronic obstructive pulmonary disease (COPD), in particular emphysema, is characterized by loss of parenchymal alveolar tissue and impaired tissue repair. Wingless and INT-1 (WNT)/β-catenin signaling is reduced in COPD; however, the mechanisms thereof, specifically the role of the frizzled (FZD) family of WNT receptors, remain unexplored. To identify and functionally characterize specific FZD receptors that control downstream WNT signaling in impaired lung repair in COPD. FZD expression was analyzed in lung homogenates and alveolar epithelial type II (ATII) cells of never-smokers, smokers, patients with COPD, and two experimental COPD models by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunofluorescence. The functional effects of cigarette smoke on FZD4, WNT/β-catenin signaling, and elastogenic components were investigated in primary ATII cells in vitro and in three-dimensional lung tissue cultures ex vivo. Gain- and loss-of-function approaches were applied to determine the effects of FZD4 signaling on alveolar epithelial cell wound healing and repair, as well as on expression of elastogenic components. FZD4 expression was reduced in human and experimental COPD lung tissues as well as in primary human ATII cells from patients with COPD. Cigarette smoke exposure down-regulated FZD4 expression in vitro and in vivo, along with reduced WNT/β-catenin activity. Inhibition of FZD4 decreased WNT/β-catenin-driven epithelial cell proliferation and wound closure, and it interfered with ATII-to-ATI cell transdifferentiation and organoid formation, which were augmented by FZD4 overexpression. Moreover, FZD4 restoration by overexpression or pharmacological induction led to induction of WNT/β-catenin signaling and expression of elastogenic components in three-dimensional lung tissue cultures ex vivo. Reduced FZD4 expression in COPD contributes to impaired alveolar repair capacity.

  5. A heteromeric molecular complex regulates the migration of lung alveolar epithelial cells during wound healing.

    Science.gov (United States)

    Ghosh, Manik C; Makena, Patrudu S; Kennedy, Joseph; Teng, Bin; Luellen, Charlean; Sinclair, Scott E; Waters, Christopher M

    2017-05-19

    Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4. In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric complex, while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex. Cell migration following wounding was decreased when PP5 expression was decreased using shRNA, but migration was increased in ATII cells isolated from ASK1 knockout mice. Interactions between FAK and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP5 was depleted. Furthermore, we found that wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine phosphorylation of FAK, and decreased association of phosphorylated ASK1 with FAK. These changes in phosphorylation were dependent upon expression of PP5. These results demonstrate a unique molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.

  6. Differential effects of hypoxic stress in alveolar epithelial cells and microvascular endothelial cells

    NARCIS (Netherlands)

    Signorelli, Sara; Jennings, Paul; Leonard, Martin O; Pfaller, Walter

    2010-01-01

    Under hypoxic conditions eukaryotic cells and tissues undergo adaptive responses involving glycolysis, angiogenesis, vasoconstriction and inflammation. The underlying molecular mechanisms are not yet fully elucidated and are most likely cell and tissue specific. In the lung, alveolar epithelial

  7. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Jacob Barbara A

    2009-02-01

    Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

  8. The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

    Science.gov (United States)

    Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P.; Williams, David B.; Kamp, David W.

    2015-01-01

    Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer. PMID:26370974

  9. Dual role for plasminogen activator inhibitor type 1 as soluble and as matricellular regulator of epithelial alveolar cell wound healing.

    Science.gov (United States)

    Maquerlot, François; Galiacy, Stephane; Malo, Michel; Guignabert, Christophe; Lawrence, Daniel A; d'Ortho, Maria-Pia; Barlovatz-Meimon, Georgia

    2006-11-01

    Epithelium repair, crucial for restoration of alveolo-capillary barrier integrity, is orchestrated by various cytokines and growth factors. Among them keratinocyte growth factor plays a pivotal role in both cell proliferation and migration. The urokinase plasminogen activator (uPA) system also influences cell migration through proteolysis during epithelial repair. In addition, the complex formed by uPAR-uPA and matrix-bound plasminogen activator inhibitor type-1 (PAI-1) exerts nonproteolytic roles in various cell types. Here we present new evidence about the dual role of PAI-1 under keratinocyte growth factor stimulation using an in vitro repair model of rat alveolar epithelial cells. Besides proteolytic involvement of the uPA system, the availability of matrix-bound-PAI-1 is also required for an efficient healing. An unexpected decrease of healing was shown when PAI-1 activity was blocked. However, the proteolytic action of uPA and plasmin were still required. Moreover, immediately after wounding, PAI-1 was dramatically increased in the newly deposited matrix at the leading edge of wounds. We thus propose a dual role for PAI-1 in epithelial cell wound healing, both as a soluble inhibitor of proteolysis and also as a matrix-bound regulator of cell migration. Matrix-bound PAI-1 could thus be considered as a new member of the matricellular protein family.

  10. Enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells

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    Kathrin Mutze

    2015-08-01

    Full Text Available The alveolar epithelium represents a major site of tissue destruction during lung injury. It consists of alveolar epithelial type I (ATI and type II (ATII cells. ATII cells are capable of self-renewal and exert progenitor function for ATI cells upon alveolar epithelial injury. Cell differentiation pathways enabling this plasticity and allowing for proper repair, however, are poorly understood. Here, we applied proteomics, expression analysis and functional studies in primary murine ATII cells to identify proteins and molecular mechanisms involved in alveolar epithelial plasticity. Mass spectrometry of cultured ATII cells revealed a reduction of carbonyl reductase 2 (CBR2 and an increase in enolase 1 (ENO1 and protein disulfide-isomerase associated 3 (PDIA3 protein expression during ATII-to-ATI cell trans-differentiation. This was accompanied by increased Wnt/β-catenin signaling, as analyzed by qRT-PCR and immunoblotting. Notably, ENO1 and PDIA3, along with T1α (podoplanin; an ATI cell marker, exhibited decreased protein expression upon pharmacological and molecular Wnt/β-catenin inhibition in cultured ATII cells, whereas CBR2 levels were stabilized. Moreover, we analyzed primary ATII cells from mice with bleomycin-induced lung injury, a model exhibiting activated Wnt/β-catenin signaling in vivo. We observed reduced CBR2 significantly correlating with surfactant protein C (SFTPC, whereas ENO1 and PDIA3 along with T1α were increased in injured ATII cells. Finally, siRNA-mediated knockdown of ENO1, as well as PDIA3, in primary ATII cells led to reduced T1α expression, indicating diminished cell trans-differentiation. Our data thus identified proteins involved in ATII-to-ATI cell trans-differentiation and suggest a Wnt/β-catenin-driven functional role of ENO1 and PDIA3 in alveolar epithelial cell plasticity in lung injury and repair.

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

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    Taylor S Cohen

    2010-06-01

    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

  12. Barrier-protective effects of activated protein C in human alveolar epithelial cells.

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    Ferranda Puig

    Full Text Available Acute lung injury (ALI is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC on mechanical tension and barrier integrity in human alveolar epithelial cells (A549 exposed to thrombin. Cells were pretreated for 3 h with APC (50 µg/ml or vehicle (control. Subsequently, thrombin (50 nM or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

  13. Alveolar epithelial type II cells induce T cell tolerance to specific antigen

    DEFF Research Database (Denmark)

    Lo, Bernice; Hansen, Søren; Evans, Kathy

    2008-01-01

    The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Ty...

  14. 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.

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

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    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.

  16. RAGE-induced changes in the proteome of alveolar epithelial cells.

    Science.gov (United States)

    Downs, Charles A; Johnson, Nicholle M; Tsaprailis, George; Helms, My N

    2018-02-12

    The receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor and member of the immunoglobulin superfamily. RAGE is constitutively expressed in the distal lung where it co-localizes with the alveolar epithelium; RAGE expression is otherwise minimal or absent, except with disease. This suggests RAGE plays a role in lung physiology and pathology. We used proteomics to identify and characterize the effects of RAGE on rat alveolar epithelial (R3/1) cells. LC-MS/MS identified 177 differentially expressed proteins and the PANTHER Classification System further segregated proteins. Proteins involved in gene transcription (RNA and mRNA splicing, mRNA processing) and transport (protein, intracellular protein) were overrepresented; genes involved in a response to stimulus were underrepresented. Immune system processes and response to stimuli were downregulated with RAGE knockdown. Western blot confirmed RAGE-dependent changes in protein expression for NFκB and NLRP3 that was functionally supported by a reduction in IL-1β and phosphorylated p65. We also assessed RAGE's effect on redox regulation and report that RAGE knockdown attenuated oxidant production, decreased protein oxidation, and increased reduced thiol pools. Collectively the data suggest that RAGE is a critical regulator of epithelial cell response and has implications for our understanding of lung disease, specifically acute lung injury. In the present study, we undertook the first proteomic evaluation of RAGE-dependent processes in alveolar epithelial cells. The alveolar epithelium is a primary target during acute lung injury, and our data support a role for RAGE in gene transcription, protein transport, and response to stimuli. More over our data suggest that RAGE is a critical driver of redox regulation in the alveolar epithelium. The conclusions of the present work assist to unravel the molecular events that underlie the function of RAGE in alveolar epithelial cells and have

  17. CXCL9 Regulates TGF-β1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells.

    Science.gov (United States)

    O'Beirne, Sarah L; Walsh, Sinead M; Fabre, Aurélie; Reviriego, Carlota; Worrell, Julie C; Counihan, Ian P; Lumsden, Robert V; Cramton-Barnes, Jennifer; Belperio, John A; Donnelly, Seamas C; Boylan, Denise; Marchal-Sommé, Joëlle; Kane, Rosemary; Keane, Michael P

    2015-09-15

    Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells. Coexpression of the epithelial marker thyroid transcription factor-1 and the mesenchymal marker α-smooth muscle actin and CXCR3 expression was examined by immunohistochemical staining of IPF surgical lung biopsies. Epithelial and mesenchymal marker expression was examined by quantitative real-time PCR, Western blotting, and immunofluorescence in human alveolar epithelial (A549) cells treated with TGF-β1 and CXCL9, with Smad2, Smad3, and Smad7 expression and cellular localization examined by Western blotting. We found that significantly more cells were undergoing EMT in fibrotic versus normal areas of lung in IPF surgical lung biopsy samples. CXCR3 was expressed by type II pneumocytes and fibroblasts in fibrotic areas in close proximity to cells undergoing EMT. In vitro, CXCL9 abrogated TGF-β1-induced EMT. A decrease in TGF-β1-induced phosphorylation of Smad2 and Smad3 occurred with CXCL9 treatment. This was associated with increased shuttling of Smad7 from the nucleus to the cytoplasm where it inhibits Smad phosphorylation. This suggests a role for EMT in the pathogenesis of IPF and provides a novel mechanism for the inhibitory effects of CXCL9 on TGF-β1-induced EMT. Copyright © 2015 by The American Association of Immunologists, Inc.

  18. Dexmedetomidine Attenuates Oxidative Stress Induced Lung Alveolar Epithelial Cell Apoptosis In Vitro

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    Jian Cui

    2015-01-01

    Full Text Available Background. Oxidative stress plays a pivotal role in the lung injuries of critical ill patients. This study investigates the protection conferred by α2 adrenoceptor agonist dexmedetomidine (Dex from lung alveolar epithelial cell injury induced by hydrogen peroxide (H2O2 and the underlying mechanisms. Methods. The lung alveolar epithelial cell line, A549, was cultured and then treated with 500 μM H2O2 with or without Dex (1 nM or Dex in combination with atipamezole (10 nM, an antagonist of α2 receptors. Their effect on mitochondrial membrane potential (Δψm, reactive oxygen species (ROS, and the cell cycle was assessed by flow cytometry. Cleaved-caspases 3 and 9, BAX, Bcl-2, phospho-mTOR (p-mTOR, ERK1/2, and E-cadherin expression were also determined with immunocytochemistry. Results. Upregulation of cleaved-caspases 3 and 9 and BAX and downregulation of Bcl-2, p-mTOR, and E-cadherin were found following H2O2 treatment, and all of these were reversed by Dex. Dex also prevented the ROS generation, cytochrome C release, and cell cycle arrest induced by H2O2. The effects of Dex were partially reversed by atipamezole. Conclusion. Our study demonstrated that Dex protected lung alveolar epithelial cells from apoptotic injury, cell cycle arrest, and loss of cell adhesion induced by H2O2 through enhancing the cell survival and proliferation.

  19. Characterization of the in vitro adhesion of Actinobacillus pleuropneumoniae to swine alveolar epithelial cells.

    Science.gov (United States)

    Van Overbeke, Ingrid; Chiers, Koen; Charlier, Gerard; Vandenberghe, Isabel; Van Beeumen, Jozef; Ducatelle, Richard; Haesebrouck, Freddy

    2002-08-02

    Actinobacillus pleuropneumoniae biovar 1 serotypes 2, 5a, 9 and 10 strains were tested for their ability to adhere to alveolar epithelial cells in culture. For the serotypes 5a, 9 and 10 strains, optimal adherence was observed after growth of bacterial cells in a NAD-restricted medium (0.001% NAD). This condition was also associated with the expression of a 55 kDa outer membrane protein (OMP) and of fimbriae. For the serotype 2 strain, adherence and expression of fimbriae and a 55 kDa OMP was less influenced by the growth conditions. The N-terminal amino acid sequence of the 55 kDa OMP had no homology with any known sequence, suggesting that it is an as yet unknown protein. Adherence capabilities were significantly reduced following treatment of the bacteria with proteolytic enzymes or heat. These findings suggest that proteins are involved in adhesion. The hydrophobic bond-breaking agent tetramethylurea was unable to inhibit the adherence of A. pleuropneumoniae to alveolar epithelial cells. Treatment of the bacteria with sodium metaperiodate resulted in lower adhesion scores for the serotypes 2 and 9 strains but the inhibition of adhesion was clearly lower than after treatment with proteolytic enzymes. This indicates that, besides proteins, carbohydrates might also be involved in adhesion of A. pleuropneumoniae to alveolar epithelial cells. The finding that inhibition of adhesion was very high when bacteria were treated with a combination of sodium metaperiodate and pronase also suggests that more than one adhesin is involved.

  20. beta-TCP Versus Autologous Bone for Repair of Alveolar Clefts in a Goat Model.

    NARCIS (Netherlands)

    Ruiter, A. de; Meijer, G.J.; Dormaar, T.; Janssen, N.; Bilt, A. van der; Slootweg, P.J.; Bruijn, J. de; Rijn, L. van; Koole, R.A.

    2011-01-01

    Objective : The aim of this study in goats was to test the hypothesis that a novel synthetic bone substitute beta tricalcium phosphate (beta-TCP) can work as well as autologous bone harvested from the iliac crest for grafting and repair of alveolar clefts. Design : Ten adult Dutch milk goats ( Capra

  1. Wnt-inducible protein (WISP-1 is a key regulator of alveolar epithelial cell hyperplasia in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Melanie Königshoff

    2006-12-01

    Full Text Available Fibrotic lung disease is characterized by distorted lung architecture and severe loss of respiratory function secondary to alveolar epithelial cell (AEC hyperplasia, enhanced extracellular matrix (ECM deposition and fibroblast proliferation. Repetitive epithelial injuries with impaired alveolar wound healing and altered AEC gene expression represent a trigger mechanism for development of fibrosis. To reveal gene regulatory networks in lung fibrosis, we compared gene expression profiles of freshly isolated AEC obtained from mice 14 days after saline or bleomycin (BM instillation using whole genome microarray analysis. Several genes of the Wnt signaling pathway, in particular WISP-1, a member of the CCN family, were highly regulated. WISP-1 protein expression was demonstrated in proliferating AEC in BM-treated lungs by immunofluorescence. When analyzing all six CCN family members, WISP-1 was upregulated the most 14 days after BM challenge, as analyzed by qRT-PCR. To elucidate WISP-1 function, cultured primary mouse AEC were stimulated with WISP-1 and demonstrated a 230% increase in proliferation, analyzed by 3H-thymidine incorporation. This was mediated through enhanced phosphorylation, but not expression of protein kinase B (PKB/Akt, as detected by immunoblot. Finally, increased expression of WISP-1 was detected in lung homogenates and isolated AEC from IPF patients, using qRT-PCR. Immunohistochemical analysis of WISP-1 and Ki67 verified the existence of hyperplastic and proliferative AEC expressing WISP-1 in vivo. Our study thus identifies WISP-1 as a novel regulator of AEC injury and repair, and suggests that WISP-1 is a key mediator in pulmonary fibrosis.

  2. In vivo metabolism of pulmonary alveolar epithelial type II pneumonocytes and macrophages from Syrian hamsters

    International Nuclear Information System (INIS)

    Pfleger, R.C.; Waide, J.J.

    1976-01-01

    Young adult Syrian hamsters were injected intraperitoneally with 14 C-glycerol and 3 H-palmitate 17 hr before they were sacrificed and pulmonary alveolar epithelial type II cells and pulmonary alveolar macrophages (PAM) were isolated. Incorporation of the two labeled components into the cellular lipids showed that the 3 H-specific activity of the phospholipids from the type II cells was three times that of the PAM and the utilization of 14 C-glycerol into phosphatidyl choline (PC) was 50% greater than incorporation into the PC from PAMs. The PC from type II cells showed that 30% was disaturated and from PAMs 21% was disaturated. Another phosphatide, phosphatidyl glycerol contained about one-third of the molecules in disaturated form. These data are consistent with the view that both type II cells and PAMs can synthesize surface-active phospholipids but it is generally accepted that only the pulmonary alveolar epithelial type II cells excrete the disaturated phospholipids which comprise the surface-active components of pulmonary surfactant

  3. Epithelial-mesenchymal transition in tissue repair and fibrosis.

    Science.gov (United States)

    Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

    2016-09-01

    The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

  4. Establishment and evaluation of a stable cattle type II alveolar epithelial cell line.

    Directory of Open Access Journals (Sweden)

    Feng Su

    Full Text Available Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-α and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.

  5. Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chunrong; Zheng, Haichong; He, Wanmei; Lu, Guifang; Li, Xia [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Deng, Yubin, E-mail: dengyub@mail.sysu.edu.cn [Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China); Zeng, Mian, E-mail: zengmian2004@163.com [Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080 (China)

    2016-05-20

    Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI. -- Graphical abstract: Ghrelin ameliorates the human alveolar epithelial A549 cells apoptosis induced by lipopolysaccharide partly through activating the PI3K/Akt and ERK pathway. Display Omitted -- Highlights: •It has been observed that LPS insult significantly increased apoptosis in A549 cells. •Both Akt and ERK signaling are critical adapter molecules to mediate the ghrelin-mediated proliferative effect. •Ghrelin may have a therapeutic effect in the prevention of LPS-induced apoptosis.

  6. Carbon black nanoparticles induce type II epithelial cells to release chemotaxins for alveolar macrophages

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    Donaldson Ken

    2005-12-01

    Full Text Available Abstract Background Alveolar macrophages are a key cell in dealing with particles deposited in the lungs and in determining the subsequent response to that particle exposure. Nanoparticles are considered a potential threat to the lungs and the mechanism of pulmonary response to nanoparticles is currently under intense scrutiny. The type II alveolar epithelial cell has previously been shown to release chemoattractants which can recruit alveolar macrophages to sites of particle deposition. The aim of this study was to assess the responses of a type II epithelial cell line (L-2 to both fine and nanoparticle exposure in terms of secretion of chemotactic substances capable of inducing macrophage migration. Results Exposure of type II cells to carbon black nanoparticles resulted in significant release of macrophage chemoattractant compared to the negative control and to other dusts tested (fine carbon black and TiO2 and nanoparticle TiO2 as measured by macrophage migration towards type II cell conditioned medium. SDS-PAGE analysis of the conditioned medium from particle treated type II cells revealed that a higher number of protein bands were present in the conditioned medium obtained from type II cells treated with nanoparticle carbon black compared to other dusts tested. Size-fractionation of the chemotaxin-rich supernatant determined that the chemoattractants released from the epithelial cells were between 5 and 30 kDa in size. Conclusion The highly toxic nature and reactive surface chemistry of the carbon black nanoparticles has very likely induced the type II cell line to release pro-inflammatory mediators that can potentially induce migration of macrophages. This could aid in the rapid recruitment of inflammatory cells to sites of particle deposition and the subsequent removal of the particles by phagocytic cells such as macrophages and neutrophils. Future studies in this area could focus on the exact identity of the substance(s released by the

  7. Alveolar epithelial type II cells induce T cell tolerance to specific antigen

    DEFF Research Database (Denmark)

    Lo, Bernice; Hansen, Søren; Evans, Kathy

    2008-01-01

    The lungs face the immunologic challenge of rapidly eliminating inhaled pathogens while maintaining tolerance to innocuous Ags. A break in this immune homeostasis may result in pulmonary inflammatory diseases, such as allergies or asthma. The observation that alveolar epithelial type II cells (Type...... II) constitutively express the class II MHC led us to hypothesize that Type II cells play a role in the adaptive immune response. Because Type II cells do not express detectable levels of the costimulatory molecules CD80 and CD86, we propose that Type II cells suppress activation of naive T cells...

  8. Cell stress induces upregulation of osteopontin via the ERK pathway in type II alveolar epithelial cells.

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    Aki Kato

    Full Text Available Osteopontin (OPN is a multifunctional protein that plays important roles in cell growth, differentiation, migration and tissue fibrosis. In human idiopathic pulmonary fibrosis and murine bleomycin-induced lung fibrosis, OPN is upregulated in type II alveolar epithelial cells (AEC II. However, the mechanism of OPN induction in AEC II is not fully understood. In this study, we demonstrate the molecular mechanism of OPN induction in AEC II and elucidate the functions of OPN in AEC II and lung fibroblasts. Human lung adenocarcinoma cells (A549 and mouse alveolar epithelial cells (MLE12, used as type II alveolar epithelial cell lines for in vitro assays, and human pulmonary alveolar epithelial cells (HPAEpiC were treated with either bleomycin, doxorubicin or tunicamycin. The mechanism of OPN induction in these cells and its function as a pro-fibrotic cytokine on A549 and lung fibroblasts were analyzed. The DNA damaging reagents bleomycin and doxorubicin were found to induce OPN expression in A549, MLE12 and HPAEpiC. OPN expression was induced via activation of the extracellular signal-regulated protein kinase (ERK-dependent signaling pathway in A549 and MLE12. The endoplasmic reticulum (ER stress-inducing reagent tunicamycin induced OPN mRNA expression in A549, MLE12 and HPAEpiC, and OPN mRNA expression was induced via activation of the ERK-dependent signaling pathway in A549 and MLE12. Another ER stress-inducing reagent thapsigargin induced the expression of OPN mRNA as well as the subsequent production of OPN in A549 and MLE12. Furthermore, OPN promoted the proliferation of A549 and the migration of normal human lung fibroblasts. Inhibition of OPN by small interference RNA or neutralizing antibody suppressed both of these responses. The results of this study suggest that cell stress induces the upregulation of OPN in AEC II by signaling through the ERK pathway, and that upregulated OPN may play a role in fibrogenesis of the lung.

  9. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    Science.gov (United States)

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Marta; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S. P.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-06-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit.Inhaled nanoparticles have a high deposition rate in

  10. Induction of Programmed Cell Death in Human Alveolar Epithelial Cells Infected with Influenza Virus

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    Sh Shahsavandi

    2015-11-01

    Full Text Available Introduction: Avian influenza viruses are considered as a serious threat to human and animal health. An increase in expression of proinflammatory cytokines and type I IFN genes, as well as host cell death responses contribute to the pathogenesis of influenza infection. Hence, this study aimed to evaluate the growth dynamics of subacute avian influenza virus in human respiratory alveolar epithelium cells (A549. Methods: The A549 cell cultures were infected at MOIs 0.1 and 2.0 viral doses in the presence and absence of trypsin. The virus growth kinetics were elucidated by the plaque assay and the cell viability was determined by MTT at various times after the infection. The induction quality of programmed cell death as well as the signal transduction pathway of death were assessed by genomic DNA fragmentation and western blotting respectively. Results: The study findings indicated that although the H9N2 virus replication did produce a marked cytopathic effect on the alveolar cells, which led to a reduction in the cell viability, the viral titers were increased in the infected cells. The virus replication of in these cells indicated repression of host defense mechanism as well as activation of cell death. The induction of apoptosis in A549 cells was correlated with the increased virus titers as well as virus replication (p< 0.05. Conclusion: H9N2 avian influenza virus were demonstrated to induce apoptosis in human alveolar epithelial cells via the intrinsic pathway in a dose-dependent manner.

  11. Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells.

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    Armstrong, Lynne; Medford, Andrew R L; Uppington, Kay M; Robertson, John; Witherden, Ian R; Tetley, Teresa D; Millar, Ann B

    2004-08-01

    The recognition of potentially harmful microorganisms involves the specific recognition of pathogen-associated molecular patterns (PAMPs) and the family of Toll-like receptors (TLRs) is known to play a central role in this process. TLR-4 is the major recognition receptor for lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, whereas TLR-2 responds to bacterial products from gram-positive organisms. Although resident alveolar macrophages are the first line of defense against microbial attack, it is now understood that the alveolar epithelium also plays a pivotal role in the innate immunity of the lung. The purpose of the current study was to determine whether human primary type II alveolar epithelial cells (ATII) express functional TLR-2 and TLR-4 and how they may be regulated by inflammatory mediators. We have used reverse transcriptase-polymerase chain reaction and flow cytometry to determine basal and inducible expression on ATII. We have used highly purified preparations of the gram-positive bacterial product lipoteichoic acid (LTA) and LPS to look at the functional consequences of TLR-2 and TLR-4 ligation, respectively, in terms of interleukin-8 release. We have shown that human primary ATII cells express mRNA and protein for both TLR-2 and TLR-4, which can be modulated by incubation with LPS and tumor necrosis factor. Furthermore, we have demonstrated that these receptors are functional. This suggests that ATII have the potential to contribute significantly to the host defense of the human alveolus against bacteria.

  12. Evidence for the involvement of cofilin in Aspergillus fumigatus internalization into type II alveolar epithelial cells.

    Science.gov (United States)

    Bao, Zhiyao; Han, Xuelin; Chen, Fangyan; Jia, Xiaodong; Zhao, Jingya; Zhang, Changjian; Yong, Chen; Tian, Shuguang; Zhou, Xin; Han, Li

    2015-08-13

    The internalization of Aspergillus fumigatus into alveolar epithelial cells (AECs) is tightly controlled by host cellular actin dynamics, which require close modulation of the ADF (actin depolymerizing factor)/cofilin family. However, the role of cofilin in A. fumigatus internalization into AECs remains unclear. Here, we demonstrated that germinated A. fumigatus conidia were able to induce phosphorylation of cofilin in A549 cells during the early stage of internalization. The modulation of cofilin activity by overexpression, knockdown, or mutation of the cofilin gene in A549 cells decreased the efficacy of A. fumigatus internalization. Reducing the phosphorylation status of cofilin with BMS-5 (LIM kinase inhibitor) or overexpression of the slingshot phosphatases also impeded A. fumigatus internalization. Both the C. botulimun C3 transferase (a specific RhoA inhibitor) and Y27632 (a specific ROCK inhibitor) reduced the internalization of A. fumigatus and the level of phosphorylated cofilin. β-1,3-glucan (the major component of the conidial cell wall) and its host cell receptor dectin-1 did not seem to be associated with cofilin phosphorylation during A. fumigatus infection. These results indicated that cofilin might be involved in the modulation of A. fumigatus internalization into type II alveolar epithelial cells through the RhoA-ROCK-LIM kinase pathway.

  13. Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation.

    Science.gov (United States)

    Loscertales, Maria; Nicolaou, Fotini; Jeanne, Marion; Longoni, Mauro; Gould, Douglas B; Sun, Yunwei; Maalouf, Faouzi I; Nagy, Nandor; Donahoe, Patricia K

    2016-07-13

    Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown. We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal-epithelial septal-like structures in co-culture. Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum.

  14. DNA repair in baboon alveolar macrophages: a system for assessing biohazardous materials

    Energy Technology Data Exchange (ETDEWEB)

    Meltz, M.L.

    1976-06-01

    The repair of DNA in the alveolar macrophages of the baboon has been investigated after treatment of the cells in vitro with ultraviolet light and with the alkylating agent, methyl methanesulfonate. Repair replication has been observed to occur after ultraviolet-light irradiation of macrophages attached to plastic dishes. The two different techniques used for measuring repair replication were a standard density-gradient procedure which separates normal-density, repair-replicated, preexisting DNA from semiconservatively synthesized DNA containing sufficient (/sup 3/H)bromodeoxyuridine to cause a density shift; and an alternative procedure applicable to nonproliferating cell systems wherein residual semiconservative synthesis is inhibited by hydroxyurea, and the increased incorporation of the DNA precursor (/sup 3/H)thymidine due to repair replication is measured. The latter technique was applied to the investigation of the concentration dependence of repair replication both after and during the treatment of the cells with the alkylating agent, methyl methanesulfonate. The labeling after treatment measures the repair of damage still present at the end of the treatment interval, while the labeling during treatment allows for greater sensitivity and detection of all repair occurring during the treatment period.

  15. Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells.

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    Mohammad Reza Etemadi

    Full Text Available Human rhinovirus (HRV is the common virus that causes acute respiratory infection (ARI and is frequently associated with lower respiratory tract infections (LRTIs. We aimed to investigate whether HRV infection induces a specific gene expression pattern in airway epithelial cells. Alveolar epithelial cell monolayers were infected with HRV species B (HRV-B. RNA was extracted from both supernatants and infected monolayer cells at 6, 12, 24 and 48 hours post infection (hpi and transcriptional profile was analyzed using Affymetrix GeneChip and the results were subsequently validated using quantitative Real-time PCR method. HRV-B infects alveolar epithelial cells which supports implication of the virus with LRTIs. In total 991 genes were found differentially expressed during the course of infection. Of these, 459 genes were up-regulated whereas 532 genes were down-regulated. Differential gene expression at 6 hpi (187 genes up-regulated vs. 156 down-regulated were significantly represented by gene ontologies related to the chemokines and inflammatory molecules indicating characteristic of viral infection. The 75 up-regulated genes surpassed the down-regulated genes (35 at 12 hpi and their enriched ontologies fell into discrete functional entities such as regulation of apoptosis, anti-apoptosis, and wound healing. At later time points of 24 and 48 hpi, predominated down-regulated genes were enriched for extracellular matrix proteins and airway remodeling events. Our data provides a comprehensive image of host response to HRV infection. The study suggests the underlying molecular regulatory networks genes which might be involved in pathogenicity of the HRV-B and potential targets for further validations and development of effective treatment.

  16. Alveolar bone repair with strontium- containing nanostructured carbonated hydroxyapatite

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    André Boziki Xavier do Carmo

    2018-01-01

    Full Text Available ABSTRACT Objective: This study aimed to evaluate bone repair in rat dental sockets after implanting nanostructured carbonated hydroxyapatite/sodium alginate (CHA and nanostructured carbonated hydroxyapatite/sodium alginate containing 5% strontium microspheres (SrCHA as bone substitute materials. Methods: Twenty male Wistar rats were randomly divided into two experimental groups: CHA and SrCHA (n=5/period/group. After one and 6 weeks of extraction of the right maxillary central incisor and biomaterial implantation, 5 μm bone blocks were obtained for histomorphometric evaluation. The parameters evaluated were remaining biomaterial, loose connective tissue and newly formed bone in a standard area. Statistical analysis was performed by Mann-Withney and and Wilcoxon tests at 95% level of significance. Results: The histomorphometric results showed that the microspheres showed similar fragmentation and bio-absorbation (p>0.05. We observed the formation of new bones in both groups during the same experimental periods; however, the new bone formation differed significantly between the weeks 1 and 6 (p=0.0039 in both groups. Conclusion: The CHA and SrCHA biomaterials were biocompatible, osteoconductive and bioabsorbable, indicating their great potential for clinical use as bone substitutes.

  17. Alveolar bone repair with strontium- containing nanostructured carbonated hydroxyapatite.

    Science.gov (United States)

    Carmo, André Boziki Xavier do; Sartoretto, Suelen Cristina; Alves, Adriana Terezinha Neves Novellino; Granjeiro, José Mauro; Miguel, Fúlvio Borges; Calasans-Maia, Jose; Calasans-Maia, Monica Diuana

    2018-01-18

    This study aimed to evaluate bone repair in rat dental sockets after implanting nanostructured carbonated hydroxyapatite/sodium alginate (CHA) and nanostructured carbonated hydroxyapatite/sodium alginate containing 5% strontium microspheres (SrCHA) as bone substitute materials. Twenty male Wistar rats were randomly divided into two experimental groups: CHA and SrCHA (n=5/period/group). After one and 6 weeks of extraction of the right maxillary central incisor and biomaterial implantation, 5 μm bone blocks were obtained for histomorphometric evaluation. The parameters evaluated were remaining biomaterial, loose connective tissue and newly formed bone in a standard area. Statistical analysis was performed by Mann-Withney and and Wilcoxon tests at 95% level of significance. The histomorphometric results showed that the microspheres showed similar fragmentation and bio-absorbation (p>0.05). We observed the formation of new bones in both groups during the same experimental periods; however, the new bone formation differed significantly between the weeks 1 and 6 (p=0.0039) in both groups. The CHA and SrCHA biomaterials were biocompatible, osteoconductive and bioabsorbable, indicating their great potential for clinical use as bone substitutes.

  18. P2X7R: independent modulation of aquaporin 5 expression in CdCl2-injured alveolar epithelial cells.

    Science.gov (United States)

    Heupel, Julia; Bläsche, Robert; Wesslau, Karl-Philipp; Kasper, Michael; Barth, Kathrin

    2018-03-01

    The expression of aquaporin 5 in alveolar epithelial type I cells under conditions of cadmium-induced injury has not yet been discovered. We investigated the effect of the P2X7R agonist BzATP under this condition, since P2X7R is involved in altered regulation of aquaporin 5 in pulmonary fibrosis. CdCl 2 /TGF-β1 treatment of lung epithelial MLE-12 cells was leading to increasing P2X7R, and aquaporin 5 protein levels. The aquaporin 5 expression was P2X7R-independent in MLE-12 cells under cadmium, as was shown in blocking experiments with oxATP. Further, the expression of both proteins increased after 24 h CdCl 2 /TGF-β1 treatment of precision-cut lung slices, but decreased after 72 h. Using immunohistochemistry, the activation of the P2X7R with the agonist BzATP modulated the aquaporin 5 immunoreactivity in the alveolar epithelium of precision-cut lung slices from wild-type but not from P2X7R knockout mice. Similarly, aquaporin 5 protein was reduced in BzATP-treated immortal lung epithelial E10 cells. Surprisingly, untreated alveolar epithelial type II cells of P2X7R knockouts exhibited a pronounced apical immunoreactivity in addition to the remaining alveolar epithelial type I cells. BzATP exposure did not alter this distribution pattern, but increased the number of apoptotic alveolar epithelial type II cells in wild-type lung slices.

  19. Environmental particulate (PM2.5 augments stiffness-induced alveolar epithelial cell mechanoactivation of transforming growth factor beta.

    Directory of Open Access Journals (Sweden)

    Marilyn M Dysart

    Full Text Available Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis (PF, chronic obstructive pulmonary disease (COPD, and tumorigenesis have been increasing over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that in response to increased transforming growth factor--beta (TGFβ signaling, the alveolar type II (ATII epithelial cell undergoes phenotypic changes that may contribute to the complex pathobiology of PF. We have previously demonstrated that increased tissue stiffness associated with PF is a potent extracellular matrix (ECM signal for epithelial cell activation of TGFβ. The work reported here explores the relationship between tissue stiffness and exposure to environmental stimuli in the activation of TGFβ. We hypothesized that exposure of ATII cells to fine particulate matter (PM2.5 will result in enhanced cell contractility, TGFβ activation, and subsequent changes to ATII cell phenotype. ATII cells were cultured on increasingly stiff substrates with or without addition of PM2.5. Exposure to PM2.5 resulted in increased activation of TGFβ, increased cell contractility, and elongation of ATII cells. Most notably, on 8 kPa substrates, a stiffness greater than normal but less than established fibrotic lung, addition of PM2.5 resulted in increased cortical cell stiffness, enhanced actin staining and cell elongation; a result not seen in the absence of PM2.5. Our work suggests that PM2.5 exposure additionally enhances the existing interaction between ECM stiffness and TGFβ that has been previously reported. Furthermore, we show that this additional enhancement is likely a consequence of intracellular reactive oxygen species (ROS leading to increased TGFβ signaling events. These results highlight the importance of both the micromechanical and biochemical environment in lung disease initiation and suggest that individuals in early stages of lung

  20. Mitochondrial quality control in alveolar epithelial cells damaged byS. aureuspneumonia in mice.

    Science.gov (United States)

    Suliman, Hagir B; Kraft, Bryan; Bartz, Raquel; Chen, Lingye; Welty-Wolf, Karen E; Piantadosi, Claude A

    2017-10-01

    Mitochondrial damage is often overlooked in acute lung injury (ALI), yet most of the lung's physiological processes, such as airway tone, mucociliary clearance, ventilation-perfusion (Va/Q) matching, and immune surveillance require aerobic energy provision. Because the cell's mitochondrial quality control (QC) process regulates the elimination and replacement of damaged mitochondria to maintain cell survival, we serially evaluated mitochondrial biogenesis and mitophagy in the alveolar regions of mice in a validated Staphylococcus aureus pneumonia model. We report that apart from cell lysis by direct contact with microbes, modest epithelial cell death was detected despite significant mitochondrial damage. Cell death by TdT-mediated dUTP nick-end labeling staining occurred on days 1 and 2 postinoculation: apoptosis shown by caspase-3 cleavage was present on days 1 and 2, while necroptosis shown by increased levels of phospho- mixed lineage kinase domain-like protein (MLKL) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was present on day 1 Cell death in alveolar type I (AT 1 ) cells assessed by bronchoalveolar lavage fluid receptor for advanced glycation end points (RAGE) levels was high, yet AT 2 cell death was limited while both mitochondrial biogenesis and mitophagy were induced. These mitochondrial QC mechanisms were evaluated mainly in AT 2 cells by localizing increases in citrate synthase content, increases in nuclear mitochondrial biogenesis regulators nuclear respiratory factor-1 (NRF-1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and increases in light chain 3B protein (LC3-I)/LC3II ratios. Concomitant changes in p62, Pink 1, and Parkin protein levels indicated activation of mitophagy. By confocal microscopy, mitochondrial biogenesis and mitophagy were often observed on day 1 within the same AT 2 cells. These findings imply that mitochondrial QC activation in pneumonia-damaged AT 2 cells promotes cell

  1. Sustained distribution of aerosolized PEGylated liposomes in epithelial lining fluids on alveolar surfaces.

    Science.gov (United States)

    Kaneko, Keita; Togami, Kohei; Yamamoto, Eri; Wang, Shujun; Morimoto, Kazuhiro; Itagaki, Shirou; Chono, Sumio

    2016-10-01

    The distribution characteristics of aerosolized PEGylated liposomes in alveolar epithelial lining fluid (ELF) were examined in rats, and the ensuing mechanisms were investigated in the in vitro uptake and protein adsorption experiments. Nonmodified or PEGylated liposomes (particle size 100 nm) were aerosolized into rat lungs. PEGylated liposomes were distributed more sustainably in ELFs than nonmodified liposomes. Furthermore, the uptake of PEGylated liposomes by alveolar macrophages (AMs) was less than that of nonmodified liposomes. In further in vitro uptake experiments, nonmodified and PEGylated liposomes were opsonized with rat ELF components and then added to NR8383 cells as cultured rat AMs. The uptake of opsonized PEGylated liposomes by NR8383 cells was lower than that of opsonized nonmodified liposomes. Moreover, the protein absorption levels in opsonized PEGylated liposomes were lower than those in opsonized nonmodified liposomes. These findings suggest that sustained distributions of aerosolized PEGylated liposomes in ELFs reflect evasion of liposomal opsonization with surfactant proteins and consequent reductions in uptake by AMs. These data indicate the potential of PEGylated liposomes as aerosol-based drug delivery system that target ELF for the treatment of respiratory diseases.

  2. Evidence-based outcomes following inferior alveolar and lingual nerve injury and repair: a systematic review.

    Science.gov (United States)

    Kushnerev, E; Yates, J M

    2015-10-01

    The inferior alveolar nerve (IAN) and lingual (LN) are susceptible to iatrogenic surgical damage. Systematically review recent clinical evidence regarding IAN/LN repair methods and to develop updated guidelines for managing injury. Recent publications on IAN/LN microsurgical repair from Medline, Embase and Cochrane Library databases were screened by title/abstract. Main texts were appraised for exclusion criteria: no treatment performed or results provided, poor/lacking procedural description, cohort injury type, injury timing, neurosensory disturbances and intra-operative findings. Best functional nerve recovery occurred after direct apposition and suturing if nerve ending gaps were nerve grafting (sural/greater auricular nerve). Timing of microneurosurgical repair after injury remains debated. Most authors recommend surgery when neurosensory deficit shows no improvement 90 days post-diagnosis. Nerve transection diagnosed intra-operatively should be repaired in situ; minor nerve injury repair can be delayed. No consensus exists regarding optimal methods and timing for IAN/LN repair. We suggest a schematic guideline for treating IAN/LN injury, based on the most current evidence. We acknowledge that additional RCTs are required to provide definitive confirmation of optimal treatment approaches. © 2015 John Wiley & Sons Ltd.

  3. Effect of cigarette smoke and dexamethasone on Hsp72 system of alveolar epithelial cells.

    Science.gov (United States)

    Gál, Krisztina; Cseh, Aron; Szalay, Balázs; Rusai, Krisztina; Vannay, Adám; Lukácsovits, József; Heemann, Uwe; Szabó, Attila J; Losonczy, György; Tamási, Lilla; Müller, Veronika

    2011-07-01

    Smoking is the leading risk factor of chronic obstructive pulmonary disease (COPD) and lung cancer. Corticosteroids are abundantly used in these patients; however, the interaction of smoking and steroid treatment is not fully understood. Heat shock proteins (Hsps) play a central role in the maintenance of cell integrity, apoptosis and cellular steroid action. To better understand cigarette smoke-steroid interaction, we examined the effect of cigarette smoke extract (CSE) and/or dexamethasone (DEX) on changes of intracellular heat shock protein-72 (Hsp72) in lung cells. Alveolar epithelial cells (A549) were exposed to increasing doses (0; 0.1; 1; and 10 μM/μl) of DEX in the medium in the absence(C) and presence of CSE. Apoptosis, necrosis, Hsp72 messenger-ribonucleic acid (mRNA) and protein expression of cells were measured, and the role of Hsp72 on steroid effect examined. CSE reduced the number of viable cells by significantly increasing the number of apoptotic and necrotic cells. DEX dose-dependently decreased the ratio of apoptosis when CSE was administered, without change in necrosis. CSE - DEX co-treatment dose-dependently increased Hsp72 mRNA and protein expression, with the highest level measured in CSE + DEX (10) cells, while significantly lower levels were noted in all respective C groups. Pretreatment with Hsp72 silencing RNA confirmed that increased survival observed following DEX administration in CSE-treated cells was mainly mediated via the Hsp72 system. CSE significantly decreases cell survival by inducing apoptosis and necrosis. DEX significantly increases Hsp72 mRNA and protein expression only in the presence of CSE resulting in increased cellular protection and survival. DEX exerts its cell protective effects by decreasing apoptotic cell death via the Hsp72 system in CSE-treated alveolar epithelial cells.

  4. Cytotoxicity and gene array analysis of alveolar epithelial A549 cells exposed to paraquat.

    Science.gov (United States)

    Mitsopoulos, Panagiotis; Suntres, Zacharias E

    2010-12-05

    Paraquat (PQ), a commonly used herbicide, is highly toxic to humans and animals. The primary injury occurs in the lung, where PQ is actively taken up by alveolar epithelial cells and consequently produces damaging reactive oxygen species (ROS) via redox cycling. ROS have also been shown to induce expression of several early response genes and to activate transcription factors, which may contribute to the inflammatory response associated with PQ injury. In order to further elucidate the mechanism(s) of PQ injury, we investigated its effects on the cellular status and gene expression profile of immortalized human alveolar epithelial A549 cells in vitro. Incubation of cells with PQ resulted in concentration- and time-dependent PQ uptake, which correlated with increases in intracellular ROS levels and decreases in intracellular glutathione content, mitochondrial membrane potential, and cell viability. Gene array analysis showed differential expression in response to PQ exposure over time, particularly increases in: (i) the expression of growth arrest and cell cycle-related genes (e.g. CDKN1A, DDIT3 GADD45A, GDF15, MDM2, EGR1, CASP10, CASP8) and (ii) the expression of pro-inflammatory genes (e.g. IL1A, IL6, IL18, NFKB1, SERPINE1), which correlated with increases in the secretion of pro-inflammatory cytokines (e.g. IL-8, IL-6). These data suggest that uptake of PQ by A549 cells altered the cellular redox status and the expression of several early response genes, including the inflammatory response, all of which might contribute to the overall cytotoxicity of PQ. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair.

    Directory of Open Access Journals (Sweden)

    Jennifer Quantius

    2016-06-01

    Full Text Available Influenza Virus (IV pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6high. This cell fraction expressed the stem cell antigen-1, highly enriched lung stem/progenitor cells previously characterized by the signature integrin(β4+CD200+, and upregulated the p63/krt5 regeneration program after IV-induced injury. Using 3-dimensional organoid cultures derived from these epithelial stem/progenitor cells (EpiSPC, and in vivo infection models including transgenic mice, we reveal that their expansion, barrier renewal and outcome after IV-induced injury critically depended on Fgfr2b signaling. Importantly, IV infected EpiSPC exhibited severely impaired renewal capacity due to IV-induced blockade of β-catenin-dependent Fgfr2b signaling, evidenced by loss of alveolar tissue repair capacity after intrapulmonary EpiSPC transplantation in vivo. Intratracheal application of exogenous Fgf10, however, resulted in increased engagement of non-infected EpiSPC for tissue regeneration, demonstrated by improved proliferative potential, restoration of alveolar barrier function and increased survival following IV pneumonia. Together, these data suggest that tropism of IV to distal lung stem cell niches represents an important factor of pathogenicity and highlight impaired Fgfr2b signaling as underlying mechanism. Furthermore, increase of

  6. Mesenchymal Stem Cell Conditioned Medium Promotes Proliferation and Migration of Alveolar Epithelial Cells under Septic Conditions In Vitro via the JNK-P38 Signaling Pathway

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    Jie Chen

    2015-11-01

    Full Text Available Background/Aims: Mesenchymal stem cell (MSC based therapies may be useful for treating acute respiratory distress syndrome (ARDS, but the underlying mechanisms are incompletely understood. We investigated the impact of human umbilical cord Wharton's jelly-derived MSC (hUC-MSC secreted factors on alveolar epithelial cells under septic conditions and determined the relevant intracellular signaling pathways. Methods: Human alveolar epithelial cells (AEC and primary human small airway epithelial cells (SAEC were subjected to lipopolysaccharide (LPS with or without the presence of hUC-MSC-conditioned medium (CM. Proliferation and migration of AEC and SAEC were determined via an MTT assay, a wound healing assay and a transwell migration assay (only for AEC. Protein phosphorylation was determined by western blot and the experiments were repeated in presence of small-molecule inhibitors. The hMSC-secretory proteins were identified by LC-MS/MS mass spectrometry. Results: MSC-CM enhanced proliferation and migration. Activation of JNK and P38, but not ERK, was required for the proliferation and migration of AEC and SAEC. Pretreatment of AEC or SAEC with SP600125, an inhibitor of JNK1 or SB200358, an inhibitor of P38, significantly reduced cell proliferation and migration. An array of proteins including TGF-beta receptor type-1, TGF-beta receptor type-2, Ras-related C3 botulinum toxin substrate 1 and Ras-related C3 botulinum toxin substrate 2 which influencing the proliferation and migration of AEC and SAEC were detected in MSC-CM. Conclusion: Our data suggest MSC promote epithelial cell repair through releasing a repertoire of paracrine factors via activation of JNK and P38 MAPK.

  7. Trichomonas vaginalis induces cytopathic effect on human lung alveolar basal carcinoma epithelial cell line A549.

    Science.gov (United States)

    Salvador-Membreve, Daile Meek C; Jacinto, Sonia D; Rivera, Windell L

    2014-12-01

    Trichomonas vaginalis, the causative agent of trichomoniasis is generally known to inhabit the genitourinary tract. However, several case reports with supporting molecular and immunological identifications have documented its occurrence in the respiratory tract of neonates and adults. In addition, the reports have documented that its occurrence is associated with respiratory failures. The medical significance or consequence of this association is unclear. Thus, to establish the possible outcome from the interaction of T. vaginalis with lung cells, the cytopathic effects of the parasites were evaluated using monolayer cultures of the human lung alveolar basal carcinoma epithelial cell line A549. The possible effect of association of T. vaginalis with A549 epithelial cells was analyzed using phase-contrast, scanning electron microscopy and fluorescence microscopy. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), crystal-violet and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) assays were conducted for cytotoxicity testing. The results demonstrate that T. vaginalis: (1) adheres to A549 epithelial cells, suggesting a density-dependent parasite-cell association; (2) adherence on A549 is through flagella, membrane and axostyle; (3) causes cell detachment and cytotoxicity (50-72.4%) to A549 and this effect is a function of parasite density; and (4) induces apoptosis in A549 about 20% after 6 h of incubation. These observations indicate that T. vaginalis causes cytopathic effects on A549 cell. To date, this is the first report showing a possible interaction of T. vaginalis with the lung cells using A549 monolayer cultures. Further studies are recommended to completely elucidate this association. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

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    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  9. ResolvinD1 stimulates epithelial wound repair and inhibits TGF-β-induced EMT whilst reducing fibroproliferation and collagen production

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    Zheng, Shengxing; Wang, Qian; D'Souza, Vijay; Bartis, Dom; Dancer, Rachel; Parekh, Dhruv; Gao, Fang; Lian, Qingquan; Jin, Shengwei; Thickett, David R

    2018-01-01

    Acute and chronic inflammatory lung diseases are often associated with epithelial cell injury/loss and fibroproliferative responses. ResolvinD1 (RvD1) is biosynthesized during the resolution phase of inflammatory response and exerts potent anti-inflammatory and promotes resolution of inflammatory lung diseases. The aim of this study was to investigate whether RvD1 exerts protective effects on alveolar epithelial cell function/differentiation and protects against fibroproliferative stimuli. Primary human alveolar type II cells were used to model the effects of RvD1 in vitro upon wound repair, proliferation, apoptosis, transdifferentiation, and epithelial–mesenchymal transition (EMT). Effects of RvD1 upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also examined. RvD1 promoted alveolar type II (ATII) cell wound repair and proliferation. RvD1 protected ATII cells against sFas-ligand/TNF-α-induced apoptosis and inhibition on cell proliferation and viability. RvD1 promoted ATII cells transdifferentiation. Moreover, we demonstrate that RvD1 inhibited EMT in response to TGF-β. Furthermore RvD1 inhibited human lung fibroblast proliferation, collagen production, and myofibroblast differentiation induced by both TGF-β and bronchoalveolar lavage fluid from acute respiratory distress syndrome (ARDS) patients. The effects of RvD1 were PI3-kinase dependent and mediated via the resolvin receptor. RvD1 seems to promote alveolar epithelial repair by stimulating ATII cells wound repair, proliferation, reducing apoptosis, and inhibiting TGF-β-induced EMT. While RvD1 reduced fibroproliferation, collagen production, and myofibroblast differentiation. Together, these results suggest a potential new therapeutic strategy for preventing and treating chronic diseases (such as idiopathic pulmonary fibrosis) as well as the fibroproliferative phase of ARDS by targeting RvD1 actions that emphasizes natural resolution signaling

  10. P2X7R-dependent regulation of glycogen synthase kinase 3β and claudin-18 in alveolar epithelial type I cells of mice lung.

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    Barth, K; Bläsche, R; Neißer, A; Bramke, S; Frank, J A; Kasper, M

    2016-12-01

    The purinergic receptor P2X7 represents an ATP-gated ionotropic receptor with a selective localization in alveolar epithelial type I cells of the lung. Despite the involvement of the receptor in inflammatory processes of the lung, it is not established whether this receptor plays a specific role in the alveolar epithelial cell biology. There is evidence that P2X7 receptor influences Wnt/β-catenin signalling pathways in alveolar epithelial cells under conditions of injury. Here, we investigated the expression of GSK-3β, a potent protein kinase involved in alveolar epithelial barrier functions, and of tight junction molecules occludin, claudin-4 and claudin-18 in wild-type and P2X7 -/- mice. Western blot analysis, immunohistochemistry and quantitative real-time RT-PCR revealed a remarkable increase in claudin-18 mRNA and protein in lungs of P2X7 -/- mice animals. Furthermore, alveolar epithelial cells from P2X7 -/- animals showed decreased levels of GSK-3β protein and its inactive form GSK-3β (pS9). Conversely, claudin-18 knockout mice exhibited decreased P2X7 mRNA transcript abundance as measured by mRNA expression microarray and quantitative PCR. Our data are consistent with the hypothesis that P2X7R contributes to alveolar epithelial barrier function through effects on GSK-3β. Furthermore, these data suggest a potential reciprocal regulation of claudin-18 and P2X7R in the alveolar epithelium.

  11. Folliculin Controls Lung Alveolar Enlargement and Epithelial Cell Survival through E-Cadherin, LKB1, and AMPK

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    Elena A. Goncharova

    2014-04-01

    Full Text Available Spontaneous pneumothoraces due to lung cyst rupture afflict patients with the rare disease Birt-Hogg-Dubé (BHD syndrome, which is caused by mutations of the tumor suppressor gene folliculin (FLCN. The underlying mechanism of the lung manifestations in BHD is unclear. We show that BHD lungs exhibit increased alveolar epithelial cell apoptosis and that Flcn deletion in mouse lung epithelium leads to cell apoptosis, alveolar enlargement, and an impairment of both epithelial barrier and overall lung function. We find that Flcn-null epithelial cell apoptosis is the result of impaired AMPK activation and increased cleaved caspase-3. AMPK activator LKB1 and E-cadherin are downregulated by Flcn loss and restored by its expression. Correspondingly, Flcn-null cell survival is rescued by the AMPK activator AICAR or constitutively active AMPK. AICAR also improves lung condition of Flcnf/f:SP-C-Cre mice. Our data suggest that lung cysts in BHD may result from an underlying defect in alveolar epithelial cell survival, attributable to FLCN regulation of the E-cadherin-LKB1-AMPK axis.

  12. Is bone transplantation the gold standard for repair of alveolar bone defects?

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    Cassio Eduardo Raposo-Amaral

    2014-01-01

    Full Text Available New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate, compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7 defects were repaired with autogenous bone grafts; Group 2 (n = 5 defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5 defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5 defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6 defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2–5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01 and 38.35% ± 19.59% (p = 0.06 of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30 and 61.80% ± 2.14% (p = 0.88 of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone.

  13. Breakdown of Epithelial Barrier Integrity and Overdrive Activation of Alveolar Epithelial Cells in the Pathogenesis of Acute Respiratory Distress Syndrome and Lung Fibrosis

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    Shigehisa Yanagi

    2015-01-01

    Full Text Available Individual alveolar epithelial cells (AECs collaboratively form a tight barrier between atmosphere and fluid-filled tissue to enable normal gas exchange. The tight junctions of AECs provide intercellular sealing and are integral to the maintenance of the AEC barrier integrity. Disruption and failure of reconstitution of AEC barrier result in catastrophic consequences, leading to alveolar flooding and subsequent devastating fibrotic scarring. Recent evidences reveal that many of the fibrotic lung diseases involve AECs both as a frequent target of injury and as a driver of ongoing pathological processes. Aberrantly activated AECs express most of the growth factors and chemokines responsible for the proliferation, migration, and activation of fibroblasts. Current evidences suggest that AECs may acquire overdrive activation in the initial step of fibrosis by several mechanisms, including abnormal recapitulation of the developmental pathway, defects of the molecules essential for epithelial integrity, and acceleration of aging-related properties. Among these initial triggering events, epithelial Pten, a multiple phosphatase that negatively regulates the PI3K/Akt pathway and is crucial for lung development, is essential for the prevention of alveolar flooding and lung fibrosis through the regulation of AEC barrier integrity after injury. Reestablishment of AEC barrier integrity also involves the deployment of specialized stem/progenitor cells.

  14. Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

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    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.

  15. Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice

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    Danyi Peng

    2017-12-01

    Full Text Available Alveolar epithelial cells (AECs injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF. Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ model, as well as a new SMARCA4-deleted alveolar type II (ATII-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.

  16. Effect of SLC34A2 gene mutation on extracellular phosphorus transport in PAM alveolar epithelial cells.

    Science.gov (United States)

    Ma, Tiangang; Qu, Danhua; Yan, Bingdi; Zhang, Qinghua; Ren, Jin; Hu, Yanbing

    2018-01-01

    A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in this study were aimed at confirming the role of the gene product in PAM by comparing phosphorylated products in extracellular fluid of alveolar epithelial cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic expression vectors were constructed and transfected into A549 human alveolar epithelial cells. There were three groups of cells including those transfected with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and those transfected with a version of the PAM SLC34A2 gene linked to the pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the concentration of inorganic phosphorus in the culture medium was detected using an automatic biochemical analyzer. Our results showed the concentration of inorganic phosphorus in the supernatant of the normal control group was significantly lower than that in the plasmid control and PAM groups (PPAM group was significantly lower than that in the plasmid control group (PPAM patients, given that the function of the phosphate transporter seems to be affected and it is conceivable that it would lead to extracellular fluid alterations in vivo .

  17. Essential role for cathepsin D in bleomycin-induced apoptosis of alveolar epithelial cells.

    Science.gov (United States)

    Li, Xiaopeng; Rayford, Heather; Shu, Ruijie; Zhuang, Jiaju; Uhal, Bruce D

    2004-07-01

    Our earlier studies showed that bleomycin-induced apoptosis of type II alveolar epithelial cells (AECs) requires the autocrine synthesis and proteolytic processing of angiotensinogen into ANG II and that inhibitors of ANG-converting enzyme (ACEis) block bleomycin-induced apoptosis (Li X, Zhang H, Soledad-Conrad V, Zhuang J, and Uhal BD. Am J Physiol Lung Cell Mol Physiol 284: L501-L507, 2003). Given the documented role of cathepsin D (CatD) in apoptosis of other cell types, we hypothesized that CatD might be the AEC enzyme responsible for the conversion of angiotensinogen into ANG I, the substrate for ACE. Primary cultures of rat type II AECs challenged with bleomycin in vitro showed upregulation and secretion of CatD enzymatic activity and immunoreactive protein but no increases in CatD mRNA. The aspartyl protease inhibitor pepstatin A, which completely blocked CatD enzymatic activity, inhibited bleomycin-induced nuclear fragmentation by 76% and reduced bleomycin-induced caspase-3 activation by 47%. Antisense oligonucleotides against CatD mRNA reduced CatD-immunoreactive protein and inhibited bleomycin-induced nuclear fragmentation by 48%. A purified fragment of angiotensinogen (F1-14) containing the CatD and ACE cleavage sites, when applied to unchallenged AEC in vitro, yielded mature ANG II peptide and induced apoptosis. The apoptosis induced by F1-14 was inhibited 96% by pepstatin A and 77% by neutralizing antibodies specific for CatD (both P CatD in bleomycin-induced apoptosis of cultured AEC and suggest that the role(s) of CatD in AEC apoptosis include the conversion of newly synthesized angiotensinogen to ANG II.

  18. Involvement of Igf1r in Bronchiolar Epithelial Regeneration: Role during Repair Kinetics after Selective Club Cell Ablation.

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    Icíar P López

    Full Text Available Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice, and revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury.

  19. Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells

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    Rahman Irfan

    2006-10-01

    Full Text Available Abstract Background Cigarette smoke mediated oxidative stress and inflammatory events in the airway and alveolar epithelium are important processes in the pathogenesis of smoking related pulmonary diseases. Previously, individual cell lines were used to assess the oxidative and proinflammatory effects of cigarette smoke with confounding results. In this study, a panel of human and rodent transformed epithelial cell lines were used to determine the effects of cigarette smoke extract (CSE on oxidative stress markers, cell toxicity and proinflammatory cytokine release and compared the effects with that of primary human small airway epithelial cells (SAEC. Methods Primary human SAEC, transformed human (A549, H1299, H441, and rodent (murine MLE-15, rat L2 alveolar epithelial cells were treated with different concentrations of CSE (0.2–10% ranging from 20 min to 24 hr. Cytotoxicity was assessed by lactate dehydrogenase release assay, trypan blue exclusion method and double staining with acridine orange and ethidium bromide. Glutathione concentration was measured by enzymatic recycling assay and 4-hydroxy-2-nonenal levels by using lipid peroxidation assay kit. The levels of proinflammatory cytokines (e.g. IL-8 and IL-6 were measured by ELISA. Nuclear translocation of the transcription factor, NF-κB was assessed by immunocytochemistry and immunoblotting. Results Cigarette smoke extract dose-dependently depleted glutathione concentration, increased 4-hydroxy-2-nonenal (4-HNE levels, and caused necrosis in the transformed cell lines as well as in SAEC. None of the transformed cell lines showed any significant release of cytokines in response to CSE. CSE, however, induced IL-8 and IL-6 release in primary cell lines in a dose-dependent manner, which was associated with the nuclear translocation of NF-κB in SAEC. Conclusion This study suggests that primary, but not transformed, lung epithelial cells are an appropriate model to study the inflammatory

  20. The influence of volatile anesthetics on alveolar epithelial permeability measured by noninvasive radionuclide lung scan

    International Nuclear Information System (INIS)

    Hung, Chih-Jen; Wu, Rick Sai-Chuen; Lin, Cheng-Chieh; Kao, Albert; Tsai, Jeffrey J.P.

    2003-01-01

    Many volatile anesthetics have long been thought to affect pulmonary functions including lung ventilation (LV) and alveolar epithelial permeability (AEP). The purpose of this study is to examine the influence of volatile anesthetics on LV and AEP by noninvasive radionuclide lung imaging of technetium-99m labeled diethylene triamine pentaacetic acid radioaerosol inhalation lung scan (DTPA lung scan). Twenty patients undergoing surgery and receiving volatile anesthesia with 1% halothane were enrolled as the study group 1. The other 20 patients undergoing surgery and receiving volatile anesthesia with 1.5% isoflurane were enrolled as the study group 2. At the same time, 20 patients undergoing surgery with intravenous anesthesia drugs were included as a control group. Before surgery, 1 hour after surgery, and 1 week after surgery, we investigated the 3 groups of patients with DTPA lung scan to evaluate LV and AEP by 99m Tc DTPA clearance halftime (T1/2). No significant change or abnormality of LV before surgery, 1 hour after surgery, or 1 week after surgery was found among the 3 groups of patients. In the control group, the 99m Tc DTPA clearance T1/2 was 63.5±16.4, 63.1±18.4, and 62.8±17.0 minutes, before surgery, 1 hour after surgery, and 1 week after surgery, respectively. In group 1, it was 65.9±9.3, 62.5±9.1, and 65.8±10.3 minutes, respectively. No significant change in AEP before surgery, 1 hour after surgery, or 1 week after surgery was found. However, in group 2, the 99m Tc DTPA clearance T1/2 was 65.5±13.2, 44.9±10.5, and 66.1±14.0 minutes, respectively. A significant transient change in AEP was found 1 hour after surgery, but it recovered 1 week after surgery. We conclude that volatile anesthesia is safe for LV and AEP, and only isoflurane can induce transient change of AEP. (author)

  1. Effect of laser phototherapy on human alveolar bone repair: micro tomographic and histomorphometrical analysis

    Science.gov (United States)

    Romão, Marcia M. A.; Marques, Márcia M.; Cortes, Arthur R. G.; Horliana, Anna C. R. T.; Moreira, Maria S.; Lascala, Cesar A.

    2015-06-01

    The immediate dental implant placement in the molars region is critical, because of the high amount of bone loss and the discrepancy between the alveolar crest thickness and the dental implant platform. Laser phototherapy (LPT) improves bone repair thus could accelerate the implant placement. Twenty patients were selected for the study. Ten patients were submitted to LPT with GaAlAs diode laser (808nm) during molar extraction, immediately after, 24h, 48h, 72h, 96h and 7 days. The irradiations were applied in contact and punctual mode (100mW, 0.04cm2, 0.75J/cm2, 30s per point, 3J per point). The control group (n=10) received the same treatment; however with the power of the laser off. Forty days later samples of the tissue formed inside the sockets were obtained for further microtomography (microCTs) and histomorphometry analyses. Data were compared by the Student t test, whereas those from the different microCT parameters were compared by the Pearson correlation test (pimplant placement.

  2. Differential replication of avian influenza H9N2 viruses in human alveolar epithelial A549 cells

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    Peiris Malik

    2010-03-01

    Full Text Available Abstract Avian influenza virus H9N2 isolates cause a mild influenza-like illness in humans. However, the pathogenesis of the H9N2 subtypes in human remains to be investigated. Using a human alveolar epithelial cell line A549 as host, we found that A/Quail/Hong Kong/G1/97 (H9N2/G1, which shares 6 viral "internal genes" with the lethal A/Hong Kong/156/97 (H5N1/97 virus, replicates efficiently whereas other H9N2 viruses, A/Duck/Hong Kong/Y280/97 (H9N2/Y280 and A/Chicken/Hong Kong/G9/97 (H9N2/G9, replicate poorly. Interestingly, we found that there is a difference in the translation of viral protein but not in the infectivity or transcription of viral genes of these H9N2 viruses in the infected cells. This difference may possibly be explained by H9N2/G1 being more efficient on viral protein production in specific cell types. These findings suggest that the H9N2/G1 virus like its counterpart H5N1/97 may be better adapted to the human host and replicates efficiently in human alveolar epithelial cells.

  3. Sequential changes of lamellar body hydrolases during ozone-induced alveolar injury and repair

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    Glew, R.H.; Basu, A.; Shelley, S.A.; Paterson, J.F.; Diven, W.F.; Montgomery, M.R.; Balis, J.U.

    1989-05-01

    Lamellar body hydrolases in acutely damaged and regenerating type II cells were determined using an established rat model with well-defined stages of bronchiolo-alveolar injury and repair. Lamellar bodies were isolated from control and ozone-exposed (3.0 ppm for 8 hours) adult male rats by sucrose density gradient centrifugation and analyzed for their content of six different lysosomal hydrolases. Immediately after 3 ppm ozone exposure (zero-time) there was a significant decrease in specific enzyme activity (units/mg protein) of five lamellar body hydrolases and these activities remained depressed for at least 24 hours after exposure. In addition, total enzyme activity (units/lung) was reduced at zero-time for beta-hexosaminidase and at 24 hours postexposure for alpha-mannosidase and alpha-L-fucosidase. During the reparative and recovery stages (48 to 96 hours) the hydrolases demonstrated variable elevations in both specific activity and total activity (units/lung). Characteristically, beta-hexosaminidase and beta-galactosidase reached supranormal values at 96 hours, whereas alpha-mannosidase remained below normal levels through the recovery stage. Moreover, at 24 to 48 hours the lamellar body fraction demonstrated prominent enzyme depletion relative to the expanding pool of stored surfactant. It is concluded that acute ozone stress initiates the development of hydrolase deficiency within the lamellar bodies of injured and regenerating type II cells. This deficiency state is followed by asynchronous lamellar body hydrolase elevations that reflect distinct patterns of response rather than uniform return to normal condition. The lysosomal enzyme changes of lamellar bodies may be pathogenetically linked to the development of associated alterations in the storage and secretion of surfactant.

  4. Mammary alveolar epithelial cells convert to brown adipocytes in post-lactating mice

    DEFF Research Database (Denmark)

    Giordano, Antonio; Perugini, Jessica; Kristensen, David Møbjerg

    2017-01-01

    found close to the mammary alveoli contain milk protein granules. Use of the Cre-loxP recombination system allowed showing that the involuting mammary gland of whey acidic protein-Cre/R26R mice, whose secretory alveolar cells express the lacZ gene during pregnancy, contains some X...

  5. Increased survival and proliferation of the epidemic strain Mycobacterium abscessus subsp. massiliense CRM0019 in alveolar epithelial cells.

    Science.gov (United States)

    Ribeiro, Giovanni Monteiro; Matsumoto, Cristianne Kayoko; Real, Fernando; Teixeira, Daniela; Duarte, Rafael Silva; Mortara, Renato Arruda; Leão, Sylvia Cardoso; de Souza Carvalho-Wodarz, Cristiane

    2017-09-13

    Outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. Mycobacterium abscessus subsp. massiliense CRM0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. To better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (RAW and BMDM) and alveolar epithelial cells (A549). For that, we assessed the following parameters, for both M. abscessus CRM0019 as well as the reference strain M. abscessus ATCC 19977: internalization, intracellular survival for up 3 days, competence to subvert lysosome fusion and the intracellular survival after cell reinfection. CRM0019 and ATCC 19977 strains showed the same internalization rate (approximately 30% after 6 h infection), in both A549 and RAW cells. However, colony forming units data showed that CRM0019 survived better in A549 cells than the ATCC 19977 strain. Phagosomal characteristics of CRM0019 showed the bacteria inside tight phagosomes in A549 cells, contrasting to the loosely phagosomal membrane in macrophages. This observation holds for the ATCC 19977 strain in both cell types. The competence to subvert lysosome fusion was assessed by acidification and acquisition of lysosomal protein. For M. abscessus strains the phagosomes were acidified in all cell lines; nevertheless, the acquisition of lysosomal protein was reduced by CRM0019 compared to the ATCC 19977 strain, in A549 cells. Conversely, in macrophages, both M. abscessus strains were located in mature phagosomes, however without bacterial death. Once recovered from macrophages M. abscessus could establish a new intracellular infection. Nevertheless, only CRM0019 showed a higher growth rate in A549, increasing nearly 10-fold after 48 and 72 h. M. abscessus CRM0019 creates a protective and replicative niche in alveolar epithelial cells mainly by

  6. Water-pipe smoke condensate increases the internalization of Mycobacterium Bovis of type II alveolar epithelial cells (A549).

    Science.gov (United States)

    Mortaz, Esmaeil; Alipoor, Shamila D; Movassaghi, Masoud; Varahram, Mohammad; Ghorbani, Jahangir; Folkerts, Gert; Garssen, Johan; Adcock, Ian M

    2017-04-21

    Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection. Here, we studied the effects of water-pipe condense (WPC) on the internalization of Mycobacterium Bovis BCG by macropinocytosis in the alveolar epithelial cell line A549. A549 cells were exposed to WPC (4 mg/ml) for 24, 48, 72 and 96 h. Cell viability was studied using the methyl thiazolyldipenyl-tetrazolium bromide (MTT) reduction assay and proliferation by bromodeoxyUridine (BrdU) incorporation. Cells were exposed to FITC-Dextran (1 mg/ml) (as a control) and FITC-BCG (MOI = 10) for 20 min at 37 °C before cells were collected and the uptake of BCG-FITC determined by flow cytometry. Similar experiments were performed at 4 °C as a control. The Rho-associated protein kinase (ROCK) inhibitor Y-27632 (1 μM) was used to assess the mechanism by which WPC enhanced BCG uptake. WPC (4 mg/ml) increased the uptake of BCG-FITC after 72 (1.3 ± 0.1 fold, p WPC also significantly increased the uptake of FITC-Dextran (2.9 ± 0.3 fold, p WPC significantly decreased cell viability after 24 (84 ± 2%, p WPC. Cell proliferation showed a decreasing trend in a time-dependent manner with WPC exposure. WPC exposure increased epithelial cell endocytosis activity and death as well as enhancing their capacity for macropinocytosis. Our in vitro data indicates possible harmful effects of WPC on the ability of lung epithelial cells to phagocytose mycobacterium.

  7. Micro-computed tomography and histomorphometric analysis of human alveolar bone repair induced by laser phototherapy: a pilot study.

    Science.gov (United States)

    Romão, M M A; Marques, M M; Cortes, A R G; Horliana, A C R T; Moreira, M S; Lascala, C A

    2015-12-01

    Immediate dental implant placement in the molar region is critical, because of the high amount of bone loss and the discrepancy between alveolar crest thickness and the implant platform. Laser phototherapy (LPT) improves bone repair. The aim of this study was to evaluate the human alveolar bone repair 40 days after molar extraction in patients submitted to LPT. Twenty patients were selected for this randomized controlled clinical trial; 10 underwent LPT (laser group) with a GaAlAs diode laser (808 nm, 100 mW, 0.04 cm(2), 75 J/cm(2), 30s per point, 3 J per point, at five points). The control group patients (n=10) were not irradiated. Forty days later, the tissue formed inside the sockets was analyzed by micro-computed tomography and histomorphometry. Data from the two groups were compared with Student's t-test and Pearson's correlation test. The relative bone volume was significantly higher in the laser group (P<0.0001). The control group showed negative correlations (P<0.01) between number and thickness, and between number and separation of trabeculae, and a positive correlation between thickness and separation of trabeculae. The laser group showed a significant negative correlation between the number and thickness of trabeculae (P<0.01). The results suggest that LPT is able to accelerate alveolar bone repair after molar extraction, leading to a more homogeneous trabecular configuration represented by thin and close trabeculae. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Human amniotic epithelial cells combined with silk fibroin scaffold in the repair of spinal cord injury

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    Ting-gang Wang

    2016-01-01

    Full Text Available Treatment and functional reconstruction after central nervous system injury is a major medical and social challenge. An increasing number of researchers are attempting to use neural stem cells combined with artificial scaffold materials, such as fibroin, for nerve repair. However, such approaches are challenged by ethical and practical issues. Amniotic tissue, a clinical waste product, is abundant, and amniotic epithelial cells are pluripotent, have low immunogenicity, and are not the subject of ethical debate. We hypothesized that amniotic epithelial cells combined with silk fibroin scaffolds would be conducive to the repair of spinal cord injury. To test this, we isolated and cultured amniotic epithelial cells, and constructed complexes of these cells and silk fibroin scaffolds. Implantation of the cell-scaffold complex into a rat model of spinal cord injury resulted in a smaller glial scar in the damaged cord tissue than in model rats that received a blank scaffold, or amniotic epithelial cells alone. In addition to a milder local immunological reaction, the rats showed less inflammatory cell infiltration at the transplant site, milder host-versus-graft reaction, and a marked improvement in motor function. These findings confirm that the transplantation of amniotic epithelial cells combined with silk fibroin scaffold can promote the repair of spinal cord injury. Silk fibroin scaffold can provide a good nerve regeneration microenvironment for amniotic epithelial cells.

  9. Current perspectives in epithelial cell injury and repair: consequences for epithelial functions

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    R. Lutter

    2005-12-01

    Full Text Available Epithelial cells lining the airways and the respiratory compartment may, and certainly when exposed to an inflammatory milieu, display an altered functioning, which could contribute to pathophysiology of inflammatory lung/airway disease. In the present review paper, several issues that were discussed at an earlier European Respiratory Society Research Seminar on conditions that affect epithelial functioning have been recapitulated and updated. These and future studies should improve understanding of epithelial functioning and may aid recovery from disease.

  10. Semaphorin-Plexin Signaling Controls Mitotic Spindle Orientation during Epithelial Morphogenesis and Repair

    DEFF Research Database (Denmark)

    Xia, Jingjing; Swiercz, Jakub M.; Bañón-Rodríguez, Inmaculada

    2015-01-01

    show that this alignment depends on epithelial cell-cell communication via semaphorin-plexin signaling. During kidney morphogenesis and repair, renal tubular epithelial cells lacking the transmembrane receptor Plexin-B2 or its semaphorin ligands fail to correctly orient the mitotic spindle, leading...... to severe defects in epithelial architecture and function. Analyses of a series of transgenic and knockout mice indicate that Plexin-B2 controls the cell division axis by signaling through its GTPase-activating protein (GAP) domain and Cdc42. Our data uncover semaphorin-plexin signaling as a central...

  11. Estudio histológico comparativo de la reparación ósea entre hueso alveolar y extra-alveolar en los cerdos sometidos a osteotomía con alta y baja velocidad, con refrigeración líquida Comparative study of bone repair between alveolar and extra-alveolar bone in pigs subjected to osteotomy at low speed and high speed with liquid refrigeration

    Directory of Open Access Journals (Sweden)

    Henrique José Baldo de Toledo

    2012-03-01

    Full Text Available Introducción: Teniendo en cuenta que el proceso de reparación ósea en los cerdos se muestra en una mayor proximidad entre las variables histológicas estudiadas en comparación con otros modelos biológicos, el presente estudio tenía como objetivo evaluar el proceso histológico de la reparación ósea de osteotomías realizadas en huesos alveolares y extra-alveolar, utilizando instrumentos rotatorios con refrigeración líquida. Material y método: Dieciocho cerdos Large White con peso comprendido entre 20 y 25Kg fueron divididos en tres grupos de seis animales cada uno, con cada grupo formado por tres animales para evaluar la reparación de osteotomías con baja y alta velocidades en el hueso alveolar y tres en área extra-alveolar en los períodos de estudio de 7, 14 y 28 días. Resultados: Se observó que en el hueso alveolar en los tiempos post-operatorio de 14 y 28 días, los mejores resultados de reparación fueron en las osteotomías realizadas con baja velocidad, mientras que en el período post-operatorio de siete días, los resultados con alta velocidad fueron ligeramente mejores tanto en áreas alveolares como extra-alveolares. Para la metodología utilizada, no se encontraron diferencias estadísticamente significativas en el proceso de reparación ósea alveolar y extra-alveolar. Conclusiones: El proceso de reparación, por medio de análisis microscópico en la región alveolar y extra-alveolar, son similares con mejores resultados observados en osteotomías hechas con taladros en baja velocidad en los tiempos de catorce y veintiocho días y en el post-operatorio de siete días, los resultados con taladros de alta velocidad y la refrigeración fueron ligeramente mejores. Los trabajos de investigación utilizando cerdos como modelo animal son perfectamente viables.Introduction: Taking into account the bone repair process in pigs has shown a greater similarity among the histological variables studied compared to other biological

  12. Brief mechanical ventilation causes differential epithelial repair along the airways of fetal, preterm lambs.

    Science.gov (United States)

    Deptula, Nicole; Royse, Emily; Kemp, Matthew W; Miura, Yuichiro; Kallapur, Suhas G; Jobe, Alan H; Hillman, Noah H

    2016-08-01

    Mechanical ventilation of preterm lambs causes lung inflammation and injury to the airway epithelium, which is repaired by 15 days after ventilation. In mice, activated basal cells (p63+, KRT14+, KRT8+) initiate injury repair to the trachea, whereas club cells coordinate distal airway repair. In both human and sheep, basal cells line the pseudostratified airways to the distal bronchioles with club cells only present in terminal bronchioles. Mechanical ventilation causes airway epithelial injury that is repaired through basal cell activation in the fetal lung. Ewes at 123 ± 1 day gestational age had the head and chest of the fetus exteriorized and tracheostomy placed. With placental circulation intact, fetal lambs were mechanically ventilated with up to 15 ml/kg for 15 min with 95% N2/5% CO2 Fetal lambs were returned to the uterus for up to 24 h. The trachea, left mainstem bronchi, and peripheral lung were evaluated for epithelial injury and cellular response consistent with repair. Peripheral lung tissue had inflammation, pro-inflammatory cytokine production, epithelial growth factor receptor ligand upregulation, increased p63 expression, and proliferation of pro-SPB, TTF-1 positive club cells. In bronchi, KRT14 and KRT8 mRNA increased without increases in Notch pathway mRNA or proliferation. In trachea, mRNA increased for Notch ligands, SAM pointed domain-containing Ets transcription factor and mucin 5B, but not for basal cell markers. A brief period of mechanical ventilation causes differential epithelial activation between trachea, bronchi, and peripheral lung. The repair mechanisms identified in adult mice occur at different levels of airway branching in fetal sheep with basal and club cell activation. Copyright © 2016 the American Physiological Society.

  13. CCR2 and CXCR3 agonistic chemokines are differently expressed and regulated in human alveolar epithelial cells type II

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    Prasse Antje

    2005-07-01

    Full Text Available Abstract The attraction of leukocytes from circulation to inflamed lungs depends on the activation of both the leukocytes and the resident cells within the lung. In this study we determined gene expression and secretion patterns for monocyte chemoattractant protein-1 (MCP-1/CCL2 and T-cell specific CXCR3 agonistic chemokines (Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11 in TNF-α-, IFN-γ-, and IL-1β-stimulated human alveolar epithelial cells type II (AEC-II. AEC-II constitutively expressed high level of CCL2 mRNA in vitro and in situ , and released CCL2 protein in vitro . Treatment of AEC-II with proinflammatory cytokines up-regulated both CCL2 mRNA expression and release of immunoreactive CCL2, whereas IFN-γ had no effect on CCL2 release. In contrast, CXCR3 agonistic chemokines were not detected in freshly isolated AEC-II or in non-stimulated epithelial like cell line A549. IFN-γ, alone or in combination with IL-1β and TNF-α resulted in an increase in CXCL10, CXCL11, and CXCL9 mRNA expression and generation of CXCL10 protein by AEC-II or A549 cells. CXCL10 gene expression and secretion were induced in dose-dependent manner after cytokine-stimulation of AEC-II with an order of potency IFN-γ>>IL-1β ≥ TNF-α. Additionally, we localized the CCL2 and CXCL10 mRNAs in human lung tissue explants by in situ hybridization, and demonstrated the selective effects of cytokines and dexamethasone on CCL2 and CXCL10 expression. These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.

  14. Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor-dependent and independent pathways.

    Science.gov (United States)

    Chen, Bi; Cai, Hou-Rong; Xue, Shan; You, Wen-Jie; Liu, Bin; Jiang, Han-Dong

    2016-08-01

    The roles of bile acid microaspiration and bile acid-activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation. Human AECs and normal or IPF-derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The AECs injury indices, epithelial-mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR-independent pathways in bile acid-induced profibrotic effects were also investigated. LCA, DCA and CDCA reduced cell viability and increased intracellular reactive oxygen species (ROS) production in A549 cells. They all induced EMT, as shown by enhanced α-SMA and vimentin and decreased E-cadherin levels. LCA directly induced differentiation of lung fibroblasts to myofibroblasts. All three bile acids promoted cellular migration but not proliferation of lung fibroblasts. FXR expression was upregulated in IPF lungs, and inhibition of FXR restrained the bile acid-induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid-stimulated A549 cells, which contained increased levels of profibrotic factors. TGF-β/Smad3 signaling was also involved in the bile acid-induced EMT and lung fibroblast differentiation. Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR-dependent and independent pathways. © 2016 Asian Pacific Society of Respirology.

  15. Micro-structured Beta-Tricalcium Phosphate for Repair of the Alveolar Cleft in Cleft Lip and Palate Patients : A Pilot Study

    NARCIS (Netherlands)

    de Ruiter, AP; Janssen, Nard; van Es, Robert; Frank, Michael; Meijer, Gert; Koole, Ron; Rosenberg, Toine

    2015-01-01

    OBJECTIVES: Can a synthetic bone substitute be used to repair the alveolar cleft to bypass donor site morbidity as well as to shorten the operating time? In earlier experimental studies, micro-structured beta-tricalcium phosphate (β-TCP) provided similar bone healing when compared with grafting with

  16. Genomic signature and toxicogenomics comparison of polycationic gene delivery nanosystems in human alveolar epithelial A549 cells

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    J Barar

    2009-10-01

    Full Text Available "nBackground and the purpose of the study: Of the gene delivery systems, non-viral polycationic gene delivery nanosystems have been alternatively exploited as a relatively safe delivery reagents compared to viral vectors. However, little is known about the genomic impacts of these delivery systems in target cells/tissues. In this study, the toxicogenomics and genotoxicity potential of some selected polycationic lipid/polymer based nanostructures (i.e., Oligofectamine® (OF, starburst polyamidoamine Polyfect® (PF and diaminobutane (DAB dendrimers were investigated in human alveolar epithelial A549 cells. "nMethods: To study the nature and the ontology of the gene expression changes in A549 cells upon treatment with polycationic nanostructures, MTT assay and microarray gene expression profiling methodology were employed. For microarray analysis, cyanine (Cy3/Cy5 labeled cDNA samples from treated and untreated cells were hybridized on target arrays housing 200 genes. "nResults and major conclusions: The polycationic nanosystems induced significant gene expression changes belonging to different genomic ontologies such as cell defence and apoptosis pathways. These data suggest that polycationic nanosystems can elicit multiple gene expression changes in A549 cells upon their chemical structures and interactions with cellular/subcellular components. Such impacts may interfere with the main goals of the desired genemedicine.

  17. The regenerative potential of epithelial stem cells in tissue repair.

    Science.gov (United States)

    Arandjelovic, Philip; Kaur, Pritinder

    2014-11-01

    Acute and chronic wounds encompass devastating injuries with significant physical, emotional and economic costs at both the individual and societal level. The pathogenesis of chronic wounds is as varied as the potential causes; however, contributing factors include repetitive ischaemia/reperfusion injury coupled with bacterial infection, inflammation and matrix degradation at the wound site. Similarly, the acute physical damage of burns may leave patients vulnerable to dehydration and infection, and in certain cases this may be followed by a body-wide systemic response with debilitating consequences. Epithelial stem cells provide a promising avenue for the treatment of burns and chronic wounds. This is exemplified by recent achievements such as the restoration of corneal epithelium using limbal stem cells, and the treatment of epidermolysis bullosa via a gene therapy approach. Nevertheless, many technical and regulatory challenges remain to be addressed. This article is part of a Directed Issue entitled: Regenerative Medicine: the challenge of translation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Epithelial cell senescence impairs repair process and exacerbates inflammation after airway injury

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    Nagai Atsushi

    2011-06-01

    Full Text Available Abstract Background Genotoxic stress, such as by exposure to bromodeoxyuridine (BrdU and cigarette smoke, induces premature cell senescence. Recent evidence indicates that cellular senescence of various types of cells is accelerated in COPD patients. However, whether the senescence of airway epithelial cells contributes to the development of airway diseases is unknown. The present study was designed to test the hypothesis that premature senescence of airway epithelial cells (Clara cells impairs repair processes and exacerbates inflammation after airway injury. Methods C57/BL6J mice were injected with the Clara-cell-specific toxicant naphthalene (NA on days 0, 7, and 14, and each NA injection was followed by a daily dose of BrdU on each of the following 3 days, during which regenerating cells were allowed to incorporate BrdU into their DNA and to senesce. The p38 MAPK inhibitor SB202190 was injected 30 minutes before each BrdU dose. Mice were sacrificed at different times until day 28 and lungs of mice were obtained to investigate whether Clara cell senescence impairs airway epithelial regeneration and exacerbates airway inflammation. NCI-H441 cells were induced to senesce by exposure to BrdU or the telomerase inhibitor MST-312. Human lung tissue samples were obtained from COPD patients, asymptomatic smokers, and nonsmokers to investigate whether Clara cell senescence is accelerated in the airways of COPD patients, and if so, whether it is accompanied by p38 MAPK activation. Results BrdU did not alter the intensity of the airway epithelial injury or inflammation after a single NA exposure. However, after repeated NA exposure, BrdU induced epithelial cell (Clara cell senescence, as demonstrated by a DNA damage response, p21 overexpression, increased senescence-associated β-galactosidase activity, and growth arrest, which resulted in impaired epithelial regeneration. The epithelial senescence was accompanied by p38 MAPK-dependent airway

  19. Overexpression of sICAM-1 in the Alveolar Epithelial Space Results in an Exaggerated Inflammatory Response and Early Death in Gram Negative Pneumonia

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    Curtis Jeffery L

    2011-01-01

    Full Text Available Abstract Background A sizeable body of data demonstrates that membrane ICAM-1 (mICAM-1 plays a significant role in host defense in a site-specific fashion. On the pulmonary vascular endothelium, mICAM-1 is necessary for normal leukocyte recruitment during acute inflammation. On alveolar epithelial cells (AECs, we have shown previously that the presence of normal mICAM-1 is essential for optimal alveolar macrophage (AM function. We have also shown that ICAM-1 is present in the alveolar space as a soluble protein that is likely produced through cleavage of mICAM-1. Soluble intercellular adhesion molecule-1 (sICAM-1 is abundantly present in the alveolar lining fluid of the normal lung and could be generated by proteolytic cleavage of mICAM-1, which is highly expressed on type I AECs. Although a growing body of data suggesting that intravascular sICAM-1 has functional effects, little is known about sICAM-1 in the alveolus. We hypothesized that sICAM-1 in the alveolar space modulates the innate immune response and alters the response to pulmonary infection. Methods Using the surfactant protein C (SPC promoter, we developed a transgenic mouse (SPC-sICAM-1 that constitutively overexpresses sICAM-1 in the distal lung, and compared the responses of wild-type and SPC-sICAM-1 mice following intranasal inoculation with K. pneumoniae. Results SPC-sICAM-1 mice demonstrated increased mortality and increased systemic dissemination of organisms compared with wild-type mice. We also found that inflammatory responses were significantly increased in SPC-sICAM-1 mice compared with wild-type mice but there were no difference in lung CFU between groups. Conclusions We conclude that alveolar sICAM-1 modulates pulmonary inflammation. Manipulating ICAM-1 interactions therapeutically may modulate the host response to Gram negative pulmonary infections.

  20. Characterisation of cellular adhesion reinforcement by multiple bond force spectroscopy in alveolar epithelial cells.

    Science.gov (United States)

    Nguyen, Ngoc-Minh; Angely, Christelle; Andre Dias, Sofia; Planus, Emmanuelle; Filoche, Marcel; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2017-07-01

    Integrin-mediated adhesion is a key process by which cells physically connect with their environment, and express sensitivity and adaptation through mechanotransduction. A critical step of cell adhesion is the formation of the first bonds which individually generate weak contacts (∼tens pN) but can sustain thousand times higher forces (∼tens nN) when associated. We propose an experimental validation by multiple bond force spectroscopy (MFS) of a stochastic model predicting adhesion reinforcement permitted by non-cooperative, multiple bonds on which force is homogeneously distributed (called parallel bond configuration). To do so, spherical probes (diameter: 6.6 μm), specifically coated by RGD-peptide to bind integrins, are used to statically indent and homogenously stretch the multiple bonds created for short contact times (2 s) between the bead and the surface of epithelial cells (A549). Using different separation speeds (v = 2, 5, 10 μm/s) and measuring cellular Young's modulus as well as the local stiffness preceding local rupture events, we obtain cell-by-cell the effective loading rates both at the global cell level and at the local level of individual constitutive bonds. Local rupture forces are in the range: f*=60-115 pN , whereas global rupture (detachment) forces reach F*=0.8-1.7 nN . Global and local rupture forces both exhibit linear dependencies with the effective loading rate, the slopes of these two linear relationships providing an estimate of the number of independent integrin bonds constituting the tested multiple bond structure (∼12). The MFS method enables to validate the reinforcement of integrin-mediated adhesion induced by the multiple bond configuration in which force is homogeneously distributed amongst parallel bonds. Local rupture events observed in the course of a spectroscopy manoeuver (MFS) lead to rupture force values considered in the literature as single-integrin bonds. Adhesion reinforcement permitted by the parallel

  1. Comparison of plasma, epithelial lining fluid, and alveolar macrophage concentrations of solithromycin (CEM-101) in healthy adult subjects.

    Science.gov (United States)

    Rodvold, Keith A; Gotfried, Mark H; Still, J Gordon; Clark, Kay; Fernandes, Prabhavathi

    2012-10-01

    The steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC(0-24) values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC(0-24) values were 10.3 and 10.0, respectively. The AUC(0-24) values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC(0-24) values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P solithromycin administration.

  2. The role of alveolar epithelial cells in initiating and shaping pulmonary immune responses: communication between innate and adaptive immune systems.

    Directory of Open Access Journals (Sweden)

    Olga D Chuquimia

    Full Text Available Macrophages and dendritic cells have been recognized as key players in the defense against mycobacterial infection. However, more recently, other cells in the lungs such as alveolar epithelial cells (AEC have been found to play important roles in the defense and pathogenesis of infection. In the present study we first compared AEC with pulmonary macrophages (PuM isolated from mice in their ability to internalize and control Bacillus Calmette-Guérin (BCG growth and their capacity as APCs. AEC were able to internalize and control bacterial growth as well as present antigen to primed T cells. Secondly, we compared both cell types in their capacity to secrete cytokines and chemokines upon stimulation with various molecules including mycobacterial products. Activated PuM and AEC displayed different patterns of secretion. Finally, we analyzed the profile of response of AEC to diverse stimuli. AEC responded to both microbial and internal stimuli exemplified by TLR ligands and IFNs, respectively. The response included synthesis by AEC of several factors, known to have various effects in other cells. Interestingly, TNF could stimulate the production of CCL2/MCP-1. Since MCP-1 plays a role in the recruitment of monocytes and macrophages to sites of infection and macrophages are the main producers of TNF, we speculate that both cell types can stimulate each other. Also, another cell-cell interaction was suggested when IFNs (produced mainly by lymphocytes were able to induce expression of chemokines (IP-10 and RANTES by AEC involved in the recruitment of circulating lymphocytes to areas of injury, inflammation, or viral infection. In the current paper we confirm previous data on the capacity of AEC regarding internalization of mycobacteria and their role as APC, and extend the knowledge of AEC as a multifunctional cell type by assessing the secretion of a broad array of factors in response to several different types of stimuli.

  3. Differential regulation of epidermal growth factor receptor by hydrogen peroxide and flagellin in cultured lung alveolar epithelial cells.

    Science.gov (United States)

    Nishi, Hiroyuki; Maeda, Noriko; Izumi, Shunsuke; Higa-Nakamine, Sayomi; Toku, Seikichi; Kakinohana, Manabu; Sugahara, Kazuhiro; Yamamoto, Hideyuki

    2015-02-05

    In previous studies, we found that stimulation of Toll-like receptor 5 (TLR5) by flagellin induced the activation of mitogen-activated protein kinase (MAPK)-activated protein kinase-2 (MAPKAPK-2) through activation of the p38 MAPK pathway in cultured alveolar epithelial A549 cells. Our studies strongly suggested that MAPKAPK-2 phosphorylated epidermal growth factor receptor (EGFR) at Ser1047. It has been reported that phosphorylation of Ser1047 after treatment with tumor necrosis factor α (TNFα) induced the internalization of EGFR. In the present study, we first found that treatment of A549 cells with hydrogen peroxide induced the activation of MAPKAPK-2 and phosphorylation of EGFR at Ser1047 within 30 min. This was different from flagellin treatment because hydrogen peroxide treatment induced the phosphorylation of EGFR at Tyr1173 as well as Ser1047, indicating the activation of EGFR. We also found that KN93, an inhibitor of CaM kinase II, inhibited the hydrogen peroxide-induced phosphorylation of EGFR at Ser1047 through inhibition of the activation of the p38 MAPK pathway. Furthermore, we examined the internalization of EGFR by three different methods. Flow cytometry with an antibody against the extracellular domain of EGFR and biotinylation of cell surface proteins revealed that flagellin, but not hydrogen peroxide, decreased the amount of cell-surface EGFR. In addition, activation of extracellular signal-regulated kinase by EGF treatment was reduced by flagellin pre-treatment. These results strongly suggested that hydrogen peroxide activated the p38 MAPK pathway via activation of CaM kinase II and that flagellin and hydrogen peroxide regulate the functions of EGFR by different mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Ethanol alters alveolar fluid balance via Nadph oxidase (NOX signaling to epithelial sodium channels (ENaC in the lung.

    Directory of Open Access Journals (Sweden)

    Charles A Downs

    Full Text Available Chronic alcohol consumption is associated with increased incidence of ICU-related morbidity and mortality, primarily from acute respiratory distress syndrome (ARDS. However, the mechanisms involved are unknown. One explanation is that alcohol regulates epithelial sodium channels (ENaC via oxidant signaling to promote a pro- injury environment. We used small rodent models to mimic acute and chronic alcohol consumption and tested the hypothesis that ethanol (EtOH would affect lung fluid clearance by up-regulating ENaC activity in the lung. Fluorescence labeling of rat lung slices and in vivo mouse lung revealed an increase in ROS production in response to acute EtOH exposure. Using western blots and fluorescein-5-maleimide labeling, we conclude that EtOH exposure modifies cysteines of α-ENaC while data from single channel patch clamp analysis confirm that 0.16% EtOH increased ENaC activity in rat alveolar cells. In vivo lung fluid clearance demonstrated a latent increase in fluid clearance in mice receiving EtOH diet. Ethanol mice given a tracheal instillation of LPS demonstrated early lung fluid clearance compared to caloric control mice and C57Bl/6 mice. Standard biochemical techniques reveal that chronic EtOH consumption resulted in greater protein expression of the catalytic gp91(phox subunit and the obligate Rac1 protein. Collectively these data suggest that chronic EtOH consumption may lead to altered regulation of ENaC, contributing to a 'pro-injury' environment in the alcohol lung.

  5. Repair mechanism of retinal pigment epithelial tears in age-related macular degeneration.

    Science.gov (United States)

    Mukai, Ryo; Sato, Taku; Kishi, Shoji

    2015-03-01

    To investigate repair mechanisms of retinal pigment epithelial (RPE) tears in age-related macular degeneration. The authors retrospectively studied 10 eyes with age-related macular degeneration that developed RPE tears during follow-up or after treatment with an anti-vascular endothelial growth factor drug or photodynamic therapy combined with ranibizumab. After development of the RPE tears, all follow-ups exceeded 13 months. Spectral domain or swept-source optical coherence tomography have been used to examine consecutive retinal changes where the RPE tears developed and attempted to determine the repair mechanisms. Retinal pigment epithelial tears developed during the natural course (n = 4) after ranibizumab treatment (n = 2) and after photodynamic therapy and ranibizumab (n = 4). Subretinal fluid persisted for more than 6 months after the RPE tears developed (n = 4), with the area where the RPE was lost found to be covered with thickened proliferative tissue. In 6 eyes where the subretinal fluid was absorbed within 2 months, optical coherence tomography showed the outer retina appeared to be directly attached to Bruch membrane, and there was attenuation of the normal hyperreflective band attributable to normal RPE during follow-up. Results suggest that two repair processes may be present in the area where RPE tears developed. Persistent subretinal fluid may lead to repair with thick proliferative tissue, while the outer retina appears to attach to Bruch membrane when there is early subretinal fluid resolution after RPE tear development.

  6. NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair

    Science.gov (United States)

    Parlato, Marianna; Yeretssian, Garabet

    2014-01-01

    The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound healing. Hence, through a sequence of events involving restitution, proliferation and differentiation of IECs the gap is resealed and homeostasis reestablished. Relapsing damage followed by healing of the inflamed mucosa is a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). While several regulatory peptides, growth factors and cytokines stimulate restitution of the epithelial layer after injury, recent evidence in the field underscores the contribution of innate immunity in controlling this process. In particular, nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Here, we review the process of intestinal epithelial tissue repair and we specifically focus on the impact of NLR-mediated signaling mechanisms involved in governing epithelial wound healing during disease. PMID:24886810

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

    Science.gov (United States)

    Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

    2015-05-01

    Autologous bone graft has been regarded as the criterion standard for the repair of alveolar cleft. However, the most prominent issue in alveolar cleft treatment is the high absorption rate of the bone graft. The authors' objective was to investigate the effects of an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture on the repair of dog alveolar cleft. Twenty beagle dogs with unilateral alveolar clefts created by surgery were divided randomly into four groups: group A underwent repair with an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture; group B underwent repair with autologous iliac bone and bone marrow-derived mesenchymal stem cells; group C underwent repair with autologous iliac bone and platelet-rich fibrin; and group D underwent repair with autologous iliac bone as the control. One day and 6 months after transplantation, the transplant volumes and bone mineral density were assessed by quantitative computed tomography. All of the transplants were harvested for hematoxylin and eosin staining 6 months later. Bone marrow-derived mesenchymal stem cells and platelet-rich fibrin transplants formed the greatest amounts of new bone among the four groups. The new bone formed an extensive union with the underlying maxilla in groups A, B, and C. Transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture retained the majority of their initial volume, whereas the transplants in the control group showed the highest absorption rate. Bone mineral density of transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture 6 months later was significantly higher than in the control group (p bone marrow-derived mesenchymal stem cells and platelet-rich fibrin mixed transplants. Hematoxylin and eosin staining showed that the structure of new bones formed the best in group A. Both bone marrow

  9. Runx3 is a key modulator during the epithelial-mesenchymal transition of alveolar type II cells in animal models of BPD.

    Science.gov (United States)

    Yang, Haiping; Fu, Jianhua; Yao, Li; Hou, Ana; Xue, Xindong

    2017-11-01

    Bronchopulmonary dysplasia (BPD) is a major challenge for premature infants; however, the underlying mechanisms remain unclear. We previously reported that epithelial-mesenchymal transition (EMT) in alveolar type II (AT2) epithelial cells influences the normal alveolar development process. In this study, we wished to examine whether Runx3 is an important factor for BPD by regulating EMT in AT2 cells. In vivo, animal models of BPD were established by placing newborn rats in hyperoxia tanks. Lung tissue and isolated AT2 cells were collected on different days following exposure to oxygen. The pathological changes in lung tissue, alveolar development and Runx3 expression were then investigated. In vitro, RLE-6TN cells were divided into 5 groups as follows: the cont-rol, Runx3, siRunx3, transforming growth factor-β1 (TGF-β1) and Runx3 + TGF-β1 groups, and the biomarkers of EMT were investigated. In the newborn rat model of BPD, Runx3 protein and mRNA levels in both lung tissue and BPD-derived AT2 cells were significantly lower than those in the control group. The correlation between Runx3 protein expression and pulmonary development indicators was analyzed; Runx3 expression positively correlated with the radial alveolar count (RAC) and the percentage of smooth muscle actin-positive secondary septa, but negatively correlated with alveolar wall thickness. EMT was observed in the RLE-6TN cells in which the Runx3 gene was knocked down and follwoing TGF-β1‑induced EMT stimulation; however, TGF-β1 failed to induce EMT in the RLE-6TN cells overexpressing Runx3. On the whole, our data indicte that low Runx3 levels may promote EMT, while high Runx3 levels inhibit TGF-β1-induced EMT. Therefore, we predict that low levels of Runx3 in BPD lung tissue may promote EMT in AT2 cells, thus affecting alveolar development.

  10. Pneumocystis carinii major surface glycoprotein induces interleukin-8 and monocyte chemoattractant protein-1 release from a human alveolar epithelial cell line

    DEFF Research Database (Denmark)

    Benfield, T L; Lundgren, Bettina; Shelhamer, J H

    1999-01-01

    (IL-8) and monocyte chemoattractant protein-1 (MCP-1) from an alveolar epithelial cell line (A549). RESULTS: Incubation of A549 cells with MSG in concentrations from 0.4 to 10 microg mL-1 for 24 h caused dose-dependent increases in IL-8 release (3.4-fold above control, P ..., suggesting that MSG stimulates A549 cells in part through carbohydrate moieties. Dexamethasone significantly inhibited MSG-induced IL-8 release in concentrations of 10-6-10-8 mol L-1 compared with control experiments (P

  11. Exposure to Bordetella pertussis adenylate cyclase toxin affects integrin-mediated adhesion and mechanics in alveolar epithelial cells.

    Science.gov (United States)

    Angely, Christelle; Nguyen, Ngoc-Minh; Andre Dias, Sofia; Planus, Emmanuelle; Pelle, Gabriel; Louis, Bruno; Filoche, Marcel; Chenal, Alexandre; Ladant, Daniel; Isabey, Daniel

    2017-08-01

    The adenylate cyclase (CyaA) toxin is a major virulent factor of Bordetella pertussis, the causative agent of whooping cough. CyaA toxin is able to invade eukaryotic cells where it produces high levels of cyclic adenosine monophosphate (cAMP) affecting cellular physiology. Whether CyaA toxin can modulate cell matrix adhesion and mechanics of infected cells remains largely unknown. In this study, we use a recently proposed multiple bond force spectroscopy (MFS) with an atomic force microscope to assess the early phase of cell adhesion (maximal detachment and local rupture forces) and cell rigidity (Young's modulus) in alveolar epithelial cells (A549) for toxin exposure 95%) at CyaA concentration of 0.5 nM, but a significant effect (≈81%) at 10 nM. MFS performed on A549 for three different concentrations (0.5, 5 and 10 nM) demonstrates that CyaA toxin significantly affects both cell adhesion (detachment forces are decreased) and cell mechanics (Young's modulus is increased). CyaA toxin (at 0.5 nM) assessed at three indentation/retraction speeds (2, 5 and 10 μm/s) significantly affects global detachment forces, local rupture events and Young modulus compared with control conditions, while an enzymatically inactive variant CyaAE5 has no effect. These results reveal the loading rate dependence of the multiple bonds newly formed between the cell and integrin-specific coated probe as well as the individual bond kinetics which are only slightly affected by the patho-physiological dose of CyaA toxin. Finally, theory of multiple bond force rupture enables us to deduce the bond number N which is reduced by a factor of 2 upon CyaA exposure (N ≈ 6 versus N ≈ 12 in control conditions). MFS measurements demonstrate that adhesion and mechanical properties of A549 are deeply affected by exposure to the CyaA toxin but not to an enzymatically inactive variant. This indicates that the alteration of cell mechanics triggered by CyaA is a consequence of the increase in

  12. Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage.

    Science.gov (United States)

    Kim, Seok-Jo; Cheresh, Paul; Jablonski, Renea P; Morales-Nebreda, Luisa; Cheng, Yuan; Hogan, Erin; Yeldandi, Anjana; Chi, Monica; Piseaux, Raul; Ridge, Karen; Michael Hart, C; Chandel, Navdeep; Scott Budinger, G R; Kamp, David W

    2016-12-01

    Alveolar epithelial cell (AEC) injury and mitochondrial dysfunction are important in the development of lung fibrosis. Our group has shown that in the asbestos exposed lung, the generation of mitochondrial reactive oxygen species (ROS) in AEC mediate mitochondrial DNA (mtDNA) damage and apoptosis which are necessary for lung fibrosis. These data suggest that mitochondrial-targeted antioxidants should ameliorate asbestos-induced lung. To determine whether transgenic mice that express mitochondrial-targeted catalase (MCAT) have reduced lung fibrosis following exposure to asbestos or bleomycin and, if so, whether this occurs in association with reduced AEC mtDNA damage and apoptosis. Crocidolite asbestos (100µg/50µL), TiO 2 (negative control), bleomycin (0.025 units/50µL), or PBS was instilled intratracheally in 8-10 week-old wild-type (WT - C57Bl/6J) or MCAT mice. The lungs were harvested at 21d. Lung fibrosis was quantified by collagen levels (Sircol) and lung fibrosis scores. AEC apoptosis was assessed by cleaved caspase-3 (CC-3)/Surfactant protein C (SFTPC) immunohistochemistry (IHC) and semi-quantitative analysis. AEC (primary AT2 cells from WT and MCAT mice and MLE-12 cells) mtDNA damage was assessed by a quantitative PCR-based assay, apoptosis was assessed by DNA fragmentation, and ROS production was assessed by a Mito-Sox assay. Compared to WT, crocidolite-exposed MCAT mice exhibit reduced pulmonary fibrosis as measured by lung collagen levels and lung fibrosis score. The protective effects in MCAT mice were accompanied by reduced AEC mtDNA damage and apoptosis. Similar findings were noted following bleomycin exposure. Euk-134, a mitochondrial SOD/catalase mimetic, attenuated MLE-12 cell DNA damage and apoptosis. Finally, compared to WT, asbestos-induced MCAT AT2 cell ROS production was reduced. Our finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role

  13. Quantitative Analysis of Proteome Modulations in Alveolar Epithelial Type II Cells in Response to PulmonaryAspergillus fumigatusInfection.

    Science.gov (United States)

    Seddigh, Pegah; Bracht, Thilo; Molinier-Frenkel, Válerie; Castellano, Flavia; Kniemeyer, Olaf; Schuster, Marc; Weski, Juliane; Hasenberg, Anja; Kraus, Andreas; Poschet, Gernot; Hager, Thomas; Theegarten, Dirk; Opitz, Christiane A; Brakhage, Axel A; Sitek, Barbara; Hasenberg, Mike; Gunzer, Matthias

    2017-12-01

    The ubiquitous mold Aspergillus fumigatus threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. A. fumigatus conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Previous studies reported the importance of the surfactant-producing AEC II during A. fumigatus infection via in vitro experiments using cell lines. We established a negative isolation protocol yielding untouched primary murine AEC II with a purity >90%, allowing ex vivo analyses of the cells, which encountered the mold in vivo By label-free proteome analysis of AEC II isolated from mice 24h after A. fumigatus or mock infection we quantified 2256 proteins and found 154 proteins to be significantly differentially abundant between both groups (ANOVA p value ≤ 0.01, ratio of means ≥1.5 or ≤0.67, quantified with ≥2 peptides). Most of these proteins were higher abundant in the infected condition and reflected a comprehensive activation of AEC II on interaction with A. fumigatus This was especially represented by proteins related to oxidative phosphorylation, hence energy production. However, the most strongly induced protein was the l-amino acid oxidase (LAAO) Interleukin 4 induced 1 (IL4I1) with a 42.9 fold higher abundance (ANOVA p value 2.91 -10 ). IL4I1 has previously been found in B cells, macrophages, dendritic cells and rare neurons. Increased IL4I1 abundance in AEC II was confirmed by qPCR, Western blot and immunohistology. Furthermore, A. fumigatus infected lungs showed high levels of IL4I1 metabolic products. Importantly, higher IL4I1 abundance was also confirmed in lung tissue from human aspergilloma. Because LAAO are key enzymes for bactericidal product generation, AEC II might actively participate in pathogen defense. We provide insights into proteome changes of primary AEC II thereby opening new avenues to analyze the molecular changes of this central lung cell on infectious threats. Data are available via Proteome

  14. Use of Gore-Tex tubing as a conduit for inferior alveolar and lingual nerve repair: experience with 6 cases.

    Science.gov (United States)

    Pitta, M C; Wolford, L M; Mehra, P; Hopkin, J

    2001-05-01

    This report evaluates treatment outcomes associated with the use of Gore-Tex (GT; W.L. Gore & Associates, Flagstaff, AZ) vein graft tubing as a conduit for repair of inferior alveolar nerve (IAN) and lingual nerve (LN) continuity defects. Six patients (5 female and 1 male) with painful dysesthesia secondary to injuries of the IAN (n = 3) or LN (n = 3) underwent surgical exploration and resection of pathologic tissue. Reconstruction of the resultant continuity defects was performed using 3-mm diameter GT tubing sutured to the epineurium of the proximal and distal nerve trunks. Nerve reconstruction was performed an average of 20 months after injury (range, 4 to 48 months). Patients were tested before and after surgery with the following tests: subjective pain level using an analogue scale, sharp stimulus, touch, cold sensation, directional sense, and 2-point discrimination. Four patients reported no change in subjective pain level, and 2 patients had minimal decrease in pain. Two patients reported some sensation to sharp stimulus, and 1 patient was hypersensitive. Three patients responded to touch, and 3 had no response. Four patients had no response to cold sensation, and 2 had a delayed response. Only 1 patient could detect brushstroke direction. Three patients had no response to 2-point discrimination, and 3 responded at greater than 20 mm. Use of GT tubing in this group of patients produced poor clinical outcomes and is not recommended for nerve reconstruction of IAN and LN continuity defects. Copyright 2001 American Association of Oral and Maxillofacial Surgeons

  15. Alveolar epithelial and endothelial cell apoptosis in emphysema: What we know and what we need to know

    Directory of Open Access Journals (Sweden)

    Mathieu C Morissette

    2008-12-01

    Full Text Available Mathieu C Morissette, Julie Parent, Julie MilotCentre de Recherche de l’Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l’Université Laval, Québec, CanadaAbstract: Emphysema is mainly caused by cigarette smoking and is characterized by the loss of alveolar integrity and an enlargement of the alveolar space. However, mechanisms involved in its development are not fully understood. Alveolar cell apoptosis has been previously investigated in the lung of emphysematous subjects as a potential contributor to the loss of alveolar cell and has been found abnormally elevated. Though, mechanisms involved in the increased alveolar apoptosis that occurs in emphysema have now become a prolific field of research. Those mechanisms are reviewed here with special focus on how they affect cell viability and how they may be implicated in emphysema. Moreover, we suggest a model that integrates all those mechanisms to explain the increased alveolar apoptosis observed in emphysema. This review also includes some reflections and suggestions on the research to come.Keywords: emphysema, apoptosis, proteases, VEGF, oxidative stress, TRAIL, autoimmunity

  16. Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane.

    Science.gov (United States)

    Orr, Galya; Panther, David J; Cassens, Kaylyn J; Phillips, Jaclyn L; Tarasevich, Barbara J; Pounds, Joel G

    2009-04-15

    The cellular interactions and pathways of engineered submicro- and nano-scale particles dictate the cellular response and ultimately determine the level of toxicity or biocompatibility of the particles. Positive surface charge can increase particle internalization, and in some cases can also increase particle toxicity, but the underlying mechanisms are largely unknown. Here we identify the cellular interaction and pathway of positively charged submicrometer synthetic amorphous silica particles, which are used extensively in a wide range of industrial applications, and are explored for drug delivery and medical imaging and sensing. Using time lapse fluorescence imaging in living cells and other quantitative imaging approaches, it is found that heparan sulfate proteoglycans play a critical role in the attachment and internalization of the particles in alveolar type II epithelial cell line (C10), a potential target cell type bearing apical microvilli. Specifically, the transmembrane heparan sulfate proteoglycan, syndecan-1, is found to mediate the initial interactions of the particles at the cell surface, their coupling with actin filaments across the cell membrane, and their subsequent internalization via macropinocytosis. The observed interaction of syndecan molecules with the particle prior to their engagement with actin filaments suggests that the particles initiate their own internalization by facilitating the clustering of the molecules, which is required for the actin coupling and subsequent internalization of syndecan. Our observations identify a new role for syndecan-1 in mediating the cellular interactions and fate of positively charged submicrometer amorphous silica particles in the alveolar type II epithelial cell, a target cell for inhaled particles.

  17. Syndecan-1 mediates the coupling of positively charged submicrometer amorphous silica particles with actin filaments across the alveolar epithelial cell membrane

    International Nuclear Information System (INIS)

    Orr, Galya; Panther, David J.; Cassens, Kaylyn J.; Phillips, Jaclyn L.; Tarasevich, Barbara J.; Pounds, Joel G.

    2009-01-01

    The cellular interactions and pathways of engineered submicro- and nano-scale particles dictate the cellular response and ultimately determine the level of toxicity or biocompatibility of the particles. Positive surface charge can increase particle internalization, and in some cases can also increase particle toxicity, but the underlying mechanisms are largely unknown. Here we identify the cellular interaction and pathway of positively charged submicrometer synthetic amorphous silica particles, which are used extensively in a wide range of industrial applications, and are explored for drug delivery and medical imaging and sensing. Using time lapse fluorescence imaging in living cells and other quantitative imaging approaches, it is found that heparan sulfate proteoglycans play a critical role in the attachment and internalization of the particles in alveolar type II epithelial cell line (C10), a potential target cell type bearing apical microvilli. Specifically, the transmembrane heparan sulfate proteoglycan, syndecan-1, is found to mediate the initial interactions of the particles at the cell surface, their coupling with actin filaments across the cell membrane, and their subsequent internalization via macropinocytosis. The observed interaction of syndecan molecules with the particle prior to their engagement with actin filaments suggests that the particles initiate their own internalization by facilitating the clustering of the molecules, which is required for the actin coupling and subsequent internalization of syndecan. Our observations identify a new role for syndecan-1 in mediating the cellular interactions and fate of positively charged submicrometer amorphous silica particles in the alveolar type II epithelial cell, a target cell for inhaled particles.

  18. Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

    Science.gov (United States)

    Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

    2017-09-16

    Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. TNF-α increases Staphylococcus aureus-induced death of human alveolar epithelial cell line A549 associated with RIP3-mediated necroptosis.

    Science.gov (United States)

    Wen, Shun-Hang; Lin, Luo-Na; Wu, Hu-Jun; Yu, Lu; Lin, Li; Zhu, Li-Li; Li, Hai-Yan; Zhang, Hai-Lin; Li, Chang-Chong

    2018-02-15

    To explore the role of tumor necrosis factor-alpha (TNF-α) on Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. The A549 alveolar epithelial cell line was pretreated with small interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then stimulated by S. aureus, where some cells were pretreated with TNF-α or TNF-α with anti-TNF-α antibody simultaneously. A549 cell death was assessed using lactate dehydrogenase (LDH) leakage and flow cytometry analyses. The protein expressions of RIP1, RIP3, cleaved caspase-1, and cleaved caspase-8 were analyzed by western blot. S. aureus-induced LDH release was increased significantly by TNF-α. In addition, flow cytometry showed that TNF-α increased A549 cell apoptosis and necrosis in S. aureus-infected cell cultures. Levels of RIP3 and cleaved caspase-1 protein in A549 cells infected with S. aureus increased at 12 h post-infection, as shown by western blot. Significant additional increases in RIP3 expression were observed following the addition of TNF-α. Decreasing RIP3 levels by siRNA significantly suppressed the release of LDH induced by TNF-α and S. aureus. RIP3 siRNA also significantly suppressed A549 cell necrosis induced by S. aureus and TNF-α at 6 and 12 h post-infection as shown by flow cytometry analysis. TNF-α enhances the damage of S. aureus on lung epithelial cells, and its mechanism is associated with RIP3 mediated necroptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival.

    Directory of Open Access Journals (Sweden)

    Renat Shaykhiev

    Full Text Available Epithelial cells (ECs continuously interact with microorganisms and detect their presence via different pattern-recognition receptors (PRRs including Toll-like receptors (TLRs. Ligation of epithelial TLRs by pathogens is usually associated with the induction of pro-inflammatory mediators and antimicrobial factors. In this study, using human airway ECs as a model, we found that detection of microbial patterns via epithelial TLRs directly regulates tissue homeostasis. Staphylococcus aureus (S. aureus and microbial patterns signaling via TLR2 and TLR5 induce a set of non-immune epithelial responses including cell migration, wound repair, proliferation, and survival of primary and cancerous ECs. Using small interfering RNA (siRNA gene targeting, receptor-tyrosine kinase microarray and inhibition studies, we determined that TLR and the epidermal growth factor receptor (EGFR mediate the stimulating effect of microbial patterns on epithelial repair. Microbial patterns signaling via Toll-like receptors 2 and 5 contribute to epithelial repair, growth and survival. This effect is independent of hematopoietic and other cells as well as inflammatory cytokines suggesting that epithelia are able to regulate their integrity in an autonomous non-inflammatory manner by sensing microbes directly via TLRs.

  1. Puerarin protects against Staphylococcus aureus-induced injury of human alveolar epithelial A549 cells via downregulating alpha-hemolysin secretion.

    Science.gov (United States)

    Tang, Feng; Li, Wen-Hua; Zhou, Xuan; Liu, Yong-Hua; Li, Zhe; Tang, Yu-Shun; Kou, Xu; Wang, Shu-De; Bao, Min; Qu, Lian-Da; Li, Min; Li, Bing

    2014-08-01

    Alpha-hemolysin, a secreted pore-forming toxin, plays an indispensable role in the pathogenicity of Staphylococcus aureus. In this study, the antimicrobial activity of puerarin against S. aureus was investigated; as a result, puerarin showed no influence on the growth of this organism. However, hemolysis and western blotting assays showed that puerarin concentration dependently inhibited the secretion of alpha-hemolysin at low concentrations. Real-time RT-PCR assay was further employed to evaluate the transcriptional level of hla, the gene encoding alpha-hemolysin, and RNAIII, an effector molecule of the agr system. The results indicated that the RNAIII expression and subsequent hla transcription were also inhibited by puerarin in a dose-dependent manner. Furthermore, puerarin significantly prevented human alveolar epithelial A549 cells from S. aureus-induced injury. Thereby, puerarin may be considered as a potential candidate for the development of antivirulence drugs in the treatment of S. aureus-mediated infections.

  2. Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model.

    Science.gov (United States)

    Sisler, Jennifer D; Pirela, Sandra V; Friend, Sherri; Farcas, Mariana; Schwegler-Berry, Diane; Shvedova, Anna; Castranova, Vincent; Demokritou, Philip; Qian, Yong

    2015-01-01

    The printer is one of the most common office equipment. Recently, it was reported that toner formulations for printing equipment constitute nano-enabled products (NEPs) and contain engineered nanomaterials (ENMs) that become airborne during printing. To date, insufficient research has been performed to understand the potential toxicological properties of printer-emitted particles (PEPs) with several studies using bulk toner particles as test particles. These studies demonstrated the ability of toner particles to cause chronic inflammation and fibrosis in animal models. However, the toxicological implications of inhalation exposures to ENMs emitted from laser printing equipment remain largely unknown. The present study investigates the toxicological effects of PEPs using an in vitro alveolar-capillary co-culture model with Human Small Airway Epithelial Cells (SAEC) and Human Microvascular Endothelial Cells (HMVEC). Our data demonstrate that direct exposure of SAEC to low concentrations of PEPs (0.5 and 1.0 µg/mL) caused morphological changes of actin remodeling and gap formations within the endothelial monolayer. Furthermore, increased production of reactive oxygen species (ROS) and angiogenesis were observed in the HMVEC. Analysis of cytokine and chemokine levels demonstrates that interleukin (IL)-6 and MCP-1 may play a major role in the cellular communication observed between SAEC and HMVEC and the resultant responses in HMVEC. These data indicate that PEPs at low, non-cytotoxic exposure levels are bioactive and affect cellular responses in an alveolar-capillary co-culture model, which raises concerns for potential adverse health effects.

  3. Hydrogen protects against hyperoxia-induced apoptosis in type II alveolar epithelial cells via activation of PI3K/Akt/Foxo3a signaling pathway.

    Science.gov (United States)

    Wu, Dan; Liang, Mulin; Dang, Hongxing; Fang, Fang; Xu, Feng; Liu, Chengjun

    2018-01-08

    Oxidative stress is regarded as a key regulator in the pathogenesis of prolonged hyperoxia-induced lung injury, which causes injury to alveolar epithelial cells and eventually leads to development of bronchopulmonary dysplasia (BPD). Many studies have shown that hydrogen has a protective effect in a variety of cells. However, the mechanisms by which hydrogen rescues cells from damage due to oxidative stress in BPD remains to be fully elucidated. This study sought to evaluate the effects of hydrogen on hyperoxia-induced lung injury and to investigate the underlying mechanism. Primary type II alveolar epithelial cells (AECIIs) were divided into four groups: control (21% oxygen), hyperoxia (95% oxygen), hyperoxia + hydrogen, and hyperoxia + hydrogen + LY294002 (a PI3K/Akt inhibitor). Proliferation and apoptosis of AECIIs were assessed using MTS assay and flow cytometry (FCM), respectively. Gene and protein expression were detected by quantitative polymerase chain reaction (q-PCR) and western blot analysis. Stimulation with hyperoxia decreased the expression of P-Akt, P- FoxO3a, cyclinD1 and Bcl-2. Hyperoxic conditions increased levels of Bim, Bax, and Foxo3a, which induced proliferation restriction and apoptosis of AECIIs. These effects of hyperoxia were reversed with hydrogen pretreatment. Furthermore, the protective effects of hydrogen were abrogated by PI3K/Akt inhibitor LY294002. The results indicate that hydrogen protects AECIIs from hyperoxia-induced apoptosis by inhibiting apoptosis factors and promoting the expression of anti-apoptosis factors. These effects were associated with activation of the PI3K/Akt/FoxO3a pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Potential in vitro model for testing the effect of exposure to nanoparticles on the lung alveolar epithelial barrier

    Directory of Open Access Journals (Sweden)

    Raymond Derk

    2015-03-01

    Full Text Available Pulmonary barrier function plays a pivotal role in protection from inhaled particles. However, some nano-scaled particles, such as carbon nanotubes (CNT, have demonstrated the ability to penetrate this barrier in animal models, resulting in an unusual, rapid interstitial fibrosis. To delineate the underlying mechanism and specific bio-effect of inhaled nanoparticles in respiratory toxicity, models of lung epithelial barriers are required that allow accurate representation of in vivo systems; however, there is currently a lack of consistent methods to do so. Thus, this work demonstrates a well-characterized in vitro model of pulmonary barrier function using Calu-3 cells, and provides the experimental conditions required for achieving tight junction complexes in cell culture, with trans-epithelial electrical resistance measurement used as a biosensor for proper barrier formation and integrity. The effects of cell number and serum constituents have been examined and we found that changes in each of these parameters can greatly affect barrier formation. Our data demonstrate that use of 5.0 × 104 Calu-3 cells/well in the Transwell cell culture system, with 10% serum concentrations in culture media is optimal for assessing epithelial barrier function. In addition, we have utilized CNT exposure to analyze the dose-, time-, and nanoparticle property-dependent alterations of epithelial barrier permeability as a means to validate this model. Such high throughput in vitro cell models of the epithelium could be used to predict the interaction of other nanoparticles with lung epithelial barriers to mimic respiratory behavior in vivo, thus providing essential tools and bio-sensing techniques that can be uniformly employed.

  5. The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy.

    Science.gov (United States)

    Honeybourne, D; Andrews, J M; Cunningham, B; Jevons, G; Wise, R

    1999-01-01

    The concentrations of clinafloxacin were measured in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid after single 200 mg oral doses of clinafloxacin had been administered to 15 subjects who were undergoing bronchoscopy. Concentrations were measured using a microbiological assay method. Mean concentrations in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid at a mean of 1.27 h post-dose were 1.54, 2.65, 15.60 and 2.71 mg/L respectively. These site concentrations exceeded the MIC90 for common respiratory pathogens and indicate that clinafloxacin is likely to be effective in the treatment of a wide range of respiratory tract infections.

  6. Tropomyosin-1 protects transformed alveolar epithelial cells against cigaret smoke extract through the stabilization of F-actin-dependent cell-cell junctions.

    Science.gov (United States)

    Gagat, Maciej; Grzanka, Dariusz; Izdebska, Magdalena; Sroka, Wiktor Dariusz; Hałas-Wiśniewska, Marta; Grzanka, Alina

    2016-04-01

    The aim of the study was to estimate the effect of tropomyosin-1-based structural stabilization of F-actin in transformed human alveolar epithelial line H1299 cells subjected to high oxidative stress induced by cigaret smoke extract. We demonstrated here that cigaret smoke extract induces cell shrinking and detachment as a consequence of F-actin cytoskeleton degradation in H1299 cells not overexpressing tropomyosin-1. Furthermore, the treatment of these cells with cigaret smoke extract resulted in the loss of peripheral localization of ZO-1 and initiated apoptosis. In contrast, structural stabilization of F-actin, by overexpression of tropomyosin-1, preserved cell to cell interactions through the attenuation of cortical actin organization into thin fibers and thus protected these cells against oxidative stress-induced degradation of actin cytoskeleton and cell death. In conclusion, we suggest that structural stabilization of thin cortical F-actin fibers increases link between tight junctions proteins and actin cytoskeleton and thus protects H1299 cells against cigaret smoke extract. Copyright © 2016 Elsevier GmbH. All rights reserved.

  7. Aerosol-based efficient delivery of telithromycin, a ketolide antimicrobial agent, to lung epithelial lining fluid and alveolar macrophages for treatment of respiratory infections.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Seki, Toshinobu; Morimoto, Kazuhiro

    2010-07-01

    The efficacy of aerosol-based delivery of telithromycin (TEL), as a model antimicrobial agent, for the treatment of respiratory infections was evaluated by comparison with oral administration. The aerosol formulation (0.2 mg/kg) was administered to rat lungs using a Liquid MicroSprayer. The time courses of the concentration of TEL in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs) following administration of an aerosol formulation to rat lungs were markedly higher than that following the administration of an oral formulation (50 mg/kg). The time course of the concentrations of TEL in plasma following administration of the aerosol formulation was markedly lower than that in ELF and AMs. These results indicate that the aerosol formulation is more effective in delivering TEL to ELF and AMs, compared to the oral formulation, despite a low dose and it avoids distribution of TEL to the blood. In addition, the antibacterial effects of TEL in ELF and AMs following administration of the aerosol formulation were estimated by pharmacokinetics/pharmacodynamics analysis. The concentrations of TEL in ELF and the AMs time curve/minimum inhibitory concentration of TEL ratio were markedly higher than the effective values. This study indicates that an antibiotic aerosol formulation may be an effective pulmonary drug delivery system for the treatment of respiratory infections.

  8. Protective Effects of Hydrogen-Rich Saline Against Lipopolysaccharide-Induced Alveolar Epithelial-to-Mesenchymal Transition and Pulmonary Fibrosis.

    Science.gov (United States)

    Dong, Wen-Wen; Zhang, Yun-Qian; Zhu, Xiao-Yan; Mao, Yan-Fei; Sun, Xue-Jun; Liu, Yu-Jian; Jiang, Lai

    2017-05-19

    BACKGROUND Fibrotic change is one of the important reasons for the poor prognosis of patients with acute respiratory distress syndrome (ARDS). The present study investigated the effects of hydrogen-rich saline, a selective hydroxyl radical scavenger, on lipopolysaccharide (LPS)-induced pulmonary fibrosis. MATERIAL AND METHODS Male ICR mice were divided randomly into 5 groups: Control, LPS-treated plus vehicle treatment, and LPS-treated plus hydrogen-rich saline (2.5, 5, or 10 ml/kg) treatment. Twenty-eight days later, fibrosis was assessed by determination of collagen deposition, hydroxyproline, and type I collagen levels. Development of epithelial-to-mesenchymal transition (EMT) was identified by examining protein expressions of E-cadherin and α-smooth muscle actin (α-SMA). Transforming growth factor (TGF)-β1 content, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, catalase (CAT), and superoxide dismutase (SOD) activity were determined. RESULTS Mice exhibited increases in collagen deposition, hydroxyproline, type I collagen contents, and TGF-β1 production in lung tissues after LPS treatment. LPS-induced lung fibrosis was associated with increased expression of α-SMA, as well as decreased expression of E-cadherin. In addition, LPS treatment increased MDA levels but decreased T-AOC, CAT, and SOD activities in lung tissues, indicating that LPS induced pulmonary oxidative stress. Hydrogen-rich saline treatment at doses of 2.5, 5, or 10 ml/kg significantly attenuated LPS-induced pulmonary fibrosis. LPS-induced loss of E-cadherin in lung tissues was largely reversed, whereas the acquisition of α-SMA was dramatically decreased by hydrogen-rich saline treatment. In addition, hydrogen-rich saline treatment significantly attenuated LPS-induced oxidative stress. CONCLUSIONS Hydrogen-rich saline may protect against LPS-induced EMT and pulmonary fibrosis through suppressing oxidative stress.

  9. A novel collagen film with micro-rough surface structure for corneal epithelial repair fabricated by freeze drying technique

    International Nuclear Information System (INIS)

    Liu, Yang; Ren, Li; Wang, Yingjun

    2014-01-01

    Highlights: • Collagen film with micro-rough surface is fabricated by freeze drying technique. • The film has suitable water uptake capability and toughness performance. • The film has good optical performance. • Human corneal epithelial cells studies confirmed the biocompatibility of the film. - Abstract: Corneal epithelial defect is a common disease and keratoplasty is a common treatment method. A collagen film with micro-rough surface was fabricated through a simple freeze drying technique in this study. Compared with the air-dried collagen film (AD-Col), this freeze-dried collagen film (FD-Col) has a more suitable water uptake capability (about 85.5%) and toughness performance. Both of the two films have good optical properties and the luminousness of them is higher than 80%. Besides, the adhesion and proliferation rate of human corneal epithelial cells on the micro-rough surface of FD-Col film is higher than that on the smooth surface of AD-Col film. The results indicate that this FD-Col film may have potential applications for corneal epithelial repair

  10. A novel collagen film with micro-rough surface structure for corneal epithelial repair fabricated by freeze drying technique

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yang [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China); Ren, Li, E-mail: psliren@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China); Wang, Yingjun, E-mail: imwangyj@163.com [School of Materials Science and Engineering, South China University of Technology, Guangzhou 510641 (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006 (China); Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006 (China)

    2014-05-01

    Highlights: • Collagen film with micro-rough surface is fabricated by freeze drying technique. • The film has suitable water uptake capability and toughness performance. • The film has good optical performance. • Human corneal epithelial cells studies confirmed the biocompatibility of the film. - Abstract: Corneal epithelial defect is a common disease and keratoplasty is a common treatment method. A collagen film with micro-rough surface was fabricated through a simple freeze drying technique in this study. Compared with the air-dried collagen film (AD-Col), this freeze-dried collagen film (FD-Col) has a more suitable water uptake capability (about 85.5%) and toughness performance. Both of the two films have good optical properties and the luminousness of them is higher than 80%. Besides, the adhesion and proliferation rate of human corneal epithelial cells on the micro-rough surface of FD-Col film is higher than that on the smooth surface of AD-Col film. The results indicate that this FD-Col film may have potential applications for corneal epithelial repair.

  11. Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties

    Directory of Open Access Journals (Sweden)

    Hua Jin

    2015-01-01

    Full Text Available The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as embryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C 6 root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C 6 brachial plexus injury site (1 × 10 6 cells/mL, 3 μL/injection, 25 injections immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C 6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also significantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effectively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals.

  12. Curcumin modulates the effect of histone modification on the expression of chemokines by type II alveolar epithelial cells in a rat COPD model

    Directory of Open Access Journals (Sweden)

    Gan L

    2016-11-01

    Full Text Available Lixing Gan,1 Chengye Li,2 Jian Wang,1 Xuejun Guo3 1Department of Respiratory Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 3Department of Respiratory Medicine, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Background: Studies have suggested that histone modification has a positive impact on various aspects associated with the progression of COPD. Histone deacetylase 2 (HDAC2 suppresses proinflammatory gene expression through deacetylation of core histones.Objective: To investigate the effect of histone modification on the expression of chemokines in type II alveolar epithelial cells (AEC II in a rat COPD model and regulation of HDAC2 expression by curcumin in comparison with corticosteroid.Materials and methods: The rat COPD model was established by cigarette smoke exposure and confirmed by histology and pathophysioloy. AEC II were isolated and cultured in vitro from the COPD models and control animals. The cells were treated with curcumin, corticosteroid, or trichostatin A, and messenger RNA (mRNA expression of interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, and macrophage inflammatory protein-2α (MIP-2α was assessed by quantitative real-time polymerase chain reaction (RT-PCR. The expression of HDAC2 was measured by Western blot. Chromatin immunoprecipitation was used to detect H3/H4 acetylation and H3K9 methylation in the promoter region of three kinds of chemokine genes (IL-8, MCP-1, and MIP-2α. Results: Compared to the control group, the mRNAs of MCP-1, IL-8, and MIP-2α were upregulated 4.48-fold, 3.14-fold, and 2.83-fold, respectively, in the AEC II from COPD model. The protein expression of HDAC2 in the AEC II from COPD model was significantly lower than from the control group (P<0

  13. Inflammatory effects induced by selected limonene oxidation products: 4-OPA, IPOH, 4-AMCH in human bronchial (16HBE14o-) and alveolar (A549) epithelial cell lines.

    Science.gov (United States)

    Lipsa, Dorelia; Leva, Paolo; Barrero-Moreno, Josefa; Coelhan, Mehmet

    2016-11-16

    Limonene, a monoterpene abundantly present in most of the consumer products (due to its pleasant citrus smell), easily undergoes ozonolysis leading to several limonene oxidation products (LOPs) such as 4-acetyl-1-methylcyclohexene (4-AMCH), 4-oxopentanal (4-OPA) and 3-isopropenyl-6-oxoheptanal (IPOH). Toxicological studies have indicated that human exposure to limonene and ozone can cause adverse airway effects. However, little attention has been paid to the potential health impact of specific LOPs, in particular of IPOH, 4-OPA and 4-AMCH. This study evaluates the cytotoxic effects of the selected LOPs on human bronchial epithelial (16HBE14o-) and alveolar epithelial (A549) cell lines by generating concentration-response curves using the neutral red uptake assay and analyzing the inflammatory response with a series of cytokines/chemokines. The cellular viability was mostly reduced by 4-OPA [IC 50 =1.6mM (A549) and 1.45mM (16HBE14o-)] when compared to IPOH [IC 50 =3.5mM (A549) and 3.4mM (16HBE14o-)] and 4-AMCH [IC 50 could not be calculated]. As a result from the inflammatory response, IPOH [50μM] induced an increase of both IL-6 and IL-8 secretion in A549 (1.5-fold change) and in 16HBE14o- (2.8- and 7-fold change respectively). 4-OPA [50μM] treatment of A549 increased IL-6 (1.4-times) and IL-8 (1.3-times) levels, while in 16HBE14o- had an opposite effect. A549 treated with 4-AMCH [50μM] elevate both IL-6 and IL-8 levels by 1.2-times, while in 16HBE14o- had an opposite effect. Based on our results, lung cellular injury characterized by inflammatory cytokine release was observed for both cell lines treated with the selected chemicals at concentrations that did not affect their cellular viability. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  14. Aerosol-based efficient delivery of clarithromycin, a macrolide antimicrobial agent, to lung epithelial lining fluid and alveolar macrophages for treatment of respiratory infections.

    Science.gov (United States)

    Togami, Kohei; Chono, Sumio; Morimoto, Kazuhiro

    2012-04-01

    Macrolide antimicrobial agents are generally given by the oral route for the treatment of respiratory infections caused by pathogenic microorganisms infected in lung epithelial lining fluid (ELF) and alveolar macrophages (AMs). However, because macrolides distribute to many different tissues via the blood after oral administration, systemic side effects are frequently induced. In contrast with oral administration, aerosolization may be an efficient method for delivering macrolides directly to ELF and AMs. In this study, the efficacy of aerosol-based delivery of clarithromycin (CAM), as a model macrolide, for the treatment of respiratory infections was evaluated by comparison with oral administration. The aerosol formulation of CAM (0.2 mg/kg) was administered to rat lungs using a Liquid MicroSprayer(®). The oral formulation of CAM (50 mg/kg) was used for comparison. Time courses of concentrations of CAM in ELF and AMs following administration were obtained, and then the bioavailability (BA) was calculated. In addition, the area under the concentrations of CAM in ELF and AMs-time curve/minimum inhibitory concentration at which 90% of isolates ratio [area under the curve (AUC/MIC(90))] were calculated to estimate the antibacterial effects in ELF and AMs. The BA of CAM in ELF and AMs following administration of aerosol formulation were markedly greater than that following administration of oral formulation. This indicates that the aerosol formulation is more effective in delivering CAM to ELF and AMs, compared with the oral formulation, despite a low dose. The AUC/MIC(90) of CAM in ELF and AMs were markedly higher than the effective values. This indicates that the aerosol formulation could be useful for the treatment of respiratory infections caused by pathogenic microorganisms infected in ELF and AMs. This study suggests that aerosol formulation of macrolides is an effective pulmonary drug delivery system for the treatment of respiratory infections.

  15. Effect of irradiation/bone marrow transplantation on alveolar epithelial type II cells is aggravated in surfactant protein D deficient mice.

    Science.gov (United States)

    Mühlfeld, Christian; Madsen, Jens; Mackay, Rose-Marie; Schneider, Jan Philipp; Schipke, Julia; Lutz, Dennis; Birkelbach, Bastian; Knudsen, Lars; Botto, Marina; Ochs, Matthias; Clark, Howard

    2017-01-01

    Irradiation followed by bone marrow transplantation (BM-Tx) is a frequent therapeutic intervention causing pathology to the lung. Although alveolar epithelial type II (AE2) cells are essential for lung function and are damaged by irradiation, the long-term consequences of irradiation and BM-Tx are not well characterized. In addition, it is unknown whether surfactant protein D (SP-D) influences the response of AE2 cells to the injurious events. Therefore, wildtype (WT) and SP-D -/- mice were subjected to a myeloablative whole body irradiation dose of 8 Gy and subsequent BM-Tx and compared with age- and sex-matched untreated controls. AE2 cell changes were investigated quantitatively by design-based stereology. Compared with WT, untreated SP-D -/- mice showed a higher number of larger sized AE2 cells and a greater amount of surfactant-storing lamellar bodies. Irradiation and BM-Tx induced hyperplasia and hypertrophy in WT and SP-D -/- mice as well as the formation of giant lamellar bodies. The experimentally induced alterations were more severe in the SP-D -/- than in the WT mice, particularly with respect to the surfactant-storing lamellar bodies which were sometimes extremely enlarged in SP-D -/- mice. In conclusion, irradiation and BM-Tx have profound long-term effects on AE2 cells and their lamellar bodies. These data may explain some of the clinical pulmonary consequences of this procedure. The data should also be taken into account when BM-Tx is used as an experimental procedure to investigate the impact of bone marrow-derived cells for the phenotype of a specific genotype in the mouse.

  16. Andrographolide antagonizes cigarette smoke extract-induced inflammatory response and oxidative stress in human alveolar epithelial A549 cells through induction of microRNA-218.

    Science.gov (United States)

    Li, Ying-jie; Yu, Chang-hai; Li, Jing-bo; Wu, Xi-ya

    2013-12-01

    Andrographolide is a major bioactive labdane diterpenoid isolated from Andrographis paniculata and has protective effects against cigarette smoke (CS)-induced lung injury. This study was done to determine whether such protective effects were mediated through modulation of microRNA (miR)-218 expression. Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke extract (CSE) with or without andrographolide pretreatment and measured the level of glutathione, nuclear factor-kappaB (NF-κB) activation, proinflammatory cytokine production, and miR-218 expression. We found that andrographolide pretreatment significantly restored the glutathione level in CSE-exposed A549 cells, coupled with reduced inhibitor κB (IκB)-α phosphorylation and p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218 expression was significantly upregulated by andrographolide pretreatment. To determine the biological role of miR-218, we overexpressed and downregulated its expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We observed that miR-218 overexpression led to a marked reduction in IκB-α phosphorylation, p65 nuclear accumulation, and NF-κB-dependent transcriptional activity in CSE-treated A549 cells. In contrast, miR-218 silencing enhanced IκB-α phosphorylation and p65 nuclear accumulation in cells with andrographolide pretreatment and reversed andrographolide-mediated reduction of IL-6 and IL-8 production. In addition, depletion of miR-218 significantly reversed the upregulation of glutathione levels in A549 cells by andrographolide. Taken together, our results demonstrate that andrographolide mitigates CSE-induced inflammatory response in A549 cells, largely through inhibition of NF-κB activation via upregulation of miR-218, and thus has preventive benefits in CS-induced inflammatory lung diseases.

  17. Non-toxic engineered carbon nanodiamond concentrations induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells.

    Science.gov (United States)

    Fresta, Claudia G; Chakraborty, Aishik; Wijesinghe, Manjula B; Amorini, Angela M; Lazzarino, Giacomo; Lazzarino, Giuseppe; Tavazzi, Barbara; Lunte, Susan M; Caraci, Filippo; Dhar, Prajnaparamita; Caruso, Giuseppe

    2018-02-14

    Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism. Particularly, we initially measured decrease in cell viability as a function of increasing ECNs doses, finding similar cytotoxic ECN effects in the two cell lines. Subsequently, using apparently non-cytotoxic ECN concentrations (2 µg/mL causing decrease in cell number < 5%) we determined NO and ROS production, and measured the concentrations of compounds related to energy metabolism, mitochondrial functions, oxido-reductive reactions, and antioxidant defences. We found that in both cell lines non-cytotoxic ECN concentrations increased NO and ROS production with sustained oxidative/nitrosative stress, and caused energy metabolism imbalance (decrease in high energy phosphates and nicotinic coenzymes) and mitochondrial malfunctioning (decrease in ATP/ADP ratio).These results underline the importance to deeply investigate the molecular and biochemical changes occurring upon the interaction of ECNs (and nanoparticles in general) with living cells, even at apparently non-toxic concentration. Since the use of ECNs in biomedical field is attracting increasing attention the complete evaluation of their biosafety, toxicity and/or possible side effects both in vitro and in vivo is mandatory before these highly promising tools might find the correct application.

  18. Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution

    International Nuclear Information System (INIS)

    Abbas, Imane; Garcon, Guillaume; Billet, Sylvain; Shirali, Pirouz; Andre, Veronique; Le Goff, Jeremie; Sichel, Francois; Roy Saint-Georges, Francoise; Mulliez, Philippe

    2012-01-01

    Because of their deep penetration in human lungs, fine airborne particulate matter were described as mainly responsible for the deleterious effects of exposure to air pollution on health. Organic constituents are adsorbed on particles surface and, after inhalation, some (polycyclic aromatic hydrocarbons, PAHs) can be activated into reactive metabolites and can bind to DNA. The formation of bulky DNA adducts has been researched after exposure of mono-and co-cultures of alveolar macrophages (AM) and human embryonic human lung epithelial (L132), to fine air pollution particulate matter Air samples have been collected with cascade impactor and characterized: size distribution (92.15% 2 /g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). 32 P post-labeling method was applied to detect bulky DNA adducts in AM and L132, in mono-and co-cultures, 72 h after their exposure to atmospheric particles at their Lethals and Effects concentrations or (LC or CE) to 50% (i.e. MA: EC 50 = 74.63 μg/mL and L132: LC-5-0 = 75.36 μg/mL). Exposure to desorbed particles (MA: C1= 61.11 μg/mL and L132 : C2 = 61.71 μg/mL) and B[a]P (1 μM) were included. Bulky PAH-DNA adducts were detected in AM in mono-culture after exposure to total particles (Pt), to B[a]P and desorbed particles (Pd). Whatever the exposure, no DNA adduct was detected in L132 in mono-culture. These results are coherent with the enzymatic activities of cytochrome P450 l Al in AM and L132. Exposure of co-culture to Pt, or Pd induced bulky adducts to DNA in AM but not in L132. Exposure to B[a]P alone has altered the DNA of AM and L132, in co-culture. Exposure to Pt is closer to the environmental conditions, but conferred an exposure to amounts of genotoxic agents compared to studies using organic extracts. The formation of bulky DNA adducts was nevertheless observed in AM exposed to Pt, in mono- or co-culture, indicating that they were competent in terms of metabolic activation of PAHs. The

  19. Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

    Science.gov (United States)

    Andrews, J; Honeybourne, D; Jevons, G; Boyce, M; Wise, R; Bello, A; Gajjar, D

    2003-03-01

    A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

  20. Foxp3+Regulatory T Cell Expression of Keratinocyte Growth Factor Enhances Lung Epithelial Proliferation.

    Science.gov (United States)

    Dial, Catherine F; Tune, Miriya K; Doerschuk, Claire M; Mock, Jason R

    2017-08-01

    Repair of the lung epithelium after injury is a critical component for resolution; however, the processes necessary to drive epithelial resolution are not clearly defined. Published data demonstrate that Foxp3 + regulatory T cells (Tregs) enhance alveolar epithelial proliferation after injury, and Tregs in vitro directly promote type II alveolar epithelial cell (AT2) proliferation, in part by a contact-independent mechanism. Therefore, we sought to determine the contribution of Treg-specific expression of a growth factor that is known to be important in lung repair, keratinocyte growth factor (kgf). The data demonstrate that Tregs express kgf and that Treg-specific expression of kgf regulates alveolar epithelial proliferation during the resolution phase of acute lung injury and in a model of regenerative alveologenesis in vivo. In vitro experiments demonstrate that AT2 cells cocultured with Tregs lacking kgf have decreased rates of proliferation compared with AT2 cells cocultured with wild-type Tregs. Moreover, Tregs isolated from lung tissue and grown in culture express higher levels of two growth factors that are important for lung repair (kgf and amphiregulin) compared with Tregs isolated from splenic tissue. Lastly, Tregs isolated from human lung tissue can be stimulated ex vivo to induce kgf expression. This study reveals mechanisms by which Tregs direct tissue-reparative effects during resolution after acute lung injury, further supporting the emerging role of Tregs in tissue repair.

  1. Hole-in-one mutant phenotypes link EGFR/ERK signaling to epithelial tissue repair in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jennifer A Geiger

    Full Text Available BACKGROUND: Epithelia act as physical barriers protecting living organisms and their organs from the surrounding environment. Simple epithelial tissues have the capacity to efficiently repair wounds through a resealing mechanism. The known molecular mechanisms underlying this process appear to be conserved in both vertebrates and invertebrates, namely the involvement of the transcription factors Grainy head (Grh and Fos. In Drosophila, Grh and Fos lead to the activation of wound response genes required for epithelial repair. ERK is upstream of this pathway and known to be one of the first kinases to be activated upon wounding. However, it is still unclear how ERK activation contributes to a proper wound response and which molecular mechanisms regulate its activation. METHODOLOGY/PRINCIPAL FINDINGS: In a previous screen, we isolated mutants with defects in wound healing. Here, we describe the role of one of these genes, hole-in-one (holn1, in the wound healing process. Holn1 is a GYF domain containing protein that we found to be required for the activation of several Grh and Fos regulated wound response genes at the wound site. We also provide evidence suggesting that Holn1 may be involved in the Ras/ERK signaling pathway, by acting downstream of ERK. Finally, we show that wound healing requires the function of EGFR and ERK signaling. CONCLUSIONS/SIGNIFICANCE: Based on these data, we conclude that holn1 is a novel gene required for a proper wound healing response. We further propose and discuss a model whereby Holn1 acts downstream of EGFR and ERK signaling in the Grh/Fos mediated wound closure pathway.

  2. Comparative study of the effects of PM1-induced oxidative stress on autophagy and surfactant protein B and C expressions in lung alveolar type II epithelial MLE-12 cells.

    Science.gov (United States)

    Bai, Ru; Guan, Longfei; Zhang, Wei; Xu, Jinxia; Rui, Wei; Zhang, Fang; Ding, Wenjun

    2016-12-01

    There is a strong link between smaller air pollution particles and a range of serious health conditions. Thus, there is a need for understanding the impacts of airborne fine particulate matter (PM) with an aerodynamic diameter of PM1) on lung alveolar epithelial cells. In the present study, mouse lung epithelial type II cell MLE-12 cells were used to examine the intracellular oxidative responses and the surfactant protein expressions after exposure to various concentrations of PM1 collected from an urban site and a steel-factory site (referred as uPM1 and sPM1 hereafter, respectively). Physicochemical characterization of PM1 was performed by using scanning electron microscopy and transmission electron microscopy. Cytotoxicity and autophagy induced by PM1 were assessed by using comprehensive approaches after MLE-12 cells were exposed to different concentrations of PM1 for various times. Expression of surfactant proteins B and C in MLE-12 cells was determined by Western blotting. All of the tested PM1 induced cytotoxicity evidenced by significant decrease of cell viability and increase of lactate dehydrogenase (LDH) release in a time- and concentration-dependent manner in the exposed cells compared with the unexposed cells. A similar pattern of increase of intercellular reactive oxygen species (ROS) generation and decrease of superoxide dismutase (SOD) and catalase (CAT) activities was also observed. PM1-induced autophagy was evidenced by an increase in microtubule-associated protein light chain-3 (LC3) puncta, accumulation of LC3II, and increased levels of beclin1. Data from Western blotting showed significant decrease of surfactant protein B and C expressions. Relatively high concentrations of transition metals, including Fe, Cu and Mn, may be responsible for the higher toxicity of sPM1 compared with uPM1. Moreover, pretreatment with N-acetylcysteine (NAC) or Chelex (a metal chelating agent, which removes a large suite of metals from PM1) prevented the increase of

  3. In vitro effects of water-pipe smoke condensate on the endocytic activity of Type II alveolar epithelial cells (A549 with bacillus Calmette–Guérin

    Directory of Open Access Journals (Sweden)

    Ian M Adcock

    2016-01-01

    Conclusion: WPC exposure increased epithelial cells' permeability and death and enhanced their capacity for macropinocytosis. Our in vitro data suggest possible harmful effects of WPC on the ability of lung epithelial cells to phagocytose mycobacteria. Further studies will be conducted to understand the mechanism of action of WPC.

  4. A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study

    Science.gov (United States)

    2012-01-01

    Background Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. There is no reliably effective therapy for IC/PBS, and no generally accepted animal model for the disorder in which potential therapies can be tested. Bladder epithelial cells from IC/PBS patients make a small glycopeptide antiproliferative factor or "APF" that inhibits proliferation, decreases tight junction protein expression, increases paracellular permeability, and induces changes in gene expression of bladder epithelial cells in vitro that mimic abnormalities in IC/PBS patient biopsy specimens in vivo. We therefore determined the ability of a synthetic APF derivative to inhibit bladder epithelial repair in mice. Methods The bladder epithelium of female CBA/J mice was stripped by transurethral infusion of 3% acetic acid, and mice were subsequently treated daily with one of three intravesical treatments [synthetic as-APF, inactive unglycosylated control peptide, or phosphate buffered saline carrier (PBS)] for 1–21 days. Fixed bladder sections were either stained with haematoxylin and eosin for determination of epithelial area by image analysis, or incubated with anti-uroplakin III (UPIII) or anti-zonula occludens type 1 (ZO-1) antibodies for immunofluorescence microscopy. Epithelial measurement data were analyzed by a two-way analysis of variance (ANOVA); post hoc comparisons of multiple groups were carried out using the Tukey-Kramer method. Results Bladder epithelial repair was significantly attenuated in as-APF-treated mice as compared to control mice on days 3–21 (p < 0.05); the mean epithelial/total area over all measured days was also significantly lower in as-APF-treated mice vs. mice in either control group by post hoc analysis (p < 0.0001 for both comparisons). UPIII and ZO-1 expression was also decreased in as-APF-treated mice as compared to mice in either

  5. Pulmonary alveolar proteinosis

    Science.gov (United States)

    PAP; Alveolar proteinosis; Pulmonary alveolar phospholipoproteinosis; Alveolar lipoproteinosis phospholipidosis ... PAP is unknown. In others, it occurs with lung infection or an immune problem. It also can ...

  6. Function and repair of dental enamel - Potential role of epithelial transport processes of ameloblasts.

    Science.gov (United States)

    Varga, Gábor; Kerémi, Beáta; Bori, Erzsébet; Földes, Anna

    2015-07-01

    The hardest mammalian tissue, dental enamel is produced by ameloblasts, which are electrolyte-transporting epithelial cells. Although the end product is very different, they show many similarities to transporting epithelia of the pancreas, salivary glands and kidney. Enamel is produced in a multi-step epithelial secretory process that features biomineralization which is an interplay of secreted ameloblast specific proteins and the time-specific transport of minerals, protons and bicarbonate. First, "secretory" ameloblasts form the entire thickness of the enamel layer, but with low mineral content. Then they differentiate into "maturation" ameloblasts, which remove organic matrix from the enamel and in turn further build up hydroxyapatite crystals. The protons generated by hydroxyapatite formation need to be buffered, otherwise enamel will not attain full mineralization. Buffering requires a tight pH regulation and secretion of bicarbonate by ameloblasts. The whole process has been the focus of many immunohistochemical and gene knock-out studies, but, perhaps surprisingly, no functional data existed for mineral ion transport by ameloblasts. However, recent studies including ours provided a better insight for molecular mechanism of mineral formation. The secretory regulation is not completely known as yet, but its significance is crucial. Impairing regulation retards or prevents completion of enamel mineralization and results in the development of hypomineralized enamel that easily erodes after dental eruption. Factors that impair this function are fluoride and disruption of pH regulators. Revealing these factors may eventually lead to the treatment of enamel hypomineralization related to genetic or environmentally induced malformation. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  7. Lipoteichoic acid induces surfactant protein-A biosynthesis in human alveolar type II epithelial cells through activating the MEK1/2-ERK1/2-NF-κB pathway

    Directory of Open Access Journals (Sweden)

    Liu Feng-Lin

    2012-10-01

    Full Text Available Abstract Background Lipoteichoic acid (LTA, a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that the gram-negative endotoxin, lipopolysaccharide (LPS, could induce surfactant protein-A (SP-A production in human alveolar epithelial (A549 cells. Objectives In this study, we further evaluated the effect of LTA on SP-A biosynthesis and its possible signal-transducing mechanisms. Methods A549 cells were exposed to LTA. Levels of SP-A, nuclear factor (NF-κB, extracellular signal-regulated kinase 1/2 (ERK1/2, and mitogen-activated/extracellular signal-regulated kinase kinase (MEK1 were determined. Results Exposure of A549 cells to 10, 30, and 50 μg/ml LTA for 24 h did not affect cell viability. Meanwhile, when exposed to 30 μg/ml LTA for 1, 6, and 24 h, the biosynthesis of SP-A mRNA and protein in A549 cells significantly increased. As to the mechanism, LTA enhanced cytosolic and nuclear NF-κB levels in time-dependent manners. Pretreatment with BAY 11–7082, an inhibitor of NF-κB activation, significantly inhibited LTA-induced SP-A mRNA expression. Sequentially, LTA time-dependently augmented phosphorylation of ERK1/2. In addition, levels of phosphorylated MEK1 were augmented following treatment with LTA. Conclusions Therefore, this study showed that LTA can increase SP-A synthesis in human alveolar type II epithelial cells through sequentially activating the MEK1-ERK1/2-NF-κB-dependent pathway.

  8. [Effects of heme oxygenase-1/carbon monoxide pathway on the mitochondrial fusion in rat alveolar epithelial type II cells stimulated by lipopolysaccharide].

    Science.gov (United States)

    Jia, Haojuan; Shi, Jia; Dong, Shu'an; Zhang, Yuan; Yu, Jianbo

    2018-03-01

    To investigate the effects of heme oxygenase-1/carbon monoxide (HO-1/CO) pathway on mitochondrial fusion in rat alveolar epithelial type II cells (AEC II) stimulated by lipopolysaccharide (LPS). Once the cultured in vitro rat AEC II cells line RLE-6TN reached confluency of 85%, they were subcultured and randomly divided into seven groups (n = 5 each). RLE-6TN cells were routinely cultured in control group. The cells in LPS group was stimulated with 10 mg/L LPS to reproduce the model of endotoxin challenge in AECII cells. The cells in carbon monoxide-releasing molecule-2 (CORM-2, in vitro CO release agent) + LPS group (CL group) and Hemin (HO-1 inducer) + LPS group (HL group) were pretreated with 100 μmol/L CORM-2 or 20 μmol/L Hemin for 1 hour, respectively, followed by 10 mg/L LPS stimulation. The cells in zinc protoporphyrin-IX (ZnPP-IX, HO-1 inhibitor) + LPS group (ZL group) was pretreated with 10 μmol/L ZnPP-IX for 0.5 hour followed by 10 mg/L LPS stimulation. The cells in CORM-2 + ZnPP-IX + LPS group (CZL group) and Hemin + ZnPP-IX + LPS group (HZL group) were pretreated with 100 μmol/L CORM-2 or 20 μmol/L Hemin respectively for 1 hour, and other treatments were similar to those previously described in ZL group. At 24 hours after LPS stimulation, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the supernatant were determined by enzyme linked immunosorbent assay (ELISA), the protein expressions of HO-1, mitochondrial fusion related proteins 1 and 2 (Mfn1, Mfn2) and optic atrophy 1 (OPA1) were determined by Western Blot. Compared with control group, IL-6 and TNF-α contents in the supernatant were increased, HO-1 protein expression was up-regulated, Mfn1, Mfn2 and OPA1 protein expressions were down-regulated in all treatment groups. Compared with LPS group, IL-6 and TNF-α contents were significantly decreased after CORM-2 or Hemin pretreatment [IL-6 (ng/L): 48.6±3.7, 48.4±3.1 vs. 58.7±2.5; TNF-α (ng/L): 40.7±5.3, 39.4±4.3 vs. 51.8±5

  9. Microsatellite instability, promoter methylation and protein expression of the DNA mismatch repair genes in epithelial ovarian cancer.

    Science.gov (United States)

    V, Shilpa; Bhagat, Rahul; C S, Premalata; V R, Pallavi; Krishnamoorthy, Lakshmi

    2014-10-01

    The role of defective mismatch repair (MMR) system in ovarian carcinoma is not well defined. The purpose of the study was to determine the relationship between microsatellite instability (MSI), promoter methylation and protein expression of MMR genes in epithelial ovarian carcinoma (EOC). MSI and promoter methylation of MLH1, MSH2 and PMS2 genes were studied using PCR methods in the study cohort. A small subset of samples was used to analyze the protein expression by immunohistochemistry (IHC). MSI was observed in >60% of tumor samples and 47% of normal ovaries. MLH1 was methylated in 37.5% and 64.3% EOCs and LMP tumors. The loss of immunoexpression of MMR genes was not seen in ovarian tumors. There was no correlation between MSI, promoter methylation and protein expression of the MMR genes suggesting that each may function independently. MSI is a common event in ovarian carcinoma and may increase the clinical awareness of the subset of tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. 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.

  11. Effects of aluminium chloride and aluminium chlorohydrate on DNA repair in MCF10A immortalised non-transformed human breast epithelial cells.

    Science.gov (United States)

    Farasani, A; Darbre, P D

    2015-11-01

    Use of underarm aluminium (Al)-based antiperspirant salts may be a contributory factor in breast cancer development. At the 10th Keele meeting, Al was reported to cause anchorage-independent growth and double strand DNA breaks in MCF10A immortalised non-transformed human breast epithelial cells. We now report that exposure of MCF10A cells to Al chloride or Al chlorohydrate also compromised DNA repair systems. Long-term (19-21 weeks) exposure to Al chloride or Al chlorohydrate at a 10(-4) M concentration resulted in reduced levels of BRCA1 mRNA as determined by real-time RT-PCR and BRCA1 protein as determined by Western immunoblotting. Reduced levels of mRNA for other DNA repair genes (BRCA2, CHK1, CHK2, Rad51, ATR) were also observed using real-time RT-PCR. Loss of BRCA1 or BRCA2 gene function has long been associated with inherited susceptibility to breast cancer but these results suggest that exposure to aluminium-based antiperspirant salts may also reduce levels of these key components of DNA repair in breast epithelial cells. If Al can not only damage DNA but also compromise DNA repair systems, then there is the potential for Al to impact on breast carcinogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Alveolar epithelial cells (A549) exposed at the air-liquid interface to diesel exhaust: First study in TNO's powertrain test center

    NARCIS (Netherlands)

    Kooter, I.M.; Alblas, M.J.; Jedynska, A.D.; Steenhof, M.; Houtzager, M.M.G.; Ras, M.G. van

    2013-01-01

    Air–liquid interface (ALI) exposures enable in vitro testing ofmixtures of gases and particles such as diesel exhaust (DE). The main objective of this study was to investigate the feasibility of exposing human lung epithelial cells at the ALI to complete DE generated by a heavy-duty truck in the

  13. Repair activity of oxidatively damaged DNA and telomere length in human lung epithelial cells after exposure to multi-walled carbon nanotubes

    DEFF Research Database (Denmark)

    Borghini, Andrea; Roursgaard, Martin; Andreassi, Maria Grazia

    2017-01-01

    One type of carbon nanotubes (CNTs) (MWCNT-7, from Mitsui) has been classified as probably carcinogenic to humans, however insufficient data does not warrant the same classification for other types of CNTs. Experimental data indicate that CNT exposure can result in oxidative stress and DNA damage...... in cultured cells, whereas these materials appear to induce low or no mutagenicity. Therefore, the present study aimed to investigate whether in vitro exposure of cultured airway epithelial cells (A549) to multi-walled CNTs (MWCNTs) could increase the DNA repair activity of oxidatively damaged DNA and drive...... the cells toward replicative senescence, assessed by attrition of telomeres. To investigate this, H2O2 and KBrO3 were used to induce DNA damage in the cells and the effect of pre-exposure to MWCNT tested for a change in repair activity inside the cells or in the extract of treated cells. The effect of MWCNT...

  14. [DNA damage and repair induced by acute exposure of microwave from mobile phone on cultured human lens epithelial cells].

    Science.gov (United States)

    Sun, Li-xia; Yao, Ke; Jiang, Huai; He, Ji-liang; Lu, De-qiang; Wang, Kai-jun; Li, Hong-wu

    2006-12-01

    To investigate the effects of acute exposure of low-power 217 Hz modulated 1. 8 GHz microwave radiation on the DNA damage of human lens epithelial cells (hLECs) and repair. Cultured hLECs were exposed to 217 Hz modulated 1. 8 GHz microwave radiation at SAR (specific absorption rate) of 1. 0, 2. 0, 3. O0 and 4. 0 W/kg for 2 hours in an sXc-1800 incubator and irradiate system, the DNA single strand breaks were detected with comet assay ( single-cell gel electrophoresis) in sham-irradiated cells and irradiated cells incubated for varying periods: 0, 30 and 60 minutes after irradiation. Images of comets were digitized and analyzed using an Imagine-pro plus software, and the indexes used in this study were tail length (TL) and tail moment (TM). BrdU was added into the medium with additional one hour incubation after radiation, the cell proliferation rate was determined using a BrdU-kit. The difference of DNA-breaks between the exposure and sham exposure groups induced by 1.0 and 2.0 W/kg irradiation were not significant in each time points (P > 0.05) ; there were significant difference in both groups at the exposure dose of 3. 0 and 4. 0 W/kg immediately and at the time of 30 minutes after irradiation (P 0. 05) compared with control, but the evidence of significant DNA damage still existed in 4. 0 W/kg group at the same time point. Cell proliferation rate had no significant difference when the application of SAR was 0. 05) , however the cell proliferation was decreased significantly at the dose of 4. 0 W/kg irradiation ( P < 0. 01). No effective DNA damage was induced using comet assay after 2 hours irradiation of 1. 8 GHz microwave on hLECs at the dose SAR < or = 3.0 W/kg. 4.0 W/kg irradiation caused significantly DNA damage and inhibition of hLECs proliferation.

  15. [Effect of Polydatin on Epithelial-Mesenchymal Transition of Human Alveolar Epithelium A549 Cells Induced by TGF-β1].

    Science.gov (United States)

    Yang, Jun-chao; Xu, Lu; Song, Kang; Wang, Yuan; Gao, Run-di; Chen, Rui-lin; Cao, Yu

    2016-04-01

    To explore the effect of polydatin on the growth of TGF-β₁induced humanalveolar epithelium A549 cells and the mechanism of polydatin for inhibiting the process of epithelial-mesenchymal transition (EMT). A549 cells in vitro cultured were randomly divided into five groups, i.e., the blank group, the control group, the low dose polydatin group, the middle dose polydatin group, the high dose polydatin group. Common culture fluid was added in A549 cells of the blank group. Five ng/mLTGF-β₁contained culture fluid was added in A549 cells of the control group. 50, 100, and 150 μmol/mL of polydatin plus 5 ng/mL TGF-β₁contained culture fluid was added in A549 cells of low, middle, and high dosepolydatin groups, respectively. Morphological changes were observed and recorded at different time points. The optimal concentration of polydatin was determined by MTT method. Protein and mRNA expressions of E-cad epithelial cell marker) and Vimentin (mesenchymal cell marker) were detected by Western blot and Real-time PCR. Under inverted phase contrast microscope, A549 cells turned from previous pebble shape to fusiform shape after intervened by polydatin and TGF-β1. The intercellular space was enlargedand the intercellular connection became loose. These phenomena were more obviously seen in the control group. A549 cells were more satiated in low, middle, and high dose polydatin groups than in the control group. The EMT inhibition was most obviously seen in the middle dose polydatin group at 48 h. Protein and mRNA expressions of E-cad showed an overall descending tendency after intervened by polydatin and TGF-β1 (P A549 cells time- and dose-dependently. It also played roles in inhibiting pulmonary fibrosis.

  16. Increased alveolar soluble Annexin V promotes lung inflammation and fibrosis

    OpenAIRE

    Buckley, S.; Shi, W.; Xu, W.; Frey, M.R.; Moats, R.; Pardo, A.; Selman, M.; Warburton, D.

    2015-01-01

    The causes underlying the self-perpetuating nature of idiopathic pulmonary fibrosis (IPF), a progressive and usually lethal disease, remain unknown. We hypothesized that alveolar soluble Annexin V contributes to lung fibrosis, based on the observation that human IPF BALF containing high Annexin V levels promoted fibroblast involvement in alveolar epithelial wound healing that was reduced when Annexin V was depleted from the BALF.

  17. Measurement of Regional and Global Pulmonary Clearance of 99mTc-DTPA (Demethylamitriptylene-Acetate): An Index of Alveolar Epithelial Permeability

    International Nuclear Information System (INIS)

    Vaskova, Olivija

    1996-01-01

    The main purpose of this study has been introduction of a new method for alveoli-capillary permeability evaluation. Many reports pointed out to the altered transit of soluble particles through this barrier. From pathophysiological aspect the main interest is the elucidation of permeability's alteration in different pulmonary pathology. We decided to use for lung epithelial permeability measurements 99m Tc-DTPA inhaled aerosols and sequential assessment of its lung clearance. The aerosols were obtained using oxygen flow nebulizers with aerosols' generators Ultra Vent (Malinkrodt) and Venticis II (CIS bio international) that enabled as to get submicron particles. Oxygen flow between 9 and 11 liters per minute was used. Optimum images were obtained with 1480 MBq of inhaled aerosols at least 2 to 3 minutes. DTPA that was used for aerosols labeling had been produced in our Department and the results were compared with DTPA provided by CIS bio international. High correlation between both agents was proven. During the whole study ex tamper prepared radiopharmaceuticals were used and quality control was done using paper chromatography method. Acquisition was done in sitting position with gamma camera interfaced to a ADAC and Scintiview. The measurements lasted for 20 minutes. Data were stored on 64x64 matrices. Regions of interest over both lungs were drown and each one was divided in three segments: apical, medial, and basal. Using computer program curves of 99m Tc-DTPA lung clearance were derived. From the obtained time activity curves half-time of the global and the regional lung clearance was assessed. In the control group comprised of 32 healthy volunteers (non-smokers) we had got values, used after works as reference range. Our normal values for global clearance are: 68±5,5 min. for left whole lung, 68,1±6,5 min for right whole lung, and 49±7,7 min for apical, 66,9±8 min for middle, and 75,9±6,4 min basal regional lung clearance, and they are in keeping with the

  18. GM-CSF produced by nonhematopoietic cells is required for early epithelial cell proliferation and repair of injured colonic mucosa.

    Science.gov (United States)

    Egea, Laia; McAllister, Christopher S; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Kagnoff, Martin F

    2013-02-15

    GM-CSF is a growth factor that promotes the survival and activation of macrophages and granulocytes, as well as dendritic cell differentiation and survival in vitro. The mechanism by which exogenous GM-CSF ameliorates the severity of Crohn's disease in humans and colitis in murine models has mainly been considered to reflect its activity on myeloid cells. We used GM-CSF-deficient (GM-CSF(-/-)) mice to probe the functional role of endogenous host-produced GM-CSF in a colitis model induced after injury to the colon epithelium. Dextran sodium sulfate (DSS), at doses that resulted in little epithelial damage and mucosal ulceration in wild type mice, caused marked colon ulceration and delayed ulcer healing in GM-CSF(-/-) mice. Colon crypt epithelial cell proliferation in vivo was significantly decreased in GM-CSF(-/-) mice at early times after DSS injury. This was paralleled by decreased expression of crypt epithelial cell genes involved in cell cycle, proliferation, and wound healing. Decreased crypt cell proliferation and delayed ulcer healing in GM-CSF(-/-) mice were rescued by exogenous GM-CSF, indicating the lack of a developmental abnormality in the epithelial cell proliferative response in those mice. Nonhematopoietic cells, and not myeloid cells, produced the GM-CSF important for colon epithelial proliferation after DSS-induced injury, as revealed by bone marrow chimera and dendritic cell-depletion experiments, with colon epithelial cells being the cellular source of GM-CSF. Endogenous epithelial cell-produced GM-CSF has a novel nonredundant role in facilitating epithelial cell proliferation and ulcer healing in response to injury of the colon crypt epithelium.

  19. Collagen based film with well epithelial and stromal regeneration as corneal repair materials: Improving mechanical property by crosslinking with citric acid

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xuan; Liu, Yang; Li, Weichang; Long, Kai; Wang, Lin; Liu, Sa; Wang, Yingjun [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China); Ren, Li, E-mail: psliren@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China)

    2015-10-01

    Corneal disease can lead to vision loss. It has become the second greatest cause of blindness in the world, and keratoplasty is considered as an effective treatment method. This paper presents the crosslinked collagen (Col)–citric acid (CA) films developed by making use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The results showed that the Col–CA films had necessary optical performance, water content. The collagenase resistance of CA crosslinked films was superior to that of EDC crosslinked films. And CA5 film (Col:CA:EDC:NHS = 60:3:10:10) had the best mechanical properties. Cell experiments showed that CA5 film was non-cytotoxic and human corneal epithelial cells could proliferate well on the films. Lamellar keratoplasty showed that the CA5 film could be sutured in the rabbit eyes and was epithelialized completely in about 10 days, and the transparency was restored quickly in 30 ± 5 days. No inflammation and corneal neovascularization were observed at 6 months. Corneal stroma had been repaired; stromal cells and neo-stroma could be seen in the area of operation from the hematoxylin–eosin stained histologic sections and anterior segment optical coherence tomography images. These results indicated that Col–CA films were highly promising biomaterials that could be used in corneal tissue engineering and a variety of other tissue engineering applications. - Highlights: • Adding different amounts of citric acid could change the properties of films. • The crosslinked films had better mechanical property than non-modified films. • Crosslinked collagen–citric acid films could tolerate suture during operation. • The films showed good ability of epithelial and stromal repair.

  20. An open randomized controlled clinical trial to evaluate ridge preservation and repair using SocketKAP(™) and SocketKAGE(™) : part 2 - three-dimensional alveolar bone volumetric analysis of CBCT imaging.

    Science.gov (United States)

    Abdelhamid, Alaa; Omran, Mostafa; Bakhshalian, Neema; Tarnow, Dennis; Zadeh, Homayoun H

    2016-06-01

    The aims of this study were (i) to evaluate the efficacy of ridge preservation and repair procedures involving the application of SocketKAP(™) and SocketKAGE(™) devices following tooth removal and (ii) to evaluate alveolar bone volumetric changes at 6 months post-extraction in intact sockets or those with facial wall dehiscence defects using 3-dimensional pre- and postoperative CBCT data. Thirty-six patients required 61 teeth extracted. Five cohorts were established: Group A: Intact Socket Negative Control Group B: Intact Socket + SocketKAP(™) Group C: Intact Socket Filled with Anorganic Bovine Bone Mineral (ABBM) + SocketKAP(™) Group D: Facial Dehiscence Socket Negative Control Group E: Facial Dehiscence Socket Filled with ABBM + SocketKAP(™) + SocketKAGE(™) . Preoperative CBCT scans were obtained followed by digital subtraction of the test teeth. At 6 months post-extraction, another CBCT scan was obtained. The pre- and postoperative scans were then superimposed, allowing highly accurate quantitative determination of the 3D volumetric alveolar bone volume changes from baseline through 6 months. Significant volumetric bone loss occurred in all sockets, localized mainly in the 0-3 mm zone apical to the ridge crest. For intact sockets, SocketKAP(™) + ABBM treatment led to a statistically significant greater percentage of remaining mineralized tissue volume when compared to negative control group. A significant difference favoring SocketKAP(™) + SocketKAGE(™) + ABBM treatment was observed for sockets with facial dehiscence defects compared to the negative control group. SocketKAP(™) , with ABBM, appears effective in limiting post-extraction volumetric bone loss in intact sockets, while SocketKAP(™) + SocketKAGE + ABBM appears effective in limiting post-extraction bone loss in sockets with dehiscence defects. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Noncanonical WNT-5A signaling impairs endogenous lung repair in COPD

    Science.gov (United States)

    Baarsma, Hoeke A.; John-Schuster, Gerrit; Heinzelmann, Katharina; Dagouassat, Maylis; Boczkowski, Jorge; Brusselle, Guy G.; Smits, Ron; Yildirim, Ali Ö.

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. One main pathological feature of COPD is the loss of functional alveolar tissue without adequate repair (emphysema), yet the underlying mechanisms are poorly defined. Reduced WNT–β-catenin signaling is linked to impaired lung repair in COPD; however, the factors responsible for attenuating this pathway remain to be elucidated. Here, we identify a canonical to noncanonical WNT signaling shift contributing to COPD pathogenesis. We demonstrate enhanced expression of noncanonical WNT-5A in two experimental models of COPD and increased posttranslationally modified WNT-5A in human COPD tissue specimens. WNT-5A was increased in primary lung fibroblasts from COPD patients and induced by COPD-related stimuli, such as TGF-β, cigarette smoke (CS), and cellular senescence. Functionally, mature WNT-5A attenuated canonical WNT-driven alveolar epithelial cell wound healing and transdifferentiation in vitro. Lung-specific WNT-5A overexpression exacerbated airspace enlargement in elastase-induced emphysema in vivo. Accordingly, inhibition of WNT-5A in vivo attenuated lung tissue destruction, improved lung function, and restored expression of β-catenin–driven target genes and alveolar epithelial cell markers in the elastase, as well as in CS-induced models of COPD. We thus identify a novel essential mechanism involved in impaired mesenchymal–epithelial cross talk in COPD pathogenesis, which is amenable to therapy. PMID:27979969

  2. Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian

    DEFF Research Database (Denmark)

    Domanska, K; Malander, S; Måsbäck, A

    2007-01-01

    At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young...... age is a hallmark of heredity, and ovarian cancers associated with HNPCC have been demonstrated to develop at a particularly early age. We used the Swedish Cancer Registry to identify a population-based series of 98 invasive epithelial ovarian cancers that developed before 40 years. Mucinous...... and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case...

  3. Pericentromeric regions are refractory to prompt repair after replication stress-induced breakage in HPV16 E6E7-expressing epithelial cells.

    Directory of Open Access Journals (Sweden)

    Wen Deng

    Full Text Available Chromosomal instability is the major form of genomic instability in cancer cells. Amongst various forms of chromosomal instability, pericentromeric or centromeric instability remains particularly poorly understood. In the present study, we found that pericentromeric instability, evidenced by dynamic formation of pericentromeric or centromeric rearrangements, breaks, deletions or iso-chromosomes, was a general phenomenon in human cells immortalized by expression of human papillomavirus type 16 E6 and E7 (HPV16 E6E7. In particular, for the first time, we surprisingly found a dramatic increase in the proportion of pericentromeric chromosomal aberrations relative to total aberrations in HPV16 E6E7-expressing cells 72 h after release from aphidicolin (APH-induced replication stress, with pericentromeric chromosomal aberrations becoming the predominant type of structural aberrations (~70% of total aberrations. In contrast, pericentromeric aberrations accounted for only about 20% of total aberrations in cells at the end of APH treatment. This increase in relative proportion of pericentromeric aberrations after release from APH treatment revealed that pericentromeric breaks induced by replication stress are refractory to prompt repair in HPV16 E6E7-expressing epithelial cells. Telomerase-immortalized epithelial cells without HPV16 E6E7 expression did not exhibit such preferential pericentromeric instability after release from APH treatment. Cancer development is often associated with replication stress. Since HPV16 E6 and E7 inactivate p53 and Rb, and p53 and Rb pathway defects are common in cancer, our finding that pericentromeric regions are refractory to prompt repair after replication stress-induced breakage in HPV16 E6E7-expressing cells may shed light on mechanism of general pericentromeric instability in cancer.

  4. Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men.

    Science.gov (United States)

    Andrews, J; Honeybourne, D; Ashby, J; Jevons, G; Fraise, A; Fry, P; Warrington, S; Hawser, S; Wise, R

    2007-09-01

    A validated microbiological assay was used to measure concentrations of iclaprim (AR-100) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF) after a single 1.6 mg/kg intravenous 60 min iv infusion of iclaprim. Male volunteers were randomly allocated to three nominal sampling time intervals 1-2 h (Group A), 3-4 h (Group B) and 5.5-7.0 h (Group C) after the start of the drug infusion. Mean iclaprim concentrations in plasma, BM, AM and ELF, respectively, were for Group A 0.59 mg/L (SD 0.18), 0.51 mg/kg (SD 0.17), 24.51 mg/L (SD 21.22) and 12.61 mg/L (SD 7.33); Group B 0.24 mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38 mg/L (SD 5.17); and Group C 0.14 mg/L (SD 0.05), no detectable level in BM, 5.28 mg/L (SD 2.30) and 2.66 mg/L (SD 2.08). Iclaprim concentrations in ELF and AM exceeded the MIC(90) for penicillin-susceptible Streptococcus pneumoniae (MIC90 0.06 mg/L), penicillin-intermediate S. pneumoniae (MIC90 2 mg/L), penicillin-resistant S. pneumoniae (MIC90 4 mg/L) for 7, 7 and 4 h, respectively, and Chlamydia pneumoniae (MIC90 0.5 mg/L) for 7 h. Mean iclaprim concentrations in ELF exceeded the MIC90 for Haemophilus influenzae (MIC90 4 mg/L) and Moraxella catarrhalis (MIC90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC90 was exceeded for up to 7 h. Furthermore, the MIC90 for methicillin-resistant Staphylococcus aureus of 0.12 mg/L was exceeded at all sites for up to 7 h. These data suggest that iclaprim reaches lung concentrations that should be effective in the treatment of community-acquired pneumonia.

  5. TNF-α-Induced cPLA2 Expression via NADPH Oxidase/Reactive Oxygen Species-Dependent NF-κB Cascade on Human Pulmonary Alveolar Epithelial Cells

    Science.gov (United States)

    Lin, Chih-Chung; Lin, Wei-Ning; Cho, Rou-Ling; Wang, Chen-yu; Hsiao, Li-Der; Yang, Chuen-Mao

    2016-01-01

    Tumor necrosis factor-α (TNF-α) triggers activation of cytosolic phospholipase A2 (cPLA2) and then enhancing the synthesis of prostaglandin (PG) in inflammatory diseases. However, the detailed mechanisms of TNF-α induced cPLA2 expression were not fully defined in human pulmonary alveolar epithelial cells (HPAEpiCs). We found that TNF-α-stimulated increases in cPLA2 mRNA (5.2 folds) and protein (3.9 folds) expression, promoter activity (4.3 folds), and PGE2 secretion (4.7 folds) in HPAEpiCs, determined by Western blot, real-time PCR, promoter activity assay and PGE2 ELISA kit. These TNF-α-mediated responses were abrogated by the inhibitors of NADPH oxidase [apocynin (APO) and diphenyleneiodonium chloride (DPI)], ROS [N-acetyl cysteine, (NAC)], NF-κB (Bay11-7082) and transfection with siRNA of ASK1, p47phox, TRAF2, NIK, IKKα, IKKβ, or p65. TNF-α markedly stimulated NADPH oxidase activation and ROS including superoxide and hydrogen peroxide production which were inhibited by pretreatment with a TNFR1 neutralizing antibody, APO, DPI or transfection with siRNA of TRAF2, ASK1, or p47phox. In addition, TNF-α also stimulated p47phox phosphorylation and translocation in a time-dependent manner. On the other hand, TNF-α induced TNFR1, TRAF2, ASK1, and p47phox complex formation in HPAEpiCs, which were attenuated by a TNF-α neutralizing antibody. We found that pretreatment with NAC, DPI, or APO also attenuated the TNF-α-stimulated IKKα/β and NF-κB p65 phosphorylation, NF-κB (p65) translocation, and NF-κB promoter activity in HPAEpiCs. Finally, we observed that TNF-α-stimulated NADPH oxidase activation and ROS generation activates NF-κB through the NIK/IKKα/β pathway. Taken together, our results demonstrated that in HPAEpiCs, up-regulation of cPLA2 by TNF-α is, at least in part, mediated through the cooperation of TNFR1, TRAF2, ASK1, and NADPH oxidase leading to ROS generation and ultimately activates NF-κB pathway. PMID:27932980

  6. Differentiated bronchiolar epithelium in alveolar ducts of rats exposed to ozone for 20 months

    Energy Technology Data Exchange (ETDEWEB)

    Pinkerton, K.E.; Dodge, D.E.; Cederdahl-Demmler, J.; Wong, V.J.; Peake, J.; Haselton, C.J.; Mellick, P.W.; Singh, G.; Plopper, C.G. (Univ. of California, Davis (United States))

    1993-03-01

    The effects of exposure to 1.0 ppm of ozone for twenty months were studied in male Fischer 344 rats. Light microscopic, morphometric, and immunohistological approaches were used to determine the distribution and degree of differentiation of ciliated and nonciliated bronchiolar epithelial (Clara) cells lining alveolar ducts of the central acinus, a primary target of ozone-induced lung injury. Alveolar duct pathways extending beyond the level of the most proximal alveolar outpocketing of terminal bronchioles were isolated in longitudinal profile. The distance that ciliated and nonciliated bronchiolar epithelial (Clara) cells projected down each alveolar duct pathway was determined by placing concentric arcs radiating outward from a single reference point at the level of the first alveolar outpocketing. A high degree of heterogeneity in the magnitude of bronchiolar epithelial cell extension into alveolar ducts was noted for each isolation and animal. Age-matched control animals also demonstrated variation in the degree of bronchiolar epithelial cell extension down alveolar ducts. In animals exposed to ozone, a striking similarity was noted by scanning electron microscopy in the surface characteristics of cells lining both terminal bronchioles and alveolar ducts. The presence of Clara cell secretory protein in cells of bronchioles and alveolar ducts was also detected immunohistochemically and visualized using confocal laser scanning microscopy in the reflectance mode. Well-differentiated ciliated and nonciliated bronchiolar epithelial cells were found lining alveolar septal tips and alveoli up to a depth of 1,000 mu into the pulmonary acinus after 20 months of exposure to ozone. No evidence of inflammation was present in alveolar ducts, suggesting that epithelial cell transformations in alveolar ducts is a natural consequence of lifetime exposures to oxidant gases.

  7. Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate

    Science.gov (United States)

    Laresgoiti, Usua; Rao, Chandrika; Brady, Jane L.; Richardson, Rachel V.; Batchen, Emma J.; Chapman, Karen E.

    2016-01-01

    Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity. PMID:27578791

  8. Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours.

    Science.gov (United States)

    Kuipers, Dorothy; Mehonic, Aida; Kajita, Mihoko; Peter, Loïc; Fujita, Yasuyuki; Duke, Tom; Charras, Guillaume; Gale, Jonathan E

    2014-03-15

    Epithelial cells maintain an essential barrier despite continuously undergoing mitosis and apoptosis. Biological and biophysical mechanisms have evolved to remove dying cells while maintaining that barrier. Cell extrusion is thought to be driven by a multicellular filamentous actin ring formed by neighbouring cells, the contraction of which provides the mechanical force for extrusion, with little or no contribution from the dying cell. Here, we use live confocal imaging, providing time-resolved three-dimensional observations of actomyosin dynamics, to reveal new mechanical roles for dying cells in their own extrusion from monolayers. Based on our observations, the clearance of dying cells can be subdivided into two stages. The first, previously unidentified, stage is driven by the dying cell, which exerts tension on its neighbours through the action of a cortical contractile F-actin and myosin ring at the cell apex. The second stage, consistent with previous studies, is driven by a multicellular F-actin ring in the neighbouring cells that moves from the apical to the basal plane to extrude the dying cell. Crucially, these data reinstate the dying cell as an active physical participant in cell extrusion.

  9. Repopulation of denuded tracheal grafts with alveolar type II cells

    International Nuclear Information System (INIS)

    Johnson, N.F.

    1988-01-01

    Repopulation of denuded heterotopic tracheal grafts with populations of specific epithelial cell types is one approach to study the differentiation potential of various cell types. This technique has been adopted to delineate the differentiation pathways of alveolar type II cells isolated from rat lungs. Under the conditions of this experiment, the reestablished epithelial lining was alveolar-like, however, ultrastructural analysis of the cells showed them to be like Clara cells. These preliminary results suggest that the secretary cells of the lung parenchyma and terminal airways may share a common ancestry. (author)

  10. Proteinosis alveolar pulmonar Pulmonary alveolar proteinosis

    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.The pulmonary alveolar proteinosis is a chronic respiratory disease characterized by surfactant metabolism alteration determining its abnormal accumulation in the alveolar space. It is a disease very rare and in literature only 500 cases have been reported; it was described for the first time in 1958. This is a case presentation of pulmonary alveolar proteinosis in an infant aged 2 months with energetic protein malnutrition admitted due to respiratory difficulty and hypoxemia and with radiologic images of the reticulonodulillary, in frosting glass, where initially is made the diagnosis of bronchopneumonia. In the face of unfavorable evolution and no response to treatment, a study was conducted to rule out chronic pulmonary diseases. Patient died confirming the diagnosis according to the pathologic anatomy. A review on subject is carried out.

  11. Epithelial cells derived from swine bone marrow express stem cell markers and support influenza virus replication in vitro.

    Directory of Open Access Journals (Sweden)

    Mahesh Khatri

    Full Text Available The bone marrow contains heterogeneous population of cells that are involved in the regeneration and repair of diseased organs, including the lungs. In this study, we isolated and characterized progenitor epithelial cells from the bone marrow of 4- to 5-week old germ-free pigs. Microscopically, the cultured cells showed epithelial-like morphology. Phenotypically, these cells expressed the stem cell markers octamer-binding transcription factor (Oct4 and stage-specific embryonic antigen-1 (SSEA-1, the alveolar stem cell marker Clara cell secretory protein (Ccsp, and the epithelial cell markers pan-cytokeratin (Pan-K, cytokeratin-18 (K-18, and occludin. When cultured in epithelial cell growth medium, the progenitor epithelial cells expressed type I and type II pneumocyte markers. Next, we examined the susceptibility of these cells to influenza virus. Progenitor epithelial cells expressed sialic acid receptors utilized by avian and mammalian influenza viruses and were targets for influenza virus replication. Additionally, differentiated type II but not type I pneumocytes supported the replication of influenza virus. Our data indicate that we have identified a unique population of progenitor epithelial cells in the bone marrow that might have airway reconstitution potential and may be a useful model for cell-based therapies for infectious and non-infectious lung diseases.

  12. Activation of the canonical bone morphogenetic protein (BMP pathway during lung morphogenesis and adult lung tissue repair.

    Directory of Open Access Journals (Sweden)

    Alexandros Sountoulidis

    Full Text Available Signaling by Bone Morphogenetic Proteins (BMP has been implicated in early lung development, adult lung homeostasis and tissue-injury repair. However, the precise mechanism of action and the spatio-temporal pattern of BMP-signaling during these processes remains inadequately described. To address this, we have utilized a transgenic line harboring a BMP-responsive eGFP-reporter allele (BRE-eGFP to construct the first detailed spatiotemporal map of canonical BMP-pathway activation during lung development, homeostasis and adult-lung injury repair. We demonstrate that during the pseudoglandular stage, when branching morphogenesis progresses in the developing lung, canonical BMP-pathway is active mainly in the vascular network and the sub-epithelial smooth muscle layer of the proximal airways. Activation of the BMP-pathway becomes evident in epithelial compartments only after embryonic day (E 14.5 primarily in cells negative for epithelial-lineage markers, located in the proximal portion of the airway-tree, clusters adjacent to neuro-epithelial-bodies (NEBs and in a substantial portion of alveolar epithelial cells. The pathway becomes activated in isolated E12.5 mesenchyme-free distal epithelial buds cultured in Matrigel suggesting that absence of reporter activity in these regions stems from a dynamic cross-talk between endoderm and mesenchyme. Epithelial cells with activated BMP-pathway are enriched in progenitors capable of forming colonies in three-dimensional Matrigel cultures.As lung morphogenesis approaches completion, eGFP-expression declines and in adult lung its expression is barely detectable. However, upon tissue-injury, either with naphthalene or bleomycin, the canonical BMP-pathways is re-activated, in bronchial or alveolar epithelial cells respectively, in a manner reminiscent to early lung development and in tissue areas where reparatory progenitor cells reside. Our studies illustrate the dynamic activation of canonical BMP

  13. Loss of Hypoxia-Inducible Factor 2 Alpha in the Lung Alveolar Epithelium of Mice Leads to Enhanced Eosinophilic Inflammation in Cobalt-Induced Lung Injury

    Science.gov (United States)

    Proper, Steven P.; Saini, Yogesh; LaPres, John J.

    2014-01-01

    Hard metal lung disease (HMLD) is an occupational lung disease specific to inhalation of cobalt-containing particles whose mechanism is largely unknown. Cobalt is a known hypoxia mimic and stabilizer of the alpha subunits of hypoxia-inducible factors (HIFs). Previous work revealed that though HIF1α contrib utes to cobalt toxicity in vitro, loss of HIF1α in the alveolar epithelial cells does not provide in vivo protection from cobalt-induced lung inflammation. HIF1α and HIF2α show unique tissue expression profiles, and HIF2α is known to be the predominant HIF mRNA isoform in the adult lung. Thus, if HIF2α activation by cobalt contributes to pathophysiology of HMLD, we hypothesized that loss of HIF2α in lung epithelium would provide protection from cobalt-induced inflammation. Mice with HIF2α-deficiency in Club and alveolar type II epithelial cells (ATIIs) (HIF2αΔ/Δ) were exposed to cobalt (60 µg/day) or saline using a subacute occupational exposure model. Bronchoalveolar lavage cellularity, cytokines, qRT-PCR, and histopathology were analyzed. Results show that loss of HIF2α leads to enhanced eosinophilic inflammation and increased goblet cell metaplasia. Additionally, control mice demonstrated a mild recovery from cobalt-induced lung injury compared with HIF2αΔ/Δ mice, suggesting a role for epithelial HIF2α in repair mechanisms. The expression of important cytokines, such as interleukin (IL)-5 and IL-10, displayed significant differences following cobalt exposure when HIF2αΔ/Δ and control mice were compared. In summary, our data suggest that although loss of HIF2α does not afford protection from cobalt-induced lung inflammation, epithelial HIF2α signaling does play an important role in modulating the inflammatory and repair response in the lung. PMID:24218148

  14. Alveolar but not intravenous S-ketamine inhibits alveolar sodium transport and lung fluid clearance in rats

    NARCIS (Netherlands)

    Berger, Marc M.; Pitzer, Bernhard; Zügel, Stefanie; Wieland, Catharina W.; Vlaar, Alexander P.; Schultz, Marcus J.; Dahan, Albert; Bärtsch, Peter; Hollmann, Markus W.; Mairbäurl, Heimo

    2010-01-01

    BACKGROUND: S-ketamine is frequently used for analgosedation, especially during sepsis and cardiovascular instability. Because S-ketamine blocks voltage-gated sodium (Na+) channels in neurons and skeletal muscle, it is conceivable that S-ketamine also blocks alveolar epithelial Na+ channels that are

  15. The studies of DNA double-strand break (DSB) rejoining and mRNA expression of repair gene XRCCs in malignant transformed cell lines of human bronchial epithelial cells generated by α-particles

    International Nuclear Information System (INIS)

    Sun Jingfen; Sui Jianli; Geng Yu; Zhou Pingkun; Wu Dechang

    2002-01-01

    Objective: To investigate the efficiency of γ-ray-induced DNA DSB rejoining and the mRNA expression of DNA repair genes in malignantly transformed cell lines of human bronchial epithelial cells generated by exposure to a-particles. Methods: Pulsed field gel electrophoresis (PFGE) was used to detect DNA. DSBs mRNA expression was analyzed by RT-PCR. Results: The residual DNA DSB damage level after 4hrs repair following 0-150 Gy of γ-irradiation in the malignantly transformed cell lines BERP35T-1 and BERP35T-4 was significantly higher than that in their parental BEP2D cells. The analysis of mRNA level revealed a 2.5-to 6.5-fold down-regulated expression of the DNA repair genes XRCC-2, XRCC-3 and Ku80 (XRCC-5) in BERP35T-1 and BERP35T-4 cells as compared with the parental BEP2D cells. In contrast, the expression of DNA-PKcs(XRCC7) was 2.4-fold up-regulated in the transformed cell line BERP35T-4, in which there was a significantly higher proportion of polyploid cells. Conclusion: This study results show that the deficiency of DNA DSB rejoining and depressed mRNA expression of DNA repair genes could be involved in the malignant transformation process of BEP2D cells induced by exposure to α-particles

  16. Transplantation of an LGR6+ Epithelial Stem Cell-Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects: The In Vitro Development of Polarized Hair-Bearing Skin.

    Science.gov (United States)

    Lough, Denver M; Wetter, Nathan; Madsen, Christopher; Reichensperger, Joel; Cosenza, Nicole; Cox, Lisa; Harrison, Carrie; Neumeister, Michael W

    2016-02-01

    Recent literature has shown that full-thickness wounds, devoid of the stem cell niche, can subsequently be reconstructed with functional skin elements following migration of the LGR6 epithelial stem cell into the wound bed. In this study, the authors use a variety of LGR6 epithelial stem cell-seeded scaffolds to determine therapeutic utility and regenerative potential in the immediate reconstruction of full-thickness wounds. Isolated LGR6 epithelial stem cells were seeded onto a spectrum of acellular matrices and monitored in both in vitro and in vivo settings to determine their relative capacity to regenerate tissues and heal wounds. Wound beds containing LGR6 stem cell-seeded scaffolds showed significantly augmented rates of healing, epithelialization, and hair growth compared with controls. Gene and proteomic expression studies indicate that LGR6 stem cell-seeded constructs up-regulate WNT, epidermal growth factor, and angiogenesis pathways. Finally, the addition of stromal vascular fraction to LGR6 stem cell-seeded constructs induces polarized tissue formation, nascent hair growth, and angiogenesis within wounds. LGR6 stem cells are able to undergo proliferation, differentiation, and migration following seeding onto a variety of collagen-based scaffolding. In addition, deployment of these constructs induces epithelialization, hair growth, and angiogenesis within wound beds. The addition of stromal vascular fraction to LGR6 stem cell-containing scaffolds initiated an early form of tissue polarization, providing for the first time a clinically applicable stem cell-based construct that is capable of the repair of full-thickness wounds and hair regeneration. Therapeutic, V.

  17. Accelerated orthodontics with alveolar decortication and augmentation: a case report.

    Science.gov (United States)

    Yezdani, A Arif

    2012-01-01

    This case report reiterates the fact that selective alveolar decortication in conjunction with periodontal alveolar augmentation with a bone graft indubitably and efficaciously produces rapid orthodontic tooth movement. A 29-year-old woman presented with a Class I malocclusion and increased bidentoalveolar protrusion with increased spacing between the maxillary and mandibular incisors. She readily agreed to selective alveolar decortication in conjunction with periodontal alveolar augmentation with a bone graft when presented with the proposal that her malocclusion could be corrected in one-third the treatment time required for conventional orthodontics. A preadjusted edgewise appliance (Roth prescription, 0.022 x 0.028-inch slot) was placed prior to the surgical procedure. One week later, full-thickness labial and lingual flaps were reflected in the maxillary and mandibular arches. The alveolar bone was selectively decorticated and periodontally augmented with a bone graft. Starting 1 week postsurgically, orthodontic adjustments were carried out every 2 weeks. From bracketing to debracketing, the entire orthodontic treatment took 7 months. The rapid orthodontic tooth movement was attributed to the regional acceleratory phenomenon, triggered by selective alveolar decortication. The subsequent periodontal alveolar augmentation with the bone graft repaired the bony dehiscences and enhanced the bone volume and dramatically improved the patient's soft tissue profile.

  18. Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis.

    OpenAIRE

    Cantin, A M; North, S L; Fells, G A; Hubbard, R C; Crystal, R G

    1987-01-01

    Lung inflammatory cells of patients with idiopathic pulmonary fibrosis (IPF) were evaluated for their ability to injure 51Cr-labeled AKD alveolar epithelial cells in the presence and absence of IPF alveolar epithelial lining fluid (ELF). The IPF cells were spontaneously releasing exaggerated amounts of superoxide (O.2) and hydrogen peroxide (H2O2) compared with normal (P less than 0.02). Cytotoxicity of the AKD cells was markedly increased when the IPF inflammatory cells were incubated with a...

  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. Asymmetric [14C]albumin transport across bullfrog alveolar epithelium

    International Nuclear Information System (INIS)

    Kim, K.J.; LeBon, T.R.; Shinbane, J.S.; Crandall, E.D.

    1985-01-01

    Bullfrog lungs were prepared as planar sheets and bathed with Ringer solution in Ussing chambers. In the presence of a constant electrical gradient (20, 0, or -20 mV) across the tissue, 14 C-labeled bovine serum albumin or inulin was instilled into the upstream reservoir and the rate of appearance of the tracer in the downstream reservoir was monitored. Two lungs from the same animal were used to determine any directional difference in tracer fluxes. An apparent permeability coefficient was estimated from a relationship between normalized downstream radioactivities and time. Results showed that the apparent permeability of albumin in the alveolar to pleural direction across the alveolar epithelial barrier is 2.3 X 10(-7) cm/s, significantly greater (P less than 0.0005) than that in the pleural to alveolar direction (5.3 X 10(-8) cm/s) when the tissue was short circuited. Permeability of inulin, on the other hand, did not show any directional dependence and averaged 3.1 X 10(-8) cm/s in both directions. There was no effect on radiotracer fluxes permeabilities of different electrical gradients across the tissue. Gel electrophoretograms and corresponding radiochromatograms suggest that the large and asymmetric isotope fluxes are not primarily due to digestion or degradation of labeled molecules. Inulin appears to traverse the alveolar epithelial barrier by simple diffusion through hydrated paracellular pathways. On the other hand, [ 14 C]albumin crosses the alveolar epithelium more rapidly than would be expected by simple diffusion. These asymmetric and large tracer fluxes suggest that a specialized mechanism is present in alveolar epithelium that may be capable of helping to remove albumin from the alveolar space

  1. Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

    OpenAIRE

    Felder Marcel; Sallin Pauline; Barbe Laurent; Haenni Beat; Gazdhar Amiq; Geiser Thomas; Guenat Olivier

    2012-01-01

    We present a microfluidic epithelial wound healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system a technique that is reported here ...

  2. Diffuse bronchiolo-alveolar carcinoma in a dog.

    Science.gov (United States)

    Bertazzolo, W; Zuliani, D; Pogliani, E; Caniatti, M; Bussadori, C

    2002-06-01

    An eight-year-old female German wirehaired pointer was presented with signs of respiratory distress. Clinical examination, laboratory results, thoracic radiography and echocardiography indicated the presence of a diffuse interstitial lung disease with secondary appropriate erythrocytosis, pulmonary hypertension and cor pulmonale. Transthoracic fine needle aspiration biopsy of the lung suggested malignant epithelial neoplasia. A primary lung cancer with an unusually diffuse distribution of miliary/micronodular lesions was found at postmortem examination. Histological diagnosis was bronchiolo-alveolar carcinoma. Bronchiolo-alveolar carcinoma can occasionally occur in a diffuse fashion involving most or all of the lung parenchyma. In man, diffuse bronchiolo-alveolar carcinoma is considered a great imitator of other, more common diffuse interstitial forms of lung disease. This case report indicates that it is also a differential diagnosis to consider in dogs.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

    Science.gov (United States)

    Felder, Marcel; Sallin, Pauline; Barbe, Laurent; Haenni, Beat; Gazdhar, Amiq; Geiser, Thomas; Guenat, Olivier

    2012-02-07

    We present a microfluidic epithelial wound-healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow-focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system, a technique that is reported here for the first time. We demonstrate that alveolar epithelial cells cultured in a microfluidic environment preserve their phenotype before and after wounding. In addition, we report a wound-healing benefit induced by addition of HGF to the cell culture medium (19.2 vs. 13.5 μm h(-1) healing rate).

  6. Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian

    DEFF Research Database (Denmark)

    Domanska, K; Malander, S; Måsbäck, A

    2007-01-01

    and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case......At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young...

  7. Prominin-1/CD133+ lung epithelial progenitors protect from bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Germano, Davide; Blyszczuk, Przemyslaw; Valaperti, Alan; Kania, Gabriela; Dirnhofer, Stephan; Landmesser, Ulf; Lüscher, Thomas F; Hunziker, Lukas; Zulewski, Henryk; Eriksson, Urs

    2009-05-15

    The mouse model of bleomycin-induced lung injury offers an approach to study idiopathic pulmonary fibrosis, a progressive interstitial lung disease with poor prognosis. Progenitor cell-based treatment strategies might combine antiinflammatory effects and the capacity for tissue repair. To expand progenitor cells with reparative and regenerative capacities and to evaluate their protective effects on pulmonary fibrosis in vivo. Prominin-1/CD133(+) epithelial progenitor cells (PEPs) were expanded from adult mouse lungs after digestion and culture of distal airways. Lung fibrosis was induced in C57Bl/6 mice by instillation of bleomycin. Two hours later, animals were transplanted with PEPs. Inflammation and fibrosis were assessed by immunohistochemistry, bronchoalveolar lavage fluid differentials, and real-time polymerase chain reaction. PEPs expanded from mouse lungs were of bone marrow origin, coexpressed stem and hematopoietic cell markers, and differentiated in vitro into alveolar type II surfactant protein-C(+) epithelial cells. In bleomycin-challenged mice, intratracheally injected PEPs engrafted into the lungs and differentiated into type II pneumocytes. Furthermore, PEPs suppressed proinflammatory and profibrotic gene expression, prevented the recruitment of inflammatory cells, and protected bleomycin-challenged mice from pulmonary fibrosis. Mechanistically, the protective effect depended on upregulation of inducible nitric oxide synthase in PEPs and nitric oxide-mediated suppression of alveolar macrophage proliferation. Accordingly, PEPs from iNOS(-/-) but not iNOS(+/+) mice failed to protect from bleomycin-induced lung injury. The combined antiinflammatory and regenerative capacity of bone marrow-derived pulmonary epithelial progenitors offers a promising approach for development of cell-based therapeutic strategies against pulmonary fibrosis.

  8. The development and plasticity of alveolar type 1 cells

    Science.gov (United States)

    Yang, Jun; Hernandez, Belinda J.; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E.; Ostrin, Edwin J.; Chen, Jichao

    2016-01-01

    Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225

  9. p53 alterations in atypical alveolar hyperplasia of the human lung

    NARCIS (Netherlands)

    Slebos, R. J.; Baas, I. O.; Clement, M. J.; Offerhaus, G. J.; Askin, F. B.; Hruban, R. H.; Westra, W. H.

    1998-01-01

    Atypical alveolar hyperplasia (AAH) is a potential precursor lesion from which lung adenocarcinomas arise and may be a good target for studying the early events of lung tumorigenesis. We have previously shown that AAHs are neoplastic epithelial proliferations that often harbor activating mutations

  10. Tissue factor deficiency increases alveolar hemorrhage and death in influenza A virus-infected mice.

    Science.gov (United States)

    Antoniak, S; Tatsumi, K; Hisada, Y; Milner, J J; Neidich, S D; Shaver, C M; Pawlinski, R; Beck, M A; Bastarache, J A; Mackman, N

    2016-06-01

    Essentials H1N1 Influenza A virus (IAV) infection is a hemostatic challenge for the lung. Tissue factor (TF) on lung epithelial cells maintains lung hemostasis after IAV infection. Reduced TF-dependent activation of coagulation leads to alveolar hemorrhage. Anticoagulation might increase the risk for hemorrhages into the lung during severe IAV infection. Background Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide. Objective To investigate the effect of genetic deficiency of tissue factor (TF) in a mouse model of IAV infection. Methods Wild-type mice, low-TF (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage, and inflammation. Results IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in BALF, but also led to alveolar hemorrhage. LTF mice and mice with selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death than controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection. Conclusion Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after IAV infection. © 2016 International Society on Thrombosis and Haemostasis.

  11. Pulp and periodontal tissue repair - regeneration or tissue metaplasia after dental trauma. A review

    DEFF Research Database (Denmark)

    Andreasen, Jens O

    2012-01-01

    Healing subsequent to dental trauma is known to be very complex, a result explained by the variability of the types of dental trauma (six luxations, nine fracture types, and their combinations). On top of that, at least 16 different cellular systems get involved in more severe trauma types each...... of them with a different potential for healing with repair, i.e. (re-establishment of tissue continuity without functional restitution) and regeneration (where the injured or lost tissue is replaced with new tissue with identical tissue anatomy and function) and finally metaplasia (where a new type...... of tissue replaces the injured). In this study, a review is given of the impact of trauma to various dental tissues such as alveolar bone, periodontal ligament, cementum, Hertvigs epithelial root sheath, and the pulp....

  12. Combustion products of 1,3-butadiene inhibit catalase activity and induce expression of oxidative DNA damage repair enzymes in human bronchial epithelial cells

    Science.gov (United States)

    Kennedy, Christopher H.; Catallo, W. James; Wilson, Vincent L.; Mitchell, James B.

    2012-01-01

    1,3-Butadiene, an important petrochemical, is commonly burned off when excess amounts need to be destroyed. This combustion process produces butadiene soot (BDS), which is composed of a complex mixture of polyaromatic hydrocarbons in particulates ranging in size from butadiene soot ethanol extract (BSEE) on both enzyme activity and expression of proteins involved in the repair of oxidative DNA damage. Catalase was found to be sensitive to BDS as catalase activity was potently diminished in the presence of BSEE. Using Western analysis, both the alpha isoform of human 8-oxoguanine DNA glycosylase (α-hOGG1) and human apurinic/apyrimidinic endonuclease (APE-1) were shown to be significantly overexpressed as compared to untreated controls after exposure of NHBE cells to BSEE. Our results indicate that BSEE is capable of effectively inactivating the antioxidant enzyme catalase, presumably via oxidation of protein amino acids. The presence of oxidized proteins may partially explain the extranuclear fluorescence that is detected when NHBE cells are treated with an organic extract of BDS. Overexpression of both α-hOGG1 and APE-1 proteins following treatment of NHBE cells with BSEE suggests that this mixture causes oxidative DNA damage. PMID:18685817

  13. Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution; Adduits encombrants a l'ADN dans des cocultures de cellules pulmonaires humaines exposees a une pollution atmospherique particulaire

    Energy Technology Data Exchange (ETDEWEB)

    Abbas, Imane; Garcon, Guillaume; Billet, Sylvain; Shirali, Pirouz [Universite Lille Nord de France - Lille (France); Unite de Chimie Environnementale et Interactions sur le Vivant, MREI, Universite du Littoral Cote d' Opale, Dunkerque (France); Andre, Veronique; Le Goff, Jeremie; Sichel, Francois [GRECAN, Universite de Caen Basse-Normandie et centre Francois Baclesse, Caen (France); Roy Saint-Georges, Francoise; Mulliez, Philippe [Service de Pneumologie, Hopital Saint-Philibert, GHICL, Lille (France)

    2012-01-15

    Because of their deep penetration in human lungs, fine airborne particulate matter were described as mainly responsible for the deleterious effects of exposure to air pollution on health. Organic constituents are adsorbed on particles surface and, after inhalation, some (polycyclic aromatic hydrocarbons, PAHs) can be activated into reactive metabolites and can bind to DNA. The formation of bulky DNA adducts has been researched after exposure of mono-and co-cultures of alveolar macrophages (AM) and human embryonic human lung epithelial (L132), to fine air pollution particulate matter Air samples have been collected with cascade impactor and characterized: size distribution (92.15% < 2.5{mu}.m), specific surface area (1 m{sup 2}/g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). {sup 32}P post-labeling method was applied to detect bulky DNA adducts in AM and L132, in mono-and co-cultures, 72 h after their exposure to atmospheric particles at their Lethals and Effects concentrations or (LC or CE) to 50% (i.e. MA: EC{sub 50} = 74.63 {mu}g/mL and L132: LC-5-0 = 75.36 {mu}g/mL). Exposure to desorbed particles (MA: C1= 61.11 {mu}g/mL and L132 : C2 = 61.71 {mu}g/mL) and B[a]P (1 {mu}M) were included. Bulky PAH-DNA adducts were detected in AM in mono-culture after exposure to total particles (Pt), to B[a]P and desorbed particles (Pd). Whatever the exposure, no DNA adduct was detected in L132 in mono-culture. These results are coherent with the enzymatic activities of cytochrome P450 l Al in AM and L132. Exposure of co-culture to Pt, or Pd induced bulky adducts to DNA in AM but not in L132. Exposure to B[a]P alone has altered the DNA of AM and L132, in co-culture. Exposure to Pt is closer to the environmental conditions, but conferred an exposure to amounts of genotoxic agents compared to studies using organic extracts. The formation of bulky DNA adducts was nevertheless observed in AM exposed to Pt, in mono- or co-culture, indicating that

  14. Role of the epithelial cell rests of Malassez in the development, maintenance and regeneration of periodontal ligament tissues.

    Science.gov (United States)

    Xiong, Jimin; Gronthos, Stan; Bartold, P Mark

    2013-10-01

    Periodontitis is a highly prevalent inflammatory disease that results in damage to the tooth-supporting tissues, potentially leading to tooth loss. Periodontal tissue regeneration is a complex process that involves the collaboration of two hard tissues (cementum and alveolar bone) and two soft tissues (gingiva and periodontal ligament). To date, no periodontal-regenerative procedures provide predictable clinical outcomes. To understand the rational basis of regenerative procedures, a better understanding of the events associated with the formation of periodontal components will help to establish reliable strategies for clinical practice. An important aspect of this is the role of the Hertwig's epithelial root sheath in periodontal development and that of its descendants, the epithelial cell rests of Malassez, in the maintenance of the periodontium. An important structure during tooth root development, the Hertwig's epithelial root sheath is not only a barrier between the dental follicle and dental papilla cells but is also involved in determining the shape, size and number of roots and in the development of dentin and cementum, and may act as a source of mesenchymal progenitor cells for cementoblasts. In adulthood, the epithelial cell rests of Malassez are the only odontogenic epithelial population in the periodontal ligament. Although there is no general agreement on the functions of the epithelial cell rests of Malassez, accumulating evidence suggests that the putative roles of the epithelial cell rests of Malassez in adult periodontal ligament include maintaining periodontal ligament homeostasis to prevent ankylosis and maintain periodontal ligament space, to prevent root resorption, to serve as a target during periodontal ligament innervation and to contribute to cementum repair. Recently, ovine epithelial cell rests of Malassez cells have been shown to harbor clonogenic epithelial stem-cell populations that demonstrate similar properties to mesenchymal stromal

  15. Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

    Directory of Open Access Journals (Sweden)

    GM Roomans

    2010-06-01

    Full Text Available Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a a ductal cell type in the submucosal glands of the proximal trachea, (b basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c variant Clara cells (Clarav-cells in the bronchioles and (d at the junctions between the bronchioles and the alveolar ducts, and (e alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a embryonic stem (ES cells, induced pluripotent stem (iPS cells, or amniotic fluid stem cells, (b side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

  16. Alveolar type II cell transplantation restores pulmonary surfactant protein levels in lung fibrosis.

    Science.gov (United States)

    Guillamat-Prats, Raquel; Gay-Jordi, Gemma; Xaubet, Antoni; Peinado, Victor I; Serrano-Mollar, Anna

    2014-07-01

    Alveolar Type II cell transplantation has been proposed as a cell therapy for the treatment of idiopathic pulmonary fibrosis. Its long-term benefits include repair of lung fibrosis, but its success partly depends on the restoration of lung homeostasis. Our aim was to evaluate surfactant protein restoration after alveolar Type II cell transplantation in an experimental model of bleomycin-induced lung fibrosis in rats. Lung fibrosis was induced by intratracheal instillation of bleomycin. Alveolar Type II cells were obtained from healthy animals and transplanted 14 days after bleomycin was administered. Furthermore, one group transplanted with alveolar macrophages and another group treated with surfactant were established to evaluate the specificity of the alveolar Type II cell transplantation. The animals were euthanized at 21 days after bleomycin instillation. Lung fibrosis was confirmed by a histologic study and an evaluation of the hydroxyproline content. Changes in surfactant proteins were evaluated by mRNA expression, Western blot and immunofluorescence studies. The group with alveolar Type II cell transplantation was the only one to show a reduction in the degree of lung fibrosis and a complete recovery to normal levels of surfactant proteins. One of the mechanisms involved in the beneficial effect of alveolar Type II cell transplantation is restoration of lung surfactant protein levels, which is required for proper respiratory function. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Resveratrol mediated cell death in cigarette smoke transformed breast epithelial cells is through induction of p21Waf1/Cip1 and inhibition of long patch base excision repair pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India); Choudhuri, Tathagata [Institute of Life Sciences, Nalco Square, Bhubaneswar, Orissa 751023 (India); Department of Biotechnology, Visva Bharati University, Santiniketan, West Bengal (India); Kundu, Chanakya Nath, E-mail: cnkundu@gmail.com [Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Orissa 751024 (India)

    2014-03-15

    Cigarette smoking is a key factor for the development and progression of different cancers including mammary tumor in women. Resveratrol (Res) is a promising natural chemotherapeutic agent that regulates many cellular targets including p21, a cip/kip family of cyclin kinase inhibitors involved in DNA damage-induced cell cycle arrest and blocking of DNA replication and repair. We have recently shown that cigarette smoke condensate (CSC) prepared from commercially available Indian cigarette can cause neoplastic transformation of normal breast epithelial MCF-10A cell. Here we studied the mechanism of Res mediated apoptosis in CSC transformed (MCF-10A-Tr) cells in vitro and in vivo. Res mediated apoptosis in MCF-10A-Tr cells was a p21 dependent event. It increased the p21 protein expression in MCF-10A-Tr cells and MCF-10A-Tr cells-mediated tumors in xenograft mice. Res treatment reduced the tumor size(s) and expression of anti-apoptotic proteins (e.g. PI3K, AKT, NFκB) in solid tumor. The expressions of cell cycle regulatory (Cyclins, CDC-2, CDC-6, etc.), BER associated (Pol-β, Pol-δ, Pol-ε, Pol-η, RPA, Fen-1, DNA-Ligase-I, etc.) proteins and LP-BER activity decreased in MCF-10A-Tr cells but remain significantly unaltered in isogenic p21 null MCF-10A-Tr cells after Res treatment. Interestingly, no significant changes were noted in SP-BER activity in both the cell lines after Res exposure. Finally, it was observed that increased p21 blocks the LP-BER in MCF-10A-Tr cells by increasing its interaction with PCNA via competing with Fen-1 after Res treatment. Thus, Res caused apoptosis in CSC-induced cancer cells by reduction of LP-BER activity and this phenomenon largely depends on p21. - Highlights: • Resveratrol (Res) caused reduction of MCF-10A-Tr cell growth by inducing apoptosis. • Res caused cell cycle arrest and DNA damage in p21 dependent manner. • Res mediated LP-BER reduction in MCF-10A-Tr cells was a p21 dependent phenomenon. • Res inhibits BER and PI

  18. Resveratrol mediated cell death in cigarette smoke transformed breast epithelial cells is through induction of p21Waf1/Cip1 and inhibition of long patch base excision repair pathway

    International Nuclear Information System (INIS)

    Mohapatra, Purusottam; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit; Choudhuri, Tathagata; Kundu, Chanakya Nath

    2014-01-01

    Cigarette smoking is a key factor for the development and progression of different cancers including mammary tumor in women. Resveratrol (Res) is a promising natural chemotherapeutic agent that regulates many cellular targets including p21, a cip/kip family of cyclin kinase inhibitors involved in DNA damage-induced cell cycle arrest and blocking of DNA replication and repair. We have recently shown that cigarette smoke condensate (CSC) prepared from commercially available Indian cigarette can cause neoplastic transformation of normal breast epithelial MCF-10A cell. Here we studied the mechanism of Res mediated apoptosis in CSC transformed (MCF-10A-Tr) cells in vitro and in vivo. Res mediated apoptosis in MCF-10A-Tr cells was a p21 dependent event. It increased the p21 protein expression in MCF-10A-Tr cells and MCF-10A-Tr cells-mediated tumors in xenograft mice. Res treatment reduced the tumor size(s) and expression of anti-apoptotic proteins (e.g. PI3K, AKT, NFκB) in solid tumor. The expressions of cell cycle regulatory (Cyclins, CDC-2, CDC-6, etc.), BER associated (Pol-β, Pol-δ, Pol-ε, Pol-η, RPA, Fen-1, DNA-Ligase-I, etc.) proteins and LP-BER activity decreased in MCF-10A-Tr cells but remain significantly unaltered in isogenic p21 null MCF-10A-Tr cells after Res treatment. Interestingly, no significant changes were noted in SP-BER activity in both the cell lines after Res exposure. Finally, it was observed that increased p21 blocks the LP-BER in MCF-10A-Tr cells by increasing its interaction with PCNA via competing with Fen-1 after Res treatment. Thus, Res caused apoptosis in CSC-induced cancer cells by reduction of LP-BER activity and this phenomenon largely depends on p21. - Highlights: • Resveratrol (Res) caused reduction of MCF-10A-Tr cell growth by inducing apoptosis. • Res caused cell cycle arrest and DNA damage in p21 dependent manner. • Res mediated LP-BER reduction in MCF-10A-Tr cells was a p21 dependent phenomenon. • Res inhibits BER and PI

  19. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients

    Directory of Open Access Journals (Sweden)

    Zabel Peter

    2005-07-01

    Full Text Available Abstract Backround Cigarette smoke exposure including biologically active lipopolysaccharide (LPS in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM and alveolar epithelial cells leading to production of inflammatory mediators. This represents a crucial mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD. Respiratory pathogens are a major cause of exacerbations leading to recurrent cycles of injury and repair. The interaction between pathogen-associated molecular patterns and the host is mediated by pattern recognition receptors (PRR's. In the present study we characterized the expression of Toll-like receptor (TLR- 2, TLR4 and CD14 on human AM compared to autologous monocytes obtained from patients with COPD, healthy smokers and non-smokers. Methods The study population consisted of 14 COPD patients without evidence for acute exacerbation, 10 healthy smokers and 17 healthy non-smokers stratified according to age. The expression of TLR2, TLR4 and CD14 surface molecules on human AM compared to autologous monocytes was assessed ex vivo using FACS analysis. In situ hybridization was performed on bronchoalveolar lavage (BAL cells by application of the new developed HOPE-fixative. Results The expression of TLR2, TLR4 and CD14 on AM from COPD patients, smokers and non-smokers was reduced as compared to autologous monocytes. Comparing AM we detected a reduced expression of TLR2 in COPD patients and smokers. In addition TLR2 mRNA and protein expression was increased after LPS stimulation on non-smokers AM in contrast to smokers and COPD patients. Conclusion Our data suggest a smoke related change in the phenotype of AM's and the cellular response to microbial stimulation which may be associated with impairment of host defenses in the lower respiratory tract.

  20. Alveolar process fractures in the permanent dentition. Part 2. The risk of healing complications in teeth involved in an alveolar process fracture

    DEFF Research Database (Denmark)

    Lauridsen, Eva; Gerds, Thomas; Andreasen, Jens Ove

    2016-01-01

    AIM: To analyze the risk of pulp canal obliteration (PCO), pulp necrosis (PN), repair-related resorption (RRR), infection-related resorption (IRR), ankylosis-related resorption (ARR), marginal bone loss (MBL), and tooth loss (TL) for teeth involved in an alveolar process fracture and to identify.......3-3.5), P = 0.003), and age >30 years (HR: 2.3 (95% CI: 1.1-4.6), P = 0.02). The type of splint (rigid or flexible), the duration of splinting (more or less than 4 weeks), and the administration of antibiotics did not affect the risk of PN. CONCLUSION: Teeth involved in alveolar process fractures appear...

  1. Alveolar bone resorption after tooth extraction

    OpenAIRE

    Dimova, Cena; Popovski, Stipica

    2012-01-01

    Alveolar ridge resorption has long been considered an unavoidable consequence of tooth extraction. Atrophy of the alveolar bone may cause significant esthetic and surgical problems in implantation, as well as at prosthetic and restorative dentistry. Alveolar ridge prophylaxis immediately upon tooth extraction may reduce such sequelae for both, the treating dentist and the patient. Attempts to reduce alveolar bone resorption have included the placement of natural roots, root analogues, and...

  2. Demineralized dentin matrix scaffolds for alveolar bone engineering

    Directory of Open Access Journals (Sweden)

    In-Woong Um

    2017-01-01

    Full Text Available From the point of view of implant dentistry, this review discusses the development and clinical use of demineralized dentin matrix (DDM scaffolds, produced from the patient's own extracted teeth, to repair alveolar bone defects. The structure and the organic and inorganic components of DDM are presented to emphasize the similarities with autogenous bone. Studies of DDM properties, such as osteoinductive and osteoconductive functions as well as efficacy and safety, which are mandatory for its use as a bone graft substitute, are also presented. The clinical applications of powder, block, and moldable DDM are discussed, along with future developments that can support growth factor and stem cell delivery.

  3. Intravascular bronchio-alveolar tumor

    International Nuclear Information System (INIS)

    Mata, J.M.; Caceres, J.; Prat, J.; Lopez, J.I.; Velilla, O.

    1991-01-01

    In 1975 Dail and Liebow described the clinical and pathological characteristics of a pulmonary tumor which they dominated intravascular bronchio-alveolar tumor (IVBAT). Our aim is to acquaint radiologists with the existence of this tumor by describing the radiologic findings in 2 patients with IVBAT, 1 with hepatic involvement ant the other with pulmonary osteoarthropathy. (author). 7 refs.; 2 figs

  4. Human alveolar echinococcosis in Kyrgyzstan.

    Science.gov (United States)

    Usubalieva, Jumagul; Minbaeva, Gulnara; Ziadinov, Iskender; Deplazes, Peter; Torgerson, Paul R

    2013-07-01

    Human echinococcosis is a reportable disease in Kyrgyzstan. Between 1995 and 2011, human alveolar echinococcosis increased from 60 cases per year. The origins of this epidemic, which started in 2004, may be linked to the socioeconomic changes that followed the dissolution of the former Soviet Union.

  5. True Fibroma of Alveolar Mucosa

    Directory of Open Access Journals (Sweden)

    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. Alveolar macrophage dysregulation in Hermansky-Pudlak syndrome type 1.

    Science.gov (United States)

    Rouhani, Farshid N; Brantly, Mark L; Markello, Thomas C; Helip-Wooley, Amanda; O'Brien, Kevin; Hess, Richard; Huizing, Marjan; Gahl, William A; Gochuico, Bernadette R

    2009-12-01

    Individuals with Hermansky-Pudlak syndrome type 1 (HPS-1), an autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, develop an accelerated form of progressive fibrotic lung disease. The etiology of pulmonary fibrosis associated with HPS-1 is unknown. To investigate the potential pathogenesis of pulmonary fibrosis in HPS-1, lung cells and proteins from individuals with HPS-1 were studied. Forty-one subjects with HPS-1 with and without pulmonary fibrosis were evaluated with pulmonary function tests, high-resolution computed tomography scan, and bronchoscopy. Bronchoalveolar lavage cells and analytes were analyzed. Concentrations of total bronchoalveolar lavage cells and alveolar macrophages were significantly higher in epithelial lining fluid from subjects with HPS-1 with and without pulmonary fibrosis compared with healthy research volunteers. Concentrations of cytokines and chemokines (i.e., monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and granulocyte-macrophage colony-stimulating factor) in alveolar epithelial lining fluid were significantly higher in subjects with HPS-1 with and without pulmonary fibrosis compared with healthy research volunteers (P system in which to study the pathogenesis and treatment of HPS pulmonary fibrosis.

  7. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  8. DNA repair

    International Nuclear Information System (INIS)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals

  9. DNA repair systems in rhabdomyosarcoma.

    Science.gov (United States)

    Tsioli, Panagiota G; Patsouris, Efstratios S; Giaginis, Constantinos; Theocharis, Stamatios E

    2013-08-01

    Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in children and adolescent population. There are two major histological subtypes, embryonal (ERMS) and alveolar (ARMS), differing in cytogenetic and morphological features. RMS pathogenesis remains controversial and several cellular mechanisms and pathways have been implicated. Application of intense chemo- and radio-therapy improves survival rates for RMS patients, but significant efficacy has not been proved as DNA damage induced-resistance frequently occurs. The present review is aimed at summarizing the current evidence on DNA repair systems, implications in RMS development, focusing on gene expression alterations and point mutations of genes encoding for DNA repair enzymes. Understanding of DNA repair systems involvement in RMS pathogenesis could diversify RMS patients and provide novel individualized therapeutic targets.

  10. Hypospadias repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003000.htm Hypospadias repair To use the sharing features on this page, please enable JavaScript. Hypospadias repair is surgery to correct a defect in ...

  11. Delineation of the key aspects in the regulation of epithelial monolayer formation

    NARCIS (Netherlands)

    Aschauer, Lydia; Gruber, Leonhard N; Pfaller, Walter; Limonciel, Alice; Athersuch, Toby J; Cavill, Rachel; Khan, Abdulhameed; Gstraunthaler, Gerhard; Grillari, Johannes; Grillari-Voglauer, Regina; Hewitt, Philip; Leonard, Martin O; Wilmes, Anja; Jennings, Paul

    The formation, maintenance, and repair of epithelial barriers are of critical importance for whole-body homeostasis. However, the molecular events involved in epithelial tissue maturation are not fully established. To this end, we investigated the molecular processes involved in renal epithelial

  12. Spectral Analysis of Word-Initial Alveolar and Velar Plosives Produced by Iranian Children with Cleft Lip and Palate

    Science.gov (United States)

    Eshghi, Marziye; Zajac, David J.; Bijankhan, Mahmood; Shirazi, Mohsen

    2013-01-01

    Spectral moment analysis (SMA) was used to describe voiceless alveolar and velar stop-plosive production in Persian-speaking children with repaired cleft lip and palate (CLP). Participants included 11 children with bilateral CLP who were undergoing maxillary expansion and 20 children without any type of orofacial clefts. Four of the children with…

  13. rhBMP-2 with a demineralized bone matrix scaffold versus autologous iliac crest bone graft for alveolar cleft reconstruction.

    Science.gov (United States)

    Francis, Cameron S; Mobin, Sheila S Nazarian; Lypka, Michael A; Rommer, Elizabeth; Yen, Stephen; Urata, Mark M; Hammoudeh, Jeffrey A

    2013-05-01

    Secondary alveolar cleft reconstruction using autologous iliac crest bone graft is currently the standard treatment for alveolar clefts. Although effective, harvesting autologous bone may result in considerable donor-site morbidity, most commonly pain and the potential for long-term sensory disturbances. In an effort to decrease patient morbidity, a novel technique using recombinant human bone morphogenetic protein (rhBMP)-2 encased in a demineralized bone matrix scaffold was developed as an alternative to autografting for secondary alveolar cleft reconstruction. A chart review was conducted for the 55 patients who underwent secondary alveolar cleft reconstruction over a 2-year period with a mean follow-up of 21 months. Of these, 36 patients received rhBMP-2/demineralized bone matrix scaffold (including 10 patients with previously failed repairs using iliac crest bone grafting) and 19 patients underwent iliac crest bone grafting. Postoperatively, bone stock was evaluated using occlusal radiographs rated according to the Bergland and Chelsea scales. Alveolar clefts repaired using rhBMP-2/demineralized bone matrix scaffold were 97.2 percent successful compared with 84.2 percent with iliac crest bone grafting. Radiographically, initial repairs with rhBMP-2/demineralized bone matrix scaffold were superior to iliac crest bone grafting according to both Bergland and Chelsea scales, and significantly more patients in the rhBMP-2/demineralized bone matrix scaffold group had coronal bridging. The postoperative intraoral infection rate following iliac crest bone grafting was significantly greater than for rhBMP-2/demineralized bone matrix scaffold. The cost of rhBMP-2/demineralized bone matrix scaffold products was offset by cost savings associated with a reduction in operative time averaging 102 minutes. rhBMP-2 encased in a demineralized bone matrix scaffold appears to be a viable alternative for secondary alveolar cleft repair. Patients are spared donor-site morbidity and

  14. Pulmonary alveolar microlithiasis in children

    International Nuclear Information System (INIS)

    Schmidt, H.; Loercher, U.; Kitz, R.; Zielen, S.; Ahrens, P.; Koenig, R.

    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.)

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

    International Nuclear Information System (INIS)

    Chuan Junlan; Li Yanzhen; Yang Likai; Sun Xun; Zhang Qiang; Gong Tao; Zhang Zhirong

    2013-01-01

    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.

  16. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy

    OpenAIRE

    Kaya, Bülent; Yildiz, Ibrahim; Baha, Reshat Mehmet; Zeytun, Neslihan Ebru Eryaşar; Yetisgen, Azize

    2015-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin.

  17. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy.

    Science.gov (United States)

    Kaya, Bülent; Yildiz, Ibrahim; Baha, Reshat Mehmet; Zeytun, Neslihan Ebru Eryaşar; Yetisgen, Azize

    2015-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin.

  18. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy

    Directory of Open Access Journals (Sweden)

    Bülent Kaya

    2015-01-01

    Full Text Available Diffuse alveolar hemorrhage (DAH is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin.

  19. CT quantification of pulmonary alveolar microlithiasis

    International Nuclear Information System (INIS)

    Wurche, K.D.; Kubale, R.; Vallee, D.; Ostertag, H.

    1987-01-01

    Pulmonary alveolar microlithiasis is a rare, familial disease with massive symmetrical intra-alveolar calcium deposition. Conventional CT findings and CT measurements with a dual energy technique were carried out in a 26-year-old patient suffering from this disease. The importance of the findings in the differential diagnosis and for estimating the progression and prognosis of the disease is discussed. (orig.) [de

  20. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

    OpenAIRE

    Cantin, A M; Fells, G A; Hubbard, R C; Crystal, R G

    1990-01-01

    We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-s...

  1. Meningocele repair

    Science.gov (United States)

    ... is surgery to repair birth defects of the spine and spinal membranes. Meningocele and myelomeningocele are types of spina bifida . Description For both meningoceles and myelomeningoceles, the surgeon ...

  2. Effect of Alveolar Segmental Sandwich Osteotomy on Alveolar Height: A Preliminary Study.

    Science.gov (United States)

    Mehta, Karan S; Prasad, Kavitha; Shetty, Vibha; Ranganath, Krishnappa; Lalitha, R M; Dexith, Jayashree; Munoyath, Sejal K; Kumar, Vineeth

    2017-12-01

    Bone loss following extraction is maximum in horizontal dimension. Height is also reduced which is pronounced on the buccal aspect. Various surgical procedures are available to correct the bone volume viz. GBR, onlay bone grafting, alveolar distraction and sandwich osteotomy. Sandwich osteotomy has been found to increase the vertical alveolar bone height successfully. The objective of the study was to assess the effect of alveolar segmental sandwich osteotomy on alveolar height and crestal width. A prospective study was undertaken from December 2012 to August 2014. Seven patients with 12 implant sites with a mean age of 36 years were recruited. All seven patients with 12 implant sites underwent alveolar segmental sandwich osteotomy and interpositional bone grafting. Alveolar bone height was assessed radiographically preoperatively, immediate post-op, and at 3 months post-op. Alveolar bone width was assessed radiographically preoperatively and at 3 months post-op. Statistical significance was inferred at p  Sandwich osteotomy can be used as an alternative technique to increase alveolar bone height prior to implant placement. Moderate alveolar deficiency can be predictably corrected by this technique.

  3. Alveolar ridge augmentation by osteoinduction in rats

    DEFF Research Database (Denmark)

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

    1990-01-01

    The purpose of this study was to evaluate bone substitutes for alveolar ridge augmentation by osteoinduction. Allogenic, demineralized, and lyophilized dentin and bone was tested for osteoinductive properties in order to establish an experimental model for further studies. Implantations were...

  4. Walking along the Fibroblast Growth Factor 10 Route: A Key Pathway to Understand the Control and Regulation of Epithelial and Mesenchymal Cell-Lineage Formation during Lung Development and Repair after Injury

    Directory of Open Access Journals (Sweden)

    Elie El Agha

    2014-01-01

    Full Text Available Basic research on embryonic lung development offers unique opportunities to make important discoveries that will impact human health. Developmental biologists interested in the molecular control of branching morphogenesis have intensively studied the developing lung, with its complex and seemingly stereotyped ramified structure. However, it is also an organ that is linked to a vast array of clinical problems in humans such as bronchopulmonary dysplasia in premature babies and emphysema, chronic obstructive pulmonary disease, fibrosis, and cancer in adults. Epithelial stem/progenitor cells reside in niches where they interact with specific extracellular matrices as well as with mesenchymal cells; the latter are still poorly characterized. Interactions of epithelial stem/progenitor cells with their microenvironments are usually instructive, controlling quiescence versus activation, proliferation, differentiation, and migration. During the past 18 years, Fgf10 has emerged not only as a marker for the distal lung mesenchyme during early lung development, but also as a key player in branching morphogenesis and a critical component of the niche for epithelial stem cells. In this paper, we will present the current knowledge regarding the lineage tree in the lung, with special emphasis on cell-lineage decisions in the lung mesenchyme and the role of Fgf10 in this context.

  5. Inactivation of Tsc2 in Mesoderm-Derived Cells Causes Polycystic Kidney Lesions and Impairs Lung Alveolarization.

    Science.gov (United States)

    Ren, Siying; Luo, Yongfeng; Chen, Hui; Warburton, David; Lam, Hilaire C; Wang, Larry L; Chen, Ping; Henske, Elizabeth P; Shi, Wei

    2016-12-01

    The tuberous sclerosis complex (TSC) proteins are critical negative regulators of the mammalian/mechanistic target of rapamycin complex 1 pathway. Germline mutations of TSC1 or TSC2 cause TSC, affecting multiple organs, including the kidney and lung, and causing substantial morbidity and mortality. The mechanisms of organ-specific disease in TSC remain incompletely understood, and the impact of TSC inactivation on mesenchymal lineage cells has not been specifically studied. We deleted Tsc2 specifically in mesoderm-derived mesenchymal cells of multiple organs in mice using the Dermo1-Cre driver. The Dermo1-Cre-driven Tsc2 conditional knockout mice had body growth retardation and died approximately 3 weeks after birth. Significant phenotypes were observed in the postnatal kidney and lung. Inactivation of Tsc2 in kidney mesenchyme caused polycystic lesions starting from the second week of age, with increased cell proliferation, tubular epithelial hyperplasia, and epithelial-mesenchymal transition. In contrast, Tsc2 deletion in lung mesenchyme led to decreased cell proliferation, reduced postnatal alveolarization, and decreased differentiation with reduced numbers of alveolar myofibroblast and type II alveolar epithelial cells. Two major findings thus result from this model: inactivation of Tsc2 in mesoderm-derived cells causes increased cell proliferation in the kidneys but reduced proliferation in the lungs, and inactivation of Tsc2 in mesoderm-derived cells causes epithelial-lined renal cysts. Therefore, Tsc2-mTOR signaling in mesenchyme is essential for the maintenance of renal structure and for lung alveolarization. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. ALVEOLAR BONE REGENERATION AFTER DEMINERALIZED FREEZE DRIED BONE ALOGRAFT (DFDBA BONE GRAFTING

    Directory of Open Access Journals (Sweden)

    Sri Oktawati

    2006-04-01

    Full Text Available Periodontal treatment by conventional way will result in healing repair, which easily cause recurrence. Modification of treatment should be done to get an effective result, that is the regeneration of alveolar bone and to reduce inflammation. The objective of this study is to determine the alveolar bone regeneration after using DFDBA (Demineralized Freeze Dried Bone Allograft. Quasi experimental designs with pre and post test method was used in this study. From 13 patients, 26 defects got conventional or regenerative treatment. The indicator of alveolar bone regenaration in bone height in radiographic appearance and level of osteocalsin in gingival crevicular fluid (GCF were checked before and after the treatment, then the changes that occurred were analyzed. The result of the research showed that alveolar bone regeneration only occurred to the group of regenerative treatment using DFDBA. The conclusion is the effective periodontal tissue regeneration occurred at regenerative treatment by using DFDBA, and the osteocalsin in GCF can be used as indicator of bone growth.

  7. [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.

  8. The influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction in rats.

    Science.gov (United States)

    Dias-da-Silva, Marco A; Pereira, Andresa C; Marin, Miguel Cc; Salgado, Miguel Ac

    2013-10-01

    The Copaiba oil has been used as an auxiliary treatment of inflammations, skin disorders and stomach ulcers, however, in dentistry, this "alternative" medicine has not been investigated yet. The purpose of this study was to evaluate the influence of topic and systemic administration of copaiba oil on the alveolar wound healing after tooth extraction. Twenty-eight wistar male rats had their lower first molar teeth extracted. Subsequently, they were divided in four groups, according to the treatment performed: (a) alveolar socket irrigation with copaiba oil; (b) alveolar socket irrigation with physiological serum; (c) daily gavage with copaiba oil or (d) daily gavage with physiological serum. After the sacrifice, the mandibles were removed and processed in order to obtain decalcified histological sections. The results demonstrated high level of epithelial migration, small number of inflammatory cells and vascular enhancement in the animals which received systemic administration of copaiba oil. The rats treated with topic administration of copaiba oil presented ulcerations and large number of inflammatory cells. An increased bone neoformation was observed in both groups treated with copaiba oil when compared with placebo group. It could be concluded that topic or systemic administration of copaiba oil leads to a better alveolar bone healing, however the topic application on connective tissue should be carefully considered, regarding the whole socket wound healing. Key words:Alveolar wound healing, oil-resin, copaiba.

  9. Hydrocele repair

    Science.gov (United States)

    ... about 4 to 7 days. Outlook (Prognosis) The success rate for hydrocele repair is very high. The ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  10. Craniosynostosis repair

    Science.gov (United States)

    ... children having an open repair may need a transfusion) Reaction to medicines Risks for this surgery are: Infection in the brain Bones connect together again, and more surgery is needed Brain swelling Damage to brain tissue

  11. Ptosis repair.

    Science.gov (United States)

    Ng, John; Hauck, Matthew J

    2013-02-01

    Acquired blepharoptosis presents as both a functional and cosmetic problem commonly encountered by facial plastic surgeons. Ptosis repair can be both challenging and frustrating, especially given ever-increasing demands for an optimal cosmetic surgical result. The authors present a brief overview of key points to consider when attempting to achieve excellent blepharoptosis repair outcomes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

    Science.gov (United States)

    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

  13. When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine.

    Science.gov (United States)

    Beers, Michael F; Moodley, Yuben

    2017-07-01

    Generating mature, differentiated, adult lung cells from pluripotent cells, such as induced pluripotent stem cells and embryonic stem cells, offers the hope of both generating disease-specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung-regenerative medicine, several groups have developed and reported on protocols using defined media, coculture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared with their primary counterparts, coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable, but yet-to-emerge second and higher generation techniques to create such assets, we were prompted to pose the question, what makes a lung epithelial cell a lung epithelial cell? More specifically for this Perspective, we also posed the question, what are the minimum features that constitute an alveolar type (AT) 2 epithelial cell? In addressing this, we summarize a body of work spanning nearly five decades, amassed by a series of "lung epithelial cell biology pioneers," which carefully describes well characterized molecular, functional, and morphological features critical for discriminately assessing an AT2 phenotype. Armed with this, we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiation protocol are indeed mature and functional AT2 epithelial cells.

  14. Novel Application of Artificial Dermis Plus Autologous Vital Epithelial Cells: Improved Wound Epithelialization

    Directory of Open Access Journals (Sweden)

    Li-Tzu Lee

    2010-02-01

    Full Text Available The purpose of this study was to evaluate artificial dermis with the simultaneous addition of autologous epithelial cells for oral lesion defect reconstruction. Surgical wounds reconstructed with artificial dermis plus scraped epithelial cells were evaluated in 5 patients with oral benign lesions or squamous cell carcinoma. Clinical follow-up indices included scar formation and tissue surface texture observation. The neomucosal layers were analyzed histologically to establish the degree of epithelialization. Clinical observation showed that the oral mucosal texture was smoother in artificial dermis with added epithelial cells at 4 weeks postoperation compared with artificial dermis alone. The wound contraction and scar formation processes were slow. Viable epithelial cells with flat rete ridges remained in the artificial dermis, and a neoepithelial layer was present in the histological findings. We showed that healthy granulation tissue and neoepithelial formation in artificial dermis with epithelial cells was beneficial for the repair of oral defects. Scraping oral epithelial cells and applying them to artificial dermis assisted in the early preparation of composite grafts and minimized requirement for donor sites. This technique may improve the treatment of patients with oral benign tumors and early-stage squamous cell carcinoma.

  15. Airway epithelial cell response to human metapneumovirus infection

    International Nuclear Information System (INIS)

    Bao, X.; Liu, T.; Spetch, L.; Kolli, D.; Garofalo, R.P.; Casola, A.

    2007-01-01

    Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and type I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-κB, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immunomodulatory mediators

  16. Pulmonary epithelial permeability in rats with bleomycin-induced pneumonitis

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-07-01

    This study was performed to investigate the mechanism by which [sup 99m]Tc-DTPA molecules pass through the pulmonary epithelium following inhalation of [sup 99m]Tc-DTPA aerosol. Interstitial pneumonitis was induced in 6-week-old male rats by instilling 1 mg/kg of bleomycin into the trachea. Disappearance of radioactivity from the lungs was measured with a gamma camera every 2 weeks to estimate pulmonary epithelial permeability, and light- and electron-microscopic histopathologic examinations were performed at the same intervals. There was a statistically significant increase in the pulmonary epithelial permeability at 2 weeks after the instillation of bleomycin. However, subsecquent changes in pulmonary epithelial permeability were not uniform; some animals showed recovery and some showed further increase and/or partial recovery. Microscopically, increase in the capillary bed, round cell infiltration, and widening of the interstitial space were observed in addition to the presence of macrophages in the alveolar spaces at 2 weeks. Electron microscopic examination revealed vacuolization, thinning and detachment of the alveolar epithelium, and denudation of the basement membrane. Prominent fibrosis, honeycombing, thinning of the pulmonary epithelium, and increase in collagen fibers were observed after 18 weeks. We consider that vacuolization, thinning, and detachment of the pulmonary epithelium and denudation of the basement membrane are related to the increase in pulmonary epithelial permeability in bleomycin-induced interstitial pneumonitis. (author).

  17. Adipose and mammary epithelial tissue engineering.

    Science.gov (United States)

    Zhu, Wenting; Nelson, Celeste M

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Fibrosis of Two: Epithelial Cell-Fibroblast Interactions in Pulmonary Fibrosis

    Science.gov (United States)

    Sakai, Norihiko; Tager, Andrew M.

    2013-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function. IPF is now thought to result from wound-healing processes that, although initiated to protect the host from injurious environmental stimuli, lead to pathological fibrosis due to these processes becoming aberrant or over-exuberant. Although the environmental stimuli that trigger IPF remain to be identified, recent evidence suggests that they initially injure the alveolar epithelium. Repetitive cycles of epithelial injury and resultant alveolar epithelial cell death provoke the migration, proliferation, activation and myofibroblast differentiation of fibroblasts, causing the accumulation of these cells and the extracellular matrix that they synthesize. In turn, these activated fibroblasts induce further alveolar epithelial cell injury and death, thereby creating a vicious cycle of pro-fibrotic epithelial cell-fibroblast interactions. Though other cell types certainly make important contributions, we focus here on the “pas de deux” (steps of two), or perhaps more appropriate to IPF pathogenesis, the “folie à deux” (madness of two) of epithelial cells and fibroblasts that drives the progression of pulmonary fibrosis. We describe the signaling molecules that mediate the interactions of these cell types in their “fibrosis of two”, including transforming growth factor-β, connective tissue growth factor, sonic hedgehog, prostaglandin E2, angiotensin II and reactive oxygen species. PMID:23499992

  20. Alveolar soft-part sarcoma in paranasal sinuses

    Directory of Open Access Journals (Sweden)

    Jie ZHANG

    2015-07-01

    Full Text Available Objective To investigate clinicopathological features, immune phenotype, diagnosis and differential diagnosis of alveolar soft-part sarcoma (ASPS in paranasal sinuses. Methods Retrospective study of clinical manifestations, histopathological features and immunohistochemical features was conducted in one case of ASPS in paranasal sinuses.  Results A 28-year-old female presented with bulging forehead for 2 months. MRI revealed a well-circumscribed lesion in left frontal and ethmoid sinuses extending to anterior skull base that showed slightly hyperintense signal on T1WI and hypointense signal on T2WI without obvious enhancement after contrast administration. The patient subsequently underwent endoscopic open surgery on left ethmoid and bilateral frontal sinuses and performed partial resection of the lesion. Three months after the initial surgery, the patient received reoperation for total removal of residual lesion and reconstructive surgery of anterior skull base. Adjuvant chemotherapy and radiotherapy were not administered. Histologically, the tumor was composed of epithelioid cells arranged in organoid nests and/or alveolar structures varying in size and shape, which were separated by connective tissue richly containing sinusoidal vascular channels. The tumor cells were generally large-sized, round, oval or polygonal with abundant eosinophilic granular or translucent vacuolated cytoplasm. The nuclei showed round or oval shape containing centrally placed and obvious nucleoli. The presence a lot of mono- or multi-nuclear giant cells served as another striking feature. Mitotic activities were rare. Reticular fiber staining indicated that reticular fibers surrounded the nest of tumor cells, and diastase-resistant periodic acid-Schiff (PAS-positive crystalline inclusions were identified within the cytoplasm of tumor cells. Immunohistochemically, the tumor cells were reactive for TFE3, while were negative for glial fibrillary acidic protein (GFAP

  1. Volumetric Analysis of Alveolar Bone Defect Using Three-Dimensional-Printed Models Versus Computer-Aided Engineering.

    Science.gov (United States)

    Du, Fengzhou; Li, Binghang; Yin, Ningbei; Cao, Yilin; Wang, Yongqian

    2017-03-01

    Knowing the volume of a graft is essential in repairing alveolar bone defects. This study investigates the 2 advanced preoperative volume measurement methods: three-dimensional (3D) printing and computer-aided engineering (CAE). Ten unilateral alveolar cleft patients were enrolled in this study. Their computed tomographic data were sent to 3D printing and CAE software. A simulated graft was used on the 3D-printed model, and the graft volume was measured by water displacement. The volume calculated by CAE software used mirror-reverses technique. The authors compared the actual volumes of the simulated grafts with the CAE software-derived volumes. The average volume of the simulated bone grafts by 3D-printed models was 1.52 mL, higher than the mean volume of 1.47 calculated by CAE software. The difference between the 2 volumes was from -0.18 to 0.42 mL. The paired Student t test showed no statistically significant difference between the volumes derived from the 2 methods. This study demonstrated that the mirror-reversed technique by CAE software is as accurate as the simulated operation on 3D-printed models in unilateral alveolar cleft patients. These findings further validate the use of 3D printing and CAE technique in alveolar defect repairing.

  2. Scaffold-based rhBMP-2 therapy in a rat alveolar defect model: implications for human gingivoperiosteoplasty.

    Science.gov (United States)

    Nguyen, Phuong D; Lin, Clarence D; Allori, Alexander C; Schachar, Jeffrey S; Ricci, John L; Saadeh, Pierre B; Warren, Stephen M

    2009-12-01

    Primary alveolar cleft repair has a 41 to 73 percent success rate. Patients with persistent alveolar defects require secondary bone grafting. The authors investigated scaffold-based therapies designed to augment the success of alveolar repair. Critical-size, 7 x 4 x 3-mm alveolar defects were created surgically in 60 Sprague-Dawley rats. Four scaffold treatment arms were tested: absorbable collagen sponge, absorbable collagen sponge plus recombinant human bone morphogenetic protein-2 (rhBMP-2), hydroxyapatite-tricalcium phosphate, hydroxyapatite-tricalcium phosphate plus rhBMP-2, and no scaffold. New bone formation was assessed radiomorphometrically and histomorphometrically at 4, 8, and 12 weeks. Radiomorphometrically, untreated animals formed 43 +/- 6 percent, 53 +/- 8 percent, and 48 +/- 3 percent new bone at 4, 8, and 12 weeks, respectively. Animals treated with absorbable collagen sponge formed 50 +/- 6 percent, 79 +/- 9 percent, and 69 +/- 7 percent new bone, respectively. Absorbable collagen sponge plus rhBMP-2-treated animals formed 49 +/- 2 percent, 71 +/- 6 percent, and 66 +/- 7 percent new bone, respectively. Hydroxyapatite-tricalcium phosphate treatment stimulated 69 +/- 12 percent, 86 +/- 3 percent (p scaffold. Radiomorphometrically, absorbable collagen sponge and hydroxyapatite-tricalcium phosphate scaffolds induced more bone formation than untreated controls. The rhBMP-2 added a small but significant histomorphometric osteogenic advantage to the hydroxyapatite-tricalcium phosphate scaffold.

  3. Lateralization Technique and Inferior Alveolar Nerve Transposition

    Directory of Open Access Journals (Sweden)

    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.

  4. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2013-09-20

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

  5. Bone graft healing in alveolar osteoplasty in patients with unilateral lip, alveolar process, and palate clefts.

    Science.gov (United States)

    Rychlik, Dariusz; Wójcicki, Piotr

    2012-01-01

    Secondary osteoplasty by means of autogenic spongy bone grafting is the most common procedure used in the reconstruction of the continuity of the maxillary alveolar process. The aim of the study was to analyze retrospectively the effect of certain factors on the course of the bone graft healing process in patients with unilateral complete clefts of the lip, alveolar process, and palate. The investigations involved 62 children aged 8 to 14 years (mean age, 11 years) with unilateral complete cleft of the lip, alveolar process, and palate operated on at the Clinic of Plastic Surgery in Polanica Zdrój from November 2007 to April 2009. All the procedures consisted in the reconstruction of the maxillary alveolar process by means of autogenic spongy bone grafting from the iliac bone. The analysis was performed on the basis of computed tomography scans presenting maxillary alveolar processes in the horizontal cross-sectional planes performed on the second or third postoperative day and after 6 months. They were used as the basis for the measurement of the volume and density (condensation) of the bone graft, the surface of its adhesion to the maxillary alveolar bone, and the volume and density of the healed bone. The following correlation coefficients were determined: between the adhesion surface of the bone to the alveolar bone and the volume of the healed bone, between the adhesion surface of the bone to the alveolar bone and the density of the healed bone, and between the density of the graft and the volume of the healed bone. Increasing the surface of the graft adhesion to the bone ridges of the alveolar cleft contributes to increased volume of the healed bone and slows down the increase in its density (on 6-month follow-up). Crushing of the bone graft increases its resorption and reduces volume of the healed bone.

  6. Alveolar wound healing in rats fed on high sucrose diet.

    Science.gov (United States)

    Baró, María A; Rocamundi, Marina R; Viotto, Javier O; Ferreyra, Ruth S

    2013-01-01

    The potential for bone repair is influenced by various biochemical, biomechanical, hormonal, and pathological mechanisms and factors such as diet and its components, all of which govern the behavior and function of the cells responsible for forming new bone. Several authors suggest that a high sucrose diet could change the calcium balance and bone composition in animals, altering hard tissue mineralization. The mechanism by which it occurs is unclear. Alveolar healing following tooth extraction has certain characteristics making this type of wound unique, in both animals and humans. The general aim of this study was to evaluate and quantify the biological response during alveolar healing following tooth extraction in rats fed on high sucrose diets, by means of osteocyte lacunae histomorphometry, counting empty lacunae and measuring areas of bone quiescence, formation and resorption. Forty-two Wistar rats of both sexes were divided into two groups: an experimental group fed on modified Stephan Harris diet (43% sucrose) and a control group fed on standard balanced diet. The animals were anesthetized and their left and right lower molars extracted. They were killed at 0 hours, 14, 28, 60 and 120 days. Samples were fixed, decalcified in EDTA and embedded in paraffin to prepare sections for optical microscopy which were stained with hematoxylin/eosin. Histomorphometric analysis showed significant differences in the size of osteocyte lacunae between groups at 28 and 60 days, with the experimental group having larger lacunae. There were more empty lacunae in the experimental group at 14 days, and no significant difference in the areas of bone activity. A high sucrose diet could modify the morphology and quality of bone tissue formed in the alveolus following tooth extraction.

  7. Alveolar Ridge Carcinoma. Two Cases Report

    International Nuclear Information System (INIS)

    Pupo Triguero, Raul J; Vivar Bauza, Miriam; Alvarez Infante, Elisa

    2008-01-01

    Two cases with alveolar ridge carcinoma due to prosthetist traumatism are discussed in this paper, after 9 and 10 years of using dental prosthesis. Both patients began with disturbance in the alveolar ridge. The clinical examination and biopsy showed a well differenced carcinoma. The treatment was radical surgery and radiotherapy in the first patient, and conservative surgery with radiotherapy in the second case .The patients had xerostomia after radiotherapy and the woman had difficulties with mastication. The advantages and disadvantages of the treatment were discussed, focused on the prevention and treatment for oral

  8. Alveolar Bone Fracture: Pathognomonic Sign for Clinical Diagnosis

    OpenAIRE

    Gutmacher, Zvi; Peled, Eli; Norman, Doron; Lin, Shaul

    2017-01-01

    Aim: Dental injuries, especially luxation and avulsion, are common. Dental trauma can cause alveolar bone fracture that can lead to tooth loss and malocclusion. Single tooth alveolar bone fractures are difficult to identify unless it protrudes through the overlying mucosa and can be visualized. Pain, malocclusion, and tooth mobility provide signs of suspected alveolar bone fractures. Integrity of the proximate alveolar bone should be examined for fractures where avulsion, luxation, or other t...

  9. Stem Cell Factor Expression after Renal Ischemia Promotes Tubular Epithelial Survival

    NARCIS (Netherlands)

    Stokman, Geurt; Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J. D.; Weening, Jan J.; Leemans, Jaklien C.; Florquin, Sandrine

    2010-01-01

    Background: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration

  10. Repair process and a repaired component

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, III, Herbert Chidsey; Simpson, Stanley F.

    2018-02-20

    Matrix composite component repair processes are disclosed. The matrix composite repair process includes applying a repair material to a matrix composite component, securing the repair material to the matrix composite component with an external securing mechanism and curing the repair material to bond the repair material to the matrix composite component during the securing by the external securing mechanism. The matrix composite component is selected from the group consisting of a ceramic matrix composite, a polymer matrix composite, and a metal matrix composite. In another embodiment, the repair process includes applying a partially-cured repair material to a matrix composite component, and curing the repair material to bond the repair material to the matrix composite component, an external securing mechanism securing the repair material throughout a curing period, In another embodiment, the external securing mechanism is consumed or decomposed during the repair process.

  11. Effects of X irradiation on the cytoskeleton of rat alveolar macrophages in vitro

    International Nuclear Information System (INIS)

    Ladyman, S.J.; Townsend, K.M.S.; Edwards, C.

    1984-01-01

    The three-dimensional visualization of Triton X-100 resistant cytoskeletons has been used to demonstrate that an absorbed dose of 120 Gy from X rays causes a distinctive and reproducible alteration of the cytoskeleton of intact rat alveolar macrophages in vitro. The alteration has also been shown to be rapidly and completely ''repaired'' and to be apparently similar to alterations caused by colchicine but dissimilar to those caused by cytochalasin B. From these observations and those of other workers who have studied the irradiation of extracted microtubular proteins in vitro, the authors think it likely that microtubules rather than microfilaments are the radiosensitive component of the macrophage cytoskeleton

  12. Motorcycle Repair.

    Science.gov (United States)

    Hein, Jim; Bundy, Mike

    This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…

  13. Teaching Alveolar Ventilation with Simple, Inexpensive Models

    Science.gov (United States)

    DiCarlo, Stephen E.

    2008-01-01

    When teaching and learning about alveolar ventilation with our class of 300 first-year medical students, we use four simple, inexpensive "models." The models, which encourage research-oriented learning and help our students to understand complex ideas, are distributed to the students before class. The students anticipate something new every day,…

  14. Alveolar ridge augmentation by osteoinduction in rats

    DEFF Research Database (Denmark)

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

    1990-01-01

    The purpose of this study was to evaluate bone substitutes for alveolar ridge augmentation by osteoinduction. Allogenic, demineralized, and lyophilized dentin and bone was tested for osteoinductive properties in order to establish an experimental model for further studies. Implantations were perf...

  15. 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.

  16. Rhinovirus infection induces cytotoxicity and delays wound healing in bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Constantopoulos Andreas G

    2005-10-01

    Full Text Available Abstract Background Human rhinoviruses (RV, the most common triggers of acute asthma exacerbations, are considered not cytotoxic to the bronchial epithelium. Recent observations, however, have questioned this knowledge. The aim of this study was to evaluate the ability of RV to induce epithelial cytotoxicity and affect epithelial repair in-vitro. Methods Monolayers of BEAS-2B bronchial epithelial cells, seeded at different densities were exposed to RV serotypes 1b, 5, 7, 9, 14, 16. Cytotoxicity was assessed chromatometrically. Epithelial monolayers were mechanically wounded, exposed or not to RV and the repopulation of the damaged area was assessed by image analysis. Finally epithelial cell proliferation was assessed by quantitation of proliferating cell nuclear antigen (PCNA by flow cytometry. Results RV1b, RV5, RV7, RV14 and RV16 were able to induce considerable epithelial cytotoxicity, more pronounced in less dense cultures, in a cell-density and dose-dependent manner. RV9 was not cytotoxic. Furthermore, RV infection diminished the self-repair capacity of bronchial epithelial cells and reduced cell proliferation. Conclusion RV-induced epithelial cytotoxicity may become considerable in already compromised epithelium, such as in the case of asthma. The RV-induced impairment on epithelial proliferation and self-repair capacity may contribute to the development of airway remodeling.

  17. 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 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.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.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.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.

  18. Alveolar Bone Fracture: Pathognomonic Sign for Clinical Diagnosis.

    Science.gov (United States)

    Gutmacher, Zvi; Peled, Eli; Norman, Doron; Lin, Shaul

    2017-01-01

    Dental injuries, especially luxation and avulsion, are common. Dental trauma can cause alveolar bone fracture that can lead to tooth loss and malocclusion. Single tooth alveolar bone fractures are difficult to identify unless it protrudes through the overlying mucosa and can be visualized. Pain, malocclusion, and tooth mobility provide signs of suspected alveolar bone fractures. Integrity of the proximate alveolar bone should be examined for fractures where avulsion, luxation, or other tooth trauma is detected. Any suggestion of alveolar fractures should be further investigated with an appropriate radiograph. This case report shows a pathognomonic sign that detects and diagnosis single tooth alveolar bone fractures, i.e. , a localized hematoma crossing the attached gingiva from the free gingival margin to the vestibular mucosa. This should serve as a warning for localized alveolar bone fracture. A visualized hematoma and gentle, careful palpation may help detect covered fractures when the overlying mucosa is not perforated.

  19. Repairing organs: lessons from intestine and liver.

    Science.gov (United States)

    Gehart, Helmuth; Clevers, Hans

    2015-06-01

    The concept of organ regeneration has fascinated humanity from ancient mythology to modern science fiction. Recent advances offer the potential to soon bring such technology within the grasp of clinical medicine. Rapidly expanding insights into the intrinsic repair processes of the intestine and liver have uncovered significant plasticity in epithelial tissues. Harnessing this knowledge, researchers have recently created culture systems that enable the expansion of stem cells into transplantable tissue in vitro. Here we discuss how the growing tool set of stem cell biology can bring organ repair from fictitious narrative to medical practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Rare Lung Diseases II: Pulmonary Alveolar Proteinosis

    Directory of Open Access Journals (Sweden)

    Stephen C Juvet

    2008-01-01

    Full Text Available The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP, a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed.

  1. 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.

  2. Alveolar ridge preservation immediately after tooth extraction.

    Science.gov (United States)

    Feller, L; Khammissa, R A G; Bouckaert, M; Lemmer, J

    2013-10-01

    Ridge preservation procedures immediately after tooth extraction, are commonly used with a view to minimising remodelling and shrinkage of the alveolar ridge, associated with socket healing. These procedures may sometimes be effective, but they cannot completely prevent reduction in dimension of the ridge. Certain biomater als used may actually hamper normal deposition of bone within the healing socket, reducing bone trabeculae that can integrate with the implant surface. However, in extraction sockets in alveolar ridges of low bone density, particles of implanted bone substitute incorporated in the healing bone, may enhance the mechanical support for the implant, provided by normal healed bone of low trabecular density alone. This paper reviews biological rationales and procedures for ridge preservation immediately after extraction and comments on their clinical use.

  3. A co-culture system with an organotypic lung slice and an immortal alveolar macrophage cell line to quantify silica-induced inflammation.

    Directory of Open Access Journals (Sweden)

    Falk Hofmann

    Full Text Available There is growing evidence that amorphous silica nanoparticles cause toxic effects on lung cells in vivo as well as in vitro and induce inflammatory processes. The phagocytosis of silica by alveolar macrophages potentiates these effects. To understand the underlying molecular mechanisms of silica toxicity, we applied a co-culture system including the immortal alveolar epithelial mouse cell line E10 and the macrophage cell line AMJ2-C11. In parallel we exposed precision-cut lung slices (lacking any blood cells as well as residual alveolar macrophages of wild type and P2rx7-/- mice with or without AMJ2-C11 cells to silica nanoparticles. Exposure of E10 cells as well as slices of wild type mice resulted in an increase of typical alveolar epithelial type 1 cell proteins like T1α, caveolin-1 and -2 and PKC-β1, whereas the co-culture with AMJ2-C11 showed mostly a slightly lesser increase of these proteins. In P2rx7-/- mice most of these proteins were slightly decreased. ELISA analysis of the supernatant of wild type and P2rx7-/- mice precision-cut lung slices showed decreased amounts of IL-6 and TNF-α when incubated with nano-silica. Our findings indicate that alveolar macrophages influence the early inflammation of the lung and also that cell damaging reagents e.g. silica have a smaller impact on P2rx7-/- mice than on wild type mice. The co-culture system with an organotypic lung slice is a useful tool to study the role of alveolar macrophages during lung injury at the organoid level.

  4. Alveolar ridge preservation in the esthetic zone.

    Science.gov (United States)

    Jung, Ronald E; Ioannidis, Alexis; Hämmerle, Christoph H F; Thoma, Daniel S

    2018-02-27

    In the esthetic zone, in the case of tooth extraction, the clinician is often confronted with a challenge regarding the optimal decision-making process for providing a solution using dental implants. This is because, after tooth extraction, alveolar bone loss and structural and compositional changes of the covering soft tissues, as well as morphological alterations, can be expected. Ideally, the therapeutic plan starts before tooth extraction and it offers three options: spontaneous healing of the extraction socket; immediate implant placement; and techniques for preserving the alveolar ridge at the site of tooth removal. The decision-making process mainly depends on: (i) the chosen time-point for implant placement and the ability to place a dental implant; (ii) the quality and quantity of soft tissue in the region of the extraction socket; (iii) the remaining height of the buccal bone plate; and (iv) the expected rates of implant survival and success. Based on scientific evidence, three time-periods for alveolar ridge preservation are described in the literature: (i) soft-tissue preservation with 6-8 weeks of healing after tooth extraction (for optimization of the soft tissues); (ii) hard- and soft-tissue preservation with 4-6 months of healing after tooth extraction (for optimization of the hard and soft tissues); and (iii) hard-tissue preservation with > 6 months of healing after tooth extraction (for optimization of the hard tissues). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Oral epithelial dysplasia classification systems

    DEFF Research Database (Denmark)

    Warnakulasuriya, S; Reibel, J; Bouquot, J

    2008-01-01

    . In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine...

  6. Repair of a defect following the removal of an impacted maxillary canine by orthodontic tooth movement: a case report.

    Science.gov (United States)

    Lei, Wai Yip; Rabie, A Bakr M; Wong, Ricky Wk

    2010-02-15

    This case report describes a 13-year-old boy with alveolar bony defect resulted from surgical removal of impacted upper canine transposed in the anterior region. The boy had a normal occlusion with malposition of upper central and lateral incisors. The treatment objectives were to align teeth, close spaces by mesial movement of the buccal segments in the upper jaw to repair bone loss. Fixed appliance with palatal root torque was used for the mesial movements, levelling, and alignment of teeth.Orthodontic tooth movement consisted of a sequence of root movement in a direction to increase the thickness of the labial cortical plate of bone, could ensure healthier periodontium. A healthier periodontium prior to space closure ensured repair of alveolar bony defect after surgical intervention. Orthodontic tooth movement should be added to our armamentarium for the repair of alveolar bony defect.

  7. [Repair effect of BMSCs on digestive tract injury].

    Science.gov (United States)

    Jia, Guiqing; Zhang, Mingming; Wu, Xiaoting

    2009-06-01

    To investigate the effect of BMSCs on the repair of digestive tract injury and its mechanisms. Recent literature on the effect of BMSCs on the repair of digestive tract injury was reviewed. BMSCs had the potency of self-replication, proliferation and multipotential differentiation, which played an important role in the repair of digestive tract injury. The probable mechanisms included: BMSCs' ability of migrating to the injured tissue and inhibiting the host immune response; BMSCs' dedifferentiation and redifferentiation; BMSCs' direct differentiation into the epithelial cells or the stem cells of digestive tract; BMSCs' fusion with the stem cells or the mature epithelial cells of digestive tract; BMSCs' participation in the reconstruction of injured microenvironment. BMSCs participates in the repair of digestive tract injury and has a bright future in the treatment of digestive system disease.

  8. Repairing organs: lessons from intestine and liver

    OpenAIRE

    Gehart Helmuth; Clevers Hans

    2015-01-01

    The concept of organ regeneration has fascinated humanity from ancient mythology to modern science fiction. Recent advances offer the potential to soon bring such technology within the grasp of clinical medicine. Rapidly expanding insights into the intrinsic repair processes of the intestine and liver have uncovered significant plasticity in epithelial tissues. Harnessing this knowledge researchers have recently created culture systems that enable the expansion of stem cells into transplantab...

  9. Three-Dimensional Cone Beam Computed Tomography Volumetric Outcomes of rhBMP-2/Demineralized Bone Matrix versus Iliac Crest Bone Graft for Alveolar Cleft Reconstruction.

    Science.gov (United States)

    Liang, Fan; Yen, Stephen L-K; Imahiyerobo, Thomas; Sanborn, Luke; Yen, Leia; Yen, Daniel; Nazarian, Sheila; Jedrzejewski, Breanna; Urata, Mark; Hammoudeh, Jeffrey

    2017-10-01

    Recent studies indicate that recombinant human bone morphogenetic protein-2 (rhBMP-2) in a demineralized bone matrix scaffold is a comparable alternative to iliac bone autograft in the setting of secondary alveolar cleft repair. Postreconstruction occlusal radiographs demonstrate improved bone stock when rhBMP-2/demineralized bone matrix (DBM) scaffold is used but lack the capacity to evaluate bone growth in three dimensions. This study uses cone beam computed tomography to provide the first clinical evaluation of volumetric and density comparisons between these two treatment modalities. A prospective study was conducted with 31 patients and 36 repairs of the alveolar cleft over a 2-year period. Twenty-one repairs used rhBMP-2/DBM scaffold and 14 repairs used iliac bone grafting. Postoperatively, occlusal radiographs were obtained at 3 months to evaluate bone fill; cone beam computed tomographic images were obtained at 6 to 9 months to compare volumetric and density data. At 3 months, postoperative occlusal radiographs demonstrated that 67 percent of patients receiving rhBMP-2/DBM scaffold had complete bone fill of the alveolus, versus 56 percent of patients in the autologous group. In contrast, cone beam computed tomographic data showed 31.6 percent (95 percent CI, 24.2 to 38.5 percent) fill in the rhBMP-2 group compared with 32.5 percent (95 percent CI, 22.1 to 42.9 percent) in the autologous population. Density analysis demonstrated identical average values between the groups (1.38 g/cc). These data demonstrate comparable bone regrowth and density values following secondary alveolar cleft repair using rhBMP-2/DBM scaffold versus autologous iliac bone graft. Cone beam computed tomography provides a more nuanced understanding of true bone regeneration within the alveolar cleft that may contribute to the information provided by occlusal radiographs alone. Therapeutic, II.

  10. Brain aneurysm repair

    Science.gov (United States)

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  11. Intranasal Fentanyl Intoxication Leading to Diffuse Alveolar Hemorrhage.

    Science.gov (United States)

    Ruzycki, Shannon; Yarema, Mark; Dunham, Michael; Sadrzadeh, Hossein; Tremblay, Alain

    2016-06-01

    Increasing rates of opioid abuse, particularly fentanyl, may lead to more presentations of unusual effects of opioid toxicity. Diffuse alveolar hemorrhage is a rare complication of fentanyl overdose. A 45-year-old male presented in hypoxic respiratory failure secondary to diffuse alveolar hemorrhage requiring intubation. Comprehensive drug screening detected fentanyl without exposure to cocaine. Further history upon the patient's recovery revealed exposure to snorted fentanyl powder immediately prior to presentation. Diffuse alveolar hemorrhage is a potential, though rare, presentation of opioid intoxication. Recognition of less common complications of opioid abuse such as diffuse alveolar hemorrhage is important in proper management of overdoses.

  12. Pulmonary epithelial permeability after inhaling saline, distilled water ''fog'' and cold air

    International Nuclear Information System (INIS)

    Borland, C.; Chamberlain, A.; Barber, B.; Higenbottam, T.

    1985-01-01

    It is recognized that hyperventilation of cold air and the inhalation of fine mists of distilled water provoke significant bronchoconstriction in the asthmatic individual, yet little is known as to how these provocations affect the structural integrity of the alveolar epithelial membrane. In 11 normal subjects, the following effects have been studied: cold air hyperventilation for three minutes, inhalation of 80 L of ultrasonically nebulized distilled water ''fog,'' and 80 L of isotonic saline ''fog'' on the half time clearance (T1/2) from the alveoli of technetium 99m diethylene triamine pentaacetate (DTPA), inhaled as an aerosol. The DTPA T1/2 provided a measurement of pulmonary epithelial permeability

  13. Mismatch Repair*

    Science.gov (United States)

    Fishel, Richard

    2015-01-01

    Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that the MSH proteins initiate MMR by recognizing a mismatch and forming multiple extremely stable ATP-bound sliding clamps that diffuse without hydrolysis along the adjacent DNA. The function(s) of MLH/PMS proteins is less clear, although they too bind ATP and are targeted to MMR by MSH sliding clamps. Structural analysis combined with recent real-time single molecule and cellular imaging technologies are providing new and detailed insight into the thermal-driven motions that animate the complete MMR mechanism. PMID:26354434

  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. DNA repair , cell repair and radiosensitivity

    International Nuclear Information System (INIS)

    Zhestyanikov, V.D.

    1983-01-01

    Data obtained in laboratory of radiation cytology and literature data testifying to a considerable role of DNA repair in cell sensitivity to radiation and chemical DNA-tropic agents have been considered. Data pointing to the probability of contribution of inducible repair of DNA into plant cells sensitivity to X-rays are obtained. Certain violations of DNA repair do not result in the increase of radiosensitivity. It is assumed that in the cases unknown mechanisms of DNA repair operate

  16. Digital radiographic evaluation of alveolar bone loss, density and lamina dura integrity on post splinting mandibular anterior with chronic periodontitis

    Science.gov (United States)

    Rafini, F.; Priaminiarti, M.; Sukardi, I.; Lessang, R.

    2017-08-01

    The healing of periodontal splinting can be detected both with clinical and radiographic examination. In this study, the alveolar bone was evaluated by radiographic digital periapical analysis. Periodontal tooth splinting is periodontal support therapy used to prevent periodontal injury during repair and regeneration of periodontal therapy. Radiographic digital periapical analysis of alveolar bone in the mandibular anterior region with chronic periodontitis and 2/3 cervical bone loss after three months of periodontal splinting. Eighty four proximal site (43 mesial and 41 distal) from 16 patients with chronic periodontitis and treated with spinting were examined by taking periapical digital radiographic at day 1 and 91. The bone loss, bone density and utility of lamina dura were evaluated. The statistical analysis after three months evaluation using T-test for bone loss, Wilcoxon sign rank test for bone density and utility lamina dura showed no significantly differences (palveolar bone loss after three months splinting.

  17. 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

  18. Alveolar soft part sarcoma: A rare diagnosis

    Directory of Open Access Journals (Sweden)

    Priyanka Sarkar

    2013-01-01

    Full Text Available Alveolar soft-part sarcoma (ASPS is an extremely rare disease arising from connective tissues with a propensity for recurrence and metastasis. Clinically, it can be confused with hemangioma or arterio-venous malformations. Thus, a high index of suspicion and histopathological examination are required to make a definitive diagnosis. We report a case of recurrent ASPS in a young female with multiple sites involvement without any features of metastasis who has been treated with excision of the symptomatic lesions followed by chemotherapy.

  19. 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.

  20. Fine structural observation on repair processes in experimental ulcer of the rat gastric mucosa

    International Nuclear Information System (INIS)

    Saito, Takiko

    1982-01-01

    Experimental stomach ulcer of the rat was produced by clamping method. Repair processes of the epithelial and glandular cells were examined by LM, SEM, TEM and autoradiograph with 3 H-thymidine at various times after removal of the clamp. The epithelial cells in the vicinity of the defect consisted of the surface cells with a few mucous granuls, parietal cells, endocrine cells and fibrillovesicular cells of Hammond and LaDuer during repair processes. The chief cells appeared after 12 days. After 5 weeks, the defect was completely covered with the epithelium. All kind of the epithelial cells except fibrillovesicular cells can incorporate thymidine precursor during regeneration. (author)

  1. Alveolar bone loss in obese subjects.

    Science.gov (United States)

    Alabdulkarim, Maher; Bissada, Nabil; Al-Zahrani, Mohammad; Ficara, Anthony; Siegel, Burton

    2005-04-01

    Obesity was found to be significantly associated with periodontal disease prevalence as measured by probing depth and clinical attachment loss. The aim of this study was to examine if obesity correlates with chronic periodontitis as diagnosed by radiographic alveolar bone loss. Four hundred subjects > or =18 years old were included; 200 with body mass index (BMI) > or =30 kg/m2 (obese) and 200 with BMI periodontitis. Obesity was found to be significantly associated with periodontitis in the uni-variate regression analysis (OR = 2.37, 95% CI, 1.55-3.63). After adjusting for age, gender, smoking, employment, diabetes, marital status, and number of teeth present, obese subjects were found to be 1.86 times more likely to have periodontitis (95% CI, 0.99-3.51) than non-obese ones. When the sample was stratified based on age, the multivariate association was statistically significant among individuals or = 40 years of age the association was statistically insignificant (OR = 1.06, 95% CI, 0.57-1.95). Stratifying the sample based on gender and smoking status revealed a stronger association among females than males (OR = 3.14 vs. 1.95) and among non-smokers than smokers (OR = 3.36 vs. 2.22). Obesity is associated with increased prevalence of periodontitis as measured by radiographic alveolar bone loss, especially among younger individuals. Prevention and management of obesity may be considered to promote better systemic and periodontal health.

  2. Prominent Intracytoplasmic Crystals in Alveolar Soft Part Sarcoma (ASPS): An Aid in Cytological Diagnosis.

    Science.gov (United States)

    Mannan, Rahul; Bhasin, Tejinder Singh; Kaur, Parampreet; Manjari, Mridu; Gill, Karamjit Singh

    2014-02-01

    Alveolar soft part sarcoma (ASPS) is a rare neoplasm of unknown histogenesis with poor prognosis. Due to the epithelioid appearance of the neoplastic cells, ASPS may resemble many neoplastic conditions, such as metastatic epithelial cell tumours with clear cell change, metastatic renal cell carcinoma, granular cell tumour, epithelioid sarcoma, malignant melanoma and even paragangliomas. Presence of abundant, rod like crystals in the cytoplasm of tumour cells is an important finding characteristic of this tumour, which helps in differentiating it from the other entities. The case study highlights the importance of correlating cytological features that help in reaching the diagnosis such as the background, cell morphology and presence of characteristic rod shaped crystals as immunohistochemical studies are often non-conclusive. The case also is unique as it demonstrates presence of intra-cytoplamic crystals in such abundance.

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

    African Journals Online (AJOL)

    2017-05-16

    May 16, 2017 ... development of alveolar osteitis were obtained and analyzed. Comparative statistics were done using ... KEY WORDS: Alveolar osteitis, chlorhexidine, prevention, warm saline. Department of Dental. Surgery .... healing by inducing vasodilatation of the vasculature of oral cavity, and thus enhances migration ...

  4. 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...

  5. 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…

  6. Classification of alveolar bone destruction patterns on maxillary ...

    African Journals Online (AJOL)

    Objective: The defective diagnosis of alveolar structures is one of most serious handicaps when assessing available periodontal treatment options for the prevention of tooth loss. The aim of this research was to classify alveolar bone defects in the maxillary molar region which is a challenging area for dental implant ...

  7. Pulmonary alveolar proteinosis in a child from an informal settlement

    African Journals Online (AJOL)

    clinical, histopathological, biochemical and genetic data.[3]. Surfactant homeostasis is critical for lung function and is tightly regulated, in part by pulmonary granulocyte-macrophage colony- stimulating factor (GM-CSF), which is required for surfactant clearance by alveolar macrophages and alveolar macrophage maturation.

  8. Alveolar ridge preservation and biologic width management for ...

    African Journals Online (AJOL)

    Alveolar bone atrophy is a chronically progressive, irreversible process which results in bone loss in both the buccal, lingual and apico-coronal region. Without bone preservation measures, bone resorption is experienced and continues for life. Preservation of alveolar ridge is indicated when a tooth-supported fixed partial ...

  9. Diffuse alveolar hemorrhage in a young woman with systemic lupus ...

    African Journals Online (AJOL)

    Diffuse Alveolar Hemorrhage (DAH) is rarely reported complication of Systemic Lupus Erythematosus (SLE). A young woman diagnosed SLE, with a previously normal plain chest radiograph, developed acute onset cough, dyspnoea and hemoptysis. The repeat urgent chest radiograph revealed alveolar opacities. The triad ...

  10. Cultured fibroblasts from alveolar and gingival mucosae are biologically and biochemically different

    International Nuclear Information System (INIS)

    Lanz, J.; Banes, A.

    1986-01-01

    Tissues removed from the alveolar or gingival mucosa of 5 patients were separated into cell populations to assess the relative contributions each might make in wound healing intraorally. Growth curves and protein synthetic patterns of fibroblasts, free of epithelial cells, were obtained at pass 5. The morphologies of the two cell types were not grossly different. However, the AM cells (alveolar mucosa) had a generation time (gt) of 18.7 hrs. whereas the gt for KG cells (keratinized gingiva) was 49.6 hrs. Cells labeled in vitro with 35 S-methionine had distinct patterns of protein synthesis. The AM cells had more of the 275, 220, 92, 80, 50 and 46 kd bands on the autoradiogram of a 7.5% PAGE slab gel than did the KG cells. The KG cells contained more of the 165, 84, 68, 60, 54, 51, 43, 36, and 32a kd bands. In a wound healing situation, the AM cells may be the first fibroblasts to rapidly divide to fill a defect, whereas the KG cells may require a longer time period to divide. This is the first report of biochemical and biological differences in these two fibroblast populations from cultured, human tissues

  11. Electron-microscopic studies of alveolar macrophages from gamma-ray irradiated guinea pigs

    International Nuclear Information System (INIS)

    Krystev, Kh.; Najdenski, Kh.M.; Velyanov, D.K.; Radoevska, S.A.

    1988-01-01

    The alveolar macrophages (AM) were obtained from whole body gamma-irradiated guinea pigs (0.5 Gy and 2 Gy; 92.5 rad/min). The cell suspension contained granulocytes, lymphocytes and disintegrating epithelial and white blood cells, as well as two types of microphages: large (possessing nuclei of saddle bag-like or highly folded form) and small (with spherical or eggshaped nuclei). Eleven electronograms were presented showing all ultrastuctural changes of both small and large AM. The morphological differences between the small and large alveolar macrophages were slight. Marked changes were observed in the large AM on day 1 following 0.5 Gy irradiation: a considerable increase in dimensions of phagosomes turning in digestive vacuoles, lamellarly limited and containing osmiophilic, irregularly formed, densely or lamellarly arranged matter; folded nuclei with slightly vacuolized cytoplasm. The ultrastructural changes in the AM of sublethal dose (2 Gy) irradiated animals were stronger and regenerative processes in them were less possible. On day 30 after irradiation several damaged AM were observed with large digestive vacuoles of fine-grain content, vacuolized endoplasmic reticulum, entirely lyzed nuclear chromatin and free nuclei without cytoplasm. All observations were a convincing indication that guinea pigs AM were more radiosensitive than that obtained from rats and mice

  12. Mannose-functionalized solid lipid nanoparticles are effective in targeting alveolar macrophages.

    Science.gov (United States)

    Costa, Ana; Sarmento, Bruno; Seabra, Vítor

    2018-03-01

    Mannose receptor is highly expressed on alveolar macrophages, being a potential target to promote the specific local drug delivery of anti-tuberculosis agents through the use of functionalized nanocarriers. In this work, isoniazid (Isn)-loaded solid lipid nanoparticles (SLN), reinforced with stearylamine (SA) were produced by double emulsion technique and further surface-functionalized with mannose in a straightforward chemical approach. Upon pre-formulation assessment, SLN close to 500 nm average size, positively charged and with association efficiency of ISN close to 50% were obtained. Functionalization with mannose was performed after SLN production and confirmed by Fourier transform infrared spectroscopy (FTIR). Both functionalized and non-functionalized SLN demonstrated to devoid of toxicity when tested in human lung epithelial cell line (NCI-H441) and differentiated THP-1 (dTHP-1), reducing the intrinsic cytotoxicity of Isn when incorporated into SLN. Uptake studies were conducted on same macrophage-like cells and the results showed that fluorescent mannosylated SLN (M-SLN) were more efficient in be internalized comparatively to SLN. Moreover, the uptake of M-SLN was reduced when cells were pre-incubated with mannose, demonstrating the receptor-dependence internalization of functionalized SLN. These functionalized nanocarriers may represent a useful platform to target alveolar macrophages for delivering anti-infective drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Serum YKL-40 is a reliable biomarker for pulmonary alveolar proteinosis.

    Science.gov (United States)

    Bonella, Francesco; Long, Xiaoping; He, Xuan; Ohshimo, Shinichiro; Griese, Matthias; Guzman, Josune; Costabel, Ulrich

    2017-10-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar filling. YKL-40, a chitinase-like protein produced by macrophages and epithelial cells, is increased in patients with interstitial lung diseases. We aimed to evaluate the role of YKL-40 as a biomarker for PAP. A total of 34 patients with autoimmune PAP and 50 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF). Chitinase coding gene polymorphisms (CHI3L1-329 and -131) were detected by PCR and pyrosequencing. Correlations between serum YKL-40 levels and disease outcome were analysed. Baseline serum and BALF levels of YKL-40 were higher in PAP patients than in controls (286 ± 27 ng/mL vs 42 ± 4 ng/mL, P 40 levels correlated with diffusing capacity of the lung for carbon monoxide (DL CO ) at baseline (P = 0.002) and over time (P 40 levels than those who remained stable or improved (P 40. YKL-40 is elevated in serum and BALF of PAP patients, and may be of clinical utility to predict outcome in PAP. © 2017 Asian Pacific Society of Respirology.

  14. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

    International Nuclear Information System (INIS)

    Lipchik, R.J.; Chauncey, J.B.; Paine, R.; Simon, R.H.; Peters-Golden, M.

    1990-01-01

    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung

  15. Decreased IGF Type 1 Receptor Signaling in Mammary Epithelium during Pregnancy Leads to Reduced Proliferation, Alveolar Differentiation, and Expression of Insulin Receptor Substrate (IRS)-1 and IRS-2

    Science.gov (United States)

    Sun, Zhaoyu; Shushanov, Sain; LeRoith, Derek

    2011-01-01

    The IGFs and the IGF type 1 receptor (IGF-1R) are essential mediators of normal mammary gland development in mice. IGF-I and the IGF-1R have demonstrated functions in formation and proliferation of terminal end buds and in ductal outgrowth and branching during puberty. To study the functions of IGF-1R during pregnancy and lactation, we established transgenic mouse lines expressing a human dominant-negative kinase dead IGF-1R (dnhIGF-1R) under the control of the whey acidic protein promoter. We provide evidence that the IGF-1R pathway is necessary for normal epithelial proliferation and alveolar formation during pregnancy. Furthermore, we demonstrate that the whey acidic protein-dnhIGF-1R transgene causes a delay in alveolar differentiation including lipid droplet formation, lumen expansion, and β-casein protein expression. Analysis of IGF-1R signaling pathways showed a decrease in P-IGF-1R and P-Akt resulting from expression of the dnhIGF-1R. We further demonstrate that disruption of the IGF-1R decreases mammary epithelial cell expression of the signaling intermediates insulin receptor substrate (IRS)-1 and IRS-2. No alterations were observed in downstream signaling targets of prolactin and progesterone, suggesting that activation of the IGF-1R may directly regulate expression of IRS-1/2 during alveolar development and differentiation. These data show that IGF-1R signaling is necessary for normal alveolar proliferation and differentiation, in part, through induction of signaling intermediates that mediate alveolar development. PMID:21628386

  16. Epithelial Myeloid-Differentiation Factor 88 Is Dispensable during Klebsiella Pneumonia.

    Science.gov (United States)

    Anas, Adam A; Claushuis, Theodora A M; Mohan, Rajiv A; Christoffels, Vincent M; Aidinis, Vassilis; Florquin, Sandrine; Van't Veer, Cornelis; Hou, Baidong; de Vos, Alex F; van der Poll, Tom

    2017-05-01

    Klebsiella pneumoniae is a common cause of pneumonia. Previous studies have documented an important role for Toll-like receptors (TLRs) expressed by myeloid cells in the recognition of K. pneumoniae and the initiation of a protective immune response. Lung epithelial cells also express TLRs and can participate in innate immune defense. The aim of this study was to examine the role of the common TLR adaptor protein myeloid-differentiation factor (MyD) 88 in lung epithelium during host defense against K. pneumoniae-induced pneumonia. To this end, we first crossed mice expressing cre recombinase under the control of the surfactant protein C (SftpCcre) or the club cell 10 kD (CC10cre) promoter with reporter mice to show that SftpCcre mice mainly express cre in type II alveolar cells, whereas CC10cre mice express cre almost exclusively in bronchiolar epithelial cells. We then generated mice with cell-targeted deletion of MyD88 in type II alveolar (SftpCcre-MyD88-lox) and bronchiolar epithelial (CC10cre-MyD88-lox) cells, and infected them with K. pneumoniae via the airways. Bacterial growth and dissemination were not affected by the loss of MyD88 in SftpCcre-MyD88-lox or CC10cre-MyD88-lox mice compared with control littermates. Furthermore, inflammatory responses induced by K. pneumoniae in the lung were not dependent on MyD88 expression in type II alveolar or bronchiolar epithelial cells. These results indicate that MyD88 expression in two distinct lung epithelial cell types does not contribute to host defense during pneumonia caused by a common human gram-negative pathogen.

  17. Hydroxyapatite paste Ostim, without elevation of full-thickness flaps, improves alveolar healing stimulating BMP- and VEGF-mediated signal pathways: an experimental study in humans.

    Science.gov (United States)

    Canuto, R A; Pol, R; Martinasso, G; Muzio, G; Gallesio, G; Mozzati, M

    2013-08-01

    Tooth extraction is considered as the starting point of jaw atrophy via osteoclast activity stimulation. The maintenance of dental alveolar bone depends on surgery procedure and use of materials to maintain prior space favoring bone regeneration. Among substitutes used in dentistry to fill bone defects, Ostim-Pastes (Ostim) is a nanocrystalline paste tested for treatment of severe clinical conditions. This research first investigated the effect of Ostim on alveolar healing, comparing in the same healthy subjects, an Ostim-filled socket with a not-filled one. Moreover, it also proposed a new surgical protocol for the post-extractive socket treatment using the graft materials without elevation of full-thickness flaps. Fourteen patients were enrolled to bilateral maxillary or mandibular extraction that was performed without elevation of full-thickness flaps. In each patient, one socket was filled using Ostim, and the other one was allowed to undergo natural healing. No suture was carried out. Clinical and biologic parameters were screened at 1, 7, and 14 days. Obtained results evidenced that nanocrystalline hydroxyapatite supports bone regeneration, increasing the synthesis of pro-osteogenic factors as bone morphogenetics protein (BMP)-4, BMP-7, alkaline phosphatase, and osteocalcin. Moreover, filling post-extractive socket with nanocrystalline hydroxyapatite paste leads to a complete epithelialization already at 7 days after extraction, despite the fact that the teeth were extracted without elevation of full-thickness flaps . The improved epithelialization is mediated by increased vascular endothelial growth factor (VEGF) expression. No significant change was observed in inflammatory parameters, with exception of an early and transient IL-1β induction, that could trigger and improve alveolar healing. Clinical and biomolecular observations of this explorative study evidenced that nanocrystalline hydroxyapatite improves alveolar socket healing, increasing angiogenesis

  18. Cleft Patient-Reported Postoperative Donor Site Pain Following Alveolar Autologous Iliac Crest Bone Grafting: Comparing Two Minimally Invasive Harvesting Techniques.

    Science.gov (United States)

    Raposo-Amaral, Cesar Augusto; Denadai, Rafael; Chammas, Danilo Zanardo; Marques, Frederico Figueiredo; Pinho, André Silveira; Roberto, Wellington Matheus; Buzzo, Celso Luiz; Raposo-Amaral, Cassio Eduardo

    2015-10-01

    Autologous bone grafting is still considered the standard method for alveolar cleft repair. However, donor site morbidities remain a relevant problem in cleft care. Thus, the authors assessed postoperative donor site pain in cleft patients who underwent alveolar cleft repair by iliac crest bone graft transferring through a prospective randomized study comparing 2 minimally invasive harvesting techniques. Fifty-six consecutive patients with cleft lip and palate who underwent iliac crest bone grafting for alveolar cleft repair were randomly divided into 2 groups: bone graft harvested by minimally invasive techniques without (group 1) and with (group 2) periosteum elevation. Postoperative donor site pain was evaluated using a unidimensional numerical pain intensity rating scale (0, "no pain;" 10, "worst pain imaginable") at 1, 3, 6, 9, and 12 hours after the procedures and on the 3rd, 7th, 14th, 21st, and 28th days after surgeries. Intergroup comparisons were performed. The mean measurements of donor site pain revealed no significant differences (all P > 0.05) in any of the evaluated postoperative period comparisons between groups 1 and 2. There was a greater number (P < 0.05) of group 1 patients who reported "no pain" in the donor site compared with group 2, suggesting that periosteum elevation may play a role in pain intensity measurement. This prospective randomized study showed no difference in pain intensity among cleft patients who had postoperative pain. However, a greater number of patients in group 1 reported "no pain" in comparison to patients in group 2.

  19. Healing of periodontal defects and calcitonin gene related peptide expression following inferior alveolar nerve transection in rats.

    Science.gov (United States)

    Lv, Linlin; Wang, Yanzhi; Zhang, Jing; Zhang, Ting; Li, Shu

    2014-06-01

    The roles of nerve and neuropeptides in the process of bone formation and remolding have been studied previously. However, the effects of nervous system and neuropeptide on periodontal alveolar bone formation remained unknown. The aim of this study was to assess the effect of innervation on regeneration of alveolar bone and expression levels of calcitonin gene related peptide (CGRP) in periodontal tissues of rats, so as to have a better understanding of the effect of nerve and its related neuropeptide on periodontal tissue regeneration. Rats received transection of the left inferior alveolar nerve and a surgery to produce bilateral periodontal defect, then the alveolar tissue was obtained from animals of each group at week 1, 2, 4, 6 and 8 weeks after operation, respectively. Hematoxylin and eosin staining, and Masson staining were performed to evaluate the ability to restore and repair periodontal tissues at 4, 6 and 8 after surgery. Then new bone formation area and mineralized area were quantified using imagepro-plus6.0 software after pictures were taken under the microscope and SPSS17.0 was used for statistical analysis. Immunohistochemical staining was applied to investigate the expression of CGRP at 1, 2, 4, 6 and 8 weeks. Rats received transection of the left inferior alveolar nerve surgery and were then sacrificed at day 1, 3, 7, 14, 21, 28 after the operation. The change of CGRP expression in periodontal tissue was detected using immunohistochemical methods. The results showed that the volume of new bone formation was not significantly difference between the experimental and control groups, but the mineralized new bone area between the two groups was statistically significant. The level of CGRP expression was lower than normal at week 1, and then it began to rise in the next stage. The plateau, at higher than normal level, was reached at 6 weeks post-surgery. Results of transection of the left inferior alveolar nerve demonstrated the expression of CGRP

  20. Iatrogenic injury to the inferior alveolar nerve

    DEFF Research Database (Denmark)

    Hillerup, Søren

    2008-01-01

    assessing tactile, thermal, and positional perception as well as two-point discrimination and pain. In 48 patients with IAN injuries of differing etiologies who did not undergo surgery, 32 patients with injury associated with third molar surgery exhibited significant spontaneous improvement of sensory...... function. Recovery improvement of sensory function was insignificant in the patients with other etiologies. In most patients the level of sensory perception was such that microsurgical repair was only occasionally indicated. Four patients had microsurgical repair; the outcome was favourable in three. IAN...

  1. Interaction of the pathogenic mold Aspergillus fumigatus with lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Nir eOsherov

    2012-09-01

    Full Text Available Aspergillus fumigatus is an opportunistic environmental mold that can cause severe allergic responses in atopic individuals and poses a life-threatening risk for severely immunocompromised patients. Infection is caused by inhalation of fungal spores (conidia into the lungs. The initial point of contact between the fungus and the host is a monolayer of lung epithelial cells. Understanding how these cells react to fungal contact is crucial to elucidating the pathobiology of Aspergillus-related disease states. The experimental systems, both in vitro and in vivo, used to study these interactions, are described. Distinction is made between bronchial and alveolar epithelial cells. The experimental findings suggest that lung epithelial cells are more than just innocent bystanders or a purely physical barrier against infection. They can be better described as an active extension of our innate immune system, operating as a surveillance mechanism that can specifically identify fungal spores and activate an offensive response to block infection. This response includes the internalization of adherent conidia and the release of cytokines, antimicrobial peptides and reactive oxygen species. In the case of allergy, lung epithelial cells can dampen an over-reactive immune response by releasing anti-inflammatory compounds such as kinurenine. This review summarizes our current knowledge regarding the interaction of A. fumigatus with lung epithelial cells. A better understanding of the interactions between A. fumigatus and lung epithelial cells has therapeutic implications, as stimulation or inhibition of the epithelial response may alter disease outcome.

  2. Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Kenji; Yokoro, Kenjiro (Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology); Clifton, K.H.; Gould, M.N.

    1991-12-01

    We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: (a) in the presence of E{sub 2} and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, (b) in cortisol deficient rats, Prl and E{sub 2} synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, (c) E{sub 2} without progesterone stimulates alveolar colony formation in the presence of cortical and high Prl, (d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E{sub 2}, cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure. (author).

  3. Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer

    International Nuclear Information System (INIS)

    Kamiya, Kenji; Yokoro, Kenjiro; Clifton, K.H.; Gould, M.N.

    1991-01-01

    We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E 2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E 2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E 2 without progesterone stimulates alveolar colony formation in the presence of cortical and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E 2 , cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure. (author)

  4. γδ T cells in homeostasis and host defence of epithelial barrier tissues.

    Science.gov (United States)

    Nielsen, Morten M; Witherden, Deborah A; Havran, Wendy L

    2017-12-01

    Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body - namely, the epidermis and the intestine - and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance. Finally, we describe epithelium-specific butyrophilin-like molecules and briefly review their emerging role in selectively shaping and regulating epidermal and intestinal γδ T cell repertoires.

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

    OpenAIRE

    Prakash B Billakanti

    2016-01-01

    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 ...

  6. Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

    OpenAIRE

    Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

    2013-01-01

    Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival sof...

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

    Directory of Open Access Journals (Sweden)

    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.

  8. [Massive alveolar haemorrhage in Wegener's granulomatosis].

    Science.gov (United States)

    Valero-Roldán, J; Nuñez-Castillo, D; Fernández-Fígares, C; López-Leiva, I

    2014-01-01

    Wegener's granulomatosis is a systemic vasculitis with involvement of primary granulomatous upper and lower respiratory tract, glomerulonephritis and vasculitis of small vessels. The lung disease ranges from asymptomatic pulmonary nodules to pulmonary infiltrates and fulminant alveolar haemorrhage. The prognosis is poor due to kidney and respiratory failure, although the data are changing due to new treatments with glucocorticoids and cyclophosphamide. We report a case with severe lung disease, which after appropriate anamnesis, multiple tests, and optimal sequential action, the patient was diagnosed with Wegener's granulomatosis. This disease has a low incidence in the Emergency Department, where the patient history supported by the appropriate additional provides a diagnostic suspicion. It is important that the Emergency Department has the skills to manage the stability in these patients in order to resolve their symptoms. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  9. Rapid road repair vehicle

    Science.gov (United States)

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  10. Identification of genes differentially regulated in rat alveolar bone wound healing by subtractive hybridization.

    Science.gov (United States)

    Ohira, T; Myokai, F; Shiomi, N; Yamashiro, K; Yamamoto, T; Murayama, Y; Arai, H; Nishimura, F; Takashiba, S

    2004-07-01

    Periodontal healing requires the participation of regulatory molecules, cells, and scaffold or matrix. Here, we hypothesized that a certain set of genes is expressed in alveolar bone wound healing. Reciprocal subtraction gave 400 clones from the injured alveolar bone of Wistar rats. Identification of 34 genes and analysis of their expression in injured tissue revealed several clusters of unique gene regulation patterns, including the up-regulation at 1 wk of cytochrome c oxidase regulating electron transfer and energy metabolism, presumably occurring at the site of inflammation; up-regulation at 2.5 wks of pro-alpha-2 type I collagen involving the formation of a connective tissue structure; and up-regulation at 1 and 2 wks and down-regulation at 2.5 and 4 wks of ubiquitin carboxyl-terminal hydrolase l3 involving cell cycle, DNA repair, and stress response. The differential expression of genes may be associated with the processes of inflammation, wound contraction, and formation of a connective tissue structure.

  11. Histomorphometric analysis of rat alveolar wound healing with hydroxyapatite alone or associated to BMPs

    Directory of Open Access Journals (Sweden)

    Brandão Alexandre C.

    2002-01-01

    Full Text Available Several materials and techniques have been proposed to improve alveolar wound healing and decrease loss of bone height and thickness that normally follow dental extraction. The objective of this research was the histologic analysis of bone morphogenetic proteins implanted into dental alveoli of rats after extraction. A total of 45 adult male Wistar rats were divided into three groups of 15 animals each: control (no treatment, implanted with pure hydroxyapatite (HA, 3 mg and implanted with hydroxyapatite plus bone morphogenetic proteins (HA/BMPs, 3 mg. Five animals from each group were sacrificed at 7, 21 and 42 days after extraction for the histometric analyses of the osteoconductive potential of hydroxyapatite associated or not with BMPs. After dissection, fixation, decalcification and serial microtomy of 6-mm thick sections, the samples were stained with hematoxylin-eosin for histologic and histometric analyses. Both HA and HA/BMPs caused a delay in wound healing compared to control animals, evaluated by the percentage of bone tissue in the alveoli. The treatment with HA/BMPs had the greatest delay at 21 days, even though it produced values similar to the control group at 42 days. The materials did not improve alveolar repair in the normal period of wound healing and the association of HA/BMPs did not have osteoconductive properties with granulated hydroxyapatite as the vehicle.

  12. 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.

  13. DNA Mismatch Repair

    Science.gov (United States)

    MARINUS, M. G.

    2014-01-01

    DNA mismatch repair functions to correct replication errors in newly synthesized DNA and to prevent recombination between related, but not identical (homeologous), DNA sequences. The mechanism of mismatch repair is best understood in Escherichia coli and is the main focus of this review. The early genetic studies of mismatch repair are described as a basis for the subsequent biochemical characterization of the system. The effects of mismatch repair on homologous and homeologous recombination are described. The relationship of mismatch repair to cell toxicity induced by various drugs is included. The VSP (Very Short Patch) repair system is described in detail. PMID:26442827

  14. Molecular genetic and biochemical responses in human airway epithelial cell cultures exposed to titanium nanoparticles in vitro.

    Science.gov (United States)

    Aydın, Elanur; Türkez, Hasan; Hacımüftüoğlu, Fazıl; Tatar, Abdulgani; Geyikoğlu, Fatime

    2017-07-01

    Titanium nanoparticles (NPs) have very wide application areas such as paint, cosmetics, pharmaceuticals, and biomedical applications. And, to translate these nanomaterials to the clinic and industrial domains, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. Therefore, in this study, we aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly titanium (as titanium carbide, titanium carbo-nitride, titanium (II) oxide, titanium (III) oxide, titanium (IV) oxide, titanium nitride, titanium silicon oxide) NPs in human alveolar epithelial (HPAEpiC) and pharynx (HPPC) cell lines in vitro since inhalation is an important pathway for exposure to these NPs. HPAEpiC and HPPC cells were treated with titanium (0-100 µg/mL), NPs for 24 and 48 h, and then cytotoxicity was detected by, [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT), uptake of neutral red (NR) and lactate dehydrogenase (LDH) release assays, while genotoxicity was also analyzed by cDNA array - RT-PCR assay. According to the results of MTT, NR and LDH assays, all tested NPs induced cytotoxicity on both HPAEpiC and HPPC cells in a time- and dose-dependent manner. Determining and analyzing the gene expression profiles of HPAEpiC and HPPC cells, titanium NPs showed more changes in genes related to DNA damage or repair, oxidative stress, and apoptosis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2056-2064, 2017. © 2017 Wiley Periodicals, Inc.

  15. Mechanisms and Treatment of Deployment-Related Lung Injury: Repair of the Injured Epithelium

    Science.gov (United States)

    2017-10-01

    dataset of CT regions of interest for airway wall thickening, centrilobular nodularity, and air trapping, and tested several classifier configurations in...Alliance and from the International Institute for the Advancement of Medicine. These cultured epithelial cells form monolayers in an air liquid...centered around the alveolar ducts with PM from both Iraq and Afghanistan. - We also studied the effects of PM from the desert area of California

  16. Expression of matrix metalloproteinase-1 in alveolar macrophages, type II pneumocytes, and airways in smokers: relationship to lung function and emphysema.

    Science.gov (United States)

    Wallace, Alison M; Loy, Leanna B; Abboud, Raja T; D'Armiento, Jeanine M; Coxson, Harvey O; Muller, Nestor L; Kalloger, Steve; Li, Xing; Mark Elliott, W; English, John C; Finley, Richard J; Paré, Peter D

    2014-08-01

    An imbalance between proteolytic enzymes and their inhibitors is thought to be involved in the pathogenesis of chronic obstructive pulmonary disease. Matrix metalloproteinase-1, also known as interstitial collagenase, has been implicated as a potentially important proteinase in the genesis of chronic obstructive pulmonary disease and, more specifically, emphysema. We performed quantitative immunohistochemical assessment of matrix metalloproteinase-1 expression in the resected lung of 20 smokers/ex-smokers who had varying severity of airflow obstruction and emphysema and compared this with the lungs of 5 nonsmokers. Emphysema was measured using a morphometric measure of the lungs' surface area/volume ratio and with qualitative and quantitative computed tomography (CT) measures of emphysema. There were significantly more matrix metalloproteinase-1-expressing alveolar macrophages and type II pneumocytes as well as a greater percentage of small airways that stained positively for matrix metalloproteinase-1 in the lungs of smokers than in those of nonsmokers (p lung surface area/volume ratio and to qualitative estimates of emphysema on CT. These findings suggest that cigarette smoking increases expression of matrix metalloproteinase-1 in alveolar macrophages as well as in alveolar and small airway epithelial cells. Smokers who develop emphysema have increased alveolar macrophage expression of matrix metalloproteinase-1.

  17. Nicotine transport in lung and non-lung epithelial cells.

    Science.gov (United States)

    Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

    2017-11-01

    Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [ 3 H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Coronaviruses in polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J. W.; Bekker, C. P.; Voorhout, W. F.; Horzinek, M. C.; van der Ende, A.; Strous, G. J.; Rottier, P. J.

    1995-01-01

    Coronaviruses have a marked tropism for epithelial cells. In this paper the interactions of the porcine transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV-A59) with epithelial cells are compared. Porcine (LLC-PK1) and murine (mTAL) epithelial cells were grown on permeable

  19. Embryonic epithelial membrane transporters.

    Science.gov (United States)

    Horster, M

    2000-12-01

    Embryonic epithelial membrane transporters are organized into transporter families that are functional in several epithelial organs, namely, in kidney, lung, pancreas, intestine, and salivary gland. Family members (subtypes) are developmentally expressed in plasma membranes in temporospatial patterns that are 1) similar for one subtype within different organs, like aquaporin-1 (AQP1) in lung and kidney; 2) different between subtypes within the same organ, like the amiloride-sensitive epithelial sodium channel (ENaC) in lung; and 3) apparently matched among members of different transporter families, as alpha-ENaC with AQP1 and -4 in lung and with AQP2 in kidney. Finally, comparison of temporal expression patterns in early embryonic development of transporters from different families [e.g., cystic fibrosis transmembrane conductance regulator (CFTR), ENaC, and outer medullary potassium channel] suggests regulatory activating or inactivating interactions in defined morphogenic periods. This review focuses on embryonic patterns, at the mRNA and immunoprotein level, of the following transporter entities expressed in epithelial cell plasma membranes: ENaC; the chloride transporters CFTR, ClC-2, bumetanide-sensitive Na-K-Cl cotransporter, Cl/OH, and Cl/HCO(3); the sodium glucose transporter-glucose transporter; the sodium/hydrogen exchanger; the sodium-phosphate cotransporter; the ATPases; and AQP. The purpose of this article is to relate temporal and spatial expression patterns in embryonic and in early postnatal epithelia to developmental changes in organ structure and function.

  20. Hypospadias repair - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000158.htm Hypospadias repair - discharge To use the sharing features on this page, please enable JavaScript. Your child had hypospadias repair to fix a birth defect in which ...

  1. Anterior vaginal wall repair

    Science.gov (United States)

    ... may have you: Learn pelvic floor muscle exercises ( Kegel exercises ) Use estrogen cream in your vagina Try ... repair; Urinary incontinence - vaginal wall repair Patient Instructions Kegel exercises - self-care Self catheterization - female Suprapubic catheter ...

  2. Retinal detachment repair

    Science.gov (United States)

    ... area (the macula). This can help prevent further detachment of the retina. It also will increase the chance of preserving ... buckling; Vitrectomy; Pneumatic retinopexy; Laser retinopexy; Rhegmatogenous retinal detachment repair Images ... detachment repair - series References Connolly BP, Regillo ...

  3. Collision Repair Campaign

    Science.gov (United States)

    The Collision Repair Campaign targets meaningful risk reduction in the Collision Repair source category to reduce air toxic emissions in their communities. The Campaign also helps shops to work towards early compliance with the Auto Body Rule.

  4. Profibrotic potential of Prominin-1+ epithelial progenitor cells in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Lüscher Thomas F

    2011-09-01

    Full Text Available Abstract Background In idiopathic pulmonary fibrosis loss of alveolar epithelium induces inflammation of the pulmonary tissue followed by accumulation of pathogenic myofibroblasts leading eventually to respiratory failures. In animal models inflammatory and resident cells have been demonstrated to contribute to pulmonary fibrosis. Regenerative potential of pulmonary and extra-pulmonary stem and progenitor cells raised the hope for successful treatment option against pulmonary fibrosis. Herein, we addressed the contribution of lung microenvironment and prominin-1+ bone marrow-derived epithelial progenitor cells in the mouse model of bleomycin-induced experimental pulmonary fibrosis. Methods Prominin-1+ bone marrow-derived epithelial progenitors were expanded from adult mouse lungs and differentiated in vitro by cytokines and growth factors. Pulmonary fibrosis was induced in C57Bl/6 mice by intratracheal instillation of bleomycin. Prominin-1+ progenitors were administered intratracheally at different time points after bleomycin challenge. Green fluorescence protein-expressing cells were used for cell tracking. Cell phenotypes were characterized by immunohistochemistry, flow cytometry and quantitative reverse transcription-polymerase chain reaction. Results Prominin-1+ cells expanded from healthy lung represent common progenitors of alveolar type II epithelial cells, myofibroblasts, and macrophages. Administration of prominin-1+ cells 2 hours after bleomycin instillation protects from pulmonary fibrosis, and some of progenitors differentiate into alveolar type II epithelial cells. In contrast, prominin-1+ cells administered at day 7 or 14 lose their protective effects and differentiate into myofibroblasts and macrophages. Bleomycin challenge enhances accumulation of bone marrow-derived prominin-1+ cells within inflamed lung. In contrast to prominin-1+ cells from healthy lung, prominin-1+ precursors isolated from inflamed organ lack regenerative

  5. 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.

  6. Radionuclide study of the action of cadmium on alveolar macrophages

    International Nuclear Information System (INIS)

    Reulet, Maryse.

    1976-01-01

    The experimental toxicity of cadmium was studied on the lung, using cadmium sulfate, cadmium acetate and the radioactive isotope cadmium 109 in chloride or acetate form. The results are given in the following order: part one is devoted to the results of investigations on chronic cadmium poisoning and the role of alveolar macrophages in this poisoning; in part two the uptake of cadmium on alveolar macrophages is studied with cadmium 109, administered intraperitoneally; in part three the action of cadmium on the phospholipid metabolism of alveolar macrophages is examined. The cadmium, as sulfate or acetate, is administered in several ways: by intraperitoneal injection; or by inhalation of cadmium dusts or aerosols. The effect of cadmium on the oxidative metabolism of alveolar macrophages is studied in part four. This work is carried out 'in vitro' and 'in vivo' after cadmium oxide dusting of the air [fr

  7. Efficacy of highly hydrophilic soft contact lenses for persistent corneal epithelial defects after anterior segment surgery

    Directory of Open Access Journals (Sweden)

    Zhi-Wei Peng

    2015-02-01

    Full Text Available AIM:To investigate the efficacy of highly hydrophilic soft contact lenses for persistent corneal epithelial defects.METHODS:In this retrospective case analysis, 28 patients(28 eyeswith persistent corneal epithelial defects after anterior segment surgery from January 2011 to June 2013 in our hospital were reviewed. After regular treatment for at least 2wk, the persistent corneal epithelial defects were treated with highly hydrophilic soft contact lenses, until the corneal epithelial healing. Continued to wear the same lens no more than 3wk, or in need of replacement the new one. All cases were followed up for 6mo. Key indicators of corneal epithelial healling, corneal fluorescein staining and ocular symptoms improvement were observed.RESULTS: Twenty-one eyes were cured(75.00%, markedly effective in 5 eyes(17.86%, effective in 2 eyes(7.14%, no invalid cases, the total efficiency of 100.00%. Ocular symptoms of 25 cases(89.29%relieved within 2d, the rest 3 cases(10.71%relieved within 1wk. The corneal epithelial of 6 cases(21.43%repaired in 3wk, 13 cases(46.43%in 6wk, 7 cases(25.00%in 9wk, 2 cases(7.14%over 12wk. There were no signs of secondary infection. And no evidence of recurrence in 6mo. CONCLUSION: Highly hydrophilic soft contact lenses could repair persistent corneal epithelial defects after anterior segment surgery significantly, while quickly and effectively relieve a variety of ocular irritation.

  8. 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

  9. Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway.

    Science.gov (United States)

    Moon, H-G; Cao, Y; Yang, J; Lee, J H; Choi, H S; Jin, Y

    2015-12-10

    Despite decades of research, the pathogenesis of acute respiratory distress syndrome (ARDS) remains poorly understood, thus impeding the development of effective treatment. Diffuse alveolar damage (DAD) and lung epithelial cell death are prominent features of ARDS. Lung epithelial cells are the first line of defense after inhaled stimuli, such as in the case of hyperoxia. We hypothesized that lung epithelial cells release 'messenger' or signaling molecules to adjacent or distant macrophages, thereby initiating or propagating inflammatory responses after noxious insult. We found that, after hyperoxia, a large amount of extracellular vesicles (EVs) were generated and released into bronchoalveolar lavage fluid (BALF). These hyperoxia-induced EVs were mainly derived from live lung epithelial cells as the result of hyperoxia-associated endoplasmic reticulum (ER) stress. These EVs were remarkably different from epithelial 'apoptotic bodies', as reflected by the significantly smaller size and differentially expressed protein markers. These EVs fall mainly in the size range of the exosomes and smaller microvesicles (MVs) (50-120 nm). The commonly featured protein markers of apoptotic bodies were not found in these EVs. Treating alveolar macrophages with hyperoxia-induced, epithelial cell-derived EVs led to an increased secretion of pro-inflammatory cytokines and macrophage inflammatory protein 2 (MIP-2). Robustly increased macrophage and neutrophil influx was found in the lung tissue of the mice intranasally treated with hyperoxia-induced EVs. It was determined that EV-encapsulated caspase-3 was largely responsible for the alveolar macrophage activation via the ROCK1 pathway. Caspase-3-deficient EVs induced less cytokine/MIP-2 release, reduced cell counts in BALF, less neutrophil infiltration and less inflammation in lung parenchyma, both in vitro and in vivo. Furthermore, the serum circulating EVs were increased and mainly derived from lung epithelial cells after

  10. Haemophilia, AIDS and lung epithelial permeability

    Energy Technology Data Exchange (ETDEWEB)

    O' Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G. (Haemophilia Centre and Coagulation Research Unit, Department of Nuclear Medicine, Rayne Institute, St. Thomas' Hospital, London (United Kingdom))

    1990-01-01

    Lung {sup 99m}Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung {sup 99m}Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of {sup 99m}Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au).

  11. Haemophilia, AIDS and lung epithelial permeability

    International Nuclear Information System (INIS)

    O'Doherty, M.J.; Page, C.J.; Harrington, C.; Nunan, T.; Savidge, G.

    1990-01-01

    Lung 99m Tc DTPA transfer was measured in HIV antibodypositive haemophiliacs (11 smokers, 26 nonsmokers, 5 patients with Pneumocystis carinii pneumonia (PCP)). Lung 99m Tc DTPA transfer as a marker of lung epithelial permeability was measured as the half time of transfer (from airspace into blood). This half time was faster in smokers compred to nonsmokers and the transfer curve was monoexponential. In nonsmokers no difference was observed between asymptomatic HIV-positive haemophiliacs and normal subjects, with the exception of the lung bases. At the lung basis in HIV-positive haemophiliac nonsmokers the transfer was faster than in normal individuals, implying increased alveolar permeability. Pneumocystis carinii pneumonia resulted in a rapid transfer of 99m Tc DTPA (mean T50 of 2 minutes) and the transfer curve was biphasic, confirming previous observations in homosexual HIV antibody-positive patients with PCP. These changes returned to a monoexponential profile by 6 weeks following successful treatment. The DTPA lung transfer study may enable clinicians to instigate therapy for PCP without the need for initial bronchoscopy and provide a noninvasive method for the reassessment of patients should further respiratory signs or symptoms develop. This method is considered to be highly cost-effective in that it obviates the use of factor VIII concentrates required to cover bronchoscopic procedures and, with its early application and ease of use as a follow-up investigation, permits the evaluation of patients on an outpatient basis, thus reducing hospital costs. (au)

  12. 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.

  13. Soft tissue healing in alveolar socket preservation technique: histologic evaluations.

    Science.gov (United States)

    Pellegrini, Gaia; Rasperini, Giulio; Obot, Gregory; Farronato, Davide; Dellavia, Claudia

    2014-01-01

    After tooth extraction, 14 alveolar sockets were grafted with porous bovine bone mineral particles and covered with non-cross-linked collagen membrane (test group), and 14 alveolar sockets were left uncovered. At 5 and 12 weeks, microvascular density (MVD), collagen content, and amount of lymphocytes (Lym) T and B were analyzed in soft tissue. At 5 weeks, MVD was significantly lower and Lym T was significantly higher in tests than in controls (P healing process of the soft tissue.

  14. Dynamic thermal performance of alveolar brick construction system

    International Nuclear Information System (INIS)

    Gracia, A. de; Castell, A.; Medrano, M.; Cabeza, L.F.

    2011-01-01

    Highlights: → Even though U-value does not measure thermal inertia, it is the commonly used parameter. → The thermal performance analysis of buildings must include the evaluation of transient parameters. → 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.

  15. 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...... of the mandible. Light microscopic evaluation revealed fibrous encapsulation, a few multinuclear giant cells, little inflammatory reaction, and no osteoinduction. It was concluded that no osteoinduction took place in goats....

  16. Postextraction Alveolar Ridge Preservation: Biological Basis and Treatments

    OpenAIRE

    Pagni, Giorgio; Pellegrini, Gaia; Giannobile, William V.; Rasperini, Giulio

    2012-01-01

    Following tooth extraction, the alveolar ridge undergoes an inevitable remodeling process that influences implant therapy of the edentulous area. Socket grafting is a commonly adopted therapy for the preservation of alveolar bone structures in combination or not with immediate implant placement although the biological bases lying behind this treatment modality are not fully understood and often misinterpreted. This review is intended to clarify the literature support to socket grafting in ord...

  17. 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.

  18. [Fatal alveolar haemorrhage following a "bang" of cannabis].

    Science.gov (United States)

    Grassin, F; André, M; Rallec, B; Combes, E; Vinsonneau, U; Paleiron, N

    2011-09-01

    The new methods of cannabis consumption (home made water pipe or "bang") may be responsible for fatal respiratory complications. We present a case, with fatal outcome, of a man of 19 years with no previous history other than an addiction to cannabis using "bang". He was admitted to intensive care with acute dyspnoea. A CT scan showed bilateral, diffuse alveolar shadowing. He was anaemic with an Hb of 9.3g/l. Bronchoalveolar lavage revealed massive alveolar haemorrhage. Investigations for infection and immunological disorder were negative and toxicology was negative except for cannabis. Antibiotic treatment was given and favourable progress allowed early discharge. Death occurred 15 days later due to alveolar haemorrhage following a further "bang" of cannabis. Autopsy showed toxic alveolar haemorrhage. The probable mechanism is pulmonary damage due to acid anhydrides released by the incomplete combustion of cannabis in contact with plastic. These acids have a double effect on the lungs: a direct toxicity with severe inflammation of the mucosa leading to alveolar haemorrhage and subsequently the acid anhydrides may lead to the syndrome of intra-alveolar haemorrhage and anaemia described in occupational lung diseases by Herbert in Oxford in 1979. It manifests itself by haemoptysis and intravascular haemolysis. We draw attention to the extremely serious potential consequences of new methods of using cannabis, particularly the use of "bang" in homemade plastic materials. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  19. Design-based stereological analysis of the lung parenchymal architecture and alveolar type II cells in surfactant protein A and D double deficient mice

    DEFF Research Database (Denmark)

    Jung, A; Allen, L; Nyengaard, Jens Randel

    2005-01-01

    Alveolar epithelial type II cells synthesize and secrete surfactant. The surfactant-associated proteins A and D (SP-A and SP-D), members of the collectin protein family, participate in pulmonary immune defense, modulation of inflammation, and surfactant metabolism. Both proteins are known to have...... overlapping as well as distinct functions. The present study provides a design-based stereological analysis of adult mice deficient in both SP-A and SP-D (A(-)D(-)) with special emphasis on parameters characterizing alveolar architecture and surfactant-producing type II cells. Compared to wild-type, A......, but the mean volume of a single lamellar body remains constant. These results demonstrate that chronic deficiency of SP-A and SP-D in mice leads to parenchymal remodeling, type II cell hyperplasia and hypertrophy, and disturbed intracellular surfactant metabolism. The design-based stereological approach...

  20. Increased mammogram-induced DNA damage in mammary epithelial cells aged in vitro.

    Directory of Open Access Journals (Sweden)

    Laia Hernández

    Full Text Available Concerned about the risks of mammography screening in the adult population, we analyzed the ability of human mammary epithelial cells to cope with mammogram-induced DNA damage. Our study shows that an X-ray dose of 20 mGy, which is the standard dose received by the breast surface per two-view mammogram X-ray exploration, induces increased frequencies of DNA double-strand breaks to in vitro aged-but not to young-human mammary epithelial cells. We provide evidence that aged epithelial breast cells are more radiosensitive than younger ones. Our studies point to an inefficient damage response of aged cells to low-dose radiation, this being due to both delayed and incomplete mobilization of repair proteins to DNA strand breaks. This inefficient damage response is translated into an important delay in double-strand break disappearance and consequent accumulation of unrepaired DNA breaks. The result of this is a significant increase in micronuclei frequency in the in vitro aged mammary epithelial cells exposed to doses equivalent to a single mammogram X-ray exploration. Since our experiments were carried out in primary epithelial cell cultures in which cells age at the same time as they undergo replication-dependent telomere shortening, we needed to determine the contribution of these two factors to their phenotype. In this paper, we report that the exogenous expression of human telomerase retrotranscriptase in late population doubling epithelial cells does not rescue its delayed repair phenotype. Therefore, retarded DNA break repair is a direct consequence of cellular aging itself, rather than a consequence of the presence of dysfunctional telomeres. Our findings of long-lasting double strand breaks and incomplete DNA break repair in the in vitro aged epithelial cells are in line with the increased carcinogenic risks of radiation exposures at older ages revealed by epidemiologic studies.

  1. Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

    Science.gov (United States)

    Gon, Yasuhiro; Hashimoto, Shu

    2018-01-01

    Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  2. Genetic manipulation of individual somatic mammary cells in vivo reveals a master role of STAT5a in inducing alveolar fate commitment and lactogenesis even in the absence of ovarian hormones.

    Science.gov (United States)

    Dong, Jie; Tong, Tammy; Reynado, Amanda M; Rosen, Jeffrey M; Huang, Shixia; Li, Yi

    2010-10-15

    Assessing the molecular control of development and cell fate in individual cells in the intact mammary epithelium has not been possible to date. By exploiting an intraductal retrovirus (RCAS)-mediated gene delivery method to introduce a marker gene, we found that ductal epithelial cells are turned over with a half time of approximately 1month in adult virgin mice. However, following RCAS-mediated introduction of a constitutively activated STAT5a (caSTAT5a), caSTAT5a-activated ductal epithelial cells expand and replace other cells in the epithelium, eventually forming a mammary gland resembling that in a late pregnant mouse, suggesting that STAT5a activation alone is sufficient to mediate pregnancy-induced mammary cell expansion, alveolar cell fate commitment, and lactogenesis. Furthermore, such caSTAT5a-induced alveolar differentiation does not require ovarian functions, although caSTAT5a-induced cell proliferation is partly reduced in ovariectomized mice. In conclusion, in this first report of studying the developmental role of a gene in a few cells in a normally developed virgin mammary ductal tree, STAT5a activation causes alveolar fate commitment and lactogenesis, and with the help of ovarian hormones, drives alveolar expansion. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Alveolar socket healing: what can we learn?

    Science.gov (United States)

    Araújo, Mauricio G; Silva, Cléverson O; Misawa, Mônica; Sukekava, Flavia

    2015-06-01

    Tooth extraction induces a series of complex and integrated local changes within the investing hard and soft tissues. These local alterations arise in order to close the socket wound and to restore tissue homeostasis, and are referred to as '"socket healing". The aims of the present report were twofold: first, to describe the socket-healing process; and, second, to discuss what can be learned from the temporal sequence of healing events, in order to improve treatment outcomes. The socket-healing process may be divided into three sequential, and frequently overlapping, phases: inflammatory; proliferative; and modeling/remodeling. Several clinical and experimental studies have demonstrated that the socket-healing process promotes up to 50% reduction of the original ridge width, greater bone resorption at the buccal aspect than at the lingual/palatal counterpart and a larger amount of alveolar bone reduction in the molar region. In conclusion, tooth extraction, once a simple and straightforward surgical procedure, should be performed in the knowledge that ridge reduction will follow and that further clinical steps should be considered to compensate for this, when considering future options for tooth replacement. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Inferior alveolar canal course: a radiographic study.

    Science.gov (United States)

    Liu, Tie; Xia, Bing; Gu, Zhiyuan

    2009-11-01

    To describe the morphology and course of the inferior alveolar canal (IAC) as it appears in digital panoramic radiographs. Three hundred and eighty-six digital rotational panoramic radiographs (OPG) were studied using the Clinview Software (6.1.3.7 version, Instrumentarium). Among the 386 radiographs, 86 radiographs with 5-mm steel balls were used to calculate the magnification. The average magnification of radiographs in this study was 7.24+/-7.55%. The course of IAC as seen in the panoramic radiograph may be classified into four types: (1) linear curve, 12.75%, (2) spoon-shaped curve, 29.25%, (3) elliptic-arc curve, 48.5%, and (4) turning curve, 9.5%. On panoramic radiographs, the IAC appeared closest to the inferior border of the mandible in the region of the first molar. In relation to the teeth, on panoramic radiographs, the IAC appeared closest to the distal root tip of the third molar and furthest from the mesial root tip of the first molar. In the OPG, there are four types of IAC: linear, spoon shape, elliptic-arc, and turning curve. The data found in the study may be useful for dental implant, mandibule surgery, and dental anesthesia. The limitations of the panoramic radiograph in depicting the true three-dimensional (3D) morphology of the IAC are recognized, computed tomography (CT) and cone beam (CB)3D imaging being more precise.

  5. Populations at Risk for Alveolar Echinococcosis, France

    Science.gov (United States)

    Piarroux, Martine; Piarroux, Renaud; Knapp, Jenny; Bardonnet, Karine; Dumortier, Jérôme; Watelet, Jérôme; Gerard, Alain; Beytout, Jean; Abergel, Armand; Bresson-Hadni, Solange

    2013-01-01

    During 1982–2007, alveolar echinococcosis (AE) was diagnosed in 407 patients in France, a country previously known to register half of all European patients. To better define high-risk groups in France, we conducted a national registry-based study to identify areas where persons were at risk and spatial clusters of cases. We interviewed 180 AE patients about their way of life and compared responses to those of 517 controls. We found that almost all AE patients lived in 22 départements in eastern and central France (relative risk 78.63, 95% CI 52.84–117.02). Classification and regression tree analysis showed that the main risk factor was living in AE-endemic areas. There, most at-risk populations lived in rural settings (odds ratio [OR] 66.67, 95% CI 6.21–464.51 for farmers and OR 6.98, 95% CI 2.88–18.25 for other persons) or gardened in nonrural settings (OR 4.30, 95% CI 1.82–10.91). These findings can help sensitization campaigns focus on specific groups. PMID:23647623

  6. Computed tomography of the alveolar bone

    International Nuclear Information System (INIS)

    Schueller, H.

    1996-01-01

    In addition to the conventional radiological methods used in odontology, computed tomography (CT) provides superposition-free images of the mandible and maxilla. Its value has been proved not only in cases of malignancy but also in many other problems. If an examination is performed with a slice thickness of less than 1.5 mm, the form and position of retained teeth in the alveolar bone, as well as subsequent lesions of neighboring permanent teeth, can be visualized so that early treatment can be planned. If the parodontal space of a retained tooth is visible, orthodontic intervention is possible. Precise assessment of horizontal or vertical bone loss is essential in inflammatory dental diseases. The morphology and extent of benign cystic lesions are also shown by CT. With CT surgical strategy of an intended implant therapy can take into account the remaining bone substance and the exact position of nerves and foramina. If such therapy is possible, the location, form and number of implants are easily defined. (orig.) [de

  7. Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

    Directory of Open Access Journals (Sweden)

    Richter Joachim

    2008-01-01

    Full Text Available Abstract Background Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. Methods Rats were randomly assigned to a control, Celsior (CE or Celsior + surfactant (CE+S group (n = 5 each. In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4°C and 50 min of reperfusion at 37°C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups or immediately after sacrifice (Control, the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. Results Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation: CE: 160 mm3 (0.61 vs. CE+S: 4 mm3 (0.75; p 3 (0.90 vs. CE+S: 0 mm3; p 3 (0.39 vs. CE+S: 268 mm3 (0.43; p 3(0.10 and CE+S (481 μm3(0.10 compared with controls (323 μm3(0.07; p Conclusion Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of

  8. 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

  9. Proteinose alveolar pulmonar: série de quatro casos Pulmonary alveolar proteinosis: four cases

    Directory of Open Access Journals (Sweden)

    João Carlos Thompson

    2006-06-01

    Full Text Available OBJETIVO: Apresentar a evolução de quatro casos de proteinose alveolar pulmonar atendidos na Faculdade de Medicina da Universidade Estadual de Londrina, enfocando a importância da lavagem pulmonar total como tratamento de escolha. MÉTODOS: Trata-se de um estudo retrospectivo de quatro pacientes, sendo três do gênero feminino, com idades de 22 a 34 anos, e histórias semelhantes de dispnéia progressiva e tosse seca. O diagnóstico final foi realizado por biópsia pulmonar a céu aberto. A lavagem pulmonar total foi realizada em três pacientes em centro cirúrgico, com anestesia geral e sonda de duplo lúme. RESULTADOS: Um paciente apresentou regressão espontânea da proteinose alveolar pulmonar, não sendo necessária a lavagem pulmonar. Nos outros três casos, o número de lavagens variou: uma única lavagem unilateral com remissão completa do quadro bilateralmente, três lavagens sem melhora significativa e quatro procedimentos intercalados com períodos de melhora. CONCLUSÃO: Constatamos em nossa casuística que a lavagem pulmonar se mostrou eficiente, apesar de alguns pacientes apresentarem certa resistência ao procedimento, enquanto que outros podem ter remissão completa da doença.OBJECTIVE: The aim of this study was to present the evolution of four patients presenting pulmonary alveolar proteinosis and treated at the State University of Londrina School of Medicine. We focus on the importance of whole-lung lavage as the treatment of choice. METHODS: A retrospective study of four patients, three females and one male, 22 to 34 years old, presenting similar histories of progressive dyspnea and dry cough. The final diagnosis was established through open-lung biopsy. Three of the patients underwent whole-lung lavage in the Department of Surgery. The procedures were performed under general anesthesia and using a double-lumen endotracheal tube. RESULTS: One patient presented spontaneous regression of the pulmonary alveolar proteinosis

  10. Gene expression profiles of human dendritic cells interacting with Aspergillus fumigatus in a bilayer model of the alveolar epithelium/endothelium interface.

    Directory of Open Access Journals (Sweden)

    Charles Oliver Morton

    Full Text Available The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549 and endothelium (human pulmonary artery epithelial cells, HPAEC on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC, monocyte-derived DC (moDC and myeloid DC (mDC, were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.

  11. Partial pulmonary embolization disrupts alveolarization in fetal sheep

    Directory of Open Access Journals (Sweden)

    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.

  12. Alveolar ridge sockets preservation with bone grafting--review.

    Science.gov (United States)

    Allegrini, Sergio; Koening, Bruno; Allegrini, Marcia Rivellino Facci; Yoshimoto, Marcelo; Gedrange, Tomasz; Fanghaenel, Jochen; Lipski, Mariusz

    2008-01-01

    Alveolar bone seems to play a key role in providing support to the teeth, which are anchored to the bone by desmodontal fibers. The progressive alveolar bone resorption process occurs due to a loss of anatomic, biologic and mechanical factors. Mechanical stimulation of alveolar bone during mastication is crucial in keeping the teeth and underlying bone healthy. Tooth extraction leads to typical bone deficiency of ridge width and height of alveolar crest and reduces the possibility of placing screw titanium implants. When tooth extraction is necessary, trauma should be minimized during the procedure and bone preservation should receive careful attention. The literature has shown that early bone loss can be significantly reduced by socket grafting. The process of socket grafting requires an understanding of wound healing and an appreciation of the biological properties of the products available for socket grafting. Augmentative measures may, thus, be required to guarantee optimal prosthetic replacement of the lost tissue. Success or failure of augmentation procedures is dependent on revascularization and remodelling of the grafted bone into a vital, load bearing bone. In contrast to a visible three-dimensional change, the concept of remodelling refers to the internal turnover of bone, which is a coupled process where osteoclastic resorption and osteoblastic formation are more or less balanced. To restore alveolar bone loss and support efficient placement of dental implants, many different bone substitute such as autografts, allografts, xenografts, synthetic biomaterials and osteoactive agents have been proposed. In order to avoid harvesting an autograft, and thereby eliminating additional surgical procedures and risks, bone grafting materials and substitutes are alternative filler materials to be used for ridge augmentation. To present a literature review about biomaterials applicable in alveolar ridge sockets preservation to future implants insertion. The

  13. Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

    NARCIS (Netherlands)

    Lawrenson, K.; Iversen, E.S.; Tyrer, J.; Weber, R.P.; Concannon, P.; Hazelett, D.J.; Li, Q.; Marks, J.R.; Berchuck, A.; Lee, J.M.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Bandera, E.V.; Bean, Y.; Beckmann, M.W.; Bisogna, M.; Bjorge, L.; Bogdanova, N.; Brinton, L.A.; Brooks-Wilson, A.; Bruinsma, F.; Butzow, R.; Campbell, I.G.; Carty, K.; Chang-Claude, J.; Chenevix-Trench, G.; Chen, A; Chen, Z.; Cook, L.S.; Cramer, D.W; Cunningham, J.M.; Cybulski, C.; Plisiecka-Halasa, J.; Dennis, J.; Dicks, E.; Doherty, J.A.; Dork, T.; Bois, A. du; Eccles, D.; Easton, D.T.; Edwards, R.P.; Eilber, U.; Ekici, A.B.; Fasching, P.A.; Fridley, B.L.; Gao, Y.T.; Gentry-Maharaj, A.; Giles, G.G.; Glasspool, R.; Goode, E.L.; Goodman, M.T.; Gronwald, J.; Harter, P.; Hasmad, H.N.; Hein, A.; Heitz, F.; Hildebrandt, M.A.T.; Hillemanns, P.; Hogdall, E.; Hogdall, C.; Hosono, S.; Jakubowska, A.; Paul, J.; Jensen, A.; Karlan, B.Y.; Kjaer, S.K.; Kelemen, L.E.; Kellar, M.; Kelley, J.L.; Kiemeney, L.A.; Krakstad, C.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, A.W.; Cannioto, R.; Leminen, A.; Lester, J.; Levine, D.A.; Liang, D.; Lissowska, J.; Lu, K.; Lubinski, J.; Lundvall, L.; Massuger, L.F.; Matsuo, K.; McGuire, V.; McLaughlin, J.R.; Nevanlinna, H.; McNeish, I.; Menon, U.; Modugno, F.; Moysich, K.B.; Narod, S.A.; Nedergaard, L.; Ness, R.B.; Azmi, M.A. Noor; Odunsi, K.; Olson, S.H.

    2015-01-01

    Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair

  14. Epithelial WNT Ligands Are Essential Drivers of Intestinal Stem Cell Activation

    Directory of Open Access Journals (Sweden)

    Winnie Y. Zou

    2018-01-01

    Full Text Available Intestinal stem cells (ISCs maintain and repair the intestinal epithelium. While regeneration after ISC-targeted damage is increasingly understood, injury-repair mechanisms that direct regeneration following injuries to differentiated cells remain uncharacterized. The enteric pathogen, rotavirus, infects and damages differentiated cells while sparing all ISC populations, thus allowing the unique examination of the response of intact ISC compartments during injury-repair. Upon rotavirus infection in mice, ISC compartments robustly expand and proliferating cells rapidly migrate. Infection results specifically in stimulation of the active crypt-based columnar ISCs, but not alternative reserve ISC populations, as is observed after ISC-targeted damage. Conditional ablation of epithelial WNT secretion diminishes crypt expansion and ISC activation, demonstrating a previously unknown function of epithelial-secreted WNT during injury-repair. These findings indicate a hierarchical preference of crypt-based columnar cells (CBCs over other potential ISC populations during epithelial restitution and the importance of epithelial-derived signals in regulating ISC behavior.

  15. NFκB signaling in alveolar rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Megan M. Cleary

    2017-09-01

    Full Text Available Alveolar rhabdomyosarcoma (aRMS is a pediatric soft tissue cancer commonly associated with a chromosomal translocation that leads to the expression of a Pax3:Foxo1 or Pax7:Foxo1 fusion protein, the developmental underpinnings of which may give clues to its therapeutic approaches. In aRMS, the NFκB–YY1–miR-29 regulatory circuit is dysregulated, resulting in repression of miR-29 and loss of the associated tumor suppressor activity. To further elucidate the role of NFκB in aRMS, we first tested 55 unique sarcoma cell lines and primary cell cultures in a large-scale chemical screen targeting diverse molecular pathways. We found that pharmacological inhibition of NFκB activity resulted in decreased cell proliferation of many of the aRMS tumor cultures. Surprisingly, mice that were orthotopically allografted with aRMS tumor cells exhibited no difference in tumor growth when administered an NFκB inhibitor, compared to control. Furthermore, inhibition of NFκB by genetically ablating its activating kinase inhibitor, IKKβ, by conditional deletion in a mouse model harboring the Pax3:Foxo1 chimeric oncogene failed to abrogate spontaneous tumor growth. Genetically engineered mice with conditionally deleted IKKβ exhibited a paradoxical decrease in tumor latency compared with those with active NFκB. However, using a synthetic-lethal approach, primary cell cultures derived from tumors with inactivated NFκB showed sensitivity to the BCL-2 inhibitor navitoclax. When used in combination with an NFκB inhibitor, navitoclax was synergistic in decreasing the growth of both human and IKKβ wild-type mouse aRMS cells, indicating that inactivation of NFκB alone may not be sufficient for reducing tumor growth, but, when combined with another targeted therapeutic, may be clinically beneficial.

  16. Prenatal cleft lip and maxillary alveolar defect repair in a 2-step fetal lamb model.

    NARCIS (Netherlands)

    Wenghoefer, M.H.; Deprest, J.; Goetz, W.; Kuijpers-Jagtman, A.M.; Bergé, S.J.

    2007-01-01

    PURPOSE: As there is no satisfying animal model simulating the complex cleft lip and palate anatomy in a standardized defect on one hand, and comprising the possibilities for extensive surgical procedures on the other hand, an improved fetal lamb model for cleft surgery was developed. MATERIALS AND

  17. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

    Science.gov (United States)

    Cantin, A M; Fells, G A; Hubbard, R C; Crystal, R G

    1990-09-01

    We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-soluble fraction in the 100-300-kD range. Plasma proteins with anti-H2O2 properties were in insufficient concentrations to provide the antioxidant protection observed. However, catalase, a normal intracellular antioxidant, was present in sufficient concentration to account for most of the observed anti-H2O2 properties of ELF. Depletion of ELF with an anticatalase antibody abolished the anti-H2O2 macromolecular defenses of ELF. Since catalase is not normally released by cells, a likely explanation for its presence in high concentrations in normal ELF is that it is released by lung inflammatory and parenchymal cells onto the epithelial surface of the lower respiratory tract during their normal turnover and collects there due to the slow turnover of ELF. It is likely that catalase in the ELF of normal individuals plays a role in protecting lung parenchymal cells against oxidants present in the extracellular milieu.

  18. Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

    Directory of Open Access Journals (Sweden)

    Dagmar A. Kuhn

    2014-09-01

    Full Text Available Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1 and a human alveolar epithelial type II cell line (A549. In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis. Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

  19. Polarity in Mammalian Epithelial Morphogenesis

    OpenAIRE

    Roignot, Julie; Peng, Xiao; Mostov, Keith

    2013-01-01

    Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture model...

  20. Chemokine Signaling during Midline Epithelial Seam Disintegration Facilitates Palatal Fusion

    Directory of Open Access Journals (Sweden)

    Christiaan M. Suttorp

    2017-10-01

    Full Text Available Disintegration of the midline epithelial seam (MES is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO, which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling.

  1. 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.

  2. Hypocapnic but Not Metabolic Alkalosis Impairs Alveolar Fluid Reabsorption

    Science.gov (United States)

    Myrianthefs, Pavlos M.; Briva, Arturo; Lecuona, Emilia; Dumasius, Vidas; Rutschman, David H.; Ridge, Karen M.; Baltopoulos, George J.; Sznajder, Jacob Iasha

    2005-01-01

    Acid-base disturbances, such as metabolic or respiratory alkalosis, are relatively common in critically ill patients. We examined the effects of alkalosis (hypocapnic or metabolic alkalosis) on alveolar fluid reabsorption in the isolated and continuously perfused rat lung model. We found that alveolar fluid reabsorption after 1 hour was impaired by low levels of CO2 partial pressure (PCO2; 10 and 20 mm Hg) independent of pH levels (7.7 or 7.4). In addition, PCO2 higher than 30 mm Hg or metabolic alkalosis did not have an effect on this process. The hypocapnia-mediated decrease of alveolar fluid reabsorption was associated with decreased Na,K-ATPase activity and protein abundance at the basolateral membranes of distal airspaces. The effect of low PCO2 on alveolar fluid reabsorption was reversible because clearance normalized after correcting the PCO2 back to normal levels. These data suggest that hypocapnic but not metabolic alkalosis impairs alveolar fluid reabsorption. Conceivably, correction of hypocapnic alkalosis in critically ill patients may contribute to the normalization of lung ability to clear edema. PMID:15764729

  3. Opposing effects of in vitro differentiated macrophages sub-type on epithelial wound healing.

    Directory of Open Access Journals (Sweden)

    Julia A Gindele

    Full Text Available Inappropriate repair responses to pulmonary epithelial injury have been linked to perturbation of epithelial barrier function and airway remodelling in a number of respiratory diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. We developed an in vitro mechanical scratch injury model in air-liquid interface differentiated primary human small airway epithelial cells that recapitulates many of the characteristics observed during epithelial wound injury in both human tissue and small animal models. Wound closure was initially associated with de-differentiation of the differentiated apical cells and rapid migration into the wound site, followed by proliferation of apical cells behind the wound edge, together with increases in FAK expression, fibronectin and reduction in PAI-1 which collectively facilitate cell motility and extracellular matrix deposition. Macrophages are intimately involved in wound repair so we sought to investigate the role of macrophage sub-types on this process in a novel primary human co-culture model. M1 macrophages promoted FAK expression and both M1 and M2 macrophages promoted epithelial de-differentiation. Interestingly, M2a macrophages inhibited both proliferation and fibronectin expression, possibly via the retinoic acid pathway, whereas M2b and M2c macrophages prevented fibronectin deposition, possibly via MMP expression. Collectively these data highlight the complex nature of epithelial wound closure, the differential impact of macrophage sub-types on this process, and the heterogenic and non-delineated function of these macrophages.

  4. 'Regular' and 'emergency' repair

    International Nuclear Information System (INIS)

    Luchnik, N.V.

    1975-01-01

    Experiments on the combined action of radiation and a DNA inhibitor using Crepis roots and on split-dose irradiation of human lymphocytes lead to the conclusion that there are two types of repair. The 'regular' repair takes place twice in each mitotic cycle and ensures the maintenance of genetic stability. The 'emergency' repair is induced at all stages of the mitotic cycle by high levels of injury. (author)

  5. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane

    Energy Technology Data Exchange (ETDEWEB)

    BARCELLOS-HOFF, M. H; AGGELER, J.; RAM, T. G; BISSELL, M. J

    1989-02-01

    An essential feature of mammary gland differentiation during pregnancy is the formation of alveoli composed of polarized epithelial cells, which, under the influence of lactogenic hormones, secrete vectorially and sequester milk proteins. Previous culture studies have described either organization of cells polarized towards lumina containing little or no demonstrable tissue-specific protein, or establishment of functional secretory cells exhibiting little or no glandular architecture. In this paper, we report that tissue-specific vectorial secretion coincides with the formation of functional alveoli-like structures by primary mammary epithelial cells cultured on a reconstituted basement membrane matrix (derived from Engelbreth-Holm-Swarm murine tumour). Morphogenesis of these unique three-dimensional structures was initiated by cell-directed remodelling of the exogenous matrix leading to reorganization of cells into matrixensheathed aggregates by 24 h after plating. The aggregates subsequently cavitated, so that by day 6 the cells were organized into hollow spheres in which apical cell surfaces faced lumina sealed by tight junctions and basal surfaces were surrounded by a distinct basal lamina. The profiles of proteins secreted into the apical (luminal) and basal (medium) compartments indicated that these alveoli-like structures were capable of an appreciable amount of vectorial secretion. Immunoprecipitation with a broad spectrum milk antiserum showed that more than 80% of caseins were secreted into the lumina, whereas iron-binding proteins (both lactoferrin and transferrin) were present in comparable amounts in each compartment. Thus, these mammary cells established protein targeting pathways directing milk-specific proteins to the luminal compartment. A time course monitoring secretory activity demonstrated that establishment of tissue-specific vectorial secretion and increased total and milk protein secretion coincided with functional alveolar

  6. Oct4+ stem/progenitor swine lung epithelial cells are targets for influenza virus replication.

    Science.gov (United States)

    Khatri, Mahesh; Goyal, Sagar M; Saif, Yehia M

    2012-06-01

    We isolated stem/progenitor epithelial cells from the lungs of 4- to 6-week-old pigs. The epithelial progenitor colony cells were surrounded by mesenchymal stromal cells. The progenitor epithelial colony cells expressed stem cell markers such as octamer binding transcription factor 4 (Oct4) and stage-specific embryonic antigen 1 (SSEA-1), as well as the epithelial markers pancytokeratin, cytokeratin-18, and occludin, but not mesenchymal (CD44, CD29, and CD90) and hematopoietic (CD45) markers. The colony cells had extensive self-renewal potential and had the capacity to undergo differentiation to alveolar type I- and type II-like pneumocytes. Additionally, these cells expressed sialic acid receptors and supported the active replication of influenza virus, which was accompanied by cell lysis. The lysis of progenitor epithelial cells by influenza virus may cause a marked reduction in the potential of progenitor cells for self renewal and for their ability to differentiate into specialized cells of the lung. These observations suggest the possible involvement of lung stem/progenitor cells in influenza virus infection.

  7. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis.

    Science.gov (United States)

    Zhang, Yue; Li, Fengyin; Song, Yongli; Sheng, Xiaole; Ren, Fazheng; Xiong, Kai; Chen, Lei; Zhang, Hongquan; Liu, Dequan; Lengner, Christopher J; Xue, Lixiang; Yu, Zhengquan

    2016-10-01

    Mammary epithelium is comprised of an inner layer of luminal epithelial cells and an outer layer of contractile myoepithelial cells with mesenchymal properties. These two compartments interact throughout mammary morphogenesis to form branching ducts during puberty and terminate in secretory alveoli during lactation. It is not known how the myoepithelial cell lineage is specified, nor how signals in myoepithelial cells contribute to lactogenesis. Here, we show that Numb and Numbl are enriched in mammary myoepithelial cells, with their expression peaking during pregnancy. We use conditional Numb- and Numbl-knockout mouse models to demonstrate that loss of Numb/Numbl compromised the myoepithelial layer and expanded the luminal layer, led epithelial cells to undergo epithelial-to-mesenchymal transition, and resulted in lactation failure as a result of abnormal alveolar formation during pregnancy. Numb and Numbl function via repression of the Notch signaling pathway and of the p53-p21 axis during mammary gland development. These findings highlight the importance of Numb and Numbl in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis.-Zhang Y., Li, F., Song, Y., Sheng, X., Ren, F., Xiong, K., Chen, L., Zhang, H., Liu, D., Lengner, C. J., Xue, L., Yu, Z. Numb and Numbl act to determine mammary myoepithelial cell fate, maintain epithelial identity, and support lactogenesis. © FASEB.

  8. Normal morphogenesis of epithelial tissues and progression of epithelial tumors.

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A

    2012-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. Copyright © 2011 John Wiley & Sons, Inc.

  9. Bone resorption and complications in alveolar distraction osteogenesis.

    Science.gov (United States)

    Ettl, Tobias; Gerlach, Till; Schüsselbauer, Thomas; Gosau, Martin; Reichert, Torsten E; Driemel, Oliver

    2010-10-01

    Distraction osteogenesis presents an alternative procedure for augmentation of atrophic alveolar bone prior to inserting dental implants. The aim of this retrospective study was to evaluate complications of this method with specific focus on bone resorption during the consolidation period and the follow-up period after dental implant insertion into distracted bone. Thirty partially edentulous patients underwent a total of 36 vertical alveolar distractions with an extraosseous distraction system. Eleven devices were placed in the maxilla and 25 in the mandible. Eighty-two dental implants were inserted after a mean consolidation period of 4.5 months. Treatment results were evaluated by means of panoramic radiographs for distraction follow-up and periapical radiographs for implant follow-up. The mean length of the transport segment was 19 mm. The average alveolar height achieved was 6.4 mm with a mean resorption of 1.8 mm (21.1%) at the time of dental implant insertion. Main problems comprised oral displacement of the transport segment (n = 15) and inadequate soft tissue extension (n = 13). Eighty-two dental implants were inserted with an overall survival rate of 95.1% after 45.8 months. For periimplant marginal bone, an average resorption of 3.5 mm was recorded 50.4 months after implant insertion. Although alveolar distraction osteogenesis seems to be an effective tool to treat vertical defects of the alveolar ridge, it is not an uncomplicated procedure. A combination with vestibular augmentation of autogenous bone grafts should be considered. Overcorrection of 20% may compensate bone relapse during the consolidation period of the distracted alveolar bone. Further bone resorption after dental implantation is common.

  10. Alveolar bone width preservation after decoronation of ankylosed anterior incisors.

    Science.gov (United States)

    Lin, Shaul; Schwarz-Arad, Dvorah; Ashkenazi, Malka

    2013-12-01

    The aim of the study was to assess the alteration of alveolar ridge dimensions after decoronation procedures in children and adolescents at least 1 year after surgery. Twelve children who underwent decoronation of ankylosed maxillary anterior incisors with at least 1 year after surgery follow-up were recalled for reevaluation. All decoronations were performed when the ankylosed teeth were submerged 1-1.5 mm. During the recall appointment, impressions of the upper arch were obtained. The bucco-palatal alveolar dimensions of the decoronated teeth were measured on the cast at the mid-mesiodistal distance from the missing tooth and were compared with the distance from the contralateral healthy incisor. Overall, 12 children (9 male and 3 female) were reevaluated up to 82 months after decoronation (mean, 49.58 ± 24 months). The mean age of the patients at the time of trauma was 9.83 ± 2.8 years. The average bucco-palatal dimension of the alveolar ridge at the mid-decoronation area was 9 ± 1 mm compared with 10.17 ± 0.9 mm at the contralateral homologous tooth (difference of 1.67 ± 1.12, P = .004). The findings show a positive statistical correlation between the duration of the follow-up period and the bucco-palatal dimension of the alveolar ridge (P = .027). Although decoronation of ankylosed young permanent incisors resulted in a decrease in the bucco-palatal dimension with time, it did not prevent additional alveolar growth that occurs with age in a developing child and thus may help maintain the alveolar bone ridge width, height, and continuity and assist in future rehabilitation with less invasive ridge augmentation procedures required for implant placement. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  11. Epithelial Cell Cultures

    Directory of Open Access Journals (Sweden)

    Imran S. Chaudhry

    2011-01-01

    Full Text Available The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(bfluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK. After a 24-hour exposure, EGFR was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells. After only a 24-hour exposure, cells exhibited atypical nuclear and cytoplasmic features. After a 48-hour exposure, EGFR staining was localized to the nucleus, BCL-2 was slightly decreased in intensity, BIRC5 was localized to the cytoplasm, and TP53 staining was increased in small and large cells. BCL2L1 was expressed in both the cytoplasm and nuclei of cells at 24- and 48-hour exposures. We illustrate that short-termexposure of a bronchial epithelial cell line to smoking-equivalent concentrations of tobacco carcinogens alters the expression of key proliferation regulatory genes, EGFR, BCL-2, BCL2L1, BIRC5, TP53, and MKI67, similar to that reported in biopsy specimens of pulmonary epithelium described to be preneoplastic lesions.

  12. Hard and Soft Tissue Management of a Localized Alveolar Ridge Atrophy with Autogenous Sources and Biomaterials: A Challenging Clinical Case

    Directory of Open Access Journals (Sweden)

    C. Maiorana

    2016-01-01

    Full Text Available Particularly in the premaxillary area, the stability of hard and soft tissues plays a pivotal role in the success of the rehabilitation from both a functional and aesthetic aspect. The present case report describes the clinical management of a localized alveolar ridge atrophy in the area of the upper right canine associated with a thin gingival biotype with a lack of keratinized tissue. An autogenous bone block harvested from the chin associated with heterologous bone particles was used to replace the missing bone, allowing for a prosthetic driven implant placement. Soft tissues deficiency was corrected by means of a combined epithelialized and subepithelial connective tissue graft. The 3-year clinical and radiological follow-up demonstrated symmetric gingival levels of the upper canines, with physiological peri-implant probing depths and bone loss. Thus, the use of autogenous tissues combined with biomaterials might be considered a reliable technique in case of highly aesthetic demanding cases.

  13. Proximal alveolar bone loss in a longitudinal radiographic investigation

    International Nuclear Information System (INIS)

    Bolin, A.; Lavstedt, S.; Henrikson, C.O.; Frithiof, L.

    1986-01-01

    The difference in proximal alveolar bone height between 1970 and 1980, the ''ABD index'', has been measured longitudinally in radiographs from an unselected material. The group constitutes 406 individuals born in 1904 - 1952 in the county of Stockholm. 13 of 18 predictors determined in 1970 were significantly related to the ABD index in the simple correlation analyses. The predictor ''the alveolar bone loss 1970'' (ABL index 1970) had the strongest correlation to the ABD index. In the stepwise multiple regression analysis the predictor ABL index 1970 and three other predictors reached significant levels. These were age, number of lost teeth and Russell's Periodontal Index

  14. Postextraction alveolar ridge preservation: biological basis and treatments.

    Science.gov (United States)

    Pagni, Giorgio; Pellegrini, Gaia; Giannobile, William V; Rasperini, Giulio

    2012-01-01

    Following tooth extraction, the alveolar ridge undergoes an inevitable remodeling process that influences implant therapy of the edentulous area. Socket grafting is a commonly adopted therapy for the preservation of alveolar bone structures in combination or not with immediate implant placement although the biological bases lying behind this treatment modality are not fully understood and often misinterpreted. This review is intended to clarify the literature support to socket grafting in order to provide practitioners with valid tools to make a conscious decision of when and why to recommend this therapy.

  15. 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...

  16. Secondary bone grafting for alveolar cleft in children with cleft lip or cleft lip and palate

    NARCIS (Netherlands)

    Guo, J.; Li, C.; Zhang, Q.; Wu, G.; Deacon, S.A.; Chen, J.; Hu, H.; Zou, S.; Ye, Q.

    2011-01-01

    BACKGROUND: Secondary alveolar bone grafting has been widely used to reconstruct alveolar cleft. However, there is still some controversy. OBJECTIVES: To compare the effectiveness and safety of different secondary bone grafting methods. SEARCH STRATEGY: The final electronic and handsearches were

  17. Parietal epithelial cells: their role in health and disease.

    Science.gov (United States)

    Romagnani, Paola

    2011-01-01

    Parietal epithelial cells of Bowman's capsules were first described by Sir William Bowman in 1842 in his paper On the Structure and Use of the Malpighian Bodies of the Kidney [London, Taylor, 1842], but since then their functions have remained poorly understood. A large body of evidence has recently suggested that parietal epithelial cells represent a reservoir of renal progenitors in adult human kidney which generate novel podocytes during childhood and adolescence, and can regenerate injured podocytes. The discovery that parietal epithelial cells represent a potential source for podocyte regeneration suggests that podocyte injury can be repaired. However, recent results also suggest that an abnormal proliferative response of renal progenitors to podocyte injury can generate hyperplastic glomerular lesions that are observed in crescentic glomerulonephritis and other types of glomerular disorders. Taken together, these results establish an entirely novel view that changes the way of thinking about renal physiology and pathophysiology, and suggest that understanding how self-renewal and fate decision of parietal epithelial cells in response to podocyte injury may be perturbed or modulated will be crucial for obtaining novel tools for prevention and treatment of glomerulosclerosis. Copyright © 2011 S. Karger AG, Basel.

  18. Unsuspected small ameloblastoma in the alveolar bone: a collaborative study of 14 cases with discussion of their cellular sources.

    Science.gov (United States)

    Ide, F; Mishima, K; Yamada, H; Horie, N; Saito, I; Shimoyama, T; Kusama, K

    2008-04-01

    Intraosseous ameloblastoma (IA) is the quintessence of epithelial odontogenic tumor and histologically and behaviorally defined as an undoubted neoplastic process. Current information must lead to the consensus that IA arises from the embryologic inclusions of odontogenic epithelium within the jawbone. Nevertheless, clinically oriented evidence is limited to this day. The clinical and radiographic features, behavior, and pathology of 14 cases of small IA confined to the alveolar region were systematically examined. Six cases were a chance finding. There was no gender predilection and half of the lesions clustered in middle age (>40 years). The posterior region of the mandible (n = 7) and the anterior segment of the maxilla (n = 4) were favored. Five radiographic characteristics were recognized: interradicular (n = 5) and periradicular (n = 3), and periapical, residual and pericoronal (n = 2 each). They showed solid (n = 12) or unicystic (n = 2) growth pattern and 12 lesions were divided into seven follicular, three desmoplastic, and two plexiform subtypes. The main location of tumor was microscopically traceable in six cases; three interradicular type outside the periodontal ligament space and two periradicular and one periapical variants inside. By in-depth evaluation of the spatial relationship between tumor and its surrounding structure, the alveolar process, periodontal ligament space, and pericoronal area are all the likely starting points of IA. This report re-awakens the oral pathologist to the histogenetic significance of incipient IA as the only available human specimen for reappraisal of their origin.

  19. Phenotypic analyses of limbal epithelial cell cultures derived from donor corneoscleral rims.

    Science.gov (United States)

    Barnard, Z; Apel, A J; Harkin, D G

    2001-06-01

    Grafted cultures of limbal epithelial cells aid repair of the corneal epithelium, but their phenotype is unclear. In this study, the phenotype of cultures that were similar in age to those used clinically were analysed. Limbal epithelial cells were isolated from donor corneoscleral rims and grown in various media, including those designed for keratinocytes. Successful cultures in each medium developed predominantly small (10 microm) tightly packed cells. Immunocytochemistry and western blotting revealed expression of keratins 3, 14 and 19. Expression of these keratins in situ was confirmed by immunohistochemistry. Basal limbal epithelial cells were positive for keratins 14 and 19, and suprabasal cells were positive for keratin 3. However intense staining for keratin 14 was also observed at the inner cut edge of corneoscleral rims. These findings demonstrate the potential importance of keratins 14 and 19 as markers of epithelial cell differentiation in the human cornea.

  20. Repairing fuel for reinsertion

    International Nuclear Information System (INIS)

    Cruickshank, A.

    1985-01-01

    The tools and techniques developed in the United States and FR Germany to repair damaged fuels assemblies are examined. Two methods of repair are considered:- removal of damaged fuel rods and replacement with sound rods (reconstitution); and removal of sound rods from one assembly structure and placing them into a fresh assembly structure (reassembly). (UK)

  1. Hydraulic fracture during epithelial stretching.

    Science.gov (United States)

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-03-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells' cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here, we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression manoeuvres. After pressure equilibration, cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics.

  2. Inositol-trisphosphate reduces alveolar apoptosis and pulmonary edema in neonatal lung injury.

    Science.gov (United States)

    Preuss, Stefanie; Stadelmann, Sabrina; Omam, Friede D; Scheiermann, Julia; Winoto-Morbach, Supandi; von Bismarck, Philipp; Knerlich-Lukoschus, Friederike; Lex, Dennis; Adam-Klages, Sabine; Wesch, Daniela; Held-Feindt, Janka; Uhlig, Stefan; Schütze, Stefan; Krause, Martin F

    2012-08-01

    D-myo-inositol-1,2,6-trisphosphate (IP3) is an isomer of the naturally occurring second messenger D-myo-inositol-1,4,5-trisphosphate, and exerts anti-inflammatory and antiedematous effects in the lung. Myo-inositol (Inos) is a component of IP3, and is thought to play an important role in the prevention of neonatal pulmonary diseases such as bronchopulmonary dysplasia and neonatal acute lung injury (nALI). Inflammatory lung diseases are characterized by augmented acid sphingomyelinase (aSMase) activity leading to ceramide production, a pathway that promotes increased vascular permeability, apoptosis, and surfactant alterations. A novel, clinically relevant triple-hit model of nALI was developed, consisting of repeated airway lavage, injurious ventilation, and lipopolysaccharide instillation into the airways, every 24 hours. Thirty-five piglets were randomized to one of four treatment protocols: control (no intervention), surfactant alone, surfactant + Inos, and surfactant + IP3. After 72 hours of mechanical ventilation, lungs were excised from the thorax for subsequent analyses. Clinically, oxygenation and ventilation improved, and extravascular lung water decreased significantly with the S + IP3 intervention. In pulmonary tissue, we observed decreased aSMase activity and ceramide concentrations, decreased caspase-8 concentrations, reduced alveolar epithelial apoptosis, the reduced expression of interleukin-6, transforming growth factor-β1, and amphiregulin (an epithelial growth factor), reduced migration of blood-borne cells and particularly of CD14(+)/18(+) cells (macrophages) into the airspaces, and lower surfactant surface tensions in S + IP3-treated but not in S + Inos-treated piglets. We conclude that the admixture of IP3 to surfactant, but not of Inos, improves gas exchange and edema in our nALI model by the suppression of the governing enzyme aSMase, and that this treatment deserves clinical evaluation.

  3. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  4. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Bill Bruce; Nancy Porter; George Ritter; Matt Boring; Mark Lozev; Ian Harris; Bill Mohr; Dennis Harwig; Robin Gordon; Chris Neary; Mike Sullivan

    2005-07-20

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  5. A novel semi-automatic segmentation protocol for volumetric assessment of alveolar cleft grafting procedures

    NARCIS (Netherlands)

    Janssen, Nard G.; Schreurs, Ruud; Bittermann, Gerhard K.P.; Borstlap, Wilfred A.; Koole, Ronald; Meijer, Gert J.; Maal, Thomas J.J.

    2017-01-01

    A novel protocol for volumetric assessment of alveolar cleft grafting procedures is presented. Eleven cone-beam computed tomography (CBCT) datasets of patients who underwent secondary alveolar cleft reconstructive surgery for a unilateral alveolar cleft were evaluated by two investigators. Residual

  6. A novel semi-automatic segmentation protocol for volumetric assessment of alveolar cleft grafting procedures.

    NARCIS (Netherlands)

    Janssen, N.G.; Schreurs, R.; Bittermann, G.K.P.; Borstlap, W.A.; Koole, R.A.; Meijer, G.J.; Maal, T.J.J.

    2017-01-01

    A novel protocol for volumetric assessment of alveolar cleft grafting procedures is presented. Eleven cone-beam computed tomography (CBCT) datasets of patients who underwent secondary alveolar cleft reconstructive surgery for a unilateral alveolar cleft were evaluated by two investigators. Residual

  7. 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.

  8. CCAAT/enhancer binding protein beta (C/EBPβ) isoform balance as a regulator of epithelial-mesenchymal transition in mouse mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Yuka; Hagiwara, Natsumi [Department of Bioscience, Graduate School of Science and Technology, Kwansei Gakuin University, Hyogo, 2-1 Gakuen, Sanda 669-1337 Japan (Japan); Radisky, Derek C. [Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32225 (United States); Hirai, Yohei, E-mail: y-hirai@kwansei.ac.jp [Department of Bioscience, Graduate School of Science and Technology, Kwansei Gakuin University, Hyogo, 2-1 Gakuen, Sanda 669-1337 Japan (Japan)

    2014-09-10

    Activation of the epithelial-mesenchymal transition (EMT) program promotes cell invasion and metastasis, and is reversed through mesenchymal-epithelial transition (MET) after formation of distant metastases. Here, we show that an imbalance of gene products encoded by the transcriptional factor C/EBPβ, LAP (liver-enriched activating protein) and LIP (liver-enriched inhibitory protein), can regulate both EMT- and MET-like phenotypic changes in mouse mammary epithelial cells. By using tetracycline repressive LIP expression constructs, we found that SCp2 cells, a clonal epithelial line of COMMA1-D cells, expressed EMT markers, lost the ability to undergo alveolar-like morphogenesis in 3D Matrigel, and acquired properties of benign adenoma cells. Conversely, we found that inducible expression of LAP in SCg6 cells, a clonal fibroblastic line of COMMA1-D cells, began to express epithelial keratins with suppression of proliferation. The overexpression of the C/EBPβ gene products in these COMMA1-D derivatives was suppressed by long-term cultivation on tissue culture plastic, but gene expression was maintained in cells grown on Matrigel or exposed to proteasome inhibitors. Thus, imbalances of C/EBPβ gene products in mouse mammary epithelial cells, which are affected by contact with basement membrane, are defined as a potential regulator of metastatic potential. - Highlights: • We created a temporal imbalance of C/EBPβ gene products in the mammary model cells. • The temporal up-regulation of LIP protein induced EMT-like cell behaviors. • The temporal up-regulation of LAP protein induced MET-like cell behaviors. • Excess amount of C/EBPβ gene products were eliminated by proteasomal-degradation. • Basement membrane components attenuated proteasome-triggered protein elimination.

  9. Splenic epithelial cyst

    International Nuclear Information System (INIS)

    Yousuf, M.; Jalali, U.

    2011-01-01

    Cysts of spleen are rare entities. Congenital splenic cysts are even more uncommon comprising of only 10% of benign non-parasitic cysts. We report a case of 22 years old female who presented with history of 2 years abdominal pain and gradual distension. Ultrasound and computed tomography (CT) both were suggestive of splenic cyst. Laboratory tests show thrombocytopenia with platelets count of 97000 per cubic millimeter and anemia with hemoglobin 8.7 gram per deciliter. Serological tests were negative for parasitic infection. Splenectomy was done and the weight of the spleen was found to be 1.5 kilogram. Histopathological findings are consistent with splenic epithelial cyst. The aetiology, diagnostic modalities and treatment options are discussed in the case report. (author)

  10. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-12-31

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  11. Interim endodontic therapy for alveolar socket bone regeneration of infected hopeless teeth prior to implant therapy.

    Science.gov (United States)

    Rass, Marwan Abou

    2010-01-01

    patients' dental care. When treated, these hopeless teeth served many preventive, biologic, and esthetic functions. The infections of the alveolar sockets were eliminated, the alveolar bone defects were repaired through normal bone regeneration, and sockets anatomies were maintained or restored. Furthermore, the patients were spared maxillary sinus surgery and the possible complications resulting from major GBR and GTR procedures. In summary, the interim treatment facilitated tooth extraction and immediate implant placement.

  12. Autochthonous human alveolar echinococcosis in a Hungarian patient.

    Science.gov (United States)

    Dezsényi, Balázs; Strausz, Tamás; Makrai, Zita; Csomor, Judit; Danka, József; Kern, Peter; Rezza, Giovanni; Barth, Thomas F E; Casulli, Adriano

    2017-02-01

    Alveolar echinococcosis is a zoonotic parasitic disease causing a severe clinical condition and is known as the most deadly of all helminth infections. Moreover, this disease is also an increasing concern in Northern and Eastern Europe due to its spread in the wildlife animal host. An asymptomatic 70-year-old woman from south-western Hungary was diagnosed with multiple liver lesions. Imaging techniques (ultrasound, computed tomography and magnetic resonance imaging), serology (ELISA, indirect hemagglutination and Western blot), and conventional staining methods (hematoxylin-eosin and periodic acid-Schiff) were used for the detection of the disease. A histopathological re-evaluation of formalin-fixed paraffin block by immunohistochemical staining with the monoclonal antibody Em2G11 definitively confirmed the diagnosis of alveolar echinococcosis. To our knowledge, this is the first confirmed autochthonous case of human alveolar echinococcosis in Hungary. To what extent diagnostic difficulties may contribute to underestimate this zoonosis in Eastern Europe is unknown. Differential diagnosis with alveolar echinococcosis should be considered for patients with multiple, tumor-like cystic lesions of the liver, in countries where this parasite is emerging.

  13. Three‑dimensional Evaluation of Alveolar Bone Thickness of ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... mandibular anterior teeth are going to be retracted, mechanics for torque control should be preferred not to have uncontrolled tipping. In Class I, light orthodontic forces should be applied using elastic arch wires, and time must be allowed for the remodeling and healing of the alveolar bone in these patient ...

  14. Advanced Alveolar Rhabdomyosarcoma of the Uterus: A Case Report

    African Journals Online (AJOL)

    Alveolar rhabdomyosarcoma is an uncommon malignant soft tissue tumour rarely found in the female genital tract and carries a very poor prognosis especially in adults. A 44 year old premenopausal woman was evaluated for a lower abdominal mass, intermittent unprovoked vaginal bleeding and weight loss. Examination ...

  15. Alveolar rhabdomyosarcoma: origin and prognostic implications of molecular findings

    Directory of Open Access Journals (Sweden)

    Pilar Eguía-Aguilar

    2016-11-01

    The aggressive behavior of alveolar rhabdomyosarcoma has been associated with the expression of oncogenic fusion proteins resulting from chromosomal translocations, particularly t(2;13 (q35;q14 PAX3/FOXO1, and t(1;13 (p36;q14 PAX7/FOXO1 which were present in this patient.

  16. Complications in alveolar distraction osteogenesis of the atrophic mandible.

    NARCIS (Netherlands)

    Perdijk, F.B.T.; Meijer, G.J.; Strijen, P.J. van; Koole, R.A.

    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. Alveolar pulmonary proteinosis: case report and literature review

    International Nuclear Information System (INIS)

    Vergara, Erika; Saenz, Alberto; Ojeda, Paulina

    2009-01-01

    We describe the case of a young women with primary alveolar proteinosis, with a short period of symptoms that are uncommon for this disease, without risk factors for this entity, the clinical evolution of the patient and some complications with the treatment. We review the literature for this entity.

  18. Buccal Infiltration versus Inferior Alveolar Nerve Block in Mandibular ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... Purpose: The purpose of this study is to compare the success rates of inferior alveolar nerve block (IANB) and buccal infiltration anesthesia of mandibular second premolar with irreversible pulpitis and to evaluate the level of patient discomfort with these methods. Matherials and Methods: Forty patients, who.

  19. Alveolar Bone Housing- A Modified Wilkodontics Approach- A Case Report

    OpenAIRE

    Awasthi, Eshan; Sanjay, Kothamachu; Bhongade, ML; Shrivastav, Sunita

    2016-01-01

    Accelerated orthodontic treatment is the need of the hour in current scenario as the conventional orthodontics is time taking. Corticotomy assisted orthodontics have been used for years to reduce the treatment duration by reducing the resistance provided by alveolar bone housing.

  20. Three‑dimensional evaluation of alveolar bone thickness of ...

    African Journals Online (AJOL)

    Aim: The aim of this randomized study was to compare the alveolar bone thickness (ABT) of the mandibular incisor teeth of dental and skeletal Class I, II, and III adult patients at labial and lingual aspects of the bone and develop recommendations for the associated movements of teeth in this region, taking vertical facial type ...

  1. 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...

  2. The Effect of Astragalus Extractive on Alveolar Bone Rebuilding ...

    African Journals Online (AJOL)

    Background: Postmenopausal osteoporosis (PMO) is an estrogen deficiency condition that causes severe loss of bone mass in the vertebrae and long bones. We explored the effect and the possible underlying mechanism of the extracts of Astragalus (AE) on the tooth alveolar bone rebuilding progress of postmenopausal ...

  3. Contribution of the tooth bud mesenchyme to alveolar bone

    Czech Academy of Sciences Publication Activity Database

    Diep, L.; Matalová, Eva; Mitsiadis, T. A.; Tucker, A. S.

    312B, č. 5 (2009), 510-517 ISSN 1552-5007 R&D Projects: GA ČR GC524/08/J032; GA AV ČR KJB500450802 Institutional research plan: CEZ:AV0Z50450515 Keywords : tooth * alveolar bone * bud Subject RIV: FF - HEENT, Dentistry Impact factor: 2.938, year: 2009

  4. Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

    International Nuclear Information System (INIS)

    Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

    2006-01-01

    A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms. Fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood a treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. it is considered eosinophilic pneumonia diagnostic by parasitary infection (Loeffler's syndrome)

  5. Pulmonary alveolar hemorrhage mimicking a pneumopathy: a rare ...

    African Journals Online (AJOL)

    Diffuse alveolar hemorrhage after percutaneous coronary intervention (PCI) is a rare complication. The diagnosis is difficult and can mimic by clinical and radiological features other diagnosis as pneumopathy. We herein report the case of a 63-year-old female admitted to the hospital for ST elevation myocardial infarction.

  6. 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.

  7. Structural changes and effect of denopamine on alveolar fluid ...

    African Journals Online (AJOL)

    GREGORY

    2010-09-13

    Sep 13, 2010 ... sectioning plane, and D = the mean caliper diameter of pulmonary cell nuclei. The frequency of occurrence of nuclear profiles per unit area of a random sectioning plane (NA) was determined using the electron microscope. ..... Chronic pulmonary artery occlusion increases alveolar fluid clearance in rats.

  8. Pulmonary alveolar proteinosis — a case report and review

    African Journals Online (AJOL)

    Enrique

    with granular, eosinophilic, proteina- ceous material (Fig. 2) with preserva- tion of the alveolar architecture. The patient was treated by whole-lung lavage, followed by a 4-week trial of subcutaneous granulocyte-macro- phage colony-stimulating factor. (GM-CSF). The trial of GM-CSF failed, however, and the patient is cur-.

  9. Alveolar occupation infiltrations, eosinophilia in peripheral blood and bronchoalveolar lavage

    International Nuclear Information System (INIS)

    Hincapie Diaz, Gustavo Adolfo; Yama Mosquera, Erica; Guevara, Jairo

    2006-01-01

    A case of a patient of 25 years old is shown with the antecedent of no potable water consumption who entered for having pulmonary symptoms, fever, presence of alveolar occupation infiltrations and eosinophilia in peripheral blood treatment with antiparasitary started with a significant improvement of the symptoms, infiltrations and eosinophilia. It is considered eosinophilic pneumonia diagnostic by parasitary infection (Loefffers Syndrome)

  10. Buccal infiltration versus inferior alveolar nerve block in mandibular ...

    African Journals Online (AJOL)

    Purpose: The purpose of this study is to compare the success rates of inferior alveolar nerve block (IANB) and buccal infiltration anesthesia of mandibular second premolar with irreversible pulpitis and to evaluate the level of patient discomfort with these methods. Materials and Methods: Forty patients, who had irreversible ...

  11. Arterial-alveolar oxygen partial pressure ratio: a theoretical reappraisal.

    Science.gov (United States)

    Viale, J P; Percival, C J; Annat, G; Rousselet, B; Motin, J

    1986-02-01

    The relationship between the arterial-alveolar oxygen partial pressure ratio (PaO2/PAO2) and different fractions of inspired oxygen (FIO2) was studied using a bicompartmental computer model. PaO2/PAO2 was found to be less stable than in previous clinical works probably because the venous admixture varied with changes in the FIO2.

  12. Hepatic regeneration and the epithelial to mesenchymal transition.

    Science.gov (United States)

    Xue, Zeng-Fu; Wu, Xiu-Min; Liu, Ming

    2013-03-07

    Liver injuries are repaired by fibrosis and regeneration. The core stage is the repair response and fibrosis formation as a scar. The cause of overly-responsive scar formation and diminished regeneration, especially in liver fibrosis and cirrhosis, is still unknown. The epithelial to mesenchymal transition (EMT), a previously discovered mechanism, plays an important role in liver fibrosis and tumor metastasis. Recently, EMT has been found to be associated with liver and bile duct cell fibrosis. Analyzing the established models and chronic disease processes, we propose that EMT liver cells may also lose their regenerative capability due to phenotype changes and that the remaining liver cells may quickly lose their regenerative capability in liver fibrosis or cirrhosis. Recognizing these phenotype changes or transition cells may play an important role in targeting therapy to reverse fibrosis not only by disrupting the transition that is necessary to produce the extracellular matrix but also by restoring the regenerative capacity of EMT-like cells.

  13. Differential and strain-specific triggering of bovine alveolar macrophage effector functions by mycoplasmas.

    Science.gov (United States)

    Jungi, T W; Krampe, M; Sileghem, M; Griot, C; Nicolet, J

    1996-12-01

    Mycoplasma strains being considered as pathogenic or non-pathogenic for cattle were tested on their capacity to activate bovine alveolar macrophages in vitro. Of particular interest was the behaviour of Mycoplasma mycoides ssp. mycoides small colony type (M.m.m. SC), the causative agent of contagious bovine pleuropneumonia (CBPP). Increases in procoagulant activity (PCA), tumor necrosis factor-alpha- (TNF-alpha) and nitrogen monoxide (NO) generation were tested. To minimize an influence of macrophage activation by mycoplasma growth media, mycoplasmas were cultured on embryonic calf nose epithelial cells. The three macrophage functions tested were not correlated, but were differentially induced in strain-specific manner. Four out of seven strains induced PCA, regardless of pathogenicity, and all strains promoted moderate NO generation at high concentrations. All tested M.m.m. SC strains (Afadé, L2 and PG1), and the pathogenic M. bovis, induced TNF-alpha production at low concentrations (10(6) colony forming units per ml). M.sp. serogroup 7 and the non-pathogenic M. bovirhinis and Acholeplasma laidlawii did not induce TNF-alpha up to 10(8) cfu/ml. Thus, strain-specific differences are reflected in differential macrophage activation patterns. The findings are consistent with an important role for TNF-alpha in pathogenesis of CBPP.

  14. An in vitro cytotoxicity assessment of graphene nanosheets on alveolar cells

    Science.gov (United States)

    Dervin, Saoirse; Murphy, James; Aviles, Ruth; Pillai, Suresh C.; Garvey, Mary

    2018-03-01

    The collection of intrinsic properties possessed by graphene family nanomaterials (GFNs) results in their continuous exploitation for biomedical applications. The materials biomedical potential has motivated an upsurge in green preparation routes for the production of graphene like materials with limited toxicity. A number of bio-friendly reducing agents have been utilized for the preparation of chemically reduced graphene oxide (GO), and their resulting cytotoxic effects examined. However, the toxicology effects of one of the first biomolecules implemented for the reduction of GO, ascorbic acid (AA) has yet to be investigated. Herein, the toxicity of three distinct GFNs; GO, hydrazine reduced GO (H.rGO) and AA.rGO, prepared through diverse chemical routes are studied, to demonstrate the cytotoxic activity of a green reducer, in comparison to an established reduction method using hydrazine hydrate. The variation in atomic structure of GO, H.rGO and AA.rGO resulting from different synthesis techniques demonstrates the dependence of toxicity on particle shape and size. All GFNs induced high levels of alveolar cell toxicity. Interaction of AA.rGO with the A549 human lung epithelial carcinoma cell line resulted in increased leakage of lactate dehydrogenase, indicative of diminished cell membrane integrity. The uncharacteristic shape of the AA.rGO may be responsible for this proliferated release of the essential protein. The presented data therefore demonstrates that modification of synthetic processes significantly alter the biological activities of GFNs.

  15. Receptor for advanced glycation end-products is a marker of type I lung alveolar cells.

    Science.gov (United States)

    Shirasawa, Madoka; Fujiwara, Naoyuki; Hirabayashi, Susumu; Ohno, Hideki; Iida, Junko; Makita, Koshi; Hata, Yutaka

    2004-02-01

    Lung alveolar epithelial cells are comprised of type I (ATI) and type II (ATII) cells. ATI cells are polarized, although they have very flat morphology. The identification of marker proteins for apical and basolateral membranes of ATI cells is important to investigate into the differentiation of ATI cells. In this paper, we characterized receptor for advanced glycation end-products (RAGE) as a marker for ATI cells. RAGE was localized on basolateral membranes of ATI cells in the immunoelectron microscopy and its expression was enhanced in a parallel manner to the differentiation of ATI cells in vivo and in primary cultures of ATII cells. RAGE and T1 alpha, a well-known ATI marker protein, were targeted to basolateral and apical membranes, respectively, when expressed in polarized Madine Darby canine kidney cells. Moreover, RAGE was expressed in ATI cells after T1 alpha in vivo and in ex in vivo organ cultures. In conclusion, RAGE is a marker for basolateral membranes of well-differentiated ATI cells. ATI cells require some signal provided by the in vivo environment to express RAGE.

  16. Alveolar process fractures in the permanent dentition. Part 2. The risk of healing complications in teeth involved in an alveolar process fracture.

    Science.gov (United States)

    Lauridsen, Eva; Gerds, Thomas; Andreasen, Jens Ove

    2016-04-01

    To analyze the risk of pulp canal obliteration (PCO), pulp necrosis (PN), repair-related resorption (RRR), infection-related resorption (IRR), ankylosis-related resorption (ARR), marginal bone loss (MBL), and tooth loss (TL) for teeth involved in an alveolar process fracture and to identify possible risk factors. A total of 91 patients with 223 traumatized teeth. The risks of PCO, PN, RRR, IRR, ARR, MBL, and TL were analyzed separately for teeth with immature and mature root development using Kaplan-Meier and Aalen-Johansen methods. Possible risk factors for PN (age, fracture in relation to apex, displacement, gingival injury, degree of repositioning, type of splint, duration of splinting, treatment delay, and antibiotics) were analyzed for mature teeth using Cox regression. The level of significance was 5%. Immature: No severe complications (PN, IRR, ARR, MBL, or TL) were diagnosed during follow up. Mature: Estimated risk after a 10-year follow up: PN: 56% (95% confidence interval (CI): 48.1-63.9), IRR: 2.5% (95% CI: 0-5.1), ARR: 2.1% (95% CI: 0.1-4.1), MBL: 2.4% (95% CI: 0.3-4.4), and TL: 7.8% (95% CI: 0-15.7). The following factors significantly increased the risk of PN in teeth with mature root development: fracture in relation to apex (hazard ratio (HR): 2.6 (95% CI: 0.2 - 5.7), P = 0.01), displacement in the horizontal part of the fracture >2 mm (HR: 1.8; 95% CI: 1.1-3.2, P = 0.03), incomplete repositioning (HR: 2.1 (95% CI: 1.3-3.5), P = 0.003), and age >30 years (HR: 2.3 (95% CI: 1.1-4.6), P = 0.02). The type of splint (rigid or flexible), the duration of splinting (more or less than 4 weeks), and the administration of antibiotics did not affect the risk of PN. Teeth involved in alveolar process fractures appear, apart from PN, to have a good prognosis. A conservative treatment approach is recommended. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-08-17

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without liners

  18. Activation of P2X7R and downstream effects in bleomycin treated lung epithelial cells.

    Science.gov (United States)

    Bläsche, Robert; Ebeling, Georg; Perike, Srikanth; Weinhold, Karina; Kasper, Michael; Barth, Kathrin

    2012-03-01

    Changes in intracellular calcium concentration [Ca(2+)](i) are believed to influence the proliferation and differentiation of airway epithelial cells both in vivo and in vitro. In the present study, using mouse alveolar epithelial E10 cells, we demonstrated that the treatment of lung epithelial cells with BLM resulted in elevated intracellular Ca(2+) levels. BLM further increased P2rx7 mRNA expression and P2X7R protein levels, paralleled by increased PKC-β1 levels. BLM treatment or stimulation of the P2X7R with the P2X7R agonist BzATP induced translocation of PKC-β1 from the cytoplasm to the membrane. The expression of PKC-β1 was repressed by the P2X7R inhibitor oxATP, suggesting that PKC-β1 is downstream of P2X7R activation. Furthermore, cells exposed to BLM contained increased amounts of P2X7R and PKC-β1 in Cav-1 containing lipid raft fractions. The comparison of lung tissues from wild-type and P2rx7(-/-) mice revealed decreased protein and mRNA levels of PKC-β1 and CaM as well as decreased immunoreactivity for PKC-β1. The knockdown of P2X7R in alveolar epithelial cells resulted also in a loss of PKC-β1. These data suggest that the effect of P2X7R on expression of PKC-β1 detected in alveolar epithelial cells is also functioning in the animal model. Immunohistochemical evaluation of fibrotic lungs derived from a BLM-induced mouse model revealed a strong increase in PKC-β1 immunoreactivity. The present experiments demonstrated that the increased expression of P2X7R influences PKC-β1. We predict that increased Ca(2+) concentration stimulates PKC-β1, whereas the prerequisite for activating PKC-β1 after P2X7R increase remained to be determined. Our findings suggest that PKC-β1 is important in the pathogenesis of pulmonary fibrosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Integrin α6β4 identifies human distal lung epithelial progenitor cells with potential as a cell-based therapy for cystic fibrosis lung disease.

    Directory of Open Access Journals (Sweden)

    Xiaopeng Li

    Full Text Available To develop stem/progenitor cell-based therapy for cystic fibrosis (CF lung disease, it is first necessary to identify markers of human lung epithelial progenitor/stem cells and to better understand the potential for differentiation into distinct lineages. Here we investigated integrin α6β4 as an epithelial progenitor cell marker in the human distal lung. We identified a subpopulation of α6β4(+ cells that localized in distal small airways and alveolar walls and were devoid of pro-surfactant protein C expression. The α6β4(+ epithelial cells demonstrated key properties of stem cells ex vivo as compared to α6β4(- epithelial cells, including higher colony forming efficiency, expression of stem cell-specific transcription factor Nanog, and the potential to differentiate into multiple distinct lineages including basal and Clara cells. Co-culture of α6β4(+ epithelial cells with endothelial cells enhanced proliferation. We identified a subset of adeno-associated virus (AAVs serotypes, AAV2 and AAV8, capable of transducing α6β4(+ cells. In addition, reconstitution of bronchi epithelial cells from CF patients with only 5% normal α6β4(+ epithelial cells significantly rescued defects in Cl(- transport. Therefore, targeting the α6β4(+ epithelial population via either gene delivery or progenitor cell-based reconstitution represents a potential new strategy to treat CF lung disease.

  20. The role of alveolar type II cells in swine leptospirosis

    Directory of Open Access Journals (Sweden)

    Ângela P. Campos

    2015-07-01

    Full Text Available Abstract: This study aimed to investigate a possible relationship between alveolar type II cells and the inflammatory response to infection with Leptospira spp., and thus comprise a further element that can be involved in the pathogenesis of lung injury in naturally infected pigs. The study group consisted of 73 adult pigs that were extensively reared and slaughtered in Teresina, Piauí state, and Timon, Maranhão state, Brazil. The diagnosis of leptospirosis was made using the microscopic agglutination test (MAT aided by immunohistochemistry and polymerase chain reaction. The MAT registered the occurrence of anti-Leptospira antibodies in 10.96% (8/73 of the pigs. Immunohistochemistry allowed for the visualization of the Leptospira spp. antigen in the lungs of 87.67% (64/73 of the pigs. There was hyperplasia of bronchus-associated lymphoid tissue and circulatory changes, such as congestion of alveolar septa, parenchymal hemorrhage and edema within the alveoli. Lung inflammation was more intense (p = 0.0312 in infected animals, which also showed increased thickening of the alveolar septa (p = 0.0006. Evaluation of alveolar type II (ATII cells using an anti-TTF-1 (Thyroid Transcription Factor-1 antibody showed that there were more immunostained cells in the non-infected pigs (53.8% than in the infected animals (46.2% and that there was an inverse correlation between TTF-1 positive cells and the inflammatory infiltrate. There was no amplification of Leptospira DNA in the lung samples, but leptospiral DNA amplification was observed in the kidneys. The results of this study showed that a relationship exists between a decrease in alveolar type II cells and a leptospire infection. Thus, this work points to the importance of studying the ATII cells as a potential marker of the level of lung innate immune response during leptospirosis in pigs.

  1. 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.

  2. Alveolar ridge atrophy related to facial morphology in edentulous patients

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    Kuć J

    2017-09-01

    Full Text Available Joanna Kuć,1 Teresa Sierpińska,2 Maria Gołębiewska1 1Department of Prosthodontics, 2Department of Dental Technology, Medical University of Bialystok, Bialystok, Poland Objectives: The morphology of the alveolar process determines the retention and stability of prosthetic restorations, thereby determining the result of the therapy. Considering that the edentulous jaws may be affected by the atrophy process, it was hypothesized that the morphology of the alveolar process of the maxilla may be dependent on the anterior facial height and anatomy of the mandible. Subjects and methods: Twenty-five healthy edentulous Caucasian individuals were randomly chosen. Each subject underwent a lateral cephalogram before and after prosthetic rehabilitation. During exposition, newly made prostheses were placed in the patient’s mouth. Teeth remained in maximal intercuspidation. Morphological parameters were evaluated according to the Ricketts, McNamara, and Tallgren’s method. Results: An inversely proportional association was observed between patient age and the distal part of the maxilla. A statistically significant connection was noted between the vertical dimension of alveolar ridge and anterior total and lower facial height conditioned by prosthetic rehabilitation. Conclusion: The height of the lateral part of the alveolar ridge of the maxilla remains in connection with the anterior total and lower facial height obtained in the course of prosthetic rehabilitation. The vertical dimension of the alveolar ridge of the maxilla seems to be in close relationship with the morphology of the lower jaw. Keywords: anterior facial height, cephalometric analysis, complete dentures, vertical occlusal dimension

  3. Glucocorticoids and erythropoietin in chronic lung disease of prematurity: Proliferative potential in lung fibroblast and epithelial cells exposed to tracheal aspirates.

    Science.gov (United States)

    Ohnishi, Satoshi; Ichiba, Hiroyuki; Saito, Mika; Hamazaki, Takashi; Matsumura, Hisako; Shintaku, Haruo

    2016-11-01

    We investigated the effects of glucocorticoids, erythropoietin (EPO) and spironolactone (SPL) n human fetal lung fibroblasts and human alveolar epithelial cells exposed to tracheal aspirate fluid (TAF) from extremely premature infants with chronic lung disease (CLD), characterized by fibrosis and changes in the alveolar epithelium. Fibroblasts and epithelial cells (FHs 738Lu and A549, respectively) were treated with different concentrations of hydrocortisone (HDC), dexamethasone (DEX), betamethasone (BET), SPL, and EPO in the absence or presence of TAF from infants with CLD (gestational age, 25.3 ± 0.8 weeks; birthweight, 658 ± 77 g; postnatal age, 0-28 days) and assayed for proliferation. Exposure to TAF resulted in a concentration-dependent proliferation of fibroblasts and epithelial cells. Proliferation of TAF-exposed fibroblasts was suppressed most significantly by 100 μmol/L DEX (21%, P = 0.046) and 300 mIU/mL EPO (18%, P = 0.02) and promoted most significantly by 0.4 μmol/L HDC (10%, P = 0.04). Epithelial proliferation was promoted by 4 μmol/L HDC (15%, P = 0.04), 10 μmol/L DEX (53%, P glucocorticoids alone did not significantly affect fibroblast proliferation. Glucocorticoids and EPO reduced fibroproliferation while promoting epithelial cell growth in vitro within certain dose ranges. Appropriate doses of glucocorticoids and EPO may be useful in the prevention and resolution of CLD in extremely premature infants. © 2016 Japan Pediatric Society.

  4. Salvage hypospadias repairs

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2008-01-01

    Full Text Available Aim: Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. Methods: This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children - buccal mucosal grafts (BMGs in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. Results: The age of children ranged from 1.5-15 years (mean 4.5. Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50% with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely - a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. Conclusions: In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4-6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised.

  5. Epithelial cell mitochondrial dysfunction and PINK1 are induced by transforming growth factor-beta1 in pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Avignat S Patel

    Full Text Available Epithelial cell death is a major contributor to fibrogenesis in the lung. In this study, we sought to determine the function of mitochondria and their clearance (mitophagy in alveolar epithelial cell death and fibrosis.We studied markers of mitochondrial injury and the mitophagy marker, PTEN-induced putative kinase 1 (PINK1, in IPF lung tissues by Western blotting, transmission electron microscopy (TEM, and immunofluorescence. In vitro experiments were carried out in lung epithelial cells stimulated with transforming growth factor-β1 (TGF-β1. Changes in cell function were measured by Western blotting, flow cytometry and immunofluorescence. In vivo experiments were performed using the murine bleomycin model of lung fibrosis.Evaluation of IPF lung tissue demonstrated increased PINK1 expression by Western blotting and immunofluorescence and increased numbers of damaged mitochondria by TEM. In lung epithelial cells, TGF-β1 induced mitochondrial depolarization, mitochondrial ROS, and PINK1 expression; all were abrogated by mitochondrial ROS scavenging. Finally, Pink1-/- mice were more susceptible than control mice to bleomycin induced lung fibrosis.TGF-β1 induces lung epithelial cell mitochondrial ROS and depolarization and stabilizes the key mitophagy initiating protein, PINK1. PINK1 ameliorates epithelial cell death and may be necessary to limit fibrogenesis.

  6. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    International Nuclear Information System (INIS)

    Meng, Erhong; Hanna, Ann; Samant, Rajeev S.; Shevde, Lalita A.

    2015-01-01

    Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair). Aberrant activation of the Hedgehog (Hh) signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer

  7. Repairing fuel for reinsertion

    International Nuclear Information System (INIS)

    Krukshenk, A.

    1986-01-01

    Eqiupment for nuclear reactor fuel assembly repairing produced by Westinghouse and Brawn Bovery companies is described. Repair of failed fuel assemblies replacement of defect fuel elements gives a noticeable economical effect. Thus if the cost of a new fuel assembly is 450-500 thousand dollars, the replacement of one fuel element in it costs approximately 40-60 thousand dollars. In simple cases repairing includes either removal of failed fuel elements from a fuel assembly and its reinsertion with the rest of fuel elements into the reactor core (reactor refueling), or replacement of unfailed fuel elements from one fuel assembly to a new one (fuel assembly overhaul and reconditioning)

  8. Immunoregulation by airway epithelial cells (AECs against respiratory virus infection

    Directory of Open Access Journals (Sweden)

    Yan YAN

    2017-11-01

    Full Text Available The respiratory tract is primary contact site of the body and environment, and it is ventilated by 10-20 thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbes, which contain the disease-causing pathogens. Airway epithelial cells (AECs are known to have innate sensor functions, which are similar to the "professional" immune cells, such as alveolar macrophage and sub- or intra-epithelial dendritic cells (DCs. Thus AECs are able to detect invading microbial danger including different types of respiratory viruses, and mount a potent host response, for example, activating type Ⅰ interferon signaling pathway genes. To avoid chronic inflammation and maintain the immunological homeostasis, the pulmonary system has developed intrinsic mechanisms to control local immune responses. Most recently, the role of AECs in control of local immunity has gained much attention, as 1 AECs express the pattern recognition receptors (PRRs, such as Toll-like receptors, retinoic acid inducible gene Ⅰ (RIG-I-like receptor, and so on, thus AECs are equipped to participate in innate detection of microbial encounter; 2 To keep immunological homeostasis in the respiratory tract, AECs behave not only as innate immune sensors but also as immune modulators in parallel, through modulating the sensitivity of innate immune sensing of both AECs per se and sub- or intra-epithelial immune cells; 3 Loss of modularity capacity of AECs might be involved in the development of chronic airway diseases. In present review, how the AECs act will be intensively discussed in response to respiratory viruses and modulate the local immunity through cis- and trans-factors (direct and indirect factors, as well as the consequence of impairment of this control of local immunity, in the development and exacerbation of airway diseases, such as acute and chronic rhinosinusitis. DOI: 10.11855/j.issn.0577-7402.2017.10.02

  9. 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.

  10. 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.

  11. Valve Repair or Replacement

    Science.gov (United States)

    ... Replacement Menu Topics Topics FAQs Valve Repair or Replacement Heart valves play a key role in this ... leaflets with a tissue patch. What is valve replacement? Severe valve damage means the valve must be ...

  12. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary

    2004-04-12

    The two broad categories of deposited weld metal repair and fiber-reinforced composite liner repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repair and for fiber-reinforced composite liner repair. Evaluation trials have been conducted using a modified fiber-reinforced composite liner provided by RolaTube and pipe sections without liners. All pipe section specimens failed in areas of simulated damage. Pipe sections containing fiber-reinforced composite liners failed at pressures marginally greater than the pipe sections without liners. The next step is to evaluate a liner material with a modulus of elasticity approximately 95% of the modulus of elasticity for steel. Preliminary welding parameters were developed for deposited weld metal repair in preparation of the receipt of Pacific Gas & Electric's internal pipeline welding repair system (that was designed specifically for 559 mm (22 in.) diameter pipe) and the receipt of 559 mm (22 in.) pipe sections from Panhandle Eastern. The next steps are to transfer welding parameters to the PG&E system and to pressure test repaired pipe sections to failure. A survey of pipeline operators was conducted to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. Completed surveys contained the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created

  13. Integrins and epithelial cell polarity.

    Science.gov (United States)

    Lee, Jessica L; Streuli, Charles H

    2014-08-01

    Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell-matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical-basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity. © 2014. Published by The Company of Biologists Ltd.

  14. Celebrating DNA's Repair Crew.

    Science.gov (United States)

    Kunkel, Thomas A

    2015-12-03

    This year, the Nobel Prize in Chemistry has been awarded to Tomas Lindahl, Aziz Sancar, and Paul Modrich for their seminal studies of the mechanisms by which cells from bacteria to man repair DNA damage that is generated by normal cellular metabolism and stress from the environment. These studies beautifully illustrate the remarkable power of DNA repair to influence life from evolution through disease susceptibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.

    Directory of Open Access Journals (Sweden)

    Victoria A Meliopoulos

    2016-08-01

    Full Text Available The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI. Although the β6 KO have morphologically normal lungs, they harbor constitutively activated lung CD11b+ alveolar macrophages (AM and elevated type I IFN signaling activity, which we traced to the loss of β6-activated transforming growth factor-β (TGF-β. Administration of exogenous TGF-β to β6 KO mice leads to reduced numbers of CD11b+ AMs, decreased type I IFN signaling activity and loss of the protective phenotype during influenza infection. Protection extended to other respiratory pathogens such as Sendai virus and bacterial pneumonia. Our studies demonstrate that the loss of one epithelial protein, αVβ6 integrin, can alter the lung microenvironment during both homeostasis and respiratory infection leading to reduced lung injury and improved survival.

  16. Protection of Meconium-Induced Lung Epithelial Injury by Protease Inhibitors

    Science.gov (United States)

    Ota, C; Gopallawa, I; Ivanov, V; Gewolb, IH; Uhal, BD

    2017-01-01

    Earlier work form this laboratory showed that exposure of alveolar epithelial cells (AECs) to meconium caused significant cell detachment and that meconium-induced detachment of cells was prevented by a protease inhibitor cocktail. Therefore, it was hypothesized that protease inhibitors might protect AEC monolayers against meconium-induced collapse of epithelial barrier function both in vitro and in vivo. To investigate this theory in vitro, albumin flux was measured across cultured, confluent monolayers of human type II derived cell line A549 on microporous filter inserts. Human meconium was collected from seven healthy full-term neonates and the samples were pooled and diluted prior to analysis. Exposure of AECs to 5% human meconium increased albumin flux across the cultured AEC monolayers, but the increase was significantly blocked by protease inhibitors (Pmeconium increased the passage of Evans Blue Dye (EBD) from the vascular compartment into the alveolar spaces, measured in bronchoalveolar lavage (BAL) fluid after intravenous injection of EBD. Moreover, intratrachial coinstillation of protease inhibitors prevented the meconium-induced increase in EBD passage into BAL fluid (Pmeconium-induced injury, and suggest the future possibility of using protease inhibitors in the treatment of meconium aspiration syndrome. PMID:29218325

  17. Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

    International Nuclear Information System (INIS)

    Dairou, Julien; Petit, Emile; Ragunathan, Nilusha; Baeza-Squiban, Armelle; Marano, Francelyne; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2009-01-01

    Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H 2 O 2 or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.

  18. Kinetics of gene expression of alkaline phosphatase during healing of alveolar bone in rats.

    Science.gov (United States)

    Rodrigues, Willian Caetano; Fabris, André Luís da Silva; Hassumi, Jaqueline Suemi; Gonçalves, Alaíde; Sonoda, Celso Koogi; Okamoto, Roberta

    2016-06-01

    Immunohistochemical studies and molecular biology have enabled us to identify numerous proteins that are involved in the metabolism of bone, and their encoding genes. Among these is alkaline phosphatase (ALP), an enzyme that is responsible for the initiation of mineralisation of the extracellular matrix during alveolar bone repair. To evaluate the gene expression of ALP during this process, we studied nine healthy adult male rats, which had their maxillary central incisors extracted from the right side and were randomly divided into three groups. During three experimental periods, 7 days, 14 days, and 28 days, the alveoli were curetted, the rats killed, and samples analysed by real-time reverse transcription polymerase chain reaction (qRT-PCR). The RNAm that encodes the gene for the synthesis of ALP was expressed during the three periods analysed, but its concentration was significantly increased at 14 and 28 days compared with at 7 days. There was no significant difference between 14 and 28 days (p=0.0005). We conclude that genes related to ALP are expressed throughout the healing process and more intensively during the later periods (14 and 28 days), which coincides with the increased formation of mineralised bone. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  19. Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes

    OpenAIRE

    R d’Aquino; A De Rosa; V Lanza; V Tirino; L Laino; A Graziano; V Desiderio; G Laino; G Papaccio

    2009-01-01

    In this study we used a biocomplex constructed from dental pulp stem/progenitor cells (DPCs) and a collagen sponge scaffold for oro-maxillo-facial (OMF) bone tissue repair in patients requiring extraction of their third molars. The experiments were carried out according to our Internal Ethical Committee Guidelines and written informed consent was obtained from the patients. The patients presented with bilateral bone reabsorption of the alveolar ridge distal to the second molar secondary to im...

  20. Reconstitution of mammary epithelial morphogenesis by murine embryonic stem cells undergoing hematopoietic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Shuxian Jiang

    2010-03-01

    Full Text Available Mammary stem cells are maintained within specific microenvironments and recruited throughout lifetime to reconstitute de novo the mammary gland. Mammary stem cells have been isolated through the identification of specific cell surface markers and in vivo transplantation into cleared mammary fat pads. Accumulating evidence showed that during the reformation of mammary stem cell niches by dispersed epithelial cells in the context of the intact epithelium-free mammary stroma, non-mammary epithelial cells may be sequestered and reprogrammed to perform mammary epithelial cell functions and to adopt mammary epithelial characteristics during reconstruction of mammary epithelium in regenerating mammary tissue in vivo.To examine whether other types of progenitor cells are able to contribute to mammary branching morphogenesis, we examined the potential of murine embryonic stem (mES cells, undergoing hematopoietic differentiation, to support mammary reconstitution in vivo. We observed that cells from day 14 embryoid bodies (EBs under hematopoietic differentiation condition, but not supernatants derived from these cells, when transplanted into denuded mammary fat pads, were able to contribute to both the luminal and myoepithelial lineages in branching ductal structures resembling the ductal-alveolar architecture of the mammary tree. No teratomas were observed when these cells were transplanted in vivo.Our data provide evidence for the dominance of the tissue-specific mammary stem cell niche and its role in directing mES cells, undergoing hematopoietic differentiation, to reprogram into mammary epithelial cells and to promote mammary epithelial morphogenesis. These studies should also provide insights into regeneration of damaged mammary gland and the role of the mammary microenvironment in reprogramming cell fate.

  1. CT findings of extrahepatic alveolar echinococcus (report of 12 cases)

    International Nuclear Information System (INIS)

    Liu Wenya; Shang Ge; Dang Jun

    2000-01-01

    Objective: To analyze the CT findings of extrahepatic alveolar echinococcus (EAE), and assess the value of CT scanning for the diagnosis of such cases. Methods: 12 patients with hepatic alveolar echinococcus (HAE) verified by operation and histology were examined by CT because of new complains. It was found that multiple organs were involved by the same lesions. Results: Brain AE (7 cases) showed single or multiple cerebral nodules, characterized by honeycombed hypodense structures or target sign after enhancement. Lung AE (3 cases) appeared as irregular, peripherally scattered nodules, with small vacuoles or cavities inside. The only 1 case with heart AE demonstrated a multiple calcifications and vacuoles within the mass. Adrenal gland AE (2 cases) presented as plaques containing different sizes of hypodense areas and calcifications. Retroperitoneal AE (2 cases) exhibited mass with plentiful calcifications. Conclusion: CT can define the location and morphology of the lesion, providing a reliable method for the diagnosis and treatment of the disease

  2. Tranexamic acid in diffuse alveolar hemorrhage (case report

    Directory of Open Access Journals (Sweden)

    Owlia MB

    2007-05-01

    Full Text Available Background: Wagener's granulomatosis (WG is a systemic necrotizing vasculitis characterized by upper and lower respiratory tract involvement and glomerulonephritis in most instances. Case Report: We report a 36 years old man with DAH secondary to WG, as the presenting feature. He successfully treated with standard immune suppressive agents including pulse methylprednisolone and cyclophospha-mide, along with tranexamic acid as adjunctive therapy for control of active bleeding. Laboratory results showed mild to moderate anemia, increased serum lactate dehydrogenase and very high c-ANCA titer. Chest radiograph showed bilateral alveolar infilterates. Conclusion: Diffuse Alveolar hemorrhage (DAH is a dread complication of Wagener’s granulomatosis. Control of acute phase of hemorrhage with tranexamic acid can improve out come of patients.

  3. Post-neonatal drop in alveolar SP-A expression

    DEFF Research Database (Denmark)

    Stray-Pedersen, Arne; Vege, Ashild; Stray-Pedersen, Asbjorg

    2008-01-01

    BACKGROUND: Surfactant protein A (SP-A) is synthesized in the lung and is a part of the innate immune system. The aim of this study was to evaluate the expression of SP-A in lung tissue from fetuses, infants, children and adults with special regard to sudden infant death syndrome (SIDS). METHODS......: A total of 160 cases were studied; 19 fetuses and neonates, 59 SIDS and 49 explained infant deaths below 1 year of age, 19 toddlers and 14 adults. Immunohistochemical detection of SP-A using monoclonal antibodies was performed by microscopy of lung tissue specimens collected at autopsy. A scoring system...... was developed enabling semi-quantitative estimation of staining intensity and distribution. RESULTS: SP-A was detected in the terminal bronchioles and alveolar spaces of fetuses >35 weeks gestation. The intra-alveolar SP-A expression increased in the perinatal period followed by a marked drop in infants aged...

  4. Diffuse alveolar hemorrhage resulting from Pauci-immune pulmonary capillaritis

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    Andreia Salarini Monteiro

    2003-08-01

    Full Text Available A 27 year-old female patient, cocaine user, presenting hemoptysis and progressive dyspnea with onset 48 hours prior to hospital admission, without any other signs or symptoms. Serum tests for infectious diseases, collagen disorders and vasculitis were negative. Urinalysis was normal. Computed tomography of the chest showed diffuse alveolar infiltrate, affecting mainly the lower left lobe. A thoracoscopic lung biopsy was performed to clarify the diagnosis. The histopathological findings showed capillaritis and diffuse intra-alveolar hemorrhage. Treated with steroid and cyclophosphamide pulse therapy, a good clinical and radiographical response was obtained. The recently described pauci-immune pulmonary capillaritis is characterized by the presence of isolated pulmonary capillaritis and negative serum testing for auto-immune diseases.

  5. AUTOMATIC SEGMENTATION AND CLASSIFICATION OF CELLS FROM BRONCHO ALVEOLAR LAVAGE

    Directory of Open Access Journals (Sweden)

    Olivier Lezoray

    2011-05-01

    Full Text Available Broncho alveolar lavage is the most commonly used diagnostic tool for confirming alveolar hemorrhage. Golde has introduced a ranking score, based on the hemosiderin content of macrophages which enables ranking cells from 0 to 4 based on the degree of Prussian blue stain. We propose a complete image analysis scheme to automatically perform both the extraction of the cellular objects and the ranking of each cell according to the Golde score. The image analysis techniques used mainly involve clustering and mathematical morphology. A 2D histogram is clustered to extract the main cellular components, a color watershed is used to determine and refine the regions. Finally, the cellular components of interest are firstly classified according to their hue and secondly according to their staining repartition. The proposed image analysis technique is very fast and produces reliable and accurate results.

  6. Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage.

    Science.gov (United States)

    Demitrack, Elise S; Aihara, Eitaro; Kenny, Susan; Varro, Andrea; Montrose, Marshall H

    2012-06-01

    The authors' goal was to measure pH at the gastric surface (pH₀) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pH₀. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. Similar rates of epithelial repair and resting pH₀ values (∼pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pH₀ was lower (2.5±0.2, P pH 3). Epithelial repair was slower at luminal pH 7 and pH₀ was higher (6.4±0.1, PpH₀ increased adjacent to damage. At luminal pH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH.

  7. Mucinous epithelial ovarian carcinoma.

    Science.gov (United States)

    Perren, T J

    2016-04-01

    Mucinous tumours involving the ovary may be benign, borderline, or malignant. Malignant tumours may be primary or metastatic. Differentiation between primary and metastatic involvement of the ovary is critical for optimal patient management. Even among skilled pathologists, this distinction can be problematic, as can the distinction between borderline ovarian tumour of intestinal type and well-differentiated invasive primary mucinous ovarian carcinoma. Primary invasive mucinous ovarian carcinoma and mucinous carcinoma metastatic to the ovary do have distinct patterns of macroscopic and microscopic involvement which will reveal the correct diagnosis in many cases. There are also well-recognized patterns of immunohistochemical staining that can further assist in this differentiation. As a result of the application of these histopathological techniques, the incidence of primary invasive mucinous epithelial carcinoma has fallen over recent years from ∼12% to ∼3%. However, even in recent multicentre clinical trials such as GOG 182, expert pathological review suggests that ∼60% of tumours originally classified as primary invasive mucinous carcinomas were in fact metastatic tumours to the ovary. Review of outcome data for patients with mucinous carcinoma entered into multicentre trials suggests that this subtype of disease has a particularly poor prognosis in comparison with other subtypes of ovarian carcinoma. Historically, patients with mucinous epithelial ovarian carcinoma (mEOC) have been treated in the same way as other subtypes of ovarian carcinoma. While there is undoubtedly a response rate to platinum-based chemotherapy, retrospective reviews of individual centre experience suggest that this is substantially lower than for high-grade papillary serous carcinoma and in the order of only 30%-40%. The mEOC trial was established to investigate the possibility that the combination of capecitabine and oxaliplatin (chemotherapy drugs more commonly used in colorectal

  8. Mammary alveolar cell as evaluation system for casein gene expression involved in glucose level

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    Young Tae Heo

    2017-06-01

    Full Text Available Objective Glucose is an essential fuel in the energy metabolism and synthesis pathways of all mammalian cells. In lactating animals, glucose is the major precursor for lactose and is a substrate for the synthesis of milk proteins and fat in mammary secretory (alveolar epithelial cells. However, clear utilization of glucose in mammary cells during lactogenesis is still unknown, due to the lack of in vitro analyzing models. Therefore, the objective of this study was to test the reliability of the mammary alveolar (MAC-T cell as an in vitro study model for glucose metabolism and lactating system. Methods Undifferentiated MAC-T cells were cultured in three types of Dulbecco’s modified Eagle’s medium with varying levels of glucose (no-glucose: 0 g/L, low-glucose: 1 g/L, and high-glucose: 4.5 g/L for 8 d, after which differentiation to casein secretion was induced. Cell proliferation and expression levels of apoptotic genes, Insulin like growth factor-1 (IGF1 receptor, oxytocin receptor, αS1, αS2, and β casein genes were analyzed at 1, 2, 4, and 8 d after differentiation. Results The proliferation of MAC-T cells with high-glucose treatment was seen to be significantly higher. Expression of apoptotic genes was not affected in any group. However, expression levels of the mammary development related gene (IGF1 receptor and lactation related gene (oxytocin receptor were significantly higher in the low-glucose group. Expressions of αS1-casein, αS2-casein, and β-casein were also higher in the low-glucose treated group as compared to that in the no-glucose and high-glucose groups. Conclusion The results demonstrated that although a high-glucose environment increases cell proliferation in MAC-T cells, a low-glucose treatment to MAC-T cells induces higher expression of casein genes. Our results suggest that the MAC-T cells may be used as an in vitro model to analyze mammary cell development and lactation connected with precise biological effects.

  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 rhabdomyosarcoma: origin and prognostic implications of molecular findings

    OpenAIRE

    Eguía-Aguilar, Pilar; López-Martínez, Briceida; Retana-Contreras, Carmen; Perezpeña-Diazconti, Mario

    2016-01-01

    We present the case of a 2-year-old male patient with a facial tumor partially treated with chemotherapy before his admission to our institution. The tumor involved from the frontal region to the maxillary floor, the orbit, and the maxillary and sphenoid sinuses. The histopathological diagnosis revealed a stage IV alveolar rhabdomyosarcoma with infiltration to bone marrow and cerebrospinal fluid. He was managed with four cycles of adriamycin, actinomycin, cyclophosphamide and vincristine; cis...

  11. Nerve damage associated with inferior alveolar nerve blocks.

    Science.gov (United States)

    Pogrel, M A; Bryan, J; Regezi, J

    1995-08-01

    The authors reviewed 12 cases in which altered sensation occurred in the distribution of the inferior alveolar or lingual nerves following injection of a local anesthetic for restorative treatment only. Most patients suffered only partial damage, but recovery was poor. The exact mechanism of the nerve damage is unknown, but a number of theories are proposed. The extent of this problem is also unknown, but many more cases probably exist than have been reported to date.

  12. [Treatment of dental accidents and associated alveolar fractures].

    Science.gov (United States)

    Teerijoki-Oksa, Tuija; Karjalainen, Sára; Soukka, Tero

    2010-01-01

    Diagnosis of dental accidents is based on patient history, clinical examination and imaging. A completely avulsed tooth should immediately be reimplanted, and a dislodged tooth urgently repositioned to the original position. Avulsed primary teeth will never be reimplanted, and primary teeth of children under three years are not repositioned. Furthermore, fractures of the alveolar process and various soft tissue injuries but not dental fractures require urgent treatment. All dental accident patients should be referred to dental consultation for further examinations and treatment.

  13. Diffuse alveolar hemorrhage in isolated pulmonary capillaritis: Case report

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    Medenica Milić

    2014-01-01

    Full Text Available Introduction. Pulmonary capillaritis is a small-diameter vessel vasculitis of the lung, which may occur in isolation as in isolated pauci-immune capillaritis, usually associated with the systemic vasculitis but it could be also related to collagen vascular diseases and in lung transplant rejection. Pulmonary capillaritis leads to diffuse alveolar hemorrhage. The clinical presentation includes symptoms like dyspnea, cough, pleuritic chest pain, fever and hemoptysis. Case Outline. A 48 year-old female patient, smoker, presented with progressive dyspnea. Serum tests for infectious diseases, collagen disorders and vasculitis were negative. Radiography and computed tomography of the chest showed diffuse alveolar infiltrates. Cytology of bronchoalveolar lavage showed presence of siderophages. A thoracoscopic lung biopsy was performed to clarify the diagnosis. The histopathological findings showed capillaritis and diffuse intraalveolar hemorrhage. Patient was treated with steroids, and good clinical and minimal radiographic response was obtained. Recently described pauci-immune pulmonary capillaritis has been characterized as p-ANCA (antineutrophil cytoplasmic antibodies negative isolated pulmonary capillaritis. Conclusion. Isolated pauci-immune pulmonary capillaritis is a rare disease. First clinical manifestations of the isolated pulmonary capillaritis were the symptoms of progressive dyspnea, radiographic and functional signs of the interstitial fibrosis. At the same time, the signs of extrapulmonary diseases were not found. Presence of siderophages in bronchoalveolar lavage indicated alveolar hemorrhage. Histopathological tests of the sample of the lung pointed to pulmonary capillaritis and intraalveolar hemorrhage. Prolonged treatment with corticosteroids was necessary.

  14. Strategies for alveolar ridge reconstruction and preservation for implant therapy.

    Science.gov (United States)

    Masaki, Chihiro; Nakamoto, Tetsuji; Mukaibo, Taro; Kondo, Yusuke; Hosokawa, Ryuji

    2015-10-01

    In dental implant treatment, ridge preservation and immediate or early implant placement are recommended to minimize bone resorption after tooth extraction and achieve esthetic outcomes. However, there is no consensus concerning the efficacy of this surgical method. There is also no consensus on the efficacy of bone and soft tissue grafts and surgical methods for alveolar ridge reconstruction. This paper reports ridge alteration in the anterior maxilla after tooth extraction, and summarizes the efficacy of various ridge preservation methods and immediate or early implant placement as alveolar ridge preservation methods to minimize bone resorption after tooth extraction. The advantages and complications of alveolar ridge reconstruction methods, and the efficacy and surgical method of soft tissue graft are reviewed. The anterior maxilla is in the esthetic zone, and the thickness of the bone on the labial side around the natural tooth is less than 1mm in many cases. Therefore, it is impossible to prevent bone resorption completely, even if ridge preservation and immediate or early implant placement are performed after tooth extraction. It is necessary to obtain stable and long-term esthetics by combining connective tissue and free gingival grafts, in addition to hard tissue augmentation. It is important to consider the burden and level of satisfaction of patients, such as in terms of donor site morbidity in hard and soft tissue grafting, and to pay attention to appropriate indications to avoid overtreatment. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  15. Quality assessment of systematic reviews on alveolar socket preservation.

    Science.gov (United States)

    Moraschini, V; Barboza, E Dos S P

    2016-09-01

    The aim of this overview was to evaluate and compare the quality of systematic reviews, with or without meta-analysis, that have evaluated studies on techniques or biomaterials used for the preservation of alveolar sockets post tooth extraction in humans. An electronic search was conducted without date restrictions using the Medline/PubMed, Cochrane Library, and Web of Science databases up to April 2015. Eligibility criteria included systematic reviews, with or without meta-analysis, focused on the preservation of post-extraction alveolar sockets in humans. Two independent authors assessed the quality of the included reviews using AMSTAR and the checklist proposed by Glenny et al. in 2003. After the selection process, 12 systematic reviews were included. None of these reviews obtained the maximum score using the quality assessment tools implemented, and the results of the analyses were highly variable. A significant statistical correlation was observed between the scores of the two checklists. A wide structural and methodological variability was observed between the systematic reviews published on the preservation of alveolar sockets post tooth extraction. None of the reviews evaluated obtained the maximum score using the two quality assessment tools implemented. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  16. Effect of Alveolar Ridge Preservation after Tooth Extraction

    Science.gov (United States)

    Avila-Ortiz, G.; Elangovan, S.; Kramer, K.W.O.; Blanchette, D.; Dawson, D.V.

    2014-01-01

    Alveolar ridge preservation strategies are indicated to minimize the loss of ridge volume that typically follows tooth extraction. The aim of this systematic review was to determine the effect that socket filling with a bone grafting material has on the prevention of postextraction alveolar ridge volume loss as compared with tooth extraction alone in nonmolar teeth. Five electronic databases were searched to identify randomized clinical trials that fulfilled the eligibility criteria. Literature screening and article selection were conducted by 3 independent reviewers, while data extraction was performed by 2 independent reviewers. Outcome measures were mean horizontal ridge changes (buccolingual) and vertical ridge changes (midbuccal, midlingual, mesial, and distal). The influence of several variables of interest (i.e., flap elevation, membrane usage, and type of bone substitute employed) on the outcomes of ridge preservation therapy was explored via subgroup analyses. We found that alveolar ridge preservation is effective in limiting physiologic ridge reduction as compared with tooth extraction alone. The clinical magnitude of the effect was 1.89 mm (95% confidence interval [CI]: 1.41, 2.36; p preservation. PMID:24966231

  17. Effects of alveolar ridge preservation on delayed implant osseointegration.

    Science.gov (United States)

    Shao, Shan; Li, Bin; Xue, Hui-Min; Huang, Hai-Yun; Liu, Gang-Li

    2015-01-01

    To evaluate the effects of alveolar ridge preservation with Bio-Oss bone substitute (Geistlich Pharma) on delayed implant osseointegration. The 3rd and 4th left and right mandibular premolars were extracted from four adult healthy male and female dogs. For the experimental group, we randomly selected two extraction sockets in each dog to be filled with Bio-Oss bone substitute (Geistlich Pharma). The two remaining extraction sockets remained untreated and served as the control group. Three months after Bio-Oss placement, dental implants were inserted into the alveolar bone of the experimental group and the control group. The osteogenic activity of the bone around the implants was assessed by evaluating the histological morphology and by estimating histomorphometric parameters at 3 and 6 months after delayed implantation. At 3 months, Goldner's trichrome staining analysis showed that the bone-implant contact rate and mineralised bone area around the implant were significantly higher in the experimental group (75.98% ± 8.97% and 69.52% ± 9.63%, respectively) than in the control group (56.13% ± 8.18% and 52.82% ± 7.25%, respectively; P alveolar ridge preservation by using Bio-Oss placement can promote osseointegration of delayed implantation. This may be a promising option for clinical use.

  18. Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide

    Directory of Open Access Journals (Sweden)

    Giuseppe Castellana

    2015-12-01

    Full Text Available Pulmonary alveolar microlithiasis (PAM is a rare disease characterised by the widespread intra-alveolar accumulation of minute calculi called microliths. It is caused by mutation of the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells. The present study explores the epidemiological, familial, genetic, clinical, diagnostic, radiological and therapeutic aspects with the aim of contributing to a better understanding of this uncommon disease. We searched articles on PAM published up to December 2014 and 544 papers were found, accounting for 1022 cases. PAM is present in all continents and in many nations, in particular in Turkey, China, Japan, India, Italy and the USA. Familiality is frequent. The clinical course is not uniform and the causes of this clinical variability seem to be largely nongenetic. The optimal diagnostic procedure is the association of chest high-resolution computed tomography (HRCT with bronchoalveolar lavage, but a chest radiograph may suffice in families in which a case has already been diagnosed. Moreover, chest radiography and HRCT allow the classification of the evolutionary phase of the disease and its severity. At present lung transplantation is the only effective therapy. However, better knowledge of the gene responsible offers hope for new therapies.

  19. Alveolar echinococcosis of the liver. Findings of magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hayasaka, Kazumasa; Tanaka, Yoshiaki; Okuhata, Yoshitaka; Yoshinobu, Takashi; Takemoto, Akiko; Himi, Kazuhisa; Mutoh, Haruomi [Nihon Univ., Tokyo (Japan). School of Medicine; Shuke, Noriyuki; Aburano, Tamio

    1995-06-01

    The purpose of the present study was to evaluate the findings of MR imaging obtained in patients with Echinococcus multilocularis involving the liver. For 10 patients with alveolar echinococcosis of the liver, the MR findings were compared with the histopathologic findings after biopsy or surgery. Conventional T1-weighted spin echo, T2-weighted spin echo and T1-weighted spin echo after Gd-DTPA were employed. The signal from the lesions of alveolar liver echinococcosis on T1-weighted images was hypointense in 16 of 23 lesions (69.6%), hyperintense in 4 (17.4%), and isointense in 3 (13.0%). The signal from the lesions on T2-weighted images was hyperintense in 20 lesions (87.0%), hypointense in 2 (8.7%), and isointense in one (4.3%). On using Gd-DTPA, 7 of 21 lesions (33.3%) were observed with rim enhancement, and 14 lesions (66.7%) were non-enhanced. We describe our clinical experience together with the various findings of MR imaging as observed in the patients with alveolar echinococcosis of the liver. MR imaging excels in visualizing a low-intensity rim and small cystic foci, with liquefaction necrotic foci displaying a variety of signal intensities. After Gd-DTPA administration, the surrounding inflammatory granulomatous foci could be more clearly visualized. (author).

  20. Requirement of alveolar bone formation for eruption of rat molars.

    Science.gov (United States)

    Wise, Gary E; He, Hongzhi; Gutierrez, Dina L; Ring, Sherry; Yao, Shaomian

    2011-10-01

    Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (Bmp6), was inhibited by injection of the first mandibular molar of the rat with a small interfering RNA (siRNA) targeted against Bmp6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption was either delayed or completely inhibited (seven molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced compared with the erupted first-molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that Bmp6 may be essential for promoting this growth. © 2011 Eur J Oral Sci.

  1. Massive Alveolar Hemorrhage During Wegener Granulomatosis: a Case Report

    Directory of Open Access Journals (Sweden)

    Gökhan Perincek

    2011-11-01

    Full Text Available This is a presentation of Wegener Granulomatosis (WG disease. Even though the lungs are rarely affected. massive alveolar hemorrhage is seen which leads to mortality. The patient was a 28 year old man. His illness was diagnosed as WG and glomerulonephritis a year previously and he was treated by administration of methylprednisolone orally. He had been treated irregularly. He applied to the emergency service with hemoptysis and asthma complaints two days earlier. After the results of his examination Hb: 3.6 gr/dl, Htc:10.3%, Üre:131 mg /dl, kreatini: 7.7 mg/dl, pH: 7.41, pO2: 55 mmHg, pCO2:33 mmHg, and being diagnosed as alveolar consolidation on lung X-ray, he was taken to the intensive care unit with a diagnosis of a massive alveolar hemorrhagei. He was intubated and attached to mechanical ventilation. He was treated with parenteral 1 mg/kg/day methylprednisolone and, siklofosfamid 2 mg/kg/day. He was extubated on the 21st day. He was taken to the chest service department on 24th day. He is still being treated.

  2. Alveolar osteitis following surgical removal of mandibular third molars.

    Science.gov (United States)

    Fridrich, K L; Olson, R A

    1990-01-01

    The purpose of this study was to evaluate 2 methods that could be used universally to reduce the incidence of alveolar osteitis. In addition, other variables including age and sex of patient, preoperative aspirin use and discomfort, and the use of oral contraceptives (OCs) were studied. A large controlled prospective study was completed with 952 surgical extraction sites in 476 patients. Postoperative dressings included lincomycin hydrochloride (Lincocin)/absorbable gelatin sponge (Gelfoam), oxytetracycline HCL-hydrocortisone acetate (Terra-Cortril)/absorbable gelatin sponge, and absorbable gelatin sponge/saline. Bilaterally impacted mandibular 3rd molars of similar surgical difficulty were selected. Standard accepted surgical technique was used. Patients were seen 1 and 7 days after surgery or as needed. Lincomycin hydrochloride/absorbable gelatin sponge and oxytetracycline HC1-hydrocortisone acetate/absorbable gelatin sponge were effective in reducing the incidence of alveolar osteitis. Lincomycin hydrochloride/absorbable gelatin sponge is preferred because of the increased morbidity associated with dressings containing petrolatum products. Absorbable gelatin sponge alone is not effective in reducing the incidence of alveolar osteitis. Age and OC use were found to be significant factors in the incidence of this problem.

  3. Transgenic expression of nonclassically secreted FGF suppresses kidney repair.

    Directory of Open Access Journals (Sweden)

    Aleksandr Kirov

    Full Text Available FGF1 is a signal peptide-less nonclassically released growth factor that is involved in angiogenesis, tissue repair, inflammation, and carcinogenesis. The effects of nonclassical FGF export in vivo are not sufficiently studied. We produced transgenic mice expressing FGF1 in endothelial cells (EC, which allowed the detection of FGF1 export to the vasculature, and studied the efficiency of postischemic kidney repair in these animals. Although FGF1 transgenic mice had a normal phenotype with unperturbed kidney structure, they showed a severely inhibited kidney repair after unilateral ischemia/reperfusion. This was manifested by a strong decrease of postischemic kidney size and weight, whereas the undamaged contralateral kidney exhibited an enhanced compensatory size increase. In addition, the postischemic kidneys of transgenic mice were characterized by hyperplasia of interstitial cells, paucity of epithelial tubular structures, increase of the areas occupied by connective tissue, and neutrophil and macrophage infiltration. The continuous treatment of transgenic mice with the cell membrane stabilizer, taurine, inhibited nonclassical FGF1 export and significantly rescued postischemic kidney repair. It was also found that similar to EC, the transgenic expression of FGF1 in monocytes and macrophages suppresses kidney repair. We suggest that nonclassical export may be used as a target for the treatment of pathologies involving signal peptide-less FGFs.

  4. Regulation of tissue repair and regeneration by electric fields.

    Science.gov (United States)

    Wang, En-tong; Zhao, Min

    2010-02-01

    Endogenous electric fields (EFs) have been detected at wounds and damaged tissues. The potential roles of EFs in tissue repair and regeneration have been an intriguing topic for centuries. Recent researches have provided significant insights into how naturally occurring EFs may participate in the control of tissue repair and regeneration. Applied EFs equivalent to the size of fields measured in vivo direct cell migration, cell proliferation and nerve sprouting at wounds. More remarkably, physiological EFs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation, wound void, contact inhibition release, population pressure and chemotaxis. EFs activate many intracellular signaling pathways in a directional manner. Modulation of endogenous wound EFs affects epithelial cell migration, cell proliferation, and nerve growth at cornea wounds in vivo. Electric stimulation is being tested clinically for the treatments of bone fracture, wound healing and spinal cord injury. EFs thus may represent a novel type of signaling paradigm in tissue repair and regeneration. Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration. This review introduces experimental evidence for the existence of endogenous EFs and discusses their roles in tissue repair and regeneration.

  5. Autotaxin induces lung epithelial cell migration through lysoPLD activity-dependent and -independent pathways

    Science.gov (United States)

    Zhao, Jing; He, Donghong; Berdyshev, Evgeny; Zhong, Mintao; Salgia, Ravi; Morris, Andrew J.; Smyth, Susan S.; Natarajan, Viswanathan; Zhao, Yutong

    2013-01-01

    SYNOPSIS Lung cell migration is a crucial step for re-epithelialization that in turn is essential for remodeling and repair after lung injury. We hypothesize that secreted autotaxin (ATX), which exhibits lysophospholipase D (lysoPLD) activity, stimulates lung epithelial cell migration through lysophosphatidic acid (LPA) generation-dependent and -independent pathways. Release of endogenous ATX protein and activity was detected in lung epithelial cell culture medium. ATX with V5 tag (ATX-V5) overexpressed conditional medium had higher LPA levels compared to control medium and stimulated cell migration through Gαi-coupled LPA receptors, cytoskeleton rearrangement, phosphorylation of PKCδ and cortactin at the leading edge of migrating cells. Inhibition of PKCδ attenuated ATX-V5 overexpressed conditional medium-mediated phosphorylation of cortactin. In addition, a recombinant ATX mutant, lacking lysoPLD activity, or heat-inactived ATX also induced lung epithelial cell migration. Extracelluar ATX bound to LPA receptor and integrin β4 complex on A549 cell surface. Finally, intratracheal administration of lipopolysaccharide into mouse airway induced ATX release and LPA production in bronchoalveolar lavage fluid. These results suggested a significant role for ATX in lung epithelial cell migration and remodeling through its ability to induce LPA production-mediated phosphorylation of PKCδ and cortactin. In addition we also demonstrated assocation of ATX with epithelial cell surface LPA receptor and integrin β4. PMID:21696367

  6. Mechanism of action and morphologic changes in the alveolar bone in response to selective alveolar decortication-facilitated tooth movement.

    Science.gov (United States)

    Baloul, S Susan; Gerstenfeld, Louis C; Morgan, Elise F; Carvalho, Roberto S; Van Dyke, Thomas E; Kantarci, Alpdogan

    2011-04-01

    The aim of this study was to test if corticotomy-induced osteoclastogenesis and bone remodeling underlie orthodontic tooth movement and how selective alveolar decortication enhances the rate of tooth movement. A total of 114 Sprague-Dawley rats were included in 3 treatment groups: selective alveolar decortication alone (SADc); tooth movement alone (TM); and "combined" therapy (SADc + TM). Surgery was performed around the buccal and palatal aspects of the left maxillary first molar tooth and included 5 decortication dots on each side. Tooth movement was performed on the first molar using a 25-g Sentalloy spring. Measurements were done at baseline (day 0: no treatment rendered) and on days 3, 7, 14, 21, 28 and 42. Microcomputed tomography, Faxitron analyses, and quantitative real-time polymerase chain reaction (q-PCR) of expressed mRNAs were used to assess changes. The combined group showed increased tooth movement (P = 0.04) at 7 days compared with the tooth movement group with significantly decreased bone volume (62%; P = 0.016) and bone mineral content (63%; P = 0.015). RNA markers of osteoclastic cells and key osteoclastic regulators (M-CSF [macrophage colony-stimulating factor], RANKL [receptor activator of nuclear factor kappa-B ligand], OPG [osteoprotegerin], calcitonin receptor [CTR], TRACP-5b [tartrate-resistant acid phosphatase 5b], cathepsin K [Ctsk]) all showed expression indicating increased osteoclastogenesis in the combined group. RNA markers of osteoblastic cells (OPN [osteopontin], BSP [bone sialoprotein], OCN [osteocalcin]) also showed increased anabolic activity in response to the combination of alveolar decortication and tooth movement. The data suggest that the alveolar decortication enhances the rate of tooth movement during the initial tooth displacement phase; this results in a coupled mechanism of bone resorption and bone formation during the earlier stages of treatment, and this mechanism underlies the rapid orthodontic tooth movement

  7. Influence of the Alveolar Cleft Type on Preoperative Estimation Using 3D CT Assessment for Alveolar Cleft

    Directory of Open Access Journals (Sweden)

    Hang Suk Choi

    2012-09-01

    Full Text Available Background The bone graft for the alveolar cleft has been accepted as one of the essentialtreatments for cleft lip patients. Precise preoperative measurement of the architecture andsize of the bone defect in alveolar cleft has been considered helpful for increasing the successrate of bone grafting because those features may vary with the cleft type. Recently, somestudies have reported on the usefulness of three-dimensional (3D computed tomography(CT assessment of alveolar bone defect; however, no study on the possible implication of thecleft type on the difference between the presumed and actual value has been conducted yet.We aimed to evaluate the clinical predictability of such measurement using 3D CT assessmentaccording to the cleft type.Methods The study consisted of 47 pediatric patients. The subjects were divided according tothe cleft type. CT was performed before the graft operation and assessed using image analysissoftware. The statistical significance of the difference between the preoperative estimationand intraoperative measurement was analyzed.Results The difference between the preoperative and intraoperative values were -0.1±0.3cm3 (P=0.084. There was no significant intergroup difference, but the groups with a cleftpalate showed a significant difference of -0.2±0.3 cm3 (P<0.05.Conclusions Assessment of the alveolar cleft volume using 3D CT scan data and image analysissoftware can help in selecting the optimal graft procedure and extracting the correct volumeof cancellous bone for grafting. Considering the cleft type, it would be helpful to extract anadditional volume of 0.2 cm3 in the presence of a cleft palate.

  8. Treatment of sharp mandibular alveolar process with hybrid prosthesis

    Directory of Open Access Journals (Sweden)

    Sukaedi Sukaedi

    2010-09-01

    Full Text Available Background: Losing posterior teeth for a long time would occasionally lead to the sharpening of alveolar process. The removable partial denture usually have problems when used during mastication, because of the pressure on the mucosa under the alveolar ridge. Purpose: The purpose of this case report was to manage patients with sharp mandibular alveolar process by wearing hybrid prosthesis with extra coronal precision attachment retention and soft liner on the surface base beneath the removable partial denture. Case: A 76 years old woman visited the Prosthodontic Clinic Faculty of Dentistry Airlangga University. The patient had a long span bridge on the upper jaw and a free end acrylic removable partial denture on the lower jaw. She was having problems with mastication. The patient did not wear her lower denture because of the discomfort with it during mastication. Hence, she would like to replace it with a new removable partial denture. Case management: The patient was treated by wearing a hybrid prosthesis with extra coronal precision attachment on the lower jaw. Soft liner was applied on the surface of the removable partial denture. Hybrid prosthesis is a complex denture consisting of removable partial denture and fixed bridge. Conclusion: It concluded that after restoration, the patient had no problems with sharp alveolar process with her new denture, and she was able to masticate well.Latar belakang: Kehilangan geligi posterior dapat menimbulkan processus alveolaris tajam. Gigi tiruan sebagian lepasan mempunyai masalah selama pengunyahan karena adanya tekanan di mukosa di bawah alveolar ridge. Tujuan: Tujuan laporan kasus ini adalah untuk menjelaskan cara menangani pasien yang mempunyai prosesus alveolaris yang tajam di rahang bawah dengan dibuatkan protesis hybrid dengan daya tahan extra coronal precision attachment dan soft liner di permukaan bawah basis gigi tiruan sebagian lepasan. Kasus: Pasien wanita berumur 76 tahun datang di klinik

  9. Postreplicative Mismatch Repair

    Science.gov (United States)

    Jiricny, Josef

    2013-01-01

    The mismatch repair (MMR) system detects non-Watson–Crick base pairs and strand misalignments arising during DNA replication and mediates their removal by catalyzing excision of the mispair-containing tract of nascent DNA and its error-free resynthesis. In this way, MMR improves the fidelity of replication by several orders of magnitude. It also addresses mispairs and strand misalignments arising during recombination and prevents synapses between nonidentical DNA sequences. Unsurprisingly, MMR malfunction brings about genomic instability that leads to cancer in mammals. But MMR proteins have recently been implicated also in other processes of DNA metabolism, such as DNA damage signaling, antibody diversification, and repair of interstrand cross-links and oxidative DNA damage, in which their functions remain to be elucidated. This article reviews the progress in our understanding of the mechanism of replication error repair made during the past decade. PMID:23545421

  10. DNA repair and cancer

    International Nuclear Information System (INIS)

    Rathore, Shakuntla; Joshi, Pankaj Kumar; Gaur, Sudha

    2012-01-01

    DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecule that encode it's genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many one million individual molecular lesions per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions include potentially harmful mutation in cell's genome which affect the survival of it's daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. Inherited mutation that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary non polyposis colorectal cancer (HNPCC) is strongly associated with specific mutation in the DNA mismatch repair pathway. BRCA1, BRCA2 two famous mutation conferring a hugely increased risk of breast cancer on carrier, are both associated with a large number of DNA repair pathway, especially NHEJ and homologous recombination. Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing most typically cancer cells are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Modern cancer treatment attempt to localize the DNA damage to cells and tissue only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). (author)

  11. Meniscal repair devices.

    Science.gov (United States)

    Barber, F A; Herbert, M A

    2000-09-01

    Meniscal repair devices not requiring accessory incisions are attractive. Many factors contribute to their clinical effectiveness including their biomechanical characteristics. This study compared several new meniscal repair devices with standard meniscal suture techniques. Using a porcine model, axis-of-insertion loads were applied to various meniscal sutures and repair devices. A single device or stitch was placed in a created meniscal tear and a load applied. Both loads and modes of failure were recorded. The load-to-failure data show stratification into 4 distinct statistical groups. Group A, 113 N for a double vertical stitch; group B, 80 N for a single vertical stitch; group C, 57 N for the BioStinger, 56 N for a horizontal mattress stitch, and 50 N for the T-Fix stitch; and group D, 33 N for the Meniscus Arrow (inserted by hand or gun), 32 N for the Clearfix screw, 31 N for the SDsorb staple, 30 N for the Mitek meniscal repair system, and 27 N for the Biomet staple. The failure mechanism varied. Sutures broke away from the knot. The Meniscus Arrow and BioStinger pulled through the inner rim with the crossbar intact. The Clearfix screw failed by multiple mechanisms, whereas 1 leg of the SDsorb staple always pulled out of the outer rim. The Mitek device usually failed by pullout from the inner rim. The Biomet staple always broke at the crosshead or just below it. Although the surgeon should be aware of the material properties of the repair technique chosen for a meniscal repair, this information is only an indication of device performance and may not correlate with clinical healing results.

  12. Nuclear fuel assembly repair

    International Nuclear Information System (INIS)

    Bassler, E.A.; Stavsky, R.

    1986-01-01

    In response to utility needs to recover investment in nuclear fuel assemblies, Westinghouse Electric Corporation has developed tools and equipment to repair damaged fuel assemblies in an economical and safe manner, to enable utilities to reinsert these assemblies in the core. There are two possible repair techniques - bottom nozzle reconstitution and top nozzle reconstitution. Both techniques have been approved through formal design review; prototype tools have been built and successfully tested. The tools are modular in nature, easily transportable, and designed to fit the spent fuel pool at a reactor site. (author)

  13. Biological radiolesions and repair

    International Nuclear Information System (INIS)

    Laskowski, W.

    1981-01-01

    In 7 chapters, the book answers the following questions: 1) What reactions are induced in biological matter by absorption of radiation energy. 2) In what parts of the cell do the radiation-induced reactions with detectable biological effects occur. 3) In which way are these cell components changed by different qualities of radiation. 4) What are the cell mechanisms by which radiation-induced changes can be repaired. 5) What is the importance of these repair processes for man, his life and evolution. At the end of each chapter, there is a bibliography of relevant publications in this field. (orig./MG) [de

  14. Comparative radiographic evaluation of alveolar bone healing associated with autologous platelet-rich plasma after impacted mandibular third molar surgery.

    Science.gov (United States)

    Célio-Mariano, Ronaldo; de Melo, Willian Morais; Carneiro-Avelino, Cássia

    2012-01-01

    This study radiographically evaluated the performance of autologous platelet-rich plasma (PRP) applied in tooth sockets. Thirty extractions of bilateral impacted mandibular third molars were performed in 15 volunteers (7 men, 8 women; 18 to 22 years old). After extraction of right and left mandibular third molars, the socket at 1 side received the autologous PRP (PRP group) and the other was filled with blood clot (control group). Millimeter periapical radiographs were obtained 7 days, 1 month, and 2, 3, and 6 months postoperatively. Radiographic bone density was quantified 3 times by the same examiner at different moments using HLImage 97 software, and data were statistically analyzed by Statgraf 7.0 software (analysis of variance and Tukey test). In general, there was significantly faster bone formation in sockets treated with PRP (P third month (P < .01) for the PRP group. No statistical differences were observed on the seventh day and sixth month of investigation, yet there were higher means of radiographic bone density in sockets treated with PRP. In the control group, men exhibited significant bone repair compared with women (P < .05). Autologous PRP was found to accelerate alveolar bone regeneration, and men presented better repair after tooth extraction. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  15. Groin hernia repair in young males: mesh or sutured repair?

    DEFF Research Database (Denmark)

    Bisgaard, T; Bay-Nielsen, M; Kehlet, H

    2010-01-01

    Large-scale data for the optimal inguinal hernia repair in younger men with an indirect hernia is not available. We analysed nationwide data for risk of reoperation in younger men after a primary repair using a Lichtenstein operation or a conventional non-mesh hernia repair....

  16. Electro active repair of concrete: innovation for increased repair durability

    NARCIS (Netherlands)

    Polder, R.B.; Geiker, M.R.

    2017-01-01

    Many repairs of chloride induced corrosion in practice fail within 10 years due to chloride remaining after cleaning the steel, causing corrosion re-activation. An improvement of conventional repair was invented, Electro Active Repair, that electrochemically removes chlorides. After concrete

  17. Effects of fibrin adhesive material (Tissucol) on alveolar healing in rats under stress.

    OpenAIRE

    Alves-Rezende, Maria C. R. [UNESP; Okamoto, Tetuo [UNESP

    1997-01-01

    The effects of Tissucol on alveolar healing following stress were evaluated histologically, comparing three groups of 28 male albino rats each. Stress was applied and their right upper incisors were extracted. Group A served as an empty control site. In Group B, Tissucol was applied into the alveolar cavity. Group C received local antifibrinolytic treatment (alveolar irrigation with epsilon-aminocaproic acid solution) before implant of Tissucol into the tooth socket. Four animals in each grou...

  18. Changes in alveolar bone support induced by the Herbst appliance: a tomographic evaluation

    OpenAIRE

    Schwartz, João Paulo; Raveli, Taisa Boamorte; Schwartz-Filho, Humberto Osvaldo; Raveli, Dirceu Barnabé

    2016-01-01

    ABSTRACT Objective: This study evaluated alveolar bone loss around mandibular incisors, induced by the Herbst appliance. Methods: The sample consisted of 23 patients (11 men, 12 women; mean age of 15.76 ± 1.75 years), Class II, Division 1 malocclusion, treated with the Herbst appliance. CBCT scans were obtained before treatment (T0) and after Herbst treatment (T1). Vertical alveolar bone level and alveolar bone thickness of mandibular incisors were assessed. Buccal (B), lingual (L) and to...

  19. Ship Repair Workflow Cost Model

    National Research Council Canada - National Science Library

    McDevitt, Mike

    2003-01-01

    The effects of intermittent work patterns and funding on the costs of ship repair and maintenance were modeled for the San Diego region in 2002 for Supervisor of Shipbuilding and Repair (SUPSHIP) San Diego...

  20. Composite Repair System, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — GTL has developed an innovative composite repair methodology known as the Composite Repair System (CRS). In this phase I effort, CRS is being developed for the...

  1. About the Collision Repair Campaign

    Science.gov (United States)

    EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.

  2. Airway Epithelial Cell Integrity Protects from Cytotoxicity of Pseudomonas aeruginosa Quorum-Sensing Signals.

    Science.gov (United States)

    Losa, Davide; Köhler, Thilo; Bacchetta, Marc; Saab, Joanna Bou; Frieden, Maud; van Delden, Christian; Chanson, Marc

    2015-08-01

    Cell-to-cell communication via gap junctions regulates airway epithelial cell homeostasis and maintains the epithelium host defense. Quorum-sensing molecules produced by Pseudomonas aeruginosa coordinate the expression of virulence factors by this respiratory pathogen. These bacterial signals may also incidentally modulate mammalian airway epithelial cell responses to the pathogen, a process called interkingdom signaling. We investigated the interactions between the P. aeruginosa N-3-oxo-dodecanoyl-L-homoserine lactone (C12) quorum-sensing molecule and human airway epithelial cell gap junctional intercellular communication (GJIC). C12 degradation and its effects on cells were monitored in various airway epithelial cell models grown under nonpolarized and polarized conditions. Its concentration was further monitored in daily tracheal aspirates of colonized intubated patients. C12 rapidly altered epithelial integrity and decreased GJIC in nonpolarized airway epithelial cells, whereas other quorum-sensing molecules had no effect. The effects of C12 were dependent on [Ca(2+)]i and could be prevented by inhibitors of Src tyrosine family and Rho-associated protein kinases. In contrast, polarized airway cells grown on Transwell filters were protected from C12 except when undergoing repair after wounding. In vivo during colonization of intubated patients, C12 did not accumulate, but it paralleled bacterial densities. In vitro C12 degradation, a reaction catalyzed by intracellular paraoxonase 2 (PON2), was impaired in nonpolarized cells, whereas PON2 expression was increased during epithelial polarization. The cytotoxicity of C12 on nonpolarized epithelial cells, combined with its impaired degradation allowing its accumulation, provides an additional pathogenic mechanism for P. aeruginosa infections.

  3. Augmentation of residual alveolar bone height with tissue engineering for dental implant placement

    Directory of Open Access Journals (Sweden)

    S M Balaji

    2014-01-01

    Full Text Available The challenge of correcting deficient vertical alveolar height for dental implant placement has been there since dental implants came in to regular clinical placement. The ability of various methods to increase the residual alveolar height has met with varying results. The primary reason is that the techniques were not quite successful in maintaining the required residual alveolar height. Use of Bone Morphogentic Protein, especially rhBMP-2 has been met with high degree of success in deficient vertical alveolar height in a mandibular ridge. The demonstration of this using a case has been presented here.

  4. Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma.

    Science.gov (United States)

    Berry, M; Hargadon, B; Morgan, A; Shelley, M; Richter, J; Shaw, D; Green, R H; Brightling, C; Wardlaw, A J; Pavord, I D

    2005-06-01

    Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation. The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration. Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mild-to-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone. In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

  5. Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse.

    Science.gov (United States)

    Lax, Siân; Rayes, Julie; Wichaiyo, Surasak; Haining, Elizabeth J; Lowe, Kate; Grygielska, Beata; Laloo, Ryan; Flodby, Per; Borok, Zea; Crandall, Edward D; Thickett, David R; Watson, Steve P

    2017-12-01

    There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (AECI)-specific or hematopoietic-specific podoplanin deficient, mice were established using cre-loxP strategies. Combining these with intratracheal (IT) instillations of lipopolysaccharide (LPS), we demonstrate that arterial oxygen saturation decline in response to IT-LPS in platelet-specific CLEC-2-deficient mice is significantly augmented. An increase in bronchoalveolar lavage (BAL) neutrophils and protein was also observed 48 h post-IT-LPS, with significant increases in pro-inflammatory chemokines detected in BAL of platelet-specific CLEC-2-deficient animals. Deletion of podoplanin from hematopoietic cells but not AECIs also reduces lung function and increases pro-inflammatory chemokine expression following IT-LPS. Furthermore, we demonstrate that following IT-LPS, platelets are present in BAL in aggregates with neutrophils, which allows for CLEC-2 interaction with podoplanin expressed on BAL inflammatory alveolar macrophages. Taken together, these data suggest that the platelet CLEC-2-podoplanin signaling axis regulates the severity of lung inflammation in mice and is a possible novel target for therapeutic intervention in patients at risk of developing ARDS. Copyright © 2017 the American Physiological Society.

  6. DNA Repair Systems

    Indian Academy of Sciences (India)

    Thanks to the pioneering research work of Lindahl, Sancar, Modrich and their colleagues, we now have an holistic awareness of how DNA damage occurs and how the damage is rectified in bacteria as well as in higher organisms including human beings. A comprehensive understanding of DNA repair has proven crucial ...

  7. DNA Repair Systems

    Indian Academy of Sciences (India)

    D N Rao is a professor at the. Department of Biochemistry,. Indian Institute of Science,. Bengaluru. His research work primarily focuses on. DNA interacting proteins in prokaryotes. This includes restriction-modification systems, DNA repair proteins from pathogenic bacteria and and proteins involved in horizontal gene ...

  8. Comprehensive Small Engine Repair.

    Science.gov (United States)

    Hires, Bill; And Others

    This curriculum guide contains the basic information needed to repair all two- and four-stroke cycle engines. The curriculum covers four areas, each consisting of one or more units of instruction that include performance objectives, suggested activities for teacher and students, information sheets, assignment sheets, job sheets, visual aids,…

  9. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R [ORNL; Peter, William H [ORNL

    2015-02-13

    The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.