Enhanced alveolar growth and remodeling in Guinea pigs raised at high altitude.

PubMed

Hsia, Connie C W; Carbayo, Juan J Polo; Yan, Xiao; Bellotto, Dennis J

2005-05-12

To examine the effects of chronic high altitude (HA) exposure on lung structure during somatic maturation, we raised male weanling guinea pigs at HA (3800m) for 1, 3, or 6 months, while their respective male littermates were simultaneously raised at low altitude (LA, 1200m). Under anaesthesia, airway pressure was measured at different lung volumes. The right lung was fixed at a constant airway pressure for morphometric analysis under light and electron microscopy. In animals raised at HA for 1 month, lung volume, alveolar surface area and alveolar-capillary blood volume (V(c)) were elevated above LA control values. Following 3-6 months of HA exposure, increases in lung volume and alveolar surface area persisted while the initial increase in V(c) normalized. Additional adaptation occurred, including a higher epithelial cell volume, septal tissue volume and capillary surface area, a lower alveolar duct volume and lower harmonic mean diffusion barrier resulting in higher membrane and lung diffusing capacities. These data demonstrate enhanced alveolar septal growth and progressive acinar remodeling during chronic HA exposure with long-term augmentation of alveolar dimensions as well as functional compensation in lung compliance and diffusive gas transport.

Management of massive diffuse alveolar hemorrhage in a child with systemic lupus erythematosus.

PubMed

Kimura, Dai; Shah, Samir; Briceno-Medina, Mario; Sathanandam, Shyam; Haberman, Brent; Zhang, Jie; Myers, Linda; Kumar, Tk Susheel; Knott-Craig, Christopher

2015-01-01

Diffuse alveolar hemorrhage (DAH) from systemic lupus erythematosus (SLE) is a rare but potentially life-threatening condition. We report the case of a 14-year-old female with SLE who developed hypoxia and shock secondary to severe alveolar hemorrhage. She was successfully managed by placement on extracorporeal membrane oxygenation (ECMO) followed by emergent pulmonary lobectomy and medical treatment including high-dose methylprednisolone, cyclophosphamide, intravenous immunoglobulin, and plasmapheresis.

Linking lung function to structural damage of alveolar epithelium in ventilator-induced lung injury.

PubMed

Hamlington, Katharine L; Smith, Bradford J; Dunn, Celia M; Charlebois, Chantel M; Roy, Gregory S; Bates, Jason H T

2018-05-06

Understanding how the mechanisms of ventilator-induced lung injury (VILI), namely atelectrauma and volutrauma, contribute to the failure of the blood-gas barrier and subsequent intrusion of edematous fluid into the airspace is essential for the design of mechanical ventilation strategies that minimize VILI. We ventilated mice with different combinations of tidal volume and positive end-expiratory pressure (PEEP) and linked degradation in lung function measurements to injury of the alveolar epithelium observed via scanning electron microscopy. Ventilating with both high inspiratory plateau pressure and zero PEEP was necessary to cause derangements in lung function as well as visually apparent physical damage to the alveolar epithelium of initially healthy mice. In particular, the epithelial injury was tightly associated with indicators of alveolar collapse. These results support the hypothesis that mechanical damage to the epithelium during VILI is at least partially attributed to atelectrauma-induced damage of alveolar type I epithelial cells. Copyright © 2018. Published by Elsevier B.V.

Irreversible Electroporation in a Swine Lung Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dupuy, Damian E., E-mail: ddupuy@lifespan.org; Aswad, Bassam, E-mail: baswad@lifespan.org; Ng, Thomas, E-mail: tng@usasurg.org

2011-04-15

Purpose: This study was designed to evaluate the safety and tissue effects of IRE in a swine lung model. Methods: This study was approved by the institutional animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3-4 monopolar electrodes) under fluoroscopic guidance and with pancuronium neuromuscular blockade and EKG gating. IRE electrodes were placed into the central and middle third of the right mid and lower lobes in all animals. Postprocedure PA and lateral chest radiographs were obtained to evaluate for pneumothorax. Three animals were sacrificed at 2more » weeks and six at 4 weeks. Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h before sacrifice. The treated lungs were removed en bloc, perfused with formalin, and sectioned. Gross pathologic and microscopic changes after standard hematoxylin and eosin staining were analyzed within the areas of IRE lesion creation. Results: No significant adverse events were identified. CT showed focal areas of spiculated high density ranging in greatest diameter from 1.1-2.2 cm. On gross inspection of the sectioned lung, focal areas of tan discoloration and increased density were palpated in the areas of IRE. Histological analysis revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory infiltration that respected the boundaries of the interlobular septae. No pathological difference could be discerned between the 2- and 4-week time points. The bronchioles and blood vessels within the areas of IRE were intact and did not show signs of tissue injury. Conclusion: IRE creates focal areas of diffuse alveolar damage without creating damage to the bronchioles or blood vessels. Short-term safety in a swine model appears to be satisfactory.« less

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats.

PubMed

Sanbe, Toshihiro; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Tamaki, Naofumi; Yamamoto, Tatsuo

2007-11-01

A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.

Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange

NASA Technical Reports Server (NTRS)

Vidal Melo, M. F.; Loeppky, J. A.; Caprihan, A.; Luft, U. C.

1993-01-01

This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.

Metastatic renal cell carcinoma complicated with diffuse alveolar hemorrhage: a rare adverse effect of sunitinib.

PubMed

Yamada, Tadaaki; Ohtsubo, Koushiro; Izumi, Kouji; Takeuchi, Shinji; Mouri, Hisatsugu; Yamashita, Kaname; Yasumoto, Kazuo; Ghenev, Peter; Kitagawa, Satoshi; Yano, Seiji

2010-12-01

We report the case of a 67-year-old man with metastatic papillary renal cell carcinoma (RCC) who developed bloody sputum after the administration of sunitinib. Chest computed tomography revealed diffuse ground-glass opacity lesions, and bloody bronchoalveolar lavage fluid was obtained by flexible bronchoscopy. The abnormal shadows promptly regressed after withdrawal of sunitinib. In four cycles of sunitinib treatment, he suffered from controllable diffuse alveolar hemorrhage. Finally, he died of respiratory failure 8 months after onset. This is the first case report of diffuse alveolar hemorrhage as an adverse effect of sunitinib in metastatic papillary RCC. Care should be taken with pulmonary hemorrhage in the use of anti-angiogenesis agents in not only squamous cell lung cancer, but also metastatic lung tumors.

Permanent nerve damage from inferior alveolar nerve blocks: a current update.

PubMed

Pogrel, M Anthony

2012-10-01

Permanent nerve involvement has been reported following inferior alveolar nerve blocks. This study provides an update on cases reported to one unit in the preceding six years. Lidocaine was associated with 25 percent of cases, articaine with 33 percent of cases, and prilocaine with 34 percent of cases. It does appear that inferior alveolar nerve blocks can cause permanent nerve damage with any local anesthetic, but the incidences may vary.

Drug-induced lung injury associated with sorafenib: analysis of all-patient post-marketing surveillance in Japan.

PubMed

Horiuchi-Yamamoto, Yuka; Gemma, Akihiko; Taniguchi, Hiroyuki; Inoue, Yoshikazu; Sakai, Fumikazu; Johkoh, Takeshi; Fujimoto, Kiminori; Kudoh, Shoji

2013-08-01

Sorafenib is a multi-kinase inhibitor currently approved in Japan for unresectable and/or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma. Although drug-induced lung injury has recently been the focus of interest in Japanese patients treated with molecular targeting agents, the clinical features of patients receiving sorafenib remain to be completely investigated. All-patient post-marketing surveillance data was obtained within the frame of Special Drug Use Investigation; between April 2008 and March 2011, we summarized the clinical information of 62 cases with drug-induced lung injury among approximately 13,600 sorafenib-treated patients in Japan. In addition, we summarized the results of evaluation by a safety board of Japanese experts in 34 patients in whom pulmonary images were available. For the calculation of reporting frequency, interim results of Special Drug Use Investigation were used. In the sets of completed reports (2,407 in renal cell carcinoma and 647 in hepatocellular carcinoma), the reporting frequency was 0.33 % (8 patients; fatal, 4/8) and 0.62 % (4 patients; fatal, 2/4), respectively. Major clinical symptoms included dyspnea, cough, and fever. Evaluation of the images showed that 18 cases out of 34 patients had a pattern of diffuse alveolar damage. The patients with hepatocellular carcinoma showed a greater incidence and earlier onset of lung injury than those with renal cell carcinoma. Although the overall reporting frequency of sorafenib-induced lung injury is not considered high, the radiological diffuse alveolar damage pattern led to a fatal outcome. Therefore, early recognition of sorafenib-induced lung injury is crucial for physicians and patients.

Transport rather than diffusion-dependent route for nitric oxide gas activity in alveolar epithelium.

PubMed

Brahmajothi, Mulugu V; Mason, S Nicholas; Whorton, A Richard; McMahon, Timothy J; Auten, Richard L

2010-07-15

The pathway by which inhaled NO gas enters pulmonary alveolar epithelial cells has not been directly tested. Although the expected mechanism is diffusion, another route is the formation of S-nitroso-L-cysteine, which then enters the cell through the L-type amino acid transporter (LAT). To determine if NO gas also enters alveolar epithelium this way, we exposed alveolar epithelial-rat type I, type II, L2, R3/1, and human A549-cells to NO gas at the air liquid interface in the presence of L- and D-cysteine+/-LAT competitors. NO gas exposure concentration dependently increased intracellular NO and S-nitrosothiol levels in the presence of L- but not D-cysteine, which was inhibited by LAT competitors, and was inversely proportional to diffusion distance. The effect of L-cysteine on NO uptake was also concentration dependent. Without preincubation with L-cysteine, NO uptake was significantly reduced. We found similar effects using ethyl nitrite gas in place of NO. Exposure to either gas induced activation of soluble guanylyl cylase in a parallel manner, consistent with LAT dependence. We conclude that NO gas uptake by alveolar epithelium achieves NO-based signaling predominantly by forming extracellular S-nitroso-L-cysteine that is taken up through LAT, rather than by diffusion. Augmenting extracellular S-nitroso-L-cysteine formation may augment pharmacological actions of inhaled NO gas. Copyright 2010 Elsevier Inc. All rights reserved.

Diffuse alveolar haemorrhage secondary to propylthiouracil-induced vasculitis

PubMed Central

Ferreira, Catarina; Costa, Teresa; Marques, Ana Vieira

2015-01-01

Propylthiouracil is a drug used to treat hyperthyroidism. It can cause several side effects including pulmonary disorders that, although rare, can be severe. The authors describe the case of a woman treated with propylthiouracil who developed diffuse alveolar haemorrhage with severe respiratory failure and anaemia, which improved with discontinuation of the antithyroid drug and on starting systemic corticosteroid therapy. PMID:25661751

Serial Histopathological Examination of the Lungs of Mice Infected with Influenza A Virus PR8 Strain

PubMed Central

Fukushi, Masaya; Ito, Tateki; Oka, Teruaki; Kitazawa, Toshio; Miyoshi-Akiyama, Tohru; Kirikae, Teruo; Yamashita, Makoto; Kudo, Koichiro

2011-01-01

Avian influenza H5N1 and pandemic (H1N1) 2009 viruses are known to induce viral pneumonia and subsequent acute respiratory distress syndrome (ARDS) with diffuse alveolar damage (DAD). The mortality rate of ARDS/DAD is extremely high, at approximately 60%, and no effective treatment for ARDS/DAD has been established. We examined serial pathological changes in the lungs of mice infected with influenza virus to determine the progress from viral pneumonia to ARDS/DAD. Mice were intranasally infected with influenza A/Puerto Rico/8/34 (PR8) virus, and their lungs were examined both macro- and micro-pathologically every 2 days. We also evaluated general condition, survival rate, body weight, viral loads in lung, and surfactant proteins in serum. As a result, all infected mice died within 9 days postinfection. At 2 days postinfection, inflammation in alveolar septa, i.e., interstitial pneumonia, was observed around bronchioles. From 4 to 6 days postinfection, interstitial pneumonia with alveolar collapse expanded throughout the lungs. From 6 to 9 days postinfection, DAD with severe alveolar collapse was observed in the lungs of all of dying and dead mice. In contrast, DAD was not observed in the live infected-mice from 2 to 6 days postinfection, despite their poor general condition. In addition, histopathological analysis was performed in mice infected with a dose of PR8 virus which was 50% of the lethal dose for mice in the 20-day observation period. DAD with alveolar collapse was observed in all dead mice. However, in the surviving mice, instead of DAD, glandular metaplasia was broadly observed in their lungs. The present study indicates that DAD with severe alveolar collapse is associated with death in this mouse infection model of influenza virus. Inhibition of the development of DAD with alveolar collapse may decrease the mortality rate in severe viral pneumonia caused by influenza virus infection. PMID:21701593

Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

PubMed Central

Wang, Hom-Lay; Sabalys, Gintautas

2011-01-01

ABSTRACT Objectives The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement. Material and Methods Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies. Results In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement. Conclusions The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management. PMID:24421983

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox.

PubMed

Shin, Hye-Won; Condorelli, Peter; Rose-Gottron, Christine M; Cooper, Dan M; George, Steven C

2004-09-01

Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21-38 yr old, n = 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (Ca(NO)) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50-500 ml/s), the slope has been previously interpreted as a nonzero Ca(NO) (range 1-5 ppb); however, the trumpet model predicts a positive slope of 0.4-2.1 ppb despite a zero Ca(NO) because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO.

Pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (Macaca fascicularis).

PubMed

Kuiken, Thijs; Buijs, Pascal; van Run, Peter; van Amerongen, Geert; Koopmans, Marion; van den Hoogen, Bernadette

2017-11-21

Although avian paramyxovirus type 1 is known to cause mild transient conjunctivitis in human beings, there are two recent reports of fatal respiratory disease in immunocompromised human patients infected with the pigeon lineage of the virus (PPMV-1). In order to evaluate the potential of PPMV-1 to cause respiratory tract disease, we inoculated a PPMV-1 isolate (hPPMV-1/Netherlands/579/2003) from an immunocompromised human patient into three healthy cynomolgus macaques (Macaca fascicularis) and examined them by clinical, virological, and pathological assays. In all three macaques, PPMV-1 replication was restricted to the respiratory tract and caused pulmonary consolidation affecting up to 30% of the lung surface. Both alveolar and bronchiolar epithelial cells expressed viral antigen, which co-localized with areas of diffuse alveolar damage. The results of this study demonstrate that PPMV-1 is a primary respiratory pathogen in cynomolgus macaques, and support the conclusion that PPMV-1 may cause fatal respiratory disease in immunocompromised human patients.

A Bloody Mess: An Unusual Case of Diffuse Alveolar Hemorrhage Because of Warfarin Overdose.

PubMed

Heffler, Enrico; Campisi, Raffaele; Ferri, Sebastian; Crimi, Nunzio

2016-01-01

We herein present the case of a patient with frank hemoptysis and hematuria, dyspnea, and cough. The patient was known to be affected by Chronic Obstructive Pulmonary Disease (COPD) and dilated cardiomyopathy with atrial fibrillation. For this latter condition, he was supposed to take 1.25 mg warfarin daily. Laboratory findings revealed very high levels of International Normalized Ratio (INR) (16), and the patient referred that he self-increased warfarin dose to 5 mg daily since 8 days before the onset of symptoms. Computed tomography scan revealed diffuse bilateral signs of alveolar hemorrhage with hydroaerial levels within emphysematous cysts. Wafarin was immediately stopped and changed with 220 mg dabigatran daily, and he was properly treated to restore a normal coagulation status. We concluded for a case of diffuse alveolar hemorrhage because of warfarin overdose.

A Case Report of an Elderly Woman With Thrombocytopenia and Bilateral Lung Infiltrates

PubMed Central

Hashmi, Hafiz Rizwan Talib; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda

2015-01-01

Abstract Etiologies for diffuse alveolar hemorrhage are wide and range from infectious to vasculitis and malignant processes. Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized by persistent thrombocytopenia, with a relatively indolent course in young patients, but a more complicated progression and high associated mortality in the older patients. Diffuse alveolar hemorrhage, complicating idiopathic thrombocytopenic purpura, is a very uncommon association, with only 2 reported cases in the literature. We present a 69-year-old healthy woman presenting with petechial rash, progressive dyspnea, and bilateral alveolar infiltrates. She was found to have idiopathic thrombocytopenic purpura associated with diffuse alveolar hemorrhage. The patient had an excellent response to high doses of pulse steroids and immunoglobulins. A high index of suspicion for noninfectious pulmonary diseases should be considered in patients with autoimmune diseases presenting with pulmonary infiltrates and hypoxia. Flexible bronchoscopy with sequential lavage is a relatively safe procedure in patients with coagulopathy and should be attempted to detect and confirm the diagnosis; absence of hemoptysis should not preclude the diagnosis. PMID:26683938

Quantitative in vivo assessment of lung microstructure at the alveolar level with hyperpolarized 3He diffusion MRI

NASA Astrophysics Data System (ADS)

Yablonskiy, Dmitriy A.; Sukstanskii, Alexander L.; Leawoods, Jason C.; Gierada, David S.; Bretthorst, G. Larry; Lefrak, Stephen S.; Cooper, Joel D.; Conradi, Mark S.

2002-03-01

The study of lung emphysema dates back to the beginning of the 17th century. Nevertheless, a number of important questions remain unanswered because a quantitative localized characterization of emphysema requires knowledge of lung structure at the alveolar level in the intact living lung. This information is not available from traditional imaging modalities and pulmonary function tests. Herein, we report the first in vivo measurements of lung geometrical parameters at the alveolar level obtained with 3He diffusion MRI in healthy human subjects and patients with severe emphysema. We also provide the first experimental data demonstrating that 3He gas diffusivity in the acinus of human lung is highly anisotropic. A theory of anisotropic diffusion is presented. Our results clearly demonstrate substantial differences between healthy and emphysematous lung at the acinar level and may provide new insights into emphysema progression. The technique offers promise as a clinical tool for early diagnosis of emphysema.

Survival predictor in patients with acute respiratory distress syndrome and diffuse alveolar damage undergoing open lung biopsy

PubMed Central

Chang, Chih-Hao; Hung, Chen-Yiu; Chiu, Li-Chung; Huang, Chung-Chi; Hu, Han-Chung

2017-01-01

Background Diffuse alveolar damage (DAD) is a typical pathological finding of open lung biopsies in patients with acute respiratory distress syndrome (ARDS). Patients with ARDS and DAD have been reported to have a poorer prognosis than those without DAD. The aim of this study was to investigate the survival predictors in patients with ARDS and DAD. Methods We retrospectively reviewed all ARDS patients who underwent an open lung biopsy which showed evidence of DAD from January 2006 to June 2015 at Chang Gung Memorial Hospital. Clinical data including baseline characteristics, medication, and survival outcomes were analyzed. Results A total of 64 ARDS patients with DAD were eligible for analysis and divided into known etiology (n = 17, 26.6%) and unknown etiology groups (n = 47, 73.4%). There was no significant difference in hospital mortality rate between the two groups (71.9% vs. 70.6%, p = 0.890). Univariate logistic regression analysis revealed that sequential organ failure assessment (SOFA) score at the time of a diagnosis of ARDS, and SOFA score, PaO2/FiO2 ratio, and positive end expiratory pressure level when the biopsy was performed were associated with hospital mortality. Multivariate analysis showed that the SOFA score on the day of the biopsy was an independent predictor of hospital mortality (odds ratio 1.413, 95% confidence interval 1.127–1.772; p = 0.03). There were no significant differences in the use, dose, duration and timing from ARDS to glucocorticoid therapy between the survivors and nonsurvivors. Conclusion For selected ARDS patients who underwent an open lung biopsy with pathological DAD, SOFA score was an independent predictor of hospital mortality. PMID:28678876

CXCR3 ligands are associated with the continuum of diffuse alveolar damage to chronic lung allograft dysfunction.

PubMed

Shino, Michael Y; Weigt, S Samuel; Li, Ning; Palchevskiy, Vyacheslav; Derhovanessian, Ariss; Saggar, Rajan; Sayah, David M; Gregson, Aric L; Fishbein, Michael C; Ardehali, Abbas; Ross, David J; Lynch, Joseph P; Elashoff, Robert M; Belperio, John A

2013-11-01

After lung transplantation, insults to the allograft generally result in one of four histopathologic patterns of injury: (1) acute rejection, (2) lymphocytic bronchiolitis, (3) organizing pneumonia, and (4) diffuse alveolar damage (DAD). We hypothesized that DAD, the most severe form of acute lung injury, would lead to the highest risk of chronic lung allograft dysfunction (CLAD) and that a type I immune response would mediate this process. Determine whether DAD is associated with CLAD and explore the potential role of CXCR3/ligand biology. Transbronchial biopsies from all lung transplant recipients were reviewed. The association between the four injury patterns and subsequent outcomes were evaluated using proportional hazards models with time-dependent covariates. Bronchoalveolar lavage (BAL) concentrations of the CXCR3 ligands (CXCL9/MIG, CXCL10/IP10, and CXCL11/ITAC) were compared between allograft injury patterns and "healthy" biopsies using linear mixed-effects models. The effect of these chemokine alterations on CLAD risk was assessed using Cox models with serial BAL measurements as time-dependent covariates. There were 1,585 biopsies from 441 recipients with 62 episodes of DAD. An episode of DAD was associated with increased risk of CLAD (hazard ratio, 3.0; 95% confidence interval, 1.9-4.7) and death (hazard ratio, 2.3; 95% confidence interval, 1.7-3.0). There were marked elevations in BAL CXCR3 ligand concentrations during DAD. Furthermore, prolonged elevation of these chemokines in serial BAL fluid measurements predicted the development of CLAD. DAD is associated with marked increases in the risk of CLAD and death after lung transplantation. This association may be mediated in part by an aberrant type I immune response involving CXCR3/ligands.

Alveolar Macrophages Prevent Lethal Influenza Pneumonia By Inhibiting Infection Of Type-1 Alveolar Epithelial Cells

PubMed Central

Cardani, Amber; Boulton, Adam; Kim, Taeg S.; Braciale, Thomas J.

2017-01-01

The Influenza A virus (IAV) is a major human pathogen that produces significant morbidity and mortality. To explore the contribution of alveolar macrophages (AlvMΦs) in regulating the severity of IAV infection we employed a murine model in which the Core Binding Factor Beta gene is conditionally disrupted in myeloid cells. These mice exhibit a selective deficiency in AlvMΦs. Following IAV infection these AlvMΦ deficient mice developed severe diffuse alveolar damage, lethal respiratory compromise, and consequent lethality. Lethal injury in these mice resulted from increased infection of their Type-1 Alveolar Epithelial Cells (T1AECs) and the subsequent elimination of the infected T1AECs by the adaptive immune T cell response. Further analysis indicated AlvMΦ-mediated suppression of the cysteinyl leukotriene (cysLT) pathway genes in T1AECs in vivo and in vitro. Inhibition of the cysLT pathway enzymes in a T1AECs cell line reduced the susceptibility of T1AECs to IAV infection, suggesting that AlvMΦ-mediated suppression of this pathway contributes to the resistance of T1AECs to IAV infection. Furthermore, inhibition of the cysLT pathway enzymes, as well as blockade of the cysteinyl leukotriene receptors in the AlvMΦ deficient mice reduced the susceptibility of their T1AECs to IAV infection and protected these mice from lethal infection. These results suggest that AlvMΦs may utilize a previously unappreciated mechanism to protect T1AECs against IAV infection, and thereby reduce the severity of infection. The findings further suggest that the cysLT pathway and the receptors for cysLT metabolites represent potential therapeutic targets in severe IAV infection. PMID:28085958

Primary pulmonary plasmacytoma with diffuse alveolar consolidation: a case report.

PubMed

Mohammad Taheri, Zohreh; Mohammadi, Forouzan; Karbasi, Mehrdad; Seyfollahi, Leila; Kahkoei, Shahram; Ghadiany, Mojtaba; Fayazi, Nader; Mansouri, Davood

2010-06-13

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

Primary Pulmonary Plasmacytoma with Diffuse Alveolar Consolidation: A Case Report

PubMed Central

Mohammad Taheri, Zohreh; Mohammadi, Forouzan; Karbasi, Mehrdad; Seyfollahi, Leila; Kahkoei, Shahram; Ghadiany, Mojtaba; Fayazi, Nader; Mansouri, Davood

2010-01-01

Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy. PMID:21151727

Cellular and Molecular Mechanisms of Alveolar Destruction in Emphysema

PubMed Central

Tuder, Rubin M.; Yoshida, Toshinori; Arap, Wadih; Pasqualini, Renata; Petrache, Irina

2006-01-01

Emphysema consists of a unique pattern of alveolar destruction, resulting in marked airspace enlargement with reduction of alveolar capillary exchange area. Classical concepts of the pathogenesis of emphysema have relied on the paradigm set by the inflammation and protease/antiprotease imbalance. We propose herein that cigarette smoke constitutes an environmental hazard that causes alveolar destruction by the interaction of apoptosis, oxidative stress, and protease/antiprotease imbalance. We draw a parallel between organismal aging, organ structural maintenance, and the damage resulting from chronic cigarette smoke inhalation. The stochastic interaction between environmental hazards and the effort of an organism or a particular organ to fend off these hazards results in the accumulation of cellular damage and features characteristic of aging. Inflammation follows as the result of the multiplication of injuries. We highlight the importance of understanding the biology of the interaction of alveolar cells in homeostasis and in alveolar destruction, and the potential role of novel processes related to senescence and stress response. An evolutionary perspective of emphysema that incorporates mechanisms related to aging may lead to important advances in the understanding and therapeutic targeting of chronic obstructive pulmonary disease. PMID:16921129

The alveolar to arterial oxygen partial pressure difference is associated with pulmonary diffusing capacity in heart failure patients.

PubMed

Morosin, Marco; Vignati, Carlo; Novi, Angela; Salvioni, Elisabetta; Veglia, Fabrizio; Alimento, Marina; Merli, Guido; Sciomer, Susanna; Sinagra, Gianfranco; Agostoni, Piergiuseppe

2016-11-01

In chronic heart failure (HF), the alveolar-capillary membrane undergoes a remodeling process that negatively affects gas exchange. In case of alveolar-capillary gas diffusion impairment, arterial desaturation (SaO 2 ) is rarely observed in HF patients. At play are 3 factors: overall pulmonary diffusing capacity (assessed as lung diffusion for CO, DLCO), global O 2 consumption (VO 2 ) and alveolar (A) to arterial (a) pO 2 gradient (AaDO 2 ). In 100 consecutive stable HF patients, DLCO, resting respiratory gases and arterial blood gases were measured to determine VO 2, paO 2 , pAO 2 and AaDO 2 . DLCO was poorly but significantly related to AaDO 2 . The correlation improved after correcting AaDO 2 for VO 2 (p<0.001, r=0.49). Both VO 2 and AaDO 2 were independently associated with DLCO (p<0.001). Patients with reduced DLCO showed no differences as regards paO 2 and pAO 2 . AaDO 2 /VO 2 showed a higher gradient in patients with lower DLCO. AaDO 2 increase and VO 2 reduction allow preventing low SaO 2 in HF patients with reduced DLCO. Accordingly, we suggest considering AaDO 2 and VO 2 combined and reporting AaDO 2 /VO 2 . Copyright © 2016 Elsevier B.V. All rights reserved.

Histopathology of ventilator-associated pneumonia (VAP) and its clinical implications.

PubMed

Torres, A; Fábregas, N; Arce, Y; López-Boado, M A

1999-01-01

Ventilator-associated pneumonia (VAP) is a diffuse polymicrobial and dynamic process, with heterogeneous distribution of lesions, showing different degrees of histological evolution predominating in the dependent lung zones, in which microbiology and histology can be dissociated. This might explain why blind endobronchial techniques to collect respiratory secretions have similar accuracy compared to visually guided samples, explaining the difficulties in validating any methods for its diagnosis. In the clinical setting the association of acute lung injury (ALI) and pneumonia is controversial. However, it is rare to detect diffuse alveolar damage (DAD) in absence of histological signs of pneumonia, probably evidencing that ALI favors the development of pneumonia. Histopathologically, it is difficult to distinguish initial and resolution phases of DAD from pneumonia and vice versa. On the other hand, there is a clear relationship between antimicrobial treatment and the decreased lung bacterial burden which strengthens the importance of distal airway sampling before starting antibiotic therapy.

Diffuse Alveolar Hemorrhage Induced by Irinotecan for a Patient with Metastatic Thymic Carcinoma: A Case Report and Literature Review.

PubMed

Kim, Sung-Ho; Minami, Seigo; Ogata, Yoshitaka; Yamamoto, Suguru; Komuta, Kiyoshi

2017-01-01

We herein report a 73-year-old Japanese woman with metastatic thymic carcinoma who developed diffuse alveolar hemorrhage (DAH) during irinotecan chemotherapy. She presented with a mild fever and exertional dyspnea after the second cycle of weekly irinotecan monotherapy. Chest images showed diffuse ground-glass opacities. The diagnosis of DAH was based on the findings of the bronchoalveolar lavage fluid, which was bloody and contained hemosiderin-laden macrophages. The discontinuation of irinotecan and introduction of oral prednisolone improved her symptoms and chest abnormal shadows. This is the first case of DAH caused by irinotecan.

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

PubMed

Oppenheimer, Beno W; Berger, Kenneth I; Ali, Saleem; Segal, Leopoldo N; Donnino, Robert; Katz, Stuart; Parikh, Manish; Goldring, Roberta M

2016-01-01

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

In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages.

PubMed

Chachuli, Siti Haziyah Mohd; Nawaz, Asif; Shah, Kifayatullah; Naharudin, Idanawati; Wong, Tin Wui

2016-06-01

Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages. Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques. The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary. Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.

A compartment model of alveolar-capillary oxygen diffusion with ventilation-perfusion gradient and dynamics of air transport through the respiratory tract.

PubMed

Jaworski, Jacek; Redlarski, Grzegorz

2014-08-01

This paper presents a model of alveolar-capillary oxygen diffusion with dynamics of air transport through the respiratory tract. For this purpose electrical model representing the respiratory tract mechanics and differential equations representing oxygen membrane diffusion are combined. Relevant thermodynamic relations describing the mass of oxygen transported into the human body are proposed as the connection between these models, as well as the influence of ventilation-perfusion mismatch on the oxygen diffusion. The model is verified based on simulation results of varying exercise intensities and statistical calculations of the results obtained during various clinical trials. The benefit of the approach proposed is its application in simulation-based research aimed to generate quantitative data of normal and pathological conditions. Based on the model presented, taking into account many essential physiological processes and air transport dynamics, comprehensive and combined studies of the respiratory efficiency can be performed. The impact of physical exercise, precise changes in respiratory tract mechanics and alterations in breathing pattern can be analyzed together with the impact of various changes in alveolar-capillary oxygen diffusion. This may be useful in simulation of effects of many severe medical conditions and increased activity level. Copyright © 2014 Elsevier Ltd. All rights reserved.

Physiology in Medicine: Understanding dynamic alveolar physiology to minimize ventilator-induced lung injury.

PubMed

Nieman, Gary F; Satalin, Josh; Kollisch-Singule, Michaela; Andrews, Penny; Aiash, Hani; Habashi, Nader M; Gatto, Louis A

2017-06-01

Acute respiratory distress syndrome (ARDS) remains a serious clinical problem with the main treatment being supportive in the form of mechanical ventilation. However, mechanical ventilation can be a double-edged sword: if set improperly, it can exacerbate the tissue damage caused by ARDS; this is known as ventilator-induced lung injury (VILI). To minimize VILI, we must understand the pathophysiologic mechanisms of tissue damage at the alveolar level. In this Physiology in Medicine paper, the dynamic physiology of alveolar inflation and deflation during mechanical ventilation will be reviewed. In addition, the pathophysiologic mechanisms of VILI will be reviewed, and this knowledge will be used to suggest an optimal mechanical breath profile (MB P : all airway pressures, volumes, flows, rates, and the duration that they are applied at both inspiration and expiration) necessary to minimize VILI. Our review suggests that the current protective ventilation strategy, known as the "open lung strategy," would be the optimal lung-protective approach. However, the viscoelastic behavior of dynamic alveolar inflation and deflation has not yet been incorporated into protective mechanical ventilation strategies. Using our knowledge of dynamic alveolar mechanics (i.e., the dynamic change in alveolar and alveolar duct size and shape during tidal ventilation) to modify the MB P so as to minimize VILI will reduce the morbidity and mortality associated with ARDS. Copyright © 2017 the American Physiological Society.

Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate: 2005-2014.

PubMed

Kellihan, Heidi B; Waller, Kenneth R; Pinkos, Alyssa; Steinberg, Howard; Bates, Melissa L

2015-09-01

To describe clinical canine patients with naturally occurring pulmonary hypertension and radiographic pulmonary alveolar infiltrates before and after treatment with sildenafil. Ten client-owned dogs. A retrospective analysis of dogs with echocardiographically-determined pulmonary hypertension and pulmonary alveolar infiltrates on thoracic radiographs was performed before (PRE) and after (POST) sildenafil therapy. Clinical scores, pulmonary alveolar infiltrate scores and tricuspid regurgitation gradients were analyzed PRE and POST sildenafil. Pulmonary alveolar infiltrates associated with pulmonary hypertension developed in a diffusely patchy distribution (10/10). Sixty percent of dogs had a suspected diagnosis of interstitial pulmonary fibrosis as the etiology of pulmonary hypertension. Median PRE clinical score was 4 (range: 3-4) compared to POST score of 0 (0-2) (p = 0.005). Median alveolar infiltrate score PRE was 10 (5-12) compared to POST score of 4 (0-6) (p = 0.006). Median tricuspid regurgitation gradient PRE was 83 mmHg (57-196) compared to 55 mmHg POST (33-151) (p = 0.002). A subset of dogs with moderate to severe pulmonary hypertension present with diffuse, patchy alveolar infiltrates consistent with non-cardiogenic pulmonary edema. The typical clinical presentation is acute dyspnea and syncope, often in conjunction with heart murmurs suggestive of valvular insufficiency. This constellation of signs may lead to an initial misdiagnosis of congestive heart failure or pneumonia; however, these dogs clinically and radiographically improve with the initiation of sildenafil. Copyright © 2015 Elsevier B.V. All rights reserved.

[Oxidative stress in patients on mechanical ventilation].

PubMed

Marjanović, Vesna; Dordević, Vidosava; Marjanović, Goran

2009-01-01

The appearance and intensity of oxidative stress were analyzed in the course of mechanical ventilation and parameters that could point toward potential lung damage. In three time intervals on day 1, 3 and 7 of mechanical ventilation, parameters such as: triglycerides, cholesterol, lactate, serum lactic dehydrogenase, acid-base balance and lipid peroxidation products--thiobarbituric acid reactive substances, were followed in 30 patients with head injuries. A decrease in the level of partial oxygen pressure (PaO2) (p < 0.01) and PaO2/FiO2 index (p < 0.05) in arterial blood was recorded on day 3 of mechanical ventilation. This was accompanied with an increase in alveolar-arterial difference (AaDO2) (p < 0.05), thiobarbituric acid reactive substances (p < 0.001) and lactic dehydrogenase (p < 0.001) comparing to day 1 of mechanical ventilation. The patients with initial PaO2 > 120 mmHg, had significant increase of thiobarbituric acid reactive substances and AaDO2 (p < 0.05) and fall of PaO2 (p < 0.001) on day 3 of mechanical ventilation. Oxidative stress and lipid peroxide production are increased during third day of mechanical ventilation leading to disruption of oxygen diffusion through alveolar-capillary membrane and reduction of parameters of oxygenation.

[Measurement of CO diffusion capacity (II): Standardization and quality criteria].

PubMed

Salcedo Posadas, A; Villa Asensi, J R; de Mir Messa, I; Sardón Prado, O; Larramona, H

2015-08-01

The diffusion capacity is the technique that measures the ability of the respiratory system for gas exchange, thus allowing a diagnosis of the malfunction of the alveolar-capillary unit. The most important parameter to assess is the CO diffusion capacity (DLCO). New methods are currently being used to measure the diffusion using nitric oxide (NO). There are other methods for measuring diffusion, although in this article the single breath technique is mainly referred to, as it is the most widely used and best standardized. Its complexity, its reference equations, differences in equipment, inter-patient variability and conditions in which the DLCO is performed, lead to a wide inter-laboratory variability, although its standardization makes this a more reliable and reproductive method. The practical aspects of the technique are analyzed, by specifying the recommendations to carry out a suitable procedure, the calibration routine, calculations and adjustments. Clinical applications are also discussed. An increase in the transfer of CO occurs in diseases in which there is an increased volume of blood in the pulmonary capillaries, such as in the polycythemia and pulmonary hemorrhage. There is a decrease in DLCO in patients with alveolar volume reduction or diffusion defects, either by altered alveolar-capillary membrane (interstitial diseases) or decreased volume of blood in the pulmonary capillaries (pulmonary embolism or primary pulmonary hypertension). Other causes of decreased or increased DLCO are also highlighted. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Coronectomy of impacted mandibular third molars: A meta-analysis and systematic review of the literature

PubMed Central

Cervera-Espert*, Juan; Pérez-Martínez*, Sara; Cervera-Ballester, Juan; Penarrocha-Oltra, David

2016-01-01

Background Coronectomy is an alternative to complete removal of an impacted mandibular third molar. Most authors have recommended coronectomy to prevent damage to the inferior alveolar nerve during surgical extraction of lower third molars. The present study offers a systematic review and metaanalysis of the coronectomy technique. Material and Methods A systematic review and meta-analysis was performed based on a PubMed and Cochrane databases search for articles published from 2014 and involving coronectomy of mandibular third molars located near the inferior alveolar nerve canal, with a minimum of 10 cases and a minimum follow-up period of 6 months. After application of the inclusion and exclusion criteria, a total of 12 articles were included in the study. Results and Discussion Coronectomy results in significantly lesser loss of sensitivity of the inferior alveolar nerve and prevents the occurrence of dry socket. No statistically significant differences were observed in the incidence of pain and infection between coronectomy and complete surgical extraction. After coronectomy, the remaining tooth fragment migrates an average of 2 mm within two years. Conclusions Coronectomy is indicated when the mandibular third molar is in contact with the inferior alveolar nerve and complete removal of the tooth may cause nerve damage. Key words:Coronectomy, included third molar, inferior alveolar nerve injury. PMID:27031064

The NS1 Glycoprotein Can Generate Dramatic Antibody-Enhanced Dengue Viral Replication in Normal Out-Bred Mice Resulting in Lethal Multi-Organ Disease

PubMed Central

Falconar, Andrew K. I.; Martinez, Fernando

2011-01-01

Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and production of antibody-enhanced disease (AED) was tested in out-bred mice. Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1) glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E) glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD50) of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS), displayed by diffuse alveolar damage (DAD) resulting from i) dramatic interstitial alveolar septa-thickening with mononuclear cells, ii) some hyperplasia of alveolar type-II pneumocytes, iii) copious intra-alveolar protein secretion, iv) some hyaline membrane-covered alveolar walls, and v) DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human “severe dengue” cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines, particularly against DENV strains that contain multiple mutations or genetic recombination within or between their DENV E and NS1 glycoprotein-encoding genes. The model provides potential for assessing DENV strain pathogenicity and anti-DENV therapies in normal mice. PMID:21731643

Impact and safety of open lung biopsy in patients with acute respiratory distress syndrome (ARDS).

PubMed

Ortiz, G; Garay, M; Mendoza, D; Cardinal-Fernández, P

2018-02-28

Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder, and its pathological hallmark is diffuse alveolar damage (DAD). Given that open lung biopsy (OLB) can sometimes result in severe side effects, it is rarely performed in patients with ARDS. The aims of this study were to describe: (a) the rate of treatment change associated with the histological result; and (b) the incidence of side effects induced by OLB. A retrospective, single-center, descriptive observational study was carried out in Hospital Santa Clara (Bogotá, Colombia) from February 2007 to January 2014. Critically ill patients over 18 years of age, undergoing invasive mechanical ventilation, diagnosed with ARDS of unknown etiology, and with OLB performed at the bedside. ARDS was diagnosed according to the Berlin definition. DAD was defined by the presence of a hyaline membrane plus at least one of the following: intra-alveolar edema, alveolar type I cell necrosis, alveolar type II cell (cuboidal cells) proliferation progressively covering the denuded alveolar-capillary membrane, interstitial proliferation of fibroblasts and myofibroblasts, or organizing interstitial fibrosis. The rate of treatment change (RTC) was established according to whether the OLB pathology report resulted in: a) the prescription or discontinuation of an antimicrobial; b) the indication of new procedures; c) medical interconsultation; or d) limitation of therapeutic effort. Patients were followed-up until death or hospital discharge. This study was approved by the Ethics Committee. A total of 32 OLBs were performed during the study period; 17 were ruled out as they did not involve ARDS, and 15 were considered for further analysis. A histological diagnosis was reached in 14 of the 15 patients (12 DAD, one case of bronchiolitis obliterans organizing pneumonia and one case of Wegener's granulomatosis with alveolar hemorrhage). The RTC rate was 0.73. The most frequent intervention was discontinuation of antimicrobial or corticosteroid treatment. No deaths but four side effects (3 airway leaks and one hemothorax) were associated with the OLB procedure. All were resolved before ICU discharge. The information provided by OLB performed at the bedside in ARDS patients of unknown etiology could be relevant, as it may optimize treatment. The risk associated with OLB seems to be acceptable. Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Coronectomy of third molar: a reduced risk technique for inferior alveolar nerve damage.

PubMed

Ahmed, Chkoura; Wafae, El Wady; Bouchra, Taleb

2011-05-01

Causing damage to the inferior alveolar nerve (IAN) when extracting lower third molars is due to the intimate relationship between the nerve and the roots of the teeth. When the proximity radiologic markers between the IAN and the root of the third molars are present, the technique of coronectomy can be proposed as an alternative to extraction to minimize the risk of nerve injury, with minimal complications. Nerve injury after the extraction of the mandibular third molar is a serious complication. The technique of coronectomy can be proposed to minimize the risk.

Salmeterol improves fluid clearance from alveolar-capillary membrane in COPD patients: a pilot study.

PubMed

Di Marco, Fabiano; Guazzi, Marco; Sferrazza Papa, Giuseppe Francesco; Vicenzi, Marco; Santus, Pierachille; Busatto, Paolo; Piffer, Federico; Blasi, Francesco; Centanni, Stefano

2012-02-01

The cardiovascular component associated with chronic obstructive pulmonary disease (COPD) plays a major role in disease prognosis, accounting for 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate fluid clearance from the alveolar airspace, with potentially positive effects on cardiogenic and noncardiogenic pulmonary oedema. This pilot study investigated the acute effects of the long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance after rapid saline intravenous infusion by evaluating diffusive and mechanical lung properties. Ten COPD and 10 healthy subjects were treated with salmeterol or placebo 4 h before the patient's mechanical and diffusive lung properties were measured during four non consecutive days, just before and after a rapid saline infusion, or during a similar period without an infusion. In both COPD and healthy subjects, rapid saline infusion with placebo or salmeterol premedication lead to a significant decrease in diffusion capacity for carbon monoxide (DLCO) and forced expiratory volume in 1 s (FEV1). Nonetheless, salmeterol pretreatment lead to a significantly reduced gas exchange impairment caused by saline infusion (-64% of DLCO reduction compared with placebo), whereas it did not affect changes in FEV1. In the control setting with no infusion, we found no significant change in either DLCO or mechanical properties of the lung. Salmeterol appears to provide a protective effect, not related to bronchodilation, against an acute alveolar fluid clearance challenge secondary to lung fluid overload in COPD patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity.

PubMed

Yoshikawa, Akira; Sato, Shuntaro; Tanaka, Tomonori; Hashisako, Mikiko; Kashima, Yukio; Tsuchiya, Tomoshi; Yamasaki, Naoya; Nagayasu, Takeshi; Yamamoto, Hiroshi; Fukuoka, Junya

2016-01-01

Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

Alveolar Thin Layer Flows and Surfactant Dynamics

NASA Astrophysics Data System (ADS)

Roumie, Ahmad; Jbaily, Abdulrahman; Szeri, Andrew J.

2017-11-01

Pulmonary surfactants play a vital role in everyday respiration. They regulate surface tension in the lungs by diffusing through the hypophase, a liquid layer that lines the interior surface of the alveoli, and adsorbing to the existing air-fluid interface. This decreases the equilibrium surface tension value by as much as a factor of 3, minimizing breathing effort and preventing lung collapse at the end of exhalation. Given that the hypophase thickness h lies within the range 0.1 μm < h <0.5 μm , and that the average alveolar radius R is 100 μm , for some purposes the hypophase may usefully be modeled as a fluid layer on a flat sheet representing the alveolar wall. Moreover, because of the large aspect ratio, the lubrication approximation can be applied. The aim of the present work is to study the interaction between the straining of the alveolar wall and the fluid flow in the hypophase. The analysis is governed by the relative magnitudes of the time scales of surfactant diffusion, adsorption, desorption, viscous dissipation and sheet straining. Cases of particular interest include non-uniform surfactant concentration at the interface, leading to Marangoni flows and a non-uniform hypophase thickness profile. The analytical formulation and numerical simulations are presented. This work is motivated by a need to understand alveolar deformation during breathing, and to do so in a way that derives from improved understanding of the fluid mechanics of the problem.

Acute Exacerbation in Interstitial Lung Disease

PubMed Central

Leuschner, Gabriela; Behr, Jürgen

2017-01-01

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field. PMID:29109947

Suicide attempt by intravenous injection of gasoline: a case report.

PubMed

Fink, Katrin; Kuehnemund, Alexander; Schwab, Tilmann; Geibel-Zehender, Annette; Bley, Thorsten; Bode, Christoph; Busch, Hans-Joerg

2010-11-01

There is much experience with intoxication by aspiration of volatile hydrocarbon products, whereas intravenous injection of these distillates is rare. There are only few reports that describe a wide variety of associated pathological changes, predominantly in the pulmonary system. We report the case of an intravenous self-injection of gasoline by a young man in a suicide attempt. Immediately after injecting gasoline, the 22-year-old man developed bradycardia, hypotension, and increasing dyspnea. Computed tomography scan of the chest showed signs consistent with diffuse alveolar-toxic damage to the lung. These symptoms and radiological findings are similar to those commonly observed after inhalation of this type of substance. This may have been due to diffusion of gasoline into the alveoli, where its presence leads to this characteristic damage. In this patient, gasoline entered the intramuscular tissue, and the patient developed a soft-tissue phlegmon at the forearm. At operation, gas emanation and superficial necrosis were noted. Nevertheless, the patient's outcome was good, with full recovery within 3 weeks. The major changes in this patient after intravenous injection of gasoline were in the pulmonary system, including hypoxemia and radiological findings that could be related to an exhalation of the volatile substance. In addition, gas in the musculature of the injection area caused a soft-tissue phlegmon. Copyright © 2010 Elsevier Inc. All rights reserved.

Transport of gases between the environment and alveoli – theoretical foundations

PubMed Central

Butler, James P.; Tsuda, Akira

2015-01-01

The transport of oxygen and carbon dioxide in the gas phase from the ambient environment to and from the alveolar gas/blood interface is accomplished through the tracheobronchial tree, and involves mechanisms of bulk or convective transport and diffusive net transport. The geometry of the airway tree and the fluid dynamics of these two transport processes combine in such a way that promotes a classical fractionation of ventilation into dead space and alveolar ventilation respectively. This simple picture continues to capture much of the essence of gas phase transport. On the other hand, a more detailed look at the interaction of convection and diffusion leads to significant new issues, many of which remain open questions. These are associated with parallel and serial inhomogeneities especially within the distal acinar units, velocity profiles in distal airways and terminal spaces subject to moving boundary conditions, and the serial transport of respiratory gases within the complex acinar architecture. This chapter focuses specifically on the theoretical foundations of gas transport, addressing two broad areas. The first deals with the reasons why the classical picture of alveolar and dead space ventilation is so successful; the second examines the underlying assumptions within current approximations to convective and diffusive transport, and how they interact to effect net gas exchange. PMID:23733643

[Choice of optimal respiratory support in acute parenchymatous respiratory failure].

PubMed

Cherniĭ, V I; Kuznetsova, I V; Kovalenko, V L

2005-01-01

The principal goals of respiratory therapy for acute respiratory failure are to correct gas exchange and to lower respiratory performance. In acute lung lesion syndrome (ALLS) and acute respiratory distress syndrome (ARDS), the oxygenation index (PaO2/FiO2) reflects the degree of alveolar-capillary membrane damage. The changes in PaO2/FiO2 between 400 to 300 at adequate ventilation can be interpreted as occult alveolar-capillary insufficiency. The principle of power saving in ALLS/ARDS is to choose a respiratory support regimen that may ensure oxygenation safety by eliminating the excess work of respiration. The ratio of PaO2/FiO2/VO2 is proposed to consider to be a criterion for the effectiveness of respiratory support in ALLS/ARDS and a marker of energy deficiency. It has been established that the function of the alveolar-capillary membrane is not impaired with the PaO2/FiO2 ratio of more than 1.5 and the ratio of less than 1.0 is typical of the severe course of the severe course of ARDS and suggests both alveolar-capillary membrane damage and energy deficiency.

[The clinical effect of root amputation in the treatment of periodontal/alveolar abscess].

PubMed

Tan, Baochun; Wu, Wenlei; Sun, Weibin; Xiao, Jianping

2012-06-01

To study the clinical effect of root amputation in the treatment of periodontal/alveolar abscess teeth with one severe lesion root. 30 periodontal/alveolar abscess teeth with one severe lesion root were chosen in the study. After root canal treatment, supragingival scaling, subgingival scaling and root planning, occlusal adjustment were done. Then the teeth were treated by root amputation. The clinical effect was evaluated 3 months, 6 months and 1 year after surgery. One year after surgery, 27 of 30 teeth were successful, 1 mandibular molar occurred root fracture, 1 mandibular molar was removed because of tooth loosening secondary to periodontal damage. 1 patient lost. Root amputation is an effective solution of periodontal/alveolar abscess.

Treatment of a case of mesangioproliferative glomerulonephritis secondary to Echinococcus alveolaris with albendazole.

PubMed

Ulusoy, Sükrü; Ozkan, Gülsüm; Mungan, Sevdegül; Arslan, Mehmet; Cansu, Ayşegül; Cansiz, Muammer; Köseoğlu, Rahman; Kaynar, Kübra

2011-01-01

Parasitic infections lead to significant morbidity and mortality, especially in tropical regions. The renal damage caused by these infections occurs via various mechanisms. Two forms of parasitic echinococcus infection widely responsible for infection in humans are Echinococcus granulosus and Echinococcus multilocularis. E. multilocularis causes Alveolar echinococcus infection in humans. Alveolar echinococcus has high mortality, and the possible limits of surgery are generally exceeded by the time of diagnosis. The literature contains no case reports of comorbidity of alveolar echinococcus and glomerulonephritis. Here we discuss the treatment of a patient with comorbid mesangioproliferative glomerulonephritis and alveolar echinococcus, behaving like a tumor, using albendazole since there was no possibility of surgery. This is the first ever such case report.

Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs.

PubMed

Dumkova, Jana; Vrlikova, Lucie; Vecera, Zbynek; Putnova, Barbora; Docekal, Bohumil; Mikuska, Pavel; Fictum, Petr; Hampl, Ales; Buchtova, Marcela

2016-06-03

The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level.

Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs

PubMed Central

Dumkova, Jana; Vrlikova, Lucie; Vecera, Zbynek; Putnova, Barbora; Docekal, Bohumil; Mikuska, Pavel; Fictum, Petr; Hampl, Ales; Buchtova, Marcela

2016-01-01

The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level. PMID:27271611

Mental nerve paresthesia secondary to initiation of endodontic therapy: a case report

PubMed Central

Alam, Sharique; Zia, Afaf; Khan, Masood Hasan; Kumar, Ashok

2014-01-01

Whenever endodontic therapy is performed on mandibular posterior teeth, damage to the inferior alveolar nerve or any of its branches is possible. Acute periapical infection in mandibular posterior teeth may also sometimes disturb the normal functioning of the inferior alveolar nerve. The most common clinical manifestation of these insults is the paresthesia of the inferior alveolar nerve or mental nerve paresthesia. Paresthesia usually manifests as burning, prickling, tingling, numbness, itching or any deviation from normal sensation. Altered sensation and pain in the involved areas may interfere with speaking, eating, drinking, shaving, tooth brushing and other events of social interaction which will have a disturbing impact on the patient. Paresthesia can be short term, long term or even permanent. The duration of the paresthesia depends upon the extent of the nerve damage or persistence of the etiology. Permanent paresthesia is the result of nerve trunk laceration or actual total nerve damage. Paresthesia must be treated as soon as diagnosed to have better treatment outcomes. The present paper describes a case of mental nerve paresthesia arising after the start of the endodontic therapy in left mandibular first molar which was managed successfully by conservative treatment. PMID:25110646

Protective effect of Shenfu injection preconditioning on lung ischemia-reperfusion injury

PubMed Central

Zhang, Hong; Wan, Zhanhai; Yan, Xiang; Wang, De-Gui; Leng, Yufang; Liu, Yongqiang; Zhang, Yan; Zhang, Haijun; Han, Xuena

2016-01-01

Lung ischemia-reperfusion injury remains a problem in thoracic surgery, as minimal progress has been made concerning its prevention and control. In the present study, the protective effects and the underlying mechanism of Shenfu injection preconditioning on a rat lung ischemia-reperfusion model was investigated. Shenfu injection is a well-known Chinese traditional medicine, which is composed of Red Radix Ginseng and Radix Aconitum carmichaelii, with ginseng saponin and aconitum alkaloids as the active ingredients. A total of 72 specific pathogen-free, healthy male Wistar rats were randomly divided into control, model and Shenfu injection (10 ml/kg injection prior to injury) groups and were assessed at the following points: Ischemia 45 min; reperfusion 60 min; and reperfusion 120 min. Blood collected from the aorta abdominalis was cryopreserved at −70°C for the analysis of malondialdehyde (MDA) and superoxide dismutase (SOD) activity. Lung tissues were divided into three equal sections in order to assess the wet-to-dry (W/D) lung ratio, tumor necrosis factor (TNF)-α expression levels, myeloperoxidase (MPO) activity, alveolar damage, total protein and hematoxylin and eosin staining. The results demonstrated that the lung W/D weight ratio, TNF-α expression levels and SOD activity in the Shenfu group were significantly lower at 120 min reperfusion (P<0.05), as compared with the model group. MPO and MDA activity significantly decreased following reperfusion at 60 and 120 min (P<0.05), as compared with the model group. In addition, the degree of alveolar damage in the Shenfu group was significantly decreased (P<0.05), as compared with the model group. In addition, compared with the model group, the degree of alveolar damage in the Shenfu group was significantly lower (P<0.05); however, no significant changes in total protein were observed. The extent of alveolar structural damage and the proportion of interstitial neutrophils and alveolar and interstitial red blood cells were lower in the Shenfu group, as compared with the model and control groups. Therefore, the results of the present study suggested that Shenfu injection may have protective effects on lung ischemia-reperfusion injury. PMID:27602083

Survival in a case of diffuse alveolar hemorrhage due to Strongyloides stercoralis hyperinfection.

PubMed

Steinhaus, Daniel A; Gainor, Justin F; Vernovsky, Inna; Winsett, Julie; Beer, Dennis J

2012-01-01

Strongyloides stercoralis is an intestinal nematode endemic to tropical and sub-tropical regions. Although infection is typically asymptomatic or self-limited, immunocompromised individuals can develop a severe form of disease marked by hyperinfection. Pulmonary involvement accompanies hyperinfection in a majority of cases, though manifestations range from asymptomatic infiltrates to diffuse alveolar hemorrhage (DAH) and respiratory failure. When complicated by DAH, the hyperinfection syndrome is usually fatal. We report a case of a 65-year-old Guatemalan woman with chronic inflammatory demyelinating polyneuropathy (CIDP) treated with chronic steroids who presented with Escherichia coli urosepsis. She was initially treated with antibiotics and corticosteroids. She subsequently developed DAH due to disseminated strongyloidiasis. She was treated with oral and subcutaneous ivermectin and had complete recovery.

Nonuniformity of diffusing capacity from small alveolar gas samples is increased in smokers.

PubMed

Cotton, D J; Mink, J T; Graham, B L

1998-01-01

Although centrilobular emphysema, and small airway, interstitial and alveoli inflammation can be detected pathologically in the lungs of smokers with relatively well preserved lung function, these changes are difficult to assess using available physiological tests. Because submaximal single breath washout (SBWSM) manoeuvres improve the detection of abnormalities in ventilation inhomogeneity in the lung periphery in smokers compared with traditional vital capacity manoeuvres, SBWSM manoeuvres were used in this study to measure temporal differences in diffusing capacity using a rapid response carbon monoxide analyzer. To determine whether abnormalities in the lung periphery can be detected in smokers with normal forced expired volumes in 1 s using the three-equation diffusing capacity (DLcoSB-3EQ) among small alveolar gas samples and whether the abnormalities correlate with increases in peripheral ventilation inhomogeneity. Cross-sectional study in 21 smokers and 21 nonsmokers all with normal forced exhaled flow rates. Both smokers and nonsmokers performed SBWSM manoeuvres consisting of slow inhalation of test gas from functional residual capacity to one-half inspiratory capacity with either 0 or 10 s of breath holding and slow exhalation to residual volume (RV). They also performed conventional vital capacity single breath (SBWVC) manoeuvres consisting of slow inhalation of test gas from RV to total lung capacity and, without breath holding, slow exhalation to RV. DLcoSB-3EQ was calculated from the total alveolar gas sample. DLcoSB-3EQ was also calculated from four equal sequential, simulated aliquots of the total alveolar gas sample. DLcoSB-3EQ values from the four alveolar samples were normalized by expressing each as a percentge of DLcoSB-3EQ from the entire alveolar gas sample. An index of variation (DI) among the small-sample DLcoSB-3EQ values was correlated with the normalized phase III helium slope (Sn) and the mixing efficiency (Emix). For SBWSM, DI was increased in smokers at 0 s of breath holding compared with nonsmokers, and correlated with age, smoking pack-years and Sn. The decrease in DI with breath holding was greater in smokers and correlated with the change in Sn with breath holding. For SBWVC manoeuvres, there were no differences due to smoking in Sn or Emix, but DI was increased in smokers and correlated with age and smoking pack-years, but not with Sn. For SBWSM manoeuvres the increase in DI in smokers correlated with breath hold time-dependent increases in Sn, suggesting that the changes in DI reflected the same structural alterations that caused increases in peripheral ventilation inhomogeneity. For SBWVC manoeuvres, the increase in DI in smokers was not associated with changes in ventilation inhomogeneity, suggesting that the effect of smoking on DI during this manoeuvre was due to smoke-related changes in alveolar capillary diffusion, rather than due solely to alterations in the distribution of ventilation.

Critical role of the axonal guidance cue EphrinB2 in lung growth, angiogenesis, and repair.

PubMed

Vadivel, Arul; van Haaften, Tim; Alphonse, Rajesh S; Rey-Parra, Gloria-Juliana; Ionescu, Lavinia; Haromy, Al; Eaton, Farah; Michelakis, Evangelos; Thébaud, Bernard

2012-03-01

Lung diseases characterized by alveolar damage currently lack efficient treatments. The mechanisms contributing to normal and impaired alveolar growth and repair are incompletely understood. Axonal guidance cues (AGC) are molecules that guide the outgrowth of axons to their targets. Among these AGCs, members of the Ephrin family also promote angiogenesis, cell migration, and organogenesis outside the nervous system. The role of Ephrins during alveolar growth and repair is unknown. We hypothesized that EphrinB2 promotes alveolar development and repair. We used in vitro and in vivo manipulation of EphrinB2 signaling to assess the role of this AGC during normal and impaired lung development. In vivo EphrinB2 knockdown using intranasal siRNA during the postnatal stage of alveolar development in rats arrested alveolar and vascular growth. In a model of O(2)-induced arrested alveolar growth in newborn rats, air space enlargement, loss of lung capillaries, and pulmonary hypertension were associated with decreased lung EphrinB2 and receptor EphB4 expression. In vitro, EphrinB2 preserved alveolar epithelial cell viability in O(2), decreased O(2)-induced alveolar epithelial cell apoptosis, and accelerated alveolar epithelial cell wound healing, maintained lung microvascular endothelial cell viability, and proliferation and vascular network formation. In vivo, treatment with intranasal EphrinB2 decreased alveolar epithelial and endothelial cell apoptosis, preserved alveolar and vascular growth in hyperoxic rats, and attenuated pulmonary hypertension. The AGC EphrinB2 may be a new therapeutic target for lung repair and pulmonary hypertension.

An improved method for the isolation of rat alveolar type II lung cells: Use in the Comet assay to determine DNA damage induced by cigarette smoke.

PubMed

Dalrymple, Annette; Ordoñez, Patricia; Thorne, David; Dillon, Debbie; Meredith, Clive

2015-06-01

Smoking is a cause of serious diseases, including lung cancer, emphysema, chronic bronchitis and heart disease. DNA damage is thought to be one of the mechanisms by which cigarette smoke (CS) initiates disease in the lung. Indeed, CS induced DNA damage can be measured in vitro and in vivo. The potential of the Comet assay to measure DNA damage in isolated rat lung alveolar type II epithelial cells (AEC II) was explored as a means to include a genotoxicity end-point in rodent sub-chronic inhalation studies. In this study, published AEC II isolation methods were improved to yield viable cells suitable for use in the Comet assay. The improved method reduced the level of basal DNA damage and DNA repair in isolated AEC II. CS induced DNA damage could also be quantified in isolated cells following a single or 5 days CS exposure. In conclusion, the Comet assay has the potential to determine CS or other aerosol induced DNA damage in AEC II isolated from rodents used in sub-chronic inhalation studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Pregabalin in the treatment of inferior alveolar nerve paraesthesia following overfilling of endodontic sealer

PubMed Central

Alonso-Ezpeleta, Oscar; Martín, Pablo J.; López-López, José; Castellanos-Cosano, Lizett; Martín-González, Jenifer; Segura-Egea, Juan J.

2014-01-01

A case of orofacial pain and inferior alveolar nerve (IAN) paraesthesia after extrusion of endodontic sealer within the mandibular canal treated with prednisone and pregabalin is described. A 36-year-old woman underwent root canal treatment of the mandibular second right premolar tooth. Post-operative panoramic radiograph revealed the presence of radiopaque canal sealer in the mandibular canal. Damage to IAN consecutive to extrusion of endodontic sealer was diagnosed. Non-surgical management was decided, including: 1 mg/kg/day prednisone 2 times/day, once-daily regimen, and 150 mg/day pregabalin, two doses per day, monitoring the progress with periodic follow-up visits. Six weeks after the incident the signs and symptoms were gone. The complete resolution of paraesthesia and the control of pain achieved suggest that a non-surgical approach, combining prednisone and the GABA analogue pregabalin, is a good option in the management of the IAN damage subsequent to endodontic sealer extrusion. Key words:Endodontics, inferior alveolar nerve, neuropathic pain, orofacial pain, paraesthesia, pregabalin. PMID:24790724

Inhalation exposure of rats to metal aerosol. II. Study of mutagenic effect on alveolar macrophages.

PubMed

Chorvatovicová, D; Kováciková, Z

1992-02-01

The effects of inhalation exposure to metal aerosol derived from nickel refinery waste were studied on the frequency of chromosome aberrations in alveolar macrophages in Wistar rats. A 4-month exposure period resulted in significant (P less than 0.01) increases in chromosome aberrations. Relatively high variability without statistical significance was observed after a 4-week exposure period. Increase in damaged alveolar macrophages with the length of exposure seems to point to the role of pulmonary metal deposits. Comparison of the results with those found after 6 months of exposure in bone marrow cells confirmed that metal particles in nickel refinery waste are genotoxic. Thus, this study indicates that alveolar macrophages are suitable for monitoring the genotoxic potential of hazardous chemicals administered by inhalation.

Sex steroid receptor expression in idiopathic pulmonary fibrosis.

PubMed

Mehrad, Mitra; Trejo Bittar, Humberto E; Yousem, Samuel A

2017-08-01

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

Carbon monoxide alleviates lipopolysaccharide-induced oxidative stress injury through suppressing the expression of Fis1 in NR8383 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Jia; Yu, Jian-bo, E-mail: yujianbo11@126.com; Liu, Wei

Acute respiratory distress syndrome (ARDS) is one of the most devastating complications of sepsis lacking of effective therapy. Mitochondrial dynamics undergoing continuous fusion and fission play a crucial role in mitochondrial structure and function. Fis1, as a small protein located on the outer membrane of mitochondria, has been thought to be an important protein mediated mitochondrial fission. During ARDS, alveolar macrophages suffer from increased oxidative stress and apoptosis, and also accompanied by disrupted mitochondrial dynamics. In addition, as one of the products of heme degradation catalyzed by heme oxygenase, carbon monoxide (CO) possesses powerful protective properties in vivo or inmore » vitro models, such as anti-inflammatory, antioxidant and anti-apoptosis function. However, there is little evidence that CO alleviates oxidative stress damage through altering mitochondrial fission in alveolar macrophages. In the present study, our results showed that CO increased cell vitality, improved mitochondrial SOD activity, reduced reactive oxygen species (ROS) production and inhibited cell apoptosis in NR8383 exposed to LPS. Meanwhile, CO decreased the expression of Fis1, increased mitochondrial membrane potential and sustained elongation of mitochondria in LPS-incubated NR8383. Overall, our study underscored a critical role of CO in suppressing the expression of Fis1 and alleviating LPS- induced oxidative stress damage in alveolar macrophages. - Highlights: • LPS exposure triggered cell injury in NR8383. • CO alleviated LPS-induced oxidative stress damage in alveolar macrophages. • CO inhibited Fis1 levels and improved mitochondrial function in LPS-induced NR8383.« less

[Intra-alveolar hemorrhage: rare presentation of fat pulmonary embolism].

PubMed

Ketata, W; Msaad, S; Bahloul, N; Marouen, F; Ayoub, A

2010-11-01

Fat embolism syndrome is a severe complication of long bone fractures, corresponding to the obstruction of small vessels by microdroplets of fat, originating from medulla ossium. Pulmonary involvement, present in 90% cases, makes the severity of the disease. We report the case of a 22-year-old man who presented, two days after industrial accident causing an opened tibial fracture, acute dyspnea with hemoptysis. Angio-CT-scan didn't show any proximal vascular obstruction, but parenchymal sections showed diffuse, bilateral and multifocal hyperdensities predominating at the periphery. Broncho-alveolar lavage brought a hemorrhagic liquid, with a high macrophage content and lipid inclusions in macrophages. Exams for the etiologic diagnosis of intra-alveolar hemorrhage were negative: renal function, 24-hour proteinuria, antinuclear antibodies, antineutrophil cytoplasmic antibodies. The diagnosis of intra-alveolar hemorrhage secondary to fat embolism was established. The outcome was spontaneously favorable. The occurrence of intra-alveolar hemorrhage in the course fat embolism is rarely reported. Its pathogenic mechanisms are not understood. It is mandatory to eliminate the other causes of alveolar hemorrhage before holding the diagnosis of fat embolism. Treatment is only symptomatic, based on respiratory reanimation. Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Alveolar hemorrhage associated with warfarin therapy: a case report and literature review.

PubMed

Erdogan, Dogan; Kocaman, Orhan; Oflaz, Huseyin; Goren, Taner

2004-04-01

A 75-year-old man was admitted to our clinic with the complaints of palpitation, fever, severe dyspnea, dizziness and bloody sputum associated with coughing. Chest radiographs revealed that the lungs were bilaterally infiltrated. A high resolution computed tomographic study of the thorax disclosed diffuse alveolar hemorrhage, of which presence was proved by histopathological study of bronchoalveolar lavage material. The hemorrhage occured at 8th day of 5 mg daily warfarin therapy, which was given for frequent atrial fibrillation attacks was controlled by fresh frozen plasma and vitamin K. Alveolar hemorrhage is difficult to diagnose and has high mortality if the treatment was not started as soon as possible. This is the first report of alveolar hemorrhage caused by 5 mg daily warfarin therapy. We propose that the patient's age, nutritional status, used drugs should be taken into consideration for true management of patients with atrial fibrillation.

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

PubMed

Alphonse, Rajesh S; Vadivel, Arul; Fung, Moses; Shelley, William Chris; Critser, Paul John; Ionescu, Lavinia; O'Reilly, Megan; Ohls, Robin K; McConaghy, Suzanne; Eaton, Farah; Zhong, Shumei; Yoder, Merv; Thébaud, Bernard

2014-05-27

Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage. © 2014 American Heart Association, Inc.

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

PubMed

Vadivel, Arul; Alphonse, Rajesh S; Collins, Jennifer J P; van Haaften, Tim; O'Reilly, Megan; Eaton, Farah; Thébaud, Bernard

2013-01-01

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.

Needle in the external auditory canal: an unusual complication of inferior alveolar nerve block.

PubMed

Ribeiro, Leandro; Ramalho, Sara; Gerós, Sandra; Ferreira, Edite Coimbra; Faria e Almeida, António; Condé, Artur

2014-06-01

Inferior alveolar nerve block is used to anesthetize the ipsilateral mandible. The most commonly used technique is one in which the anesthetic is injected directly into the pterygomandibular space, by an intraoral approach. The fracture of the needle, although uncommon, can lead to potentially serious complications. The needle is usually found in the pterygomandibular space, although it can migrate and damage adjacent structures, with variable consequences. The authors report an unusual case of a fractured needle, migrating to the external auditory canal, as a result of an inferior alveolar nerve block. Copyright © 2014 Elsevier Inc. All rights reserved.

Diffuse alveolar hemorrhage due to metastatic angiosarcoma of the lung: A case report

PubMed Central

PAN, ZHIJIE; AN, ZHOU; LI, YANYUAN; ZHOU, JIANYING

2015-01-01

Angiosarcoma is a rare, heterogeneous malignant tumor that derives from endothelial cells, and it has aggressive characteristics with a marked tendency for distant metastasis. Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome, however, it is rare as the presentation of pulmonary angiosarcoma. To increase awareness with regard to angiosarcoma and DAH, the current study presents a case of angiosarcoma that originated from the subcutaneous soft tissue of the mastoid process, but was subject to a delayed diagnosis and rapid invasion into the brain and lung. The metastatic angiosarcoma of the lung presented with DAH as the initial manifestation. The pathological examination of a biopsy of the subcutaneous mass and pulmonary lesions confirmed the diagnosis of angiosarcoma. The patient succumbed to respiratory failure at 1 month post-diagnosis. PMID:26788222

High-resolution computed tomography findings of acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis.

PubMed

Ichikado, Kazuya

2014-02-01

Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. © 2013 Published by Elsevier Inc.

The relationship between alveolar oxygen tension and the single-breath carbon monoxide diffusing capacity.

PubMed

Kanner, R E; Crapo, R O

1986-04-01

The effects of alveolar oxygen tension (PAO2) on the single-breath carbon monoxide diffusing capacity (DLCO) were quantified and a factor was derived to accommodate for differences in PAO2 over commonly encountered altitudes and/or varying concentrations of oxygen in the test gas mixture (FIO2) We performed duplicate measurements of DLCO in 7 normal subjects with 6 different oxygen fractions (0.176, 0.196, 0.211, 0.22, 0.25, and 0.27). The PAO2 for each test was measured as the PO2 in the alveolar gas sample bag. DLCO varied inversely with PAO2 and changed by 0.35% for each mmHg change in PAO2 (r = -0.62, p less than 0.001). At an FIO2 of 0.25, PAO2 varied between subjects and was highly correlated with each subject's residual volume to total lung capacity ratio (r = -0.84, p less than 0.001). We suggest that laboratories can adjust the measured DLCO when PAO2 is not congruent to 120 mmHg by the following formula: DLCO (corrected = DLCO (measured) x [1.0 + 0.0035 (PAO2 - 120)].

Pulmonary manifestations in systemic lupus erythematosus: pleural involvement, acute pneumonitis, chronic interstitial lung disease and diffuse alveolar hemorrhage.

PubMed

Aguilera-Pickens, Georgina; Abud-Mendoza, Carlos

2018-05-14

Systemic lupus erythematosus is the diffuse autoimmune connective tissue disease that most frequently involves pulmonary involvement, affecting 20% of 90% of the patients. The percentage varies depending on the defining criteria (symptoms, pulmonary tests or histopathological studies). At least once during the disease course, 50% of those affected have pleural and/or pulmonary manifestations, which are associated with higher morbidity and mortality. Pulmonary involvement has no correlation with lupus activity biomarkers, and it is necessary to rule out infectious processes in the initial approach. Bacterial infection is most frequently the cause of lung involvement in lupus and is one of the most important causes of death. Pulmonary involvement is considered to be primary when it is associated with disease activity, and secondary when other causes participate. Drugs have been reported to be associated with pulmonary damage, including interstitial disease. The incidence of malignant lung diseases is increased in systemic lupus erythematosus. Treatment depends on the type and severity of pulmonary involvement. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

Butyrfentanyl overdose resulting in diffuse alveolar hemorrhage.

PubMed

Cole, Jon B; Dunbar, John F; McIntire, Sarah A; Regelmann, Warren E; Slusher, Tina M

2015-03-01

Butyrfentanyl is a potent short-acting opioid and a fentanyl analog with uncertain clinical effects. A review of the literature reveals no human case reports of butyrfentanyl overdose. As the use of analog and synthetic drugs continues to increase, clinicians are often faced with tremendous uncertainty when they encounter patients exposed to these synthetic drugs. We describe, to our knowledge, the first case of a butyrfentanyl overdose that resulted in clinically significant hemoptysis, acute lung injury, hypoxic respiratory failure, and diffuse alveolar hemorrhage. Complicating this case was a false-positive urine drug screen for fentanyl. Clinicians who encounter fentanyl exposures should be aware they may in fact be dealing with butyrfentanyl. As little is known of butyrfentanyl and our patient suffered a significant pulmonary hemorrhage, those who encounter butyrfentanyl exposures should monitor for hemorrhagic complications. Copyright © 2015 by the American Academy of Pediatrics.

Critical Determinants of Uptake and Translocation of Nanoparticles by the Human Pulmonary Alveolar Epithelium

PubMed Central

2015-01-01

The ability to manipulate the size and surface properties of nanomaterials makes them a promising vector for improving drug delivery and efficacy. Inhalation is a desirable route of administration as nanomaterials preferentially deposit in the alveolar region, a large surface area for drug absorption. However, as yet, the mechanisms by which particles translocate across the alveolar epithelial layer are poorly understood. Here we show that human alveolar type I epithelial cells internalize nanoparticles, whereas alveolar type II epithelial cells do not, and that nanoparticles translocate across the epithelial monolayer but are unable to penetrate the tight junctions between cells, ruling out paracellular translocation. Furthermore, using siRNA, we demonstrate that 50 nm nanoparticles enter largely by passive diffusion and are found in the cytoplasm, whereas 100 nm nanoparticles enter primarily via clathrin- and also caveolin-mediated endocytosis and are found in endosomes. Functionalization of nanoparticles increases their uptake and enhances binding of surfactant which further promotes uptake. Thus, we demonstrate that uptake and translocation across the pulmonary epithelium is controlled by alveolar type I epithelial cells, and furthermore, we highlight a number of factors that should be considered when designing new nanomedicines in order to improve drug delivery to the lung. PMID:25360809

Diffusion Lung Imaging with Hyperpolarized Gas MRI

PubMed Central

Yablonskiy, Dmitriy A; Sukstanskii, Alexander L; Quirk, James D

2015-01-01

Lung imaging using conventional 1H MRI presents great challenges due to low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T2* is about 1-2 ms). MRI with hyperpolarized gases (3He and 129Xe) provides a valuable alternative due to a very strong signal originated from inhaled gas residing in the lung airspaces and relatively slow gas T2* relaxation (typical T2* is about 20-30 ms). Though in vivo human experiments should be done very fast – usually during a single breath-hold. In this review we describe the recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of modeling results of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows extracting quantitative information on the lung microstructure at the alveolar level. This approach, called in vivo lung morphometry, allows from a less than 15-second MRI scan, providing quantitative values and spatial distributions of the same physiological parameters as are measured by means of the “standard” invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli, etc.). Besides, the approach makes it possible to evaluate some advanced Weibel parameters characterizing lung microstructure - average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, providing in vivo information on the integrity of pulmonary acinar airways and their changes in different diseases, are of great importance and interest to a broad range of physiologists and clinicians. We also discuss a new type of experiments that are based on the in vivo lung morphometry technique combined with quantitative CT measurements as well as with the Gradient Echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on the blood vessel volume fraction, specific gas volume, the length of acinar airways, and allows evaluation of lung parenchymal and non-parenchymal tissue. PMID:26676342

Hyperplasia of type 2 pneumocytes following 0. 34 ppm nitrogen dioxide exposure: quantitation by image analysis. [Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sherwin, R.P.; Richters, V.

1982-09-01

Swiss Webster male mice were exposed to intermittent 0.34 ppm nitrogen dioxide for 6 wk. Quantitative image analysis showed increased Type 2 cell numbers in each of the three lobes measured, with and without adjustment to alveolar wall measurements for lung volume normalization (e.g., P < .037 for Type 2 cell number adjusted to alveolar wall perimeters, combined lobe analysis of variance). The exposed animals dominated the upper quartile ranking of the cell number/alveolar area ratio computations (P < .025), which implied the presence of an especially susceptible subpopulation of animals. The Type 2 cell increase is believed to resultmore » from damage and loss of Type 1 cells, the reversibility and progression of which are presently unknown. The data also suggest an increased size of the Type 2 cell, and possibly slight atelectasis and/or edema of the alveolar walls.« less

ENHANCED BINDING OF AUTOLOGOUS RED CELLS TO THE MACROPHAGE PLASMA MEMBRANE AS A SENSITIVE INDICATOR OF POLLUTANT DAMAGE

EPA Science Inventory

The alveolar macrophage (AM) represents the primary line of defense in host protection against inhaled infectious organisms. Following exposure to oxidant gases, the ability of the host to resist airborne bacterial infection is severely impaired, and damage to the AM defense syst...

Unsteady Oxygen Transfer in Space-Filling Models of the Pulmonary Acinus

NASA Astrophysics Data System (ADS)

Hofemeier, Philipp; Shachar-Berman, Lihi; Filoche, Marcel; Sznitman, Josue

2014-11-01

Diffusional screening in the pulmonary acinus is a well-known physical phenomenon that results from the depletion of fresh oxygen in proximal acinar generations diffusing through the alveolar wall membranes and effectively creating a gradient in the oxygen partial pressure along the acinar airways. Until present, most studies have focused on steady-state oxygen diffusion in generic sub-acinar structures and discarded convective oxygen transport due to low Peclet numbers in this region. Such studies, however, fall typically short in capturing the complex morphology of acinar airways as well as the oscillatory nature of convecive acinar breathing. Here, we revisit this problem and solve the convective-diffusive transport equations in breathing 3D acinar structures, underlining the significance of convective flows in proximal acinar generations as well as recirculating alveolar flow patterns. In particular, to assess diffusional screening, we monitor time-dependent efficiencies of the acinus under cyclic breathing motion. Our study emphasizes the necessity of capturing both a dynamically breathing and anatomically-realistic model of the sub-acinus to characterize unsteady oxygen transport across the acinar walls.

Integrated Stress Response Mediates Epithelial Injury in Mechanical Ventilation.

PubMed

Dolinay, Tamas; Himes, Blanca E; Shumyatcher, Maya; Lawrence, Gladys Gray; Margulies, Susan S

2017-08-01

Ventilator-induced lung injury (VILI) is a severe complication of mechanical ventilation that can lead to acute respiratory distress syndrome. VILI is characterized by damage to the epithelial barrier with subsequent pulmonary edema and profound hypoxia. Available lung-protective ventilator strategies offer only a modest benefit in preventing VILI because they cannot impede alveolar overdistension and concomitant epithelial barrier dysfunction in the inflamed lung regions. There are currently no effective biochemical therapies to mitigate injury to the alveolar epithelium. We hypothesize that alveolar stretch activates the integrated stress response (ISR) pathway and that the chemical inhibition of this pathway mitigates alveolar barrier disruption during stretch and mechanical ventilation. Using our established rat primary type I-like alveolar epithelial cell monolayer stretch model and in vivo rat mechanical ventilation that mimics the alveolar overdistension seen in acute respiratory distress syndrome, we studied epithelial responses to mechanical stress. Our studies revealed that the ISR signaling pathway is a key modulator of epithelial permeability. We show that prolonged epithelial stretch and injurious mechanical ventilation activate the ISR, leading to increased alveolar permeability, cell death, and proinflammatory signaling. Chemical inhibition of protein kinase RNA-like endoplasmic reticulum kinase, an upstream regulator of the pathway, resulted in decreased injury signaling and improved barrier function after prolonged cyclic stretch and injurious mechanical ventilation. Our results provide new evidence that therapeutic targeting of the ISR can mitigate VILI.

Noninvasive quantification of alveolar morphometry in elderly never- and ex-smokers

PubMed Central

Paulin, Gregory A; Ouriadov, Alexei; Lessard, Eric; Sheikh, Khadija; McCormack, David G; Parraga, Grace

2015-01-01

Diffusion-weighted magnetic resonance imaging (MRI) provides a way to generate in vivo lung images with contrast sensitive to the molecular displacement of inhaled gas at subcellular length scales. Here, we aimed to evaluate hyperpolarized 3He MRI estimates of the alveolar dimensions in 38 healthy elderly never-smokers (73 ± 6 years, 15 males) and 21 elderly ex-smokers (70 ± 10 years, 14 males) with (n = 8, 77 ± 6 years) and without emphysema (n = 13, 65 ± 10 years). The ex-smoker and never-smoker subgroups were significantly different for FEV1/FVC (P = 0.0001) and DLCO (P = 0.009); while ex-smokers with emphysema reported significantly diminished FEV1/FVC (P = 0.02) and a trend toward lower DLCO (P = 0.05) than ex-smokers without emphysema. MRI apparent diffusion coefficients (ADC) and CT measurements of emphysema (relative area–CT density histogram, RA950) were significantly different (P = 0.001 and P = 0.007) for never-smoker and ex-smoker subgroups. In never-smokers, the MRI estimate of mean linear intercept (260 ± 27 μm) was significantly elevated as compared to the results previously reported in younger never-smokers (210 ± 30 μm), and trended smaller than in the age-matched ex-smokers (320 ± 72 μm, P = 0.06) evaluated here. Never-smokers also reported significantly smaller internal (220 ± 24 μm, P = 0.01) acinar radius but greater alveolar sheath thickness (120 ± 4 μm, P < 0.0001) than ex-smokers. Never-smokers were also significantly different than ex-smokers without emphysema for alveolar sheath thickness but not ADC, while ex-smokers with emphysema reported significantly different ADC but not alveolar sheath thickness compared to ex-smokers without CT evidence of emphysema. Differences in alveolar measurements in never- and ex-smokers demonstrate the sensitivity of MRI measurements to the different effects of smoking and aging on acinar morphometry. PMID:26462748

Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa.

PubMed

Strayer, David R; Carter, William A; Stouch, Bruce C; Stittelaar, Koert J; Thoolen, Robert J M M; Osterhaus, Albert D M E; Mitchell, William M

2014-10-01

Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. Copyright © 2014. Published by Elsevier B.V.

A novel swine model of ricin-induced acute respiratory distress syndrome

PubMed Central

Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Kronman, Chanoch

2017-01-01

ABSTRACT Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. PMID:28067630

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

NASA Astrophysics Data System (ADS)

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

2013-06-01

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

A disseminated alveolar rhabdomyosarcoma in a 9-year-old boy disclosed by chromosomal translocation (2;13) (q35;q14)

PubMed

Brichard, B; Ninane, J; Gosseye, S; Verellen-Dumoulin, C; Vermylen, C; Rodhain, J; Cornu, G

1991-01-01

A 9-year-old boy presented with a small subcutaneous tumor of the trunk and diffuse bone marrow involvement. The first histological diagnosis given was undifferentiated malignancy possibly of neural crest origin and chemotherapy was started immediately using vincristine, cyclophosphamide, cisplatin, and teniposide (OPEC). Complete response was achieved after four courses of chemotherapy. Histological slides were then reviewed and the final diagnosis of alveolar rhabdomyosarcoma (RMS) was retained. Moreover, chromosome analysis of malignant cells in the bone marrow revealed a translocation involving chromosomes 2 and 13:t(2;13) (q35;q14). This specific karyotype finding has been recently reported in a few cases and could be specific for alveolar RMS. The patient had a relapse 7 months after diagnosis and died 4 months later.

Coronectomy of the mandibular third molar: Respect for the inferior alveolar nerve.

PubMed

Kouwenberg, A J; Stroy, L P P; Rijt, E D Vree-V D; Mensink, G; Gooris, P J J

2016-05-01

The aim of this study was to evaluate the outcomes of coronectomy as an alternative surgical procedure to complete removal of the impacted mandibular third molar in patients with a suspected close relationship between the tooth root(s) and the mandibular canal. A total of 151 patients underwent coronectomy and were followed up with clinical examinations and panoramic radiographs for a minimum of 6 months after surgery. None of the patients exhibited inferior alveolar nerve injury. Eruption of the retained root(s) was more frequent in younger patients (18-35 years). Thirty-six patients (23.8%) exhibited insufficient growth of new bone in the alveolar defect, and 11.3% required a second surgical procedure to remove the root remnant(s). Our results indicate that coronectomy can be a reliable alternative to complete removal of the impacted mandibular third molar in patients exhibiting an increased risk of damage to the inferior alveolar nerve on panoramic radiographs. Copyright © 2016. Published by Elsevier Ltd.

Importance of carbon dioxide in the critical patient: Implications at the cellular and clinical levels.

PubMed

Morales Quinteros, Luis; Bringué Roque, Josep; Kaufman, David; Artigas Raventós, Antonio

2018-02-24

Important recent insights have emerged regarding the cellular and molecular role of carbon dioxide (CO 2 ) and the effects of hypercapnia. The latter may have beneficial effects in patients with acute lung injury, affording reductions in pulmonary inflammation, lessened oxidative alveolar damage, and the regulation of innate immunity and host defenses by inhibiting the expression of inflammatory cytokines. However, other studies suggest that CO 2 can have deleterious effects upon the lung, reducing alveolar wound repair in lung injury, decreasing the rate of reabsorption of alveolar fluid, and inhibiting alveolar cell proliferation. Clearly, hypercapnia has both beneficial and harmful consequences, and it is important to determine the net effect under specific conditions. The purpose of this review is to describe the immunological and physiological effects of carbon dioxide, considering their potential consequences in patients with acute respiratory failure. Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Acute respiratory distress syndrome and acute lung injury.

PubMed

Dushianthan, A; Grocott, M P W; Postle, A D; Cusack, R

2011-09-01

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development of ARDS are identified with sepsis, pneumonia, and trauma with multiple transfusions accounting for most cases. Despite the absence of a robust diagnostic definition, extensive epidemiological investigations suggest ARDS remains a significant health burden with substantial morbidity and mortality. Improvements in outcome following ARDS over the past decade are in part due to improved strategies of mechanical ventilation and advanced support of other failing organs. Optimal treatment involves judicious fluid management, protective lung ventilation with low tidal volumes and moderate positive end expiratory pressure, multi-organ support, and treatment where possible of the underlying cause. Moreover, advances in general supportive measures such as appropriate antimicrobial therapy, early enteral nutrition, prophylaxis against venous thromboembolism and gastrointestinal ulceration are likely contributory reasons for the improved outcomes. Although therapies such as corticosteroids, nitric oxide, prostacyclins, exogenous surfactants, ketoconazole and antioxidants have shown promising clinical effects in animal models, these have failed to translate positively in human studies. Most recently, clinical trials with β2 agonists aiding alveolar fluid clearance and immunonutrition with omega-3 fatty acids have also provided disappointing results. Despite these negative studies, mortality seems to be in decline due to advances in overall patient care. Future directions of research are likely to concentrate on identifying potential biomarkers or genetic markers to facilitate diagnosis, with phenotyping of patients to predict outcome and treatment response. Pharmacotherapies remain experimental and recent advances in the modulation of inflammation and novel cellular based therapies, such as mesenchymal stem cells, may reduce lung injury and facilitate repair.

The Use of High-Frequency Percussive Ventilation for Whole-Lung Lavage: A Case Report.

PubMed

Kinthala, Sudhakar; Liang, Mark; Khusid, Felix; Harrison, Sebron

2018-04-23

Whole-lung lavage (WLL) remains the gold standard in the treatment of pulmonary alveolar proteinosis. However, anesthetic management during WLL can be challenging because of the risk of intraoperative hypoxemia and various cardiorespiratory complications of 1-lung ventilation. Here, we describe a novel strategy involving the application of high-frequency percussive ventilation using a volumetric diffusive respirator (VDR-4) during WLL in a 47-year-old woman with pulmonary alveolar proteinosis. Our observations suggest that high-frequency percussive ventilation is a potentially effective ventilation strategy during WLL that may reduce the risk of hypoxemia and facilitate lavage.

Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice.

PubMed

Ruscitti, Francesca; Ravanetti, Francesca; Essers, Jeroen; Ridwan, Yanto; Belenkov, Sasha; Vos, Wim; Ferreira, Francisca; KleinJan, Alex; van Heijningen, Paula; Van Holsbeke, Cedric; Cacchioli, Antonio; Villetti, Gino; Stellari, Franco Fabio

2017-01-01

The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage. Here we investigated the use of the Micro-CT technique to allow the evaluation of disease onset and progression at different time-points in the mouse bleomycin model of lung fibrosis. Micro-CT was throughout coupled with histological analysis for the validation of the imaging results. In bleomycin-instilled and control mice, airways and lung morphology changes were assessed and reconstructed at baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft score, percentage of collagen content and percentage of alveolar air area were detected on lung slides processed by histology and subsequently compared with Micro-CT parameters. Extent (%) of fibrosis measured by Micro-CT correlated with Ashcroft score, the percentage of collagen content and the percentage of alveolar air area ( r 2  = 0.91; 0.77; 0.94, respectively). Distal airway radius also correlated with the Ashcroft score, the collagen content and alveolar air area percentage ( r 2  = 0.89; 0.78; 0.98, respectively). Micro-CT data were in good agreement with histological read-outs as micro-CT was able to quantify effectively and non-invasively disease progression longitudinally and to reduce the variability and number of animals used to assess the damage. This suggests that this technique is a powerful tool for understanding experimental pulmonary fibrosis and that its use could translate into a more efficient drug discovery process, also helping to fill the gap between preclinical setting and clinical practice.

Lungs in Heart Failure

PubMed Central

Apostolo, Anna; Giusti, Giuliano; Gargiulo, Paola; Bussotti, Maurizio; Agostoni, Piergiuseppe

2012-01-01

Lung function abnormalities both at rest and during exercise are frequently observed in patients with chronic heart failure, also in the absence of respiratory disease. Alterations of respiratory mechanics and of gas exchange capacity are strictly related to heart failure. Severe heart failure patients often show a restrictive respiratory pattern, secondary to heart enlargement and increased lung fluids, and impairment of alveolar-capillary gas diffusion, mainly due to an increased resistance to molecular diffusion across the alveolar capillary membrane. Reduced gas diffusion contributes to exercise intolerance and to a worse prognosis. Cardiopulmonary exercise test is considered the “gold standard” when studying the cardiovascular, pulmonary, and metabolic adaptations to exercise in cardiac patients. During exercise, hyperventilation and consequent reduction of ventilation efficiency are often observed in heart failure patients, resulting in an increased slope of ventilation/carbon dioxide (VE/VCO2) relationship. Ventilatory efficiency is as strong prognostic and an important stratification marker. This paper describes the pulmonary abnormalities at rest and during exercise in the patients with heart failure, highlighting the principal diagnostic tools for evaluation of lungs function, the possible pharmacological interventions, and the parameters that could be useful in prognostic assessment of heart failure patients. PMID:23365739

The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity.

PubMed

De Luca, Daniele; van Kaam, Anton H; Tingay, David G; Courtney, Sherry E; Danhaive, Olivier; Carnielli, Virgilio P; Zimmermann, Luc J; Kneyber, Martin C J; Tissieres, Pierre; Brierley, Joe; Conti, Giorgio; Pillow, Jane J; Rimensberger, Peter C

2017-08-01

Acute respiratory distress syndrome (ARDS) is undefined in neonates, despite the long-standing existing formal recognition of ARDS syndrome in later life. We describe the Neonatal ARDS Project: an international, collaborative, multicentre, and multidisciplinary project which aimed to produce an ARDS consensus definition for neonates that is applicable from the perinatal period. The definition was created through discussions between five expert members of the European Society for Paediatric and Neonatal Intensive Care; four experts of the European Society for Paediatric Research; two independent experts from the USA and two from Australia. This Position Paper provides the first consensus definition for neonatal ARDS (called the Montreux definition). We also provide expert consensus that mechanisms causing ARDS in adults and older children-namely complex surfactant dysfunction, lung tissue inflammation, loss of lung volume, increased shunt, and diffuse alveolar damage-are also present in several critical neonatal respiratory disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

An unusual autopsy case of cytokine storm-derived influenza-associated encephalopathy without typical histopathological findings: autopsy case report.

PubMed

Nara, Akina; Nagai, Hisashi; Yamaguchi, Rutsuko; Yoshida, Ken-ichi; Iwase, Hirotaro; Mizuguchi, Masashi

2015-03-01

Cytokine storm-derived influenza-associated encephalopathy is a severe complication, affecting not only the brain but also multiple systemic organs including the heart and lungs. Hundreds of Japanese children are afflicted by influenza-associated encephalopathy every year. Influenza-associated encephalopathy can be diagnosed by pathological changes, such as advanced brain edema and disruption of astrocytic projections, which is known as clasmatodendrosis. In the present case, despite the absence of significant histopathological findings in the brain, the diagnosis of influenza-associated encephalopathy was made on the basis of autopsy findings such as brain swelling, pathological findings including diffuse alveolar damage, and increase in the concentrations of interleukin-6 in both the serum and cerebrospinal fluid. In this case, the interval from high fever to death was approximately 7 hours and may have been too short for histopathological features to develop. This is an unusual autopsy case of cytokine storm-derived influenza-associated encephalopathy without typical histopathological findings.

Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics.

PubMed

Pavone, Lucio A; Albert, Scott; Carney, David; Gatto, Louis A; Halter, Jeffrey M; Nieman, Gary F

2007-01-01

Acute respiratory distress syndrome causes a heterogeneous lung injury, and without protective mechanical ventilation a secondary ventilator-induced lung injury can occur. To ventilate noncompliant lung regions, high inflation pressures are required to 'pop open' the injured alveoli. The temporal impact, however, of these elevated pressures on normal alveolar mechanics (that is, the dynamic change in alveolar size and shape during ventilation) is unknown. In the present study we found that ventilating the normal lung with high peak pressure (45 cmH(2)0) and low positive end-expiratory pressure (PEEP of 3 cmH(2)O) did not initially result in altered alveolar mechanics, but alveolar instability developed over time. Anesthetized rats underwent tracheostomy, were placed on pressure control ventilation, and underwent sternotomy. Rats were then assigned to one of three ventilation strategies: control group (n = 3, P control = 14 cmH(2)O, PEEP = 3 cmH(2)O), high pressure/low PEEP group (n = 6, P control = 45 cmH(2)O, PEEP = 3 cmH(2)O), and high pressure/high PEEP group (n = 5, P control = 45 cmH(2)O, PEEP = 10 cmH(2)O). In vivo microscopic footage of subpleural alveolar stability (that is, recruitment/derecruitment) was taken at baseline and than every 15 minutes for 90 minutes following ventilator adjustments. Alveolar recruitment/derecruitment was determined by measuring the area of individual alveoli at peak inspiration (I) and end expiration (E) by computer image analysis. Alveolar recruitment/derecruitment was quantified by the percentage change in alveolar area during tidal ventilation (%I - E Delta). Alveoli were stable in the control group for the entire experiment (low %I - E Delta). Alveoli in the high pressure/low PEEP group were initially stable (low %I - E Delta), but with time alveolar recruitment/derecruitment developed. The development of alveolar instability in the high pressure/low PEEP group was associated with histologic lung injury. A large change in lung volume with each breath will, in time, lead to unstable alveoli and pulmonary damage. Reducing the change in lung volume by increasing the PEEP, even with high inflation pressure, prevents alveolar instability and reduces injury. We speculate that ventilation with large changes in lung volume over time results in surfactant deactivation, which leads to alveolar instability.

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).

PubMed

Dancer, Rachel C A; Parekh, Dhruv; Lax, Sian; D'Souza, Vijay; Zheng, Shengxing; Bassford, Chris R; Park, Daniel; Bartis, D G; Mahida, Rahul; Turner, Alice M; Sapey, Elizabeth; Wei, Wenbin; Naidu, Babu; Stewart, Paul M; Fraser, William D; Christopher, Kenneth B; Cooper, Mark S; Gao, Fang; Sansom, David M; Martineau, Adrian R; Perkins, Gavin D; Thickett, David R

2015-07-01

Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated. To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity. Human, murine and in vitro primary alveolar epithelial cell work were included in this study. Vitamin D deficiency (plasma 25(OH)D levels <50 nmol/L) was ubiquitous in patients with ARDS and present in the vast majority of patients at risk of developing ARDS following oesophagectomy. In a murine model of intratracheal lipopolysaccharide challenge, dietary-induced vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage and hypoxia. In vitro, vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients. Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed. UKCRN ID 11994. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Probing sub-alveolar length scales with hyperpolarized-gas diffusion NMR

NASA Astrophysics Data System (ADS)

Miller, Wilson; Carl, Michael; Mooney, Karen; Mugler, John; Cates, Gordon

2009-05-01

Diffusion MRI of the lung is a promising technique for detecting alterations of normal lung microstructure in diseases such as emphysema. The length scale being probed using this technique is related to the time scale over which the helium-3 or xenon-129 diffusion is observed. We have developed new MR pulse sequence methods for making diffusivity measurements at sub-millisecond diffusion times, allowing one to probe smaller length scales than previously possible in-vivo, and opening the possibility of making quantitative measurements of the ratio of surface area to volume (S/V) in the lung airspaces. The quantitative accuracy of simulated and experimental measurements in microstructure phantoms will be discussed, and preliminary in-vivo results will be presented.

Pathophysiology and classification of primary graft dysfunction after lung transplantation

PubMed Central

Morrison, Morvern Isabel; Pither, Thomas Leonard

2017-01-01

The term primary graft dysfunction (PGD) incorporates a continuum of disease severity from moderate to severe acute lung injury (ALI) within 72 h of lung transplantation. It represents the most significant obstacle to achieving good early post-transplant outcomes, but is also associated with increased incidence of bronchiolitis obliterans syndrome (BOS) subsequently. PGD is characterised histologically by diffuse alveolar damage, but is graded on clinical grounds with a combination of PaO2/FiO2 (P/F) and the presence of radiographic infiltrates, with 0 being absence of disease and 3 being severe PGD. The aetiology is multifactorial but commonly results from severe ischaemia-reperfusion injury (IRI), with tissue-resident macrophages largely responsible for stimulating a secondary ‘wave’ of neutrophils and lymphocytes that produce severe and widespread tissue damage. Donor history, recipient health and operative factors may all potentially contribute to the likelihood of PGD development. Work that aims to minimise the incidence of PGD in ongoing, with techniques such as ex vivo perfusion of donor lungs showing promise both in research and in clinical studies. This review will summarise the current clinical status of PGD before going on to discuss its pathophysiology, current therapies available and future directions for clinical management of PGD. PMID:29268419

The Role of Viral, Host, and Secondary Bacterial Factors in Influenza Pathogenesis

PubMed Central

Kash, John C.; Taubenberger, Jeffery K.

2016-01-01

Influenza A virus infections in humans generally cause self-limited infections, but can result in severe disease, secondary bacterial pneumonias, and death. Influenza viruses can replicate in epithelial cells throughout the respiratory tree and can cause tracheitis, bronchitis, bronchiolitis, diffuse alveolar damage with pulmonary edema and hemorrhage, and interstitial and airspace inflammation. The mechanisms by which influenza infections result in enhanced disease, including development of pneumonia and acute respiratory distress, are multifactorial, involving host, viral, and bacterial factors. Host factors that enhance risk of severe influenza disease include underlying comorbidities, such as cardiac and respiratory disease, immunosuppression, and pregnancy. Viral parameters enhancing disease risk include polymerase mutations associated with host switch and adaptation, viral proteins that modulate immune and antiviral responses, and virulence factors that increase disease severity, which can be especially prominent in pandemic viruses and some zoonotic influenza viruses causing human infections. Influenza viral infections result in damage to the respiratory epithelium that facilitates secondary infection with common bacterial pneumopathogens and can lead to secondary bacterial pneumonias that greatly contribute to respiratory distress, enhanced morbidity, and death. Understanding the molecular mechanisms by which influenza and secondary bacterial infections, coupled with the role of host risk factors, contribute to enhanced morbidity and mortality is essential to develop better therapeutic strategies to treat severe influenza. PMID:25747532

Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.

PubMed

Lutz, Dennis; Gazdhar, Amiq; Lopez-Rodriguez, Elena; Ruppert, Clemens; Mahavadi, Poornima; Günther, Andreas; Klepetko, Walter; Bates, Jason H; Smith, Bradford; Geiser, Thomas; Ochs, Matthias; Knudsen, Lars

2015-02-01

Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function. Design-based stereology and invasive pulmonary function tests were performed 1, 3, 7, and 14 days after intratracheal bleomycin-instillation in rats. The number and size of open alveoli was correlated to mechanical properties. Active surfactant subtypes declined by Day 1, associated with a progressive alveolar derecruitment and a decrease in compliance. Alveolar epithelial damage was more pronounced in closed alveoli compared with ventilated alveoli. Collapse induration occurred on Day 7 and Day 14 as indicated by collapsed alveoli overgrown by a hyperplastic alveolar epithelium. This pathophysiology was also observed for the first time in human IPF lung explants. Before the onset of collapse induration, distal airspaces were easily recruited, and lung elastance could be kept low after recruitment by positive end-expiratory pressure (PEEP). At later time points, the recruitable fraction of the lung was reduced by collapse induration, causing elastance to be elevated at high levels of PEEP. Surfactant inactivation leading to alveolar collapse and subsequent collapse induration might be the primary pathway for the loss of alveoli in this animal model. Loss of alveoli is highly correlated with the degradation of lung function. Our ultrastructural observations suggest that collapse induration is important in human IPF.

Dynamics of Gas Exchange through the Fractal Architecture of the Human Lung, Modeled as an Exactly Solvable Hierarchical Tree

NASA Astrophysics Data System (ADS)

Mayo, Michael; Pfeifer, Peter; Gheorghiu, Stefan

2008-03-01

The acinar airways lie at the periphery of the human lung and are responsible for the transfer of oxygen from air to the blood during respiration. This transfer occurs by the diffusion-reaction of oxygen over the irregular surface of the alveolar membranes lining the acinar airways. We present an exactly solvable diffusion-reaction model on a hierarchically branched tree, allowing a quantitative prediction of the oxygen current over the entire system of acinar airways responsible for the gas exchange. We discuss the effect of diffusional screening, which is strongly coupled to oxygen transport in the human lung. We show that the oxygen current is insensitive to a loss of permeability of the alveolar membranes over a wide range of permeabilities, similar to a ``constant-current source'' in an electric network. Such fault tolerance has been observed in other treatments of the gas exchange in the lung and is obtained here as a fully analytical result.

Effects of water immersion to the neck on pulmonary circulation and tissue volume in man

NASA Technical Reports Server (NTRS)

Begin, R.; Epstein, M.; Sackner, M. A.; Levinson, R.; Dougherty, R.; Duncan, D.

1976-01-01

A rapid noninvasive breathing method is used to obtain serial measurements of the pulmonary capillary blood flow, diffusing capacity per unit of alveolar volume, combined pulmonary tissue plus capillary volume, functional residual capacity, and oxygen consumption in five normal subjects undergoing 6 h of sitting, 4 h of sitting while immersed to the neck in thermoneutral water, and 4 h of lying in thermoneutral water to the neck. The rebreathing method employed a test gas mixture containing 0.5% C2H2, 0.3% C(18)O, 10% He, 21% O2, and balance N2. It is shown that immersion to the neck in the seated posture results in significant increases in sodium excretion cardiac output, and diffusing capacity per unit of alveolar volume. The pulmonary tissue plus capillary volume did not change, demonstrating that the central vascular engorgement induced by water immersion is not accompanied by significant extravasation of fluid into the pulmonary interstitial space.

Microlithiasis of Seminal Vesicles and Severe Oligoasthenospermia in Pulmonary Alveolar Microlithiasis (PAM): Report of An Unusual Sporadic Case.

PubMed

Castellana, Giuseppe; Carone, Domenico; Castellana, Marco

2015-01-01

Pulmonary alveolar microlithiasis (PAM) is classified as an elective dysmetabolic thesaurotic pneumoalveolitis and characterized by the presence within the alveoli of the lungs of myriad of tiny calculi. The classic presentation of the chest radiography is unmistakable with multiple small "sand-like" opacities diffusely involving both lung fields. We present a case of male infertility for hypoposia and severe oligoasthenospermia in a young patient with recurrent haematuria and small calcifications in the seminal vesicles similar to pulmonary microliths. PAM was diagnosed on routine chest radiography, com- puter tomography (CT), transbronchial biopsy and bronchoalveolar lavage (BAL).

A novel swine model of ricin-induced acute respiratory distress syndrome.

PubMed

Katalan, Shahaf; Falach, Reut; Rosner, Amir; Goldvaser, Michael; Brosh-Nissimov, Tal; Dvir, Ayana; Mizrachi, Avi; Goren, Orr; Cohen, Barak; Gal, Yoav; Sapoznikov, Anita; Ehrlich, Sharon; Sabo, Tamar; Kronman, Chanoch

2017-02-01

Pulmonary exposure to the plant toxin ricin leads to respiratory insufficiency and death. To date, in-depth study of acute respiratory distress syndrome (ARDS) following pulmonary exposure to toxins is hampered by the lack of an appropriate animal model. To this end, we established the pig as a large animal model for the comprehensive study of the multifarious clinical manifestations of pulmonary ricinosis. Here, we report for the first time, the monitoring of barometric whole body plethysmography for pulmonary function tests in non-anesthetized ricin-treated pigs. Up to 30 h post-exposure, as a result of progressing hypoxemia and to prevent carbon dioxide retention, animals exhibited a compensatory response of elevation in minute volume, attributed mainly to a large elevation in respiratory rate with minimal response in tidal volume. This response was followed by decompensation, manifested by a decrease in minute volume and severe hypoxemia, refractory to oxygen treatment. Radiological evaluation revealed evidence of early diffuse bilateral pulmonary infiltrates while hemodynamic parameters remained unchanged, excluding cardiac failure as an explanation for respiratory insufficiency. Ricin-intoxicated pigs suffered from increased lung permeability accompanied by cytokine storming. Histological studies revealed lung tissue insults that accumulated over time and led to diffuse alveolar damage. Charting the decline in PaO2/FiO2 ratio in a mechanically ventilated pig confirmed that ricin-induced respiratory damage complies with the accepted diagnostic criteria for ARDS. The establishment of this animal model of pulmonary ricinosis should help in the pursuit of efficient medical countermeasures specifically tailored to deal with the respiratory deficiencies stemming from ricin-induced ARDS. © 2017. Published by The Company of Biologists Ltd.

Microsurgical Decompression of Inferior Alveolar Nerve After Endodontic Treatment Complications.

PubMed

Bianchi, Bernardo; Ferri, Andrea; Varazzani, Andrea; Bergonzani, Michela; Sesenna, Enrico

2017-07-01

Iatrogenic injury in oral surgery is the most frequent cause of sensory disturbance in the distribution of the inferior alveolar nerve (IAN) and mental nerve.Inferior alveolar nerve damage can occur during third molar extraction, implant location, orthognathic surgery, preprosthetic surgery, salivary gland surgery, local anesthetic injections or during the resection of benign or malignant tumors.Injuries to the IAN can be caused also by endodontic treatment of mandibular molars and premolars when filling material is forced into the tooth and mandibular canal.The sensory disturbances that could follow a damage of the IAN could be hypoesthesia, dysesthesia, hyperesthesia, anesthesia, and sometimes a painful anesthesia that strike ipsilateral lower lip, chin, and teeth. These can undermine life quality by affecting speech, chewing, and social interaction.Treatment of these complications is sometimes difficult and could consist in observation or in surgical decompression of the involved nerve to relieve the patient's symptoms and improve sensory recovery. The most debated points are the timing of intervention and the effective role of decompression in clinical outcome-improvement.The purpose of this article is to show authors' experience with 2 patients treated with microsurgical nerve decompression to remove endodontic material from the mandibular canal and providing also a comprehensive review of the literature.

Accidental injury of the inferior alveolar nerve due to the extrusion of calcium hydroxide in endodontic treatment: a case report

PubMed Central

2016-01-01

During clinical endodontic treatment, we often find radiopaque filling material beyond the root apex. Accidental extrusion of calcium hydroxide could cause the injury of inferior alveolar nerve, such as paresthesia or continuous inflammatory response. This case report presents the extrusion of calcium hydroxide and treatment procedures including surgical intervention. A 48 yr old female patient experienced Calcipex II extrusion in to the inferior alveolar canal on left mandibular area during endodontic treatment. After completion of endodontic treatment on left mandibular first molar, surgical intervention was planned under general anesthesia. After cortical bone osteotomy and debridement, neuroma resection and neurorrhaphy was performed, and prognosis was observed. But no improvement in sensory nerve was seen following surgical intervention after 20 mon. A clinician should be aware of extrusion of intracanal medicaments and the possibility of damage on inferior alveolar canal. Injectable type of calcium hydroxide should be applied with care for preventing nerve injury. The alternative delivery method such as lentulo spiral was suggested on the posterior mandibular molar. PMID:26877992

Endovascular embolization for the management of inferior alveolar artery bleeding after a third molar extraction: A case report.

PubMed

Bianchi, Bernardo; Varazzani, Anea; Ferri, Anea; Menozzi, Roberto; Sesenna, Enrico

2016-03-01

Removal of third molars is a common surgical procedure with low complication rates. Localized alveolar osteitis, infection, bleeding, and paresthesia are the four most common postoperative complications of third molar extraction reported in the literature. Postoperative severe hemorrhages are rare and are usually related to inferior alveolar artery damage. Although most bleeding is usually managed effectively by local compression or packing of the socket, even life-threatening complications may occur. Endovascular embolization has been rarely reported as treatment for such a complication and represents an ideal solution, with a low complication rate and excellent control of bleeding. The authors report a case of potentially life-threatening hemorrhage continuing 4 days after extraction of the mandibular right third molar, resulting in significant anemia (Hb 6.6 g/dL) and treated successfully with endovascular embolization of the inferior alveolar artery. The authors consider it important for general practitioners to know this treatment and how to manage this rare complication in the correct way, saving time if satisfactory hemostasis cannot be reached with common procedures.

The development and plasticity of alveolar type 1 cells

PubMed Central

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

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

PubMed Central

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

Gallium uptake in tryptophan-related pulmonary disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, S.M.; Park, C.H.; Intenzo, C.M.

1991-02-01

We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking high doses of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.

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

PubMed

Hofmann, Falk; Bläsche, Robert; Kasper, Michael; Barth, Kathrin

2015-01-01

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.

Brain metastasis of crystal-deficient, CD68-positive alveolar soft part sarcoma: ultrastructural features and differential diagnosis

PubMed Central

Cykowski, Matthew D.; Hicks, John; Sandberg, David I.; Olar, Adriana; Bridge, Julia A.; Greipp, Patricia T.; Navarro, Patricia; Kolodziej, Steven; Bhattacharjee, Meenakshi B.

2014-01-01

We report a case of alveolar soft part sarcoma (ASPS) presenting as an isolated frontal lobe metastasis. The tumor demonstrated little or no immunoreactivity for a broad panel of antibodies yet strong, diffuse immunoreactivity with CD68. On electron microscopy, characteristic rectangular to rhomboid crystalline inclusions were not present. Electron-dense granules resembling peroxisomes were present, sometimes in association with elongated granular structures having a periodic, lattice-like arrangement. Metastatic ASPS was confirmed by demonstration of an ASPSCR1-TFE3 fusion and imaging studies that excluded metastatic Xp11.2 translocation renal cell carcinoma. The primary site was subsequently identified in the lower extremity. PMID:25268941

Intermuscular pterygoid-temporal abscess following inferior alveolar nerve block anesthesia–A computer tomography based navigated surgical intervention: Case report and review

PubMed Central

Wallner, Jürgen; Reinbacher, Knut Ernst; Pau, Mauro; Feichtinger, Matthias

2014-01-01

Inferior alveolar nerve block (IANB) anesthesia is a common local anesthetic procedure. Although IANB anesthesia is known for its safety, complications can still occur. Today immediately or delayed occurring disorders following IANB anesthesia and their treatment are well-recognized. We present a case of a patient who developed a symptomatic abscess in the pterygoid region as a result of several inferior alveolar nerve injections. Clinical symptoms included diffuse pain, reduced mouth opening and jaw's hypomobility and were persistent under a first step conservative treatment. Since image-based navigated interventions have gained in importance and are used for various procedures a navigated surgical intervention was initiated as a second step therapy. Thus precise, atraumatic surgical intervention was performed by an optical tracking system in a difficult anatomical region. A symptomatic abscess was treated by a computed tomography-based navigated surgical intervention at our department. Advantages and disadvantages of this treatment strategy are evaluated. PMID:24987612

Intermuscular pterygoid-temporal abscess following inferior alveolar nerve block anesthesia-A computer tomography based navigated surgical intervention: Case report and review.

PubMed

Wallner, Jürgen; Reinbacher, Knut Ernst; Pau, Mauro; Feichtinger, Matthias

2014-01-01

Inferior alveolar nerve block (IANB) anesthesia is a common local anesthetic procedure. Although IANB anesthesia is known for its safety, complications can still occur. Today immediately or delayed occurring disorders following IANB anesthesia and their treatment are well-recognized. We present a case of a patient who developed a symptomatic abscess in the pterygoid region as a result of several inferior alveolar nerve injections. Clinical symptoms included diffuse pain, reduced mouth opening and jaw's hypomobility and were persistent under a first step conservative treatment. Since image-based navigated interventions have gained in importance and are used for various procedures a navigated surgical intervention was initiated as a second step therapy. Thus precise, atraumatic surgical intervention was performed by an optical tracking system in a difficult anatomical region. A symptomatic abscess was treated by a computed tomography-based navigated surgical intervention at our department. Advantages and disadvantages of this treatment strategy are evaluated.

Evidence for minimal oxygen heterogeneity in the healthy human pulmonary acinus

PubMed Central

Tawhai, Merryn H.

2011-01-01

It has been suggested that the human pulmonary acinus operates at submaximal efficiency at rest due to substantial spatial heterogeneity in the oxygen partial pressure (Po2) in alveolar air within the acinus. Indirect measurements of alveolar air Po2 could theoretically mask significant heterogeneity if intra-acinar perfusion is well matched to Po2. To investigate the extent of intra-acinar heterogeneity, we developed a computational model with anatomically based structure and biophysically based equations for gas exchange. This model yields a quantitative prediction of the intra-acinar O2 distribution that cannot be measured directly. Temporal and spatial variations in Po2 in the intra-acinar air and blood are predicted with the model. The model, representative of a single average acinus, has an asymmetric multibranching respiratory airways geometry coupled to a symmetric branching conducting airways geometry. Advective and diffusive O2 transport through the airways and gas exchange into the capillary blood are incorporated. The gas exchange component of the model includes diffusion across the alveolar air-blood membrane and O2-hemoglobin binding. Contrary to previous modeling studies, simulations show that the acinus functions extremely effectively at rest, with only a small degree of intra-acinar Po2 heterogeneity. All regions of the model acinus, including the peripheral generations, maintain a Po2 >100 mmHg. Heterogeneity increases slightly when the acinus is stressed by exercise. However, even during exercise the acinus retains a reasonably homogeneous gas phase. PMID:21071589

Lung Structure and the Intrinsic Challenges of Gas Exchange

PubMed Central

Hsia, Connie C.W.; Hyde, Dallas M.; Weibel, Ewald R.

2016-01-01

Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints. PMID:27065169

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

PubMed

Dane, D Merrill; Yan, Xiao; Tamhane, Rahul M; Johnson, Robert L; Estrera, Aaron S; Hogg, Deborah C; Hogg, Richard T; Hsia, Connie C W

2004-03-01

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema.

PubMed

Ozawa, Chihiro; Horiguchi, Michiko; Akita, Tomomi; Oiso, Yuki; Abe, Kaori; Motomura, Tomoki; Yamashita, Chikamasa

2016-01-01

Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair. Here, we demonstrate that treatment using a high-affinity PPARβ/δ agonist, GW0742, reverses the lung tissue damage induced by elastase in emphysema-model mice and improves respiratory function. Mice treated with elastase, which collapsed their alveoli, were then treated with either 10% dimethyl sulfoxide (DMSO) in saline (control group) or GW0742 (1.0 mg/kg twice a week) by pulmonary administration. Treatment with GW0742 for 2 weeks increased the in vivo expression of surfactant proteins A and D, which are known alveolar type II epithelial cell markers. GW0742 treatment also shortened the average distance between alveolar walls in the lungs of emphysema model mice, compared with a control group treated with 10% DMSO in saline. Treatment with GW0742 for 3 weeks also improved tissue elastance (cm H2O/mL), as well as the ratio of the forced expiratory volume in the first 0.05 s to the forced vital capacity (FEV 0.05/FVC). In each of these experiments, GW0742 treatment reversed the damage caused by elastase. In conclusion, PPARβ/δ agonists are potential therapeutic agents for pulmonary emphysema.

Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies.

PubMed

Wallace, William Dean; Li, Ning; Andersen, Claus B; Arrossi, A Valeria; Askar, Medhat; Berry, Gerry J; DeNicola, Matthew M; Neil, Desley A; Pavlisko, Elizabeth N; Reed, Elaine F; Remmelink, Myriam; Weigt, S Sam; Weynand, Birgit; Zhang, Jennifer Q; Budev, Marie M; Farver, Carol F

2016-01-01

The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs). We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed. We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage (p = 0.0008), in the presence of capillary neutrophilic inflammation (p = 0.0014), and in samples with endotheliitis (p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs. Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: experimental study.

PubMed

Yavuz, Yucel; Kaya, Eser; Yurumez, Yusuf; Sahin, Onder; Bas, Orhan; Fidan, Huseyin; Sezer, Murat

2008-09-01

The aim of this experimental study was to investigate pathological signs of lung damages caused by acute organophosphate (OP) poisoning by using Tc-99m DTPA radioaerosol scintigraphy and histopathological investigation. Fourteen rabbits were divided into two equal groups (n = 7). Group 1 (control group) received normal saline (same volume of fenthion, 2 ml/kg) via orogastric tube. Group 2 (OP toxicity group) received 150 mg/kg of fenthion (diluted fenthion, 2 ml/kg) via orogastric tube. Six hours later, Tc-99m-DTPA aerosol inhalation lung scintigraphy was performed in both groups. Then all rabbits were anesthetized with ketamine hydrochloride (35 mg/kg, i.p.) and xysilazine (5 mg/kg, i.p.), and sacrificed by intracardiac blood discharge. The lungs were then removed. There was a significant difference in T1/2 values of Tc-99m DTPA clearance between control group and OP toxicity group (p = 0.04). Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar, and bronchial lumen, alveolar destruction, emphysematous changes, and bronchoalveolar hemorrhage scores were significantly higher in the rabbits exposed to OP compared with the control group (p < 0.05). This study showed that OP toxicity caused a decrease in the alveolar clearance. Tc-99m DTPA radioaerosol inhalation lung scintigraphy was found to be a sensitive determination of acute lung damage in OP poisoning.

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke.

PubMed

Wolf, Lisa; Herr, Christian; Niederstraßer, Julia; Beisswenger, Christoph; Bals, Robert

2017-01-01

The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

Structural Measurements from Images of Noble Gas Diffusion

NASA Astrophysics Data System (ADS)

Cadman, Robert V.; Kadlecek, Stephen J.; Emami, Kiarash; MacDuffie Woodburn, John; Vahdat, Vahid; Ishii, Masaru; Rizi, Rahim R.

2009-03-01

Magnetic resonance imaging of externally polarized noble gases such as ^3He has been used for pulmonary imaging for more than a decade. Because gas diffusion is impeded by the alveoli, the diffusion coefficient of gas in the lung, measured on a time scale of milliseconds, is reduced compared to that of the same gas mixture in the absence of restrictions. When the alveolar walls decay, as in emphysema, diffusivity in the lung increases. In this paper, the relationship between diffusion measurements and the size of the restricting structures will be discussed. The simple case of diffusion in an impermeable cylinder, a structure similar to the upper respiratory airways in mammals, has been studied. A procedure will be presented by which airways of order 2 mm in diameter may be accurately measured; demonstration experiments with plastic tubes will also be presented. The additional developments needed before this technique becomes practical will be briefly discussed.

A novel method for computing effective diffusivity: Application to helium implanted α-Fe thin films

NASA Astrophysics Data System (ADS)

Dunn, Aaron; Agudo-Merida, Laura; Martin-Bragado, Ignacio; McPhie, Mathieu; Cherkaoui, Mohammed; Capolungo, Laurent

2014-05-01

The effective diffusivity of helium in thin iron films is quantified using spatially resolved stochastic cluster dynamics and object kinetic Monte Carlo simulations. The roles of total displacement dose (in DPA), damage rate, helium to DPA ratio, layer thickness, and damage type (cascade damage vs Frenkel pair implantation) on effective He diffusivity are investigated. Helium diffusivity is found to decrease with increasing total damage and decreasing damage rate. Arrhenius plots show strongly increased helium diffusivity at high temperatures, high total implantation, and low implantation rates due to decreased vacancy and vacancy cluster concentrations. At low temperatures, effective diffusivity is weakly dependent on foil thickness while at high temperatures, narrower foils prevent defect accumulation by releasing all defects at the free surfaces. Helium to DPA ratio is not shown to strongly change helium diffusivity in the range of irradiation conditions simulated. Frenkel pair implantation is shown to cause higher effective diffusivity and more complex diffusion mechanisms than cascade implantation. The results of these simulations indicate that the differences in damage rates between implantation experiments and fission or fusion environments may result in differences in the final microstructure.

Tissue engineering in periodontal tissue.

PubMed

Iwata, Takanori; Yamato, Masayuki; Ishikawa, Isao; Ando, Tomohiro; Okano, Teruo

2014-01-01

Periodontitis, a recognized disease worldwide, is bacterial infection-induced inflammation of the periodontal tissues that results in loss of alveolar bone. Once it occurs, damaged tissue cannot be restored to its original form, even if decontaminating treatments are performed. For more than half a century, studies have been conducted to investigate true periodontal regeneration. Periodontal regeneration is the complete reconstruction of the damaged attachment apparatus, which contains both hard tissue (alveolar bone and cementum) and soft tissue (periodontal ligament). Several treatments, including bone grafts, guided tissue regeneration with physical barriers for epithelial cells, and growth factors have been approved for clinical use; however, their indications and outcomes are limited. To overcome these limitations, the concept of "tissue engineering" was introduced. Combination treatment using cells, growth factors, and scaffolds, has been studied in experimental animal models, and some studies have been translated into clinical trials. In this review, we focus on recent progressive tissue engineering studies and discuss future perspectives on periodontal regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Probing Lung Microstructure with Hyperpolarized 3He Gradient Echo MRI

PubMed Central

Sukstanskii, Alexander L; Quirk, James D; Yablonskiy, Dmitriy A

2014-01-01

In this paper we demonstrate that Gradient Echo MRI with hyperpolarized 3He gas can be used for simultaneously extracting in vivo information about lung ventilation properties, alveolar geometrical parameters, and blood vessel network structure. This new approach is based on multi-gradient-echo experimental measurements of hyperpolarized 3He gas MRI signal from human lungs and a proposed theoretical model of this signal. Based on computer simulations of 3He atoms diffusing in the acinar airway tree in the presence of an inhomogeneous magnetic field induced by the susceptibility differences between lung tissue (alveolar septa, blood vessels) and lung airspaces we derive analytical expressions relating the time-dependent MR signal to the geometrical parameters of acinar airways and blood vessel network. Data obtained on 8 healthy volunteers are in good agreement with literature values. This information is complementary to the information that is obtained by means of in vivo lung morphometry technique with hyperpolarized 3He diffusion MRI previously developed by our group and opens new opportunities to study lung microstructure in health and disease. PMID:24920182

Inferior alveolar nerve cutting; legal liability versus desired patient outcomes.

PubMed

Kim, Soung Min; Lee, Jong Ho

2017-10-01

Mandibular angle reduction or reduction genioplasty is a routine well-known facial contouring surgery that reduces the width of the lower face resulting in an oval shaped face. During the intraoral resection of the mandibular angle or chin using an oscillating saw, unexpected peripheral nerve damage including inferior alveolar nerve (IAN) damage could occur. This study analyzed cases of damaged IANs during facial contouring surgery, and asked what the basic standard of care in these medical litigation-involved cases should be. We retrospectively reviewed a total of 28 patients with IAN damage after mandibular contouring from August 2008 to July 2015. Most of the patients did not have an antipathy to medical staff because they wanted their faces to be ovoid shaped. We summarized three representative cases according to each patient's perceptions and different operation procedures under the approvement by the Institutional Review Board of Seoul National University. Most of the patients did not want to receive any further operations not due to fear of an operation but because of the changes in their facial appearance. Thus, their fear may be due to a desire for a better perfect outcome, and to avoid unsolicited patient complaints related litigation. This article analyzed representative IAN cutting cases that occurred during mandibular contouring esthetic surgery and evaluated a questionnaire on the standard of care for the desired patient outcomes and the specialized surgeon's position with respect to legal liability.

[Pulmonary cystic disease may be a rare complication to recurrent respiratory human papilloma virus infection].

PubMed

Laurberg, Peter Thaysen; Weinreich, Ulla M Øller

2014-12-08

A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.

Simulation of lung alveolar epithelial wound healing in vitro.

PubMed

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.

Glycosylases utilize ``stop and go'' motion to locate DNA damage

NASA Astrophysics Data System (ADS)

Nelson, Shane

2015-03-01

Oxidative damage to DNA results in alterations that are mutagenic or even cytotoxic. Base excision repair is a mechanism that functions to identify and correct these lesions, and is present in organisms ranging from bacteria to humans. DNA glycosylases are the first enzymes in this pathway and function to locate and remove oxidatively damaged bases, and do so utilizing only thermal energy. However, the question remains of how these enzymes locate and recognize a damaged base among millions of undamaged bases. Utilizing fluorescence video microscopy with high spatial and temporal resolution, we have observed a number of different fluorescently labeled glycosylases (including bacterial FPG, NEI, and NTH as well as mammalian MutyH and OGG). These enzymes diffuse along DNA tightropes at approximately 0.01 +/- 0.005 μm2/s with binding lifetimes ranging from one second to several minutes. Chemically induced damage to the DNA substrate causes a ~ 50% reduction in diffusion coefficients and a ~ 400% increase in binding lifetimes, while mutation of the key ``wedge residue'' - which has been shown to be responsible for damage detection - results in a 200% increase in the diffusion coefficient. Utilizing a sliding window approach to measure diffusion coefficients within individual trajectories, we observe that distributions of diffusion coefficients are bimodal, consistent with periods of diffusive motion interspersed with immobile periods. Utilizing a unique chemo-mechanical simulation approach, we demonstrate that the motion of these glycosylases can be explained as free diffusion along the helical pitch of the DNA, punctuated with two different types of pauses: 1) rapid, short-lived pauses as the enzyme rapidly probes DNA bases to interrogate for damage and, 2) less frequent, longer lived pauses that reflect the enzyme bound to and catalytically removing a damaged base. These simulations also indicate that the wedge residue is critical for interrogation and recognition of damage, and thus enzymes missing this residue diffuse faster. Similarly, chemically induced damage increases the frequency with which the enzymes encounter damaged bases, resulting in slower diffusion.

A Pathophysiologic Approach to Biomarkers in Acute Respiratory Distress Syndrome

PubMed Central

Blondonnet, Raiko; Constantin, Jean-Michel; Sapin, Vincent; Jabaudon, Matthieu

2016-01-01

Acute respiratory distress syndrome (ARDS) is an acute-onset hypoxic condition with radiographic bilateral lung infiltration. It is characterized by an acute exudative phase combining diffuse alveolar damage and lung edema followed by a later fibroproliferative phase. Despite an improved understanding of ARDS pathobiology, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. After a short description of ARDS pathobiology, here, we review the scientific evidence that supports the value of various ARDS biomarkers with regard to their major biological roles in ARDS-associated lung injury and/or repair. Ongoing research aims at identifying and characterizing novel biomarkers, in order to highlight relevant mechanistic explorations of lung injury and repair, and to ultimately develop innovative therapeutic approaches for ARDS patients. This review will focus on the pathophysiologic, diagnostic, and therapeutic implications of biomarkers in ARDS and on their utility to ultimately improve patient care. PMID:26980924

Curcumin Modulates the Inflammatory Response and Inhibits Subsequent Fibrosis in a Mouse Model of Viral-induced Acute Respiratory Distress Syndrome

PubMed Central

Liu, Guangliang; Wang, Ruixue; London, Steven D.; London, Lucille

2013-01-01

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 107 pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation. PMID:23437361

Bacterial infection and acute lung injury in hamsters.

PubMed

Seidenfeld, J J; Mullins, R C; Fowler, S R; Johanson, W G

1986-07-01

Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.

SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism.

PubMed

Frieman, Matthew B; Chen, Jun; Morrison, Thomas E; Whitmore, Alan; Funkhouser, William; Ward, Jerrold M; Lamirande, Elaine W; Roberts, Anjeanette; Heise, Mark; Subbarao, Kanta; Baric, Ralph S

2010-04-08

Severe acute respiratory syndrome coronavirus (SARS-CoV) infection often caused severe end stage lung disease and organizing phase diffuse alveolar damage, especially in the elderly. The virus-host interactions that governed development of these acute end stage lung diseases and death are unknown. To address this question, we evaluated the role of innate immune signaling in protection from human (Urbani) and a recombinant mouse adapted SARS-CoV, designated rMA15. In contrast to most models of viral pathogenesis, infection of type I, type II or type III interferon knockout mice (129 background) with either Urbani or MA15 viruses resulted in clinical disease outcomes, including transient weight loss, denuding bronchiolitis and alveolar inflammation and recovery, identical to that seen in infection of wildtype mice. This suggests that type I, II and III interferon signaling play minor roles in regulating SARS pathogenesis in mouse models. In contrast, infection of STAT1-/- mice resulted in severe disease, high virus titer, extensive pulmonary lesions and 100% mortality by day 9 and 30 post-infection with rMA15 or Urbani viruses, respectively. Non-lethal in BALB/c mice, Urbani SARS-CoV infection in STAT1-/- mice caused disseminated infection involving the liver, spleen and other tissues after day 9. These findings demonstrated that SARS-CoV pathogenesis is regulated by a STAT1 dependent but type I, II and III interferon receptor independent, mechanism. In contrast to a well documented role in innate immunity, we propose that STAT1 also protects mice via its role as an antagonist of unrestrained cell proliferation.

Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

PubMed

Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

2017-09-01

Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

PubMed

Avasarala, Sreedevi; Zhang, Fangfang; Liu, Guangliang; Wang, Ruixue; London, Steven D; London, Lucille

2013-01-01

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

Coal Mine Dust Desquamative Chronic Interstitial Pneumonia: A Precursor of Dust-Related Diffuse Fibrosis and of Emphysema.

PubMed

Jelic, Tomislav M; Estalilla, Oscar C; Sawyer-Kaplan, Phyllis R; Plata, Milton J; Powers, Jeremy T; Emmett, Mary; Kuenstner, John T

2017-07-01

Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. To identify the precursor of dust-related diffuse fibrosis and emphysema. Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Coal miners had 331 birefringent particles/high power field while smokers had 4 (p<0.001). Every coal miner had intra-alveolar macrophages with silica/silicate particles and interstitial fibrosis ranging from minimal to extreme. All coal miners, including those who never smoked, had emphysema. Fibrotic septa of centrilobular emphysema contained numerous silica/silicate particles while only a few were present in adjacent normal lung tissue. In coal miners who smoked, tobacco-associated interstitial fibrosis was replaced by fibrosis caused by silica/silicate particles. The presence of silica/silicate particles and anthracotic pigment-laden macrophages inside the alveoli with various degrees of interstitial fibrosis indicated a new disease: coal mine dust desquamative chronic interstitial pneumonia, a precursor of both dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis caused by smoking is insignificant in comparison with fibrosis caused by silica/silicate particles. Counting birefringent particles in the macrophages from bronchioalveolar lavage may help detect coal mine dust desquamative chronic interstitial pneumonia, and may initiate early therapy and preventive measures.

Lung Structure and the Intrinsic Challenges of Gas Exchange.

PubMed

Hsia, Connie C W; Hyde, Dallas M; Weibel, Ewald R

2016-03-15

Structural and functional complexities of the mammalian lung evolved to meet a unique set of challenges, namely, the provision of efficient delivery of inspired air to all lung units within a confined thoracic space, to build a large gas exchange surface associated with minimal barrier thickness and a microvascular network to accommodate the entire right ventricular cardiac output while withstanding cyclic mechanical stresses that increase several folds from rest to exercise. Intricate regulatory mechanisms at every level ensure that the dynamic capacities of ventilation, perfusion, diffusion, and chemical binding to hemoglobin are commensurate with usual metabolic demands and periodic extreme needs for activity and survival. This article reviews the structural design of mammalian and human lung, its functional challenges, limitations, and potential for adaptation. We discuss (i) the evolutionary origin of alveolar lungs and its advantages and compromises, (ii) structural determinants of alveolar gas exchange, including architecture of conducting bronchovascular trees that converge in gas exchange units, (iii) the challenges of matching ventilation, perfusion, and diffusion and tissue-erythrocyte and thoracopulmonary interactions. The notion of erythrocytes as an integral component of the gas exchanger is emphasized. We further discuss the signals, sources, and limits of structural plasticity of the lung in alveolar hypoxia and following a loss of lung units, and the promise and caveats of interventions aimed at augmenting endogenous adaptive responses. Our objective is to understand how individual components are matched at multiple levels to optimize organ function in the face of physiological demands or pathological constraints. Copyright © 2016 John Wiley & Sons, Inc.

Airway delivery of mesenchymal stem cells prevents arrested alveolar growth in neonatal lung injury in rats.

PubMed

van Haaften, Timothy; Byrne, Roisin; Bonnet, Sebastien; Rochefort, Gael Y; Akabutu, John; Bouchentouf, Manaf; Rey-Parra, Gloria J; Galipeau, Jacques; Haromy, Alois; Eaton, Farah; Chen, Ming; Hashimoto, Kyoko; Abley, Doris; Korbutt, Greg; Archer, Stephen L; Thébaud, Bernard

2009-12-01

Bronchopulmonary dysplasia (BPD) and emphysema are characterized by arrested alveolar development or loss of alveoli; both are significant global health problems and currently lack effective therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) prevent adult lung injury, but their therapeutic potential in neonatal lung disease is unknown. We hypothesized that intratracheal delivery of BMSCs would prevent alveolar destruction in experimental BPD. In vitro, BMSC differentiation and migration were assessed using co-culture assays and a modified Boyden chamber. In vivo, the therapeutic potential of BMSCs was assessed in a chronic hyperoxia-induced model of BPD in newborn rats. In vitro, BMSCs developed immunophenotypic and ultrastructural characteristics of type II alveolar epithelial cells (AEC2) (surfactant protein C expression and lamellar bodies) when co-cultured with lung tissue, but not with culture medium alone or liver. Migration assays revealed preferential attraction of BMSCs toward oxygen-damaged lung versus normal lung. In vivo, chronic hyperoxia in newborn rats led to air space enlargement and loss of lung capillaries, and this was associated with a decrease in circulating and resident lung BMSCs. Intratracheal delivery of BMSCs on Postnatal Day 4 improved survival and exercise tolerance while attenuating alveolar and lung vascular injury and pulmonary hypertension. Engrafted BMSCs coexpressed the AEC2-specific marker surfactant protein C. However, engraftment was disproportionately low for cell replacement to account for the therapeutic benefit, suggesting a paracrine-mediated mechanism. In vitro, BMSC-derived conditioned medium prevented O(2)-induced AEC2 apoptosis, accelerated AEC2 wound healing, and enhanced endothelial cord formation. BMSCs prevent arrested alveolar and vascular growth in part through paracrine activity. Stem cell-based therapies may offer new therapeutic avenues for lung diseases that currently lack efficient treatments.

Type XVIII collagen degradation products in acute lung injury

PubMed Central

Perkins, Gavin D; Nathani, Nazim; Richter, Alex G; Park, Daniel; Shyamsundar, Murali; Heljasvaara, Ritva; Pihlajaniemi, Taina; Manji, Mav; Tunnicliffe, W; McAuley, Danny; Gao, Fang; Thickett, David R

2009-01-01

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge. Methods Endostatin was measured by ELISA and western blotting. Results Endostatin is elevated within the plasma and bronchoalveolar lavage fluid of patients with acute lung injury. Lavage endostatin reflected the degree of alveolar neutrophilia and the extent of the loss of protein selectivity of the alveolar-capillary barrier. Plasma levels of endostatin correlated with the severity of physiological derangement. Western blotting confirmed elevated type XVIII collagen precursor levels in the plasma and lavage and multiple endostatin-like fragments in the lavage of patients. One lung ventilation and LPS challenge rapidly induce increases in lung endostatin levels. Conclusions Endostatin may adversely affect both alveolar barrier endothelial and epithelial cells, so its presence within both the circulation and the lung may have a pathophysiological role in acute lung injury that warrants further evaluation. PMID:19358707

Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.

PubMed

Hasan, Djo; Blankman, Paul; Nieman, Gary F

2017-09-01

Severe pulmonary infection or vigorous cyclic deformation of the alveolar epithelial type I (AT I) cells by mechanical ventilation leads to massive extracellular ATP release. High levels of extracellular ATP saturate the ATP hydrolysis enzymes CD39 and CD73 resulting in persistent high ATP levels despite the conversion to adenosine. Above a certain level, extracellular ATP molecules act as danger-associated molecular patterns (DAMPs) and activate the pro-inflammatory response of the innate immunity through purinergic receptors on the surface of the immune cells. This results in lung tissue inflammation, capillary leakage, interstitial and alveolar oedema and lung injury reducing the production of surfactant by the damaged AT II cells and deactivating the surfactant function by the concomitant extravasated serum proteins through capillary leakage followed by a substantial increase in alveolar surface tension and alveolar collapse. The resulting inhomogeneous ventilation of the lungs is an important mechanism in the development of ventilation-induced lung injury. The high levels of extracellular ATP and the upregulation of ecto-enzymes and soluble enzymes that hydrolyse ATP to adenosine (CD39 and CD73) increase the extracellular adenosine levels that inhibit the innate and adaptive immune responses rendering the host susceptible to infection by invading microorganisms. Moreover, high levels of extracellular adenosine increase the expression, the production and the activation of pro-fibrotic proteins (such as TGF-β, α-SMA, etc.) followed by the establishment of lung fibrosis.

Impact of Different Tidal Volume Levels at Low Mechanical Power on Ventilator-Induced Lung Injury in Rats.

PubMed

Moraes, Lillian; Silva, Pedro L; Thompson, Alessandra; Santos, Cintia L; Santos, Raquel S; Fernandes, Marcos V S; Morales, Marcelo M; Martins, Vanessa; Capelozzi, Vera L; de Abreu, Marcelo G; Pelosi, Paolo; Rocco, Patricia R M

2018-01-01

Tidal volume (V T ) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high V T should not be injurious. The present study aimed to investigate the impact of different V T levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation [interleukin (IL)-6], alveolar stretch (amphiregulin), epithelial [club cell secretory protein (CC)16] and endothelial [intercellular adhesion molecule (ICAM)-1] cell injury, and extracellular matrix damage [syndecan-1, decorin, and metalloproteinase (MMP)-9] in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation. Twenty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 21 animals were randomly assigned to ventilation (2 h) with low mechanical power at three different V T levels ( n = 7/group): (1) V T = 6 mL/kg and RR adjusted to normocapnia; (2) V T = 13 mL/kg; and 3) V T = 22 mL/kg. In the second and third groups, RR was adjusted to yield low mechanical power comparable to that of the first group. Mechanical power was calculated as [(Δ[Formula: see text]/Est, L )/2]× RR (ΔP, L = transpulmonary driving pressure, Est, L = static lung elastance). Seven rats were not mechanically ventilated (NV) and were used for molecular biology analysis. Mechanical power was comparable among groups, while V T gradually increased. ΔP, L and mechanical energy were higher in V T = 22 mL/kg than V T = 6 mL/kg and V T = 13 mL/kg ( p < 0.001 for both). Accordingly, DAD score increased in V T = 22 mL/kg compared to V T = 6 mL/kg and V T = 13 mL/kg [23(18.5-24.75) vs. 16(12-17.75) and 16(13.25-18), p < 0.05, respectively]. V T = 22 mL/kg was associated with higher IL-6, amphiregulin, CC16, MMP-9, and syndecan-1 mRNA expression and lower decorin expression than V T = 6 mL/kg. Multiple linear regression analyses indicated that V T was able to predict changes in IL-6 and CC16, whereas ΔP, L predicted pHa, oxygenation, amphiregulin, and syndecan-1 expression. In the model of ARDS used herein, even at low mechanical power, high V T resulted in VILI. V T control seems to be more important than RR control to mitigate VILI.

[Torque control evaluated by lateral cephalometric radiography and cone-beam CT after retraction of the upper anterior teeth].

PubMed

Yang, Xue; Qian, Yu-Fen

2016-08-01

To investigate the relationship between torque control and movement type of the teeth and to investigate the correlation between reconstruction of the alveolar bone and retraction of the upper anterior teeth. Cephalograms of pre-treatment and post-treatment of 111 cases and cone-beam computed tomography of pre-retraction and post-retraction of 7 cases were collected. The inclination degree of the upper anterior teeth, the horizontal and vertical displacement of edge and apex,and the thickness of the alveolar bone at the apex level were measured. Student's t test and Pearson χ2 test were performed for statistical analysis with SAS 8.02 software package. Cases who received torque control during the period of retraction displayed less change of inclination degree of the upper anterior teeth, less lingual displacement of the edge, more lingual displacement of the apex. The total thickness of the alveolar bone at the apex level and the length of the teeth significantly decreased after retraction(P<0.05). The amount of the alveolar bone rebuilt after retraction was less than that of the tooth movement, and there was no significant difference between teenagers and adults. During retraction of the upper anterior teeth, cases who received torque control showed less inclination degree change of the upper anterior teeth, less lingual displacement of the edge, more lingual displacement of the apex. More bodily movement and partially controlled tipping movement as well as higher incident rate of severe root resorption would also arise. There was correlation between reconstruction of the alveolar bone and the tooth movement. Since the amount of adaptive reconstruction of the lingual alveolar bone was limited, and there was no difference between teenagers and adults, excessive lingual displacement would surpass its adaption ability, and gave rise to alveolar bone and tooth damage.

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

PubMed Central

Yang, Lu; Chen, Xufeng; Simet, Samantha M.; Hu, Guoku; Cai, Yu; Niu, Fang; Kook, Yeonhee

2016-01-01

Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell–substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2–related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension. PMID:27391108

Characterization of Ultrasound Energy Diffusion Due to Small-Size Damage on an Aluminum Plate Using Piezoceramic Transducers

PubMed Central

Lu, Guangtao; Feng, Qian; Li, Yourong; Wang, Hao; Song, Gangbing

2017-01-01

During the propagation of ultrasonic waves in structures, there is usually energy loss due to ultrasound energy diffusion and dissipation. The aim of this research is to characterize the ultrasound energy diffusion that occurs due to small-size damage on an aluminum plate using piezoceramic transducers, for the future purpose of developing a damage detection algorithm. The ultrasonic energy diffusion coefficient is related to the damage distributed in the medium. Meanwhile, the ultrasonic energy dissipation coefficient is related to the inhomogeneity of the medium. Both are usually employed to describe the characteristics of ultrasound energy diffusion. The existence of multimodes of Lamb waves in metallic plate structures results in the asynchronous energy transport of different modes. The mode of Lamb waves has a great influence on ultrasound energy diffusion as a result, and thus has to be chosen appropriately. In order to study the characteristics of ultrasound energy diffusion in metallic plate structures, an experimental setup of an aluminum plate with a through-hole, whose diameter varies from 0.6 mm to 1.2 mm, is used as the test specimen with the help of piezoceramic transducers. The experimental results of two categories of damages at different locations reveal that the existence of damage changes the energy transport between the actuator and the sensor. Also, when there is only one dominate mode of Lamb wave excited in the structure, the ultrasound energy diffusion coefficient decreases approximately linearly with the diameter of the simulated damage. Meanwhile, the ultrasonic energy dissipation coefficient increases approximately linearly with the diameter of the simulated damage. However, when two or more modes of Lamb waves are excited, due to the existence of different group velocities between the different modes, the energy transport of the different modes is asynchronous, and the ultrasonic energy diffusion is not strictly linear with the size of the damage. Therefore, it is recommended that only one dominant mode of Lamb wave should be excited during the characterization process, in order to ensure that the linear relationship between the damage size and the characteristic parameters is maintained. In addition, the findings from this paper demonstrate the potential of developing future damage detection algorithms using the linear relationships between damage size and the ultrasound energy diffusion coefficient or ultrasonic energy dissipation coefficient when a single dominant mode is excited. PMID:29207530

A computer model for the simulation of nanoparticle deposition in the alveolar structures of the human lungs.

PubMed

Sturm, Robert

2015-11-01

According to epidemiological and experimental studies, inhalation of nanoparticles is commonly believed as a main trigger for several pulmonary dysfunctions and lung diseases. Concerning the transport and deposition of such nano-scale particles in the different structures of the human lungs, some essential questions are still in need of a clarification. Therefore, main objective of the study was the simulation of nanoparticle deposition in the alveolar region of the human respiratory tract (HRT). Respective factors describing the aerodynamic behavior of spherical and non-spherical particles in the inhaled air stream (i.e., Cunningham slip correction factors, dynamic shape factors, equivalent-volume diameters, aerodynamic diameters) were computed. Alveolar deposition of diverse nanomaterials according to several known mechanisms, among which Brownian diffusion and sedimentation play a superior role, was approximated by the use of empirical and analytical formulae. Deposition calculations were conducted with a currently developed program, termed NANODEP, which allows the variation of numerous input parameters with regard to particle geometry, lung morphometry, and aerosol inhalation. Generally, alveolar deposition of nanoparticles concerned for this study varies between 0.1% and 12.4% during sitting breathing and between 2.0% and 20.1% during heavy-exercise breathing. Prolate particles (e.g., nanotubes) exhibit a significant increase in deposition, when their aspect ratio is enhanced. In contrast, deposition of oblate particles (e.g., nanoplatelets) is remarkably declined with any reduction of the aspect ratio. The study clearly demonstrates that alveolar deposition of nanoparticles represents a topic certainly being of superior interest for physicists and respiratory physicians in future.

Alpha-Recoil Damage Annealing Effecfs on Zircon Crystallinity and He Diffusivity: Improving Damage-Diffusivity Models

NASA Astrophysics Data System (ADS)

Thurston, O. G.; Guenthner, W.; Garver, J. I.

2017-12-01

The effects of radiation damage on He diffusion in zircon has been a major research focus in thermochronology over the past decade. In the zircon-He system, alpha-recoil damage effects He diffusivity in two ways: a decrease in He diffusivity at low radiation damage levels, and an increase in He diffusivity at high radiation damage levels. The radiation damage accumulation process within zircon is well understood; however, the kinetics of annealing of alpha-recoil damage at geologic timescales as they pertain to damage-diffusivity models, and for metamict zircon (i.e. transition from crystalline to amorphous glass via damage accumulation), has not been well constrained. This study aims to develop a more complete model that describes the annealing kinetics for zircon grains with a broad range of pre-annealing, alpha-induced radiation damage. A suite of zircon grains from the Lucerne pluton, ME were chosen for this study due to their simple thermal history (monotonic cooling), notable range of effective uranium (eU, eU = [U] +0.235*[Th]) (15 - 34,239 ppm eU), and large range of radiation damage as measured by Raman shift from crystalline (>1005 cm-1) to metamict (<1000 cm-1). The zircon grains selected represent the full range of eU and radiation damage present in the pluton. The zircon grains were first mapped for overall crystallinity using Raman spectroscopy, then annealed at different time-temperature (t-T) schedules from 1 hr to 24 hrs at temperatures ranging from 700-1100 °C, followed by remapping with Raman spectroscopy to track the total Raman shift for each t-T step. The temperature window selected is at the "roll-over" point established in prior studies (Zhang et al., 2000), at which most laboratory annealing occurs. Our data show that high radiation damage zircon grains show larger Raman shifts than low radiation damage zircon grains when exposed to the same t-T step. The high damage zircon grains typically show a Raman shift of 4 cm-1 toward crystalline, while low radiation damage grains show a shift of 2 cm-1. These shifts suggest that the annealing process occurs at a faster rate in high damage zircon grains, and slower rates in more crystalline grains. That is, the initial level of radiation damage prior to annealing must be considered in damage-diffusivity models that contain thermal histories from zircon-He dates.

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone.

PubMed

Rivera, César; Monsalve, Francisco; Salas, Juan; Morán, Andrea; Suazo, Iván

2013-12-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H 2 O (n=3), distilled water without the drug and alveolar bone damage; BD/H 2 O/PRP (n=3), BD and PRP; BD/H 2 O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects.

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone

PubMed Central

RIVERA, CÉSAR; MONSALVE, FRANCISCO; SALAS, JUAN; MORÁN, ANDREA; SUAZO, IVÁN

2013-01-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H2O (n=3), distilled water without the drug and alveolar bone damage; BD/H2O/PRP (n=3), BD and PRP; BD/H2O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects. PMID:24250728

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

PubMed Central

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

2016-01-01

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 maladaptbed hematopoietic-vascular niche, in which macrophages, PCECs and perivascular fibroblasts interact, may help to develop therapy to spur lung regeneration and alleviate fibrosis. PMID:26779814

Alterations in the alveolar epithelium after injury leading to pulmonary fibrosis.

PubMed

Kasper, M; Haroske, G

1996-04-01

This review discusses current knowledge of the involvement of the alveolar epithelium in tissue remodelling during fibrogenesis. The purpose of the present paper is to give an overview, including the authors' own results, of knowledge of ultrastructural alterations, proliferation kinetics and phenotypic changes of pneumocytes in experimental and clinical pathology of pulmonary fibrosis. After lung injury, the alveolar epithelial cells show ultrastructural alterations, hypertrophy and hyperplasia, and a modulation of a series of structural and membrane proteins such as cytoskeletal changes, loss or de novo expression of epithelial adhesion molecules, and altered lectin binding. Furthermore, enhanced secretion of proteases, of cytokines and other soluble factors can be observed in the alveolar epithelium. These findings suggest the contribution of the epithelium in the remodelling process to be greater than expected. Estimations of the cell kinetics show that type II pneumocytes have the proliferative capacity to restore high proportions of damaged type I cells within few hours. In fibrosis this capacity also seems to be affected seriously, resulting in transitional phenotypes between type II and type I cells. Additionally, in the light of the detection of CD44 type of adhesion molecules at the foot processes of type II pneumocytes, some aspects of epithelial-fibroblast interaction are described.

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

PubMed

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.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

PubMed

Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Simulation of lung alveolar epithelial wound healing in vitro

PubMed Central

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

2010-01-01

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. PMID:20236957

Traffic-related air pollution and alveolar nitric oxide in southern California children.

PubMed

Eckel, Sandrah P; Zhang, Zilu; Habre, Rima; Rappaport, Edward B; Linn, William S; Berhane, Kiros; Zhang, Yue; Bastain, Theresa M; Gilliland, Frank D

2016-05-01

Mechanisms for the adverse respiratory effects of traffic-related air pollution (TRAP) have yet to be established. We evaluated the acute effects of TRAP exposure on proximal and distal airway inflammation by relating indoor nitric oxide (NO), a marker of TRAP exposure in the indoor microenvironment, to airway and alveolar sources of exhaled nitric oxide (FeNO).FeNO was collected online at four flow rates in 1635 schoolchildren (aged 12-15 years) in southern California (USA) breathing NO-free air. Indoor NO was sampled hourly and linearly interpolated to the time of the FeNO test. Estimated parameters quantifying airway wall diffusivity (DawNO) and flux (J'awNO) and alveolar concentration (CANO) sources of FeNO were related to exposure using linear regression to adjust for potential confounders.We found that TRAP exposure indoors was associated with elevated alveolar NO. A 10 ppb higher indoor NO concentration at the time of the FeNO test was associated with 0.10 ppb higher average CANO (95% CI 0.04-0.16) (equivalent to a 7.1% increase from the mean), 4.0% higher J'awNO (95% CI -2.8-11.3) and 0.2% lower DawNO (95% CI -4.8-4.6).These findings are consistent with an airway response to TRAP exposure that was most marked in the distal airways. Copyright ©ERS 2016.

A helium-based model for the effects of radiation damage annealing on helium diffusion kinetics in apatite

NASA Astrophysics Data System (ADS)

Willett, Chelsea D.; Fox, Matthew; Shuster, David L.

2017-11-01

Widely used to study surface processes and the development of topography through geologic time, (U-Th)/He thermochronometry in apatite depends on a quantitative description of the kinetics of 4He diffusion across a range of temperatures, timescales, and geologic scenarios. Empirical observations demonstrate that He diffusivity in apatite is not solely a function of temperature, but also depends on damage to the crystal structure from radioactive decay processes. Commonly-used models accounting for the influence of thermal annealing of radiation damage on He diffusivity assume the net effects evolve in proportion to the rate of fission track annealing, although the majority of radiation damage results from α-recoil. While existing models adequately quantify the net effects of damage annealing in many geologic scenarios, experimental work suggests different annealing rates for the two damage types. Here, we introduce an alpha-damage annealing model (ADAM) that is independent of fission track annealing kinetics, and directly quantifies the influence of thermal annealing on He diffusivity in apatite. We present an empirical fit to diffusion kinetics data and incorporate this fit into a model that tracks the competing effects of radiation damage accumulation and annealing on He diffusivity in apatite through geologic time. Using time-temperature paths to illustrate differences between models, we highlight the influence of damage annealing on data interpretation. In certain, but not all, geologic scenarios, the interpretation of low-temperature thermochronometric data can be strongly influenced by which model of radiation damage annealing is assumed. In particular, geologic scenarios involving 1-2 km of sedimentary burial are especially sensitive to the assumed rate of annealing and its influence on He diffusivity. In cases such as basement rocks in Grand Canyon and the Canadian Shield, (U-Th)/He ages predicted from the ADAM can differ by hundreds of Ma from those predicted by other models for a given thermal path involving extended residence between ∼40-80 °C.

Thirteen Week Oral Toxicity Study of WR242511 in Rats. Volume 1

DTIC Science & Technology

1994-01-14

hypercholesterolemia and hypertriglyceridemia seen in high dose females, as previously discussed. Heptatobiliary changes were suggested by significant elevations in...lung (alveolar histiocytosis) lesions. Severe thymic lymphocyte depletion was also observed in these animals where the thymus could be identified...this animal, but it was attributed to the severe and diffuse chronic-active inflammation. As indicated above, treatment-related histopathologic

Acute diffuse alveolar haemorrhage accompanied by gastrointestinal bleeding in a patient with serious systemic lupus erythematosus: A case report.

PubMed

Du, Jing; Wang, Ying; Li, Yan-Chun; Wang, Tong-Tong; Zhou, Yong-Lie; Ying, Zhen-Hua

2018-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects many organs, but multisystem dysfunction is rare. Here, we report a case of a 29-year-old woman who was initially diagnosed with SLE complications including lupus nephritis, lupus encephalopathy, renal hypertension, thrombocytopenia, anaemia and hyperkalaemia. She recovered following treatment with high dose methylprednisolone, intravenous immunoglobulin (IVIG) and continuous renal replacement therapy (CRRT). However, a few days after hospital discharge, she developed gastrointestinal bleeding. Although intensive treatment was administered, the patient deteriorated rapidly and had a progressive decline in oxygen saturation followed by diffuse alveolar haemorrhage and acute left heart failure. Inotropic therapy, mechanical ventilation, blood transfusion, CRRT, antibiotics, intravenous glucocorticoids and other support therapies were initiated and gradually the patient's vital signs stabilized and haemoptysis subsided. This case report emphasises that complications of SLE can occur at any stage of the disease, especially in patients with active SLE. Therefore, it is important for clinicians to be aware of the rare presentations of SLE and its complex management. For multisystem dysfunction, early intensive treatment with high dose corticosteroids and cyclophosphamide is advocated.

Airway diffusing capacity of nitric oxide and steroid therapy in asthma.

PubMed

Shin, Hye-Won; Rose-Gottron, Christine M; Cooper, Dan M; Newcomb, Robert L; George, Steven C

2004-01-01

Exhaled nitric oxide (NO) concentration is a noninvasive index for monitoring lung inflammation in diseases such as asthma. The plateau concentration at constant flow is highly dependent on the exhalation flow rate and the use of corticosteroids and cannot distinguish airway and alveolar sources. In subjects with steroid-naive asthma (n = 8) or steroid-treated asthma (n = 12) and in healthy controls (n = 24), we measured flow-independent NO exchange parameters that partition exhaled NO into airway and alveolar regions and correlated these with symptoms and lung function. The mean (+/-SD) maximum airway flux (pl/s) and airway tissue concentration [parts/billion (ppb)] of NO were lower in steroid-treated asthmatic subjects compared with steroid-naive asthmatic subjects (1,195 +/- 836 pl/s and 143 +/- 66 ppb compared with 2,693 +/- 1,687 pl/s and 438 +/- 312 ppb, respectively). In contrast, the airway diffusing capacity for NO (pl.s-1.ppb-1) was elevated in both asthmatic groups compared with healthy controls, independent of steroid therapy (11.8 +/- 11.7, 8.71 +/- 5.74, and 3.13 +/- 1.57 pl.s-1.ppb-1 for steroid treated, steroid naive, and healthy controls, respectively). In addition, the airway diffusing capacity was inversely correlated with both forced expired volume in 1 s and forced vital capacity (%predicted), whereas the airway tissue concentration was positively correlated with forced vital capacity. Consistent with previously reported results from Silkoff et al. (Silkoff PE, Sylvester JT, Zamel N, and Permutt S, Am J Respir Crit Med 161: 1218-1228, 2000) that used an alternate technique, we conclude that the airway diffusing capacity for NO is elevated in asthma independent of steroid therapy and may reflect clinically relevant changes in airways.

Alveolar-Membrane Diffusing Capacity Limits Performance in Boston Marathon Qualifiers

PubMed Central

Lavin, Kaleen M.; Straub, Allison M.; Uhranowsky, Kathleen A.; Smoliga, James M.; Zavorsky, Gerald S.

2012-01-01

Purpose (1) to examine the relation between pulmonary diffusing capacity and marathon finishing time, and (2), to evaluate the accuracy of pulmonary diffusing capacity for nitric oxide (DLNO) in predicting marathon finishing time relative to that of pulmonary diffusing capacity for carbon monoxide (DLCO). Methods 28 runners [18 males, age = 37 (SD 9) years, body mass = 70 (13) kg, height = 173 (9) cm, percent body fat = 17 (7) %] completed a test battery consisting of measurement of DLNO and DLCO at rest, and a graded exercise test to determine running economy and aerobic capacity prior to the 2011 Steamtown Marathon (Scranton, PA). One to three weeks later, all runners completed the marathon (range: 2∶22:38 to 4∶48:55). Linear regressions determined the relation between finishing time and a variety of anthropometric characteristics, resting lung function variables, and exercise parameters. Results In runners meeting Boston Marathon qualification standards, 74% of the variance in marathon finishing time was accounted for by differences in DLNO relative to body surface area (BSA) (SEE = 11.8 min, p<0.01); however, the relation between DLNO or DLCO to finishing time was non-significant in the non-qualifiers (p = 0.14 to 0.46). Whereas both DLCO and DLNO were predictive of finishing time for all finishers, DLNO showed a stronger relation (r2 = 0.30, SEE = 33.4 min, p<0.01) compared to DLCO when considering BSA. Conclusion DLNO is a performance-limiting factor in only Boston qualifiers. This suggests that alveolar-capillary membrane conductance is a limitation to performance in faster marathoners. Additionally, DLNO/BSA predicts marathon finishing time and aerobic capacity more accurately than DLCO. PMID:22984520

Locally Produced BDNF Promotes Sclerotic Change in Alveolar Bone after Nerve Injury

PubMed Central

Ida-Yonemochi, Hiroko; Yamada, Yurie; Yoshikawa, Hiroyuki

2017-01-01

Brain-derived neurotrophic factor (BDNF), which is released due to nerve injury, is known to promote the natural healing of injured nerves. It is often observed that damage of mandibular canal induces local sclerotic changes in alveolar bone. We reported that peripheral nerve injury promotes the local production of BDNF; therefore, it was possible to hypothesize that peripheral nerve injury affects sclerotic changes in the alveolar bone. This study aimed to evaluate the effect of BDNF on osteogenesis using in vitro osteoblast-lineage cell culture and an in vivo rat osteotomy model. MC3T3-E1 cells were cultured with BDNF and were examined for cell proliferative activity, chemotaxis and mRNA expression levels of osteoblast differentiation markers. For in vivo study, inferior alveolar nerve (IAN) injury experiments and mandibular cortical osteotomy were performed using a rat model. In the osteotomy model, exogenous BDNF was applied to bone surfaces after corticotomy of the mandible, and we morphologically analyzed the new bone formation. As a result, mRNA expression of osteoblast differentiation marker, osteocalcin, was significantly increased by BDNF, although cell proliferation and migration were not affected. In the in vivo study, osteopontin-positive new bone formation was significantly accelerated in the BDNF-grafted groups, and active bone remodeling, involving trkB-positive osteoblasts and osteocytes, continued after 28 days. In conclusion, BDNF stimulated the differentiation of MC3T3-E1 cells and it promoted new bone formation and maturation. These results suggested that local BDNF produced by peripheral nerve injury contributes to accelerating sclerotic changes in the alveolar bone. PMID:28072837

Endoscopic sensing of pH in the distal lung (Conference Presentation)

NASA Astrophysics Data System (ADS)

Choudhury, Debaditya; Tanner, Michael G.; McAughtrie, Sarah; Yu, Fei; Mills, Bethany; Choudhary, Tushar R.; Seth, Sohan; Craven, Thomas; Stone, James M.; Mati, Ioulia K.; Campbell, Colin J.; Bradley, Mark; Williams, Christopher K.; Dhaliwal, Kevin; Birks, Timothy A.; Thomson, Robert R.

2017-04-01

In healthy humans, the physiological state in the distal lung alveolar acinar units is tightly regulated by normal homeostatic mechanisms. Pulmonary abnormalities such as chronic obstructive pulmonary disease, that are characterized by recurrent cycles of inflammation and infection involving dense infiltration by myeloid derived peripheral blood cells, may result in significant perturbation of the homeostatic baselines of physiology in addition to host tissue damage. Therefore, the ability to quantify and monitor physiology (e.g. pH, glucose level, oxygen tension) within the alveolar acinar units would provide a key biomarker of distal lung innate defence. Although in vitro modeling of fundamental biological processes show remarkable sensitivity to physiological aberrations, little is known about the physiological state of the distal lung due to the inability to concurrently access the alveolar sacs and perform real-time sensing. Here we report on previously unobtainable measurements of alveolar pH using a fiber-optic optrode and surface enhanced Raman spectroscopy (SERS) and show that alveolar pH changes in response to ventilation. The endoscope-deployable optrode consisted of para-mercaptobenzoic acid functionalized 150 nm gold nanoshells located at the distal end, and an asymmetric dual-core optical fiber designed for spatially separated optical pump delivery and SERS signal collection in order to circumvent the unwanted Raman signal originating from the fiber itself. We demonstrate a 100-fold increase in SERS signal-to-fiber background ratio and pH sensing at multiple sites in the respiratory acinar units of a whole ex vivo ovine lung model with a measurement accuracy of ± 0.07 pH units.

Inferior Alveolar Nerve Lateralization and Transposition for Dental Implant Placement. Part II: a Systematic Review of Neurosensory Complications.

PubMed

Abayev, Boris; Juodzbalys, Gintaras

2015-01-01

This article, the second in a two-part series, continues the discussion of inferior alveolar nerve lateralization/transposition for dental implant placement. The aim of this article is to review the scientific literature and clinical reports in order to analyse the neurosensory complications, risks and disadvantages of lateralization/transposition of the inferior alveolar nerve followed by implant placement in an edentulous atrophic posterior mandible. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed and PMC databases, as well as academic sites and books. The articles were searched from January 1997 to July 2014. Articles in English language, which included adult patients between 18 - 80 years of age who had minimal residual bone above the mandibular canal and had undergone inferior alveolar nerve (IAN) repositioning, with minimum 6 months of follow-up, were included. A total of 21 studies were included in this review. Ten were related to IAN transposition, 7 to IAN lateralization and 4 to both transposition and lateralization. The IAN neurosensory disturbance function was present in most patients (99.47% [376/378]) for 1 to 6 months. In total, 0.53% (2/378) of procedures the disturbances were permanent. Inferior alveolar nerve repositioning is related to initial transient change in sensation in the majority of cases. The most popular causes of nerve damage are spatula-caused traction in the mucoperiosteal flap, pressure due to severe inflammation or retention of fluid around the nerve and subsequent development of transient ischemia, and mandibular body fracture.

Insight into He diffusion in apatite by ion beam experiments and quantum calculations: implication for the (U-Th)/He thermochronometer

NASA Astrophysics Data System (ADS)

Gautheron, C.; Mbongo-Djimbi, D.; Gerin, C.; Roques, J.; Bachelet, C.; Oliviero, E.; Tassan-Got, L.

2015-12-01

The apatite (U-Th)/He (AHe) system has rapidly become a very popular thermochronometer, however, interpretation of AHe age depends on a precise knowledge of He diffusion. Several studies suggest that He retention is function of the amount of damage that is controlled by U-Th concentration, grain chemistry and thermal history. Still, the models are not well constrained and do not fully explain the mechanism of He retention. In order to have a deeper insight into this issue, a multidisciplinary study on apatite combining physical methods such as multi-scale theoretical diffusion calculations based on Density Functional Theory (DFT) with diffusion experiments by ion beam Elastic Recoil Diffusion Analysis (ERDA) were performed. Quantum calculations permit to quantify He diffusivity base level for damage-free crystal and to estimate the additional energy cost to extract He atoms trapped in point defects (i.e. vacancies). On the other hand ion beam ERDA experiments allow to measure He diffusivity in artificially damaged crystals. We show that damage-free apatite crystals are characterized by low retention behavior and closure temperature of ~35°C for pure F-apatite to higher value for Cl rich apatite (up to 12°C higher), for typical grain size and cooling rate (Mbongo-Djimbi et al., 2015). Our computed closure temperature is slightly lower than previously reported experimental values (~50°C). Using ERDA and DFT modeling of damage, we show how He diffusivity is influenced by damage. Finally, we are able to propose a new modeling of He diffusion incorporating mechanisms not included in classical damage models, and taking into account the level of damage and apatite chemistry. We show that it could affect significantly AHe age interpretation. Mbongo-Djimbi D. et al. 2015. Apatite composition effect on (U-Th)/He thermochronometer: an atomistic point of view. Geohimica Cosmochim. Acta.

Pulmonary function in space

NASA Technical Reports Server (NTRS)

West, J. B.; Elliott, A. R.; Guy, H. J.; Prisk, G. K.

1997-01-01

The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

Damage and recovery characteristics of lithium-containing solar cells.

NASA Technical Reports Server (NTRS)

Faith, T. J.

1971-01-01

Damage and recovery characteristics were measured on lithium-containing solar cells irradiated by 1-MeV electrons. Empirical expressions for cell recovery time, diffusion-length damage coefficient immediately after irradiation, and diffusion-length damage coefficient after recovery were derived using results of short-circuit current, diffusion-length, and reverse-bias capacitance measurements. The damage coefficients were expressed in terms of a single lithium density parameter, the lithium gradient. A fluence dependence was also established, this dependence being the same for both the immediate-post-irradiation and post-recovery cases. Cell recovery rates were found to increase linearly with lithium gradient.

Juglone alleviates pneumolysin-induced human alveolar epithelial cell injury via inhibiting the hemolytic activity of pneumolysin.

PubMed

Song, Meng; Lu, Gejin; Li, Meng; Deng, Xuming; Wang, Jianfeng

2017-08-01

Streptococcus pneumoniae (the pneumococcus) is an opportunistic pathogen responsible for several human diseases, including acute otitis media, pneumonia, sepsis and bacterial meningitis, and possesses numerous virulence factors associated with pneumococcal infection and pathogenesis. With the capacity to form pores in cholesterol-rich membranes, pneumolysin (PLY) is a key virulence factor of S. pneumoniae and causes severe tissue damage during pneumococcal infection. Juglone (JG), a natural 1,4-naphthoquinone widely found in the roots, leaves, woods and fruits of Juglandaceae walnut trees, inhibits PLY-induced hemolysis via inhibition of the oligomerization of PLY and exhibits minimal anti-S. pneumoniae activity. In addition, when human alveolar epithelial (A549) cells were co-cultured with PLY and JG, PLY-mediated cell injury was significantly alleviated. These results indicate that JG directly interacts with PLY to reduce the cytotoxicity of the toxin in human alveolar epithelial cells. Hence, JG is an effective inhibitor of PLY and protects lung cells from PLY-mediated cell injury. This study also provides the basis for the development of anti-virulence drugs for the treatment of S. pneumoniae infections.

SOLUBLE COMPONENTS OF UTAH VALLEY PARTICULATE POLLUTION ALTER ALVEOLAR MACROPHAGE FUNCTION IN VIVO AND IN VITRO

EPA Science Inventory

Water-soluble extracts of Utah Valley dust (UVD) have been found to cause inflammatory injury of the lung in both humans and rodents. The degree of lung damage found correlated with the metal content in the extracts. In the present study, extracts of a set of UVD PM(10) filters c...

Modeling and Measuring the Effects of Radiation Damage Annealing on Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Fox, M.; Shuster, D. L.

2016-12-01

Understanding helium diffusion kinetics in apatite is critical for the accurate interpretation of (U-Th)/He thermochronometric data. This problem is complicated by the observation that helium diffusivity is not a simple function of temperature, but may evolve as a function of damage to the apatite crystal lattice resulting from alpha recoil. This `radiation damage' increases as a function of the amount of radiometric parent products, or effective uranium concentration, and time, but decreases due to thermal annealing of damage, necessitating a detailed understanding of radiation damage production and annealing in cases of burial heating over geologic timescales. Published observations [1,2] suggest that annealing rates of damage caused by alpha recoil and fission tracks in apatite differ. Existing models, however, assume the diffusion kinetics resulting from the two sources of damage are identical [3], demonstrating the need for further investigation of these damage sources. We present modeling and experimental work designed to interrogate the effects of radiation damage and its annealing on helium diffusion kinetics in apatite. Using previously published results [4] that investigated the effects of annealing temperature and duration on measured helium diffusivity, we fit a set of functions that are then integrated into a numerical model that tracks the evolution of radiation damage and apparent (U-Th)/He age. We compare the results of this model calibration to existing models [3]. In addition, we present data from two suites of diffusion experiments. The first suite, intended to test the published methodology and results, uses Durango apatite, while the second uses Sierran (CA) granite as a first test to determine if apatite of varying chemistry and age responds differently to the thermal annealing of radiation damage. Ultimately, the updated model and experimental results will benefit the interpretation of the effects of radiation damage accumulation and annealing in apatite and expand the range of geologic settings that can be studied using low-temperature thermochronology. References: [1] Fox, M., Shuster, D. (2014), EPSL 397, 174-183; [2] Gautheron, C. et al. (2013), Chem. Geol. 351, 257-267; [3] Flowers, R. et al. (2009), GCA 73, 2347-2365; [4] Shuster, D., Farley, K. (2009), GCA 73, 6183-6196.

Acyloxyacyl hydrolase promotes the resolution of lipopolysaccharide-induced acute lung injury

PubMed Central

Tang, Zihui; Yang, Qian; Qian, Guojun; Qian, Jing; Zeng, Wenjiao; Gu, Jie; Chu, Tianqing; Zhu, Ning; Zhang, Wenhong; Yan, Dapeng; He, Rui; Chu, Yiwei

2017-01-01

Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS). We report here that alveolar macrophages increase AOAH expression upon exposure to LPS and that Aoah+/+ mice recover more rapidly than do Aoah-/- mice from ALI induced by nasally instilled LPS or Klebsiella pneumoniae. Aoah-/- mouse lungs had more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer-lasting alveolar barrier damage. We also describe evidence that the persistently bioactive LPS in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Distinct from the prolonged tolerance observed in LPS-exposed Aoah-/- peritoneal macrophages, alveolar macrophages that lacked AOAH maintained or increased their responses to bioactive LPS and sustained inflammation. Inactivation of LPS by AOAH is a previously unappreciated mechanism for promoting resolution of pulmonary inflammation/injury induced by Gram-negative bacterial infection. PMID:28622363

Morpho-histological assessment of the periodontal support structures under the action of excessive occlusal forces and under the influence of nicotine.

PubMed

Ispas, Ana; Mihu, Carmen Mihaela; Crăciun, Antarinia Maria; Constantiniuc, Mariana

2018-01-01

Smoking and occlusal trauma are two factors that can interfere with bone homeostasis. The aim of this study was to evaluate the histocellular changes occurring in the periodontal ligament and alveolar bone during the action of excessive occlusal forces, and to assess the influence of nicotine on the alveolar bone loss in teeth subjected to occlusal trauma. Fifty-six Wistar rats were randomized into seven groups (n=8). Animals were exposed to nicotine and occlusal trauma for 7, 14 and 30 days. Three groups were exposed to occlusal trauma alone, another three groups were exposed to occlusal trauma and nicotine, and one group was not exposed to any treatment. Periodontal lesions induced in the first stage (7-14 days) manifested by a moderate increase of the periodontal space, a multiplication, thickening and elongation of periodontal fibers, as well as their condensation in the middle area of the periradicular space. Regarding bone changes induced by occlusal trauma, groups 5 and 7 (occlusal trauma and nicotine administration) had higher bone losses compared to groups 1, 2, 3, 4 and 6. This study demonstrated that nicotine significantly affected the alveolar bone. The induced occlusal trauma caused obvious tissue damage. At the same time, it was found that nicotine enhanced alveolar bone resorption, increased tooth mobility and induced an exacerbation of inflammatory processes.

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth

PubMed Central

Liu, Shing-Hwa; Su, Chin-Chuan; Lee, Kuan-I; Chen, Ya-Wen

2016-01-01

Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (Kfc), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway. PMID:27982077

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth.

PubMed

Liu, Shing-Hwa; Su, Chin-Chuan; Lee, Kuan-I; Chen, Ya-Wen

2016-12-16

Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (K fc ), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway.

Radiographic appearance of bronchoalveolar carcinoma in nine cats.

PubMed

Ballegeer, Elizabeth A; Forrest, Lisa J; Stepien, Rebecca L

2002-01-01

Thoracic radiographs of nine cats with confirmed bronchoalveolar carcinoma (BAC) were reviewed retrospectively. Radiographic appearance of BAC was divided into three categories: mixed bronchoalveolar pattern, ill-defined alveolar mass, or mass with cavitation. In addition to these radiographic signs, all nine cats had evidence of some form of bronchial disease. Cavitary lesions were the most common finding (n = 5). In addition, three cats in this category had diffuse bronchointerstitial opacity and one cat had focal peribronchial cuffing. Five cats had either a mixed bronchoalveolar pattern with bronchiectasis (n = 3) or an ill-defined alveolar mass with peribronchial cuffing (n = 2). One cat had both a mixed bronchoalveolar pattern and a cavitary mass. Each of these nine cats had some form of bronchial disease (bronchointerstitial pattern, peribronchial cuffing, or bronchiectasis), which aids in the radiographic diagnosis of bronchoalveolar carcinoma and may represent airway metastasis.

Experimental evaluation of a new system for laser tissue welding applied on damaged lungs.

PubMed

Schiavon, Marco; Marulli, Giuseppe; Zuin, Andrea; Lunardi, Francesca; Villoresi, Paolo; Bonora, Stefano; Calabrese, Fiorella; Rea, Federico

2013-05-01

Alveolar air leaks represent a challenging problem in thoracic surgery, leading to increased patient morbidity and prolonged hospitalization. Several methods have been used, but no ideal technique exists yet. We investigated the lung-sealing capacity of an experimental kit for laser tissue welding. The kit is composed of a semiconductor laser system applied on a protein substrate associated with a chromophore that increases absorption. In vitro tests on porcine lung tissue were done to define ideal laser parameters (power 100 Å, frequency 50 Hz, pulse duration 400 µs) and protein substrate dilution (50%). For in vivo tests, through a left thoracotomy, 14 pigs received two different lung damages: a linear incision and a circular incision. Protein substrate applied on damaged areas was treated with laser to obtain a layer that reconstituted the integrity of the visceral pleura. Air leaks were intraoperatively evaluated by water submersion test with an airway pressure of 20 cmH2O. Animals were sacrificed at postoperative days 0 and 7 to study early and late pathological features. After applying laser treatment, no air leaks were seen in all proofs except in 2 cases in which a second application was required. At time 0, pathological damage mostly consisted of superficial alveolar necrotic tissue covered by protein membrane. At time 7, a complete recovery of lung lesions by fibrous scar with slight inflammatory reaction of adjacent lung tissue was seen. This experimental study demonstrated the effectiveness of laser tissue welding applied to seal air leaks after lung surgery. Further studies are needed to verify acceptability for human application.

Non-local damage rheology and size effect

NASA Astrophysics Data System (ADS)

Lyakhovsky, V.

2011-12-01

We study scaling relations controlling the onset of transiently-accelerating fracturing and transition to dynamic rupture propagation in a non-local damage rheology model. The size effect is caused principally by growth of a fracture process zone, involving stress redistribution and energy release associated with a large fracture. This implies that rupture nucleation and transition to dynamic propagation are inherently scale-dependent processes. Linear elastic fracture mechanics (LEFM) and local damage mechanics are formulated in terms of dimensionless strain components and thus do not allow introducing any space scaling, except linear relations between fracture length and displacements. Generalization of Weibull theory provides scaling relations between stress and crack length at the onset of failure. A powerful extension of the LEFM formulation is the displacement-weakening model which postulates that yielding is complete when the crack wall displacement exceeds some critical value or slip-weakening distance Dc at which a transition to kinetic friction is complete. Scaling relations controlling the transition to dynamic rupture propagation in slip-weakening formulation are widely accepted in earthquake physics. Strong micro-crack interaction in a process zone may be accounted for by adopting either integral or gradient type non-local damage models. We formulate a gradient-type model with free energy depending on the scalar damage parameter and its spatial derivative. The damage-gradient term leads to structural stresses in the constitutive stress-strain relations and a damage diffusion term in the kinetic equation for damage evolution. The damage diffusion eliminates the singular localization predicted by local models. The finite width of the localization zone provides a fundamental length scale that allows numerical simulations with the model to achieve the continuum limit. A diffusive term in the damage evolution gives rise to additional damage diffusive time scale associated with the structural length scale. The ratio between two time scales associated with damage accumulation and diffusion, the damage diffusivity ratio, reflects the role of the diffusion-controlled delocalization. We demonstrate that localized fracturing occurs at the damage diffusivity ratio below certain critical value leading to a linear scaling between stress and crack length compatible with size effect for failures at crack initiation. A subseuqent quasi-static fracture growth is self-similar with increasing size of the process zone proportional to the fracture length. At a certain stage, controlled by dynamic weakening, the self-similarity breaks down and crack velocity significantly deviates from that predicted by the quasi-static regime, the size of the process zone decreases, and the rate of crack growth ceases to be controlled by the rate of damage increase. Furthermore, the crack speed approaches that predicted by the elasto-dynamic equation. The non-local damage rheology model predicts that the nucleation size of the dynamic fracture scales with fault zone thickness distance of the stress interraction.

Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung diseases*

PubMed Central

Yamada, Tsutomu; Kawabata, Yoshinori

2015-01-01

Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs). Histological markers of pneumocyte injury and inflammation include pneumocyte necrosis, erosion, hyaline membrane and fibrin exudation with subsequent intraluminal granulation tissue formation. We found that intracytoplasmic inclusions in pneumocytes are ubiquitin-positive (Ub+) and that the number of Ub+ pneumocytes shows positive correlation with the extent of diffuse alveolar damage (DAD). To determine the role of Ub+ pneumocytes and inclusions in IPs, we studied their relationship with pathological and clinical features of DAD, usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including airspace enlargement with fibrosis (AEF). We analysed Ub+ pneumocytes, inclusions, erosions and intraluminal granulation tissue in relation to pneumocyte injury. The numbers of immunohistochemically identified Ub+ inclusions in each IP were higher than the number of inclusions detected by light microscopy. The inclusions detected by Ub+ immunostaining were identical to the inclusions observed by light microscopy. UIP and DAD had many Ub+ inclusions, while OP and AEF had fewer Ub+ inclusions. These results suggest that the extent of Ub+ inclusions reflects the severity of pneumocyte injury among IPs. Thus, Ub+ inclusions are a histological marker of pneumocyte injury that may be helpful in determining the severity and prognosis of IPs. PMID:25123224

Recurrent Spontaneous Pneumothorax during the Recovery Phase of ARDS Due to H1N1 Infection.

PubMed

Bor, Canan; Demirağ, Kubilay; Uyar, Mehmet; Cankayalı, Ilkin; Moral, Ali Reşat

2013-03-01

The pregnant patients are prone to influenza A (H1N1) virus infection, which may rapidly progress to lower respiratory tract infection and subsequent respiratory failure and acute respiratory distress syndrome (ARDS). Pneumothorax might develop in ARDS under mechanical ventilation. But post-ARDS pneumothorax in spontaneously breathing patient has not been reported in the literature. We report a 31-year old pregnant woman infected with influenza A (H1N1) virus and progressed to ARDS. Mechanical ventilation with high PEEP improved patient's gas exchange parameters within 3 weeks. However spontaneous pneumothorax was developed one week after she weaned off the ventilator. After successful drainage therapy, the patient was discharged. However she re-admitted to the hospital because of a recurrent pneumothorax one week later. She was discharged in good health after being treated with negative continuous pleural aspiration for 10 days. Influenza might cause severe pulmonary infection and death. In addition to diffuse alveolar damage, sub-pleural and intrapulmonary air cysts might occur in influenza-related ARDS and may lead to spontaneous pneumothorax. This complication should always be considered during the recovery period of ARDS and a long-term close follow-up is necessary.

Acute interstitial pneumonia (Hamman-Rich syndrome) in idiopathic pulmonary fibrosis and bronchoalveolar carcinoma: a case report.

PubMed

Plasek, Jiri; Dvorackova, Jana; Jahoda, Jan; Trulikova, Kristina; Mokosova, Radka; Danek, Tomas; Hrabovsky, Vladimir; Martinek, Arnost

2011-12-01

Acute interstitial pneumonia is characterized by rapid progressive dyspnoea degenerating into respiratory failure requiring mechanical ventilation. Acute interstitial pneumonia (AIP) and idiopathic pulmonary fibrosis (IPF) are separate clinic/pathological entities although overlap may be present. It is well-known that patients with IPF have increased risk of lung carcinoma; Adenocarcinoma in connection with IPF is less common. Moreover the subtype of adenocarcinoma, diffuse bronchoalveolar carcinoma has not yet been described. We report the case of 45 yr old former hockey player with increased bilateral reticular shadowing on chest radiograph, dyspnoea, velcro-like crackles, restrictive respiratory disease and mixed high-resolution computed tomography finding. During brief in-patient treatment the patient developed acute respiratory failure accompanied by multiorgan failure and disseminated coagulopathy. Deterioration of the microcirculation was followed by loss of peripheral vascular resistance, which was irreversible even with normalization of the blood gases achieved by extracorporeal membrane oxygenation. At autopsy, bronchoalveolar carcinoma in usual interstitial pneumonia (UIP) combined with areas of alveolar damage with hyaline membranes was found. This case alerts clinicians to unusual idiopathic pulmonary fibrosis manifestations and its complications. Close collaboration between clinicians, pathologists and laboratory physicians is highly recommended for early diagnosis and appropriate treatment.

Conidial heads (Fruiting Bodies) as a hallmark for histopathological diagnosis of angioinvasive aspergillosis

PubMed Central

Lanzarin, Luciana Depiere; Mariano, Livia Caroline Barbosa; Macedo, Maria Cristina Martins de Almeida; Batista, Marjorie Vieira

2015-01-01

Aspergillosis is a mycosis that afflicts immunocompetent and immunocompromised hosts; among the former it exhibits different clinical pictures, and among the latter the infection renders an invasive form of the disease. The histologic diagnosis of invasive aspergillosis is somewhat challenging mostly because of some morphological similarities between other fungi. However, when present, the conidial heads are pathognomonic of aspergillosis. The authors present the case of a 68-year-old woman who was submitted to autologous hematopoietic stem cell transplantation in the pursuit of multiple myeloma treatment. The post-transplantation period was troublesome with the development of severe neutropenia, human respiratory syncytial virus pneumonia, and disseminated aspergillosis, which was suspected because of a positive serum galactomannan antigen determination, and resulted in a fatal outcome. The autopsy findings showed diffuse alveolar damage associated with angioinvasive pulmonary aspergillosis with numerous hyphae and conidial heads in the lung parenchyma histology. The authors call attention to the aid of autopsy in confirming the diagnosis of this deep mycosis, since only the research of the galactomannan antigen may be insufficient and uncertain due to its specificity and of the possibility of false-positive results. PMID:26894041

Serum antibody-negative Goodpasture syndrome with delta granule pool storage deficiency and eosinophilia.

PubMed

Kussman, Ashleigh; Gohara, Amira

2012-12-01

Goodpasture syndrome is a rare, life-threatening autoimmune disease characterized by a triad of rapidly progressive glomerulonephritis, a hemorrhagic pulmonary condition and the presence of anti-glomerular basement membrane (anti-GBM) antibodies. The antibodies initiate destruction of the kidney glomeruli, resulting in a focal necrotizing glomerulitis, which may progress rapidly to renal failure. Autoantibody-mediated damage of alveolar basement membranes leads to diffuse pulmonary hemorrhage, which in some cases may be severe enough to cause respiratory failure. Many clinicians use a variety of assays to detect serum anti-GBM antibodies; however, these tests may be falsely negative in up to 15% of patients with Goodpasture syndrome. Here, we report an unusual case of a 40-year-old man with clinical evidence of Goodpasture syndrome, a negative anti-GBM antibody serum result, eosinophilia and delta granule pool storage deficiency. After a 14-day hospital stay and extensive workup, as well as treatment with antibiotics, steroids and ventilator support for respiratory failure, the patient continued to deteriorate and entered multisystem organ failure. The family decided to withdraw ventilator support, and the patient expired. Immunofluorescence testing for anti-GBM autoantibodies on lung and kidney tissues during an autopsy confirmed the diagnosis of Goodpasture syndrome.

The influence of artificial radiation damage and thermal annealing on helium diffusion kinetics in apatite

NASA Astrophysics Data System (ADS)

Shuster, David L.; Farley, Kenneth A.

2009-01-01

Recent work [Shuster D. L., Flowers R. M. and Farley K. A. (2006) The influence of natural radiation damage on helium diffusion kinetics in apatite. Earth Planet. Sci. Lett.249(3-4), 148-161] revealing a correlation between radiogenic 4He concentration and He diffusivity in natural apatites suggests that helium migration is retarded by radiation-induced damage to the crystal structure. If so, the He diffusion kinetics of an apatite is an evolving function of time and the effective uranium concentration in a cooling sample, a fact which must be considered when interpreting apatite (U-Th)/He ages. Here we report the results of experiments designed to investigate and quantify this phenomenon by determining He diffusivities in apatites after systematically adding or removing radiation damage. Radiation damage was added to a suite of synthetic and natural apatites by exposure to between 1 and 100 h of neutron irradiation in a nuclear reactor. The samples were then irradiated with a 220 MeV proton beam and the resulting spallogenic 3He used as a diffusant in step-heating diffusion experiments. In every sample, irradiation increased the activation energy ( E a) and the frequency factor ( D o/ a2) of diffusion and yielded a higher He closure temperature ( T c) than the starting material. For example, 100 h in the reactor caused the He closure temperature to increase by as much as 36 °C. For a given neutron fluence the magnitude of increase in closure temperature scales negatively with the initial closure temperature. This is consistent with a logarithmic response in which the neutron damage is additive to the initial damage present. In detail, the irradiations introduce correlated increases in E a and ln( D o/a 2) that lie on the same array as found in natural apatites. This strongly suggests that neutron-induced damage mimics the damage produced by U and Th decay in natural apatites. To investigate the potential consequences of annealing of radiation damage, samples of Durango apatite were heated in vacuum to temperatures up to 550 °C for between 1 and 350 h. After this treatment the samples were step-heated using the remaining natural 4He as the diffusant. At temperatures above 290 °C a systematic change in T c was observed, with values becoming lower with increasing temperature and time. For example, reduction of T c from the starting value of 71 to ˜52 °C occurred in 1 h at 375 °C or 10 h at 330 °C. The observed variations in T c are strongly correlated with the fission track length reduction predicted from the initial holding time and temperature. Furthermore, like the neutron irradiated apatites, these samples plot on the same E a - ln( D o/ a2) array as natural samples, suggesting that damage annealing is simply undoing the consequences of damage accumulation in terms of He diffusivity. Taken together these data provide unequivocal evidence that at these levels, radiation damage acts to retard He diffusion in apatite, and that thermal annealing reverses the process. The data provide support for the previously described radiation damage trapping kinetic model of Shuster et al. (2006) and can be used to define a model which fully accommodates damage production and annealing.

Construction of a three-dimensional finite element model of maxillary first molar and it's supporting structures

PubMed Central

Begum, M. Sameena; Dinesh, M. R.; Tan, Kenneth F. H.; Jairaj, Vani; Md Khalid, K.; Singh, Varun Pratap

2015-01-01

The finite element method (FEM) is a powerful computational tool for solving stress-strain problems; its ability to handle material inhomogeneity and complex shapes makes the FEM, the most suitable method for the analysis of internal stress levels in the tooth, periodontium, and alveolar bone. This article intends to explain the steps involved in the generation of a three-dimensional finite element model of tooth, periodontal ligament (PDL) and alveolar bone, as the procedure of modeling is most important because the result is based on the nature of the modeling systems. Finite element analysis offers a means of determining strain-stress levels in the tooth, ligament, and bone structures for a broad range of orthodontic loading scenarios without producing tissue damage. PMID:26538895

[Orthodontic partial disimpaction of mandibular third molars prior to surgical extraction].

PubMed

Derton, Nicolà; Perini, Alessandro; Giordanetto, José; Biondi, Giovanni; Siciliani, Giuseppe

2009-06-01

Odontodysplasia of the third molars is a relatively common anomaly. The frequent complications associated with this disorder very often constitute an indication for extraction of the third molar. This surgical treatment can damage the lower alveolar nerve and/or trigger distal bone loss of the second molar, thus jeopardizing the future status of the periodontium. The author presents two case studies treated exclusively with miniscrews with no dental anchorage in order to achieve partial eruption of the third molar moving it away from the lower alveolar nerve and to avoid unwanted impact on other teeth. Following this procedure, the third molar was extracted without complications. In conclusion, this approach can offer an alternative to surgical treatment alone in cases where the proximity of tooth and nerve poses a significant risk.

He diffusion in zircon: Observations from (U-Th)/He age suites and 4He diffusion experiments and implications for radiation damage and anisotropic effects

NASA Astrophysics Data System (ADS)

Guenthner, W. R.; Reiners, P. W.

2009-12-01

Despite widespread use of zircon (U-Th)/He thermochronometry in many geologic applications, our understanding of the kinetics of He diffusion in this system is rudimentary. Previous studies have shown that both radiation damage and crystallographic anisotropy may strongly influence diffusion kinetics and ages. We present observations of zircon He ages from multiple single-grain analyses from both detrital and bedrock suites from a wide variety of locations, showing relationships consistent with effects arising from the interaction of radiation damage and anisotropy. Individual zircons in each suite have experienced the same post-depositional or exhumational t-T history but grains appear to have experienced differential He loss that is correlated with effective uranium (eU) content, a proxy for the relative extent of radiation damage within each suite. Several suites of zircons heated to partial resetting upon burial or that have experienced slow cooling show positive correlations between age and eU. Examples of partially reset detrital samples include Cretaceous Sevier foreland basin sandstones buried to ~6-8 km depth, with ages ranging from 88-309 Ma across an eU range of 215-1453 ppm, and Apennines and Olympics greywackes heated to >~120 °C, showing similar trends. Some slowly-cooled bedrock samples also show positive age-eU correlations, suggesting increasing closure temperature with higher extents of radiation damage. Conversely, zircons from cratonal bedrock samples with high levels of radiation damage—measured as accumulated alpha dosage (in this case >~10^18 α/g)—generally show negative age-eU correlations. We interpret these contrasting age-eU relationships as a manifestation of the interaction of radiation damage and anisotropic diffusion: at low damage, He diffusivity is relatively high and preferentially through c-axis-parallel channels. As suggested by Farley (2007), however, with increasing damage, channels are progressively blocked and He diffusivity decreases. Eventually, a crystal reaches a threshold level (>~10^18 α/g ) wherein radiation damage is so extensive that damage zones become interconnected and He diffusivity increases once again. In order to evaluate these assertions, we conducted a series of step-heating experiments on several pairs of zircon slabs. Individual slabs were crystallographically oriented either orthogonal or parallel to the c-axis and each pair possessed varying degrees of radiation damage. Results from these experiments provide new closure temperature estimates, explain age-eU correlations within a data set, and allow us to construct diffusion models that more accurately describe the t-T history of a given sample.

Radiation damage limits to XPCS studies of protein dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vodnala, Preeti, E-mail: preeti.vodnala@gmail.com; Karunaratne, Nuwan; Lurio, Laurence

2016-07-27

The limitations to x-ray photon correlation spectroscopy (XPCS) imposed by radiation damage have been evaluated for suspensions of alpha crystallin. We find that the threshold for radiation damage to the measured protein diffusion rate is significantly lower than the threshold for damage to the protein structure. We provide damage thresholds beyond which the measured diffusion coeffcients have been modified using both XPCS and dynamic light scattering (DLS).

Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment.

PubMed

Maghsoudlou, Panagiotis; Georgiades, Fanourios; Tyraskis, Athanasios; Totonelli, Giorgia; Loukogeorgakis, Stavros P; Orlando, Giuseppe; Shangaris, Panicos; Lange, Peggy; Delalande, Jean-Marie; Burns, Alan J; Cenedese, Angelo; Sebire, Neil J; Turmaine, Mark; Guest, Brogan N; Alcorn, John F; Atala, Anthony; Birchall, Martin A; Elliott, Martin J; Eaton, Simon; Pierro, Agostino; Gilbert, Thomas W; De Coppi, Paolo

2013-09-01

Tissue engineering of autologous lung tissue aims to become a therapeutic alternative to transplantation. Efforts published so far in creating scaffolds have used harsh decellularization techniques that damage the extracellular matrix (ECM), deplete its components and take up to 5 weeks to perform. The aim of this study was to create a lung natural acellular scaffold using a method that will reduce the time of production and better preserve scaffold architecture and ECM components. Decellularization of rat lungs via the intratracheal route removed most of the nuclear material when compared to the other entry points. An intermittent inflation approach that mimics lung respiration yielded an acellular scaffold in a shorter time with an improved preservation of pulmonary micro-architecture. Electron microscopy demonstrated the maintenance of an intact alveolar network, with no evidence of collapse or tearing. Pulsatile dye injection via the vasculature indicated an intact capillary network in the scaffold. Morphometry analysis demonstrated a significant increase in alveolar fractional volume, with alveolar size analysis confirming that alveolar dimensions were maintained. Biomechanical testing of the scaffolds indicated an increase in resistance and elastance when compared to fresh lungs. Staining and quantification for ECM components showed a presence of collagen, elastin, GAG and laminin. The intratracheal intermittent decellularization methodology could be translated to sheep lungs, demonstrating a preservation of ECM components, alveolar and vascular architecture. Decellularization treatment and methodology preserves lung architecture and ECM whilst reducing the production time to 3 h. Cell seeding and in vivo experiments are necessary to proceed towards clinical translation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity.

PubMed

Privalova, L I; Katsnelson, B A; Osipenko, A B; Yushkov, B N; Babushkina, L G

1980-04-01

The adaptation of the alveolar phagocytosis response to the quantitative and qualitative features of dust deposited during inhalation consists not only in enhanced recruitment of alveolar macrophages (AM), but also in adding a more or less pronounced neutrophil leukocyte (NL) recruitment as an auxiliary participant of particle clearance. The NL contribution to clearance is especially typical for response to cytotoxic particles (quartz, in particular). An important feature of the adaptation considered is the limitation of the number of AM and NL recruited when an efficient clearance can be achieved by a lesser number of cells due to increased AM reistance to the damaging actin of phagocytized particles. The main mechanism providing the adequacy of the alveolar phagocytosis response is its self-regulation thrugh the products of macrophage breakdown (PMB). In a series of experiments with intraperitoneal and intratracheal injections of syngenetic PMB into rats and mice, it was shown that these products stimulate respiration and migration of phagocytic cells, their dose-dependent attraction to the site of PMB formation with the predominant NL contribution, increasing with the increase of amount of PMB, the AM and NL precursor cells recruitment from reserve pools, and the replenishment of these reserves in the process of hemopoiesis. At least some of the above effects are connected with the action of the lipid components of PMB. The action of specialized regulative systems of the organism can modify the response to PMB, judging by the results obtained by hydrocortisone injection. Autocontrol of alveolar phagocytosis requires great care in attempts at artificial stimulation of this process, as an excessive cell recruitment may promote the retention of particles in lungs.

Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity.

PubMed Central

Privalova, L I; Katsnelson, B A; Osipenko, A B; Yushkov, B N; Babushkina, L G

1980-01-01

The adaptation of the alveolar phagocytosis response to the quantitative and qualitative features of dust deposited during inhalation consists not only in enhanced recruitment of alveolar macrophages (AM), but also in adding a more or less pronounced neutrophil leukocyte (NL) recruitment as an auxiliary participant of particle clearance. The NL contribution to clearance is especially typical for response to cytotoxic particles (quartz, in particular). An important feature of the adaptation considered is the limitation of the number of AM and NL recruited when an efficient clearance can be achieved by a lesser number of cells due to increased AM reistance to the damaging actin of phagocytized particles. The main mechanism providing the adequacy of the alveolar phagocytosis response is its self-regulation thrugh the products of macrophage breakdown (PMB). In a series of experiments with intraperitoneal and intratracheal injections of syngenetic PMB into rats and mice, it was shown that these products stimulate respiration and migration of phagocytic cells, their dose-dependent attraction to the site of PMB formation with the predominant NL contribution, increasing with the increase of amount of PMB, the AM and NL precursor cells recruitment from reserve pools, and the replenishment of these reserves in the process of hemopoiesis. At least some of the above effects are connected with the action of the lipid components of PMB. The action of specialized regulative systems of the organism can modify the response to PMB, judging by the results obtained by hydrocortisone injection. Autocontrol of alveolar phagocytosis requires great care in attempts at artificial stimulation of this process, as an excessive cell recruitment may promote the retention of particles in lungs. PMID:6997028

Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

PubMed

Rathi, N K; Tanner, A R; Dinh, A; Dong, W; Feng, L; Ensor, J; Wallace, S K; Haque, S A; Rondon, G; Price, K J; Popat, U; Nates, J L

2015-03-01

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

Topical Application of Liposomal Antioxidants for Protection Against CEES Induced Skin Damage

DTIC Science & Technology

2007-07-01

alveolar macrophages. J Nutr Sci Vitaminol (Tokyo) 1999, 45:675-686. 13. Thirunavukkarasu V, Anuradha CV: Influence of alpha - lipoic acid on lipid...33 4 ABBREVIATIONS: ALA, α- Lipoic acid AT, α-tocopherol CEES, half mustard or 2...Vitamin E (tocopherols and tocotrienols), GSH, N-acetylcysteine (NAC), and lipoic acid are very effective antioxidants. Their antioxidative potential

Consent for third molar tooth extractions in Australia and New Zealand: a review of current practice.

PubMed

Badenoch-Jones, E K; Lynham, A J; Loessner, D

2016-06-01

Informed consent is the legal requirement to educate a patient about a proposed medical treatment or procedure so that he or she can make informed decisions. The purpose of the study was to examine the current practice for obtaining informed consent for third molar tooth extractions (wisdom teeth) by oral and maxillofacial surgeons in Australia and New Zealand. An online survey was sent to 180 consultant oral and maxillofacial surgeons in Australia and New Zealand. Surgeons were asked to answer (yes/no) whether they routinely warned of a specific risk of third molar tooth extraction in their written consent. Seventy-one replies were received (39%). The only risks that surgeons agreed should be routinely included in written consent were a general warning of infection (not alveolar osteitis), inferior alveolar nerve damage (temporary and permanent) and lingual nerve damage (temporary and permanent). There is significant variability among Australian and New Zealand oral and maxillofacial surgeons regarding risk disclosure for third molar tooth extractions. We aim to improve consistency in consent for third molar extractions by developing an evidence-based consent form. © 2016 Australian Dental Association.

Lead intoxication under environmental hypoxia impairs oral health.

PubMed

Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Martínez, María Pilar; Conti, María Ines

2014-01-01

We have reported that chronic lead intoxication under hypoxic environment induces alveolar bone loss that can lead to periodontal damage with the subsequent loss of teeth. The aim of the present study was to assess the modification of oral inflammatory parameters involved in the pathogenesis of periodontitis in the same experimental model. In gingival tissue, hypoxia increased inducible nitric oxid synthase (iNOS) activity (p < .01) and meanwhile lead decreased prostaglandin E2 (PGE2) content (p < .05). In submandibular gland (SMG), iNOS activity was enhanced by lead and PGE2 content was increased by both lead and hypoxia (p < .01) and even more by combined treatments (p < .001). In the SMG, hypoxia stimulated angiogenesis (p < .01) with blood extravasation. Adrenal glands were 22% bigger in those animals exposed to lead under hypoxic conditions. Results suggest a wide participation of inflammatory markers that mediate alveolar bone loss induced by these environmental conditions. The lack of information regarding oral health in lead-contaminated populations that coexist with hypoxia induced us to evaluate the alteration of inflammatory parameters in rat oral tissues to elucidate the link between periodontal damage and these environmental conditions.

Standardisation and application of the single-breath determination of nitric oxide uptake in the lung.

PubMed

Zavorsky, Gerald S; Hsia, Connie C W; Hughes, J Michael B; Borland, Colin D R; Guénard, Hervé; van der Lee, Ivo; Steenbruggen, Irene; Naeije, Robert; Cao, Jiguo; Dinh-Xuan, Anh Tuan

2017-02-01

Diffusing capacity of the lung for nitric oxide ( D LNO ), otherwise known as the transfer factor, was first measured in 1983. This document standardises the technique and application of single-breath D LNO This panel agrees that 1) pulmonary function systems should allow for mixing and measurement of both nitric oxide (NO) and carbon monoxide (CO) gases directly from an inspiratory reservoir just before use, with expired concentrations measured from an alveolar "collection" or continuously sampled via rapid gas analysers; 2) breath-hold time should be 10 s with chemiluminescence NO analysers, or 4-6 s to accommodate the smaller detection range of the NO electrochemical cell; 3) inspired NO and oxygen concentrations should be 40-60 ppm and close to 21%, respectively; 4) the alveolar oxygen tension ( P AO 2 ) should be measured by sampling the expired gas; 5) a finite specific conductance in the blood for NO (θNO) should be assumed as 4.5 mL·min -1 ·mmHg -1 ·mL -1 of blood; 6) the equation for 1/θCO should be (0.0062· P AO 2 +1.16)·(ideal haemoglobin/measured haemoglobin) based on breath-holding P AO 2 and adjusted to an average haemoglobin concentration (male 14.6 g·dL -1 , female 13.4 g·dL -1 ); 7) a membrane diffusing capacity ratio ( D MNO / D MCO ) should be 1.97, based on tissue diffusivity. Copyright ©ERS 2017.

Radiation damage-He diffusivity models applied to deep-time thermochronology: Zircon and titanite (U-Th)/He datasets from cratonic settings

NASA Astrophysics Data System (ADS)

Guenthner, W.; DeLucia, M. S.; Marshak, S.; Reiners, P. W.; Drake, H.; Thomson, S.; Ault, A. K.; Tillberg, M.

2017-12-01

Advances in understanding the effects of radiation damage on He diffusion in uranium-bearing accessory minerals have shown the utility of damage-diffusivity models for interpreting datasets from geologic settings with long-term, low-temperature thermal histories. Craton interiors preserve a billion-year record of long-term, long-wavelength vertical motions of the lithosphere. Prior thermochronologic work in these settings has focused on radiation damage models used in conjunction with apatite (U-Th)/He dates to constrain Phanerozoic thermal histories. Owing to the more complex damage-diffusivity relationship in zircon, the zircon (U-Th)/He system yields both higher and, in some cases, lower temperature sensitivities than the apatite system, and this greater range in turn allows researchers to access deeper time (i.e., Proterozoic) segments of craton time-temperature histories. Here, we show two examples of this approach by focusing on zircon (U-Th)/He datasets from 1.8 Ga granitoids of the Fennoscandian Shield in southeastern Sweden, and 1.4 Ga granites and rhyolites of the Ozark Plateau in southeastern Missouri. In the Ozark dataset, the zircon (U-Th)/He data, combined with a damage-diffusivity model, predict negative correlations between date and effective uranium (eU) concentration (a measurement proportional to radiation damage) from thermal histories that include an episode of Proterozoic cooling (interpreted as exhumation) following reheating (interpreted as burial) to temperature of 260°C at 850-680 Ma. In the Fennoscandian Shield, a similar damage model-based approach yields time-temperature constraints with burial to 217°C between 944 Ma and 851 Ma, followed by exhumation from 850 to 500 Ma, and burial to 154°C between 366 Ma and 224 Ma. Our Fennoscandian Shield samples also include titanite (U-Th)/He dates that span a wide range (945-160 Ma) and are negatively correlated with eU concentration, analogous to our zircon He dataset. These results support the initial findings of Baughman et al. (2017, Tectonics), and suggest that further research into the radiation damage effect on He diffusion in titanite could yield a comprehensive damage-diffusivity model for the titanite (U-Th)/He thermochronometer.

Maxillary Interdental Osteotomies Have Low Morbidity for Alveolar Crestal Bone and Adjacent Teeth: A Cone Beam Computed Tomography-Based Study.

PubMed

Rodrigues, Daniel B; Campos, Paulo S F; Wolford, Larry M; Ignácio, Jaqueline; Gonçalves, João R

2018-02-19

Maxillary segmentation involving interdental osteotomies can have an adverse effect on the interdental crestal bone and adjacent teeth. The purpose of the present study was to evaluate the effect of interdental osteotomies on surrounding osseous and dental structures, including adjacent teeth, using cone beam computed tomography (CBCT), in patients who underwent segmental maxillary osteotomies. The present retrospective cohort study evaluated interdental osteotomy (IDO) sites between the lateral incisors and canines in patients treated with 3-piece Le Fort I osteotomies. CBCT scans were assessed using Kodac Dental Imaging software at specific intervals: T0 (before surgery), T1 (immediately after surgery), and T2 (a minimum of 11 months after surgery). The statistical analysis using a linear regression model was adjusted to compare the variables at the different intervals. Injury to the dental structures was assessed by radiological evidence of dental damage, the requirement for endodontic treatment, or tooth loss. We evaluated 94 IDO sites in 47 patients in the present study. The mean inter-radicular distance at T0 was 2.5 mm. A statistically significant increase was seen in the inter-radicular distance (between T1 and T0) of 0.72 mm, with a reduction of the alveolar bone crest height (between T2 and T0) of 0.19 mm (P < .001) for the group that underwent IDO. A weak correlation was found for this increase in the inter-radicular distance, with changes in the alveolar crest bone height. The potential complications associated with interdental osteotomies such as iatrogenic damage to the tooth structure, the need for endodontic treatment, and tooth loss were not encountered in any patients. We found very low morbidity for the interdental alveolar crest and the integrity of teeth adjacent to interdental osteotomies for patients who underwent maxillary segmentation between the lateral incisors and canines. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Silica crystals and aluminum salts mediate NALP-3 inflammasome activation via phagosomal destabilization

PubMed Central

Hornung, Veit; Bauernfeind, Franz; Halle, Annett; Samstad, Eivind O.; Kono, Hajime; Rock, Kenneth L.; Fitzgerald, Katherine A.; Latz, Eicke

2010-01-01

Inhalation of silica crystals causes inflammation in the alveolar space. Prolonged silica exposure can lead to the development of silicosis, an irreversible, fibrotic pulmonary disease. The mechanisms by which silica and other crystals activate immune cells are not well understood. Here, we demonstrate that silica and aluminum salt crystals activate the NALP3 inflammasome. NALP3 activation requires crystal phagocytosis and crystal uptake leads to lysosomal damage and rupture. Sterile lysosomal damage is also sufficient to induce NALP3 activation and inhibition of phagosomal acidification or cathepsin B impairs NALP3 activation. These results indicate that the NALP3 inflammasome can sense lysosomal damage induced by various means as an endogenous danger signal. PMID:18604214

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiss, T.F.; Golden, J.

Pneumocystis carinii pneumonia was suggested by a diffuse, bilateral pulmonary uptake of gallium-67 in an asymptomatic, homosexual male with the antibody to the immunodeficiency virus (HIV) who was undergoing staging evaluation for lymphoma clinically localized to a left inguinal lymph node. Chest radiograph and pulmonary function evaluation, including lung volumes, diffusing capacity and arterial blood gases, were within normal limits. Bronchoalveolar lavage revealed Pneumocystis carinii organisms. In this asymptomatic, HIV-positive patient, active alveolar infection, evidenced by abnormal gallium-67 scanning, predated pulmonary physiologic abnormalities. This observation raises questions concerning the natural history of this disease process and the specificity of physiologicmore » tests for excluding disease. It also has implications for the treatment of neoplasia in the HIV-positive patient population.« less

Transverse Diffusivity of Cerebral Parenchyma Predicts Visual Tracking Performance in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Warlop, Nele P.; Achten, Eric; Fieremans, Els; Debruyne, Jan; Vingerhoets, Guy

2009-01-01

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing-remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined…

Characterization and modeling of low energy ion-induced damage in III-V semiconductors

NASA Astrophysics Data System (ADS)

Chen, Ching-Hui

1997-11-01

Low energy ion-induced damage (sub-keV) created during dry etching processes can extend quite deeply into materials. A systematic study on the deep penetration of dry etch-induced damage is necessary to improve device performance and helpful in further understanding the nature of defect propagation in semiconductors. In this study, a phenomenological model of dry etching damage that includes both effects of ion channeling and defect diffusion has been developed. It underscores that in addition to ion channeling, enhanced defect diffusion also plays an important role in establishing the damage profile. Further, the enhanced diffusion of dry etch- induced damage was experimentally observed for the first time by investigating the influences of concurrent above- bandgap laser illumination and low energy Ar+ ion bombardment on the damage profiles of GaAs/AlGaAs and InP-GaAs/InP heterostructures. The results indicate that non-radiative recombination of electron and hole pairs at defect sites is responsible for the observed radiation enhanced diffusion. DLTS measurements are also employed to characterize the nature of the enhanced diffusion in n-GaAs and reveal that a major component of the ion- induced defects is associated with primary point defects. Using the better understanding of the damage propagation in dry etched materials, a thin layer of low temperature grown GaAs (~200A) was utilized to stop defect propagation during dry etching process. This approach has been successfully applied to reduce ion damage that would occur during the formation of a dry-etch gate recess of a high electron mobility transistor. Finally, some future experiments are proposed and conceptually described, which would further clarify some of the many outstanding issues in the understanding and mitigation of etch- induced damage.

Coronectomy of Deeply Impacted Lower Third Molar: Incidence of Outcomes and Complications after One Year Follow-Up

PubMed Central

Heijsters, Guido; Salem, Ahmed Sobhy; Van Slycke, Sarah; Schepers, Serge; Politis, Constantinus; Vrielinck, Luc

2015-01-01

ABSTRACT Objectives The purpose of present study was to assess the surgical management of impacted third molar with proximity to the inferior alveolar nerve and complications associated with coronectomy in a series of patients undergoing third molar surgery. Material and Methods The position of the mandibular canal in relation to the mandibular third molar region and mandibular foramen in the front part of the mandible (i.e., third molar in close proximity to the inferior alveolar nerve [IAN] or not) was identified on panoramic radiographs of patients scheduled for third molar extraction. Results Close proximity to the IAN was observed in 64 patients (35 females, 29 males) with an impacted mandibular third molar. Coronectomy was performed in these patients. The most common complication was tooth migration away from the mandibular canal (n = 14), followed by root exposure (n = 5). Re-operation to remove the root was performed in cases with periapical infection and root exposure. Conclusions The results indicate that coronectomy can be considered a reasonable and safe treatment alternative for patients who demonstrate elevated risk for injury to the inferior alveolar nerve with removal of the third molars. Coronectomy did not increase the incidence of damage to the inferior alveolar nerve and would be safer than complete extraction in situations in which the root of the mandibular third molar overlaps or is in close proximity to the mandibular canal. PMID:26229580

Stem cell research: applicability in dentistry.

PubMed

Mathur, Shivani; Chopra, Rahul; Pandit, I K; Srivastava, Nikhil; Gugnani, Neeraj

2014-01-01

In the face of extraordinary advances in the prevention, diagnosis, and treatment of human diseases, the inability of most tissues and organs to repair and regenerate after damage is a problem that needs to be solved. Stem cell research is being pursued in the hope of achieving major medical breakthroughs. Scientists are striving to create therapies that rebuild or replace damaged cells with tissues grown from stem cells that will offer hope to people suffering from various ailments. Regeneration of damaged periodontal tissue, bone, pulp, and dentin is a problem that dentists face today. Stem cells present in dental pulp, periodontal ligament, and alveolar bone marrow have the potential to repair and regenerate teeth and periodontal structures. These stem cells can be harvested from dental pulp, periodontal ligament, and/or alveolar bone marrow; expanded; embedded in an appropriate scaffold; and transplanted back into a defect to regenerate bone and tooth structures. These cells have the potential to regenerate dentin, periodontal ligament, and cementum and can also be used to restore bone defects. The kind of scaffold, the source of cells, the type of in vitro culturing, and the type of surgical procedure to be used all require careful consideration. The endeavor is clearly multidisciplinary in nature, and the practicing dental surgeon has a critical role in it. Playing this role in the most effective way requires awareness of the huge potential associated with the use of stem cells in a clinical setting, as well as a proper understanding of the related problems.

Microstructural and ultrastructural assessment of inferior alveolar nerve damage following nerve lateralization and implant placement: an experimental study in rabbits.

PubMed

Yoshimoto, Marcelo; Watanabe, Il-sei; Martins, Marília T; Salles, Marcos B; Ten Eyck, Gary R; Coelho, Paulo G

2009-01-01

The present study assessed damage to the inferior alveolar nerve (IAN) following nerve lateralization and implant placement surgery through optical and transmission electron microscopy (TEM). IAN lateralization was performed in 16 adult female rabbits (Oryctolagus cuniculus). During the nerve lateralization procedure, one implant was placed through the mandibular canal, and the IAN was replaced in direct contact with the implant. The implant was placed in the right mandible, and the left side was used as a control (no surgical procedure). After 8 weeks, the animals were sacrificed and samples were prepared for optical and TEM analysis of IAN structural damage. Histomorphometric analysis was performed to determine the number and cross-sectional dimensions of nerve fascicles and myelin sheath thickness between experimental and control groups. The different parameters were compared by one-way analysis of variance at the 95% significance level. Alterations in the perineural and endoneural regions of the IAN, with higher degrees of vascularization, were observed in the experimental group. TEM showed that the majority of the myelinated nerve fibers were not affected in the experimental samples. No significant variation in the number of fascicles was observed, significantly larger fascicle height and width were observed in the control group, and significantly thicker myelin sheaths were observed in the experimental samples. IAN lateralization resulted in substantial degrees of tissue disorganization at the microstructural level because of the presence of edema. However, at the ultrastructural level, small amounts of fiber degeneration were observed.

Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway

PubMed Central

Weeden, Clare E.; Chen, Yunshun; Ma, Stephen B.; Hu, Yifang; Ramm, Georg; Sutherland, Kate D.; Smyth, Gordon K.

2017-01-01

Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonhomologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilection for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC. PMID:28125611

Calcitonin gene-related peptide protects type II alveolar epithelial cells from hyperoxia-induced DNA damage and cell death.

PubMed

Fu, Hongmin; Zhang, Tiesong; Huang, Rongwei; Yang, Zhen; Liu, Chunming; Li, Ming; Fang, Fang; Xu, Feng

2017-04-01

Hyperoxia therapy for acute lung injury (ALI) may unexpectedly lead to reactive oxygen species (ROS) production and cause additional ALI. Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide that regulates inflammasome activation. However, the role of CGRP in DNA damage during hyperoxia is unclear. Therefore, the aim of the present study was to investigate the effects of CGRP on DNA damage and the cell death of alveolar epithelial type II cells (AEC II) exposed to 60% oxygen. AEC II were isolated from 19-20 gestational day fetal rat lungs and were exposed to air or to 60% oxygen during treatment with CGRP or the specific CGRP receptor antagonist CGRP 8-37 . The cells were evaluated using immunofluorescence to examine surfactant protein-C and ROS levels were measured by probing with 2',7'-dichlorofluorescin diacetate. The apoptosis rate and cell cycle of AEC II were analyzed by flow cytometry, and apoptosis was determined by western blotting analysis of activated caspase 3. The DNA damage was confirmed with immunofluorescence of H2AX via high-content analysis. The ROS levels, apoptotic cell number and the expression of γH2AX were markedly increased in the hyperoxia group compared with those in the air group. Concordantly, ROS levels, apoptotic cell number and the expression of γH2AX were significantly lower with a significant arrest of S and G2/M phases in the CGRP/O 2 group than in the hyperoxia or CGRP 8-37 /O 2 groups. CGRP was concluded to protect lung epithelium cells against hyperoxic insult, and upregulation of CGRP may be a possible novel therapeutic target to treat hyperoxic lung injury.

Involvement of lysosomal dysfunction in silver nanoparticle-induced cellular damage in A549 human lung alveolar epithelial cells.

PubMed

Miyayama, Takamitsu; Matsuoka, Masato

2016-01-01

While silver nanoparticles (AgNPs) are widely used in consumer and medical products, the mechanism by which AgNPs cause pulmonary cytotoxicity is not clear. AgNP agglomerates are found in endo-lysosomal structures within the cytoplasm of treated cells. In this study, the functional role of lysosomes in AgNP-induced cellular damage was examined in A549 human lung alveolar epithelial cells. We evaluated the intracellular distribution of AgNPs, lysosomal pH, cellular viability, Ag dissolution, and metallothionein (MT) mRNA levels in AgNP-exposed A549 cells that were treated with bafilomycin A1, the lysosomal acidification inhibitor. Exposure of A549 cells to citrate-coated AgNPs (20 nm diameter) for 24 h induced cellular damage and cell death at 100 and 200 μg Ag/ml, respectively. Confocal laser microscopic examination of LysoTracker-stained cells showed that AgNPs colocalized with lysosomes and their agglomeration increased in a dose-dependent manner (50-200 μg Ag/ml). In addition, the fluorescence signals of LysoTracker were reduced following exposure to AgNPs, suggesting the elevation of lysosomal pH. Treatment of A549 cells with 200 nM bafilomycin A1 and AgNPs (50 μg Ag/ml) further reduced the fluorescence signals of LysoTracker. AgNP-induced cell death was also increased by bafilomycin A1 treatment. Finally, treatment with bafilomycin A1 suppressed the dissolution of Ag and decreased the mRNA expression levels of MT-I and MT-II following exposure to AgNPs. The perturbation of lysosomal pH by AgNP exposure may play a role in AgNP agglomeration and subsequent cellular damage in A549 cells.

[Intraoperative monitoring in artificial respiration of premature and newborn infants. I. Monitoring of respiratory parameters and alveolar ventilation].

PubMed

Lenz, G; Heipertz, W; Leidig, E; Madee, S

1986-06-01

Monitoring of ventilation serves to ensure adequate alveolar ventilation and arterial oxygenation, and to avoid pulmonary damage due to mechanical ventilation. Basic clinical monitoring, i.e., inspection, auscultation (including precordial or oesophageal stethoscope) and monitoring of heart rate and blood pressure, is mandatory. Mechanical ventilation is monitored by ventilation pressures (peak pressure, plateau pressure and endexpiratory pressure), ventilation volumes (measured at the in/expiratory valve of the respirator and by hot-wire anemometry at the tube connector), ventilation rate, and inspiratory oxygen concentration (FiO2). Alveolar ventilation should be continuously and indirectly recorded by capnometry (pECO2) and by measurement of transcutaneous pCO2 (tcpCO2), whereas oxygenation is determined via measurement of transcutaneous pO2 (tcpO2). Invasive monitoring of gas exchange is essential in prolonged or intrathoracic interventions as well as in neonates with cardiopulmonary problems. paCO2 may be estimated by capillary or venous blood gas analysis; arterial blood gas analysis is required for exact determination of paCO2 as well as arteriocutaneous pCO2 (atcDCO2) and arterio-end-expiratory (aEDCO2) gradients.

Endodontic-related inferior alveolar nerve injuries: A review and a therapeutic flow chart.

PubMed

Castro, R; Guivarc'h, M; Foletti, J M; Catherine, J H; Chossegros, C; Guyot, L

2018-05-03

Inferior alveolar nerve (IAN) lesions related to endodontic treatments can be explained by the anatomical proximity between the apices of the mandibular posterior teeth and the mandibular canal. The aim of this article is to review the management of inferior alveolar nerve lesions due to endodontic treatments and to establish a therapeutic flow chart. A review of publications reporting IAN damage related to endodontic treatment over the past 20 years has been conducted, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist; it combines an electronic search of the Pubmed ® and Google Scholar ® databasis. Forty-two full-text articles corresponding to 115 clinical cases have been selected. Two personal clinical cases were additionally reported. IAN lesions due to endodontic treatments require urgent management. Early surgical removal of the excess of endodontic material, in contact with the nerve allows the best recovery prognosis (72h). Beyond this delay, irreversible nervous lesions prevail and a medical symptomatic treatment, most of the time with pregabalin, must be/can be carried out. A delayed surgical procedure shows some good benefits for patients. However, the healing prognosis remains poorly predictable. Copyright © 2018. Published by Elsevier Masson SAS.

The structural basis of moderate disability after traumatic brain damage

PubMed Central

Adams, J; Graham, D; Jennett, B

2001-01-01

The objective was to discover the nature of brain damage in survivors of head injury who are left with moderate disability. Macroscopic and microscopic examination was carried out on the brains of 20 persons who had died long after a head injury that had been treated in a neurosurgical unit. All had become independent but had various disabilities (moderate disability on the Glasgow outcome scale) Most deaths had been sudden, which had led to their referral from forensic pathologists. Post-traumatic epilepsy was a feature in 75%. An intracranial haematoma had been evacuated in 75%, and in 11 of the 15 with epilepsy. Diffuse axonal injury was found in six patients, five of the mildest type (grade 1) and one of grade 2. No patient had diffuse thalamic damage but one had a small focal ischaemic lesion in the thalamus. No patient had severe ischaemic brain damage, but three had moderate lesions which were bilateral in only one. No patient had severe cortical contusions. In conclusion, the dominant lesion was focal damage from an evacuated intracranial haematoma. Severe diffuse damage was not found, with diffuse axonal injury only mild and thalamic damage in only one patient.

 PMID:11561038

Microstructural consequences of blast lung injury characterised with digital volume correlation

NASA Astrophysics Data System (ADS)

Arora, Hari; Nila, Alex; Vitharana, Kalpani; Sherwood, Joseph M.; Nguyen, Thuy-Tien N.; Karunaratne, Angelo; Mohammed, Idris K.; Bodey, Andrew J.; Hellyer, Peter J.; Overby, Darryl R.; Schroter, Robert C.; Hollis, Dave

2017-12-01

This study focuses on microstructural changes that occur within the mammalian lung when subject to blast and how these changes influence strain distributions within the tissue. Shock tube experiments were performed to generate the blast injured specimens (cadaveric Sprague-Dawley rats). Blast overpressures of 100 kPa and 180 kPa were studied. Synchrotron tomography imaging was used to capture volumetric image data of lungs. Specimens were ventilated using a custom-built system to study multiple inflation pressures during each tomography scan. This data enabled the first digital volume correlation (DVC) measurements in lung tissue to be performed. Quantitative analysis was performed to describe the damaged architecture of the lung. No clear changes in the microstructure of the tissue morphology were observed due to controlled low to moderate level blast exposure. However, significant focal sites of injury were observed using DVC, which allowed detection of bias and concentration in the patterns of strain level. Morphological analysis corroborated the findings, illustrating that the focal damage caused by a blast can give rise to diffuse influence across the tissue. It is important to characterise the non-instantly fatal doses of blast, given the transient nature of blast lung in the clinical setting. This research has highlighted the need for better understanding of focal injury and its zone of influence (alveolar inter-dependency and neighbouring tissue burden as a result of focal injury). Digital volume correlation techniques show great promise as a tool to advance this endeavour, providing a new perspective on lung mechanics post-blast.

Positive End-Expiratory Pressure and Variable Ventilation in Lung-Healthy Rats under General Anesthesia

PubMed Central

Camilo, Luciana M.; Ávila, Mariana B.; Cruz, Luis Felipe S.; Ribeiro, Gabriel C. M.; Spieth, Peter M.; Reske, Andreas A.; Amato, Marcelo; Giannella-Neto, Antonio; Zin, Walter A.; Carvalho, Alysson R.

2014-01-01

Objectives Variable ventilation (VV) seems to improve respiratory function in acute lung injury and may be combined with positive end-expiratory pressure (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized that VV in combination with moderate levels of PEEP reduce the deterioration of pulmonary function related to general anesthesia. Hence, we aimed at evaluating the alveolar stability and lung protection of the combination of VV at different PEEP levels. Design Randomized experimental study. Setting Animal research facility. Subjects Forty-nine male Wistar rats (200–270 g). Interventions Animals were ventilated during 2 hours with protective low tidal volume (VT) in volume control ventilation (VCV) or VV and PEEP adjusted at the level of minimum respiratory system elastance (Ers), obtained during a decremental PEEP trial subsequent to a recruitment maneuver, and 2 cmH2O above or below of this level. Measurements and Main Results Ers, gas exchange and hemodynamic variables were measured. Cytokines were determined in lung homogenate and plasma samples and left lung was used for histologic analysis and diffuse alveolar damage scoring. A progressive time-dependent increase in Ers was observed independent on ventilatory mode or PEEP level. Despite of that, the rate of increase of Ers and lung tissue IL-1 beta concentration were significantly lower in VV than in VCV at the level of the PEEP of minimum Ers. A significant increase in lung tissue cytokines (IL-6, IL-1 beta, CINC-1 and TNF-alpha) as well as a ventral to dorsal and cranial to caudal reduction in aeration was observed in all ventilated rats with no significant differences among groups. Conclusions VV combined with PEEP adjusted at the level of the PEEP of minimal Ers seemed to better prevent anesthesia-induced atelectasis and might improve lung protection throughout general anesthesia. PMID:25383882

Restricted diffusion in a model acinar labyrinth by NMR: Theoretical and numerical results

NASA Astrophysics Data System (ADS)

Grebenkov, D. S.; Guillot, G.; Sapoval, B.

2007-01-01

A branched geometrical structure of the mammal lungs is known to be crucial for rapid access of oxygen to blood. But an important pulmonary disease like emphysema results in partial destruction of the alveolar tissue and enlargement of the distal airspaces, which may reduce the total oxygen transfer. This effect has been intensively studied during the last decade by MRI of hyperpolarized gases like helium-3. The relation between geometry and signal attenuation remained obscure due to a lack of realistic geometrical model of the acinar morphology. In this paper, we use Monte Carlo simulations of restricted diffusion in a realistic model acinus to compute the signal attenuation in a diffusion-weighted NMR experiment. We demonstrate that this technique should be sensitive to destruction of the branched structure: partial removal of the interalveolar tissue creates loops in the tree-like acinar architecture that enhance diffusive motion and the consequent signal attenuation. The role of the local geometry and related practical applications are discussed.

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

PubMed

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 for AEC mitochondrial H 2 O 2 -induced mtDNA damage in promoting lung fibrosis. We reason that strategies aimed at limiting AEC mtDNA damage arising from excess mitochondrial H 2 O 2 production may be a novel therapeutic target for mitigating pulmonary fibrosis. Published by Elsevier Inc.

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

PubMed Central

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

2018-01-01

Rationale 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. Objective 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. Methods Crocidolite asbestos (100 μg/50 μL), TiO2 (negative control), bleomycin (0.025 units/50 μL), or PBS was instilled intratracheally in 8–10 week-old wild-type (WT - C57Bl/6 J) or MCAT mice. The lungs were harvested at 21 d. 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. Results 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. Conclusions Our finding that MCAT mice have reduced pulmonary fibrosis, AEC mtDNA damage and apoptosis following exposure to asbestos or bleomycin suggests an important role for AEC mitochondrial H2O2-induced mtDNA damage in promoting lung fibrosis. We reason that strategies aimed at limiting AEC mtDNA damage arising from excess mitochondrial H2O2 production may be a novel therapeutic target for mitigating pulmonary fibrosis. PMID:27840320

Basal and induced NO formation in the pharyngo-oral tract influences estimates of alveolar NO levels.

PubMed

Malinovschi, Andrei; Janson, Christer; Holm, Lena; Nordvall, Lennart; Alving, Kjell

2009-02-01

The present study analyzed how models currently used to distinguish alveolar from bronchial contribution to exhaled nitric oxide (NO) are affected by manipulation of NO formation in the pharyngo-oral tract. Exhaled NO was measured at multiple flow rates in 15 healthy subjects in two experiments: 1) measurements at baseline and 5 min after chlorhexidine (CHX) mouthwash and 2) measurements at baseline, 60 min after ingestion of 10 mg NaNO(3)/kg body wt, and 5 min after CHX mouthwash. Alveolar NO concentration (Calv(NO)) and bronchial flux (J'aw(NO)) were calculated by using the slope-intercept model with or without adjustment for trumpet shape of airways and axial diffusion (TMAD). Salivary nitrate and nitrite were measured in the second experiment. Calv(NO) [median (range)] was reduced from 1.16 ppb (0.77, 1.96) at baseline to 0.84 ppb (0.57, 1.48) 5 min after CHX mouthwash (P < 0.001). The TMAD-adjusted Calv(NO) value after CHX mouthwash was 0.50 ppb (0, 0.85). The nitrate load increased J'aw(NO) from 32.2 nl/min (12.2, 60.3) to 57.1 nl/min (22.0, 119) in all subjects and Calv(NO) from 1.47 ppb (0.73, 1.95) to 1.87 ppb (10.85, 7.20) in subjects with high nitrate turnover (>10-fold increase of salivary nitrite after nitrate load). CHX mouthwash reduced Calv(NO) levels to 1.15 ppb (0.72, 2.07) in these subjects with high nitrate turnover. All these results remained consistent after TMAD adjustment. We conclude that estimated alveolar NO concentration is affected by pharyngo-oral tract production of NO in healthy subjects, with a decrease after CHX mouthwash. Moreover, unknown ingestion of dietary nitrate could significantly increase estimated alveolar NO in subjects with high nitrate turnover, and this might be falsely interpreted as a sign of peripheral inflammation. These findings were robust for TMAD.

Alveolar hemorrhage in systemic lupus erythematosus: a cohort review.

PubMed

Andrade, C; Mendonça, T; Farinha, F; Correia, J; Marinho, A; Almeida, I; Vasconcelos, C

2016-01-01

Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%. © The Author(s) 2015.

Replacing Heavily Damaged Teeth by Third Molar Autotransplantation With the Use of Cone-Beam Computed Tomography and Rapid Prototyping.

PubMed

Verweij, Jop P; Anssari Moin, David; Wismeijer, Daniel; van Merkesteyn, J P Richard

2017-09-01

This article describes the autotransplantation of third molars to replace heavily damaged premolars and molars. Specifically, this article reports on the use of preoperative cone-beam computed tomographic planning and 3-dimensional (3D) printed replicas of donor teeth to prepare artificial tooth sockets. In the present case, an 18-year-old patient underwent autotransplantation of 3 third molars to replace 1 premolar and 2 molars that were heavily damaged after trauma. Approximately 1 year after the traumatic incident, autotransplantation with the help of 3D planning and rapid prototyping was performed. The right maxillary third molar replaced the right maxillary first premolar. The 2 mandibular wisdom teeth replaced the left mandibular first and second molars. During the surgical procedure, artificial tooth sockets were prepared with the help of 3D printed donor tooth copies to prevent iatrogenic damage to the actual donor teeth. These replicas of the donor teeth were designed based on the preoperative cone-beam computed tomogram and manufactured with the help of 3D printing techniques. The use of a replica of the donor tooth resulted in a predictable and straightforward procedure, with extra-alveolar times shorter than 2 minutes for all transplantations. The transplanted teeth were placed in infraocclusion and fixed with a suture splint. Postoperative follow-up showed physiologic integration of the transplanted teeth and a successful outcome for all transplants. In conclusion, this technique facilitates a straightforward and predictable procedure for autotransplantation of third molars. The use of printed analogues of the donor teeth decreases the risk of iatrogenic damage and the extra-alveolar time of the transplanted tooth is minimized. This facilitates a successful outcome. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage.

PubMed

He, Yifan; Zhu, Jihong; Huang, Fang; Qin, Liu; Fan, Wenguo; He, Hongwen

2014-11-15

The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that tooth extraction should be avoided in these populations.

Platelet secretion of CXCL4 is Rac1-dependent and regulates neutrophil infiltration and tissue damage in septic lung damage.

PubMed

Hwaiz, Rundk; Rahman, Milladur; Zhang, Enming; Thorlacius, Henrik

2015-11-01

Platelets are potent regulators of neutrophil accumulation in septic lung damage. We hypothesized that platelet-derived CXCL4 might support pulmonary neutrophilia in a murine model of abdominal sepsis. Polymicrobial sepsis was triggered by coecal ligation and puncture (CLP) in C57BL/6 mice. Platelet secretion of CXCL4 was studied by using confocal microscopy. Plasma and lung levels of CXCL4, CXCL1 and CXCL2 were determined by elisa. Flow cytometry was used to examine surface expression of Mac-1 on neutrophils. CLP increased CXCL4 levels in plasma, and platelet depletion reduced plasma levels of CXCL4 in septic animals. Rac1 inhibitor NSC23766 decreased the CLP-enhanced CXCL4 in plasma by 77%. NSC23766 also abolished PAR4 agonist-induced secretion of CXCL4 from isolated platelets. Inhibition of CXCL4 reduced CLP-evoked neutrophil recruitment, oedema formation and tissue damage in the lung. However, immunoneutralization of CXCL4 had no effect on CLP-induced expression of Mac-1 on neutrophils. Targeting CXCL4 attenuated plasma and lung levels of CXCL1 and CXCL2 in septic mice. CXCL4 had no effect on neutrophil chemotaxis in vitro, indicating it has an indirect effect on pulmonary neutrophilia. Intratracheal CXCL4 enhanced infiltration of neutrophils and formation of CXCL2 in the lung. CXCR2 antagonist SB225002 markedly reduced CXCL4-provoked neutrophil accumulation in the lung. CXCL4 caused secretion of CXCL2 from isolated alveolar macrophages. Rac1 controls platelet secretion of CXCL4 and CXCL4 is a potent stimulator of neutrophil accumulation in septic lungs via generation of CXCL2 in alveolar macrophages. Platelet-derived CXCL4 plays an important role in lung inflammation and tissue damage in polymicrobial sepsis. © 2015 The British Pharmacological Society.

Platelet secretion of CXCL4 is Rac1‐dependent and regulates neutrophil infiltration and tissue damage in septic lung damage

PubMed Central

Hwaiz, Rundk; Rahman, Milladur; Zhang, Enming

2015-01-01

Background and Purpose Platelets are potent regulators of neutrophil accumulation in septic lung damage. We hypothesized that platelet‐derived CXCL4 might support pulmonary neutrophilia in a murine model of abdominal sepsis. Experimental Approach Polymicrobial sepsis was triggered by coecal ligation and puncture (CLP) in C57BL/6 mice. Platelet secretion of CXCL4 was studied by using confocal microscopy. Plasma and lung levels of CXCL4, CXCL1 and CXCL2 were determined by elisa. Flow cytometry was used to examine surface expression of Mac‐1 on neutrophils. Key Results CLP increased CXCL4 levels in plasma, and platelet depletion reduced plasma levels of CXCL4 in septic animals. Rac1 inhibitor NSC23766 decreased the CLP‐enhanced CXCL4 in plasma by 77%. NSC23766 also abolished PAR4 agonist‐induced secretion of CXCL4 from isolated platelets. Inhibition of CXCL4 reduced CLP‐evoked neutrophil recruitment, oedema formation and tissue damage in the lung. However, immunoneutralization of CXCL4 had no effect on CLP‐induced expression of Mac‐1 on neutrophils. Targeting CXCL4 attenuated plasma and lung levels of CXCL1 and CXCL2 in septic mice. CXCL4 had no effect on neutrophil chemotaxis in vitro, indicating it has an indirect effect on pulmonary neutrophilia. Intratracheal CXCL4 enhanced infiltration of neutrophils and formation of CXCL2 in the lung. CXCR2 antagonist SB225002 markedly reduced CXCL4‐provoked neutrophil accumulation in the lung. CXCL4 caused secretion of CXCL2 from isolated alveolar macrophages. Conclusions and Implications Rac1 controls platelet secretion of CXCL4 and CXCL4 is a potent stimulator of neutrophil accumulation in septic lungs via generation of CXCL2 in alveolar macrophages. Platelet‐derived CXCL4 plays an important role in lung inflammation and tissue damage in polymicrobial sepsis. PMID:26478565

Iatrogenic Damage to the Periodontium Caused by Periodontal Treatment Procedures

PubMed Central

Latheef, P; Sirajuddin, Syed; Gundapaneni, Veenadharini; MN, Kumuda; Apine, Ashwini

2015-01-01

Periodontitis is an inflammatory disease affecting the periodontium i.e. the tissues that surround and support the teeth. Periodontitis manifests as progressive loss of the alveolar bone around the teeth, and if left untreated, can cause loosening and subsequent loss of teeth. Periodontitis is initiated by microorganisms that adhere to and grow on the tooth's surfaces, besides an over -aggressive immune response against these microorganisms. The primary goal of periodontal therapy is to preserve the natural dentition by accomplishing and preserving a healthy functional periodontium. Many treatment modalities have been introduced to improve the therapeutic result of periodontal treatment which may also damage the periodontiumiatrogenically. PMID:26312087

Overcoming Rapid Inactivation of Lung Surfactant: Analogies Between Competitive Adsorption and Colloid Stability

PubMed Central

Zasadzinski, Joseph A.; Stenger, Patrick C.; Shieh, Ian; Dhar, Prajnaparamita

2009-01-01

Lung surfactant (LS) is a mixture of lipids and proteins that line the alveolar air-liquid interface, lowering the interfacial tension to levels that make breathing possible. In acute respiratory distress syndrome (ARDS), inactivation of LS is believed to play an important role in the development and severity of the disease. This review examines the competitive adsorption of LS and surface-active contaminants, such as serum proteins, present in the alveolar fluids of ARDS patients, and how this competitive adsorption can cause normal amounts of otherwise normal LS to be ineffective in lowering the interfacial tension. LS and serum proteins compete for the air-water interface when both are present in solution either in the alveolar fluids or in a Langmuir trough. Equilibrium favors LS as it has the lower equilibrium surface pressure, but the smaller proteins are kinetically favored over multi-micron LS bilayer aggregates by faster diffusion. If albumin reaches the interface, it creates an energy barrier to subsequent LS adsorption that slows or prevents the adsorption of the necessary amounts of LS required to lower surface tension. This process can be understood in terms of classic colloid stability theory in which an energy barrier to diffusion stabilizes colloidal suspensions against aggregation. This analogy provides qualitative and quantitative predictions regarding the origin of surfactant inactivation. An important corollary is that any additive that promotes colloid coagulation, such as increased electrolyte concentration, multivalent ions, hydrophilic non-adsorbing polymers such as PEG, dextran, etc. or polyelectrolytes such as chitosan, added to LS, also promotes LS adsorption in the presence of serum proteins and helps reverse surfactant inactivation. The theory provides quantitative tools to determine the optimal concentration of these additives and suggests that multiple additives may have a synergistic effect. A variety of physical and chemical techniques including isotherms, fluorescence microscopy, electron microscopy and X-ray diffraction show that LS adsorption is enhanced by this mechanism without substantially altering the structure or properties of the LS monolayer. PMID:20026298

Scaling laws for oxygen transport across the space-filling system of respiratory membranes in the human lung

NASA Astrophysics Data System (ADS)

Hou, Chen

Space-filling fractal surfaces play a fundamental role in how organisms function at various levels and in how structure determines function at different levels. In this thesis, we develop a quantitative theory of oxygen transport to and across the surface of the highly branched, space-filling system of alveoli, the fundamental gas exchange unit (acinar airways), in the human lung. Oxygen transport in the acinar airways is by diffusion, and we treat the two steps---diffusion through the branched airways, and transfer across the alveolar membranes---as a stationary diffusion-reaction problem, taking into account that there may be steep concentration gradients between the entrance and remote alveoli (screening). We develop a renormalization treatment of this screening effect and derive an analytic formula for the oxygen current across the cumulative alveolar membrane surface, modeled as a fractal, space-filling surface. The formula predicts the current from a minimum of morphological data of the acinus and appropriate values of the transport parameters, through a number of power laws (scaling laws). We find that the lung at rest operates near the borderline between partial screening and no screening; that it switches to no screening under exercise; and that the computed currents agree with measured values within experimental uncertainties. From an analysis of the computed current as a function of membrane permeability, we find that the space-filling structure of the gas exchanger is simultaneously optimal with respect to five criteria. The exchanger (i) generates a maximum oxygen current at minimum permeability; (ii) 'wastes' a minimum of surface area; (iii) maintains a minimum residence time of oxygen in the acinar airways; (iv) has a maximum fault tolerance to loss of permeability; and (v) generates a maximum current increase when switching from rest to exercise.

Diffusion of hyperpolarized 129Xe in the lung: a simplified model of 129Xe septal uptake and experimental results

NASA Astrophysics Data System (ADS)

Patz, Samuel; Muradyan, Iga; Hrovat, Mirko I.; Dabaghyan, Mikayel; Washko, George R.; Hatabu, Hiroto; Butler, James P.

2011-01-01

We used hyperpolarized 129Xe NMR to measure pulmonary alveolar surface area per unit gas volume SA/Vgas, alveolar septal thickness h and capillary transit time τ, three critical determinants of the lung's primary role as a gas exchange organ. An analytical solution for a simplified diffusion model is described, together with a modification of the xenon transfer contrast imaging technique utilizing 90° radio-frequency pulses applied to the dissolved phase, rather than traditional 180° pulses. With this approach, three-dimensional (3D) maps of SA/Vgas were obtained. We measured global SA/Vgas, h and τ in four normal subjects, two subjects with mild interstitial lung disease (ILD) and two subjects with mild chronic obstructive pulmonary disease (COPD). In normals, SA/Vgas decreased with increasing lung volume from ~320 to 80 cm-1 both h~13 μm and τ~1.5 s were relatively constant. For the two ILD subjects, h was, respectively, 36 and 97% larger than normal, quantifying an increased gas/blood tissue barrier; SA/Vgas and τ were normal. The two COPD subjects had SA/Vgas values ~25% that of normals, quantifying septal surface loss in emphysema; h and τ were normal. These are the first noninvasive, non-radiation-based, quantitative measurements of h and τ in patients with pulmonary disease.

Clinical significance of computed tomography assessment for third molar surgery

PubMed Central

Nakamori, Kenji; Tomihara, Kei; Noguchi, Makoto

2014-01-01

Surgical extraction of the third molar is the most commonly performed surgical procedure in the clinical practice of oral surgery. Third molar surgery is warranted when there is inadequate space for eruption, malpositioning, or risk for cyst or odontogenic tumor formation. Preoperative assessment should include a detailed morphologic analysis of the third molar and its relationship to adjacent structures and surrounding tissues. Due to developments in medical engineering technology, computed tomography (CT) now plays a critical role in providing the clear images required for adequate assessment prior to third molar surgery. Removal of the maxillary third molar is associated with a risk for maxillary sinus perforation, whereas removal of the mandibular third molar can put patients at risk for a neurosensory deficit from damage to the lingual nerve or inferior alveolar nerve. Multiple factors, including demographic, anatomic, and treatment-related factors, influence the incidence of nerve injury during or following removal of the third molar. CT assessment of the third molar prior to surgery can identify some of these risk factors, such as the absence of cortication between the mandibular third molar and the inferior alveolar canal, prior to surgery to reduce the risk for nerve damage. This topic highlight presents an overview of the clinical significance of CT assessment in third molar surgery. PMID:25071882

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

Reactive oxygen species mediated DNA damage in human lung alveolar epithelial (A549) cells from exposure to non-cytotoxic MFI-type zeolite nanoparticles.

PubMed

Bhattacharya, Kunal; Naha, Pratap C; Naydenova, Izabela; Mintova, Svetlana; Byrne, Hugh J

2012-12-17

Increasing utilization of engineered nanoparticles in the field of electronics and biomedical applications demands an assessment of risk associated with deliberate or accidental exposure. Metal based nanoparticles are potentially most important of all the nanoparticles in terms of health risks. Microporous alumino-silicates and pure silicates named as zeolites and zeo-type materials with variety of structures, chemical compositions, particle sizes and morphologies have a significant number of industrial uses such as in catalysis, sorption and ion-exchange processes. In particular, the nanosized particles due to their unique properties are used in hybrid organic-inorganic materials for photography, photonics, electronics, labeling, imaging, and sensing. The aim of the current study is to investigate pure silica MFI-type zeolites nanoparticles with sizes of 50nm and 100nm (samples MFI-50 and MFI-100) under suspended conditions and their toxicological effects on human lung alveolar (A549) cells under in vitro conditions. Live cell imaging showed that the nanoparticles precipitated from the colloidal suspension of cell culture media as large agglomerates, coming in contact with the cell surface through sedimentation. A cellular proliferative capacity test showed the zeolite nanoparticles to exhibit no significant cytotoxicity below a concentration of 100μg/ml. However, both the MFI-50 and MFI-100 nanoparticles induced high intracellular reactive oxygen species (ROS) generation and elevated mitochondrial membrane potential in the A549 cells over the measured time period of 12h and at concentrations up to ≤50μg/ml. DNA fragmentation analysis using the comet assay showed that the MFI-50 and MFI-100 nanoparticles cause genotoxicity in a concentration dependent manner. Furthermore, the rate at which maximum genomic damage was caused by MFI-100 nanoparticles in the A549 cells was found to be high as compared to the MFI-50 nanoparticles. However, the damage caused by the MFI-50 nanoparticles was found to accumulate over a longer period of time as compared to MFI-100 nanoparticles. The study therefore points towards the capability of the non-cytotoxic zeolite nanoparticles to induce oxidative stress resulting in short-term altered cellular metabolism up-regulation and genomic instability. Although the damage was found to be short-lived, its persistence over longer durations, or stabilization cannot be neglected. Further studies are in progress to yield a better understanding of the mechanisms for oxidative stress and resulting cascade of events leading to genetic damage in the human lung alveolar epithelial cells following exposure to zeolite nanoparticles of different sizes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Orthodontic elastic separator-induced periodontal abscess: a case report.

PubMed

Becker, Talia; Neronov, Alex

2012-01-01

Aim. Orthodontic elastic bands were proposed as being the source of gingival abscesses that can rapidly lead to bone loss and teeth exfoliation. We report an adolescent, otherwise, healthy patient whose periodontal status was sound. Shortly after undergoing preparations for orthodontic treatment consisting of orthodontic separators, he presented with a periodontal abscess for which there was no apparent etiology. A non-orthoradial X-ray was inconclusive, but an appropriate one revealed a subgingival orthodontic separator as the cause of the abscess. Removal of the separator and thorough scaling led to complete resolution of the abscess, but there was already residual mild damage to the alveolar bone. Summary. Failure to use appropriate imaging to reveal the cause of gingival abscesses can result in the delay of implementing treatment and halting irreversible alveolar bone loss. An inflammatory process restricted to the gingiva and refractive to conventional therapy should raise the possibility of a foreign body etiology.

Orthodontic Elastic Separator-Induced Periodontal Abscess: A Case Report

PubMed Central

Becker, Talia; Neronov, Alex

2012-01-01

Aim. Orthodontic elastic bands were proposed as being the source of gingival abscesses that can rapidly lead to bone loss and teeth exfoliation. We report an adolescent, otherwise, healthy patient whose periodontal status was sound. Shortly after undergoing preparations for orthodontic treatment consisting of orthodontic separators, he presented with a periodontal abscess for which there was no apparent etiology. A non-orthoradial X-ray was inconclusive, but an appropriate one revealed a subgingival orthodontic separator as the cause of the abscess. Removal of the separator and thorough scaling led to complete resolution of the abscess, but there was already residual mild damage to the alveolar bone. Summary. Failure to use appropriate imaging to reveal the cause of gingival abscesses can result in the delay of implementing treatment and halting irreversible alveolar bone loss. An inflammatory process restricted to the gingiva and refractive to conventional therapy should raise the possibility of a foreign body etiology. PMID:22567456

Peripapillary choroidal thickness in healthy controls and patients with focal, diffuse, and sclerotic glaucomatous optic disc damage.

PubMed

Roberts, Kenneth F; Artes, Paul H; O'Leary, Neil; Reis, Alexandre S C; Sharpe, Glen P; Hutchison, Donna M; Chauhan, Balwantray C; Nicolela, Marcelo T

2012-08-01

To examine peripapillary choroidal thickness in healthy controls and in patients with glaucoma who have focal, diffuse, and sclerotic optic disc damage. Healthy controls (n=92) and patients with glaucoma who have focal (n=34), diffuse (n=35), and sclerotic (n=34) optic disc damage were imaged with spectral-domain optical coherence tomography (12° circular scan protocol centered on optic nerve head). Peripapillary choroidal thickness was measured as the distance between the automatically segmented retinal pigment epithelium/Bruch's membrane and the manually outlined interface between the posterior choroid and the anterior border of the sclera in eyes in which the anterior scleral border was visible over more than 85% of the scan circumference. The anterior scleral border was visible in 76 controls (83%) and 89 patients (86%). Peripapillary choroidal thickness in healthy controls decreased linearly with age (-11 μm/decade; P.001; r2=0.16), with a predicted value of 137 μm at age 70 years (95% prediction interval, 62-212 μm). While this value was similar in patients with focal and diffuse optic disc damage (126 and 130 μm, respectively; P=.22 compared with controls), it was approximately 30% lower in patients with sclerotic optic disc damage (96 μm; P.001 compared with controls). The peripapillary choroid of patients with glaucoma who have sclerotic optic disc damage was approximately 25% to 30% thinner compared with that in patients with focal and diffuse optic disc damage and with that in healthy controls. The role of the choroid in the pathophysiology of sclerotic glaucomatous optic disc damage needs further investigation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu; Patel, Kinal J., E-mail: kinalv5@gmail.com; Shen, Jianliang, E-mail: jianliangs@gmail.com

Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of themore » lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.« less

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia

PubMed Central

Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom

2016-01-01

Objective Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. Design We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. Results We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. Conclusions This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut–lung axis in bacterial infections. PMID:26511795

Investigation of alveolar tissue deformations using OCT combined with fluorescence microscopy

NASA Astrophysics Data System (ADS)

Gaertner, Maria; Cimalla, Peter; Knels, Lilla; Meissner, Sven; Schnabel, Christian; Kuebler, Wolfgang M.; Koch, Edmund

2011-06-01

In critical care medicine, artificial ventilation is a life saving tool providing sufficient blood oxygenation to patients suffering from respiratory failure. Essential for their survival is the use of protective ventilation strategies to prevent further lung damage due to ventilator induced lung injury (VILI). Since there is only little known about implications of lung tissue overdistension on the alveolar level, especially in the case of diseased lungs, this research deals with the investigation of lung tissue deformation on a microscale. A combined setup utilizing optical coherence tomography (OCT) and confocal fluorescence microscopy, is used to study the elastic behavior of the alveolar tissue. Three-dimensional geometrical information with voxel sizes of 6 μm × 6 μm × 11 μm (in air) is provided by OCT, structural information about localization of elastin fibers is elucidated via confocal fluorescence microscopy with a lateral resolution of around 1 μm. Imaging depths of 90 μm for OCT and 20 μm for confocal fluorescence microscopy were obtained. Dynamic studies of subpleural tissue were carried out on the basis of an in vivo mouse model post mortem, mimicking the physiological environment of an intact thorax and facilitating a window for the application of optical methods. Morphological changes were recorded by applying constant positive airway pressures of different values. With this, alveolar volume changes could clearly be recognized and quantified to form a compliance value of 3.5 • 10-6(see manuscript). The distribution of elastin fibers was detected and will be subject to further elasticity analysis.

Serum antibody-negative Goodpasture syndrome with delta granule pool storage deficiency and eosinophilia

PubMed Central

Kussman, Ashleigh; Gohara, Amira

2012-01-01

Goodpasture syndrome is a rare, life-threatening autoimmune disease characterized by a triad of rapidly progressive glomerulonephritis, a hemorrhagic pulmonary condition and the presence of anti-glomerular basement membrane (anti-GBM) antibodies. The antibodies initiate destruction of the kidney glomeruli, resulting in a focal necrotizing glomerulitis, which may progress rapidly to renal failure. Autoantibody-mediated damage of alveolar basement membranes leads to diffuse pulmonary hemorrhage, which in some cases may be severe enough to cause respiratory failure. Many clinicians use a variety of assays to detect serum anti-GBM antibodies; however, these tests may be falsely negative in up to 15% of patients with Goodpasture syndrome. Here, we report an unusual case of a 40-year-old man with clinical evidence of Goodpasture syndrome, a negative anti-GBM antibody serum result, eosinophilia and delta granule pool storage deficiency. After a 14-day hospital stay and extensive workup, as well as treatment with antibiotics, steroids and ventilator support for respiratory failure, the patient continued to deteriorate and entered multisystem organ failure. The family decided to withdraw ventilator support, and the patient expired. Immunofluorescence testing for anti-GBM autoantibodies on lung and kidney tissues during an autopsy confirmed the diagnosis of Goodpasture syndrome. PMID:26069804

Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

PubMed Central

Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

2013-01-01

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

Extracorporeal Membrane Oxygenation for Refractory Severe Respiratory Failure in Acute Interstitial Pneumonia.

PubMed

Gonçalves-Venade, Gabriela; Lacerda-Príncipe, Nuno; Roncon-Albuquerque, Roberto; Paiva, José Artur

2018-05-01

Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease with rapid progressive respiratory failure and high mortality. In the present report, three cases of AIP complicated by refractory respiratory failure supported with extracorporeal membrane oxygenation (ECMO) are presented. One male and two female patients (ages 27-59) were included. Venovenous ECMO support was provided using miniaturized systems, with two-site femoro-jugular circuit configuration. Despite lung protective ventilation, prone position and neuromuscular blockade, refractory respiratory failure of unknown etiology supervened (ratio of arterial oxygen partial pressure to fractional inspired oxygen 46-130) and ECMO was initiated after 3-7 days of mechanical ventilation. AIP diagnosis was established after exclusion of infectious and noninfectious acute respiratory distress syndrome on the basis of clinical and analytical data, bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical lung biopsy revealing diffuse alveolar damage of unknown etiology. Immunosuppressive treatment consisted in high-dose corticosteroids and cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO allowed AIP diagnosis and treatment in the presence of refractory respiratory failure, therefore reducing ventilator-induced lung injury and bridging lung recovery in two patients. ECMO referral should be considered in refractory respiratory failure if AIP is suspected. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Lycium barbarum polysaccharide protects against LPS-induced ARDS by inhibiting apoptosis, oxidative stress, and inflammation in pulmonary endothelial cells.

PubMed

Chen, Lan; Li, Wen; Qi, Di; Wang, Daoxin

2018-04-01

Acute respiratory distress syndrome (ARDS) is a heterogenous syndrome characterised by diffuse alveolar damage, with an increase in lung endothelial and epithelial permeability. Lycium barbarum polysaccharide (LBP), the most biologically active fraction of wolfberry, possesses antiapoptotic and antioxidative effects in distinct situations. In the present study, the protective effects and potential molecular mechanisms of LBP against lipopolysaccharide (LPS)-induced ARDS were investigated in the mice and in the human pulmonary microvascular endothelial cells (HPMECs). The data indicated that pretreatment with LBP significantly attenuated LPS-induced lung inflammation and pulmonary oedema in vivo. LBP significantly reversed LPS-induced decrease in cell viability, increase in apoptosis and oxidative stress via inhibiting caspase-3 activation and intracellular reactive oxygen species (ROS) production in vitro. Moreover, the scratch assay verified that LBP restored the dysfunction of endothelial cells (ECs) migration induced by LPS stimulation. Furthermore, LBP also significantly suppressed LPS-induced NF-κB activation, and subsequently reversed the release of cytochrome c. These results showed the antiapoptosis and antioxidant LBP could partially protect against LPS-induced ARDS through promoting the ECs survival and scavenging ROS via inhibition of NF-κB signalling pathway. Thus, LBP could be potentially used for ARDS against pulmonary inflammation and pulmonary oedema.

Inhibition of the alveolar macrophage oxidative burst by a diffusible component from the surface of the spores of the fungus Aspergillus fumigatus.

PubMed Central

Slight, J.; Nicholson, W. J.; Mitchell, C. G.; Pouilly, N.; Beswick, P. H.; Seaton, A.; Donaldson, K.

1996-01-01

BACKGROUND: Aspergillus fumigatus is a fungus that grows on dead and decaying organic matter in the environment and whose spores are present ubiquitously in the air. The fungus causes a range of diseases in the human lung. A study was undertaken to demonstrate and partially characterise an inhibitor of the macrophage respiratory burst from the surface of A fumigatus spores that could be an important factor in allowing the fungus to colonise the lung. METHODS: The spore-derived inhibitor of the respiratory burst of rat alveolar macrophages, as measured by generation of superoxide anion, was demonstrated in Hank's balanced salt solution extracts of four clinical isolates and an environmental isolate of A fumigatus. The time course of the release of the inhibitor into aqueous solution was assessed and the cytotoxic potential of the spore-derived inhibitor towards macrophages was tested using the propidium iodide method. An oxygen electrode was used to confirm the superoxide anion measurements. Molecular weight cutoff filters were used to determine the size of the inhibitor as assessed in the respiratory burst assay and also by its ability to inhibit macrophage spreading on glass. The crude diffusate from the spore surface was fractionated by reversed phase high pressure liquid chromatography (HPLC) and the fractions analysed for inhibitory activity, protein, and carbohydrate content. RESULTS: A small molecular weight (< 10 kD) heat stable toxin was released from the spores of clinical and environmental isolates of A fumigatus within minutes of deposition in aqueous solution. The key effect of the toxin demonstrated here was its ability to inhibit the oxidative burst of macrophages as measured by superoxide anion release. The inhibition was not due to cell death or detectable loss of membrane integrity as measured by permeability to propidium iodide. The toxin was not a scavenger of superoxide anion. Oxygen electrode studies suggested indirectly that the inhibitor acted to inhibit the assembly of the macrophage NADPH-oxidase complex. Fractions of < 10 kD also inhibited the spreading of alveolar macrophages, confirming that the toxin had an additional effect on macrophages that leads to loss of adherence or impairment of cytoskeletal function. In reversed phase HPLC fractions the inhibitory activity eluted with an associated carbohydrate, although the exact chemical nature of the toxin remains to be elucidated. CONCLUSIONS: This spore toxin may, through its ability to diffuse rapidly into lung lining fluid, diminish the macrophage respiratory burst and play a part in allowing A fumigatus to persist in the lung and manifest its well known pathogenic effects. Future research will be focused on further molecular characterisation of the toxin and elaboration of the effect of the toxin on intracellular signalling pathways involved in the activation of alveolar macrophages. PMID:8733491

Divergent Mitochondrial Antioxidant Activities and Lung Alveolar Architecture in the Lungs of Rats and Mice at High Altitude.

PubMed

Jochmans-Lemoine, Alexandra; Revollo, Susana; Villalpando, Gabriella; Valverde, Ibana; Gonzales, Marcelino; Laouafa, Sofien; Soliz, Jorge; Joseph, Vincent

2018-01-01

Compared with mice, adult rats living at 3,600 m above sea level (SL-La Paz, Bolivia) have high hematocrit, signs of pulmonary hypertension, and low lung volume with reduced alveolar surface area. This phenotype is associated with chronic mountain sickness in humans living at high altitude (HA). We tested the hypothesis that this phenotype is associated with impaired gas exchange and oxidative stress in the lungs. We used rats and mice (3 months old) living at HA (La Paz) and SL (Quebec City, Canada) to measure arterial oxygen saturation under graded levels of hypoxia (by pulse oximetry), the alveolar surface area in lung slices and the activity of pro- (NADPH and xanthine oxidases-NOX and XO) and anti- (superoxide dismutase, and glutathione peroxidase-SOD and GPx) oxidant enzymes in cytosolic and mitochondrial lung protein extracts. HA rats have a lower arterial oxygen saturation and reduced alveolar surface area compared to HA mice and SL rats. Enzymatic activities (NOX, XO, SOD, and GPx) in the cytosol were similar between HA and SL animals, but SOD and GPx activities in the mitochondria were 2-3 times higher in HA vs. SL rats, and only marginally higher in HA mice vs. SL mice. Furthermore, the maximum activity of cytochrome oxidase-c (COX) measured in mitochondrial lung extracts was also 2 times higher in HA rats compared with SL rats, while there was only a small increase in HA mice vs. SL mice. Interestingly, compared with SL controls, alterations in lung morphology are not observed for young rats at HA (15 days after birth), and enzymatic activities are only slightly altered. These results suggest that rats living at HA have a gradual reduction of their alveolar surface area beyond the postnatal period. We can speculate that the elevation of SOD, GPx, and COX activities in the lung mitochondria are not sufficient to compensate for oxidative stress, leading to damage of the lung tissue in rats.

Divergent Mitochondrial Antioxidant Activities and Lung Alveolar Architecture in the Lungs of Rats and Mice at High Altitude

PubMed Central

Jochmans-Lemoine, Alexandra; Revollo, Susana; Villalpando, Gabriella; Valverde, Ibana; Gonzales, Marcelino; Laouafa, Sofien; Soliz, Jorge; Joseph, Vincent

2018-01-01

Compared with mice, adult rats living at 3,600 m above sea level (SL—La Paz, Bolivia) have high hematocrit, signs of pulmonary hypertension, and low lung volume with reduced alveolar surface area. This phenotype is associated with chronic mountain sickness in humans living at high altitude (HA). We tested the hypothesis that this phenotype is associated with impaired gas exchange and oxidative stress in the lungs. We used rats and mice (3 months old) living at HA (La Paz) and SL (Quebec City, Canada) to measure arterial oxygen saturation under graded levels of hypoxia (by pulse oximetry), the alveolar surface area in lung slices and the activity of pro- (NADPH and xanthine oxidases—NOX and XO) and anti- (superoxide dismutase, and glutathione peroxidase—SOD and GPx) oxidant enzymes in cytosolic and mitochondrial lung protein extracts. HA rats have a lower arterial oxygen saturation and reduced alveolar surface area compared to HA mice and SL rats. Enzymatic activities (NOX, XO, SOD, and GPx) in the cytosol were similar between HA and SL animals, but SOD and GPx activities in the mitochondria were 2–3 times higher in HA vs. SL rats, and only marginally higher in HA mice vs. SL mice. Furthermore, the maximum activity of cytochrome oxidase-c (COX) measured in mitochondrial lung extracts was also 2 times higher in HA rats compared with SL rats, while there was only a small increase in HA mice vs. SL mice. Interestingly, compared with SL controls, alterations in lung morphology are not observed for young rats at HA (15 days after birth), and enzymatic activities are only slightly altered. These results suggest that rats living at HA have a gradual reduction of their alveolar surface area beyond the postnatal period. We can speculate that the elevation of SOD, GPx, and COX activities in the lung mitochondria are not sufficient to compensate for oxidative stress, leading to damage of the lung tissue in rats. PMID:29670534

Dynamics of the DNA repair proteins WRN and BLM in the nucleoplasm and nucleoli.

PubMed

Bendtsen, Kristian Moss; Jensen, Martin Borch; May, Alfred; Rasmussen, Lene Juel; Trusina, Ala; Bohr, Vilhelm A; Jensen, Mogens H

2014-11-01

We have investigated the mobility of two EGFP-tagged DNA repair proteins, WRN and BLM. In particular, we focused on the dynamics in two locations, the nucleoli and the nucleoplasm. We found that both WRN and BLM use a "DNA-scanning" mechanism, with rapid binding-unbinding to DNA resulting in effective diffusion. In the nucleoplasm WRN and BLM have effective diffusion coefficients of 1.62 and 1.34 μm(2)/s, respectively. Likewise, the dynamics in the nucleoli are also best described by effective diffusion, but with diffusion coefficients a factor of ten lower than in the nucleoplasm. From this large reduction in diffusion coefficient we were able to classify WRN and BLM as DNA damage scanners. In addition to WRN and BLM we also classified other DNA damage proteins and found they all fall into one of two categories. Either they are scanners, similar to WRN and BLM, with very low diffusion coefficients, suggesting a scanning mechanism, or they are almost freely diffusing, suggesting that they interact with DNA only after initiation of a DNA damage response.

The fraction of NO in exhaled air and estimates of alveolar NO in adolescents with asthma: methodological aspects.

PubMed

Heijkenskjöld-Rentzhog, Charlotte; Alving, Kjell; Kalm-Stephens, Pia; Lundberg, Jon O; Nordvall, Lennart; Malinovschi, Andrei

2012-10-01

This study investigated the oral contribution to exhaled NO in young people with asthma and its potential effects on estimated alveolar NO (Calv(NO) ), a proposed marker of inflammation in peripheral airways. Secondary aims were to investigate the effects of various exhalation flow-rates and the feasibility of different proposed adjustments of (Calv(NO) ) for trumpet model and axial diffusion (TMAD). Exhaled NO at flow rates of 50-300 ml/sec, and salivary nitrite was measured before and after antibacterial mouthwash in 29 healthy young people (10-20 years) and 29 with asthma (10-19 years). Calv(NO) was calculated using the slope-intercept model with and without TMAD adjustment. Exhaled NO at 50 ml/sec decreased significantly after mouthwash, to a similar degree in asthmatic and healthy subjects (8.8% vs. 9.8%, P = 0.49). The two groups had similar salivary nitrite levels (56.4 vs. 78.4 µM, P = 0.25). Calv(NO) was not significantly decreased by mouthwash. Calv(NO) levels were similar when flow-rates between 50-200 or 100-300 ml/sec were used (P = 0.34 in asthmatics and P = 0.90 in healthy subjects). A positive association was found between bronchial and alveolar NO in asthmatic subjects and this disappeared after the TMAD-adjustment. Negative TMAD-adjusted Calv(NO) values were found in a minority of the subjects. Young people with and without asthma have similar salivary nitrite levels and oral contributions to exhaled NO and therefore no antibacterial mouthwash is necessary in routine use. TMAD corrections of alveolar NO could be successfully applied in young people with asthma and yielded negative results only in a minority of subjects. Copyright © 2012 Wiley Periodicals, Inc.

Pulmonary NO and C18O2 uptake during pressure-induced lung expansion in rabbits.

PubMed

Heller, Hartmut; Schuster, Klaus-Dieter

2007-01-01

In artificially ventilated animals we investigated the dependence of the pulmonary diffusing capacities of nitric oxide (NO) and doubly 18O-labeled carbon dioxide (DLNO, DLC18O2) on lung expansion with respect to ventilator-driven increases in intrapulmonary pressure. For this purpose we applied computerized single-breath experiments to 11 anesthetized paralyzed rabbits (weight 2.8-3.8 kg) at various alveolar volumes (45-72 ml) by studying the almost entire inspiratory limb of the respective pressure/volume curves (intrapulmonary pressure: 6-27 cmH2O). The animals were ventilated with room air, employing a computerized ventilatory servo-system that we designed to maintain mechanical ventilation and to execute the particular lung function tests automatically. Each single-breath maneuver was started from residual volume (13.5+/-2 ml, mean+/-SD) by inflating the rabbit lungs with 35-55 ml indicator gas mixture containing 0.05% NO in N2 or 0.9% C18O2 in N2. Alveolar partial pressures of NO and C18O2 were measured by respiratory mass spectrometry. Values of DLNO and DLC18O2 ranged between 1.55 and 2.49 ml/(mmHg min) and 11.7 and 16.6 ml/(mmHg min), respectively. Linear regression analyses yielded a significant increase in DLNO with simultaneous increase in alveolar volume (P<0.005) and intrapulmonary pressure (P<0.023) whereas DLC18O2 was not improved. Our results suggest that the ventilator-driven lung expansion impaired the C18O2 blood uptake conductance, finally compensating for the beneficial effect of the increase in alveolar volume on DLC18O2 values.

Mitigating effects of captopril and losartan on lung histopathology in a rat model of fat embolism.

PubMed

McIff, Terence E; Poisner, Alan M; Herndon, Betty; Lankachandra, Kamani; Molteni, Agostino; Adler, Federico

2011-05-01

Fat embolization (FE) is an often overlooked and poorly understood complication of skeletal trauma and some orthopedic procedures. Fat embolism can lead to major pulmonary damage associated with fat embolism syndrome (FES). A model of FE in unanesthetized rats, using intravenous injection of the neutral fat triolein, was used to study the potential therapeutic effect on lung histopathology of altering the production of, or response to, endogenous angiotensin (Ang) II. Either captopril, an Ang I converting enzyme inhibitor, or losartan, an Ang II type 1 receptor blocker, was injected 1 hour after FE by triolein injection. After euthanasia at 48 hours, histopathologic evaluation was used to compare the drug-treated animals with control animals that received only triolein. Histology of the lungs of rats treated only with triolein revealed severe, diffuse pathology. Alveolar septa showed severe, diffuse inflammation. Bronchial lumina showed severe mucosal epithelial loss. The media of the pulmonary small arteries and arterioles was thicker, and the lumen patency was reduced 60% to 70%. Trichrome staining confirmed the abundant presence of collagen in the media and adventitia, as well as collagen infiltrating the bronchial musculature. Both captopril and losartan treatments reduced the inflammatory, vasoconstrictor, and profibrotic effects present at 48 hours (p<0.001). With treatment, the vascular lumen remained patent, and the fat droplets were reduced in size and number. There was a reduction in the number of infiltrating leukocytes, macrophages, myofibroblasts, and eosinophils, along with a significant decrease in hemorrhage and collagen deposition (p<0.001). Pathologic changes in bronchial epithelium were also diminished. The results suggest that the use of drugs that act on the renin-Ang system might provide an effective and targeted therapy for fat embolism syndrome.

Complete suppression of boron transient-enhanced diffusion and oxidation-enhanced diffusion in silicon using localized substitutional carbon incorporation

NASA Astrophysics Data System (ADS)

Carroll, M. S.; Chang, C.-L.; Sturm, J. C.; Büyüklimanli, T.

1998-12-01

In this letter, we show the ability, through introduction of a thin Si1-x-yGexCy layer, to eliminate the enhancement of enhanced boron diffusion in silicon due to an oxidizing surface or ion implant damage. This reduction of diffusion is accomplished through a low-temperature-grown thin epitaxial Si1-x-yGexCy layer which completely filters out excess interstitials introduced by oxidation or ion implant damage. We also quantify the oxidation-enhanced diffusion (OED) and transient-enhanced diffusion (TED) dependence on substitutional carbon level, and further report both the observation of carbon TED and OED, and its dependence on carbon levels.

The prognostic value of panoramic radiography of inferior alveolar nerve damage after mandibular third molar removal: retrospective study of 400 cases.

PubMed

Szalma, József; Lempel, Edina; Jeges, Sára; Szabó, Gyula; Olasz, Lajos

2010-02-01

The aim of the study was to estimate the accuracy of panoramic radiographic signs predicting inferior alveolar nerve (IAN) paresthesia after lower third molar removal. In a case-control study the sample was composed of 41 cases with postoperative IAN paresthesia and 359 control cases without it. The collected data included "classic" specific signs indicating a close spatial relationship between third molar root and inferior alveolar canal (IAC), root curvatures, and the extent of IAC-root tip overlap. Bivariate and multivariate logistic regression analyses were completed to estimate the association between radiographic findings and IAN paresthesia. The multivariate logistic analysis identified 3 signs significantly associated with IAN paresthesia (P < .001): interruption of the superior cortex of the canal wall, diversion of the canal, and darkening of the root. The sensitivities and specificities ranged from 14.6% to 68.3% and from 85.5% to 96.9%, respectively. The positive predictive values, calculated to factor a 1.1% prevalence of paresthesia, ranged from 3.6% to 10.9%, whereas the negative predictive values >99%. Panoramic radiography is an inadequate screening method for predicting IAN paresthesia after mandibular third molar removal. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Welding fume exposure and associated inflammatory and hyperplastic changes in the lungs of tumor susceptible a/j mice.

PubMed

Solano-Lopez, Claudia; Zeidler-Erdely, Patti C; Hubbs, Ann F; Reynolds, Steven H; Roberts, Jenny R; Taylor, Michael D; Young, Shih-Houng; Castranova, Vincent; Antonini, James M

2006-01-01

It has been suggested that welding fume (WF) exposure increases lung cancer risk in welders. Epidemiology studies have failed to conclude that WF alone causes lung cancer and animal studies are lacking. We examined the course of inflammation, damage, and repair in the lungs of A/J mice, a lung tumor susceptible strain, caused by stainless steel WF. Mice were exposed by pharyngeal aspiration to 40 mg/kg of WF, silica, or saline. Bronchoalveolar lavage (BAL) was performed 24 hours, 1 and 16 weeks to assess lung injury and inflammation and histopathology was done 1, 8, 16, 24, and 48 weeks postexposure. Both exposures increased inflammatory cells, lactate dehydrogenase and albumin at 24 hr and 1 week. At 16 weeks, these parameters remained elevated in silica-exposed but not WF-exposed mice. Histopathologic evaluation at 1 week indicated that WF induced bronchiolar epithelial hyperplasia with associated cellular atypia, alveolar bronchiolo-alveolar hyperplasia (BAH) in peribronchiolar alveoli, and peribronchiolar lymphogranulomatous inflammation. Persistent changes included foci of histiocytic inflammation, fibrosis, atypical bronchiolar epithelial cells, and bronchiolar BAH. The principle changes in silica-exposed mice were histiocytic and suppurative inflammation, fibrosis, and alveolar BAH. Our findings that WF causes persistent bronchiolar and peribronchiolar epithelial changes, suggest a need for studies of bronchiolar changes after WF exposure.

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium.

PubMed

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-08-10

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage.

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium

PubMed Central

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-01-01

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage. PMID:26256764

Realising damage-tolerant nacre-inspired CFRP

NASA Astrophysics Data System (ADS)

Narducci, F.; Lee, K.-Y.; Pinho, S. T.

2018-07-01

In this work, a nacre-inspired Carbon Fibre Reinforced Polymer (CFRP) composite is designed, synthesised and tested. Analytical and numerical models are used to design a tiled micro-structure, mimicking the staggered arrangement of ceramic platelets in nacre and exploiting geometrical interlocks for crack deflection and damage diffusion. The designed pattern of tiles is then laser-engraved in the laminate plies. In order to increase the damage-spreading capability of the material, a thin layer of poly(lactic acid) (PLA) is film-cast on the interlaminar region, both as a continuous film and as a pattern of fractal-shaped patches. Three-point bending tests show how the nacre-like micro-structure succeeds in deflecting cracks, with damage diffusion being significantly improved by the addition of PLA at the interface between tiles. It is observed that a texture of discontinuous fractal-shaped PLA patches can increase damage diffusion, by promoting the unlocking of tiles whilst preserving the interface strength.

A conservative management of iatrogenically damaged distal root of the mandibular second molar.

PubMed

Bansal, Rashmi; Roy, Sonali; Chandra, Praveen; Gurtu, Anuraag; Pandey, Rahul

2017-01-01

Trauma to the adjacent hard and soft tissue is the most common iatrogenic injury during extraction of the mandibular third molar. As every functional component of the dental arch is of prime importance in contemporary dental practice, the major concern must be in conserving the tooth and its structure as much as possible. The present case discusses the application of this conservative approach for management of iatrogenically damaged distal root of the mandibular second molar during extraction of impacted third molar, in which excessive guttering of alveolar bone and fractured apical third of distal root of 37 was observed radiographically. A conservative and noninvasive approach was successfully achieved to restore the damaged root by the bioactive material. Sealing of the remaining root with mineral trioxide aggregate allowed regeneration of soft and hard tissue around it.

The multiple roles of small-angle tilt grain boundaries in annihilating radiation damage in SiC

DOE PAGES

Jiang, Hao; Wang, Xing; Szlufarska, Izabela

2017-02-09

Lattice defects generated by radiation damage can diffuse to grain boundaries (GBs) and be annihilated at GBs. However, the precise role of GBs in annihilating the segregated defects remains unclear. Here, we employed multi-scale models to determine how interstitials are annihilated at small-angle tilt GBs (STGBs) in SiC. First of all, we found the pipe diffusion of interstitials in STGBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, we found both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled andmore » can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of STGBs in annihilating radiation damage. This model includes defect flux to GBs, pipe diffusion in STGBs, and the interaction of defects with jogs. The model predicts the role of STGBs in annihilating defects depends on the rate of defects segregation to and diffusion along STGBs. STGBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. As a result, when defect diffusivity is low, most of the defects segregated to STGBs are annihilated by dislocation climb.« less

The multiple roles of small-angle tilt grain boundaries in annihilating radiation damage in SiC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Hao; Wang, Xing; Szlufarska, Izabela

Lattice defects generated by radiation damage can diffuse to grain boundaries (GBs) and be annihilated at GBs. However, the precise role of GBs in annihilating the segregated defects remains unclear. Here, we employed multi-scale models to determine how interstitials are annihilated at small-angle tilt GBs (STGBs) in SiC. First of all, we found the pipe diffusion of interstitials in STGBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, we found both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled andmore » can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of STGBs in annihilating radiation damage. This model includes defect flux to GBs, pipe diffusion in STGBs, and the interaction of defects with jogs. The model predicts the role of STGBs in annihilating defects depends on the rate of defects segregation to and diffusion along STGBs. STGBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. As a result, when defect diffusivity is low, most of the defects segregated to STGBs are annihilated by dislocation climb.« less

Use of Aminocaproic Acid in Combination With Extracorporeal Membrane Oxygenation in a Case of Leptospirosis Pulmonary Hemorrhage Syndrome.

PubMed

Pardinas, Miguel; Mendirichaga, Rodrigo; Budhrani, Gaurav; Garg, Rajan; Rosario, Luis; Rico, Rene; Panos, Anthony; Baier, Horst; Krick, Stefanie

2017-01-01

A 32-year-old man presented with a 10-day history of fever, chills, nausea, vomiting, myalgia, nonproductive cough, and worsening dyspnea after freshwater swimming in the Caribbean 1 week prior to presentation. Shortly after arrival at the hospital, the patient developed severe respiratory distress with massive hemoptysis. Based on serologic workup, he was diagnosed with leptospirosis pulmonary hemorrhage syndrome leading to diffuse alveolar hemorrhage, severe hypoxemic respiratory failure, and multiorgan failure. He received appropriate antibiotic coverage along with hemodynamic support with norepinephrine and vasopressin, mechanical ventilation, and renal replacement therapy in an intensive care unit. Introduction of extracorporeal membrane oxygenation was initiated to provide lung-protective ventilation supporting the recovery of his pulmonary function. Aminocaproic acid was used to stop and prevent further alveolar hemorrhage. He fully recovered thereafter; however, it is uncertain whether it was the use of aminocaproic acid that led to the resolution of his disease.

Use of Aminocaproic Acid in Combination With Extracorporeal Membrane Oxygenation in a Case of Leptospirosis Pulmonary Hemorrhage Syndrome

PubMed Central

Pardinas, Miguel; Mendirichaga, Rodrigo; Budhrani, Gaurav; Garg, Rajan; Rosario, Luis; Rico, Rene; Panos, Anthony; Baier, Horst; Krick, Stefanie

2017-01-01

A 32-year-old man presented with a 10-day history of fever, chills, nausea, vomiting, myalgia, nonproductive cough, and worsening dyspnea after freshwater swimming in the Caribbean 1 week prior to presentation. Shortly after arrival at the hospital, the patient developed severe respiratory distress with massive hemoptysis. Based on serologic workup, he was diagnosed with leptospirosis pulmonary hemorrhage syndrome leading to diffuse alveolar hemorrhage, severe hypoxemic respiratory failure, and multiorgan failure. He received appropriate antibiotic coverage along with hemodynamic support with norepinephrine and vasopressin, mechanical ventilation, and renal replacement therapy in an intensive care unit. Introduction of extracorporeal membrane oxygenation was initiated to provide lung-protective ventilation supporting the recovery of his pulmonary function. Aminocaproic acid was used to stop and prevent further alveolar hemorrhage. He fully recovered thereafter; however, it is uncertain whether it was the use of aminocaproic acid that led to the resolution of his disease. PMID:28469503

The lung in amyloidosis.

PubMed

Milani, Paolo; Basset, Marco; Russo, Francesca; Foli, Andrea; Palladini, Giovanni; Merlini, Giampaolo

2017-09-30

Amyloidosis is a disorder caused by misfolding of autologous protein and its extracellular deposition as fibrils, resulting in vital organ dysfunction and eventually death. Pulmonary amyloidosis may be localised or part of systemic amyloidosis.Pulmonary interstitial amyloidosis is symptomatic only if the amyloid deposits severely affect gas exchange alveolar structure, thus resulting in serious respiratory impairment. Localised parenchymal involvement may be present as nodular amyloidosis or as amyloid deposits associated with localised lymphomas. Finally, tracheobronchial amyloidosis, which is usually not associated with evident clonal proliferation, may result in airway stenosis.Because the treatment options for amyloidosis are dependent on the fibril protein type, the workup of all new cases should include accurate determination of the amyloid protein. Most cases are asymptomatic and need only a careful follow-up. Diffuse alveolar-septal amyloidosis is treated according to the underlying systemic amyloidosis. Nodular pulmonary amyloidosis is usually localised, conservative excision is usually curative and the long-term prognosis is excellent. Tracheobronchial amyloidosis is usually treated with bronchoscopic interventions or external beam radiation therapy. Copyright ©ERS 2017.

Influenza Virus A/Anhui/1/2013 (H7N9) Replicates Efficiently in the Upper and Lower Respiratory Tracts of Cynomolgus Macaques

PubMed Central

de Wit, Emmie; Rasmussen, Angela L.; Feldmann, Friederike; Bushmaker, Trenton; Martellaro, Cynthia; Haddock, Elaine; Okumura, Atsushi; Proll, Sean C.; Chang, Jean; Gardner, Don; Katze, Michael G.

2014-01-01

ABSTRACT In March 2013, three fatal human cases of infection with influenza A virus (H7N9) were reported in China. Since then, human cases have been accumulating. Given the public health importance of this virus, we performed a pathogenicity study of the H7N9 virus in the cynomolgus macaque model, focusing on clinical aspects of disease, radiographic, histological, and gene expression profile changes in the upper and lower respiratory tracts, and changes in systemic cytokine and chemokine profiles during infection. Cynomolgus macaques developed transient, mild to severe disease with radiographic evidence of pulmonary infiltration. Virus replicated in the upper as well as lower respiratory tract, with sustained replication in the upper respiratory tract until the end of the experiment at 6 days after inoculation. Virus shedding occurred mainly via the throat. Histopathological changes in the lungs were similar to those observed in humans, albeit less severe, with diffuse alveolar damage, infiltration of polymorphonuclear cells, formation of hyaline membranes, pneumocyte hyperplasia, and fibroproliferative changes. Analysis of gene expression profiles in lung lesions identified pathways involved in tissue damage during H7N9 infection as well as leads for development of therapeutics targeting host responses rather than virus replication. Overall, H7N9 infection was not as severe in cynomolgus macaques as in humans, supporting the possible role of underlying medical complications in disease severity as discussed for human H7N9 infection (H. N. Gao et al., N. Engl. J. Med. 368:2277–2285, 2013, doi:10.1056/NEJMoa1305584). PMID:25118237

Reference values for pulmonary diffusing capacity for adult native Finns.

PubMed

Kainu, Annette; Toikka, Jyri; Vanninen, Esko; Timonen, Kirsi L

2017-04-01

Measurement standards for pulmonary diffusing capacity were updated in 2005 by the ATS/ERS Task Force. However, in Finland reference values published in 1982 by Viljanen et al. have been used to date. The main aim of this study was to produce updated reference models for single-breath diffusing capacity for carbon monoxide for Finnish adults. Single-breath diffusing capacity for carbon monoxide was measured in 631 healthy non-smoking volunteers (41.5% male). Reference values for diffusing capacity (DLCO), alveolar volume (VA), diffusing capacity per unit of lung volume (DLCO/VA), and lung volumes were calculated using a linear regression model. Previously used Finnish reference values were found to produce too low predicted values, with mean predicted DLCO 111.0 and 104.4%, and DLCO/VA of 103.5 and 102.7% in males and females, respectively. With the European Coalition for Steel and Coal (ECSC) reference values there was a significant sex difference in DLCO/VA with mean predicted 105.4% in males and 92.8% in females (p < .001). New reference values for DLCO, DLCO/VA, VA, vital capacity (VC), inspiratory vital capacity (IVC), and inspiratory capacity (IC) are suggested for clinical use to replace technically outdated reference values for clinical applications.

Lung Morphometry with Hyperpolarized 129Xe: Theoretical Background

PubMed Central

Sukstanskii, A.L.; Yablonskiy, D.A.

2011-01-01

The 3He lung morphometry technique, based on MRI measurements of hyperpolarized 3He gas diffusion in lung airspaces, provides unique information on the lung microstructure at the alveolar level. In vivo 3D tomographic images of standard morphological parameters (airspace chord length, lung parenchyma surface-to-volume ratio, number of alveoli per unit volume) can be generated from a rather short (several seconds) MRI scan. The technique is based on a theory of gas diffusion in lung acinar airways and experimental measurements of diffusion attenuated MRI signal. The present work aims at developing the theoretical background of a similar technique based on hyperpolarized 129Xe gas. As the diffusion coefficient and gyromagnetic ratio of 129Xe gas are substantially different from those of 3He gas, the specific details of the theory and experimental measurements with 129Xe should be amended. We establish phenomenological relationships between acinar airway geometrical parameters and the diffusion attenuated MR signal for human and small animal lungs, both normal lungs and lungs with mild emphysema. Optimal diffusion times are shown to be about 5 ms for human and 1.3 ms for small animals. The expected uncertainties in measuring main morphometrical parameters of the lungs are estimated in the framework of Bayesian probability theory. PMID:21713985

Types of traumatic brain injury and regional cerebral blood flow assessed by 99mTc-HMPAO SPECT.

PubMed

Yamakami, I; Yamaura, A; Isobe, K

1993-01-01

To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethyl propyleneamine oxime. Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient.

Longitudinal diffusion tensor magnetic resonance imaging study of radiation-induced white matter damage in a rat model.

PubMed

Wang, Silun; Wu, Ed X; Qiu, Deqiang; Leung, Lucullus H T; Lau, Ho-Fai; Khong, Pek-Lan

2009-02-01

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia.

PubMed

Schuijt, Tim J; Lankelma, Jacqueline M; Scicluna, Brendon P; de Sousa e Melo, Felipe; Roelofs, Joris J T H; de Boer, J Daan; Hoogendijk, Arjan J; de Beer, Regina; de Vos, Alex; Belzer, Clara; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

2016-04-01

Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota supports local mucosal immunity and is increasingly recognised as an important modulator of the systemic immune system. The precise role of the gut microbiota in bacterial pneumonia, however, is unknown. Here, we investigate the function of the gut microbiota in the host defence against Streptococcus pneumoniae infections. We depleted the gut microbiota in C57BL/6 mice and subsequently infected them intranasally with S. pneumoniae. We then performed survival and faecal microbiota transplantation (FMT) experiments and measured parameters of inflammation and alveolar macrophage whole-genome responses. We found that the gut microbiota protects the host during pneumococcal pneumonia, as reflected by increased bacterial dissemination, inflammation, organ damage and mortality in microbiota-depleted mice compared with controls. FMT in gut microbiota-depleted mice led to a normalisation of pulmonary bacterial counts and tumour necrosis factor-α and interleukin-10 levels 6 h after pneumococcal infection. Whole-genome mapping of alveolar macrophages showed upregulation of metabolic pathways in the absence of a healthy gut microbiota. This upregulation correlated with an altered cellular responsiveness, reflected by a reduced responsiveness to lipopolysaccharide and lipoteichoic acid. Compared with controls, alveolar macrophages derived from gut microbiota-depleted mice showed a diminished capacity to phagocytose S. pneumoniae. This study identifies the intestinal microbiota as a protective mediator during pneumococcal pneumonia. The gut microbiota enhances primary alveolar macrophage function. Novel therapeutic strategies could exploit the gut-lung axis in bacterial infections. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Mild hypothermia for treatment of diffuse axonal injury: a quantitative analysis of diffusion tensor imaging

PubMed Central

Jing, Guojie; Yao, Xiaoteng; Li, Yiyi; Xie, Yituan; Li, Wang#x2019;an; Liu, Kejun; Jing, Yingchao; Li, Baisheng; Lv, Yifan; Ma, Baoxin

2014-01-01

Fractional anisotropy values in diffusion tensor imaging can quantitatively reflect the consistency of nerve fibers after brain damage, where higher values generally indicate less damage to nerve fibers. Therefore, we hypothesized that diffusion tensor imaging could be used to evaluate the effect of mild hypothermia on diffuse axonal injury. A total of 102 patients with diffuse axonal injury were randomly divided into two groups: normothermic and mild hypothermic treatment groups. Patient's modified Rankin scale scores 2 months after mild hypothermia were significantly lower than those for the normothermia group. The difference in average fractional anisotropy value for each region of interest before and after mild hypothermia was 1.32-1.36 times higher than the value in the normothermia group. Quantitative assessment of diffusion tensor imaging indicates that mild hypothermia therapy may be beneficial for patients with diffuse axonal injury. PMID:25206800

Quantification of lung microstructure with hyperpolarized 3He diffusion MRI

PubMed Central

Sukstanskii, Alexander L.; Woods, Jason C.; Gierada, David S.; Quirk, James D.; Hogg, James C.; Cooper, Joel D.; Conradi, Mark S.

2009-01-01

The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized 3He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii—parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials. PMID:19661452

Diffusion length variation and proton damage coefficients for InP/In(x)Ga(1-x)As/GaAs solar cells

NASA Technical Reports Server (NTRS)

Jain, R. K.; Weinberg, I.; Flood, D. J.

1993-01-01

Indium phosphide solar cells are more radiation resistant than gallium arsenide and silicon solar cells, and their growth by heteroepitaxy offers additional advantages leading to the development of lighter, mechanically strong and cost-effective cells. Changes in heteroepitaxial InP cell efficiency under 0.5 and 3 MeV proton irradiations are explained by the variation in the minority-carrier diffusion length. The base diffusion length versus proton fluence is calculated by simulating the cell performance. The diffusion length damage coefficient K(L) is plotted as a function of proton fluence.

Structural and Mechanical Repair of Diffuse Damage in Cortical Bone in vivo

PubMed Central

Seref-Ferlengez, Zeynep; Basta-Pljakic, Jelena; Kennedy, Oran D.; Philemon, Claudy J.; Schaffler, Mitchell B.

2014-01-01

Physiological wear and tear causes bone microdamage at several hierarchical levels, and these have different biological consequences. Bone remodeling is widely held to be the mechanism by which bone microdamage is repaired. However, recent studies showed that unlike typical linear microcracks, small crack damage, the clusters of submicron-sized matrix cracks also known as diffuse damage (Dif.Dx), does not activate remodeling. Thus, the fate of diffuse damage in vivo is not known. To examine this, we induced selectively Dif.Dx in rat ulnae in vivo by using end-load ulnar bending creep model. Changes in damage content were assessed by histomorphometry and mechanical testing immediately after loading (i.e., acute loaded) or at 14 days after damage induction (i.e., survival ulnae). Dif.Dx area was markedly reduced over the 14-day survival period after loading (p<0.02). We did not observe any intracortical resorption and there was no increase in cortical bone area in survival ulnae. The reduction in whole bone stiffness in acute loaded ulnae was restored to baseline levels in survival ulnae (p>0.6). Microindentation studies showed that Dif.Dx caused a highly localized reduction in elastic modulus in diffuse damage regions of the ulnar cortex. Moduli in these previously damaged bone areas were restored to control values by 14 days after loading. Our current findings indicate that small crack damage in bone can be repaired without bone remodeling, and suggest that alternative repair mechanisms exist in bone to deal with submicron-sized matrix cracks. Those mechanisms are currently unknown and further investigations are needed to elucidate the mechanisms by which this direct repair occurs. PMID:25042459

Clinical usefulness of free subcutaneous fat pad for reduction of intraoperative air leakage during thoracoscopic pulmonary resection in lung cancer cases.

PubMed

Shintani, Yasushi; Inoue, Masayoshi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Okumura, Meinoshin

2015-10-01

Intraoperative alveolar air leaks remain a significant problem in thoracoscopic surgery (TS) cases. We examined the usefulness of covering damaged lung tissue with a subcutaneous fat pad for preventing postoperative air leakage in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC underwent a thoracoscopic lobectomy or segmentectomy. When alveolar air leakage from the superficial pulmonary parenchyma was found, fibrin glue in combination with an absorbable mesh sheet was applied (S group; n = 100). When leakage originated from deep within the pulmonary parenchyma, a subcutaneous fat pad about 2 × 2 cm in size was harvested from the utility incision and placed on the damaged lung tissue with fibrin glue and sutures (F group; n = 66). Patient characteristics, air leak duration, and chest-tube removal time were analyzed. The homogeneity of each group was consistent, with no statistical differences for age, respiratory function, surgical procedures, pathologic stage, and histological type. The air leak duration was significantly shorter (p = 0.015), and the chest tube was removed significantly earlier (p = 0.002) in patients in the F group. Use of a free subcutaneous fat pad during pulmonary resection for TS patients with NSCLC reduced the duration of air leakage and chest tube drainage. The present method is easy, safe, and effective for repairing an air leak from remaining lung tissues in such cases.

Time-based understanding of DLCO and DLNO.

PubMed

Kang, Min-Yeong; Sapoval, Bernard

2016-05-01

Capture of CO and NO by blood requires molecules to travel by diffusion from alveolar gas to haemoglobin molecules inside RBCs and then to react. One can attach to these processes two times, a time for diffusion and a time for reaction. This reaction time is known from chemical kinetics and, therefore, constitutes a unique physical clock. This paper presents a time-based bottom-up theory that yields a simple expression for DLCO and DLNO that produces quantitative predictions which compare successfully with experiments. Specifically, when this new approach is applied to DLCO experiments, it can be used to determine the value of the characteristic diffusion time, and the value of capillary volume (Vc). The new theory also provides a simple explanation for still unexplained correlations such as the observed proportionality between the so-called membrane conductance DM and Vc of Roughton and Forster's interpretation. This new theory indicates that DLCO should be proportional to the haematocrit as found in several experiments. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN BULK TUNGSTEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.

2015-09-22

We used our recently developed lattice based OKMC code; KSOME [1] to carryout simulations of radiation damage in bulk W. We study the effect of dimensionality of self interstitial atom (SIA) diffusion i.e. 1D versus 3D on the defect accumulation during irradiation with a primary knock-on atom (PKA) energy of 100 keV at 300 K for the dose rates of 10-5 and 10-6 dpa/s. As expected 3D SIA diffusion significantly reduces damage accumulation due to increased probability of recombination events. In addition, dose rate, over the limited range examined here, appears to have no effect in both cases of SIAmore » diffusion.« less

Nerve damage assessment following implant placement in human cadaver jaws: an ex vivo comparative study.

PubMed

Murat, Sema; Kamburoğlu, Kıvanç; Kılıç, Cenk; Ozen, Tuncer; Gurbuz, Ayhan

2014-02-01

The present study compared the use of cone beam computerized tomography (CBCT) images and intra-oral radiographs in the placement of final implant drills in terms of nerve damage to cadaver mandibles. Twelve cadaver hemimandibles obtained from 6 cadavers were used. Right hemimandibles were imaged using peri-apical radiography and left hemimandibles using CBCT, and the images obtained were used in treatment planning for the placement of implant drills (22 for each modality, for a total of 44 final drills). Specimens were dissected, and the distances between the apex of the final implant drill and the inferior alveolar neurovascular bundle and incisive nerve were measured using a digital calliper. Nerves were assessed as damaged or not damaged, and the Chi-square test was used to compare nerve damage between modalities (P < 0.05). Nerve damage occurred with 7 final drills placed based on peri-apical radiography (31.8%) and 1 final drill placed using CBCT images (4.5%). The difference in nerve damage between imaging modalities was statistically significant (P = 0.023), with CBCT outperforming intraoral film in the placement of final implant drills ex vivo. In order to prevent nerve damage, CBCT is recommended as the principal imaging modality for pre-implant assessment.

Interplay between high energy impulse noise (blast) and antioxidants in the lung.

PubMed

Elsayed, Nabil M; Gorbunov, Nikolai V

2003-07-15

High-energy impulse noise (BLAST) is a physical event characterized by an abrupt rise in atmospheric pressure above ambient lasting for a very short period, but potentially causing significant material and biological damage. Exposure to high-level BLAST can be destructive and lethal. Low-level BLAST similar to what is encountered repeatedly by military personnel during training and combat from detonation of munitions and firing of large caliber weapons, and during occupational use of explosives and some heavy machinery, can also cause significant injury. Globally, civilians are increasingly exposed to BLAST resulting from terrorist bombings or abandoned unmarked mines following numerous wars and conflicts. We have shown previously in several animal models that exposure to non-lethal BLAST results in pathological changes, mostly to the hollow organs characterized in the lungs, the most sensitive organ, by rupture of alveolar septa, and pulmonary hemorrhage and edema. These events potentially can cause alveolar flooding, respiratory insufficiency and adult respiratory distress syndrome (ARDS), leading to varying degrees of hypoxia, antioxidant depletion and oxidative damage. We have also observed progressive formation of nitric oxide in blood and other tissues. The totality of these observations supports our general hypothesis that exposure to BLAST can lead to antioxidant depletion and oxidative damage. Understanding the mechanism(s) of BLAST-induced oxidative stress may have important implications that include a potential beneficial role for antioxidants as a prophylaxis or as secondary treatment of injury after exposure alongside other protective and therapeutic modalities. In addition, it suggests a role for endogenous nitric oxide in the injury. This report reviews experimental evidence of BLAST-induced antioxidant depletion, and the potential benefit from antioxidant supplementation before exposure.

The Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain-Containing 3 Inflammasome Regulates Bronchial Epithelial Cell Injury and Proapoptosis after Exposure to Biomass Fuel Smoke.

PubMed

Li, Chen; Zhihong, Huang; Wenlong, Li; Xiaoyan, Liu; Qing, Chen; Wenzhi, Luo; Siming, Xie; Shengming, Liu

2016-12-01

The number of individuals in the population exposed to biomass fuel smoke (BS) is far greater than the number of cigarette smokers. About 20% of cigarette smokers develop chronic obstructive pulmonary disease (COPD) due to smoke-induced irreversible damage and sustained inflammation of the airway epithelium. However, the role of BS in COPD pathogenesis remains to be elucidated. In this study, we investigated the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 and caspase-1 in the bronchial epithelium from patients with COPD, and further determined the specific role of the NLRP3 inflammasome in bronchial epithelium injury using two in vitro models (BS and cigarette smoke [CS]) in the human bronchial epithelial (HBE) cell line (16HBE). After exposure to BS and CS, the release of damage-associated molecular patterns, the transcriptional and translational up-regulation of NLRP3, and the activation of caspase-1 were observed in cells at different time points. Because IL-1β secretion was dependent on the NLRP3 inflammasome, we assessed CXCL-8 production in response to smoke. Using a transwell migration assay in which 16HBE cells and human alveolar macrophages were cocultured, we showed that smoke-induced NLRP3 activation in 16HBE cells increased the migration of human alveolar macrophages. When the NLRP3 expression was silenced, the average migration distance of 16HBE was increased in scratch assay, because the activation of NLRP3 induced apoptosis by the p53-Bax mitochondrial pathway in the smoke-induced response. These results demonstrate the importance of the NLRP3 inflammasome in mediating BS- and CS-induced HBE cell damage and proapoptosis.

Comparison of two preoperative protocols for mandibular symphyseal distraction osteogenesis to reduce the risk of tooth damage.

PubMed

Winsauer, Heinz; Ploder, Oliver; Juengling, Katharina; Walter, Andre; Kolk, Andreas

2017-04-01

Two techniques to separate the lower incisors prior to mandibular symphyseal distraction osteogenesis (MSDO) were evaluated with respect to avoiding tooth damage. Fifty patients (20.2 ± 7.0 years) requiring MSDO were treated with a tooth-borne appliance by utilizing two preoperative protocols to separate the central incisors: i) brackets and a V-bent wire with an open coil spring (two-step; TS; n = 24) and ii) a wire attached from the appliance to the central incisors with subsequent dento-alveolar expansion prior to surgery (one-step; OS; n = 26). The distance between the lower incisors was measured preoperatively on radiographs and measurements at the cast models were performed. Complications and radiographs were analyzed. The mean distance (±SD) between the lower central incisors for OS and TS prior to surgery was 3.44 ± 1.05 and 3.18 ± 1.13 mm, respectively. The mean expansion for OS and TS was 4.3 ± 2.9 and 4.3 ± 2.7 mm at the dental level and 3.8 ± 3.2 and 4.0 ± 2.1 mm at the bone level, respectively. Four patients undergoing the TS and one patient undergoing the OS showed transient dental complications. Pre-surgical dento-alveolar expansion by utilizing a one-step technique to separate the lower central incisors reduces the risk of permanent tooth damage and weakens the mandibular bone in the midline. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Frederick J.; Reynolds, Lucy J.; Toward, Toby J.

This study investigated whether a correlation between leukocyte-derived elastolytic activity, alveolar epithelial type-1 cell damage, and leukocyte infiltration of the airways existed in guinea-pigs chronically exposed to inhaled lipopolysaccharide (LPS). The airway pathology of this model, notably the neutrophilia, resembles chronic obstructive pulmonary disease (COPD). The effect of the corticosteroid, dexamethasone, or the phosphodiesterase-4 (PDE4)-inhibitor, rolipram, on these features was studied. Conscious guinea-pigs were exposed for 1 h to single or repeated (nine) doses of LPS (30 {mu}g ml{sup -1}). Dexamethasone (20 mg kg{sup -1}, ip) or rolipram (1 mg kg{sup -1}, ip) was administered 24 and 0.5 h beforemore » the first exposure and daily thereafter. Bronchoalveolar lavage fluid (BALF) was removed and elastolytic activity determined as the elastase-like release of Congo Red from impregnated elastin. The presence of the specific epithelial cell type-1 protein (40-42 kDa) RT1{sub 40} in BALF was identified by Western blotting using a rat monoclonal antibody and semi-quantified by dot-blot analysis. The antibody was found to identify guinea-pig RT1{sub 40}. BALF inflammatory cells, particularly neutrophils and macrophages, and elastolytic activity were increased in chronic LPS-exposed guinea-pigs, the latter by 90%. Chronic LPS exposure also increased (10.5-fold) RT1{sub 40} levels, indicating significant alveolar epithelial type-1 cell damage. Dexamethasone or rolipram treatment reduced the influx of inflammatory cells, the elastolytic activity (by 40% and 38%, respectively), and RT1{sub 40} levels (by 50% and 57%, respectively). In conclusion, chronic LPS-exposed guinea-pigs, like COPD, exhibit elastolytic lung damage. This was prevented by a PDE4 inhibitor and supports their development for suppressing this leukocyte-mediated pathology.« less

Analysis of dental injuries with clinical implications: A forensic case report.

PubMed

Tan, Si-Lei; Peng, Shu-Ya; Wan, Lei; Chen, Jie-Min; Xia, Wen-Tao

2018-01-01

Dental injuries, especially of the incisors, caused by punches in violent criminal attacks could be seen in daily forensic casework involving the identification of injuries to a living body. Sometimes, when there is neither circumstantial evidence nor information about the surrounding circumstances, it is difficult to discern the cause of these injuries and the manner in which they were inflicted. As an example of clinical forensic medicine, we present the case of a 58-year-old woman whose teeth were injured when fighting with her son-in-law over household affairs with no witnesses present. The two parties had conflicting stories about the cause of the woman's injury. The woman claimed that her teeth were lost while she was being beaten by her son-in-law, and the man argued that the damage to his mother-in-law's teeth was self-inflicted when she bit his fingers. The police attending the crime called for a forensic examination. Forensic practitioners analysed the mechanism of the tooth loss using multi-slice spiral computed tomography (MSCT) and imaging reconstruction technology. Local alveolar bone (medial alveolar) fracture and a small area of alveolar bone loss were found on MSCT. Thus, forensic medical experts speculated that the woman's lower central and lateral incisors were lost as a result of a violent attack and were not self-inflicted. Finally, forensic practitioners helped police in avoiding a miscarriage of justice and wrongful conviction.

The cytoprotective role of DJ-1 and p45 NFE2 against human primary alveolar type II cell injury and emphysema.

PubMed

Tan, Li Hui; Bahmed, Karim; Lin, Chih-Ru; Marchetti, Nathaniel; Bolla, Sudhir; Criner, Gerard J; Kelsen, Steven; Madesh, Muniswamy; Kosmider, Beata

2018-02-23

Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides. Low expression of p45 NFE2 in patients with emphysema correlated with a high ECM degradation. Moreover, we found that NFE2 knockdown increased cell death induced by cigarette smoke extract. We also studied the cross talk between p45 NFE2 and DJ-1. DJ-1 protein is a redox-sensitive chaperone that protects cells from oxidative stress. We detected that cigarette smoke significantly increased p45 NFE2 levels in DJ-1 KO mice compared to wild-type mice. Our results indicate that p45 NFE2 expression is induced by exposure to cigarette smoke, has a cytoprotective activity against cell injury, and its downregulation in human primary ATII cells may contribute to emphysema pathogenesis.

Edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia injury: heme oxygenase-1 and PI3K/Akt pathway may be involved.

PubMed

Cao, Huifang; Feng, Ying; Ning, Yunye; Zhang, Zinan; Li, Weihao; Li, Qiang

2015-01-01

Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. As yet, no specific treatment is available for HALI. The present study aims to investigate the effects of edaravone on hyperoxia-induced oxidative injury and the underlying mechanism. We treated rats and human pulmonary alveolar epithelial cells with hyperoxia and different concentration of edaravone, then examined the effects of edaravone on cell viability, cell injury and two oxidative products. The roles of heme oxygenase-1 (HO-1) and PI3K/Akt pathway were explored using Western blot and corresponding inhibitors. The results showed that edaravone reduced lung biochemical alterations induced by hyperoxia and mortality of rats, dose-dependently alleviated cell mortality, cell injury, and peroxidation of cellular lipid and DNA oxidative damage. It upregulated cellular HO-1 expression and activity, which was reversed by PI3K/Akt pathway inhibition. The administration of zinc protoporphyrin-IX, a HO-1 inhibitor, and LY249002, a PI3K/Akt pathway inhibitor, abolished the protective effects of edaravone in cells. This study indicates that edaravone protects rats and human pulmonary alveolar epithelial cells against hyperoxia-induced injury and the antioxidant effect may be related to upregulation of HO-1, which is regulated by PI3K/Akt pathway.

Non-Contact Measurement of Thermal Diffusivity in Ion-Implanted Nuclear Materials

NASA Astrophysics Data System (ADS)

Hofmann, F.; Mason, D. R.; Eliason, J. K.; Maznev, A. A.; Nelson, K. A.; Dudarev, S. L.

2015-11-01

Knowledge of mechanical and physical property evolution due to irradiation damage is essential for the development of future fission and fusion reactors. Ion-irradiation provides an excellent proxy for studying irradiation damage, allowing high damage doses without sample activation. Limited ion-penetration-depth means that only few-micron-thick damaged layers are produced. Substantial effort has been devoted to probing the mechanical properties of these thin implanted layers. Yet, whilst key to reactor design, their thermal transport properties remain largely unexplored due to a lack of suitable measurement techniques. Here we demonstrate non-contact thermal diffusivity measurements in ion-implanted tungsten for nuclear fusion armour. Alloying with transmutation elements and the interaction of retained gas with implantation-induced defects both lead to dramatic reductions in thermal diffusivity. These changes are well captured by our modelling approaches. Our observations have important implications for the design of future fusion power plants.

Non-Contact Measurement of Thermal Diffusivity in Ion-Implanted Nuclear Materials

DOE PAGES

Hofmann, F.; Mason, D. R.; Eliason, J. K.; ...

2015-11-03

Knowledge of mechanical and physical property evolution due to irradiation damage is essential for the development of future fission and fusion reactors. Ion-irradiation provides an excellent proxy for studying irradiation damage, allowing high damage doses without sample activation. Limited ion-penetration-depth means that only few-micron-thick damaged layers are produced. Substantial effort has been devoted to probing the mechanical properties of these thin implanted layers. Yet, whilst key to reactor design, their thermal transport properties remain largely unexplored due to a lack of suitable measurement techniques. Here we demonstrate non-contact thermal diffusivity measurements in ion-implanted tungsten for nuclear fusion armour. Alloying withmore » transmutation elements and the interaction of retained gas with implantation-induced defects both lead to dramatic reductions in thermal diffusivity. These changes are well captured by our modelling approaches. Our observations have important implications for the design of future fusion power plants.« less

Non-Contact Measurement of Thermal Diffusivity in Ion-Implanted Nuclear Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hofmann, F.; Mason, D. R.; Eliason, J. K.

Knowledge of mechanical and physical property evolution due to irradiation damage is essential for the development of future fission and fusion reactors. Ion-irradiation provides an excellent proxy for studying irradiation damage, allowing high damage doses without sample activation. Limited ion-penetration-depth means that only few-micron-thick damaged layers are produced. Substantial effort has been devoted to probing the mechanical properties of these thin implanted layers. Yet, whilst key to reactor design, their thermal transport properties remain largely unexplored due to a lack of suitable measurement techniques. Here we demonstrate non-contact thermal diffusivity measurements in ion-implanted tungsten for nuclear fusion armour. Alloying withmore » transmutation elements and the interaction of retained gas with implantation-induced defects both lead to dramatic reductions in thermal diffusivity. These changes are well captured by our modelling approaches. Our observations have important implications for the design of future fusion power plants.« less

Non-Contact Measurement of Thermal Diffusivity in Ion-Implanted Nuclear Materials

PubMed Central

Hofmann, F.; Mason, D. R.; Eliason, J. K.; Maznev, A. A.; Nelson, K. A.; Dudarev, S. L.

2015-01-01

Knowledge of mechanical and physical property evolution due to irradiation damage is essential for the development of future fission and fusion reactors. Ion-irradiation provides an excellent proxy for studying irradiation damage, allowing high damage doses without sample activation. Limited ion-penetration-depth means that only few-micron-thick damaged layers are produced. Substantial effort has been devoted to probing the mechanical properties of these thin implanted layers. Yet, whilst key to reactor design, their thermal transport properties remain largely unexplored due to a lack of suitable measurement techniques. Here we demonstrate non-contact thermal diffusivity measurements in ion-implanted tungsten for nuclear fusion armour. Alloying with transmutation elements and the interaction of retained gas with implantation-induced defects both lead to dramatic reductions in thermal diffusivity. These changes are well captured by our modelling approaches. Our observations have important implications for the design of future fusion power plants. PMID:26527099

Interrogating the Effects of Radiation Damage Annealing on Helium Diffusion Kinetics in Apatite

NASA Astrophysics Data System (ADS)

Willett, C. D.; Fox, M.; Shuster, D. L.

2015-12-01

Apatite (U-Th)/He thermochronology is commonly used to study landscape evolution and potential links between climate, erosion and tectonics. The technique relies on a quantitative understanding of (i) helium diffusion kinetics in apatite, (ii) an evolving 4He concentration, (iii) accumulating damage to the crystal lattice caused by radioactive decay[1], and (iv) the thermal annealing of such damage[2],[3], which are each functions of both time and temperature. Uncertainty in existing models of helium diffusion kinetics has resulted in conflicting conclusions, especially in settings involving burial heating through geologic time. The effects of alpha recoil damage annealing are currently assumed to follow the kinetics of fission track annealing (e.g., reference [3]), although this assumption is difficult to fully validate. Here, we present results of modeling exercises and a suite of experiments designed to interrogate the effects of damage annealing on He diffusivity in apatite that are independent of empirical calibrations of fission track annealing. We use the existing experimental results for Durango apatite[2] to develop and calibrate a new function that predicts the effects of annealing temperature and duration on measured diffusivity. We also present a suite of experiments conducted on apatite from Sierra Nevada, CA granite to establish whether apatites with different chemical compositions have the same behavior as Durango apatite. Crystals were heated under vacuum to temperatures between 250 and 500°C for 1, 10, or 100 hours. The samples were then irradiated with ~220 MeV protons to produce spallogenic 3He, the diffusant then used in step-heating diffusion experiments. We compare the results of these experiments and model calibrations to existing models. Citations: [1]Shuster, D., Flowers R., and Farley K., (2006), EPSL 249(3-4), 148-161; [2]Shuster, D. and Farley, K., (2009), GCA 73 (1), 6183-6196; [3]Flowers, R., Ketcham, R., Shuster, D. and Farley, K., (2009), GCA 73, 2347-2365.

In vitro Toxicity and Inflammatory Response Induced by Copper Nanoparticles in Rat Alveolar Macrophages

DTIC Science & Technology

2008-03-01

the cupric form is most prevalent (Linder and Hazegh-Azam, 1996:797S). Cupric compounds are blue-green in color and highly soluble in water...reduced clearance of particles due to macrophage damage after exposure to various doses of titanium dioxide ( TiO2 )(5, 50, and 250 mg/m3) (Warheit, et al...viability. The assay measures cell viability when the tetrazolium compound is bioreduced by viable cells to a colored formazan product (see Figure 3

Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallaert, B.; Ramon, P.; Fournier, E.C.

1986-01-01

Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted inmore » 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung.« less

A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

PubMed Central

Agnihothram, Sudhakar; Yount, Boyd L.; Donaldson, Eric F.; Huynh, Jeremy; Menachery, Vineet D.; Gralinski, Lisa E.; Graham, Rachel L.; Becker, Michelle M.; Tomar, Sakshi; Scobey, Trevor D.; Osswald, Heather L.; Whitmore, Alan; Gopal, Robin; Ghosh, Arun K.; Mesecar, Andrew; Zambon, Maria; Heise, Mark; Denison, Mark R.; Baric, Ralph S.

2014-01-01

ABSTRACT Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis. PMID:24667706

Integrative Conductance of Oxygen During Exercise at Altitude.

PubMed

Calbet, José A L; Lundby, Carsten; Boushel, Robert

2016-01-01

In the oxygen (O2) cascade downstream steps can never achieve higher flows of O2 than the preceding ones. At the lung the transfer of O2 is determined by the O2 gradient between the alveolar space and the lung capillaries and the O2 diffusing capacity (DLO2). While DLO2 may be increased several times during exercise by recruiting more lung capillaries and by increasing the oxygen carrying capacity of blood due to higher peripheral extraction of O2, the capacity to enhance the alveolocapillary PO2 gradient is more limited. The transfer of oxygen from the alveolar space to the hemoglobin (Hb) must overcome first the resistance offered by the alveolocapillary membrane (1/DM) and the capillary blood (1/θVc). The fractional contribution of each of these two components to DLO2 remains unknown. During exercise these resistances are reduced by the recruitment of lung capillaries. The factors that reduce the slope of the oxygen dissociation curve of the Hb (ODC) (i.e., lactic acidosis and hyperthermia) increase 1/θVc contributing to limit DLO2. These effects are accentuated in hypoxia. Reducing the size of the active muscle mass improves pulmonary gas exchange during exercise and reduces the rightward shift of the ODC. The flow of oxygen from the muscle capillaries to the mitochondria is pressumably limited by muscle O2 conductance (DmcO2) (an estimation of muscle oxygen diffusing capacity). However, during maximal whole body exercise in normoxia, a higher flow of O2 is achieved at the same pressure gradients after increasing blood [Hb], implying that in healthy humans exercising in normoxia there is a functional reserve in DmcO2. This conclusion is supported by the fact that during small muscle exercise in chronic hypoxia, peak exercise DmcO2 is similar to that observed during exercise in normoxia despite a markedly lower O2 pressure gradient driving diffusion.

Interstitial lung disease in patients with polymyositis, dermatomyositis and amyopathic dermatomyositis.

PubMed

Kang, E H; Lee, E B; Shin, K C; Im, C H; Chung, D H; Han, S K; Song, Y W

2005-10-01

To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) < or =60% (P = 0.024). ILD was observed in 40.3% of Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC < or =60% were associated with poor survival in ILD.

New-onset systemic lupus erythematosus in a long-term hemodialysis patient with acute pleuritis and pneumonitis.

PubMed

Hiyamuta, Hiroto; Yamada, Shunsuke; Yotsueda, Ryusuke; Hasegawa, Shoko; Nakano, Toshiaki; Taniguchi, Masatomo; Tsukamoto, Hiroshi; Kitazono, Takanari; Tsuruya, Kazuhiko

2015-11-01

A 61-year-old woman, with a 25-year history of maintenance hemodialysis due to end-stage renal disease of unknown causes, was admitted because of systemic joint pain and inflammatory response of unknown etiology that persisted for 1 month. Laboratory data on admission revealed leukocytopenia, lymphocytopenia, high serum C-reactive protein, and positivity for antinuclear antibody (ANA) and anti-double strand DNA. After admission, she progressively developed cough and dyspnea. A chest radiograph revealed bilateral ground glass opacity and pleural effusion. A thoracentesis revealed lupus erythematosus cells, suggesting lupus pleuritis. A chest computed tomography showed a pattern of diffuse alveolar damage compatible with acute lupus pneumonitis. She fulfilled the American Rheumatism Association diagnostic criteria for systemic lupus erythematosus (SLE). Methylprednisolone pulse therapy followed by oral prednisone treatment improved the clinical symptoms and laboratory abnormalities. ANA was negative 25 years earlier when she first started hemodialysis and she had neither clinical nor serological abnormalities related to SLE during the last 25 years. Further, she had neither received drugs that can cause drug-induced SLE, nor had a history of ultraviolet ray exposure, pregnancy, blood transfusion, trauma and smoking. This report suggests that new-onset SLE can develop in patients undergoing long-term dialysis. Hence, when we encounter dialysis patients with arthralgia and/or respiratory disorders, we should consider the possibility of new-onset SLE.

Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study.

PubMed

Alsaad, Khaled O; Hajeer, Ali H; Al Balwi, Mohammed; Al Moaiqel, Mohammed; Al Oudah, Nourah; Al Ajlan, Abdulaziz; AlJohani, Sameera; Alsolamy, Sami; Gmati, Giamal E; Balkhy, Hanan; Al-Jahdali, Hamdan H; Baharoon, Salim A; Arabi, Yaseen M

2018-02-01

The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome - coronavirus (MERS-CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology. We analysed the post-mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles. The results highlight the pulmonary and extrapulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS-CoV in kidney. © 2017 John Wiley & Sons Ltd.

Pathology of lethal and sublethal doses of aerosolized ricin in rhesus macaques.

PubMed

Bhaskaran, Manoj; Didier, Peter J; Sivasubramani, Satheesh K; Doyle, Lara A; Holley, Jane; Roy, Chad J

2014-01-01

Ricin toxin, a type 2 ribosome-inactivating protein and a category B bioterrorism agent, is produced from the seeds of castor oil plant (Ricinus communis). Chronic pathological changes in survivors of aerosolized ricin exposure have not been reported in primates. Here we compare and contrast the pathological changes manifested between rhesus macaques (RM) that succumbed to lethal dose of ricin (group I) and survivor RM exposed to low dose of ricin (group II). All animals in group I exhibited severe diffuse, necrotizing bronchiolitis and alveolitis with fibrinopurulent bronchointerstitial pneumonia, massive alveolar, perivascular and peribronchial/bronchiolar edema with hemorrhage, and necropurulent and hemorrhagic tracheobronchial lymphadenitis. All animals from group II had multifocal, fibrosing interstitial pneumonia with prominent alveolar histiocytosis and type II pneumocyte hyperplasia. Subacute changes like infiltration by lymphocytes and plasma cells and persistence of edematous fluid were occasionally present in lung and tracheobronchial lymph nodes. The changes appear to be a continuum wherein the inflammatory response shifts from an acute to subacute/chronic reparative process if the animals can survive the initial insult.

Locating and characterizing a crack in concrete with diffuse ultrasound: A four-point bending test.

PubMed

Larose, Eric; Obermann, Anne; Digulescu, Angela; Planès, Thomas; Chaix, Jean-Francois; Mazerolle, Frédéric; Moreau, Gautier

2015-07-01

This paper describes an original imaging technique, named Locadiff, that benefits from the diffuse effect of ultrasound waves in concrete to detect and locate mechanical changes associated with the opening of pre-existing cracks, and/or to the development of diffuse damage at the tip of the crack. After giving a brief overview of the theoretical model to describe the decorrelation of diffuse waveforms induced by a local change, the article introduces the inversion procedure that produces the three dimensional maps of density of changes. These maps are interpreted in terms of mechanical changes, fracture opening, and damage development. In addition, each fracture is characterized by its effective scattering cross section.

Ventilation-perfusion matching during exercise

NASA Technical Reports Server (NTRS)

Wagner, P. D.

1992-01-01

In normal subjects, exercise widens the alveolar-arterial PO2 difference (P[A-a]O2) despite a more uniform topographic distribution of ventilation-perfusion (VA/Q) ratios. While part of the increase in P(A-a)O2 (especially during heavy exercise) is due to diffusion limitation, a considerable amount is caused by an increase in VA/Q mismatch as detected by the multiple inert gas elimination technique. Why this occurs is unknown, but circumstantial evidence suggests it may be related to interstitial pulmonary edema rather than to factors dependent on ventilation, airway gas mixing, airway muscle tone, or pulmonary vascular tone. In patients with lung disease, the gas exchange consequences of exercise are variable. Thus, arterial PO2 may increase, remain the same, or fall. In general, patients with advanced chronic obstructive pulmonary disease (COPD) or interstitial fibrosis who exercise show a fall in PO2. This is usually not due to worsening VA/Q relationships but mostly to the well-known fall in mixed venous PO2, which itself results from a relatively smaller increase in cardiac output than VO2. However, in interstitial fibrosis (but not COPD), there is good evidence that a part of the fall in PO2 on exercise is caused by alveolar-capillary diffusion limitation of O2 transport; in COPD (but not interstitial fibrosis), a frequent additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that minute ventilation does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and PO2 to fall.

Pulmonary arterial hypertension and cor pulmonale associated with chronic domestic woodsmoke inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandoval, J.; Salas, J.; Martinez-Guerra, M.L.

1993-01-01

We describe the clinical, radiologic, functional, and pulmonary hemodynamic characteristics of a group of 30 nonsmoking patients with a lung disease that may be related to intense, long-standing indoor wood-smoke exposure. The endoscopic and some of the pathologic findings are also presented. Intense and prolonged wood-smoke inhalation may produce a chronic pulmonary disease that is similar in many aspects to other forms of inorganic dust-exposure interstitial lung disease. It affects mostly country women in their 60s, and severe dyspnea and cough are the outstanding complaints. The chest roentgenograms show a diffuse, bilateral, reticulonodular pattern, combined with normalized or hyperinflated lungs,more » as well as indirect signs of pulmonary arterial hypertension (PAH). On the pulmonary function test the patients show a mixed restrictive-obstructive pattern with severe hypoxemia and variable degrees of hypercapnia. Endoscopic findings are those of acute and chronic bronchitis and intense anthracotic staining of the airways appears to be quite characteristic. Fibrous and inflammatory focal thickening of the alveolar septa as well as diffuse parenchymal anthracotic deposits are the most prominent pathologic findings, although inflammatory changes of the bronchial epithelium are also present. The patients had severe PAH in which, as in other chronic lung diseases, chronic alveolar hypoxia may play the main pathogenetic role. However, PAH in wood-smoke inhalation-associated lung disease (WSIALD) appears to be more severe than in other forms of interstitial lung disease and tobacco-related COPD. The patients we studied are a selected group and they may represent one end of the spectrum of the WSIALD.« less

Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span

PubMed Central

Morales-Nebreda, Luisa; Cuda, Carla M.; Walter, James M.; Chen, Ching-I; Anekalla, Kishore R.; Joshi, Nikita; Williams, Kinola J.N.; Abdala-Valencia, Hiam; Yacoub, Tyrone J.; Chi, Monica; Gates, Khalilah; Homan, Philip J.; Soberanes, Saul; Dominguez, Salina; Saber, Rana; Hinchcliff, Monique; Marshall, Stacy A.; Bharat, Ankit; Berdnikovs, Sergejs; Bhorade, Sangeeta M.; Balch, William E.; Chandel, Navdeep S.; Jain, Manu; Ridge, Karen M.; Bagheri, Neda; Shilatifard, Ali

2017-01-01

Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion. PMID:28694385

Aerosolized liposomes with dipalmitoyl phosphatidylcholine enhance pulmonary absorption of encapsulated insulin compared with co-administered insulin.

PubMed

Chono, Sumio; Togami, Kohei; Itagaki, Shirou

2017-11-01

We have previously shown that aerosolized liposomes with dipalmitoyl phosphatidylcholine (DPPC) enhance the pulmonary absorption of encapsulated insulin. In this study, we aimed to compare insulin encapsulated into the liposomes versus co-administration of empty liposomes and unencapsulated free insulin, where the DPCC liposomes would serve as absorption enhancer. The present study provides the useful information for development of noninvasive treatment of diabetes. Co-administration of empty DPPC liposomes and unencapsulated free insulin was investigated in vivo to assess the potential enhancement in protein pulmonary absorption. Co-administration was compared to DPPC liposomes encapsulating insulin, and free insulin. DPPC liposomes enhanced the pulmonary absorption of unencapsulated free insulin; however, the enhancing effect was lower than that of the DPPC liposomes encapsulating insulin. The mechanism of the pulmonary absorption of unencapsulated free insulin by DPPC liposomes involved the opening of epithelial cell space in alveolar mucosa, and not mucosal cell damage, similar to that of the DPPC liposomes encapsulating insulin. In an in vitro stability test, insulin in the alveolar mucus layer that covers epithelial cells was stable. These findings suggest that, although unencapsulated free insulin spreads throughout the alveolar mucus layer, the concentration of insulin released near the absorption surface is increased by the encapsulation of insulin into DPPC liposomes and the absorption efficiency is also increased. We revealed that the encapsulation of insulin into DPPC liposomes is more effective for pulmonary insulin absorption than co-administration of DPPC liposomes and unencapsulated free insulin.

Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses

PubMed Central

2013-01-01

EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed. PMID:24289102

Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.

PubMed

Bolfa, Pompei; Nolf, Marie; Cadoré, Jean-Luc; Catoi, Cornel; Archer, Fabienne; Dolmazon, Christine; Mornex, Jean-François; Leroux, Caroline

2013-12-01

EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed.

Assessment of Temperature Rise and Time of Alveolar Ridge Splitting by Means of Er:YAG Laser, Piezosurgery, and Surgical Saw: An Ex Vivo Study

PubMed Central

Flieger, Rafał; Dominiak, Marzena

2016-01-01

The most common adverse effect after bone cutting is a thermal damage. The aim of our study was to evaluate the bone temperature rise during an alveolar ridge splitting, rating the time needed to perform this procedure and the time to raise the temperature of a bone by 10°C, as well as to evaluate the bone carbonization occurrence. The research included 60 mandibles (n = 60) of adult pigs, divided into 4 groups (n = 15). Two vertical and one horizontal cut have been done in an alveolar ridge using Er:YAG laser with set power of 200 mJ (G1), 400 mJ (G2), piezosurgery unit (G3), and a saw (G4). The temperature was measured by K-type thermocouple. The highest temperature gradient was noted for piezosurgery on the buccal and lingual side of mandible. The temperature rises on the bone surface along with the increase of laser power. The lower time needed to perform ridge splitting was measured for a saw, piezosurgery, and Er:YAG laser with power of 400 mJ and 200 mJ, respectively. The temperature rise measured on the bone over 10°C and bone carbonization occurrence was not reported in all study groups. Piezosurgery, Er:YAG laser (200 mJ and 400 mJ), and surgical saw are useful and safe tools in ridge splitting surgery. PMID:27957502

Assessment of Temperature Rise and Time of Alveolar Ridge Splitting by Means of Er:YAG Laser, Piezosurgery, and Surgical Saw: An Ex Vivo Study.

PubMed

Matys, Jacek; Flieger, Rafał; Dominiak, Marzena

2016-01-01

The most common adverse effect after bone cutting is a thermal damage. The aim of our study was to evaluate the bone temperature rise during an alveolar ridge splitting, rating the time needed to perform this procedure and the time to raise the temperature of a bone by 10°C, as well as to evaluate the bone carbonization occurrence. The research included 60 mandibles ( n = 60) of adult pigs, divided into 4 groups ( n = 15). Two vertical and one horizontal cut have been done in an alveolar ridge using Er:YAG laser with set power of 200 mJ (G1), 400 mJ (G2), piezosurgery unit (G3), and a saw (G4). The temperature was measured by K-type thermocouple. The highest temperature gradient was noted for piezosurgery on the buccal and lingual side of mandible. The temperature rises on the bone surface along with the increase of laser power. The lower time needed to perform ridge splitting was measured for a saw, piezosurgery, and Er:YAG laser with power of 400 mJ and 200 mJ, respectively. The temperature rise measured on the bone over 10°C and bone carbonization occurrence was not reported in all study groups. Piezosurgery, Er:YAG laser (200 mJ and 400 mJ), and surgical saw are useful and safe tools in ridge splitting surgery.

Depth estimation of multi-layered impact damage in PMC using lateral thermography

NASA Astrophysics Data System (ADS)

Whitlow, Travis; Kramb, Victoria; Reibel, Rick; Dierken, Josiah

2018-04-01

Characterization of impact damage in polymer matrix composites (PMCs) continues to be a challenge due to the complex internal structure of the material. Nondestructive characterization approaches such as normal incident immersion ultrasound and flash thermography are sensitive to delamination damage, but do not provide information regarding damage obscured by the delaminations. Characterization of material state below a delamination requires a technique which is sensitive to in-plane damage modes such as matrix cracking and fiber breakage. Previous studies of the lateral heat flow through a composite laminate showed that the diffusion time was sensitive to the depth of the simulated damage zone. The current study will further evaluate the lateral diffusion model to provide sensitivity limits for the modeled flaw dimensions. Comparisons between the model simulations and experimental data obtained using a concentrated heat source and machined targets will also be presented.

Aspirin reduces lipopolysaccharide-induced pulmonary inflammation in human models of ARDS.

PubMed

Hamid, U; Krasnodembskaya, A; Fitzgerald, M; Shyamsundar, M; Kissenpfennig, A; Scott, C; Lefrancais, E; Looney, M R; Verghis, R; Scott, J; Simpson, A J; McNamee, J; McAuley, D F; O'Kane, C M

2017-11-01

Platelets play an active role in the pathogenesis of acute respiratory distress syndrome (ARDS). Animal and observational studies have shown aspirin's antiplatelet and immunomodulatory effects may be beneficial in ARDS. To test the hypothesis that aspirin reduces inflammation in clinically relevant human models that recapitulate pathophysiological mechanisms implicated in the development of ARDS. Healthy volunteers were randomised to receive placebo or aspirin 75  or 1200 mg (1:1:1) for seven days prior to lipopolysaccharide (LPS) inhalation, in a double-blind, placebo-controlled, allocation-concealed study. Bronchoalveolar lavage (BAL) was performed 6 hours after inhaling 50 µg of LPS. The primary outcome measure was BAL IL-8. Secondary outcome measures included markers of alveolar inflammation (BAL neutrophils, cytokines, neutrophil proteases), alveolar epithelial cell injury, systemic inflammation (neutrophils and plasma C-reactive protein (CRP)) and platelet activation (thromboxane B2, TXB2). Human lungs, perfused and ventilated ex vivo (EVLP) were randomised to placebo or 24 mg aspirin and injured with LPS. BAL was carried out 4 hours later. Inflammation was assessed by BAL differential cell counts and histological changes. In the healthy volunteer (n=33) model, data for the aspirin groups were combined. Aspirin did not reduce BAL IL-8. However, aspirin reduced pulmonary neutrophilia and tissue damaging neutrophil proteases (Matrix Metalloproteinase (MMP)-8/-9), reduced BAL concentrations of tumour necrosis factor α and reduced systemic and pulmonary TXB2. There was no difference between high-dose and low-dose aspirin. In the EVLP model, aspirin reduced BAL neutrophilia and alveolar injury as measured by histological damage. These are the first prospective human data indicating that aspirin inhibits pulmonary neutrophilic inflammation, at both low and high doses. Further clinical studies are indicated to assess the role of aspirin in the prevention and treatment of ARDS. NCT01659307 Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

High times, low sats: diffuse pulmonary infiltrates associated with chronic synthetic cannabinoid use.

PubMed

Alhadi, Sameir; Tiwari, Anupama; Vohra, Rais; Gerona, Roy; Acharya, Janak; Bilello, Kathryn

2013-06-01

In recent years, cases of severe adverse effects from recreational use of synthetic cannabinoids (SC) have established that these agents represent a novel toxicologic hazard. A 21-year-old male presenting as a vehicular trauma victim was noted with diffuse pulmonary infiltrates related to chronic inhalation of multiple synthetic cannabinoid-containing products. Chest imaging revealed bilateral, subacute lung infiltrates; histopathological analysis of bronchial and alveolar tissues revealed an inflammatory process. An extensive workup failed to identify infectious, malignant, autoimmune, or hematologic causes of the syndrome, and toxicological analysis of the blood and body fluids confirmed the presence of multiple synthetic cannabinoids and metabolites. The patient recovered after an 8-day ICU course, wherein he received antibiotics, steroids, and mechanical ventilation. This case contributes to the currently evolving knowledge about SC agents, adding a rarely described pulmonary complication to the growing list of adverse effects associated with these products.

Apatite (U-Th)/He thermochronology dataset interpretation: New insights from physical point of view

NASA Astrophysics Data System (ADS)

Gautheron, Cécile; Mbongo-Djimbi, Duval; Gerin, Chloé; Roques, Jérôme; Bachelet, Cyril; Oliviero, Erwan; Tassan-Got, Laurent

2015-04-01

The apatite (U-Th)/He (AHe) system has rapidly become a very popular thermochronometer to constrain burial and exhumation phases in a variety of geological contexts. However, the interpretation of AHe data depends on a precise knowledge of He diffusion in apatite. Several studies suggest that radiation damage generated by U and Th decay can create traps for He atoms, increasing He retention for irradiated minerals. The radiation damage also anneals with temperature and the amount of damage in an apatite crystal is at any time a balance between production and annealing, controlled by U-Th concentration, grain chemistry and thermal history (Flowers et al., 2009; Gautheron et al., 2009; 2013). However the models are not well constrained and do not fully explain the mechanism of He retention. In order to have a deeper insight on this issue, multidisciplinary studies on apatite combining diffusion experiments by Elastic Recoil Diffusion Analysis (ERDA) with a multi-scale theoretical diffusion calculation based on Density Functional Theory (DFT) and Kinetic Monte Carlo were performed. ERDA experiments were conducted on different macro-crystals, and we probed the shape of a He profile implanted into a planar and polished surface of the crystal. The helium profile evolves with temperature and allows quantifying the He diffusivity and damage impact. Additionally, DFT calculations of a damage-free crystal of apatite with different F and Cl compositions, in similar proportion as natural ones, have been run to find the favored paths of a helium atom between interstitial sites, leading to a computation of the activation energy and the diffusion coefficient. We show that damage free apatite crystals are characterized by low retention behavior and closure temperature range from 33-36°C for pure F-apatite to higher value for Cl riche apatite (up to 12°C higher), for typical grain size and cooling rate (Mbongo-Djimbi et al., in review). Using ERDA and DFT approaches, we demonstrate that in addition to grain chemistry, He diffusivity will be strongly influenced by damage and propose a new physical model. Finally, we propose a new way of interpreting AHe datasets and practical geological examples will be given. Flowers, R., Ketcham, R.A., Shuster, D., Farley, K.A., 2009. Apatite (U-Th)/He thermochronology using a radiation damage accumulation and annealing model. Geochimica et Cosmochimica Acta 73, 2347-2365. Gautheron, C., Tassan-got, L., Barbarand, J., Pagel, M., 2009. Effect of alpha-damage annealing on apatite (U-Th)/He thermochronology. Chemical Geology 266, 166-179. Gautheron, C., Barbarand, J., Ketcham R.A., Tassan-got, L., van der Beek, P., Pagel, M., Pinna-Jamme, R., Couffignal, F., Fialin, M., 2013. Chemical influence on α-recoil damage annealing in apatite: implications for (U-Th)/He dating. Chemical Geology 351, 257-267. Mbongo-Djimbi D., Gautheron C., Roques, J., Tassan-Got, L., Gerin, C., Simoni, E.. Apatite composition effect on (U-Th)/He thermochronometer: an atomistic point of view. In review at Geochimica Cosmochimica Acta.

A case report of Gorlin–Goltz syndrome as a rare hereditary disorder

PubMed Central

Sirous, Mehri; Tayari, Nazila

2011-01-01

Gorlin–Goltz syndrome is an autosomal dominant and a rare hereditary disease. Diagnosis of this syndrome is based on major and minor criteria. We report a Gorlin–Goltz syndrome in a 25-year-old male who was presented with progressive pain of maxilla and mandible over 5 years. The pain was diffuse and compatible with expansile cyst in alveolar ridges on panoramic radiography. In physical examination, he had coarse face and prognathism. Computer tomography of face revealed two expansile maxillary and one mandibular cyst. Calcification of entire length in falx and tentorium were detected in bone window. PMID:22091315

A case report of Gorlin-Goltz syndrome as a rare hereditary disorder.

PubMed

Sirous, Mehri; Tayari, Nazila

2011-06-01

Gorlin-Goltz syndrome is an autosomal dominant and a rare hereditary disease. Diagnosis of this syndrome is based on major and minor criteria. We report a Gorlin-Goltz syndrome in a 25-year-old male who was presented with progressive pain of maxilla and mandible over 5 years. The pain was diffuse and compatible with expansile cyst in alveolar ridges on panoramic radiography. In physical examination, he had coarse face and prognathism. Computer tomography of face revealed two expansile maxillary and one mandibular cyst. Calcification of entire length in falx and tentorium were detected in bone window.

Volumetric Optical Frequency Domain Imaging of Pulmonary Pathology With Precise Correlation to Histopathology

PubMed Central

Hariri, Lida P.; Applegate, Matthew B.; Mino-Kenudson, Mari; Mark, Eugene J.; Medoff, Benjamin D.; Luster, Andrew D.; Bouma, Brett E.; Tearney, Guillermo J.

2013-01-01

Background: Lung cancer is the leading cause of cancer-related mortality. Radiology and bronchoscopy techniques do not have the necessary resolution to evaluate lung lesions on the microscopic scale, which is critical for diagnosis. Bronchial biopsy specimens can be limited by sampling error and small size. Optical frequency domain imaging (OFDI) provides volumetric views of tissue microstructure at near-histologic resolution and may be useful for evaluating pulmonary lesions to increase diagnostic accuracy. Bronchoscopic OFDI has been evaluated in vivo, but a lack of correlated histopathology has limited the ability to develop accurate image interpretation criteria. Methods: We performed OFDI through two approaches (airway-centered and parenchymal imaging) in 22 ex vivo lung specimens, using tissue dye to precisely correlate imaging and histology. Results: OFDI of normal airway allowed visualization of epithelium, lamina propria, cartilage, and alveolar attachments. Carcinomas exhibited architectural disarray, loss of normal airway and alveolar structure, and rapid light attenuation. Squamous cell carcinomas showed nested architecture. Atypical glandular formation was appreciated in adenocarcinomas, and uniform trabecular gland formation was seen in salivary gland carcinomas. Mucinous adenocarcinomas showed alveolar wall thickening with intraalveolar mucin. Interstitial fibrosis was visualized as signal-dense tissue, with an interstitial distribution in mild interstitial fibrotic disease and a diffuse subpleural pattern with cystic space formation in usual interstitial pneumonitis. Conclusions: To our knowledge, this study is the first demonstration of volumetric OFDI with precise correlation to histopathology in lung pathology. We anticipate that OFDI may play a role in assessing airway and parenchymal pathology, providing fresh insights into the volumetric features of pulmonary disease. PMID:22459781

Induced sputum deposition improves diagnostic yields of pulmonary alveolar proteinosis: A clinicopathological and methodological study of 17 cases.

PubMed

Huang, Ziling; Yi, Xianghua; Luo, Benfang; Zhu, Jian; Wu, Yunjin; Jiang, Wenxia; Chu, Haiqing; Yang, Zhongmin; Li, Shuai; Zhu, Hailong; Zhang, Suxia; Zhang, Lanjing; Zeng, Yu

2016-01-01

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by the accumulation of intra-alveolar lipoprotein-like surfactants. Lung core biopsy and bronchoalveolar lavage (BAL) fluid are currently the two major sources of sampling for diagnosis. In the present study, we assessed the value of induced sputum in diagnosing PAP by transmission electron microscopy and examined the PAP 2-year death rate in Asians. Transmission electron microscopy was performed on the samples from 17 patients with PAP, 13 patients with inflammatory lung diseases, and 13 healthy adults. The PAP patients were followed up for 3-156 months, and inflammatory lung diseases patients or healthy adults for 12-36 months. The ultrastructural features including diagnostic lamellar bodies of induced sputum deposition (ISD) samples were similar to that of the BAL fluid sediment. However, the rates of lamellar bodies were 73.7% in the ISD group, significantly higher than the spontaneous sputum deposition (SSD) group (42.1%, P < .0487) and similar to the BAL sediment (76.2%) and the lung biopsy (54.5%) groups. The overall 2-year death rate of our PAP patients was 17.6% (3/17), not statistically different from the healthy adults and patients with inflammatory diseases (0/13, P = .237 for both). ISD may be the preferred non-invasive sampling method for diagnosing PAP by electronic microscopy because of the higher diagnostic yield than SSD. The diagnostic yields of this noninvasive method were similar to that of lung core biopsy and BAL.

Fatal acute pulmonary injury associated with everolimus.

PubMed

Depuydt, Pieter; Nollet, Joke; Benoit, Dominique; Praet, Marleen; Caes, Frank

2012-03-01

To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant. In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage. Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale. This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.

mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma following multi-walled carbon nanotube inhalation exposure in mice

PubMed Central

Snyder-Talkington, Brandi N.; Dong, Chunlin; Sargent, Linda M.; Porter, Dale W.; Staska, Lauren M.; Hubbs, Ann F.; Raese, Rebecca; McKinney, Walter; Chen, Bean T.; Battelli, Lori; Lowry, David T.; Reynolds, Steven H.; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2015-01-01

Inhalation exposure to multi-walled carbon nanotubes (MWCNT) in mice results in inflammation, fibrosis, and the promotion of lung adenocarcinoma; however, the molecular basis behind these pathologies is unknown. This study determined global mRNA and miRNA profiles in whole blood from mice exposed by inhalation to MWCNT that correlated with the presence of lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma. Six-week-old, male, B6C3F1 mice received a single intraperitoneal injection of either the DNA-damaging agent methylcholanthrene (MCA, 10 μg/g body weight) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5 mg/m³, 5 hours/day, 5 days/week) or filtered air (control) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for the development of pathological changes in the lung, and whole blood was collected and analyzed using microarray analysis for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up- or down-regulated in animals developing pathological changes in the lung after MCA/corn oil administration followed by MWCNT/air inhalation, including fcrl5 and miR-122-5p in the presence of hyperplasia, mthfd2 and miR-206-3p in the presence of fibrosis, fam178a and miR-130a-3p in the presence of bronchiolo-alveolar adenoma, and il7r and miR-210-3p in the presence of bronchiolo-alveolar adenocarcinoma, among others. The changes in miRNA and mRNA expression, and their respective regulatory networks, identified in this study may potentially serve as blood biomarkers for MWCNT-induced lung pathological changes. PMID:25926378

Surface-based reconstruction and diffusion MRI in the assessment of gray and white matter damage in multiple sclerosis

NASA Astrophysics Data System (ADS)

Caffini, Matteo; Bergsland, Niels; LaganÃ, Marcella; Tavazzi, Eleonora; Tortorella, Paola; Rovaris, Marco; Baselli, Giuseppe

2014-03-01

Despite advances in the application of nonconventional MRI techniques in furthering the understanding of multiple sclerosis pathogenic mechanisms, there are still many unanswered questions, such as the relationship between gray and white matter damage. We applied a combination of advanced surface-based reconstruction and diffusion tensor imaging techniques to address this issue. We found significant relationships between white matter tract integrity indices and corresponding cortical structures. Our results suggest a direct link between damage in white and gray matter and contribute to the notion of gray matter loss relating to clinical disability.

Chloride Permeability of Damaged High-Performance Fiber-Reinforced Cement Composite by Repeated Compressive Loads.

PubMed

Lee, Byung Jae; Hyun, Jung Hwan; Kim, Yun Yong; Shin, Kyung Joon

2014-08-11

The development of cracking in concrete structures leads to significant permeability and to durability problems as a result. Approaches to controlling crack development and crack width in concrete structures have been widely debated. Recently, it was recognized that a high-performance fiber-reinforced cement composite (HPFRCC) provides a possible solution to this inherent problem of cracking by smearing one or several dominant cracks into many distributed microcracks under tensile loading conditions. However, the chloride permeability of HPFRCC under compressive loading conditions is not yet fully understood. Therefore, the goal of the present study is to explore the chloride diffusion characteristics of HPFRCC damaged by compressive loads. The chloride diffusivity of HPFRCC is measured after being subjected to various repeated loads. The results show that the residual axial strain, lateral strain and specific crack area of HPFRCC specimens increase with an increase in the damage induced by repeated loads. However, the chloride diffusion coefficient increases only up to 1.5-times, whereas the specific crack area increases up to 3-times with an increase in damage. Although HPFRCC shows smeared distributed cracks in tensile loads, a significant reduction in the diffusion coefficient of HPFRCC is not obtained compared to plain concrete when the cyclic compressive load is applied below 85% of the strength.

Clinical associations of white matter damage in cART-treated HIV-positive children in South Africa.

PubMed

Hoare, Jacqueline; Fouche, Jean-Paul; Phillips, Nicole; Joska, John A; Donald, Kirsten A; Thomas, Kevin; Stein, Dan J

2015-04-01

A range of factors contributes to white matter damage in vertically infected HIV-positive children. These may include combination antiretroviral treatment (cART) regimen, sociodemographic factors, nutritional-hematological status, HIV-relevant clinical variables, and cognitive functioning. We explored associations between a number of these factors and diffusion tensor imaging (DTI) measures in 50 cART-treated children aged 6 to 15 years. Fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), and axial diffusion (AD) were derived from 48 cerebral white matter regions. Significant associations between a number of the clinical variables and white matter integrity were found. Decreased FA, a measure of neuronal damage, was associated with being on second-line cART, low hemoglobin, and younger age. Children with increased MD, a measure of neuronal damage, were younger, had reduced albumin and hemoglobin, and increased viral load. Decreased AD, a measure of axonal damage, was associated with increased viral load and total protein, decreased albumin and hemoglobin, younger age, poorer fronto-striatal cognition, and being on second-line cART. Increased RD, a measure of myelin loss, was associated with younger age, low current CD4 count, low albumin and hemoglobin, and higher viral load and total protein. The current findings underline the possible association of first-line treatment failure with white matter brain dysfunction in pediatric neuroHIV and the importance of examining the effects of HIV disease in the context of treatable clinical variables such as anemia and nutritional status.

[Effect of dust aerosol exposure on lung function and lung histopathology in rats].

PubMed

Lei, Fengfeng; Wang, Xuebin; Liu, Hua; Chen, Qizhang; Ma, Hui; Dong, Zhibao; Sang, Yingzhu

2015-08-25

To investigate the effect of dust aerosol exposure on lung function and lung histopathology in rats. According to random number table method, 120 Wistar male rats were divided into untreated control group, treated control group and experimental group, with 40 rats in each group. Experimental group were exposed to the wind tunnel simulation of sandstorm for 5 hours in every day; the untreated control group were put in the standard living environment next to the wind tunnel; the treated control group were exposed to the same wind tunnel simulation of sandstorm for 5 hours in every day, and the speed of wind was the same as the experimental group, but excluding dust. At different time points, the lung function and electron microscopy were performed in all rats. The level of Dynamic Compliance (Cdyn) ((0.227 ± 0.023), (0.198 ± 0.022) ml/cmH₂O, 1 cmH₂O=0.098 kPa) and forced vital capacity (FVC) ((6.24 ± 0.29), (5.59 ± 0.19) ml) were lower in the experimental group at 90 and 120 days, as compared to the untreated control group (Cdyn: (0.266 ± 0.014), (0.265 ± 0.018) ml/cmH2O; FVC: (7.15 ± 0.23), (7.17 ± 0.20) ml) and treated control group (Cdyn: (0.269 ± 0.015), (0.264 ± 0.019) ml/cmH2O; FVC: (7.14 ± 0.19), (7.15 ± 0.21) ml) (all P<0.05). At 120 days, The level of the forced expiratory flow after 50% of the FVC ((12.3 ± 2.2) ml/s) and peak expiratory flow ((25.79 ± 0.42) ml/s) were lower in the experimental group, as compared to the untreated control group ((15.9 ± 2.5), (27.99 ± 0.36) ml/s) and treated control group ((15.8 ± 2.1), (27.90 ± 0.38) ml/s) (all P<0.01). The FVC rate of 0.2 second in the experimental group was higher than that in the untreated control group and treated control group ( (85 ± 5)%, (73 ± 4)%, (73 ± 4)%, all P<0.05). The electron microscopy showed that the lung tissues had no obvious abnormalities at 30, 60, 90 and 120 days in untreated control group and treated control group. But in the experimental group, at 30 days, the endothelial cells of alveolar type I cells were swelled and the number of alveolar type II cells were increased; at 60 days, alveolar type II cells hyperplastic, basement membrane thinned and destructed; at 90 days, the number of alveolar type II cells decreased, Lamellar body evacuation; at 120 days, a lot of collagen fiber was formed in the alveolar septa. The strong sandstorm environmental exposure to a certain period of time can cause the decline of lung function and the damage of lung histopathology in rats. Exposure time was positively correlated with the damage of lung tissue.

Graphistrength© C100 MultiWalled Carbon Nanotubes (MWCNT): thirteen-week inhalation toxicity study in rats with 13- and 52-week recovery periods combined with comet and micronucleus assays

NASA Astrophysics Data System (ADS)

Régnier, Jean-François; Pothmann-Krings, Daniela; Simar, Sophie; Dony, Eva; Le Net, Jean-Loïc; Beausoleil, Julien

2017-06-01

Graphistrength© C100 provides superior electrical and mechanical properties for various applications and is one of the industrial MWCNT referenced in the OECD sponsorship program for the safety testing of nanomaterials. Graphistrength© C100 is formed of MWCNT (ca. 12 walls, outer mean diameter ca. 12 nm, length ca. 1 µm) agglomerated in particles with a granulometry centered on 400 µm. A general feature of MWCNT after inhalation or intratracheal exposures is the induction of an inflammatory reaction in the lungs sometimes associated with local genotoxic effects. Most of the in vitro and in vivo genotoxicity data available on Graphistrength© C100 are negative. However, a weak DNA damage activity in the in vitro and in vivo FPG-modified Comet assays and a weak clastogenic effect in the in vitro micronucleus test were reported. After investigating different parameters for the aerosol generation, male and female Wistar rats were exposed by nose-only inhalation (6h/day, 5d/week) to target concentrations of 0.05, 0.25 and 5.0 mg/m3 air of a respirable aerosol (MMAD < 3 µm) and sacrificed immediately after 4 and 13 weeks of exposure and 13 and 52 weeks of recovery after the 13-week exposure. Clinical, biological and histological evaluations were performed according to the OECD TG 413. Broncho-alveolar lavage fluid (BALF) was collected and analysed for cytokines and inflammatory parameters. Immediately after 13 weeks of exposure, chromosomal aberrations in the bone marrow cells of males and females were evaluated by the micronucleus test (OECD TG 474) and DNA damage in the lung, kidney and liver cells of males were assessed by both the standard and the human 8-oxoguanine DNA N-glycosylase 1 (hOGG1)-modified comet assay (OECD TG 489). Concentration-related deposition of black particles (MWCNT) was observed in lungs. At all sacrifice periods, an inflammatory lung reaction was observed in rats exposed to 5.0 mg/m3 associated with changes in the differential white blood cells counts. The lung inflammation was characterized by changes in the cytological, biochemical and cytokine parameters of the BALF, an increase of the lung weight, an interstitial inflammation mainly around the alveolar ducts at the bronchiole-alveolar junction and a cell hypertrophy/hyperplasia in the terminal and respiratory bronchioles. The slight changes in BALF parameters observed at 0.25 mg/m3 recovered after the 13-week treatment-free period and were not associated with any of the histological changes observed in lungs at 5.0 mg/m3. Signs of lung clearance of the MWCNT were observed at 0.05 and 0.25 mg/m3. After a one year treatment-free period, the inflammatory lung reaction was slight and of similar intensity that at the earlier sacrifice periods. Additional findings were minimal/slight bronchiolar/alveolar cell hypertrophy/hyperplasia and focally extensive alveolar septal fibrosis. No other pathological change was observed, nor was there any brain translocation via the olfactory bulb. The microscopic observations of the pleura were unremarkable. Neither increase in the number of micronucleated polychromatic erythrocytes nor increase in percent DNA damage were observed at any concentration. In conclusion, a lung inflammation characteristic of an overload with insoluble particles was observed after a 13-week inhalation exposure to 5.0 mg/m3 of Graphistrength© C100. A No-Observed Adverse Effect Concentration (NOAEC) of 0.25 mg/m3 was established for the repeated-dose toxicity and Graphistrength© C100 appears of low concern in term of local and systemic genotoxicity.

Alveolar macrophage development in mice requires L-plastin for cellular localization in alveoli.

PubMed

Todd, Elizabeth M; Zhou, Julie Y; Szasz, Taylor P; Deady, Lauren E; D'Angelo, June A; Cheung, Matthew D; Kim, Alfred H J; Morley, Sharon Celeste

2016-12-15

Alveolar macrophages are lung-resident sentinel cells that develop perinatally and protect against pulmonary infection. Molecular mechanisms controlling alveolar macrophage generation have not been fully defined. Here, we show that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveolar macrophages. Mice expressing a conditional allele of LPL (CD11c.Cre pos -LPL fl/fl ) exhibited significant reductions in alveolar macrophages and failed to effectively clear pulmonary pneumococcal infection, showing that immunodeficiency results from reduced alveolar macrophage numbers. We next identified the phase of alveolar macrophage development requiring LPL. In mice, fetal monocytes arrive in the lungs during a late fetal stage, maturing to alveolar macrophages through a prealveolar macrophage intermediate. LPL was required for the transition from prealveolar macrophages to mature alveolar macrophages. The transition from prealveolar macrophage to alveolar macrophage requires the upregulation of the transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ), which is induced by exposure to granulocyte-macrophage colony-stimulating factor (GM-CSF). Despite abundant lung GM-CSF and intact GM-CSF receptor signaling, PPAR-γ was not sufficiently upregulated in developing alveolar macrophages in LPL -/- pups, suggesting that precursor cells were not correctly localized to the alveoli, where GM-CSF is produced. We found that LPL supports 2 actin-based processes essential for correct localization of alveolar macrophage precursors: (1) transmigration into the alveoli, and (2) engraftment in the alveoli. We thus identify a molecular pathway governing neonatal alveolar macrophage development and show that genetic disruption of alveolar macrophage development results in immunodeficiency. © 2016 by The American Society of Hematology.

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

PubMed Central

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

2013-01-01

Alveolar fluid clearance driven by active epithelial Na+ and secondary Cl− absorption counteracts edema formation in the intact lung. Recently, we showed that impairment of alveolar fluid clearance because of inhibition of epithelial Na+ channels (ENaCs) promotes cardiogenic lung edema. Concomitantly, we observed a reversal of alveolar fluid clearance, suggesting that reversed transepithelial ion transport may promote lung edema by driving active alveolar fluid secretion. We, therefore, hypothesized that alveolar ion and fluid secretion may constitute a pathomechanism in lung edema and aimed to identify underlying molecular pathways. In isolated perfused lungs, alveolar fluid clearance and secretion were determined by a double-indicator dilution technique. Transepithelial Cl− secretion and alveolar Cl− influx were quantified by radionuclide tracing and alveolar Cl− imaging, respectively. Elevated hydrostatic pressure induced ouabain-sensitive alveolar fluid secretion that coincided with transepithelial Cl− secretion and alveolar Cl− influx. Inhibition of either cystic fibrosis transmembrane conductance regulator (CFTR) or Na+-K+-Cl− cotransporters (NKCC) blocked alveolar fluid secretion, and lungs of CFTR−/− mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride reproduced alveolar fluid and Cl− secretion that were again CFTR-, NKCC-, and Na+-K+-ATPase–dependent. Our findings show a reversal of transepithelial Cl− and fluid flux from absorptive to secretory mode at hydrostatic stress. Alveolar Cl− and fluid secretion are triggered by ENaC inhibition and mediated by NKCC and CFTR. Our results characterize an innovative mechanism of cardiogenic edema formation and identify NKCC1 as a unique therapeutic target in cardiogenic lung edema. PMID:23645634

Single shot damage mechanism of Mo/Si multilayer optics under intense pulsed XUV-exposure.

PubMed

Khorsand, A R; Sobierajski, R; Louis, E; Bruijn, S; van Hattum, E D; van de Kruijs, R W E; Jurek, M; Klinger, D; Pelka, J B; Juha, L; Burian, T; Chalupsky, J; Cihelka, J; Hajkova, V; Vysin, L; Jastrow, U; Stojanovic, N; Toleikis, S; Wabnitz, H; Tiedtke, K; Sokolowski-Tinten, K; Shymanovich, U; Krzywinski, J; Hau-Riege, S; London, R; Gleeson, A; Gullikson, E M; Bijkerk, F

2010-01-18

We investigated single shot damage of Mo/Si multilayer coatings exposed to the intense fs XUV radiation at the Free-electron LASer facility in Hamburg - FLASH. The interaction process was studied in situ by XUV reflectometry, time resolved optical microscopy, and "post-mortem" by interference-polarizing optical microscopy (with Nomarski contrast), atomic force microscopy, and scanning transmission electron microcopy. An ultrafast molybdenum silicide formation due to enhanced atomic diffusion in melted silicon has been determined to be the key process in the damage mechanism. The influence of the energy diffusion on the damage process was estimated. The results are of significance for the design of multilayer optics for a new generation of pulsed (from atto- to nanosecond) XUV sources.

Mild traumatic brain injury: is diffusion imaging ready for primetime in forensic medicine?

PubMed

Grossman, Elan J; Inglese, Matilde; Bammer, Roland

2010-12-01

Mild traumatic brain injury (MTBI) is difficult to accurately assess with conventional imaging because such approaches usually fail to detect any evidence of brain damage. Recent studies of MTBI patients using diffusion-weighted imaging and diffusion tensor imaging suggest that these techniques have the potential to help grade tissue damage severity, track its development, and provide prognostic markers for clinical outcome. Although these results are promising and indicate that the forensic diagnosis of MTBI might eventually benefit from the use of diffusion-weighted imaging and diffusion tensor imaging, healthy skepticism and caution should be exercised with regard to interpreting their meaning because there is no consensus about which methods of data analysis to use and very few investigations have been conducted, of which most have been small in sample size and examined patients at only one time point after injury.

Is there a relation between local bone quality as assessed on panoramic radiographs and alveolar bone level?

PubMed

Nackaerts, Olivia; Gijbels, Frieda; Sanna, Anna-Maria; Jacobs, Reinhilde

2008-03-01

The aim was to explore the relation between radiographic bone quality on panoramic radiographs and relative alveolar bone level. Digital panoramic radiographs of 94 female patients were analysed (mean age, 44.5; range, 35-74). Radiographic density of the alveolar bone in the premolar region was determined using Agfa Musica software. Alveolar bone level and bone quality index (BQI) were also assessed. Relationships between bone density and BQI on one hand and the relative loss of alveolar bone level on the other were assessed. Mandibular bone density and loss of alveolar bone level were weakly but significantly negatively correlated for the lower premolar area (r = -.27). The BQI did not show a statistically significant relation to alveolar bone level. Radiographic mandibular bone density on panoramic radiographs shows a weak but significant relation to alveolar bone level, with more periodontal breakdown for less dense alveolar bone.

Differences between co-cultures and monocultures in testing the toxicity of particulate matter derived from log wood and pellet combustion.

PubMed

Kasurinen, Stefanie; Happo, Mikko S; Rönkkö, Teemu J; Orasche, Jürgen; Jokiniemi, Jorma; Kortelainen, Miika; Tissari, Jarkko; Zimmermann, Ralf; Hirvonen, Maija-Riitta; Jalava, Pasi I

2018-01-01

In vitro studies with monocultures of human alveolar cells shed deeper knowledge on the cellular mechanisms by which particulate matter (PM) causes toxicity, but cannot account for mitigating or aggravating effects of cell-cell interactions on PM toxicity. We assessed inflammation, oxidative stress as well as cytotoxic and genotoxic effects induced by PM from the combustion of different types of wood logs and softwood pellets in three cell culture setups: two monocultures of either human macrophage-like cells or human alveolar epithelial cells, and a co-culture of these two cell lines. The adverse effects of the PM samples were compared between these setups. We detected clear differences in the endpoints between the mono- and co-cultures. Inflammatory responses were more diverse in the macrophage monoculture and the co-culture compared to the epithelial cells where only an increase of IL-8 was detected. The production of reactive oxygen species was the highest in epithelial cells and macrophages seemed to have protective effects against oxidative stress from the PM samples. With no metabolically active cells at the highest doses, the cytotoxic effects of the PM samples from the wood log combustion were far more pronounced in the macrophages and the co-culture than in the epithelial cells. All samples caused DNA damage in macrophages, whereas only beech and spruce log combustion samples caused DNA damage in epithelial cells. The organic content of the samples was mainly associated with cytotoxicity and DNA damage, while the metal content of the samples correlated with the induction of inflammatory responses. All of the tested PM samples induce adverse effects and the chemical composition of the samples determines which pathway of toxicity is induced. In vitro testing of the toxicity of combustion-derived PM in monocultures of one cell line, however, is inadequate to account for all the possible pathways of toxicity.

Exercise Training Mitigates Water Pipe Smoke Exposure-Induced Pulmonary Impairment via Inhibiting NF-κB and Activating Nrf2 Signalling Pathways

PubMed Central

Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H.

2018-01-01

Water pipe smoking is a tobacco smoking method commonly used in Eastern countries and is gaining popularity in Europe and North America, in particular among adolescents and young adults. Several clinical and experimental studies have reported that exposure to water pipe smoke (WPS) induces lung inflammation and impairment of pulmonary function. However, the mechanisms of such effects are not understood, as are data on the possible palliative effect of exercise training. The present study evaluated the effects of regular aerobic exercise training (treadmill: 5 days/week, 40 min/day) on subchronic exposure to WPS (30 minutes/day, 5 days/week for 2 months). C57BL/6 mice were exposed to air or WPS with or without exercise training. Airway resistance measured using forced oscillation technique was significantly and dose-dependently increased in the WPS-exposed group when compared with the air-exposed one. Exercise training significantly prevented the effect of WPS on airway resistance. Histologically, the lungs of WPS-exposed mice had focal moderate interstitial inflammatory cell infiltration consisting of neutrophil polymorphs, plasma cells, and lymphocytes. There was a mild increase in intra-alveolar macrophages and a focal damage to alveolar septae in some foci. Exercise training significantly alleviated these effects and also decreased the WPS-induced increase of tumor necrosis factor α and interleukin 6 concentrations and attenuated the increase of 8-isoprostane in lung homogenates. Likewise, the lung DNA damage induced by WPS was significantly inhibited by exercise training. Moreover, exercise training inhibited nuclear factor kappa-B (NF-κB) expression induced by WPS and increased that of nuclear factor erythroid 2-related factor 2 (Nrf2). Our findings suggest that exercise training significantly mitigated WPS-induced increase in airway resistance, inflammation, oxidative stress, and DNA damage via mechanisms that include inhibiting NF-κB and activating Nrf2 signalling pathways. PMID:29692875

Differences between co-cultures and monocultures in testing the toxicity of particulate matter derived from log wood and pellet combustion

PubMed Central

Happo, Mikko S.; Rönkkö, Teemu J.; Orasche, Jürgen; Jokiniemi, Jorma; Kortelainen, Miika; Tissari, Jarkko; Zimmermann, Ralf; Hirvonen, Maija-Riitta; Jalava, Pasi I.

2018-01-01

Background In vitro studies with monocultures of human alveolar cells shed deeper knowledge on the cellular mechanisms by which particulate matter (PM) causes toxicity, but cannot account for mitigating or aggravating effects of cell-cell interactions on PM toxicity. Methods We assessed inflammation, oxidative stress as well as cytotoxic and genotoxic effects induced by PM from the combustion of different types of wood logs and softwood pellets in three cell culture setups: two monocultures of either human macrophage-like cells or human alveolar epithelial cells, and a co-culture of these two cell lines. The adverse effects of the PM samples were compared between these setups. Results We detected clear differences in the endpoints between the mono- and co-cultures. Inflammatory responses were more diverse in the macrophage monoculture and the co-culture compared to the epithelial cells where only an increase of IL-8 was detected. The production of reactive oxygen species was the highest in epithelial cells and macrophages seemed to have protective effects against oxidative stress from the PM samples. With no metabolically active cells at the highest doses, the cytotoxic effects of the PM samples from the wood log combustion were far more pronounced in the macrophages and the co-culture than in the epithelial cells. All samples caused DNA damage in macrophages, whereas only beech and spruce log combustion samples caused DNA damage in epithelial cells. The organic content of the samples was mainly associated with cytotoxicity and DNA damage, while the metal content of the samples correlated with the induction of inflammatory responses. Conclusions All of the tested PM samples induce adverse effects and the chemical composition of the samples determines which pathway of toxicity is induced. In vitro testing of the toxicity of combustion-derived PM in monocultures of one cell line, however, is inadequate to account for all the possible pathways of toxicity. PMID:29466392

Boat Hull Blisters: Repair Techniques and Long Term Effects on Hull Degradation

DTIC Science & Technology

1988-08-01

Swelling Stresses Produced by Diffusion; Long Term Damage by Water Absorption ; Effects of Gel Coat on Leaching of Water Soluble Material from...leinforcesents 5. Swelling Stresses Produced by Diffusion 6. Long Term Damage by Water Absorption 7. Effects of Gel Coat on Leaching of Water Soluble...the importance of bilge side water pick-up is emphasized. A second method for preventing blister formation is to eliminate or minimize the water soluble

Diffuse alveolar hemorrhage: retrospective review of clinical outcome in allogeneic transplant recipients treated with aminocaproic acid.

PubMed

Wanko, Sam O; Broadwater, Gloria; Folz, Rodney J; Chao, Nelson J

2006-09-01

Diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (HSCT) is often fatal. Standard therapy with high-dose corticosteroid is not always effective. There is paucity of data in the literature about other potentially useful agents, such as aminocaproic acid (Amicar) in the post-transplantation setting. We retrospectively reviewed our data on 115 consecutive patients who underwent HSCT and had pulmonary complications, with the aim of determining the overall clinical outcome in recipients of allogeneic transplants and in the subgroup of these patients who were treated with concomitant Solu-Medrol and aminocaproic acid. Aminocaproic acid was added at the discretion of the attending physician. We identified 14 allogeneic transplant recipients (median age, 41 years) with 15 episodes of DAH who were treated with Solu-Medrol (250 mg to 1 g intravenously per day). Of these, 8 patients also received concomitant aminocaproic acid at 1000 mg intravenously every 6 hours. Failure to improve was the most common reason for adding aminocaproic acid. The incidence of DAH was 12.2% (10.3% in myeloablative versus 1.9% in nonmyeloablative recipients). The overall 100-day DAH mortality and median transplantation survival were 60% and 99 days, respectively. Among the subset of patients treated with the combination of Solu-Medrol and aminocaproic acid, we observed a 100-day DAH mortality and median transplantation survival of 44% and 167 days, respectively, compared with 83% and 96.5 days in those treated with Solu-Medrol alone. The median time to DAH was 40.5 days, and the median time to death was 53 days in the combined treatment group compared with 29.5 days in those treated with steroid alone. There were no significant differences in coagulation parameters between subsets. Infections (yeast, respiratory syncytial virus, herpes simplex virus, and parainfluenza) were isolated and treated from 6 diagnostic bronchial alveolar lavage samples and were more common in the subgroup treated with Solu-Medrol only. Respiratory failure was the documented cause of death in 89% of patients. There were no clinically significant side effects from aminocaproic acid. Although these historically lower DAH outcomes are intriguing, prospective studies are needed to confirm the role of aminocaproic acid in DAH occurring in the allogeneic transplantation setting.

The severe pathogenicity of alveolar macrophage-depleted ferrets infected with 2009 pandemic H1N1 influenza virus.

PubMed

Kim, Heui Man; Kang, Young Myong; Ku, Keun Bon; Park, Eun Hye; Yum, Jung; Kim, Jeong Cheol; Jin, Seo Yeon; Lee, Joo Sub; Kim, Hyun Soo; Seo, Sang Heui

2013-09-01

The in vivo role of alveolar macrophages in the infections with 2009 pandemic H1N1 influenza virus is not as yet known. Ferret study shows that alveolar macrophages are critical for lowering the risk of severe outcomes in 2009 pandemic H1N1 influenza virus infections. Up to 40% of the infected ferrets depleted of alveolar macrophages died, with elevated body temperature and major loss of body weight in contrast to infected ferrets not depleted of alveolar macrophages. The higher viral titers in the lungs were detected in infected ferrets depleted of alveolar macrophages than infected ferrets not depleted of alveolar macrophages 5 days after infection. The inflammatory chemokines were induced at greater levels in the lungs of infected ferrets depleted of alveolar macrophages than in those of infected ferrets not depleted of alveolar macrophages. Our study implies that alveolar macrophages are important for controlling the infections of 2009 pandemic H1N1 influenza virus. © 2013 Elsevier Inc. All rights reserved.

Hyperpolarized 129Xe MRI: A Viable Functional Lung Imaging Modality?

PubMed Central

Patz, Samuel; Hersman, F. William; Muradian, Iga; Hrovat, Mirko I.; Ruset, Iulian C.; Ketel, Stephen; Jacobson, Francine; Topulos, George P.; Hatabu, Hiroto; Butler, James P.

2008-01-01

The majority of researchers investigating hyperpolarized gas MRI as a candidate functional lung imaging modality have used 3He as their imaging agent of choice rather than 129Xe. This preference has been predominantly due to, 3He providing stronger signals due to higher levels of polarization and higher gyromagnetic ratio, as well as its being easily available to more researchers due to availability of polarizers (USA) or ease of gas transport (Europe). Most researchers agree, however, that hyperpolarized 129Xe will ultimately emerge as the imaging agent of choice due to its unlimited supply in nature and its falling cost. Our recent polarizer technology delivers vast improvements in hyperpolarized 129Xe output. Using this polarizer, we have demonstrated the unique property of xenon to measure alveolar surface area noninvasively. In this article, we describe our human protocols and their safety, and our results for the measurement of the partial pressure of pulmonary oxygen (pO2) by observation of 129Xe signal decay. We note that the measurement of pO2 by observation of 129Xe signal decay is more complex than that for 3He because of an additional signal loss mechanism due to interphase diffusion of 129Xe from alveolar gas spaces to septal tissue. This results in measurements of an equivalent pO2 that accounts for both traditional T1 decay from pO2 and that from interphase diffusion. We also provide an update on new technological advancements that form the foundation for an improved compact design polarizer as well as improvements that provide another order-of-magnitude scale-up in xenon polarizer output. PMID:17890035

[Interpretation and use of routine pulmonary function tests: Spirometry, static lung volumes, lung diffusion, arterial blood gas, methacholine challenge test and 6-minute walk test].

PubMed

Bokov, P; Delclaux, C

2016-02-01

Resting pulmonary function tests (PFT) include the assessment of ventilatory capacity: spirometry (forced expiratory flows and mobilisable volumes) and static volume assessment, notably using body plethysmography. Spirometry allows the potential definition of obstructive defect, while static volume assessment allows the potential definition of restrictive defect (decrease in total lung capacity) and thoracic hyperinflation (increase in static volumes). It must be kept in mind that this evaluation is incomplete and that an assessment of ventilatory demand is often warranted, especially when facing dyspnoea: evaluation of arterial blood gas (searching for respiratory insufficiency) and measurement of the transfer coefficient of the lung, allowing with the measurement of alveolar volume to calculate the diffusing capacity of the lung for CO (DLCO: assessment of alveolar-capillary wall and capillary blood volume). All these pulmonary function tests have been the subject of an Americano-European Task force (standardisation of lung function testing) published in 2005, and translated in French in 2007. Interpretative strategies for lung function tests have been recommended, which define abnormal lung function tests using the 5th and 95th percentiles of predicted values (lower and upper limits of normal values). Thus, these recommendations need to be implemented in all pulmonary function test units. A methacholine challenge test will only be performed in the presence of an intermediate pre-test probability for asthma (diagnostic uncertainty), which is an infrequent setting. The most convenient exertional test is the 6-minute walk test that allows the assessment of walking performance, the search for arterial desaturation and the quantification of dyspnoea complaint. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

PubMed Central

Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

2013-01-01

Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from 8 CF subjects and 8 healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared to controls. CF subjects had lower serum and BAL IGF-1 levels compared to healthy controls. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, while IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo, results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment. PMID:23698746

The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion: The Pathway for Oxygen.

PubMed

Bassingthwaighte, James B; Raymond, Gary M; Dash, Ranjan K; Beard, Daniel A; Nolan, Margaret

2016-01-01

The 'Pathway for Oxygen' is captured in a set of models describing quantitative relationships between fluxes and driving forces for the flux of oxygen from the external air source to the mitochondrial sink at cytochrome oxidase. The intervening processes involve convection, membrane permeation, diffusion of free and heme-bound O2 and enzymatic reactions. While this system's basic elements are simple: ventilation, alveolar gas exchange with blood, circulation of the blood, perfusion of an organ, uptake by tissue, and consumption by chemical reaction, integration of these pieces quickly becomes complex. This complexity led us to construct a tutorial on the ideas and principles; these first PathwayO2 models are simple but quantitative and cover: (1) a 'one-alveolus lung' with airway resistance, lung volume compliance, (2) bidirectional transport of solute gasses like O2 and CO2, (3) gas exchange between alveolar air and lung capillary blood, (4) gas solubility in blood, and circulation of blood through the capillary syncytium and back to the lung, and (5) blood-tissue gas exchange in capillaries. These open-source models are at Physiome.org and provide background for the many respiratory models there.

The Pathway for Oxygen: Tutorial Modelling on Oxygen Transport from Air to Mitochondrion

PubMed Central

Bassingthwaighte, James B.; Raymond, Gary M.; Dash, Ranjan K.; Beard, Daniel A.; Nolan, Margaret

2016-01-01

The ‘Pathway for Oxygen’ is captured in a set of models describing quantitative relationships between fluxes and driving forces for the flux of oxygen from the external air source to the mitochondrial sink at cytochrome oxidase. The intervening processes involve convection, membrane permeation, diffusion of free and heme-bound O2 and enzymatic reactions. While this system’s basic elements are simple: ventilation, alveolar gas exchange with blood, circulation of the blood, perfusion of an organ, uptake by tissue, and consumption by chemical reaction, integration of these pieces quickly becomes complex. This complexity led us to construct a tutorial on the ideas and principles; these first PathwayO2 models are simple but quantitative and cover: 1) a ‘one-alveolus lung’ with airway resistance, lung volume compliance, 2) bidirectional transport of solute gasses like O2 and CO2, 3) gas exchange between alveolar air and lung capillary blood, 4) gas solubility in blood, and circulation of blood through the capillary syncytium and back to the lung, and 5) blood-tissue gas exchange in capillaries. These open-source models are at Physiome.org and provide background for the many respiratory models there. PMID:26782201

Preliminary observations on the effect of hypoxic and hyperbaric stress on pulmonary gas exchange in breath-hold divers.

PubMed

Garbella, Erika; Piarulli, Andrea; Fornai, Edo; Pingitore, Alessandro; Prediletto, Renato

2011-06-01

To evaluate pulmonary alveolar-capillary membrane integrity and ventilation/perfusion mismatch after breath-hold diving. Pulmonary diffusing capacity to carbon monoxide (DLCO) and nitric oxide (DLNO), haemoglobin (Hb) and haematocrit (Hct) were measured in six elite divers before and at 2, 10 and 25 minutes after a maximal breath-hold dive to a depth of 10 metres' sea water. Compared to pre-dive, DLCO showed a slight increase at 2 minutes in five subjects and a tendency to decrease at 25 minutes (P < 0.001) in all subjects. DLNO showed an increase at 10 minutes in three divers and a slight decrease at 25 minutes in five subjects. There was a small but significant (P < 0.001) increase in Hb and Hct at 2 minutes, possibly affecting the DLCO measurements. An early but transient increase in DLCO in five divers may reflect the central shift in blood volume during a breath-hold dive. The late parallel decrease in DLCO and DLNO likely reflects alveolar-capillary distress (interstitial oedema). The DLNO increase in three subjects at 10 minutes may suggest ventilation/perfusion mismatch.

Quantitative Examination of Corrosion Damage by Means of Thermal Response Measurements

NASA Technical Reports Server (NTRS)

Rajic, Nik

1998-01-01

Two computational methods are presented that enable a characterization of corrosion damage to be performed from thermal response measurements derived from a standard flash thermographic inspection. The first is based upon a one dimensional analytical solution to the heat diffusion equation and presumes the lateral extent of damage is large compared to the residual structural thickness, such that lateral heat diffusion effects can be considered insignificant. The second proposed method, based on a finite element optimization scheme, addresses the more general case where these conditions are not met. Results from an experimental application are given to illustrate the precision, robustness and practical efficacy of both methods.

Nicotine inhibits collagen synthesis and alkaline phosphatase activity, but stimulates DNA synthesis in osteoblast-like cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramp, W.K.; Lenz, L.G.; Galvin, R.J.

1991-05-01

Use of smokeless tobacco is associated with various oral lesions including periodontal damage and alveolar bone loss. This study was performed to test the effects of nicotine on bone-forming cells at concentrations that occur in the saliva of smokeless tobacco users. Confluent cultures of osteoblast-like cells isolated from chick embryo calvariae were incubated for 2 days with nicotine added to the culture medium (25-600 micrograms/ml). Nicotine inhibited alkaline phosphatase in the cell layer and released to the medium, whereas glycolysis (as indexed by lactate production) was unaffected or slightly elevated. The effects on medium and cell layer alkaline phosphatase weremore » concentration dependent with maximal inhibition occurring at 600 micrograms nicotine/ml. Nicotine essentially did not affect the noncollagenous protein content of the cell layer, but did inhibit collagen synthesis (hydroxylation of ({sup 3}H)proline and collagenase-digestible protein) at 100, 300, and 600 micrograms/ml. Release of ({sup 3}H)hydroxyproline to the medium was also decreased in a dose-dependent manner, as was the collagenase-digestible protein for both the medium and cell layer. In contrast, DNA synthesis (incorporation of ({sup 3}H)thymidine) was more than doubled by the alkaloid, whereas total DNA content was slightly inhibited at 600 micrograms/ml, suggesting stimulated cell turnover. Morphologic changes occurred in nicotine-treated cells including rounding up, detachment, and the occurrence of numerous large vacuoles. These results suggest that steps to reduce the salivary concentration of nicotine in smokeless tobacco users might diminish damaging effects of this product on alveolar bone.« less

A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma.

PubMed

Catal, F; Mete, E; Tayman, C; Topal, E; Albayrak, A; Sert, H

2015-01-01

A few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model. Twelve-week-old BALB/c (H-2d/d) female rats (n=18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab (n=6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed. Severity of lung damage was found to be reduced significantly in the asthma induced with OVA+treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score=1, p=0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration. Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Idiopathic pulmonary fibrosis may be a disease of recurrent, tractional injury to the periphery of the aging lung: a unifying hypothesis regarding etiology and pathogenesis.

PubMed

Leslie, Kevin O

2012-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal lung disease occurring in older individuals. Despite 50 years of accrued data about the disease, little progress has been made in slowing functional loss or in decreasing patient mortality. To present a novel hypothesis on the etiology and pathogenesis of idiopathic pulmonary fibrosis. Published data are reviewed regarding the epidemiology, clinical presentation, natural history, radiologic findings, and pathologic findings in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis may be predisposed genetically to tractional injury to the peripheral lung. The result is recurrent damage to the epithelial-mesenchymal interface, preferentially at the outer edges of the basilar lung lobules where tractional stress is high during inspiration, compliance is relatively low, and there is a greater tendency for alveolar collapse at end-expiration. A distinctive "reticular network of injury" (the fibroblast focus) forms, attended by a prolonged phase of wound repair (tear and slow repair). Discrete areas of alveolar collapse are observed in scar at the periphery of the lung lobules. The cycle repeats over many years resulting in progressive fibrous remodeling and replacement of the alveoli in a lobule by bronchiolar cysts surrounded by scar (honeycomb lung). Abnormalities in surfactant function are proposed as a potential mechanism of initial lung damage. Age of onset may be a function of a required threshold of environmental exposures (eg, cigarette smoking) or other comorbid injury to the aging lung. Evidence supporting this hypothesis is presented and potential mechanisms are discussed. A potential role for contributing cofactors is presented.

Comparative inhalation toxicology of selected materials. Phase 2. Final report, January-July 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snipes, M.B.; Bice, D.E.; Burt, D.G.

1988-05-01

Male and female F344/N rats were exposed nose-only to a respirable powder of copper-zinc alloy. No rats died as a result of the exposures. Body weights were reduced relative to sham-exposed rats for rats exposed to 240 and 480 mg. hr Cu-Zn/cu.m week. All of the additional observed biological responses to inhaled Cu-Zn were restricted to the respiratory tract. Lung weights were increased due to an inflammatory response for rats exposed to 120 mg. hr Cu-Zn/cu.m or more per week. Exposure to 240 mg. hr Cu-zn/cu.m per week caused restrictive pulmonary functional disorder, as evidenced by a reduced lung capacity,more » reduced quasi-static compliance, reduced carbon monoxide diffusing capacity, and increased percent forced vital capacity exhaled in 0.1 second. Exposure-related responses in lavage-fluid indicators of lung damage included increased beta-glucuronidase, increased lactate dehydrogenase, and increases in inflammatory cells, total protein, and collagen. Histological lesions produced by Cu-Zn were atrophy of the nasal olfactory epithelium and hyperplasia of goblet cells in the respiratory epithelium, focal necrotizing alveolitis, alveolar macrophage hyperplasia, and goblet cell hyperplasia of bronchial and bronchiolar epithelium. The inhaled Cu-Zn alloy caused exposure-related inflammatory and cytotoxic responses in the respiratory tract, but the inhaled Cu-Zn cleared rapidly and the responses largely resolved after cessation of exposures.« less

Keratin14 mRNA expression in human pneumocytes during quiescence, repair and disease

PubMed Central

Confalonieri, Marco; Buratti, Emanuele; Grassi, Gabriele; Bussani, Rossana; Chilosi, Marco; Farra, Rossella; Abrami, Michela; Stuani, Cristiana; Salton, Francesco; Ficial, Miriam; Confalonieri, Paola; Zandonà, Lorenzo; Romano, Maurizio

2017-01-01

The lung alveoli slowly self-renew pneumocytes, but their facultative regeneration capacity is rapidly efficient after an injury, so fibrosis infrequently occurs. We recently observed Keratin 14 (KRT14) expression during diffuse alveolar damage (DAD), but not in controls. We wonder if KRT14 may be a marker of pneumocyte transition from quiescence to regeneration. Quantitative PCR and Western blot analyses highlighted the presence of KRT14 (mRNA and protein) only in human lung samples with DAD or interstitial lung disease (ILD). In the exponentially growing cell lines A549 and H441, the mRNA and protein levels of KRT14 peaked at day one after cell seeding and decreased at day two, opposite to what observed for the proliferation marker E2F1. The inverse relation of KRT14 versus E2F1 expression holds true also for other proliferative markers, such as cyclin E1 and cyclin D1. Of interest, we also found that E2F1 silencing caused cell cycle arrest and increased KRT14 expression, whilst E2F1 stimulation induced cell cycle progression and decreased KRT14. KRT14 also increased in proliferative pneumocytes (HPAEpiC) just before transdifferentiation. Overall, our results suggest that KRT14 is a viable biomarker of pneumocyte activation, and repair/regeneration. The involvement of KRT14 in regenerative process may suggest a novel pharmaceutical target to accelerate lung repair. PMID:28199407

Keratin14 mRNA expression in human pneumocytes during quiescence, repair and disease.

PubMed

Confalonieri, Marco; Buratti, Emanuele; Grassi, Gabriele; Bussani, Rossana; Chilosi, Marco; Farra, Rossella; Abrami, Michela; Stuani, Cristiana; Salton, Francesco; Ficial, Miriam; Confalonieri, Paola; Zandonà, Lorenzo; Romano, Maurizio

2017-01-01

The lung alveoli slowly self-renew pneumocytes, but their facultative regeneration capacity is rapidly efficient after an injury, so fibrosis infrequently occurs. We recently observed Keratin 14 (KRT14) expression during diffuse alveolar damage (DAD), but not in controls. We wonder if KRT14 may be a marker of pneumocyte transition from quiescence to regeneration. Quantitative PCR and Western blot analyses highlighted the presence of KRT14 (mRNA and protein) only in human lung samples with DAD or interstitial lung disease (ILD). In the exponentially growing cell lines A549 and H441, the mRNA and protein levels of KRT14 peaked at day one after cell seeding and decreased at day two, opposite to what observed for the proliferation marker E2F1. The inverse relation of KRT14 versus E2F1 expression holds true also for other proliferative markers, such as cyclin E1 and cyclin D1. Of interest, we also found that E2F1 silencing caused cell cycle arrest and increased KRT14 expression, whilst E2F1 stimulation induced cell cycle progression and decreased KRT14. KRT14 also increased in proliferative pneumocytes (HPAEpiC) just before transdifferentiation. Overall, our results suggest that KRT14 is a viable biomarker of pneumocyte activation, and repair/regeneration. The involvement of KRT14 in regenerative process may suggest a novel pharmaceutical target to accelerate lung repair.

Causes of death of patients with lung cancer.

PubMed

Nichols, Larry; Saunders, Rachel; Knollmann, Friedrich D

2012-12-01

The causes of death for patients with lung cancer are inadequately described. To categorize the immediate and contributing causes of death for patients with lung cancer. The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

The simultaneous enhancement of photorefraction and optical damage resistance in MgO and Bi2O3 co-doped LiNbO3 crystals

PubMed Central

Zheng, Dahuai; Kong, Yongfa; Liu, Shiguo; Chen, Muling; Chen, Shaolin; Zhang, Ling; Rupp, Romano; Xu, Jingjun

2016-01-01

For a long time that optical damage was renamed as photorefraction, here we find that the optical damage resistance and photorefraction can be simultaneously enhanced in MgO and Bi2O3 co-doped LiNbO3 (LN:Bi,Mg). The photorefractive response time of LN:Bi,Mg was shortened to 170 ms while the photorefractive sensitivity reached up to 21 cm2/J. Meanwhile, LN:Bi,Mg crystals could withstand a light intensity higher than 106  W/cm2 without apparent optical damage. Our experimental results indicate that photorefraction doesn’t equal to optical damage. The underground mechanism was analyzed and attributed to that diffusion dominates the transport process of charge carriers, that is to say photorefraction causes only slight optical damage under diffusion mechanism, which is very important for the practical applications of photorefractive crystals, such as in holographic storage, integrated optics and 3D display. PMID:26837261

Three-dimensional analysis of alveolar wall destruction in the early stage of pulmonary emphysema.

PubMed

Kobayashi, Yukihiro; Uehara, Takeshi; Kawasaki, Kenji; Sugano, Mitsutoshi; Matsumoto, Takehisa; Matsumoto, Gou; Honda, Takayuki

2015-03-01

The morphological mechanism of alveolar wall destruction during pulmonary emphysema has not been clarified. The aim of this study was to elucidate this process three-dimensionally. Lung specimens from five patients with pulmonary emphysema were used, and five controls with normal alveolar structure were also examined. Sections 150 μm thick were stained with hematoxylin and eosin, elastica, and silver impregnation, and immunostained with selected antibodies. We examined these sections three-dimensionally using a laser confocal microscope and a light microscope. There were only a few Kohn's pores and no fenestrae in the normal alveoli from the controls. In the lungs of the emphysema patients a small rupture appeared in the extremely thin alveolar wall among the alveolar capillaries. This rupture enlarged to form a circle surrounded by the capillaries, which was called an alveolar fenestra. Two neighboring fenestrae fused by breakdown of the collapsed or cord-like capillary between them to form a large fenestra. The large fenestrae fused repeatedly to become larger, and these were bordered by thick elastic fibers constructing an alveolar framework. Alveolar wall destruction during emphysema could start from small ruptures of the alveolar wall that become fenestrae surrounded by capillaries, which fuse repeatedly to become larger fenestrae rimmed with elastic fibers. The alveolar capillary network could initially prevent enlargement of the fenestrae, and the thick elastic fibers constituting the alveolar framework could secondarily prevent destruction of the alveolar wall structure. © 2014 Wiley Periodicals, Inc.

Binding of anti-basement membrane antibody to alveolar basement membrane after intratracheal gasoline instillation in rabbits.

PubMed Central

Yamamoto, T.; Wilson, C. B.

1987-01-01

A possible causal relationship has been suggested between hydrocarbon (gasoline, solvents, etc.) exposure and development of anti-basement membrane antibody-associated Goodpasture's syndrome in man. The authors evaluated the effect of hydrocarbons on pulmonary capillary permeability and binding of heterologous anti-basement membrane antibodies in the lungs after intratracheal instillation of minute amounts of unleaded gasoline into rabbits. The anti-glomerular basement membrane (GBM) antibodies used reacted with the alveolar basement membrane (ABM) in vitro by indirect immunofluorescence. The gasoline treatment altered pulmonary capillary permeability, judging from the increased accumulation of systemically administered radioiodinated bovine serum albumin in the alveolar and extravascular spaces of lungs; it also induced focal macroscopic and microscopic pulmonary histologic lesions. The gasoline caused focal in vivo binding of the anti-GBM antibodies to the ABM detectable by immunofluorescence microscopy. No binding was observed in lungs from control rabbits given saline instillations when assayed by immunofluorescence. The paired label radioisotope technique confirmed the increased antibody binding to lungs injured with gasoline (1.08 +/- 0.03 micrograms) versus 0.37 +/- 0.07 microgram after saline (P less than 0.001). These results indicate that gasoline exposure damages a pulmonary barrier that normally prevents binding of anti-GBM/ABM antibody to ABM and suggest that hydrocarbon exposure may be one of perhaps several pneumotoxic events that contribute to the episodic pulmonary hemorrhage in Goodpasture's syndrome by temporarily allowing ABM binding of anti-basement membrane antibodies. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3548409

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

PubMed

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  < 0.05. The mean vertical augmentation at immediate post-op was 6.58 mm ( p  = 0.001). The vertical augmentation that was achieved 3 months post-op was a mean of 3.75 mm which was statistically significant ( p  = 0.004). The change in alveolar height from immediate post-op to 3 month post-op was a mean 1.69 mm. The mean change in alveolar crestal width at 3 months was a mean of -0.29 mm ( p  = 0.57). 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.

Rate of disappearance of labeled carbon dioxide from the lungs of humans during breath holding: a method for studying the dynamics of pulmonary CO2 exchange

PubMed Central

Hyde, Richard W.; Puy, Ricardo J. M.; Raub, William F.; Forster, Robert E.

1968-01-01

The dynamics of CO2 exchange in the lungs of man was studied by observing the rate of disappearance of a stable isotope of CO2 (13CO2) from the alveolar gas during breath holding. Over 50% of the inspired isotope disappeared within the first 3 sec followed by a moderately rapid logarithmic decline in which one-half of the remaining 13CO2 disappeared every 10 sec. The large initial disappearance of 13CO2 indicated that alveolar 13CO2 equilibrated in less than 3 sec with the CO2 stored in the pulmonary tissues and capillary blood. The volume of CO2 in the pulmonary tissues calculated from this initial disappearance was 200 ml or 0.33 ml of CO2 per milliliter of pulmonary tissue volume. The alveolar to end-capillary gradient for 13CO2 was calculated by comparing the simultaneous disappearance rates of 13CO2 and acetylene. At rest and during exercise this gradient for 13CO2 was either very small or not discernible, and diffusing capacity for CO2 (DLCO2) exceeded 200 ml/(min × mm Hg). After the administration of a carbonic anhydrase inhibitor the rate of disappearance of 13CO2 decreased markedly. DLCO2 fell to 42 ml/(min × mm Hg) and at least 70% of the exchange of 13CO2 with the CO2 stores in the pulmonary tissues and blood was blocked by the inhibitor. These changes were attributed to impairment of exchange of 13CO2 with the bicarbonate in the pulmonary tissues and blood. The pH of the pulmonary tissues (Vtis) was determined by a method based on the premise that the CO2 space in the pulmonary tissues blocked by the inhibitor represented total bicarbonate content. At an alveolar PCO2 of 40 mm Hg pH of Vtis equalled 6.97 ± 0.09. PMID:5658586

3He Lung Morphometry Technique: Accuracy Analysis and Pulse Sequence Optimization

PubMed Central

Sukstanskii, A.L.; Conradi, M.S.; Yablonskiy, D.A.

2010-01-01

The 3He lung morphometry technique (Yablonskiy et al, JAP, 2009), based on MRI measurements of hyperpolarized gas diffusion in lung airspaces, provides unique information on the lung microstructure at the alveolar level. 3D tomographic images of standard morphological parameters (mean airspace chord length, lung parenchyma surface-to-volume ratio, and the number of alveoli per unit lung volume) can be created from a rather short (several seconds) MRI scan. These parameters are most commonly used to characterize lung morphometry but were not previously available from in vivo studies. A background of the 3He lung morphometry technique is based on a previously proposed model of lung acinar airways, treated as cylindrical passages of external radius R covered by alveolar sleeves of depth h, and on a theory of gas diffusion in these airways. The initial works approximated the acinar airways as very long cylinders, all with the same R and h. The present work aims at analyzing effects of realistic acinar airway structures, incorporating airway branching, physiological airway lengths, a physiological ratio of airway ducts and sacs, and distributions of R and h. By means of Monte Carlo computer simulations, we demonstrate that our technique allows rather accurate measurements of geometrical and morphological parameters of acinar airways. In particular, the accuracy of determining one of the most important physiological parameter of acinar airways – surface-to-volume ratio – does not exceed several percent. Second, we analyze the effect of the susceptibility induced inhomogeneous magnetic field on the parameter estimate and demonstrate that this effect is rather negligible at B0 ≤ 3T and becomes substantial only at higher B0 Third, we theoretically derive an optimal choice of MR pulse sequence parameters, which should be used to acquire a series of diffusion attenuated MR signals, allowing a substantial decrease in the acquisition time and improvement in accuracy of the results. It is demonstrated that the optimal choice represents three not equidistant b-values: b1 = 0, b2 ~ 2 s/cm2, b3 ~ 8 s/cm2. PMID:20937564

The large lungs of elite swimmers: an increased alveolar number?

PubMed

Armour, J; Donnelly, P M; Bye, P T

1993-02-01

In order to obtain further insight into the mechanisms relating to the large lung volumes of swimmers, tests of mechanical lung function, including lung distensibility (K) and elastic recoil, pulmonary diffusion capacity, and respiratory mouth pressures, together with anthropometric data (height, weight, body surface area, chest width, depth and surface area), were compared in eight elite male swimmers, eight elite male long distance athletes and eight control subjects. The differences in training profiles of each group were also examined. There was no significant difference in height between the subjects, but the swimmers were younger than both the runners and controls, and both the swimmers and controls were heavier than the runners. Of all the training variables, only the mean total distance in kilometers covered per week was significantly greater in the runners. Whether based on: (a) adolescent predicted values; or (b) adult male predicted values, swimmers had significantly increased total lung capacity ((a) 145 +/- 22%, (mean +/- SD) (b) 128 +/- 15%); vital capacity ((a) 146 +/- 24%, (b) 124 +/- 15%); and inspiratory capacity ((a) 155 +/- 33%, (b) 138 +/- 29%), but this was not found in the other two groups. Swimmers also had the largest chest surface area and chest width. Forced expiratory volume in one second (FEV1) was largest in the swimmers ((b) 122 +/- 17%) and FEV1 as a percentage of forced vital capacity (FEV1/FVC)% was similar for the three groups. Pulmonary diffusing capacity (DLCO) was also highest in the swimmers (117 +/- 18%). All of the other indices of lung function, including pulmonary distensibility (K), elastic recoil and diffusion coefficient (KCO), were similar. These findings suggest that swimmers may have achieved greater lung volumes than either runners or control subjects, not because of greater inspiratory muscle strength, or differences in height, fat free mass, alveolar distensibility, age at start of training or sternal length or chest depth, but by developing physically wider chests, containing an increased number of alveoli, rather than alveoli of increased size. However, in this cross-sectional study, hereditary factors cannot be ruled out, although we believe them to be less likely.

Surface-structure dependence of healing radiation-damage mechanism in nanoporous tungsten

NASA Astrophysics Data System (ADS)

Duan, Guohua; Li, Xiangyan; Sun, Jingjing; Hao, Congyu; Xu, Yichun; Zhang, Yange; Liu, Wei; Liu, C. S.

2018-01-01

Under nuclear fusion environments, displacement damage in tungsten (W) is usually caused by neutrons irradiation through producing large quantities of vacancies (Vs) and self-interstitial atoms (SIAs). These defects not only affect the mechanical properties of W, but also act as the trap sites for implanted hydrogen isotopes and helium. Nano-porous (NP) W with a high fraction of free surfaces has been developed to mitigate the radiation damage. However, the mechanism of the surface reducing defects accumulation is not well understood. By using multi-scale simulation methods, we investigated the interaction of the SIA and V with different surfaces on across length and time scales. We found that, at a typical operation temperature of 1000 K, surface (1 1 0) preferentially heals radiation damage of W compared with surface (1 0 0) and boundary (3 1 0). On surface (1 1 0), the diffusion barrier for the SIA is only 0.68 eV. The annihilation of the SIA-V happens via the coupled motion of the V segregation towards the surface from the bulk and the two-dimensional diffusion of the SIA on the surface. Such mechanism makes the surface (1 1 0) owe better healing capability. On surface (1 0 0), the diffusion energy barrier for the SIA is 2.48 eV, higher than the diffusion energy barrier of the V in bulk. The annihilation of the SIA-V occurs via the V segregation and recombination. The SIA was found to migrate one-dimensionally along a boundary (3 1 0) with a barrier of 0.21 eV, leading to a lower healing efficiency in the boundary. This study suggested that the on-surface process plays an important role in healing radiation damage of NP W in addition to surface-enhanced diffusion and annihilation near the surface. A certain surface structure renders nano-structured W more radiation-tolerant.

Unexpected death of a ventilator-dependent amyotrophic lateral sclerosis patient.

PubMed

di Paolo, M; Evangelisti, L; Ambrosino, N

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive, neurodegenerative disease and most patients affected die of respiratory compromise and/or pneumonia within 2-3 years of diagnosis. As ALS progresses, ventilator assistance is required. In the end stages of the disease, patients suffer from respiratory failure and may become ventilator-dependent. Deaths due to malfunction of mechanical ventilators are reported but there are very few forensic autopsy records. We report the case of a 69-year-old ALS female ventilator-dependent, trachostomised patient who was found dead by her husband, with the ventilator in "stand-by" mode. A forensic autopsy was performed. Samples of internal organs were taken for histological and toxicological examination. The ventilator internal memory was also analysed and tested in order to find possible malfunction. Gross examination did not reveal any sign of trauma but showed brain and lung congestion. Pulmonary histological examination revealed thickening of peribronchial interstitial space, alveolar over-distension, break of inter-alveolar walls and diffuse alveolar haemorrhages. Focal microhemorrhages were also detected in other organs. Analysis of the ventilator internal memory showed that during the night of death, there had been several voltage drops. Specific tests revealed malfunction of the internal battery which was unable to provide the necessary voltage, as a consequence the ventilator switched off, stopping ventilation. Battery malfunction reduced the volume of the ventilator alarm, which was not heard by the caregiver. Histological pattern, with acute pulmonary emphysema and focal polivisceral haemorrhages, is strongly suggestive of a death due to "acute" asphyxia. The authors also discuss the need for strict supervision and follow up of these ventilatory dependent patients and their devices. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

[Lipoid pneumonia related to workplace exposure to paint].

PubMed

Abad Fernández, A; de Miguel Díez, J; López Vime, R; Gómez Santos, D; Nájera Botello, L; Jara Chinarro, B

2003-03-01

A 49-year-old man with no known history of pulmonary disease was treated at our hospital after observation of an interstitial pattern on a chest film. The patient was a smoker and professional painter. Computed tomography of the chest showed a diffuse bilateral ground-glass pattern. The lung biopsy showed intra-alveolar lipid accumulation in the form of vacuoles of varying sizes surrounded by numerous focally multinucleated macrophages, establishing a definitive diagnosis of exogenous lipoid pneumonia. Given the patient's profession, he was recommended to avoid workplace exposure to paraffins and oily sprays. The clinical course was favorable after exposure was stopped, with improved lung function and symptoms.

Analysis of InP-based single photon avalanche diodes based on a single recess-etching process

NASA Astrophysics Data System (ADS)

Lee, Kiwon

2018-04-01

Effects of the different etching techniques have been investigated by analyzing electrical and optical characteristics of two-types of single-diffused single photon avalanche diodes (SPADs). The fabricated two-types of SPADs have no diffusion depth variation by using a single diffusion process at the same time. The dry-etched SPADs show higher temperature dependence of a breakdown voltage, larger dark-count-rate (DCR), and lower photon-detection-efficiency (PDE) than those of the wet-etched SPADs due to plasma-induced damage of dry-etching process. The results show that the dry etching damages can more significantly affect the performance of the SPADs based on a single recess-etching process.

In vivo lung morphometry with hyperpolarized 3He diffusion MRI: Theoretical background

NASA Astrophysics Data System (ADS)

Sukstanskii, A. L.; Yablonskiy, D. A.

2008-02-01

MRI-based study of 3He gas diffusion in lungs may provide important information on lung microstructure. Lung acinar airways can be described in terms of cylinders covered with alveolar sleeve [Haefeli-Bleuer, Weibel, Anat. Rec. 220 (1988) 401]. For relatively short diffusion times (on the order of a few ms) this geometry allows description of the 3He diffusion attenuated MR signal in lungs in terms of two diffusion coefficients—longitudinal (D) and transverse (D) with respect to the individual acinar airway axis [Yablonskiy et al., PNAS 99 (2002) 3111]. In this paper, empirical relationships between D and D and the geometrical parameters of airways and alveoli are found by means of computer Monte Carlo simulations. The effects of non-Gaussian signal behavior (dependence of D and D on b-value) are also taken into account. The results obtained are quantitatively valid in the physiologically important range of airway parameters characteristic of healthy lungs and lungs with mild emphysema. In lungs with advanced emphysema, the results provide only "apparent" characteristics but still could potentially be used to evaluate emphysema progression. This creates a basis for in vivo lung morphometry—evaluation of the geometrical parameters of acinar airways from hyperpolarized 3He diffusion MRI, despite the airways being too small to be resolved by direct imaging. These results also predict a rather substantial dependence of 3He ADC on the experimentally-controllable diffusion time, Δ. If Δ is decreased from 3 ms to 1 ms, the ADC in normal human lungs may increase by almost 50%. This effect should be taken into account when comparing experimental data obtained with different pulse sequences.

Effect of nickel on point defects diffusion in Fe – Ni alloys

DOE PAGES

Anento, Napoleon; Serra, Anna; Osetsky, Yury N.

2017-05-05

Iron-Nickel alloys are perspective alloys as nuclear energy structural materials because of their good radiation damage tolerance and mechanical properties. Understanding of experimentally observed features such as the effect of Ni content to radiation defects evolution is essential for developing predictive models of radiation. Recently an atomic-scale modelling study has revealed one particular mechanism of Ni effect related to the reduced mobility of clusters of interstitial atoms in Fe-Ni alloys. In this paper we present results of the microsecond-scale molecular dynamics study of point defects, i.e. vacancies and self-interstitial atoms, diffusion in Fe-Ni alloys. It is found that the additionmore » of Ni atoms affects diffusion processes: diffusion of vacancies is enhanced in the presence of Ni, whereas diffusion of interstitials is reduced and these effects increase at high Ni concentration and low temperature. As a result, the role of Ni solutes in radiation damage evolution in Fe-Ni alloys is discussed.« less

Cardio-pulmonary effects of inhaled solvents: computer-assisted measurement and analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engwall, M.J.

The physiological effects of the inhalation of three solvent vapors were measured on anesthetized dogs. The tested solvents were: acetone, ethanol, and toluene. Measurements of respiratory mechanics, pulmonary and systemic hemodynamics, cardiac output, and gas-exchange were taken while exposing the animals to the vaporized solvents. After the exposures, the animals were terminated and lung tissue and alveolar lining material (ALM) were collected. The ALM was analyzed by high performance liquid chromatography for the amounts of component phospholipids. The tissues were inspected under light microscopy for evidence of acute damage associated with the solvent exposures.

Simulation of radiation damage in minerals by sequential ion irradiations

NASA Astrophysics Data System (ADS)

Nakasuga, W. M.; Li, W.; Ewing, R. C.

2015-12-01

Radiation effects due to α-decay of U and Th and spontaneous fission of 238U control the production and recovery of the radiation-induced structure of minerals, as well as the diffusion of elements through the mineral host. However, details of how the damage microstructure is produced and annealed remain unknown. Our recent ion beam experiments demonstrate that ionizing radiation from the α-particle recovers the damage structure. Thus, the damage structure is not only the result of the thermal hisotry of the sample, but also of the complex interaction between ionizing and ballistic damage mechanisms. By combining ion irradiations with transmission electron microscopy (TEM), we have simulated the damage produced by α-decay and fission. The α-particle induced annealing has been simulated by in situ TEM observation of consecutive ion-irradiations: i.) 1 MeV Kr2+ (simulating 70 keV α-recoils induced damage), ii.) followed by 400 keV He+ (simulating 4.5 MeV α-particle induced annealing). Thus, in addition to the well-established effects of thermal annealing, the α-particle annealing effects, as evidenced by partical recrystallization of the originally, fully-amorphous apatite upon the α-particle irriadations, should also be considered when evaluating diffusion and release of elements, such as He. In addition, the fission track annealing has been simulated by a new sample preparation method that allows for direct observation of radiation damage recovery at each point along the length of latent tracks created by 80 MeV Xe ions (a typical fission fragment). The initial, rapid reduction in etched track length during isothermal annealing is explained by the rapid annealing of those sections of the track with smaller diameters, as observed directly by in situ TEM. In summary, the atomic-scale investigation of radiation damage in minerals is critical to understanding of the influence of raidation damage on diffusion and kinetics that are fundamental to geochronology.

An automatic early stage alveolar-bone-resorption evaluation method on digital dental panoramic radiographs

NASA Astrophysics Data System (ADS)

Zhang, Min; Katsumata, Akitoshi; Muramatsu, Chisako; Hara, Takeshi; Suzuki, Hiroki; Fujita, Hiroshi

2014-03-01

Periodontal disease is a kind of typical dental diseases, which affects many adults. The presence of alveolar bone resorption, which can be observed from dental panoramic radiographs, is one of the most important signs of the progression of periodontal disease. Automatically evaluating alveolar-bone resorption is of important clinic meaning in dental radiology. The purpose of this study was to propose a novel system for automated alveolar-bone-resorption evaluation from digital dental panoramic radiographs for the first time. The proposed system enables visualization and quantitative evaluation of alveolar bone resorption degree surrounding the teeth. It has the following procedures: (1) pre-processing for a test image; (2) detection of tooth root apices with Gabor filter and curve fitting for the root apex line; (3) detection of features related with alveolar bone by using image phase congruency map and template matching and curving fitting for the alveolar line; (4) detection of occlusion line with selected Gabor filter; (5) finally, evaluation of the quantitative alveolar-bone-resorption degree in the area surrounding teeth by simply computing the average ratio of the height of the alveolar bone and the height of the teeth. The proposed scheme was applied to 30 patient cases of digital panoramic radiographs, with alveolar bone resorption of different stages. Our initial trial on these test cases indicates that the quantitative evaluation results are correlated with the alveolar-boneresorption degree, although the performance still needs further improvement. Therefore it has potential clinical practicability.

Orthodontic extrusion of the lower third molar with an orthodontic mini implant.

PubMed

Park, Wonse; Park, Joon-Soo; Kim, Yun-Mi; Yu, Hyung-Seog; Kim, Kee-Deog

2010-10-01

Neurologic changes owing to damage to the inferior alveolar nerve (IAN) are the most serious complication of lower third molar (M3) extraction because of their close spatial relationship. We adopted the concept of regional orthodontic treatment and extrusion, using skeletal anchorage with an orthodontic mini implant. Two malformed M3s that were closely apposed to the IAN were extruded with the aid of 3 or 4 orthodontic brackets and a mini implant. Both of the M3s were extruded successfully. The patients experienced little discomfort with the orthodontic appliances and there was neither permanent neurologic damage nor fracture of the root fragments following subsequent M3 extraction. Orthodontic treatment using a miniscrew to separate the IAN and M3, or luxation of the M3 may be a good alternative treatment option for extrusion of a vertically impacted lower M3 with fragile roots. Copyright © 2010 Mosby, Inc. All rights reserved.

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

PubMed

Hubbard, Nicholas A; Turner, Monroe P; Ouyang, Minhui; Himes, Lyndahl; Thomas, Binu P; Hutchison, Joanna L; Faghihahmadabadi, Shawheen; Davis, Scott L; Strain, Jeremy F; Spence, Jeffrey; Krawczyk, Daniel C; Huang, Hao; Lu, Hanzhang; Hart, John; Frohman, Teresa C; Frohman, Elliot M; Okuda, Darin T; Rypma, Bart

2017-11-01

Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO 2 ) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO 2 . However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO 2 was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375-5390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

ALA-PDT of the normal rat esophagus: efficiency and safety largely depends on the timing of illumination

NASA Astrophysics Data System (ADS)

van den Boogert, Jolanda; de Bruin, Ron W. F.; van Staveren, Hugo J.; Siersema, Peter D.; van Hillegersberg, Richard

1999-02-01

Photodynamic therapy (PDT) is an experimental treatment modality for (pre)malignant oesophageal lesions. 5- Aminolevulinic acid (ALA)-induced, protoporphyrin IX (PpIX)- mediated photo-sensitization could be very useful as ALA- induced porphrin accumulation selectively occurs in the oesophageal epithelium. The present study aimed to optimize the time between illumination and the administration of ALA. 200 mg/kg ALA was given orally to 24 rats (allocated to 6 groups of 4 animals each). Four animals served as controls and received phosphate buffered saline orally. The animals were illuminated at various time-points (either 1, 2, 3, 4, 6, or 12 hours) after ALA administration. Illumination was performed with a cylindrical diffuser placed in a balloon catheter. The device was originally made for percutaneous transluminal coronary angioplasty and consisted of a semi-flexible catheter and an inflatable cylindric optically clear balloon. The diffuser was placed centrally in the catheter. The same illumination parameters (633 nm, 25 J radiant energy/cm diffuser, power output 100 mW/cm diffuser) were used for each animal. During illumination, fluorescence measurements and light dosimetry were performed. The animals were sacrificed at 48 hours after PDT for histological assessment. Highest PpIX fluorescence was found at 2, 3, and 4 hours after ALA administration. Dosimetric measurements showed a 2 - 3 times higher in vivo fluence rate compared to the estimated fluence rate. Histology at 48 hours after PDT showed diffuse epithelial damage at the laser site only in rats illuminated at 2 hours after ALA administration. Illumination at 3, 4, and 6 hours after ALA administration resulted in diffuse epithelial damage in only one of four rats. In none of the rats illuminated at 1 and 12 hours after administration of ALA epithelial damage was found. These results show that illumination at 2 hours after oral ALA administration provides an efficient and safe scheme for ALA-PDT in the normal rat oesophagus. Illumination at other time points results in incomplete epithelial damage.

A Radiation Chemistry Code Based on the Greens Functions of the Diffusion Equation

NASA Technical Reports Server (NTRS)

Plante, Ianik; Wu, Honglu

2014-01-01

Ionizing radiation produces several radiolytic species such as.OH, e-aq, and H. when interacting with biological matter. Following their creation, radiolytic species diffuse and chemically react with biological molecules such as DNA. Despite years of research, many questions on the DNA damage by ionizing radiation remains, notably on the indirect effect, i.e. the damage resulting from the reactions of the radiolytic species with DNA. To simulate DNA damage by ionizing radiation, we are developing a step-by-step radiation chemistry code that is based on the Green's functions of the diffusion equation (GFDE), which is able to follow the trajectories of all particles and their reactions with time. In the recent years, simulations based on the GFDE have been used extensively in biochemistry, notably to simulate biochemical networks in time and space and are often used as the "gold standard" to validate diffusion-reaction theories. The exact GFDE for partially diffusion-controlled reactions is difficult to use because of its complex form. Therefore, the radial Green's function, which is much simpler, is often used. Hence, much effort has been devoted to the sampling of the radial Green's functions, for which we have developed a sampling algorithm This algorithm only yields the inter-particle distance vector length after a time step; the sampling of the deviation angle of the inter-particle vector is not taken into consideration. In this work, we show that the radial distribution is predicted by the exact radial Green's function. We also use a technique developed by Clifford et al. to generate the inter-particle vector deviation angles, knowing the inter-particle vector length before and after a time step. The results are compared with those predicted by the exact GFDE and by the analytical angular functions for free diffusion. This first step in the creation of the radiation chemistry code should help the understanding of the contribution of the indirect effect in the formation of DNA damage and double-strand breaks.

Selenium Alleviates Oxidative Stress and Lung Damage Induced by Aluminum Chloride in Adult Rats: Biochemical and Histological Approach.

PubMed

Ghorbel, Imen; Elwej, Awatef; Chaabane, Mariem; Jamoussi, Kamel; Mnif, Hela; Boudawara, Tahia; Zeghal, Najiba

2017-03-01

Our study pertains to the potential ability of selenium, used as a nutritional supplement, to alleviate oxidative stress induced by aluminum chloride in the lung tissue. Rats have received during 21 days either aluminum chloride (AlCl 3 ) (400 ppm) via drinking water, AlCl 3 associated with Na 2 SeO 3 (0.5 mg/kg of diet), or only Na 2 SeO 3 . Exposure of rats to AlCl 3 induced lung oxidative stress with an increase of malondialdehyde, hydrogen peroxide, and protein carbonyls levels. An alteration of lactate dehydrogenase activities and antioxidant redox status, enzymatic (catalase, superoxide dismutase, and glutathione peroxidase), and non-enzymatic (non-protein thiols, glutathione, metallothionein, and vitamin C) was also observed. These biochemical modifications were substantiated by histopathological data showing alveolar edema, a large number of hemosiderin-laden macrophages, and emphysema. Se supplementation attenuated the levels of oxidative stress by restoring antioxidant state and improved lung histological damage. Our results revealed that Se, a trace element with antioxidant properties, was effective in preventing lung damage.

Telomere Damage Response and Low-Grade Inflammation.

PubMed

Wang, Lihui; Yu, Xianhua; Liu, Jun-Ping

2017-01-01

Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. The senescence-associated low-grade inflammation (SALI) is characteristic of alveolar stem cell replicative senescence, increased proinflammatory and anti-inflammatory cytokines, infiltrated immune cells, and spillover effects. To date, the mechanisms underlying SALI remain unclear. Investigations demonstrate that senescent epithelial stem cells with telomere erosion are not the source of secreted cytokines, containing no significant increase in expression of the genes coding for increased cytokines, suggesting an alternative senescence-associated secretory phenotype (A-SASP). Given that telomere loss results in significant alterations in the genomes and accumulations of the cleaved telomeric DNA in the cells and milieu externe, we conclude that telomere position effects (TPEs) on gene expression and damage-associated molecular patterns (DAMPs) in antigen presentation are involved in A-SASP and SALI in response to telomere damage in mammals.

Evolution and development of gas exchange structures in Mammalia: the placenta and the lung.

PubMed

Mess, Andrea M; Ferner, Kirsten J

2010-08-31

Appropriate oxygen supply is crucial for organisms. Here we examine the evolution of structures associated with the delivery of oxygen in the pre- and postnatal phases in mammals. There is an enormous structural and functional variability in the placenta that has facilitated the evolution of specialized reproductive strategies, such as precociality. In particular the cell layers separating fetal and maternal blood differ markedly: a non-invasive epitheliochorial placenta, which increases the diffusion distance, represents a derived state in ungulates. Rodents and their relatives have an invasive haemochorial placental type as optimum for the diffusion distance. In contrast, lung development is highly conserved and differences in the lungs of neonates can be explained by different developmental rates. Monotremes and marsupials have altricial stages with lungs at the early saccular phase, whereas newborn eutherians have lungs at the late saccular or alveolar phase. In conclusion, the evolution of exchange structures in the pre- and postnatal periods does not follow similar principles. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Pulmonary alveolar proteinosis

MedlinePlus

... phospholipoproteinosis; Alveolar lipoproteinosis phospholipidosis Patient Instructions Interstitial lung disease - adults - discharge Images Respiratory system References Levine SM. Alveolar filling disorders. In: ...

Clinical and laboratory features of children with community-acquired pneumonia are associated with distinct radiographic presentations.

PubMed

Falup-Pecurariu, Oana G; Diez-Domingo, Javier; Esposito, Susanna; Finn, Adam; Rodrigues, Fernanda; Spoulou, Vana; Syrogiannopoulos, George A; Usonis, Vytautas; Greenberg, David

2018-07-01

Chest radiographs from children with community-acquired pneumonia (CAP) were categorized into three distinct presentations and each presentation was correlated to clinical and laboratory findings. Children < 59 months with CAP presenting to pediatric emergency rooms during two years were enrolled prospectively in eight centers across Europe. Clinical and laboratory data were documented and radiographs obtained from patients. Of the 1107 enrolled patients, radiographs were characterized as 74.9% alveolar CAP, 8.9% non-alveolar CAP, and 16.3% clinical CAP. Alveolar CAP patients had significantly higher rates of fever (90.7%), vomiting (27.6%), and abdominal pain (18.6%), while non-alveolar CAP patients presented more with cough (96.9%). A model using independent parameters that characterize alveolar, non-alveolar, and clinical CAP demonstrated that alveolar CAP patients were significantly older (OR = 1.02) and had significantly lower oxygen saturation than non-alveolar CAP patients (OR = 0.54). Alveolar CAP patients had significantly higher mean WBC (17,760 ± 8539.68 cells/mm 3 ) and ANC (11.5 ± 7.5 cells/mm 3 ) than patients categorized as non-alveolar CAP (WBC 15,160 ± 5996 cells/mm 3 , ANC 9.2 ± 5.1 cells/mm 3 ) and clinical CAP (WBC 13,180 ± 5892, ANC 7.3 ± 4.7). Alveolar CAP, non-alveolar CAP, and clinical CAP are distinct entities differing not only by chest radiographic appearance but also in clinical and laboratory characteristics. Alveolar CAP has unique characteristics, which suggest association with bacterial etiology. Trial number 3075 (Soroka Hospital, Israel) What is Known: • Community-acquired pneumonia in children is diagnosed based on clinical and radiological definitions. • Radiological criteria were standardized by WHO-SICR and have been utilized in vaccine studies. What is New: • Correlation between the WHO-SICR radiological definitions and clinical and laboratory parameters has not been studied. • Using the WHO-SICR radiological definitions for alveolar community-acquired pneumonia (CAP) and non-alveolar CAP and the study definition for clinical CAP, it was found that the groups are distinct, differing clinically and in laboratory parameters.

Disruption of THY-1 signaling in alveolar lipofibroblasts in experimentally induced congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Hofmann, Alejandro Daniel; Takahashi, Hiromizu; Takahashi, Toshiaki; Gosemann, Jan-Hendrik; Puri, Prem

2014-02-01

Pulmonary hypoplasia (PH), characterized by alveolar immaturity, remains the main cause of neonatal mortality and long-term morbidity in infants with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) are critically important for normal alveolar development. Thymocyte antigen 1 (Thy-1) is a highly expressed cell-surface protein in this specific subset of lung fibroblasts, which plays a key role in fetal alveolarization by coordinating the differentiation and lipid homeostasis of alveolar LIFs. Thy-1 increases the lipid content of LIFs by upregulation of adipocyte differentiation-related protein (ADRP), a lipogenic molecular marker characterizing pulmonary LIFs. Thy-1 (-/-) mice further show impaired alveolar development with reduced proliferation of pulmonary LIFs, resulting in a PH-similar phenotype. We hypothesized that pulmonary Thy-1 signaling is disrupted in experimentally induced CDH, which may has an adverse effect on the lipid content of alveolar LIFs. Timed-pregnant Sprague-Dawley rats were treated with either 100 mg nitrofen or vehicle on embryonic day 9.5 (E9.5). Fetuses were killed on E21.5, and lungs were divided into controls (n = 14) and CDH-associated PH (n = 14). Pulmonary gene expression levels of Thy-1 and ADRP were assessed by quantitative real-time PCR. ADRP immunohistochemistry and oil-red-O staining were used to localize alveolar LIF expression and lipid droplets. Immunofluorescence double staining for Thy-1 and oil-red-O was performed to evaluate Thy-1 expression and lipid content in alveolar LIFs. Radial alveolar count was significantly reduced in CDH-associated PH with significant downregulation of pulmonary Thy-1 and ADRP mRNA expression compared to controls. ADRP immunoreactivity and lipid droplets were markedly diminished in alveolar interstitial cells, which coincided with decreased alveolar LIF expression in CDH-associated PH compared to controls. Confocal laser scanning microscopy confirmed markedly decreased Thy-1 expression and lipid content in alveolar LIFs of CDH-associated PH compared to controls. Our study provides strong evidence that disruption of pulmonary Thy-1 signaling results in reduced lipid droplets in alveolar LIFs and may thus contribute to PH in the nitrofen-induced CDH model. Treatment modalities aimed at increasing lipid content in alveolar LIFs may therefore have a therapeutic potential in attenuating CDH-associated PH.

[Evaluation of diffuse cerebral atrophy in patients with a history of traumatic brain injury and its relation to cognitive deterioration].

PubMed

Narberhaus, A; Segarra-Castells, M D; Verger-Maestre, K; Serra-Grabulosa, J M; Salgado-Pineda, P; Bartomeus-Jené, F; Mercader-Sobrequés, J M

Diffuse damage secondary to traumatic brain injury (TBI) can be studied through volumetric analysis of several structures that are sensible to this kind of injury, such as corpus callosum, ventricular system, hippocampus, basal ganglia and the volume of cerebrospinal fluid spaces. Our aim is to describe how closed head injury (CHI) occurred in early years produce diffuse damage, and how this damage affects general cognitive functioning at long term. Initially the group of subjects was composed of 27 head injured children and adolescents following paediatric moderate to severe TBI. From this initial group we selected 15 patients without focal lesion, or in case of having suffered focal lesion, this was smaller than 2,600 mm3. These subjects were assessed by means of volumetric analysis of cerebrospinal fluid spaces, corpus callosum, hippocampus and caudate nucleus, comparing the results with a matched control group. We calculated the degree of general cognitive ability of these subjects through tests of intellectual, memory, frontal lobe and motor speed functioning. This study demonstrates that early CHI produce a volume decrease in all measured structures. Corpus callosum atrophy is the factor that better explains general cognitive impairment. Diffuse damage secondary to moderate to severe peadiatric TBI has long term effects on several cerebral structures and on cognitive performance. Corpus callosum atrophy is the best predictor for general cognitive impairment, compared with other affected structures.

Alveolar edema dispersion and alveolar protein permeability during high volume ventilation: effect of positive end-expiratory pressure.

PubMed

de Prost, Nicolas; Roux, Damien; Dreyfuss, Didier; Ricard, Jean-Damien; Le Guludec, Dominique; Saumon, Georges

2007-04-01

To evaluate whether PEEP affects intrapulmonary alveolar edema liquid movement and alveolar permeability to proteins during high volume ventilation. Experimental study in an animal research laboratory. 46 male Wistar rats. A (99m)Tc-labeled albumin solution was instilled in a distal airway to produce a zone of alveolar flooding. Conventional ventilation (CV) was applied for 30 min followed by various ventilation strategies for 3 h: CV, spontaneous breathing, and high volume ventilation with different PEEP levels (0, 6, and 8 cmH(2)O) and different tidal volumes. Dispersion of the instilled liquid and systemic leakage of (99m)Tc-albumin from the lungs were studied by scintigraphy. The instillation protocol produced a zone of alveolar flooding that stayed localized during CV or spontaneous breathing. High volume ventilation dispersed alveolar liquid in the lungs. This dispersion was prevented by PEEP even when tidal volume was the same and thus end-inspiratory pressure higher. High volume ventilation resulted in the leakage of instilled (99m)Tc-albumin from the lungs. This increase in alveolar albumin permeability was reduced by PEEP. Albumin permeability was more affected by the amplitude of tidal excursions than by overall lung distension. PEEP prevents the dispersion of alveolar edema liquid in the lungs and lessens the increase in alveolar albumin permeability due to high volume ventilation.

Occult White Matter Damage Contributes to Intellectual Disability in Tuberous Sclerosis Complex

ERIC Educational Resources Information Center

Yu, Chunshui; Lin, Fuchun; Zhao, Li; Ye, Jing; Qin, Wen

2009-01-01

Whether patients with tuberous sclerosis complex (TSC) have brain normal-appearing white matter (NAWM) damage and whether such damage contributes to their intellectual disability were examined in 15 TSC patients and 15 gender- and age-matched healthy controls using diffusion tensor imaging (DTI). Histogram and region of interest (ROI) analyses of…

Impairment of aminopyrine clearance in aspirin-damaged canine gastric mucosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, T.A.; Henagan, J.M.; Loy, T.M.

Using an in vivo canine chambered stomach preparation, the clearance of (/sup 14/C)aminopyrine across mucosa when intravenously infused and the back-diffusion of this substance from gastric lumen to mucosa when topically applied to gastric epithelium were evaluated in aspirin-damaged gastric epithelium. In mucosa damaged by either 20 mM or 40 mM aspirin, the recovery of (/sup 14/C)aminopyrine, when topically mixed with acid (pH . 1.1) perfusate solution, was not significantly different from nondamaged control mucosa. In addition, the degree of ''trapping'' of this substance from back-diffusion was not different in damaged mucosa from that observed in nondamaged epithelium. In contrast,more » when (/sup 14/C)aminopyrine was intravenously infused, its clearance was significantly impaired in aspirin-damaged mucosa when compared with control studies, as evidenced by the increased ''trapping'' of this substance in injured epithelium. These findings indicate that movement of aminopyrine from plasma to gastric lumen is impaired in damaged epithelium, making the aminopyrine clearance technique an unreliable method to accurately measure absolute gastric blood flow in this experimental setting.« less

Dynamic measurements of CO diffusing capacity using discrete samples of alveolar gas.

PubMed

Graham, B L; Mink, J T; Cotton, D J

1983-01-01

It has been shown that measurements of the diffusing capacity of the lung for CO made during a slow exhalation [DLCO(exhaled)] yield information about the distribution of the diffusing capacity in the lung that is not available from the commonly measured single-breath diffusing capacity [DLCO(SB)]. Current techniques of measuring DLCO(exhaled) require the use of a rapid-responding (less than 240 ms, 10-90%) CO meter to measure the CO concentration in the exhaled gas continuously during exhalation. DLCO(exhaled) is then calculated using two sample points in the CO signal. Because DLCO(exhaled) calculations are highly affected by small amounts of noise in the CO signal, filtering techniques have been used to reduce noise. However, these techniques reduce the response time of the system and may introduce other errors into the signal. We have developed an alternate technique in which DLCO(exhaled) can be calculated using the concentration of CO in large discrete samples of the exhaled gas, thus eliminating the requirement of a rapid response time in the CO analyzer. We show theoretically that this method is as accurate as other DLCO(exhaled) methods but is less affected by noise. These findings are verified in comparisons of the discrete-sample method of calculating DLCO(exhaled) to point-sample methods in normal subjects, patients with emphysema, and patients with asthma.

Language Dysfunction After Stroke and Damage to White Matter Tracts Evaluated Using Diffusion Tensor Imaging

PubMed Central

Breier, J.I.; Hasan, K.M.; Zhang, W.; Men, D.; Papanicolaou, A.C.

2011-01-01

BACKGROUND AND PURPOSE Knowledge of the anatomic basis of aphasia after stroke has both theoretic and clinical implications by informing models of cortical connectivity and providing data for diagnosis and prognosis. In this study we use diffusion tensor imaging to address the relationship between damage to specific white matter tracts and linguistic deficits after left hemisphere stroke. MATERIALS AND METHODS Twenty patients aged 38–77 years with a history of stroke in the left hemisphere underwent diffusion tensor imaging, structural MR imaging, and language testing. All of the patients were premorbidly right handed and underwent imaging and language testing at least 1 month after stroke. RESULTS Lower fractional anisotropy (FA) values in the superior longitudinal and arcuate fasciculi of the left hemisphere, an indication of greater damage to these tracts, were correlated with decreased ability to repeat spoken language. Comprehension deficits after stroke were associated with lower FA values in the arcuate fasciculus of the left hemisphere. The findings for repetition were independent of MR imaging ratings of the degree of damage to cortical areas of the left hemisphere involved in language function. There were no findings for homotopic tracts in the right hemisphere. CONCLUSION This study provides support for a specific role for damage to the superior longitudinal and arcuate fasciculi in the left hemisphere in patients with deficits in repetition of speech in aphasia after stroke. PMID:18039757

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro.

PubMed

Ward, Roberta J; Lallemand, Frederic; de Witte, Philippe; Crichton, Robert R; Piette, Jacques; Tipton, Keith; Hemmings, Karl; Pitard, Arnaud; Page, Mike; Della Corte, Laura; Taylor, Deanna; Dexter, David

2011-03-15

The ability of a taurine prodrug, ethane β-sultam, to reduce cellular inflammation has been investigated, in vitro, in primary cultures of alveolar macrophages and an immortilised N9 microglial cell line and in vivo in an animal model of inflammation and control rats. Ethane β-sultam showed enhanced ability to reduce the inflammatory response in alveolar macrophages, as assayed by the lipopolysaccharide-stimulated-nitric oxide release, (LPS stimulated-NO), in comparison to taurine both in vitro (10 nM, 50 nM) and in vivo (0.15 mmol/kg/day by gavage). In addition, ethane β-sultam, (50, 100 and 1000 nM) significantly reduced LPS-stimulated glutamate release from N9 microglial cells to a greater extent than taurine. The anti-inflammatory response of taurine was shown to be mediated via stabilisation of IkBα. The use of a taurine prodrug as therapeutic agents, for the treatment of neurological conditions, such as Parkinson's and Alzheimer's disease and alcoholic brain damage, where activated phagocytic cells contribute to the pathogenesis, may be of great potential. Copyright © 2011 Elsevier Inc. All rights reserved.

Rehabilitation of a periodontal patient with rapidly progressing marginal alveolar bone loss: 1-year follow-up.

PubMed

Sewón, L A; Ampula, L; Vallittu, P K

2000-08-01

The present case report describes a 1-year follow-up of functional rehabilitation of a young periodontal patient with severely advanced, rapidly progressing marginal bone loss treated by using a new splinting material, i.e., glass fiber-reinforced composite (FRC). Apart from one single tooth, the young man had retained all his natural teeth. Periodontal treatment was based on cleaning and root planing enabled by partial-thickness-flap operations. This method was selected to avoid further damage to the remaining alveolar bone. After healing for 6 months, a cavity retained internal FRC splint was constructed and 1 missing lower molar was replaced by an inlay-retained FRC resin-bonded fixed partial denture (FPD). A 12 months follow-up period revealed a healthy periodontium and good functional and esthetic results. The new material allows the use of periodontal treatment methods instead of prosthetic alternatives, which until now have been a more generally used approach in the treatment of severely advanced periodontal cases. Internal fiber-reinforced composite splinting being affordable for the patient, easy for the clinician to construct and giving good esthetic and functional results, suggests that the method may be a valuable aid in periodontal treatment.

Comparative proteomic analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and lung transplant donor lungs.

PubMed

Korfei, Martina; Schmitt, Sigrid; Ruppert, Clemens; Henneke, Ingrid; Markart, Philipp; Loeh, Benjamin; Mahavadi, Poornima; Wygrecka, Malgorzata; Klepetko, Walter; Fink, Ludger; Bonniaud, Philippe; Preissner, Klaus T; Lochnit, Günter; Schaefer, Liliana; Seeger, Werner; Guenther, Andreas

2011-05-06

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease for which no effective therapy exists to date. To identify the molecular mechanisms underlying IPF, we performed comparative proteome analysis of lung tissue from patients with sporadic IPF (n = 14) and human donor lungs (controls, n = 10) using two-dimensional gel electrophoresis and MALDI-TOF-MS. Eighty-nine differentially expressed proteins were identified, from which 51 were up-regulated and 38 down-regulated in IPF. Increased expression of markers for the unfolded protein response (UPR), heat-shock proteins, and DNA damage stress markers indicated a chronic cell stress-response in IPF lungs. By means of immunohistochemistry, induction of UPR markers was encountered in type-II alveolar epithelial cells of IPF but not of control lungs. In contrast, up-regulation of heat-shock protein 27 (Hsp27) was exclusively observed in proliferating bronchiolar basal cells and associated with aberrant re-epithelialization at the bronchiolo-alveolar junctions. Among the down-regulated proteins in IPF were antioxidants, members of the annexin family, and structural epithelial proteins. In summary, our results indicate that IPF is characterized by epithelial cell injury, apoptosis, and aberrant epithelial proliferation.

Signed, Sealed, Delivered: Microenvironmental Modulation of Extracellular Vesicle-Dependent Immunoregulation in the Lung.

PubMed

Schneider, Daniel J; Speth, Jennifer M; Peters-Golden, Marc

2016-01-01

Unconventional secretion and subsequent uptake of molecular cargo via extracellular vesicles (EVs) is an important mechanism by which cells can exert paracrine effects. While this phenomenon has been widely characterized in the context of their ability to promote inflammation, less is known about the ability of EVs to transfer immunosuppressive cargo. Maintenance of normal physiology in the lung requires suppression of potentially damaging inflammatory responses to the myriad of insults to which it is continually exposed. Recently, our laboratory has reported the ability of alveolar macrophages (AMs) to secrete suppressors of cytokine signaling (SOCS) proteins within microvesicles (MVs) and exosomes (Exos). Uptake of these EVs by alveolar epithelial cells (AECs) resulted in inhibition of pro-inflammatory STAT activation in response to cytokines. Moreover, AM packaging of SOCS within EVs could be rapidly tuned in response to exogenous or AEC-derived substances. In this article we will highlight gaps in knowledge regarding microenvironmental modulation of cargo packaging and utilization as well as EV secretion and uptake. Advances in these areas are critical for improving understanding of intercellular communication in the immune system and for therapeutic application of artificial vesicles aimed at treatment of diseases characterized by dysregulated inflammation.

Signed, Sealed, Delivered: Microenvironmental Modulation of Extracellular Vesicle-Dependent Immunoregulation in the Lung

PubMed Central

Schneider, Daniel J.; Speth, Jennifer M.; Peters-Golden, Marc

2016-01-01

Unconventional secretion and subsequent uptake of molecular cargo via extracellular vesicles (EVs) is an important mechanism by which cells can exert paracrine effects. While this phenomenon has been widely characterized in the context of their ability to promote inflammation, less is known about the ability of EVs to transfer immunosuppressive cargo. Maintenance of normal physiology in the lung requires suppression of potentially damaging inflammatory responses to the myriad of insults to which it is continually exposed. Recently, our laboratory has reported the ability of alveolar macrophages (AMs) to secrete suppressors of cytokine signaling (SOCS) proteins within microvesicles (MVs) and exosomes (Exos). Uptake of these EVs by alveolar epithelial cells (AECs) resulted in inhibition of pro-inflammatory STAT activation in response to cytokines. Moreover, AM packaging of SOCS within EVs could be rapidly tuned in response to exogenous or AEC-derived substances. In this article we will highlight gaps in knowledge regarding microenvironmental modulation of cargo packaging and utilization as well as EV secretion and uptake. Advances in these areas are critical for improving understanding of intercellular communication in the immune system and for therapeutic application of artificial vesicles aimed at treatment of diseases characterized by dysregulated inflammation. PMID:27626032

Endotoxin-induced lung alveolar cell injury causes brain cell damage.

PubMed

Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia R M; Pelosi, Paolo; Villar, Jesús

2015-01-01

Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. © 2014 by the Society for Experimental Biology and Medicine.

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.

2006-02-15

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs.more » On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.« less

Superficial white matter damage in anti-NMDA receptor encephalitis.

PubMed

Phillips, Owen Robert; Joshi, Shantanu H; Narr, Katherine L; Shattuck, David W; Singh, Manpreet; Di Paola, Margherita; Ploner, Christoph J; Prüss, Harald; Paul, Friedemann; Finke, Carsten

2018-05-01

Clinical brain MRI is normal in the majority of patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

PubMed

Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

2018-03-01

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

White matter damage in primary progressive aphasias: a diffusion tensor tractography study.

PubMed

Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M; Henry, Maya L; Filippi, Massimo; Agosta, Federica; Dronkers, Nina F; Henry, Roland G; Ogar, Jennifer M; Miller, Bruce L; Gorno-Tempini, Maria Luisa

2011-10-01

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.

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

PubMed

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.

The IκB family member Bcl-3 coordinates the pulmonary defense against Klebsiella pneumoniae infection.

PubMed

Pène, Frédéric; Paun, Andrea; Sønder, Søren Ulrik; Rikhi, Nimisha; Wang, Hongshan; Claudio, Estefania; Siebenlist, Ulrich

2011-02-15

Bcl-3 is an atypical member of the IκB family that has the potential to positively or negatively modulate nuclear NF-κB activity in a context-dependent manner. Bcl-3's biologic impact is complex and includes roles in tumorigenesis and diverse immune responses, including innate immunity. Bcl-3 may mediate LPS tolerance, suppressing cytokine production, but it also seems to contribute to defense against select systemic bacterial challenges. However, the potential role of Bcl-3 in organ-specific host defense against bacteria has not been addressed. In this study, we investigated the relevance of Bcl-3 in a lung challenge with the Gram-negative pathogen Klebsiella pneumoniae. In contrast to wild-type mice, Bcl-3-deficient mice exhibited significantly increased susceptibility toward K. pneumoniae pneumonia. The mutant mice showed increased lung damage marked by neutrophilic alveolar consolidation, and they failed to clear bacteria in lungs, which correlated with increased bacteremic dissemination. Loss of Bcl-3 incurred a dramatic cytokine imbalance in the lungs, which was characterized by higher levels of IL-10 and a near total absence of IFN-γ. Moreover, Bcl-3-deficient mice displayed increased lung production of the neutrophil-attracting chemokines CXCL-1 and CXCL-2. Alveolar macrophages and neutrophils are important to antibacterial lung defense. In vitro stimulation of Bcl-3-deficient alveolar macrophages with LPS or heat-killed K. pneumoniae recapitulated the increase in IL-10 production, and Bcl-3-deficient neutrophils were impaired in intracellular bacterial killing. These findings suggest that Bcl-3 is critically involved in lung defense against Gram-negative bacteria, modulating functions of several cells to facilitate efficient clearance of bacteria.

Selective targeting of alveolar type II respiratory epithelial cells by anti-surfactant protein-C antibody-conjugated lipoplexes

PubMed Central

Wu, Yun; Ma, Junyu; Woods, Parker S.; Chesarino, Nicholas M.; Liu, Chang; Lee, L. James; Nana-Sinkam, Serge P.; Davis, Ian C.

2015-01-01

Alveolar type II (ATII) respiratory epithelial cells are essential to normal lung function. They may be also central to the pathogenesis of diseases such as acute lung injury, pulmonary fibrosis, and pulmonary adenocarcinoma. Hence, ATII cells are important therapeutic targets. However, effective ATII cell-specific drug delivery in vivo requires carriers of an appropriate size, which can cross the hydrophobic alveolar surfactant film and polar aqueous layer overlying ATII cells, and be taken up without inducing ATII cell dysfunction, pulmonary inflammation, lung damage, or excessive systemic spread and side-effects. We have developed lipoplexes as a versatile nanoparticle carrier system for drug/RNA delivery. To optimize their pulmonary localization and ATII cell specificity, lipoplexes were conjugated to an antibody directed against the ATII cell-specific antigen surfactant protein-C (SP-C) then administered to C57BL/6 mice via the nares. Intranasally-administered, anti-SP-C-conjugated lipoplexes targeted mouse ATII cells with >70% specificity in vivo, were retained within ATII cells for at least 48 hours, and did not accumulate at significant levels in other lung cell types or viscera. 48 hours after treatment with anti-SP-C-conjugated lipoplexes containing the test microRNA miR-486, expression of mature miR-486 was approximately 4-fold higher in ATII cells than whole lung by qRT-PCR, and was undetectable in other viscera. Lipoplexes induced no weight loss, hypoxemia, lung dysfunction, pulmonary edema, or pulmonary inflammation over a 6-day period. These findings indicate that ATII cell-targeted lipoplexes exhibit all the desired characteristics of an effective drug delivery system for treatment of pulmonary diseases that result primarily from ATII cell dysfunction. PMID:25687308

Follistatin-like 1 expression is decreased in the alveolar epithelium of hypoplastic rat lungs with nitrofen-induced congenital diaphragmatic hernia.

PubMed

Takahashi, Toshiaki; Zimmer, Julia; Friedmacher, Florian; Puri, Prem

2017-05-01

Pulmonary hypoplasia (PH), characterized by incomplete alveolar development, remains a major therapeutic challenge associated with congenital diaphragmatic hernia (CDH). Follistatin-like 1 (Fstl1) is a crucial regulator of alveolar formation and maturation, which is strongly expressed in distal airway epithelium. Fstl1-deficient mice exhibit reduced airspaces, impaired alveolar epithelial cell differentiation, and insufficient production of surfactant proteins similar to PH in human CDH. We hypothesized that pulmonary Fstl1 expression is decreased during alveolarization in the nitrofen-induced CDH model. Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D18 and D21 and divided into control-/nitrofen-exposed specimens. Alveolarization was assessed using morphometric analysis techniques. Pulmonary gene expression of Fstl1 was determined by qRT-PCR. Immunofluorescence-double-staining for Fstl1 and alveolar epithelial marker surfactant protein C (SP-C) was performed to evaluate protein expression/localization. Radial alveolar count was significantly reduced in hypoplastic lungs of nitrofen-exposed fetuses with significant down regulation of Fstl1 mRNA expression on D18 and D21 compared to controls. Confocal-laser-scanning-microscopy revealed strikingly diminished Fstl1 immunofluorescence and SP-C expression in distal alveolar epithelium of nitrofen-exposed fetuses with CDH-associated PH on D18 and D21 compared to controls. Decreased expression of Fstl1 in alveolar epithelium may disrupt alveolarization and pulmonary surfactant production, thus contributing to the development of PH in the nitrofen-induced CDH model. 2b (Centre for Evidence-Based Medicine, Oxford). Copyright © 2017 Elsevier Inc. All rights reserved.

Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma.

PubMed

Jin, E; Ghazizadeh, M; Fujiwara, M; Nagashima, M; Shimizu, H; Ohaki, Y; Arai, S; Gomibuchi, M; Takemura, T; Kawanami, O

2001-09-01

Normal alveolar capillary endothelium is quiescent in nature and displays anticoagulant thrombomodulin (TM) on its surface. The cytoplasms of these endothelial cells are ultrastructurally non-fenestrated type, and they barely express von Willebrand factor (vWf). Alveolar fibrosis is accompanied by a capillary endothelium reactive for vWf, and a loss of TM expression. In primary lung adenocarcinoma, neovascularization occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor-bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt-1), and proliferating markers (Ki-67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription-polymerase chain reaction (RT-PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic-like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumor-bearing alveolar walls showed significant expression of mRNA of VEGF165 and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor-associated VEGF165 and of KDR in the alveolar walls in primary lung adenocarcinoma.

Comparative analysis between the alveolar recruitment maneuver and breath stacking technique in patients with acute lung injury

PubMed Central

Porto, Elias Ferreira; Tavolaro, Kelly Cristiani; Kumpel, Claudia; Oliveira, Fernanda Augusta; Sousa, Juciaria Ferreira; de Carvalho, Graciele Vieira; de Castro, Antonio Adolfo Mattos

2014-01-01

Objective To compare the effectiveness of the alveolar recruitment maneuver and the breath stacking technique with respect to lung mechanics and gas exchange in patients with acute lung injury. Methods Thirty patients were distributed into two groups: Group 1 - breath stacking; and Group 2 - alveolar recruitment maneuver. After undergoing conventional physical therapy, all patients received both treatments with an interval of 1 day between them. In the first group, the breath stacking technique was used initially, and subsequently, the alveolar recruitment maneuver was applied. Group 2 patients were initially subjected to alveolar recruitment, followed by the breath stacking technique. Measurements of lung compliance and airway resistance were evaluated before and after the use of both techniques. Gas analyses were collected before and after the techniques were used to evaluate oxygenation and gas exchange. Results Both groups had a significant increase in static compliance after breath stacking (p=0.021) and alveolar recruitment (p=0.03), but with no significant differences between the groups (p=0.95). The dynamic compliance did not increase for the breath stacking (p=0.22) and alveolar recruitment (p=0.074) groups, with no significant difference between the groups (p=0.11). The airway resistance did not decrease for either groups, i.e., breath stacking (p=0.91) and alveolar recruitment (p=0.82), with no significant difference between the groups (p=0.39). The partial pressure of oxygen increased significantly after breath stacking (p=0.013) and alveolar recruitment (p=0.04), but there was no significant difference between the groups (p=0.073). The alveolar-arterial O2 difference decreased for both groups after the breath stacking (p=0.025) and alveolar recruitment (p=0.03) interventions, and there was no significant difference between the groups (p=0.81). Conclusion Our data suggest that the breath stacking and alveolar recruitment techniques are effective in improving the lung mechanics and gas exchange in patients with acute lung injury. PMID:25028951

Comparative analysis between the alveolar recruitment maneuver and breath stacking technique in patients with acute lung injury.

PubMed

Porto, Elias Ferreira; Tavolaro, Kelly Cristiani; Kumpel, Claudia; Oliveira, Fernanda Augusta; Sousa, Juciaria Ferreira; Carvalho, Graciele Vieira de; Castro, Antonio Adolfo Mattos de

2014-01-01

To compare the effectiveness of the alveolar recruitment maneuver and the breath stacking technique with respect to lung mechanics and gas exchange in patients with acute lung injury. Thirty patients were distributed into two groups: Group 1 - breath stacking; and Group 2 - alveolar recruitment maneuver. After undergoing conventional physical therapy, all patients received both treatments with an interval of 1 day between them. In the first group, the breath stacking technique was used initially, and subsequently, the alveolar recruitment maneuver was applied. Group 2 patients were initially subjected to alveolar recruitment, followed by the breath stacking technique. Measurements of lung compliance and airway resistance were evaluated before and after the use of both techniques. Gas analyses were collected before and after the techniques were used to evaluate oxygenation and gas exchange. Both groups had a significant increase in static compliance after breath stacking (p=0.021) and alveolar recruitment (p=0.03), but with no significant differences between the groups (p=0.95). The dynamic compliance did not increase for the breath stacking (p=0.22) and alveolar recruitment (p=0.074) groups, with no significant difference between the groups (p=0.11). The airway resistance did not decrease for either groups, i.e., breath stacking (p=0.91) and alveolar recruitment (p=0.82), with no significant difference between the groups (p=0.39). The partial pressure of oxygen increased significantly after breath stacking (p=0.013) and alveolar recruitment (p=0.04), but there was no significant difference between the groups (p=0.073). The alveolar-arterial O2 difference decreased for both groups after the breath stacking (p=0.025) and alveolar recruitment (p=0.03) interventions, and there was no significant difference between the groups (p=0.81). Our data suggest that the breath stacking and alveolar recruitment techniques are effective in improving the lung mechanics and gas exchange in patients with acute lung injury.

Alveolar type II cell-fibroblast interactions, synthesis and secretion of surfactant and type I collagen.

PubMed

Griffin, M; Bhandari, R; Hamilton, G; Chan, Y C; Powell, J T

1993-06-01

During alveolar development and alveolar repair close contacts are established between fibroblasts and lung epithelial cells through gaps in the basement membrane. Using co-culture systems we have investigated whether these close contacts influence synthesis and secretion of the principal surfactant apoprotein (SP-A) by cultured rat lung alveolar type II cells and the synthesis and secretion of type I collagen by fibroblasts. The alveolar type II cells remained cuboidal and grew in colonies on fibroblast feeder layers and on Matrigel-coated cell culture inserts but were progressively more flattened on fixed fibroblast monolayers and plastic. Alveolar type II cells cultured on plastic released almost all their SP-A into the medium by 4 days. Alveolar type II cells cultured on viable fibroblasts or Matrigel-coated inserts above fibroblasts accumulated SP-A in the medium at a constant rate for the first 4 days, and probably recycle SP-A by endocytosis. The amount of mRNA for SP-A was very low after 4 days of culture of alveolar type II cells on plastic, Matrigel-coated inserts or fixed fibroblast monolayers: relatively, the amount of mRNA for SP-A was increased 4-fold after culture of alveolar type II cells on viable fibroblasts. Co-culture of alveolar type II cells with confluent human dermal fibroblasts stimulated by 2- to 3-fold the secretion of collagen type I into the culture medium, even after the fibroblasts' growth had been arrested with mitomycin C. Collagen secretion, by fibroblasts, also was stimulated 2-fold by conditioned medium from alveolar type II cells cultured on Matrigel. The amount of mRNA for type I collagen increased only modestly when fibroblasts were cultured in this conditioned medium. This stimulation of type I collagen secretion diminished as the conditioned medium was diluted out, but at high dilutions further stimulation occurred, indicating that a factor that inhibited collagen secretion also was being diluted out. The conditioned medium contained low levels of IGF-1 and the stimulation of type I collagen secretion was abolished when the conditioned medium was pre-incubated with antibodies to insulin-like growth factor 1 (IGF-1). There are important reciprocal interactions between alveolar type II cells and fibroblasts in co-culture. Direct contacts between alveolar type II cells and fibroblasts appear to have a trophic effect on cultured alveolar type II cells, increasing the levels of mRNA for SP-A. Rat lung alveolar type II cells appear to release a factor (possibly IGF-1) that stimulates type I collagen secretion by fibroblasts.

[The efficacy of phlebotomy with a low iron diet in the management of pulmonary iron overload].

PubMed

Fukuda, Tomoko; Kimura, Fumiaki; Watanabe, Yoichi; Yoshino, Tadasi; Kimura, Ikuro

2003-05-01

Numerous studies have shown that workers in ferriferous industries have an elevated risk of respiratory tract neoplasia and other airway diseases. Evidence is presented that iron is a carcinogenic and tissue toxic hazard as regarding the inhalation of ferriferous substances. Elimination of the inhaled iron and prevention from accumulation of iron in the lung seems to be very important. A 26-year-old man was admitted to our hospital complaining of right chest pain. He had worked as an arc welder for two years without a mask. A chest CT showed diffuse ground glass opacity in the bilateral lung fields. A transbronchial lung biopsy specimen showed numerous alveolar and interstitial iron-laden macrophages. A 200 ml phlebotomy was carried out biweekly in combination with a low iron diet (8 mg/day). When serum ferritin reached 20 ng/ml, phlebotomy was stopped. After that, serum ferritin level was kept at around 20 ng/ml with the low iron diet alone. A transbronchial lung biopsy was carried out again 7 months later and the specimen showed remarkable reduction in the number of iron-laden alveolar and interstitial macrophages. Phlebotomy in combination with a low iron diet might become a useful strategy in the management of pulmonary conditions associated with iron loading.

Diagnostic pitfall on the histological spectrum of adult-onset renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.

PubMed

Kuroda, Naoto; Katto, Kazunobu; Tanaka, Yukichi; Yamaguchi, Tadanori; Inoue, Kaori; Ohara, Masahiko; Mizuno, Keiko; Hes, Ondrej; Michal, Michal; Lee, Gang-Hong

2010-06-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion recently has been found. In this article, we demonstrate an unusual features of such a case. A 73-year-old Japanese woman presented with macroscopic hematuria. The imaging examinations disclosed the renal tumor. Histological examination showed the finding of ASPL-TFE3 RCC, which was characterized by papillary, alveolar, or solid growth of voluminous cell with clear and eosinophilic cells, and stromal psammoma body and hyaline nodules. Additionally, shrunken nuclei, thick cell border, and perinuclear clearing characteristic of chromophobe renal cell carcinoma were observed in the alveolar growth area and the transitional zone between stromal hyalinization, and osseous metaplasia was identified. Immunohistochemically, nuclei of tumorous cell were diffusely positive for TFE3. A RT-PCR study revealed the ASPL-TFE3 chimeric transcript. Finally, pathologists should recognize that the histology of RCC associated with Xp11.2 translocation/TFE3 gene fusion may focally resemble that of chromophobe RCC, but TFE3 immunohistochemistry and molecular genetic study may be helpful in the differential diagnosis. Moreover, osseous metaplasia as well as psammoma bodies should be added to the histological spectrum of the stromal change in RCC associated with Xp11.2 translocations/TFE3 gene fusions.

International Airport Impacts to Air Quality: Size and Related Properties of Large Increases in Ultrafine Particle Number Concentrations.

PubMed

Hudda, N; Fruin, S A

2016-04-05

We measured particle size distributions and spatial patterns of particle number (PN) and particle surface area concentrations downwind from the Los Angeles International Airport (LAX) where large increases (over local background) in PN concentrations routinely extended 18 km downwind. These elevations were mostly comprised of ultrafine particles smaller than 40 nm. For a given downwind distance, the greatest increases in PN concentrations, along with the smallest mean sizes, were detected at locations under the landing jet trajectories. The smaller size of particles in the impacted area, as compared to the ambient urban aerosol, increased calculated lung deposition fractions to 0.7-0.8 from 0.5-0.7. A diffusion charging instrument (DiSCMini), that simulates alveolar lung deposition, measured a fivefold increase in alveolar-lung deposited surface area concentrations 2-3 km downwind from the airport (over local background), decreasing steadily to a twofold increase 18 km downwind. These ratios (elevated lung-deposited surface area over background) were lower than the corresponding ratios for elevated PN concentrations, which decreased from tenfold to twofold over the same distance, but the spatial patterns of elevated concentrations were similar. It appears that PN concentration can serve as a nonlinear proxy for lung deposited surface area downwind of major airports.

Role of alveolar topology on acinar flows and convective mixing.

PubMed

Hofemeier, Philipp; Sznitman, Josué

2014-06-01

Due to experimental challenges, computational simulations are often sought to quantify inhaled aerosol transport in the pulmonary acinus. Commonly, these are performed using generic alveolar topologies, including spheres, toroids, and polyhedra, to mimic the complex acinar morphology. Yet, local acinar flows and ensuing particle transport are anticipated to be influenced by the specific morphological structures. We have assessed a range of acinar models under self-similar breathing conditions with respect to alveolar flow patterns, convective flow mixing, and deposition of fine particles (1.3 μm diameter). By tracking passive tracers over cumulative breathing cycles, we find that irreversible flow mixing correlates with the location and strength of the recirculating vortex inside the cavity. Such effects are strongest in proximal acinar generations where the ratio of alveolar to ductal flow rates is low and interalveolar disparities are most apparent. Our results for multi-alveolated acinar ducts highlight that fine 1 μm inhaled particles subject to alveolar flows are sensitive to the alveolar topology, underlining interalveolar disparities in particle deposition patterns. Despite the simplicity of the acinar models investigated, our findings suggest that alveolar topologies influence more significantly local flow patterns and deposition sites of fine particles for upper generations emphasizing the importance of the selected acinar model. In distal acinar generations, however, the alveolar geometry primarily needs to mimic the space-filling alveolar arrangement dictated by lung morphology.

Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

PubMed

Sasaki, Takanori; Nakamura, Wataru; Inokuma, Shigeko; Matsubara, Erika

2016-02-01

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases.

Genetics and biological property analysis of Korea lineage of influenza A H9N2 viruses.

PubMed

Kang, Min; Jang, Hyung-Kwan

2017-05-01

H9N2 influenza viruses have been detected from wild and domestic avian species including chickens and ducks worldwide. Few studies have compared the biological properties of different H9N2 lineages or determined whether certain lineages might pose a higher risk to mammals, especially H9N2 viruses of Korean lineage. The objective of this study was to characterize the genetic and biological properties of 22 Korean H9N2 viruses and assess their potential risks to mammals. Their complete genomes were analyzed. Some Korean H9N2 viruses were found to carry mammalian host-specific mutations. Based on genomic diversities, these H9N2 viruses were divided into 12 genotypes. All 22 showed preferential binding to human-like receptor. Two of eight H9N2 viruses were highly lethal to mice, causing 90-100% mortality without prior adaptation and severe respiratory syndromes associated with diffuse lung injury, severe pneumonia, and alveolar damage. These findings suggest that recent Korean H9N2 viruses might have established a stable sublineage with enhanced pathogenicity to mice. Various H9N2 strains pathogenic to mice were endemic in wild bird, poultry farm, and live bird markets, suggesting that Korean H9N2 viruses could evolve to become a threat to humans. The findings emphasize the necessity of careful, continuous, and thorough surveillance paired with risk-assessment for circulating H9N2 influenza viruses. Copyright © 2017 Elsevier B.V. All rights reserved.

Lung Metabolic Activation as an Early Biomarker of the Acute Respiratory Distress Syndrome and Local Gene Expression Heterogeneity

PubMed Central

Wellman, Tyler J.; de Prost, Nicolas; Tucci, Mauro; Winkler, Tilo; Baron, Rebecca M.; Filipczak, Piotr; Raby, Benjamin; Chu, Jen-hwa; Harris, R. Scott; Musch, Guido; dos Reis Falcao, Luiz F.; Capelozzi, Vera; Venegas, Jose; Melo, Marcos F. Vidal

2016-01-01

Background The acute respiratory distress syndrome (ARDS) is an inflammatory condition comprising diffuse lung edema and alveolar damage. ARDS frequently results from regional injury mechanisms. However, it is unknown whether detectable inflammation precedes lung edema and opacification, and whether topographically differential gene expression consistent with heterogeneous injury occurs in early ARDS. We aimed to determine the temporal relationship between pulmonary metabolic activation and density in a large animal model of early ARDS, and to assess gene expression in differentially activated regions. Methods We produced ARDS in sheep with intravenous LPS (10ng/kg/h) and mechanical ventilation for 20h. Using positron emission tomography, we assessed regional cellular metabolic activation with 2-deoxy-2-[(18)F]fluoro-D-glucose, perfusion and ventilation with 13NN-saline, and aeration using transmission scans. Species-specific micro-array technology was used to assess regional gene expression. Results Metabolic activation preceded detectable increases in lung density (as required for clinical diagnosis) and correlated with subsequent histological injury, suggesting its predictive value for severity of disease progression. Local time-courses of metabolic activation varied, with highly perfused and less aerated dependent lung regions activated earlier than non-dependent regions. These regions of distinct metabolic trajectories demonstrated differential gene expression for known and potential novel candidates for ARDS pathogenesis. Conclusions Heterogeneous lung metabolic activation precedes increases in lung density in the development of ARDS due to endotoxemia and mechanical ventilation. Local differential gene expression occurs in these early stages and reveals molecular pathways relevant to ARDS biology and of potential use as treatment targets. PMID:27611185

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

PubMed

Marchioni, Alessandro; Tonelli, Roberto; Ball, Lorenzo; Fantini, Riccardo; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Malerba, Mario; Pelosi, Paolo; Clini, Enrico

2018-03-23

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Concrescence of permanent maxillary second and third molars: case report of non-surgical root canal treatment.

PubMed

Foran, Denise; Komabayashi, Takashi; Lin, Louis M

2012-03-01

Concrescence is a rare developmental anomaly with an overall incidence of 0.8% in the permanent dentition. While many case reports describe the treatment of concrescence with extraction, there are few reports of non-surgical root canal treatment (NSRCT), due to the atypical root form, canal morphology, and technical difficulties involved in concrescence. This unique case report describes a technical modification of NSRCT that can retain joined posterior maxillary teeth to maintain natural posterior occlusion without surgical intervention or dental implants, thereby avoiding the risk of damage to a large portion of the alveolar bone near the maxillary sinus.

Nerve Damage From Bone Allografts and Xenografts-A Case Series.

PubMed

Pogrel, M Anthony

2017-07-01

The concept of socket preservation by placing a particulate bone allograft or xenograft into a tooth socket or on the alveolar ridge after tooth removal remains a somewhat controversial topic. The concept is that it will preserve the ridge from resorption and such that subsequent implant insertion will be easier, with fewer complications. However, one particular issue is that these materials, although not directly neurotoxic, appear to be an irritant to the nerves if they come in contact with them. We present a case series demonstrating this complication. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

Mean alveolar bone crest height decrement in subjects with an osteoporosis risk

NASA Astrophysics Data System (ADS)

Effrianto, H. P. S.; Priminiarti, M.; Makes, B. N.

2017-08-01

People 40-75 years of age have an osteoporosis risk that may be signaled by a decrease in alveolar bone crest height. Thus, this measure can be used as an indicator of osteoporosis risk. This study was conducted to provide a database of decreased alveolar bone crest heights in ages at risk of osteoporosis by using intraoral radiographs. Forty periapical radiographs of the posterior region of tooth 36 (or 46) were measured twice at different times by two different observers. The interproximal decrease in alveolar bone crest height was measured from the alveolar bone crest to the cementoenamel junction (CEJ) for each tooth on the mesial and distal sides using a ruler (mm). The mean decrease in alveolar bone crest height in at-risk ages for osteoporosis was 3.50±1.085 mm, with a mean of 3.15±0.864 mm for those 45-59 years of age, and 3.90±1.156 mm for those aged 60-75 years. The mean decrease in alveolar bone crest height in people 60-75 years of age was larger than in people 45-59 years of age. There was a medium correlation between age and decreased alveolar bone crest height.

Relationship between changes in alveolar surfactant levels and lung defence mechanisms.

PubMed

Pozzi, E; Luisetti, M; Spialtini, L; Coccia, P; Rossi, A; Donnini, M; Cetta, G; Salmona, M

1989-01-01

Pulmonary surfactant, besides its mechanical properties, is thought to be involved in lung defence mechanisms. We previously described that: (1) in healthy animals, surfactant synthesis stimulation with ambroxol was accompanied by alveolar macrophage activation and a shift of the alveolar elastase/antielastase balance towards increased antielastase activity, and (2) in bleomycin-treated rats alveolar phospholipidosis was obvious 14 days after drug administration, ambroxol protection reduced the phospholipid peak and the morphological apperance of lung fibrosis at the 14th day of the experiment. The present study found that: (1) in healthy rats, the ambroxol-induced increase of alveolar antielastase activity did not appear due to reactivation of alpha 1-antitrypsin normally oxidized in the alveolar milieu; (2) in bleomycin-induced pulmonary fibrosis, ambroxol protection reduced total long collagen content at day 28, and (3) in paraquat-induced pulmonary fibrosis, alveolar phospholipids were markedly reduced throughout the 21 days of the experiment. On increasing the dose of paraquat, ambroxol protection significantly reduced the animals' death rate.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hausmann, E.

1990-03-01

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

Impurity gettering in semiconductors

DOEpatents

Sopori, B.L.

1995-06-20

A process for impurity gettering in a semiconductor substrate or device such as a silicon substrate or device is disclosed. The process comprises hydrogenating the substrate or device at the back side thereof with sufficient intensity and for a time period sufficient to produce a damaged back side. Thereafter, the substrate or device is illuminated with electromagnetic radiation at an intensity and for a time period sufficient to cause the impurities to diffuse to the back side and alloy with a metal there present to form a contact and capture the impurities. The impurity gettering process also can function to simultaneously passivate defects within the substrate or device, with the defects likewise diffusing to the back side for simultaneous passivation. Simultaneously, substantially all hydrogen-induced damage on the back side of the substrate or device is likewise annihilated. Also taught is an alternate process comprising thermal treatment after hydrogenation of the substrate or device at a temperature of from about 500 C to about 700 C for a time period sufficient to cause the impurities to diffuse to the damaged back side thereof for subsequent capture by an alloying metal. 1 fig.

Impurity gettering in semiconductors

DOEpatents

Sopori, Bhushan L.

1995-01-01

A process for impurity gettering in a semiconductor substrate or device such as a silicon substrate or device. The process comprises hydrogenating the substrate or device at the back side thereof with sufficient intensity and for a time period sufficient to produce a damaged back side. Thereafter, the substrate or device is illuminated with electromagnetic radiation at an intensity and for a time period sufficient to cause the impurities to diffuse to the back side and alloy with a metal there present to form a contact and capture the impurities. The impurity gettering process also can function to simultaneously passivate defects within the substrate or device, with the defects likewise diffusing to the back side for simultaneous passivation. Simultaneously, substantially all hydrogen-induced damage on the back side of the substrate or device is likewise annihilated. Also taught is an alternate process comprising thermal treatment after hydrogenation of the substrate or device at a temperature of from about 500.degree. C. to about 700.degree. C. for a time period sufficient to cause the impurities to diffuse to the damaged back side thereof for subsequent capture by an alloying metal.

Temperature dependence of damage coefficient in electron irradiated solar cells

NASA Technical Reports Server (NTRS)

Faith, T. J.

1973-01-01

Measurements of light-generated current vs cell temperature on electron-irradiated n/p silicon solar cells show the temperature coefficient of this current to increase with increasing fluence for both 10-ohm and 20-ohm cells. A relationship between minority-carrier diffusion length and light-generated current was derived by combining measurements of these two parameters: vs fluence at room temperature, and vs cell temperature in cells irradiated to a fluence of 1 x 10 to the 15th power e/sq cm. This relationship was used, together with the light-generated current data, to calculate the temperature dependence of the diffusion-length damage coefficient. The results show a strong decrease in the damage coefficient with increasing temperature in the range experienced by solar panels in synchronous earth orbit.

Back-diffusion--fact or fiction?

PubMed

Thjodleifsson, B; Wormsley, K G

1977-01-01

Alterations in the concentration of acid in gastric juice secreted at different flow rates and disappearance of acid from the gastric lumen, when the gastric mucosa is exposed to acid luminal contents, have been interpreted as indicating "back-diffusion" of acid into the gastric mucosa from the luminal contents. The loss of acid from the gastric contents increases when the mucosa is exposed to certain drugs or is diseased, giving rise to the suggestion that the increased degree of "back-diffusion" of acid indicates mucosal damage, reflecting a breakdown of the gastric mucosal "barrier" to back-diffusion of acid from the gastric lumen. The change in the "barrier" properties of the gastric mucosa has been found to be associated with change in the electrical properties of the mucosa, so that alterations of the transmucosal potential difference has been considered to denote gastric mucosal damage. The case for every one of these hypotheses and for their underlying assumptions is discussed and found wanting for lack of direct evidence.

Ozone exposure during the early postnatal period alters the timing and pattern of alveolar growth and development in nonhuman primates.

PubMed

Avdalovic, Mark V; Tyler, Nancy K; Putney, Lei; Nishio, Susie J; Quesenberry, Sherri; Singh, Parmjit J; Miller, Lisa A; Schelegle, Edward S; Plopper, Charles G; Vu, Thiennu; Hyde, Dallas M

2012-10-01

Exposure to oxidant air pollutants in early childhood, with ozone as the key oxidant, has been linked to significant decrements in pulmonary function in young adults and exacerbation of airway remodeling in asthma. Development of lung parenchyma in rhesus monkeys is rapid during the first 2 years of life (comparable to the first 6 years in humans). Our hypothesis is that ozone inhalation during infancy alters alveolar morphogenesis. We exposed infant rhesus monkeys biweekly to 5, 8 hr/day, cycles of 0.5 ppm ozone with or without house dust mite allergen from 1 to 3 or 1 to 6 months of age. Monkeys were necropsied at 3 and 6 months of age. A morphometric approach was used to quantify changes in alveolar volume and number, the distribution of alveolar size, and capillary surface density per alveolar septa. Quantitative real time PCR was used to measure the relative difference in gene expression over time. Monkeys exposed to ozone alone or ozone combined with allergen had statistically larger alveoli that were less in number at 3 months of age. Alveolar capillary surface density was also decreased in the ozone exposed groups at 3 months of age. At 6 months of age, the alveolar number was similar between treatment groups and was associated with a significant rise in alveolar number from 3 to 6 months of age in the ozone exposed groups. This increase in alveolar number was not associated with any significant increase in microvascular growth as measured by morphometry or changes in angiogenic gene expression. Inhalation of ozone during infancy alters the appearance and timing of alveolar growth and maturation. Understanding the mechanism involved with this altered alveolar growth may provide insight into the parenchymal injury and repair process that is involved with chronic lung diseases such as severe asthma and COPD. Copyright © 2012 Wiley Periodicals, Inc.

Lung injury via oxidative stress in mice induced by inhalation exposure to rocket kerosene

PubMed Central

Xu, Bingxin; Li, Chenglin; Wang, Jianying; Wu, Jihua; Si, Shaoyan; Liu, Zhiguo; Li, Jianzhong; Zhang, Jianzhong; Cui, Yan

2015-01-01

Rocket kerosene (RK) is a new rocket propellant. Toxicity occurs if a high level of RK is inhaled. To study the toxicity of RK in lung and the mechanisms of RK-induced lung jury, a total of 72 male ICR mice (1.5 months, adult) were randomly assigned to the RK exposure group (RKEG) and normal control group (NCG). Mice were whole-body exposed to room air or aerosol of 18000 mg/m3 RK for 4 hours. Histopathological analysis was performed to evaluate the pulmonary lesions. Oxidative stress was assessed by assay of MDA, SOD, GSH-PX and TAOC. Inflammatory response was estimated by detecting inflammatory cell counts, TNF-α and IL-6 protein levels in serum. The results showed that after 2 to 6 hours of RK exposure, pulmonary vascular dilatation, congestion and edematous widening of the alveolar septum were noted. After 12 to 24 hours post-exposure, diffuse hemorrhage in alveolar space were found, along with the progressive pulmonary vascular dilatation and edematous widening of alveolar septum. During 3 to 7 days of RK-exposure, inflammatory cells were scattered in the lung tissue. The pathological alterations of the lung were alleviated after 14 days post-exposure, and showed significant improvement after 21 days post-exposure. After 30 days of RK exposure, the pathological changes in the lung tissue were nearly recovered except the local thickening of the alveolar wall. Compared with NCG, RK inhalation produced a significant increase of MDA levels and a significant decrease of SOD, GSH-Px and TAOC activity in the lung after 2 hours post-exposure (P < 0.05). There were significant increases of TNF-α and IL-6 protein levels in serum of mice in RKEG after 2, 6 and 12 hours and 1, 4 and 7 days post-exposure compared with NCG (P < 0.05). TNF-α protein levels had a sharp increase after 4 days of exposure. IL-6 protein level was increased at early phase of experiment and then gradually decreased along with the prolonged course of exposure. Considering that the RK-induced lung injury was through the oxidative stress, inhibition of oxidative stress after RK exposure may be urgently needed. PMID:26191256

Lung injury via oxidative stress in mice induced by inhalation exposure to rocket kerosene.

PubMed

Xu, Bingxin; Li, Chenglin; Wang, Jianying; Wu, Jihua; Si, Shaoyan; Liu, Zhiguo; Li, Jianzhong; Zhang, Jianzhong; Cui, Yan

2015-01-01

Rocket kerosene (RK) is a new rocket propellant. Toxicity occurs if a high level of RK is inhaled. To study the toxicity of RK in lung and the mechanisms of RK-induced lung jury, a total of 72 male ICR mice (1.5 months, adult) were randomly assigned to the RK exposure group (RKEG) and normal control group (NCG). Mice were whole-body exposed to room air or aerosol of 18000 mg/m3 RK for 4 hours. Histopathological analysis was performed to evaluate the pulmonary lesions. Oxidative stress was assessed by assay of MDA, SOD, GSH-PX and TAOC. Inflammatory response was estimated by detecting inflammatory cell counts, TNF-α and IL-6 protein levels in serum. The results showed that after 2 to 6 hours of RK exposure, pulmonary vascular dilatation, congestion and edematous widening of the alveolar septum were noted. After 12 to 24 hours post-exposure, diffuse hemorrhage in alveolar space were found, along with the progressive pulmonary vascular dilatation and edematous widening of alveolar septum. During 3 to 7 days of RK-exposure, inflammatory cells were scattered in the lung tissue. The pathological alterations of the lung were alleviated after 14 days post-exposure, and showed significant improvement after 21 days post-exposure. After 30 days of RK exposure, the pathological changes in the lung tissue were nearly recovered except the local thickening of the alveolar wall. Compared with NCG, RK inhalation produced a significant increase of MDA levels and a significant decrease of SOD, GSH-Px and TAOC activity in the lung after 2 hours post-exposure (P<0.05). There were significant increases of TNF-α and IL-6 protein levels in serum of mice in RKEG after 2, 6 and 12 hours and 1, 4 and 7 days post-exposure compared with NCG (P<0.05). TNF-α protein levels had a sharp increase after 4 days of exposure. IL-6 protein level was increased at early phase of experiment and then gradually decreased along with the prolonged course of exposure. Considering that the RK-induced lung injury was through the oxidative stress, inhibition of oxidative stress after RK exposure may be urgently needed.

Phenotypic heterogeneity in lung capillary and extra-alveolar endothelial cells. Increased extra-alveolar endothelial permeability is sufficient to decrease compliance.

PubMed

Lowe, Kevin; Alvarez, Diego; King, Judy; Stevens, Troy

2007-11-01

In acute respiratory distress syndrome, pulmonary vascular permeability increases, causing intravascular fluid and protein to move into the lung's interstitium. The classic model describing the formation of pulmonary edema suggests that fluid crossing the capillary endothelium is drawn by negative interstitial pressure into the potential space surrounding extra-alveolar vessels and, as interstitial pressure builds, is forced into the alveolar air space. However, the validity of this model is challenged by animal models of acute lung injury in which extra-alveolar vessels are more permeable than capillaries under a variety of conditions. In the current study, we sought to determine whether extravascular fluid accumulation can be produced because of increased permeability of either the capillary or extra-alveolar endothelium, and whether different pathophysiology results from such site-specific increases in permeability. We perfused isolated lungs with either the plant alkaloid thapsigargin, which increases extra-alveolar endothelial permeability, or with 4alpha-phorbol 12, 13-didecanoate, which increases capillary endothelial permeability. Both treatments produced equal increases in whole lung vascular permeability, but caused fluid accumulations in separate anatomical compartments. Light microscopy of isolated lungs showed that thapsigargin caused fluid cuffing of large vessels, while 4alpha-phorbol 12, 13-didecanoate caused alveolar flooding. Dynamic compliance was reduced in lungs with cuffing of large vessels, but not in lungs with alveolar flooding. Phenotypic differences between vascular segments resulted in site-specific increases in permeability, which have different pathophysiological outcomes. Our findings suggest that insults leading to acute respiratory distress syndrome may increase permeability in extra-alveolar or capillary vascular segments, resulting in different pathophysiological sequela.

[Evaluation of the thermal effects of the plasma microtorch by infrared thermography].

PubMed

Lhuisset, F; Zeboulon, S; Bouchier, G

1991-01-01

This study presents a detailed example of the examination of the tooth treated by thermal therapy, by infrared thermography and the different manners to show the results of the examination. The results of the work shows: the thermal diffusion into the tooth is similar to the thermal diffusion into an isotropic environment, the fusion heat of the dentine is reached without any damage to the pulp. The study of the tooth treated by the thermal action of the MICRO PLASMA SYSTEM confirms the thérapeutical effects of the thermal treatment without any damage to the pulp.

Permeability, storage and hydraulic diffusivity controlled by earthquakes

NASA Astrophysics Data System (ADS)

Brodsky, E. E.; Fulton, P. M.; Xue, L.

2016-12-01

Earthquakes can increase permeability in fractured rocks. In the farfield, such permeability increases are attributed to seismic waves and can last for months after the initial earthquake. Laboratory studies suggest that unclogging of fractures by the transient flow driven by seismic waves is a viable mechanism. These dynamic permeability increases may contribute to permeability enhancement in the seismic clouds accompanying hydraulic fracking. Permeability enhancement by seismic waves could potentially be engineered and the experiments suggest the process will be most effective at a preferred frequency. We have recently observed similar processes inside active fault zones after major earthquakes. A borehole observatory in the fault that generated the M9.0 2011 Tohoku earthquake reveals a sequence of temperature pulses during the secondary aftershock sequence of an M7.3 aftershock. The pulses are attributed to fluid advection by a flow through a zone of transiently increased permeability. Directly after the M7.3 earthquake, the newly damaged fault zone is highly susceptible to further permeability enhancement, but ultimately heals within a month and becomes no longer as sensitive. The observation suggests that the newly damaged fault zone is more prone to fluid pulsing than would be expected based on the long-term permeability structure. Even longer term healing is seen inside the fault zone of the 2008 M7.9 Wenchuan earthquake. The competition between damage and healing (or clogging and unclogging) results in dynamically controlled permeability, storage and hydraulic diffusivity. Recent measurements of in situ fault zone architecture at the 1-10 meter scale suggest that active fault zones often have hydraulic diffusivities near 10-2 m2/s. This uniformity is true even within the damage zone of the San Andreas fault where permeability and storage increases balance each other to achieve this value of diffusivity over a 400 m wide region. We speculate that fault zones may evolve to a preferred diffusivity in a dynamic equilibrium.

Synthesis of Dipalmitoyl Lecithin by Alveolar Macrophages

PubMed Central

Mason, Robert J.; Huber, Gary; Vaughan, Martha

1972-01-01

A reliable, relatively simple method for isolation and quantification of disaturated lecithins is described. In rabbit lung, 34% of the lecithins were disaturated, in alveolar macrophages, 19%. More than 95% of the fatty acids of the disaturated lecithins from lung and alveolar macrophages was palmitic. Hence, the disaturated lecithins from these sources were essentially all dipalmitoyl lecithin. Both heterophils and alveolar macrophages incorporated 14C-labeled choline and palmitate into disaturated lecithins. Liver slices in which only about 1% of the lecithins were disaturated incorporated very little of these precursors into this fraction. Of the palmitate incorporated in vitro into disaturated lecithins by alveolar macrophages, heterophils, and lung slices, 37% was in the 1 position. In disaturated lecithins isolated from pulmonary lavage fluid, alveolar macrophages, and lung of rabbit 8-12 hr after a single intravenous injection of palmitic-1-14C acid, 45% of the 14C was in position 1. At earlier times, from 20-240 min after injection, the distribution of 14C was similar in the samples from lung, but in those from alveolar macrophages and lavage fluid, the percentage in position 1 was slightly lower. Glycerol-U-14C was incorporated into disaturated lecithins by alveolar macrophages and by lung slices in vitro. Both tissues incorporated very little label from ethanolamine or from methyl-labeled methionine into this fraction. All of the data are consistent with the view that alveolar macrophages synthesize dipalmitoyl lecithin via the cytidine diphosphate-choline pathway. PMID:5066597

Diffusion tensor imaging can detect the early stages of cartilage damage: a comparison study.

PubMed

Ukai, Taku; Sato, Masato; Yamashita, Tomohiro; Imai, Yutaka; Mitani, Genya; Takagaki, Tomonori; Serigano, Kenji; Mochida, Joji

2015-02-21

In the present study, we measured damaged areas of cartilage with diffusion tensor (DT) imaging and T2 mapping, and investigated the extent to which cartilage damage could be determined using these techniques. Forty-one patients underwent arthroscopic knee surgery for osteoarthritis of the knee, a meniscus injury, or an anterior cruciate ligament injury. Preoperative magnetic resonance imaging of the knee was performed, including T2 mapping and diffusion tensor imaging. The presence of cartilage injury involving the medial and lateral femoral condyles and tibia plateau was assessed during surgery using the Outerbridge scale. The ADC, T2 values and fractional anisotropy of areas of cartilage injury were then retrospectively analysed. The ADC results identified significant differences between Outerbridge grades 0 and 2 (P = 0.041); 0 and 3 (P < 0.001); 1 and 2 (P = 0.045); 1 and 3 (P < 0.001); and 2 and 3 (P = 0.028). The FA results identified significant differences between grades 0 and 1 (P < 0.001); 0 and 2 (P < 0.001); and 0 and 3 (P < 0.001). T2 mapping identified significant differences between Outerbridge grades 0 and 2 (P = 0.032); 0 and 3 (P < 0.001); 1 and 3 (P < 0.001); and 2 and 3 (P < 0.001). Both the T2 mapping (R(2) = 0.7883) and the ADC (R(2) = 0.9184) correlated significantly with the Outerbridge grade. The FA (R(2) = 0.6616) correlated slightly with the Outerbridge grade. T2 mapping can be useful for detecting moderate or severe cartilage damage, and the ADC can be used to detect early stage cartilage damage. The FA can also distinguish normal from damaged cartilage.

Healing of polymer interfaces: Interfacial dynamics, entanglements, and strength

NASA Astrophysics Data System (ADS)

Ge, Ting; Robbins, Mark O.; Perahia, Dvora; Grest, Gary S.

2014-07-01

Self-healing of polymer films often takes place as the molecules diffuse across a damaged region, above their melting temperature. Using molecular dynamics simulations we probe the healing of polymer films and compare the results with those obtained for thermal welding of homopolymer slabs. These two processes differ from each other in their interfacial structure since damage leads to increased polydispersity and more short chains. A polymer sample was cut into two separate films that were then held together in the melt state. The recovery of the damaged film was followed as time elapsed and polymer molecules diffused across the interface. The mass uptake and formation of entanglements, as obtained from primitive path analysis, are extracted and correlated with the interfacial strength obtained from shear simulations. We find that the diffusion across the interface is significantly faster in the damaged film compared to welding because of the presence of short chains. Though interfacial entanglements increase more rapidly for the damaged films, a large fraction of these entanglements are near chain ends. As a result, the interfacial strength of the healing film increases more slowly than for welding. For both healing and welding, the interfacial strength saturates as the bulk entanglement density is recovered across the interface. However, the saturation strength of the damaged film is below the bulk strength for the polymer sample. At saturation, cut chains remain near the healing interface. They are less entangled and as a result they mechanically weaken the interface. Chain stiffness increases the density of entanglements, which increases the strength of the interface. Our results show that a few entanglements across the interface are sufficient to resist interfacial chain pullout and enhance the mechanical strength.

Pulmonary hyperpolarized (129) Xe morphometry for mapping xenon gas concentrations and alveolar oxygen partial pressure: Proof-of-concept demonstration in healthy and COPD subjects.

PubMed

Ouriadov, A; Farag, A; Kirby, M; McCormack, D G; Parraga, G; Santyr, G E

2015-12-01

Diffusion-weighted (DW) hyperpolarized (129) Xe morphometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro-structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pA O2 ) maps by extracting the unrestricted diffusion coefficient (D0 ) of xenon as a morphometric parameter. In this proof-of-concept demonstration, morphometry was performed using multi b-value (0, 12, 20, 30 s/cm(2) ) DW hyperpolarized (129) Xe images obtained in four never-smokers and four COPD ex-smokers. Morphometric parameters and D0 maps were computed and the latter used to generate [Xe] and pA O2 maps. Xenon concentration phantoms estimating a range of values mimicking those observed in vivo were also investigated. Xenon D0 was significantly increased (P = 0.035) in COPD (0.14 ± 0.03 cm(2) /s) compared with never-smokers (0.12 ± 0.02 cm(2) /s). COPD ex-smokers also had significantly decreased [Xe] (COPD = 8 ± 7% versus never-smokers = 13 ± 8%, P = 0.012) and increased pA O2 (COPD = 18 ± 3% versus never-smokers = 15 ± 3%, P = 0.009) compared with never-smokers. Phantom measurements showed the expected dependence of D0 on [Xe] over the range of concentrations anticipated in vivo. DW hyperpolarized (129) Xe MRI morphometry can be used to simultaneously map [Xe] and pA O2 in addition to providing micro-structural biomarkers of emphysematous destruction in COPD. Phantom measurements of D0 ([Xe]) supported the hypotheses that differences in subjects may reflect differences in functional residual capacity. © 2014 Wiley Periodicals, Inc.

Preventive Effects of Drinking Hydrogen-Rich Water on Gingival Oxidative Stress and Alveolar Bone Resorption in Rats Fed a High-Fat Diet

PubMed Central

Yoneda, Toshiki; Tomofuji, Takaaki; Kunitomo, Muneyoshi; Ekuni, Daisuke; Irie, Koichiro; Azuma, Tetsuji; Machida, Tatsuya; Miyai, Hisataka; Fujimori, Kouhei; Morita, Manabu

2017-01-01

Obesity induces gingival oxidative stress, which is involved in the progression of alveolar bone resorption. The antioxidant effect of hydrogen-rich water may attenuate gingival oxidative stress and prevent alveolar bone resorption in cases of obesity. We examined whether hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption in obese rats fed a high-fat diet. Male Fischer 344 rats (n = 18) were divided into three groups of six rats each: a control group (fed a regular diet and drinking distilled water) and two experimental groups (fed a high-fat diet and drinking distilled water or hydrogen-rich water). The level of 8-hydroxydeoxyguanosine was determined to evaluate oxidative stress. The bone mineral density of the alveolar bone was analyzed by micro-computerized tomography. Obese rats, induced by a high-fat diet, showed a higher gingival level of 8-hydroxydeoxyguanosine and a lower level of alveolar bone density compared to the control group. Drinking hydrogen-rich water suppressed body weight gain, lowered gingival level of 8-hydroxydeoxyguanosine, and reduced alveolar bone resorption in rats on a high-fat diet. The results indicate that hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption by limiting obesity. PMID:28098768

Preventive Effects of Drinking Hydrogen-Rich Water on Gingival Oxidative Stress and Alveolar Bone Resorption in Rats Fed a High-Fat Diet.

PubMed

Yoneda, Toshiki; Tomofuji, Takaaki; Kunitomo, Muneyoshi; Ekuni, Daisuke; Irie, Koichiro; Azuma, Tetsuji; Machida, Tatsuya; Miyai, Hisataka; Fujimori, Kouhei; Morita, Manabu

2017-01-13

Obesity induces gingival oxidative stress, which is involved in the progression of alveolar bone resorption. The antioxidant effect of hydrogen-rich water may attenuate gingival oxidative stress and prevent alveolar bone resorption in cases of obesity. We examined whether hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption in obese rats fed a high-fat diet. Male Fischer 344 rats ( n = 18) were divided into three groups of six rats each: a control group (fed a regular diet and drinking distilled water) and two experimental groups (fed a high-fat diet and drinking distilled water or hydrogen-rich water). The level of 8-hydroxydeoxyguanosine was determined to evaluate oxidative stress. The bone mineral density of the alveolar bone was analyzed by micro-computerized tomography. Obese rats, induced by a high-fat diet, showed a higher gingival level of 8-hydroxydeoxyguanosine and a lower level of alveolar bone density compared to the control group. Drinking hydrogen-rich water suppressed body weight gain, lowered gingival level of 8-hydroxydeoxyguanosine, and reduced alveolar bone resorption in rats on a high-fat diet. The results indicate that hydrogen-rich water could suppress gingival oxidative stress and alveolar bone resorption by limiting obesity.

VDR deficiency affects alveolar bone and cementum apposition in mice.

PubMed

Zhang, Xueming; Rahemtulla, Firoz; Zhang, Ping; Thomas, Huw F

2011-07-01

To compare the mineralisation density (MD), morphology and histology of alveolar bone and cementum amongst VDR +/+, VDR -/-, and VDR -/- groups supplemented with a diet TD 96348, containing 20% lactose, 2.0% calcium and 1.25% phosphorous. Four groups of mice (6 mice/group) were identified by genotyping: VDR +/+ mice (VDR wild type), VDR -/- mice (VDR deficient), VDR -/- offsprings derived from VDR -/- parents receiving a supplemental diet (early rescued), and VDR -/- mice fed with a supplemental diet beginning at age one month (late rescued). All mice were sacrificed at age 70.5 days. Micro-CT was used to compare MD and morphology of alveolar bone and cementum. H-E and Toluidine blue staining was used to examine the ultrastructure of the alveolar bone and cementum at matched locations. In VDR -/- group, alveolar bone and cementum failed to mineralise normally. Early rescue increased MD of alveolar bone in VDR -/- mice with excessive alveolar bone formation, but which not observed in late rescue group. MD and morphology of cementum-dentine complex in both early and late rescue groups were comparable with VDR +/+ group when feeding with high-calcium rescue diet. VDR affects alveolar bone mineralisation and formation systemically and locally. However, cementum apposition and mineralisation is mainly regulated by calcium concentrations in serum. Copyright © 2010 Elsevier Ltd. All rights reserved.

Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages.

PubMed

Nayak, Deepak K; Mendez, Oscar; Bowen, Sara; Mohanakumar, Thalachallour

2018-04-20

Alveolar macrophages are terminally differentiated, lung-resident macrophages of prenatal origin. Alveolar macrophages are unique in their long life and their important role in lung development and function, as well as their lung-localized responses to infection and inflammation. To date, no unified method for identification, isolation, and handling of alveolar macrophages from humans and mice exists. Such a method is needed for studies on these important innate immune cells in various experimental settings. The method described here, which can be easily adopted by any laboratory, is a simplified approach to harvesting alveolar macrophages from bronchoalveolar lavage fluid or from lung tissue and maintaining them in vitro. Because alveolar macrophages primarily occur as adherent cells in the alveoli, the focus of this method is on dislodging them prior to harvest and identification. The lung is a highly vascularized organ, and various cell types of myeloid and lymphoid origin inhabit, interact, and are influenced by the lung microenvironment. By using the set of surface markers described here, researchers can easily and unambiguously distinguish alveolar macrophages from other leukocytes, and purify them for downstream applications. The culture method developed herein supports both human and mouse alveolar macrophages for in vitro growth, and is compatible with cellular and molecular studies.

Incorporation of Prior Knowledge of Signal Behavior Into the Reconstruction to Accelerate the Acquisition of Diffusion MRI Data.

PubMed

Abascal, Juan F P J; Desco, Manuel; Parra-Robles, Juan

2018-02-01

Diffusion MRI data are generally acquired using hyperpolarized gases during patient breath-hold, which yields a compromise between achievable image resolution, lung coverage, and number of -values. In this paper, we propose a novel method that accelerates the acquisition of diffusion MRI data by undersampling in both the spatial and -value dimensions and incorporating knowledge about signal decay into the reconstruction (SIDER). SIDER is compared with total variation (TV) reconstruction by assessing its effect on both the recovery of ventilation images and the estimated mean alveolar dimensions (MADs). Both methods are assessed by retrospectively undersampling diffusion data sets ( =8) of healthy volunteers and patients with Chronic Obstructive Pulmonary Disease (COPD) for acceleration factors between x2 and x10. TV led to large errors and artifacts for acceleration factors equal to or larger than x5. SIDER improved TV, with a lower solution error and MAD histograms closer to those obtained from fully sampled data for acceleration factors up to x10. SIDER preserved image quality at all acceleration factors, although images were slightly smoothed and some details were lost at x10. In conclusion, we developed and validated a novel compressed sensing method for lung MRI imaging and achieved high acceleration factors, which can be used to increase the amount of data acquired during breath-hold. This methodology is expected to improve the accuracy of estimated lung microstructure dimensions and provide more options in the study of lung diseases with MRI.

Apatite (U-Th)/He thermochronometry using a radiation damage accumulation and annealing model

NASA Astrophysics Data System (ADS)

Flowers, Rebecca M.; Ketcham, Richard A.; Shuster, David L.; Farley, Kenneth A.

2009-04-01

Helium diffusion from apatite is a sensitive function of the volume fraction of radiation damage to the crystal, a quantity that varies over the lifetime of the apatite. Using recently published laboratory data we develop and investigate a new kinetic model, the radiation damage accumulation and annealing model (RDAAM), that adopts the effective fission-track density as a proxy for accumulated radiation damage. This proxy incorporates creation of crystal damage proportional to α-production from U and Th decay, and the elimination of that damage governed by the kinetics of fission-track annealing. The RDAAM is a version of the helium trapping model (HeTM; Shuster D. L., Flowers R. M. and Farley K. A. (2006) The influence of natural radiation damage on helium diffusion kinetics in apatite. Earth Planet. Sci. Lett.249, 148-161), calibrated by helium diffusion data in natural and partially annealed apatites. The chief limitation of the HeTM, now addressed by RDAAM, is its use of He concentration as the radiation damage proxy for circumstances in which radiation damage and He are not accumulated and lost proportionately from the crystal. By incorporating the RDAAM into the HeFTy computer program, we explore its implications for apatite (U-Th)/He thermochronometry. We show how (U-Th)/He dates predicted from the model are sensitive to both effective U concentration (eU) and details of the temperature history. The RDAAM predicts an effective He closure temperature of 62 °C for a 28 ppm eU apatite of 60 μm radius that experienced a 10 °C/Ma monotonic cooling rate; this is 8 °C lower than the 70 °C effective closure temperature predicted using commonly assumed Durango diffusion kinetics. Use of the RDAAM is most important for accurate interpretation of (U-Th)/He data for apatite suites that experienced moderate to slow monotonic cooling (1-0.1 °C/Ma), prolonged residence in the helium partial retention zone, or a duration at temperatures appropriate for radiation damage accumulation followed by reheating and partial helium loss. Under common circumstances the RDAAM predicts (U-Th)/He dates that are older, sometimes much older, than corresponding fission-track dates. Nonlinear positive correlations between apatite (U-Th)/He date and eU in apatites subjected to the same temperature history are a diagnostic signature of the RDAAM for many but not all thermal histories. Observed date-eU correlations in four different localities can be explained with the RDAAM using geologically reasonable thermal histories consistent with independent fission-track datasets. The existence of date-eU correlations not only supports a radiation damage based kinetic model, but can significantly limit the range of acceptable time-temperature paths that account for the data. In contrast, these datasets are inexplicable using the Durango diffusion model. The RDAAM helps reconcile enigmatic data in which apatite (U-Th)/He dates are older than expected using the Durango model when compared with thermal histories based on apatite fission-track data or other geological constraints. It also has the potential to explain at least some cases in which (U-Th)/He dates are actually older than the corresponding fission-track dates.

Tomographic findings of acute pulmonary toxoplasmosis in immunocompetent patients.

PubMed

de Souza Giassi, Karina; Costa, Andre Nathan; Apanavicius, Andre; Teixeira, Fernando Bin; Fernandes, Caio Julio Cesar; Helito, Alfredo Salim; Kairalla, Ronaldo Adib

2014-11-25

Toxoplasmosis is one of the most common human zoonosis, and is generally benign in most of the individuals. Pulmonary involvement is common in immunocompromised subjects, but very rare in immunocompetents and there are scarce reports of tomographic findings in the literature. The aim of the study is to describe three immunocompetent patients diagnosed with acute pulmonary toxoplasmosis and their respective thoracic tomographic findings. Acute toxoplasmosis was diagnosed according to the results of serological tests suggestive of recent primary infection and the absence of an alternative etiology. From 2009 to 2013, three patients were diagnosed with acute respiratory failure secondary to acute toxoplasmosis. The patients were two female and one male, and were 38, 56 and 36 years old. Similarly they presented a two-week febrile illness and progressive dyspnea before admission. Laboratory tests demonstrated lymphocytosis, slight changes in liver enzymes and high inflammatory markers. Tomographic findings were bilateral smooth septal and peribronchovascular thickening (100%), ground-glass opacities (100%), atelectasis (33%), random nodules (33%), lymph node enlargement (33%) and pleural effusion (66%). All the patients improved their symptoms after treatment, and complete resolution of tomographic findings were found in the followup. These cases provide a unique description of the presentation and evolution of pulmonary tomographic manifestations of toxoplasmosis in immunocompetent patients. Toxoplasma pneumonia manifests with fever, dyspnea and a non-productive cough that may result in respiratory failure. In animal models, changes were described as interstitial pneumonitis with focal infiltrates of neutrophils that can finally evolve into a pattern of diffuse alveolar damage with focal necrosis. The tomographic findings are characterized as ground glass opacities, smooth septal and marked peribronchovascular thickening; and may mimic pulmonary congestion, lymphangitis, atypical pneumonia and pneumocystosis. This is the largest series of CT findings of acute toxoplasmosis in immunocompetent hosts, and the diagnosis should be considered as patients that present with acute respiratory failure in the context of a subacute febrile illness with bilateral and diffuse interstitial infiltrates with marked peribronchovascular thickening. If promptly treated, pulmonary toxoplasmosis can result in complete clinical and radiological recovery in immunocompetent hosts.

Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never‐ and ex‐smokers

PubMed Central

Kirby, Miranda; Ouriadov, Alexei; Svenningsen, Sarah; Owrangi, Amir; Wheatley, Andrew; Etemad‐Rezai, Roya; Santyr, Giles E.; McCormack, David G.; Parraga, Grace

2014-01-01

Abstract Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, 3He (b = 1.6 sec/cm2) and 129Xe (b = 12, 20, and 30 sec/cm2) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior–posterior (APG) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater 3He ADC (P = 0.006), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different APG for 3He ADC (P = 0.02), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for 3He ADC (P = 0.046), but not for 129Xe ADC (P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex‐smokers, CT relative area <−950 HU (RA950) correlated with 3He ADC (r = 0.90, P = 0.008) and 129Xe ADCb12 (r = 0.85, P = 0.03). In conclusion, while 129Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never‐smokers and ex‐smokers with moderate‐to‐severe emphysema, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure. PMID:25347853

An uptake of cationized ferritin by alveolar type I cells in airway-instilled goat lung: distribution of anionic sites on the epithelial surface.

PubMed

Atwal, O S; Viel, L; Minhas, K J

1990-07-01

The present study has investigated ultrastructural localization of anionic sites on the luminal surface of the alveolar epithelium of goat lung by direct airway instillation of cationized ferritin (CF) in the cranial lobe of the right lung through a bronchoscope. The cationic probe decorated preferentially the luminal plasmalemmal vesicles and plasmalemma proper of alveolar type I cell. This indicated the presence of highly charged anionic microdomains at these binding sites. The ligand was internalized in the free plasmalemmal vesicles of alveolar type I cell within 2 min. Heavy decoration of vesicles at 5 min of perfusion indicated that the amount of CF internalization increased with its concentration in the alveoli. It is suggested that exposure of alveolar surface to several gases of ruminal-origin induces changes in the surface charge of luminal plasmalemma of alveolar type I cells. The significance of these anionic plasmalemmal sites is discussed in relation to the adjustment of osmotic pressure gradient across the alveolar-capillary membrane of the ruminant lung.

Injectable bone substitute to preserve alveolar ridge resorption after tooth extraction: a study in dog.

PubMed

Boix, D; Weiss, P; Gauthier, O; Guicheux, J; Bouler, J-M; Pilet, P; Daculsi, G; Grimandi, G

2006-11-01

The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute on the prevention of alveolar ridge resorption after tooth extraction. Maxillary and mandibular premolars were extracted from 3 Beagle dogs with preservation of alveolar bone. Thereafter, distal sockets were filled with an injectable bone substitute (IBS), obtained by combining a polymer solution and granules of a biphasic calcium phosphate (BCP) ceramic. As a control, the mesial sockets were left unfilled. After a 3 months healing period, specimens were removed and prepared for histomorphometric evaluation with image analysis. Histomorphometric study allowed to measure the mean and the maximal heights of alveolar crest modifications. Results always showed an alveolar bone resorption in unfilled sockets. Resorption in filled maxillary sites was significantly lower than in control sites. Interestingly, an alveolar ridge augmentation was measured in mandibular filled sockets including 30% of newly-formed bone. It was concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate can significantly increase alveolar ridge preservation after tooth extraction.

Remodeling of alveolar bone crest after molar intrusion with skeletal anchorage system in dogs.

PubMed

Kanzaki, Reiko; Daimaruya, Takayoshi; Takahashi, Ichiro; Mitani, Hideo; Sugawara, Junji

2007-03-01

The aim of this study was to clarify the influence of supra-alveolar fibers on alveolar bone crest remodeling when several teeth are intruded simultaneously. The skeletal anchorage system was used to bilaterally intrude the second and third premolars of 10 beagles; supracrestal fiberotomies were performed on 1 side only. The amount of intrusion was greater and the amount of alveolar bone resorption was smaller in the fiberotomy group compared with the nonfiberotomy group. The health status (pocket depth <3 mm) of the dentogingival unit was maintained in the nonfiberotomy group during the experimental period. In the fiberotomy group, the number of osteoclasts on the marginal alveolar crest was less than in the nonfiberotomy group. The dense fiber bundles connecting the second and third premolars and the gingival attachments were maintained in the nonfiberotomy group. Pressure from the supra-alveolar fibers generated by segmental molar intrusion with the skeletal anchorage system induced alveolar bone crest resorption and remodeling, and, as a result, it prevented deepening of the gingival pocket. Periodontal status was good during tooth intrusion.

Micro-imaging of the Mouse Lung via MRI

NASA Astrophysics Data System (ADS)

Wang, Wei

Quantitative measurement of lung microstructure is of great significance in assessment of pulmonary disease, particularly in the earliest stages. Conventional stereological assessment of ex-vivo fixed tissue specimens under the microscope has a long and successful tradition and is regarded as a gold standard, but the invasive nature limits its applications and the practicality of use in longitudinal studies. The technique for diffusion MRI-based 3He lung morphometry was previously developed and validated for human lungs, and was recently extended to ex-vivo mouse lungs. The technique yields accurate, quantitative information about the microstructure and geometry of acinar airways. In this dissertation, the 3He lung morphometry technique is for the first time successfully implemented for in-vivo studies of mice. It can generate spatially-resolved maps of parameters that reveal the microstructure of mouse lung. Results in healthy mice indicate excellent agreement between in-vivo morphometry via 3He MRI and microscopic morphometry after sacrifice. The implementation and validation of 3He morphometry in healthy mice open up new avenues for application of the technique as a precise, noninvasive, in-vivo biomarker of changes in lung microstructure, within various mouse models of lung disease. We have applied 3He morphometry to the Sendai mouse model of lung disease. Specifically, the Sendai-virus model of chronic obstructive lung disease has demonstrated an innate immune response in mouse airways that exhibits similarities to the chronic airway inflammation in human COPD and asthma, but the effect on distal lung parenchyma had not been investigated. We imaged the time course and regional distribution of mouse lung microstructural changes in vivo after Sendai virus (SeV) infection with 1H and 3He diffusion MRI. 1H MR images detected the SeV-induced pulmonary inflammation in vivo and 3He lung morphometry showed modest increase in alveolar duct radius distal to airway inflammation, particularly in the lung periphery, indicating airspace enlargement after virus infection. Another important application of the imaging technique is the study of lung regeneration in a pneumonectomy (PNX) model. Partial resection of the lung by unilateral PNX is a robust model of compensatory lung growth. It is typically studied by postmortem morphometry in which longitudinal assessment in the same animal cannot be achieved. Here we successfully assess the microstructural changes and quantify the compensatory lung growth in vivo in the PNX mouse model via 1H and hyperpolarized 3He diffusion MRI. Our results show complete restoration in lung volume and total alveolar number with enlargement of alveolar size, which is consistent with prior histological studies conducted in different animals at various time points. This dissertation demonstrates that 3He lung morphometry has good sensitivity in quantifying small microstructural changes in the mouse lung and can be applied to a variety of mouse pulmonary models. Particularly, it has great potential to become a valuable tool in understanding the time course and the mechanism of lung growth in individual animals and may provide insight into post-natal lung growth and lung regeneration.

Alcohol potentiates post burn remote organ damage through shifts in fluid compartments mediated by bradykinin

PubMed Central

Chen, Michael M.; O’Halloran, Eileen B.; Ippolito, Jill A.; Choudhry, Mashkoor A.; Kovacs, Elizabeth J.

2014-01-01

Of the 450,000 burn patients each year, 50% have a positive blood alcohol content and this predisposes them to worsened clinical outcomes. Despite high prevalence and established consequences, the mechanisms responsible for alcohol-mediated complications of post burn remote organ damage are currently unknown. To this end, mice received a single dose of alcohol (1.12 g/kg) or water by oral gavage and were subjected to a 15% total body surface area burn. Animals with a burn alone lost ~5% of their body weight in 24 hours whereas intoxicated and burned mice lost only 1% body weight (p<0.05) despite a 17% increase in hematocrit (p<0.05) and a 57% increase in serum creatinine (p<0.05) over burn injury alone. This retention of water weight despite increased dehydration suggests that intoxication at the time of a burn causes a shift in fluid compartments that may exacerbate end organ ischemia and damage as evidenced by a 3-fold increase in intestinal bacterial translocation (p<0.05), a 30% increase (p<0.05) in liver weight to body weight ratio, and an increase in alveolar wall thickness over a burn alone. Furthermore, administration of the bradykinin antagonist HOE140 30 minutes after intoxication and burn restored fluid balance and alleviated end organ damage. These findings suggest that alcohol potentiates post burn remote organ damage through shifts in fluid compartments mediated by bradykinin. PMID:25243425

Alcohol potentiates postburn remote organ damage through shifts in fluid compartments mediated by bradykinin.

PubMed

Chen, Michael M; O'Halloran, Eileen B; Ippolito, Jill A; Choudhry, Mashkoor A; Kovacs, Elizabeth J

2015-01-01

Of the 450,000 burn patients each year, 50% have a positive blood alcohol content, and this predisposes them to worsened clinical outcomes. Despite high prevalence and established consequences, the mechanisms responsible for alcohol-mediated complications of postburn remote organ damage are currently unknown. To this end, mice received a single dose of alcohol (1.12 g/kg) or water by oral gavage and were subjected to a 15% total body surface area burn. Animals with a burn alone lost ∼5% of their body weight in 24 h, whereas intoxicated and burned mice lost only 1% body weight (P < 0.05) despite a 17% increase in hematocrit (P < 0.05) and a 57% increase in serum creatinine (P < 0.05) over burn injury alone. This retention of water weight despite increased dehydration suggests that intoxication at the time of a burn causes a shift in fluid compartments that may exacerbate end-organ ischemia and damage as evidenced by a 3-fold increase in intestinal bacterial translocation (P < 0.05), a 30% increase (P < 0.05) in liver weight-to-body weight ratio, and an increase in alveolar wall thickness over a burn alone. Furthermore, administration of the bradykinin antagonist HOE140 30 min after intoxication and burn restored fluid balance and alleviated end-organ damage. These findings suggest that alcohol potentiates postburn remote organ damage through shifts in fluid compartments mediated by bradykinin.

Molecular Basis of Asbestos-Induced Lung Disease

PubMed Central

Liu, Gang; Cheresh, Paul; Kamp, David W.

2013-01-01

Asbestos causes asbestosis and malignancies by molecular mechanisms that are not fully understood. The modes of action underlying asbestosis, lung cancer, and mesothelioma appear to differ depending on the fiber type, lung clearance, and genetics. After reviewing the key pathologic changes following asbestos exposure, we examine recently identified pathogenic pathways, with a focus on oxidative stress. Alveolar epithelial cell apoptosis, which is an important early event in asbestosis, is mediated by mitochondria- and p53-regulated death pathways and may be modulated by the endoplasmic reticulum. We review mitochondrial DNA (mtDNA)-damage and -repair mechanisms, focusing on 8-oxoguanine DNA glycosylase, as well as cross talk between reactive oxygen species production, mtDNA damage, p53, OGG1, and mitochondrial aconitase. These new insights into the molecular basis of asbestos-induced lung diseases may foster the development of novel therapeutic targets for managing degenerative diseases (e.g., asbestosis and idiopathic pulmonary fibrosis), tumors, and aging, for which effective management is lacking. PMID:23347351

Intrusive luxation in primary teeth – Review of literature and report of a case

PubMed Central

Gupta, Megha

2011-01-01

Luxation injuries such as intrusion are commonly seen in the primary dentition. Intrusion drives the tooth deeper into the alveolar socket, which results in damage to the pulp and peridontium. Difficulty in gaining compliance from a very young child and the risk of damaging the permanent tooth germ makes the management of these injuries challenging. Careful clinical and radiographic examination along with regular follow-up is essential. A case of intrusive luxation to the maxillary central incisor in a 3-year-old patient is reported. Spontaneous reeruption was noted 4 months after injury, but the tooth had developed an abscess and external root resorption. Hence, extraction of the tooth was done and an anterior esthetic fixed space maintainer was placed. Traumatic injuries to the primary dentition should not be ignored by the parents or by the dentist. The paper also includes a literature review of intrusive luxation in the primary dentition. PMID:23960512

Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres.

PubMed

Povedano, Juan Manuel; Martinez, Paula; Serrano, Rosa; Tejera, Águeda; Gómez-López, Gonzalo; Bobadilla, Maria; Flores, Juana Maria; Bosch, Fátima; Blasco, Maria A

2018-01-30

Pulmonary fibrosis is a fatal lung disease characterized by fibrotic foci and inflammatory infiltrates. Short telomeres can impair tissue regeneration and are found both in hereditary and sporadic cases. We show here that telomerase expression using AAV9 vectors shows therapeutic effects in a mouse model of pulmonary fibrosis owing to a low-dose bleomycin insult and short telomeres. AAV9 preferentially targets regenerative alveolar type II cells (ATII). AAV9- Tert -treated mice show improved lung function and lower inflammation and fibrosis at 1-3 weeks after viral treatment, and improvement or disappearance of the fibrosis at 8 weeks after treatment. AAV9- Tert treatment leads to longer telomeres and increased proliferation of ATII cells, as well as lower DNA damage, apoptosis, and senescence. Transcriptome analysis of ATII cells confirms downregulation of fibrosis and inflammation pathways. We provide a proof-of-principle that telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres. © 2018, Povedano et al.

Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres

PubMed Central

Serrano, Rosa; Tejera, Águeda; Gómez-López, Gonzalo; Bobadilla, Maria; Flores, Juana Maria; Bosch, Fátima

2018-01-01

Pulmonary fibrosis is a fatal lung disease characterized by fibrotic foci and inflammatory infiltrates. Short telomeres can impair tissue regeneration and are found both in hereditary and sporadic cases. We show here that telomerase expression using AAV9 vectors shows therapeutic effects in a mouse model of pulmonary fibrosis owing to a low-dose bleomycin insult and short telomeres. AAV9 preferentially targets regenerative alveolar type II cells (ATII). AAV9-Tert-treated mice show improved lung function and lower inflammation and fibrosis at 1–3 weeks after viral treatment, and improvement or disappearance of the fibrosis at 8 weeks after treatment. AAV9-Tert treatment leads to longer telomeres and increased proliferation of ATII cells, as well as lower DNA damage, apoptosis, and senescence. Transcriptome analysis of ATII cells confirms downregulation of fibrosis and inflammation pathways. We provide a proof-of-principle that telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres. PMID:29378675

Cytocompatibility and cellular internalization mechanisms of SiC/SiO2 nanowires.

PubMed

Cacchioli, A; Ravanetti, F; Alinovi, R; Pinelli, S; Rossi, F; Negri, M; Bedogni, E; Campanini, M; Galetti, M; Goldoni, M; Lagonegro, P; Alfieri, R; Bigi, F; Salviati, G

2014-08-13

First evidence of in vitro cytocompatibility of SiC/SiO2 core-shell nanowires is reported. Different internalization mechanisms by adenocarcinomic alveolar basal epithelial cells, monocytic cell line derived from an acute monocytic leukemia, breast cancer cells, and normal human dermal fibroblasts are shown. The internalization occurs mainly for macropinocytosis and sporadically by direct penetration in all cell models considered, whereas it occurred for phagocytosis only in monocytic leukemia cells. The cytocompatibility of the nanowires is proved by the analysis of cell proliferation, cell cycle progression, and oxidative stress on the cells treated with NWs as compared to controls. Reactive oxygen species generation was detected as an early event that then quickly run out with a rapid decrease only in adenocarcinomic alveolar basal epithelial and human dermal fibroblasts cells. In all the cell lines, the intracellular presence of NWs induce the same molecular events but to a different extent: peroxidation of membrane lipids and oxidation of proteins. The NWs do not elicit either midterm (72 h) or long-term (10 days) cytotoxic activity leading to irreversible cellular damages or death. Our results are important in view of a possible use of SiC/SiO2 core-shell structures acting as biomolecule-delivery vectors or intracellular electrodes.

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

PubMed

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 <3 patients. Of 366 retrieved papers, 27 were suitable for final analysis. Treatment type for injured IANs/LNs depended on 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 <10 mm; larger gaps required 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.

A novel minimal invasive mouse model of extracorporeal circulation.

PubMed

Luo, Shuhua; Tang, Menglin; Du, Lei; Gong, Lina; Xu, Jin; Chen, Youwen; Wang, Yabo; Lin, Ke; An, Qi

2015-01-01

Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury.

A Novel Minimal Invasive Mouse Model of Extracorporeal Circulation

PubMed Central

Luo, Shuhua; Tang, Menglin; Du, Lei; Gong, Lina; Xu, Jin; Chen, Youwen; Wang, Yabo; Lin, Ke; An, Qi

2015-01-01

Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury. PMID:25705092

Silicosis and coal workers' pneumoconiosis.

PubMed Central

Castranova, V; Vallyathan, V

2000-01-01

Exposure to coal mine dust and/or crystalline silica results in pneumoconiosis with initiation and progression of pulmonary fibrosis. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10931786

Protective effects of chebulic acid on alveolar epithelial damage induced by urban particulate matter.

PubMed

Lee, Kyung-Won; Nam, Mi-Hyun; Lee, Hee-Ra; Hong, Chung-Oui; Lee, Kwang-Won

2017-07-19

Chebulic acid (CA) isolated from T. chebula, which has been reported for treating asthma, as a potent anti-oxidant resources. Exposure to ambient urban particulate matter (UPM) considered as a risk for cardiopulmonary vascular dysfunction. To investigate the protective effect of CA against UPM-mediated collapse of the pulmonary alveolar epithelial (PAE) cell (NCI-H441), barrier integrity parameters, and their elements were evaluated in PAE. CA was acquired from the laboratory previous reports. UPM was obtained from the National Institutes of Standards and Technology, and these were collected in St. Louis, MO, over a 24-month period and used as a standard reference. To confirm the protection of PAE barrier integrity, paracellular permeability and the junctional molecules were estimated with determination of transepithelial electrical resistance, Western Blotting, RT-PCR, and fluorescent staining. UPM aggravated the generation of reactive oxygen species (ROS) in PAE and also decreased mRNA and protein levels of junction molecules and barrier integrity in NCI-H441. However, CA repressed the ROS in PAE, also improved barrier integrity by protecting the junctional parameters in NCI-H411. These data showed that CA resulted in decreased UPM-induced ROS formation, and the protected the integrity of the tight junctions against UPM exposure to PAE barrier.

Hsp90/Sec22b promotes unconventional secretion of mature-IL-1β through an autophagosomal carrier in porcine alveolar macrophages during Mycoplasma hyopneumoniae infection.

PubMed

Zhang, Zhenzhen; Wei, Yanna; Liu, Beibei; Wu, Yuzi; Wang, Haiyan; Xie, Xing; Feng, Zhixin; Shao, Guoqing; Xiong, Qiyan

2018-06-20

Interleukin-1β (IL-1β) is a critical inflammatory regulator in response to Mycoplasma hyopneumoniae infection. However, the mechanism involved in the secretion of IL-1β during Mycoplasma hyopneumoniae infection is unclear. In this study, we demonstrated that Mycoplasma hyopneumoniae infection increased the secretion of mature-IL-1β (m-IL-1β), but not pro-IL-1β, in porcine alveolar macrophages. Moreover, Mycoplasma hyopneumoniae infection promoted the generation of autophagosomes, which attributed to the unconventional secretion of m-IL-1β. Further results revealed that Hsp90 was required for the entry of m-IL-1β into autophagosomes during Mycoplasma hyopneumoniae infection. The fusion of m-IL-1β-containing autophagosome and plasma membranes was regulated by Sec22b and independent of lysosomal dysfunction. In conclusion, we provide evidence that Hsp90/Sec22b promotes the unconventional secretion of IL-1β through an autophagosomal carrier during Mycoplasma hyopneumoniae infection. The elucidation of the molecular and cellular machinery in Mycoplasma hyopneumoniae infected mammalian cells in this study suggests avenues for further study and applications and paves the way for novel therapeutic strategies to prevent tissue damage in mycoplasma-associated diseases. Copyright © 2018. Published by Elsevier Ltd.

relationship between diffusion tensor imaging findings and cognitive outcomes following adult traumatic brain injury: A meta-analysis.

PubMed

Wallace, E J; Mathias, J L; Ward, L

2018-05-24

Cognitive impairments are common following a traumatic brain injury (TBI) and frequently result from white matter (WM) damage. This damage can be quantified using diffusion tensor imaging (DTI), which measures the directionality (fractional anisotropy: FA) and amount (mean diffusivity/apparent diffusion coefficient: MD/ADC) of water diffusion in WM, with high FA and low MD/ADC thought to indicate greater WM integrity. However, the relationship between DTI and cognitive outcomes is currently unclear. The data from 20 studies that examined the relationship between WM integrity (measured using DTI) and cognition (categorised into seven domains) following mild-severe adult TBI were meta-analysed. Overall, high FA and low MD/ADC in most brain regions was associated with better cognitive performance, with memory and attention most strongly related to DTI findings. Specifically, memory and/or attention were very strongly related to DTI findings in the corpus callosum, fornix, internal capsule, arcuate and uncinate fasciculi. However, most findings were based on single studies and therefore await replication. Larger-scale, longitudinal studies are now needed to determine the predictive utility of DTI. Copyright © 2018. Published by Elsevier Ltd.

Bioheat model evaluations of laser effects on tissues: role of water evaporation and diffusion

NASA Astrophysics Data System (ADS)

Nagulapally, Deepthi; Joshi, Ravi P.; Thomas, Robert J.

2011-03-01

A two-dimensional, time-dependent bioheat model is applied to evaluate changes in temperature and water content in tissues subjected to laser irradiation. Our approach takes account of liquid-to-vapor phase changes and a simple diffusive flow of water within the biotissue. An energy balance equation considers blood perfusion, metabolic heat generation, laser absorption, and water evaporation. The model also accounts for the water dependence of tissue properties (both thermal and optical), and variations in blood perfusion rates based on local tissue injury. Our calculations show that water diffusion would reduce the local temperature increases and hot spots in comparison to simple models that ignore the role of water in the overall thermal and mass transport. Also, the reduced suppression of perfusion rates due to tissue heating and damage with water diffusion affect the necrotic depth. Two-dimensional results for the dynamic temperature, water content, and damage distributions will be presented for skin simulations. It is argued that reduction in temperature gradients due to water diffusion would mitigate local refractive index variations, and hence influence the phenomenon of thermal lensing. Finally, simple quantitative evaluations of pressure increases within the tissue due to laser absorption are presented.

Diffusion tensor imaging, white matter lesions, the corpus callosum, and gait in the elderly

USDA-ARS?s Scientific Manuscript database

Gait impairment is common in the elderly, especially affected by stroke and white matter hyper intensities found in conventional brain magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) is more sensitive to white matter damage than conventional MRI. The relationship between DTI measure...

Ion implantation of indium gallium arsenide

NASA Astrophysics Data System (ADS)

Almonte, Marlene Isabel

The ternary compound In0.53Ga0.47As, lattice-matched to Inp, is a semiconductor alloy of technological importance for numerous electronic and optoelectronic device applications. One of these applications includes photodiodes to be developed for the 1.3--1.55 mum wavelength range where silica fibers have their lowest optical loss. With a rapid increase in its use there is an essential need to understand the effects of ion implantation of this alloy semiconductor for implant isolation purposes in which highly resistive layers are required. Due to the small band gap (0.75 eV at 300K) of In0.53Ga0.47As, the estimated maximum resistivity is of the order of 1000 O-cm. Implant isolation can be achieved by the implantation of either inert noble gas ions or electrically active ions. Ion bombardment with inert species introduces defects which trap charge carriers. In the case of implant isolation by electrically active ions, the implanted impurities form an electronic level located close to the middle of the bandgap. Studies of the effects of implantation in In0.53Ga0.47 As due to damage by implantation of Ne+ ions and to compensation by implantation of Fe+ ions are reported in this thesis. The former only involves lattice damage related effects while the latter leads to damage and dopant induced compensation. From the Ne+ implantation results it appears that the damage related energy levels in In0.53 Ga0.47M produced by ion bombardment of chemically inactive species, are not sufficiently deep to lead to effective isolation. A higher resistivity of the order of 770 O-cm is achieved with Fe+ implantation, indicating that Fe introduces an energy level deep in the bandgap. The changes in the electrical properties of the layers are correlated to the lattice damage (damage induced effects) and/or the diffusion of the compensating dopants (dopant induced compensation). Structural characterization of the layers is performed with channeling Rutherford Backscattering Spectrometry (RBS). The distribution of the compensating dopants in the as-implanted and annealed layers is examined by Secondary Ion Mass Spectrometry (SIMS). SIMS analysis shows Fe out-diffusion which results in the loss of the semi-insulating electrical characteristics. To further our understanding of Fe diffusion in In0.53Ga0.47As, the diffusion coefficient of Fe is measured for the first time. The diffusivity of Fe was measured to be 4 x 10-13 cm2 s-1 at 550°C. The thermal stability of these damage and compensation induced effects producing implant isolation is discussed in detail.

High CO2 levels impair alveolar epithelial function independently of pH.

PubMed

Briva, Arturo; Vadász, István; Lecuona, Emilia; Welch, Lynn C; Chen, Jiwang; Dada, Laura A; Trejo, Humberto E; Dumasius, Vidas; Azzam, Zaher S; Myrianthefs, Pavlos M; Batlle, Daniel; Gruenbaum, Yosef; Sznajder, Jacob I

2007-11-28

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

Hypoxia-inducible factors promote alveolar development and regeneration.

PubMed

Vadivel, Arul; Alphonse, Rajesh S; Etches, Nicholas; van Haaften, Timothy; Collins, Jennifer J P; O'Reilly, Megan; Eaton, Farah; Thébaud, Bernard

2014-01-01

Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in disease states is critical for developing effective therapies for lung regeneration. Recent evidence suggests that lung angiogenesis promotes lung development and repair. Vascular endothelial growth factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2-induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin 1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple O2-sensitive genes, including those encoding for angiogenic growth factors, but their role during postnatal lung growth is incompletely understood. By inducing the expression of a range of angiogenic factors in a coordinated fashion, HIF may orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized that HIF inhibition impairs alveolarization and that HIF activation regenerates irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal dominant-negative adenovirus (dnHIF-1α)-mediated gene transfer or chetomin decreased lung HIF-1α, HIF-2α, and VEGF expression and led to air space enlargement and arrested lung vascular growth. In experimental O2-induced arrested alveolar growth in newborn rats, the characteristic features of air space enlargement and loss of lung capillaries were associated with decreased lung HIF-1α and HIF-2α expression. Intratracheal administration of Ad.HIF-1α restored HIF-1α, endothelial nitric oxide synthase, VEGF, VEGFR2, and Tie2 expression and preserved and rescued alveolar growth and lung capillary formation in this model. HIFs promote normal alveolar development and may be useful targets for alveolar regeneration.

White matter damage in primary progressive aphasias: a diffusion tensor tractography study

PubMed Central

Galantucci, Sebastiano; Tartaglia, Maria Carmela; Wilson, Stephen M.; Henry, Maya L.; Filippi, Massimo; Agosta, Federica; Dronkers, Nina F.; Henry, Roland G.; Ogar, Jennifer M.; Miller, Bruce L.

2011-01-01

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts’ mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia. PMID:21666264

Selective white matter pathology induces a specific impairment in spatial working memory.

PubMed

Coltman, Robin; Spain, Aisling; Tsenkina, Yanina; Fowler, Jill H; Smith, Jessica; Scullion, Gillian; Allerhand, Mike; Scott, Fiona; Kalaria, Rajesh N; Ihara, Masafumi; Daumas, Stephanie; Deary, Ian J; Wood, Emma; McCulloch, James; Horsburgh, Karen

2011-12-01

The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing parallel pathology and behavior in the same mice. Copyright © 2011. Published by Elsevier Inc.

ALVEOLAR BREATH SAMPLING AND ANALYSIS IN HUMAN EXPOSURE ASSESSMENT STUDIES

EPA Science Inventory

Alveolar breath sampling and analysis can be extremely useful in exposure assessment studies involving volatile organic compounds (VOCs). Over recent years scientists from the EPA's National Exposure Research Laboratory have developed and refined an alveolar breath collection ...

Effects of inspiratory pause on CO2 elimination and arterial PCO2 in acute lung injury

PubMed Central

Devaquet, Jérôme; Jonson, Björn; Niklason, Lisbet; Si Larbi, Anne-Gaëlle; Uttman, Leif; Aboab, Jérôme; Brochard, Laurent

2008-01-01

A high respiratory rate associated with the use of small tidal volumes, recommended for acute lung injury (ALI), shortens time for gas diffusion in the alveoli. This may decrease CO2 elimination. We hypothesized that a post-inspiratory pause could enhance CO2 elimination and reduce PaCO2 by reducing dead space in ALI. In 15 mechanically ventilated patients with ALI and hypercapnia, a 20% post-inspiratory pause (Tp20) was applied during a period of 30 min between two ventilation periods without post-inspiratory pause (Tp0). Other parameters were kept unchanged. The single breath test for CO2 was recorded every 5 minutes to measure tidal CO2 elimination (VtCO2), airway dead space (VDaw) and slope of the alveolar plateau. PaO2, PaCO2, physiological and alveolar dead space (VDphys, VDalv) were determined at the end of each 30 minute period. The post-inspiratory pause, 0.7±0.2 s, induced on average less than 0.5 cm H2O of intrinsic PEEP. During Tp20, VtCO2 increased immediately by 28±10% (14±5 ml per breath compared to 11±4 for Tp0) and then decreased without reaching the initial value within 30 minutes. The addition of a post-inspiratory pause decreased significantly VDaw by 14% and VDphys by 11% with no change in VDalv. During Tp20, the slope of alveolar plateau initially fell to 65±10 % of baseline value and continued to decrease. Tp20 induced a 10±3% decrease in PaCO2 at 30 minutes (from 55±10 to 49±9 mmHg, p<0.001) with no significant variation in PaO2. Post-inspiratory pause has a significant influence on CO2 elimination when small tidal volumes are used during mechanical ventilation for ALI. PMID:18801962

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Evan A.; Birch, M. Eileen; Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu

Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wallmore » CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector function of AMs. • MyD88 may be a potential target for intervention in CNT lung exposures.« less

Lung Toxicity of Condensed Aerosol from E-CIG Liquids: Influence of the Flavor and the In Vitro Model Used.

PubMed

Bengalli, Rossella; Ferri, Emanuele; Labra, Massimo; Mantecca, Paride

2017-10-20

The diffusion of e-cigarette (e-CIG) opens a great scientific and regulatory debate about its safety. The huge number of commercialized devices, e-liquids with almost infinite chemical formulations and the growing market demand for a rapid and efficient toxicity screen system that is able to test all of these references and related aerosols. A consensus on the best protocols for the e-CIG safety assessment is still far to be achieved, since the huge number of variables characterizing these products (e.g., flavoring type and concentration, nicotine concentration, type of the device, including the battery and the atomizer). This suggests that more experimental evidences are needed to support the regulatory frameworks. The present study aims to contribute in this field by testing the effects of condensed aerosols (CAs) from three main e-liquid categories (tobacco, mint, and cinnamon as food-related flavor), with (18 mg/mL) or without nicotine. Two in vitro models, represented by a monoculture of human epithelial alveolar cells and a three-dimensional (3D) co-culture of alveolar and lung microvascular endothelial cells were used. Cell viability, pro-inflammatory cytokines release and alveolar-blood barrier (ABB) integrity were investigated as inhalation toxicity endpoints. Results showed that nicotine itself had almost no influence on the modulation of the toxicity response, while flavor composition did have. The cell viability was significantly decreased in monoculture and ABB after exposure to the mints and cinnamon CAs. The barrier integrity was significantly affected in the ABB after exposure to cytotoxic CAs. With the exception of the significant IL-8 release in the monoculture after Cinnamon exposure, no increase of inflammatory cytokines (IL-8 and MCP-1) release was observed. These findings point out that multiple assays with different in vitro models are able to discriminate the acute inhalation toxicity of CAs from liquids with different flavors, providing the companies and regulatory bodies with useful tools for the preliminary screening of marketable products.

Contour changes in human alveolar bone following tooth extraction of the maxillary central incisor.

PubMed

Li, Bei; Wang, Yao

2014-12-01

The purpose of this study was to apply cone-beam computed tomography (CBCT) to observe contour changes in human alveolar bone after tooth extraction of the maxillary central incisor and to provide original morphological evidence for aesthetic implant treatment in the maxillary anterior area. Forty patients were recruited into the study. Each patient had two CBCT scans (CBCT I and CBCT II), one taken before and one taken three months after tooth extraction of maxillary central incisor (test tooth T). A fixed anatomic reference point was used to orient the starting axial slice of the two scans. On three CBCT I axial slices, which represented the deep, middle, and shallow layers of the socket, labial and palatal alveolar bone widths of T were measured. The number of sagittal slices from the start point to the pulp centre of T was recorded. On three CBCT II axial slices, the pulp centres of extracted T were oriented according to the number of moved sagittal slices recorded in CBCT I. Labial and palatal alveolar bone widths at the oriented sites were measured. On the CBCT I axial slice which represented the middle layer of the socket, sagittal slices were reconstructed. Relevant distances of T on the sagittal slice were measured, as were the alveolar bone width and tooth length of the opposite central incisor. On the CBCT II axial slice, which represented the middle layer of the socket, relevant distances recorded in CBCT I were transferred on the sagittal slice. The height reduction of alveolar bone on labial and palatal sides was measured, as were the alveolar bone width and tooth length of the opposite central incisor at the oriented site. Intraobserver reliability assessed by intraclass correlation coefficients (ICCs) was high. Paired sample t-tests were performed. The alveolar bone width and tooth length of the opposite central incisor showed no statistical differences (P<0.05). The labial alveolar bone widths of T at the deep, middle, and shallow layers all showed statistical differences. However, no palatal alveolar bone widths showed any statistical differences. The width reduction of alveolar bone was 1.2, 1.6, and 2.7 mm at the deep, middle, and shallow layers, respectively. The height reduction of alveolar bone on labial and palatal sides of T both showed statistical differences, which was 1.9 and 1.1 mm, respectively.

Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: inner versus outer retina, parafovea versus peripheral fovea.

PubMed

de Sisternes, Luis; Hu, Julia; Rubin, Daniel L; Marmor, Michael F

2015-05-01

To evaluate the relative involvement of inner and outer retina in hydroxychloroquine (HCQ) retinopathy while on the drug, and after drug cessation, using data from spectral-domain optical coherence tomography (SD-OCT). A total of 102 SD-OCT scans were obtained from 11 patients (classified as having early, moderate, or severe stages of toxicity) over a period of 4 years after cessation of HCQ. The inner and outer retina boundaries were identified automatically to measure thickness and characterize progression topographically. The segmentation of retinal layers was verified in SD-OCT cross-sections for all eyes and scans included in this study (a total of 102 scans). Topographic analysis showed that inner retina was not involved in HCQ toxicity to any meaningful degree, either between stages of retinopathy or after the drug is stopped. The characteristic bull's eye pattern of outer macula thinning appears when comparing moderate retinopathy (before any RPE damage) to the early stage. Later damage, as toxicity evolved to a severe stage, was diffuse across most of the macula. If the drug was stopped at an early or moderate stage, progression was limited to the first year and occurred diffusely without parafoveal localization. Hydroxychloroquine retinopathy primarily involves outer retina (photoreceptors). Outer retinal thinning while using HCQ initially involves the parafovea, but becomes diffuse across the macula as damage progresses or after drug cessation. When HCQ is stopped at an early or moderate stage (before RPE damage), progression seems to be limited to the first year.

Extreme Tetralogy of Fallot With Polycythemia in a Ferret (Mustela putorius furo).

PubMed

Dias, Sara; Planellas, Marta; Canturri, Albert; Martorell, Jaume

2017-06-01

A 5-month-old, intact male ferret (Mustela putorius furo) was presented with apathy, tachypnea and exercise intolerance. On initial physical examination, tachypnea and cyanosis were the two primary clinical signs detected. The complete blood count also revealed a severe polycythemia, with lymphopenia, neutrophilia and eosinophilia. Further diagnostic imaging tests were performed. The thoracic radiographs revealed cardiomegaly and a diffuse alveolar pulmonary pattern. Consequently, an echocardiography was performed and showed an interventricular septal defect, pulmonic artery occlusion, overriding of the aorta and right ventricle hypertrophy. All abnormalities were compatible with a tetralogy of Fallot (TOF). As a treatment plan, a phlebotomy was performed and the ferret was posteriorly maintained with oxygen and fluid therapy. The following day, the hematocrit decreased 11% and the respiratory distress improved. Four days later, the ferret got clinically worse and was euthanized. A necropsy was performed and confirmed the presence of an extreme TOF with a diffused interstitial pneumonia secondary to Pneumocystis carinii. To the author's knowledge, this is the first report of an extreme tetralogy of Fallot with polycythemia in a ferret. Copyright © 2017 Elsevier Inc. All rights reserved.

On the contribution of height to predict lung volumes, capacities and diffusion in healthy school children of 10-17 years.

PubMed

Gupta, C K; Mishra, G; Mehta, S C; Prasad, J

1993-01-01

Lung volumes, capacities, diffusion and alveolar volumes with physical characteristics (age, height and weight) were recorded for 186 healthy school children (96 boys and 90 girls) of 10-17 years age group. The objective was to study the relative importance of physical characteristics as regressor variables in regression models to estimate lung functions. We observed that height is best correlated with all the lung functions. Inclusion of all physical characteristics in the models have little gain compared to the ones having just height as regressor variable. We also find that exponential models were not only statistically valid but fared better compared to the linear ones. We conclude that lung functions covary with height and other physical characteristics but do not depend upon them. The rate of increase in the functions depend upon initial lung functions. Further, we propose models and provide ready reckoners to give estimates of lung functions with 95 per cent confidence limits based on heights from 125 to 170 cm for the age group of 10 to 17 years.

The effect of varying alveolar carbon dioxide levels on free recall.

PubMed

Marangoni, A H; Hurford, D P

1990-05-01

A recent study suggested that students who have increased minute ventilation receive poorer grades. The present study was interested in determining the role alveolar carbon dioxide (CO2) levels play with cognitive abilities. A free recall task was used to examine list learning under two conditions of alveolar CO2 level: normal and decreased. The results suggested that decreased alveolar CO2 level affect the participant's ability to rehearse and recall information. It was concluded that conditions that reduce alveolar CO2 levels, such as hyperventilation resulting from stress, nervousness, or inappropriate breathing habits, can lead to poorer learning. If these conditions produce a habitual breathing pattern, the academic performance of the individual may suffer.

Inferior alveolar nerve block: Alternative technique

PubMed Central

Thangavelu, K.; Kannan, R.; Kumar, N. Senthil

2012-01-01

Background: Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. Aim and Objective: The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. Materials and Methods: This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. Conclusion: This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages. PMID:25885503

Inferior alveolar nerve block: Alternative technique.

PubMed

Thangavelu, K; Kannan, R; Kumar, N Senthil

2012-01-01

Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages.

Endothelial-monocyte activating polypeptide II disrupts alveolar epithelial type II to type I cell transdifferentiation

PubMed Central

2012-01-01

Background Distal alveolar morphogenesis is marked by differentiation of alveolar type (AT)-II to AT-I cells that give rise to the primary site of gas exchange, the alveolar/vascular interface. Endothelial-Monocyte Activating Polypeptide (EMAP) II, an endogenous protein with anti-angiogenic properties, profoundly disrupts distal lung neovascularization and alveolar formation during lung morphogenesis, and is robustly expressed in the dysplastic alveolar regions of infants with Bronchopulmonary dysplasia. Determination as to whether EMAP II has a direct or indirect affect on ATII→ATI trans-differentiation has not been explored. Method In a controlled nonvascular environment, an in vitro model of ATII→ATI cell trans-differentiation was utilized to demonstrate the contribution that one vascular mediator has on distal epithelial cell differentiation. Results Here, we show that EMAP II significantly blocked ATII→ATI cell transdifferentiation by increasing cellular apoptosis and inhibiting expression of ATI markers. Moreover, EMAP II-treated ATII cells displayed myofibroblast characteristics, including elevated cellular proliferation, increased actin cytoskeleton stress fibers and Rho-GTPase activity, and increased nuclear:cytoplasmic volume. However, EMAP II-treated cells did not express the myofibroblast markers desmin or αSMA. Conclusion Our findings demonstrate that EMAP II interferes with ATII → ATI transdifferentiation resulting in a proliferating non-myofibroblast cell. These data identify the transdifferentiating alveolar cell as a possible target for EMAP II's induction of alveolar dysplasia. PMID:22214516

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

PubMed

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.

Pulmonary hemorrhage in acute heroin overdose: a report of two cases.

PubMed

Riccardello, Gerald J; Maldjian, Pierre D

2017-12-01

Diffuse alveolar hemorrhage (DAH) is a clinical syndrome characterized by pulmonary hemorrhage, respiratory failure, and high early mortality rates. DAH typically appears on chest radiographs as bilateral parenchymal consolidations. To our knowledge, pulmonary hemorrhage associated with heroin overdose has not been reported. We report the clinical and radiographic findings in two cases of acute DAH following heroin overdose. We speculate that an adulterating agent may be the underlying etiology in these cases. While pulmonary edema as a consequence of heroin overdose is well-documented and usually first suspected when consolidations are present on a chest radiograph in a patient with a history of recent heroin use, we believe that DAH should also be considered in the proper clinical context.

Assessing the Impact of Mechanical Damage on Full-Thickness Porcine and Human Skin Using an In Vitro Approach

PubMed Central

Builles, Nicolas; Frouin, Éric; Scott, Dan; Ramos, Jeanne; Marti-Mestres, Gilberte

2015-01-01

For most xenobiotics, the rates of percutaneous absorption are limited by diffusion through the horny layer of skin. However, percutaneous absorption of chemicals may seriously increase when the skin is damaged. The aim of this work was to develop an in vitro representative model of mechanically damaged skins. The epidermal barrier was examined following exposure to a razor, a rotating brush, and a microneedle system in comparison to tape-stripping which acted as a reference. Excised full-thickness skins were mounted on a diffusion chamber in order to evaluate the effect of injuries and to mimic physiological conditions. The transepidermal water loss (TEWL) was greatly increased when the barrier function was compromised. Measurements were made for all the damaged biopsies and observed histologically by microscopy. On human and porcine skins, the tape-stripping application (0 to 40 times) showed a proportional increase in TEWL which highlights the destruction of the stratum corneum. Similar results were obtained for all cosmetic instruments. This is reflected in our study by the nonsignificant difference of the mean TEWL scores between 30 strips and mechanical damage. For a specific appreciation, damaged skins were then selected to qualitatively evaluate the absorption of a chlorogenic acid solution using fluorescence microscopy. PMID:26247021

Characterizing mutagenesis in the hprt gene of rat alveolar epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Driscoll, K.E.; Deyo, L.C.; Howard, B.W.

1995-12-31

A clonal selection assay was developed for mutation in the hypoxanthine-guanine phosphoribosyl transferase (hprt) gene of rat alveolar epithelial cells. Studies were conducted to establish methods for isolation and long-term culture of rat alveolar epithelial cells. When isolated by pronase digestion purified on a Nycodenz gradient and cultured in media containing 7.5% fetal bovine serum (FBS), pituitary extract, EGF, insulin, and IGF-1, rat alveolar epithelial cells could be maintained in culture for several weeks with cell doubling times of 2-4 days. The rat alveolar epithelial cell cultures were exposed in vitro to the mutagens ethylnitrosourea (ENU) and H{sub 2}O{sub 2},more » and mutation in the hprt gene was selected for by culture in the presence of the toxic purine analog, 6-thioguanine (6TG). In vitro exposure to ENU or H{sub 2}O produced a dose-dependent increase in hprt mutation frequency in the alveolar epithelial cells. To determine if the assay system could be used to evaluate mutagenesis in alveolar type II cells after in vivo mutagen or carcinogen exposure, cells were isolated from rats treated previously with ENU or {alpha}-quartz. A significant increase in hprt mutation frequency was detected in alveolar epithelial cells obtained from rats exposed to ENU or {alpha}-quartz; the latter observation is the first demonstration that crystalline silica exposure is mutagenic in vivo. In summary, these studies show that rat alveolar epithelial cells isolated by pronase digestion and Nycodenz separation techniques and cultured in a defined media can be used in a clonal selection assay for mutation in the hprt gene. This assay demonstrates that ENU and H{sub 2}O{sub 2} in vitro and ENU and {alpha}-quartz in vivo are mutagenic for rat alveolar epithelial cells. This model should be useful for investigating the genotoxic effects of chemical and physical agents on an important lung cell target for neoplastic transformation. 41 refs., 4 figs., 3 tabs.« less

Is endodontic treatment necessary during coronectomy procedure?

PubMed

Sencimen, Metin; Ortakoglu, Kerim; Aydin, Cumhur; Aydintug, Yavuz S; Ozyigit, Aykut; Ozen, Tuncer; Gunaydin, Yilmaz

2010-10-01

Close proximity of the inferior alveolar nerve (IAN) to the third molar roots can result in nerve injuries during extraction of third molars. Consequently, it is necessary to determine the relationship of the nerve and roots to avoid damage to the IAN. Computed tomography scans are widely used to determine the correct relationship between the IAN and lower third molars. The study consisted of 10 patients with 16 lower third molars in close relationship with the IAN who were divided into a study group and a control group. The patients in the study group were treated via coronectomies performed with endodontic treatments. The patients in the control group underwent coronectomies without endodontic treatment. The patients were followed up for at least 1 year. We had to extract 7 of the roots because of the infection in 8 patients belonging to the study group, which were treated endodontically. Moreover, there were 3 cases of IAN damage because of the extraction in the study group. However, in the control group, no infection was determined and IAN damage was absent. Coronectomy appears to be a reliable technique to protect the IAN from damage. This procedure has a low incidence of complications. Endodontic treatment does not affect the success of this method according to our results. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Thermally ruggedized ITO transparent electrode films for high power optoelectronics.

PubMed

Yoo, Jae-Hyuck; Matthews, Manyalibo; Ramsey, Phil; Barrios, Antonio Correa; Carter, Austin; Lange, Andrew; Bude, Jeff; Elhadj, Selim

2017-10-16

We present two strategies to minimize laser damage in transparent conductive films. The first consists of improving heat dissipation by selection of substrates with high thermal diffusivity or by addition of capping layer heatsinks. The second is reduction of bulk energy absorption by lowering free carrier density and increasing mobility, while maintaining film conductance with thicker films. Multi-pulse laser damage tests were performed on tin-doped indium oxide (ITO) films configured to improve optical lifetime damage performance. Conditions where improvements were not observed are also described. When bulk heating is not the dominant damage process, discrete defect-induced damage limits damage behavior.

Understanding the developmental pathways pulmonary fibroblasts may follow during alveolar regeneration.

PubMed

McGowan, Stephen

2017-03-01

Although pulmonary alveolar interstitial fibroblasts are less specialized than their epithelial and endothelial neighbors, they play essential roles during development and in response to lung injury. At birth, they must adapt to the sudden mechanical changes imposed by the onset of respiration and to a higher ambient oxygen concentration. In diseases such as bronchopulmonary dysplasia and interstitial fibrosis, their adaptive responses are overwhelmed leading to compromised gas-exchange function. Thus, although fibroblasts do not directly participate in gas-exchange, they are essential for creating and maintaining an optimal environment at the alveolar epithelial-endothelial interface. This review summarizes new information and concepts about the ontogeny differentiation, and function of alveolar fibroblasts. Alveolar development will be emphasized, because the development of strategies to evoke alveolar repair and regeneration hinges on thoroughly understanding the way that resident fibroblasts populate specific locations in which extracellular matrix must be produced and remodeled. Other recent reviews have described the disruption that diseases cause to the fibroblast niche and so my objective is to illustrate how the unique developmental origins and differentiation pathways could be harnessed favorably to augment certain fibroblast subpopulations and to optimize the conditions for alveolar regeneration.

Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

Comprehensive 3D Model of Shock Wave-Brain Interactions in Blast-Induced Traumatic Brain Injuries

DTIC Science & Technology

2009-10-01

waves can cause brain damage by other mechanisms including excess pressure (leading to contusions), excess strain (leading to subdural ... hematomas and/or diffuse axonal injuries), and, in particular, cavitation effects (leading to subcellular damage). This project aims at the development of a

Crystal surface integrity and diffusion measurements on Earth and planetary materials

NASA Astrophysics Data System (ADS)

Watson, E. B.; Cherniak, D. J.; Thomas, J. B.; Hanchar, J. M.; Wirth, R.

2016-09-01

Characterization of diffusion behavior in minerals is key to providing quantitative constraints on the ages and thermal histories of Earth and planetary materials. Laboratory experiments are a vital source of the needed diffusion measurements, but these can pose challenges because the length scales of diffusion achievable in a laboratory time are commonly less than 1 μm. An effective strategy for dealing with this challenge is to conduct experiments involving inward diffusion of the element of interest from a surface source, followed by quantification of the resulting diffusive-uptake profile using a high-resolution depth-profiling technique such as Rutherford backscattering spectroscopy (RBS), nuclear reaction analysis (NRA), or ion microprobe (SIMS). The value of data from such experiments is crucially dependent on the assumption that diffusion in the near-surface of the sample is representative of diffusion in the bulk material. Historical arguments suggest that the very process of preparing a polished surface for diffusion studies introduces defects-in the form of dislocations and cracks-in the outermost micrometer of the sample that make this region fundamentally different from the bulk crystal in terms of its diffusion properties. Extensive indirect evidence suggests that, in fact, the near-surface region of carefully prepared samples is no different from the bulk crystal in terms of its diffusion properties. A direct confirmation of this conclusion is nevertheless clearly important. Here we use transmission electron microscopy to confirm that the near-surface regions of olivine, quartz and feldspar crystals prepared using careful polishing protocols contain no features that could plausibly affect diffusion. This finding does not preclude damage to the mineral structure from other techniques used in diffusion studies (e.g., ion implantation), but even in this case the role of possible structural damage can be objectively assessed and controlled. While all evidence points to the reliability of diffusivities obtained from in-diffusion experiments, we do not recommend experiments of this type using a powder source as a means of obtaining diffusant solubility or partitioning information for the mineral of interest.

Diffusion Tensor Imaging Tractography Detecting Isolated Oculomotor Nerve Damage After Traumatic Brain Injury.

PubMed

Jacquesson, Timothée; Frindel, Carole; Cotton, Francois

2017-04-01

A 24-year-old woman was hit by a bus and suffered an isolated complete oculomotor nerve palsy. Computed tomography scan did not show a skull base fracture. T2*-weighted magnetic resonance imaging revealed petechial cerebral hemorrhages sparing the brainstem. T2 constructive interference in steady state suggested a partial sectioning of the left oculomotor nerve just before entering the superior orbital fissure. Diffusion tensor imaging fiber tractography confirmed a sharp arrest of the left oculomotor nerve. This recent imaging technique could be of interest to assess white fiber damage and help make a diagnosis or prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Elastase-Induced Parenchymal Disruption and Airway Hyper Responsiveness in Mouse Precision Cut Lung Slices: Toward an Ex vivo COPD Model.

PubMed

Van Dijk, Eline M; Culha, Sule; Menzen, Mark H; Bidan, Cécile M; Gosens, Reinoud

2016-01-01

Background: COPD is a progressive lung disease characterized by emphysema and enhanced bronchoconstriction. Current treatments focused on bronchodilation can delay disease progression to some extent, but recovery or normalization of loss of lung function is impossible. Therefore, novel therapeutic targets are needed. The importance of the parenchyma in airway narrowing is increasingly recognized. In COPD, the parenchyma and extracellular matrix are altered, possibly affecting airway mechanics and enhancing bronchoconstriction. Our aim was to set up a comprehensive ex vivo Precision Cut Lung Slice (PCLS) model with a pathophysiology resembling that of COPD and integrate multiple readouts in order to study the relationship between parenchyma, airway functionality, and lung repair processes. Methods: Lungs of C57Bl/6J mice were sliced and treated ex vivo with elastase (2.5 μg/ml) or H 2 O 2 (200 μM) for 16 h. Following treatment, parenchymal structure, airway narrowing, and gene expression levels of alveolar Type I and II cell repair were assessed. Results: Following elastase, but not H 2 O 2 treatment, slices showed a significant increase in mean linear intercept (Lmi), reflective of emphysema. Only elastase-treated slices showed disorganization of elastin and collagen fibers. In addition, elastase treatment lowered both alveolar Type I and II marker expression, whereas H 2 O 2 stimulation lowered alveolar Type I marker expression only. Furthermore, elastase-treated slices showed enhanced methacholine-induced airway narrowing as reflected by increased pEC50 (5.87 at basal vs. 6.50 after elastase treatment) and Emax values (47.96 vs. 67.30%), and impaired chloroquine-induced airway opening. The increase in pEC50 correlated with an increase in mean Lmi. Conclusion: Using this model, we show that structural disruption of elastin fibers leads to impaired alveolar repair, disruption of the parenchymal compartment, and altered airway biomechanics, enhancing airway contraction. This finding may have implications for COPD, as the amount of elastin fiber and parenchymal tissue disruption is associated with disease severity. Therefore, we suggest that PCLS can be used to model certain aspects of COPD pathophysiology and that the parenchymal tissue damage observed in COPD contributes to lung function decline by disrupting airway biomechanics. Targeting the parenchymal compartment may therefore be a promising therapeutic target in the treatment of COPD.

Effects of peroxisome proliferator-activated receptor-β/δ on sepsis induced acute lung injury.

PubMed

Wang, Cairui; Zhou, Guopeng; Zeng, Zeng

2014-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the first steps in the development of multiple organ failure induced by sepsis. A systemic excessive inflammatory reaction is currently the accepted mechanism of the pathogenesis of sepsis. Several studies have suggested a protective role of the peroxisome proliferator activated receptor-β/δ (PPAR-β/δ) in related inflammatory diseases. But the role of PPARβ/δ in ALI remains uncertain. The aim of this study was to investigate the role and possible mechanism of PPARβ/δ in ALI induced by sepsis. Cecal ligation and puncture (CLP) was used as a sepsis model. Rats were randomly divided into four groups, the control group (CON, n = 6), sham-operation group (SHAM, n = 12), cecal ligation and puncture group (CLP, n = 30), GW501516 group (CLP+GW, n = 25), which underwent CLP and were subcutaneously injected with the PPAR-β/δ agonist GW501516 (0.05 mg/100 g body weight). Survival was monitored to 24 hours after operation. Blood pressure, serum creatinine, blood urea nitrogen, aspartate aminotrasferase and alanine aminotrasferase were measured after CLP. Concentrations of tumor necrosis factor α (TNF-α) and interleukin (IL)-1β in serum were detected by enzyme linked immunosorbent assay (ELISA) kits. Lung tissue samples were stained with H&E and scored according to the degree of inflammation. Bacterial colonies were counted in the peritoneal fluid. Alveolar macrophages were cultured and incubated with GW501516 (0.15 µmol/L) and PPARβ/δ adenovirus and then treated with Lipopolysaccharide (2 µg/ml) for 2 hours. The TNF-α, IL-1β and IL-6 RNA in lung and alveolar macrophages were determined by real-time PCR. Phosphorylation of signal transducer and activator of transcription 3 (STAT3) in lung and alveolar macrophages was detected by Western blotting. GW501516 significantly increased the survival of septic rats, decreased histological damage of the lungs, reduced inflammatory cytokines in serum and lung tissues of septic rats and did not increase counts of peritoneal bacteria. In vitro, GW501516 and over-expression of PPARβ/δ attenuated gene expression of TNF-α, IL-1β and IL-6 in alveolar macrophages. Both in vivo and in vitro, PPARβ/δ inhibited the phosphorylation of STAT3. PPARβ/δ plays a protective role in sepsis induced ALI via suppressing excessive inflammation.

Blunt Chest Trauma in Mice after Cigarette Smoke-Exposure: Effects of Mechanical Ventilation with 100% O2.

PubMed

Wagner, Katja; Gröger, Michael; McCook, Oscar; Scheuerle, Angelika; Asfar, Pierre; Stahl, Bettina; Huber-Lang, Markus; Ignatius, Anita; Jung, Birgit; Duechs, Matthias; Möller, Peter; Georgieff, Michael; Calzia, Enrico; Radermacher, Peter; Wagner, Florian

2015-01-01

Cigarette smoking (CS) aggravates post-traumatic acute lung injury and increases ventilator-induced lung injury due to more severe tissue inflammation and apoptosis. Hyper-inflammation after chest trauma is due to the physical damage, the drop in alveolar PO2, and the consecutive hypoxemia and tissue hypoxia. Therefore, we tested the hypotheses that 1) CS exposure prior to blunt chest trauma causes more severe post-traumatic inflammation and thereby aggravates lung injury, and that 2) hyperoxia may attenuate this effect. Immediately after blast wave-induced blunt chest trauma, mice (n=32) with or without 3-4 weeks of CS exposure underwent 4 hours of pressure-controlled, thoraco-pulmonary compliance-titrated, lung-protective mechanical ventilation with air or 100% O2. Hemodynamics, lung mechanics, gas exchange, and acid-base status were measured together with blood and tissue cytokine and chemokine concentrations, heme oxygenase-1 (HO-1), activated caspase-3, and hypoxia-inducible factor 1-α (HIF-1α) expression, nuclear factor-κB (NF-κB) activation, nitrotyrosine formation, purinergic receptor 2X4 (P2XR4) and 2X7 (P2XR7) expression, and histological scoring. CS exposure prior to chest trauma lead to higher pulmonary compliance and lower PaO2 and Horovitz-index, associated with increased tissue IL-18 and blood MCP-1 concentrations, a 2-4-fold higher inflammatory cell infiltration, and more pronounced alveolar membrane thickening. This effect coincided with increased activated caspase-3, nitrotyrosine, P2XR4, and P2XR7 expression, NF-κB activation, and reduced HIF-1α expression. Hyperoxia did not further affect lung mechanics, gas exchange, pulmonary and systemic cytokine and chemokine concentrations, or histological scoring, except for some patchy alveolar edema in CS exposed mice. However, hyperoxia attenuated tissue HIF-1α, nitrotyrosine, P2XR7, and P2XR4 expression, while it increased HO-1 formation in CS exposed mice. Overall, CS exposure aggravated post-traumatic inflammation, nitrosative stress and thereby organ dysfunction and injury; short-term, lung-protective, hyperoxic mechanical ventilation have no major beneficial effect despite attenuation of nitrosative stress, possibly due to compensation of by regional alveolar hypoxia and/or consecutive hypoxemia, resulting in down-regulation of HIF-1α expression.

Reverse Engineering of Oxygen Transport in the Lung: Adaptation to Changing Demands and Resources through Space-Filling Networks

PubMed Central

Hou, Chen; Gheorghiu, Stefan; Huxley, Virginia H.; Pfeifer, Peter

2010-01-01

The space-filling fractal network in the human lung creates a remarkable distribution system for gas exchange. Landmark studies have illuminated how the fractal network guarantees minimum energy dissipation, slows air down with minimum hardware, maximizes the gas- exchange surface area, and creates respiratory flexibility between rest and exercise. In this paper, we investigate how the fractal architecture affects oxygen transport and exchange under varying physiological conditions, with respect to performance metrics not previously studied. We present a renormalization treatment of the diffusion-reaction equation which describes how oxygen concentrations drop in the airways as oxygen crosses the alveolar membrane system. The treatment predicts oxygen currents across the lung at different levels of exercise which agree with measured values within a few percent. The results exhibit wide-ranging adaptation to changing process parameters, including maximum oxygen uptake rate at minimum alveolar membrane permeability, the ability to rapidly switch from a low oxygen uptake rate at rest to high rates at exercise, and the ability to maintain a constant oxygen uptake rate in the event of a change in permeability or surface area. We show that alternative, less than space-filling architectures perform sub-optimally and that optimal performance of the space-filling architecture results from a competition between underexploration and overexploration of the surface by oxygen molecules. PMID:20865052

Expression of mutant Sftpcin murine alveolar epithelia drives spontaneous lung fibrosis.

PubMed

Nureki, Shin-Ichi; Tomer, Yaniv; Venosa, Alessandro; Katzen, Jeremy; Russo, Scott J; Jamil, Sarita; Barrett, Matthew; Nguyen, Vivian; Kopp, Meghan; Mulugeta, Surafel; Beers, Michael F

2018-06-19

Epithelial cell dysfunction is postulated as an important component in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Mutations in the Surfactant Protein C [SP-C] gene [SFTPC], an alveolar type 2 (AT2) cell restricted protein, have been found in sporadic and familial IPF. To causally link these events, we developed a knock-in mouse model capable of regulated expression of an IPF-associated Isoleucine to Threonine substitution at codon 73 [I73T] in Sftpc (SP-CI73T). Tamoxifen treated SP-CI73T cohorts developed rapid increases in SftpcI73T mRNA and misprocessed proSP-CI73T protein accompanied by increased early mortality (days 7-14). This acute phase was marked by diffuse parenchymal lung injury, tissue infiltration by monocytes, polycellular alveolitis, and elevations in bronchoalveolar lavage and AT2 mRNA contents of select inflammatory cytokines. Resolution of alveolitis (2-4 weeks), commensurate with a rise in TGFB1, was followed by aberrant remodeling marked by collagen deposition, AT2 cell hyperplasia, a-SMA positive cells, and restrictive lung physiology. The translational relevance of the model was supported by detection of multiple IPF biomarkers previously reported in human cohorts. These data provide proof of principle that mutant SP-C expression in vivo causes spontaneous lung fibrosis strengthening the role of AT2 dysfunction as a key upstream driver of IPF pathogenesis.

In Vitro Assessment of Uptake and Lysosomal Sequestration of Respiratory Drugs in Alveolar Macrophage Cell Line NR8383.

PubMed

Ufuk, Ayşe; Somers, Graham; Houston, J Brian; Galetin, Aleksandra

2015-12-01

To assess accumulation and lysosomal sequestration of 9 drugs used in respiratory indications (plus imipramine as positive control) in the alveolar macrophage (AM) cell line NR8383. For all drugs, uptake at 5 μM was investigated at 37 and 4°C to delineate active uptake and passive diffusion processes. Accumulation of basic clarithromycin, formoterol and imipramine was also assessed over 0.1-100 μM concentration range. Lysosomal sequestration was investigated using ammonium chloride (NH4Cl), monensin and nigericin. Impact of lysosomal sequestration on clarithromycin accumulation kinetics was investigated. Both cell-to-medium concentration ratio (Kp) and uptake clearance (CLuptake) ranged > 400-fold for the drugs investigated. The greatest Kp was observed for imipramine (391) and clarithromycin (82), in contrast to no accumulation seen for terbutaline. A concentration-dependent accumulation was evident for the basic drugs investigated. Imipramine and clarithromycin Kp and CLuptake were reduced by 59-85% in the presence of NH4Cl and monensin/nigericin, indicating lysosomal accumulation, whereas lysosomal sequestration was not pronounced for the other 8 respiratory drugs. Clarithromycin uptake rate was altered by NH4Cl, highlighting the impact of subcellular distribution on accumulation kinetics. This study provides novel evidence of the utility of NR8383 for investigating accumulation and lysosomal sequestration of respiratory drugs in AMs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fabbri, L.M.; Danieli, D.; Crescioli, S.

We report the case of a 43-yr-old car painter who died within 1 h of exposure to a polyurethane paint in the workplace. A diagnosis of asthma induced by toluene diisocyanate (TDI) had been established 6 yr before, when he underwent inhalation challenges with carbachol and with TDI. The subject had airway hyperresponsiveness to carbachol (PD20FEV1 carbachol = 0.32 mg; normal value greater than 1.0 mg) and developed an early and long-lasting asthmatic reaction after exposure to TDI in the laboratory. Although it was recommended that he change his job or stop using paints containing isocyanates, he continued to workmore » as a car painter, taking antiasthmatic drugs both at work and at home to control asthma symptoms. On Monday, October 6, 1986, at 11:30 A. M., he developed a severe attack of asthma while he was mixing the 2 components of a polyurethane paint. Taken to hospital, he was dead on arrival. Autopsy showed no evidence of cardiac or brain disease; lungs were overinflated, the cut surface showed grey glistening mucous plugs in in the airways. Histologic examination showed denudation of airway epithelium and thickening of the basement membrane with infiltration of the lamina propria by polymorphonuclear leukocytes, mainly eosinophils, and diffuse mucous plugging of bronchioles. Bronchial smooth muscle appeared hyperplastic and disarrayed, and lung parenchyma showed focal areas of alveolar destruction adjacent to areas of perfectly intact alveolar walls.« less

An Unusual Consolidation: Lobar Pulmonary Hemorrhage Due to Antithrombotic Therapy.

PubMed

D'Amore, Katrina; Traficante, David; McGovern, Terrance; Propersi, Marco; Barnes, Stacey

2017-11-01

Alveolar hemorrhage is a rare yet devastating clinical entity if not identified and treated aggressively. Exceedingly rare are the cases of anticoagulant-induced alveolar hemorrhage with very few cases described in the current literature. The nonspecific presentation of an alveolar hemorrhage makes its diagnosis and appropriate treatment difficult in the emergency department. We report a case of a patient on warfarin for atrial fibrillation who was initially misdiagnosed as having community-acquired pneumonia, but subsequently was identified to have a fatal alveolar hemorrhage.

A Green's Function Approach to Simulate DNA Damage by the Indirect Effect

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cicinotta, Francis A.

2013-01-01

The DNA damage is of fundamental importance in the understanding of the effects of ionizing radiation. DNA is damaged by the direct effect of radiation (e.g. direct ionization) and by indirect effect (e.g. damage by.OH radicals created by the radiolysis of water). Despite years of research, many questions on the DNA damage by ionizing radiation remains. In the recent years, the Green's functions of the diffusion equation (GFDE) have been used extensively in biochemistry [1], notably to simulate biochemical networks in time and space [2]. In our future work on DNA damage, we wish to use an approach based on the GFDE to refine existing models on the indirect effect of ionizing radiation on DNA. To do so, we will use the code RITRACKS [3] developed at the NASA Johnson Space Center to simulate the radiation track structure and calculate the position of radiolytic species after irradiation. We have also recently developed an efficient Monte-Carlo sampling algorithm for the GFDE of reversible reactions with an intermediate state [4], which can be modified and adapted to simulate DNA damage by free radicals. To do so, we will use the known reaction rate constants between radicals (OH, eaq, H,...) and the DNA bases, sugars and phosphates and use the sampling algorithms to simulate the diffusion of free radicals and chemical reactions with DNA. These techniques should help the understanding of the contribution of the indirect effect in the formation of DNA damage and double-strand breaks.

Inverted Apatite (U-Th)/He and Fission-track Dates from the Rae craton, Baffin Island, Canada and Implications for Apatite Radiation Damage-He Diffusivity Models

NASA Astrophysics Data System (ADS)

Ault, A. K.; Reiners, P. W.; Thomson, S. N.; Miller, G. H.

2015-12-01

Coupled apatite (U-Th)/He and fission-track (AFT) thermochronology data from the same sample can be used to decipher complex low temperature thermal histories and evaluate compatibility between these two methods. Existing apatite He damage-diffusivity models parameterize radiation damage annealing as fission-track annealing and yield inverted apatite He and AFT dates for samples with prolonged residence in the He partial retention zone. Apatite chemistry also impacts radiation damage and fission-track annealing, temperature sensitivity, and dates in both systems. We present inverted apatite He and AFT dates from the Rae craton, Baffin Island, Canada, that cannot be explained by apatite chemistry or existing damage-diffusivity and fission track models. Apatite He dates from 34 individual analyses from 6 samples range from 237 ± 44 Ma to 511 ± 25 Ma and collectively define a positive date-eU relationship. AFT dates from these same samples are 238 ± 15 Ma to 350 ± 20 Ma. These dates and associated track length data are inversely correlated and define the left segment of a boomerang diagram. Three of the six samples with 20-90 ppm eU apatite grains yield apatite He and AFT dates inverted by 300 million years. These samples have average apatite Cl chemistry of ≤0.02 wt.%, with no correlation between Cl content and Dpar. Thermal history simulations using geologic constraints, an apatite He radiation damage accumulation and annealing model, apatite He dates with the range of eU values, and AFT date and track length data, do not yield any viable time-temperature paths. Apatite He and AFT data modeled separately predict thermal histories with Paleozoic-Mesozoic peaks reheating temperatures differing by ≥15 °C. By modifying the parameter controlling damage annealing (Rmr0) from the canonical 0.83 to 0.5-0.6, forward models reproduce the apatite He date-eU correlation and AFT dates with a common thermal history. Results imply apatite radiation damage anneals at higher temperatures than fission-track damage and the impact on coupled apatite He and AFT dates is magnified for protracted cooling histories. Further experimental and field-based tests are important for refining radiation damage and fission-track annealing parameters for accurate interpretation of apatite He- and AFT-derived thermal histories.

Using quantum filters to process images of diffuse axonal injury

NASA Astrophysics Data System (ADS)

Pineda Osorio, Mateo

2014-06-01

Some images corresponding to a diffuse axonal injury (DAI) are processed using several quantum filters such as Hermite Weibull and Morse. Diffuse axonal injury is a particular, common and severe case of traumatic brain injury (TBI). DAI involves global damage on microscopic scale of brain tissue and causes serious neurologic abnormalities. New imaging techniques provide excellent images showing cellular damages related to DAI. Said images can be processed with quantum filters, which accomplish high resolutions of dendritic and axonal structures both in normal and pathological state. Using the Laplacian operators from the new quantum filters, excellent edge detectors for neurofiber resolution are obtained. Image quantum processing of DAI images is made using computer algebra, specifically Maple. Quantum filter plugins construction is proposed as a future research line, which can incorporated to the ImageJ software package, making its use simpler for medical personnel.

Experimental tests of truncated diffusion in fault damage zones

NASA Astrophysics Data System (ADS)

Suzuki, Anna; Hashida, Toshiyuki; Li, Kewen; Horne, Roland N.

2016-11-01

Fault zones affect the flow paths of fluids in groundwater aquifers and geological reservoirs. Fault-related fracture damage decreases to background levels with increasing distance from the fault core according to a power law. This study investigated mass transport in such a fault-related structure using nonlocal models. A column flow experiment is conducted to create a permeability distribution that varies with distance from a main conduit. The experimental tracer response curve is preasymptotic and implies subdiffusive transport, which is slower than the normal Fickian diffusion. If the surrounding area is a finite domain, an upper truncated behavior in tracer response (i.e., exponential decline at late times) is observed. The tempered anomalous diffusion (TAD) model captures the transition from subdiffusive to Fickian transport, which is characterized by a smooth transition from power-law to an exponential decline in the late-time breakthrough curves.

The protective effect of Rhizoma Dioscoreae extract against alveolar bone loss in ovariectomized rats via regulating Wnt and p38 MAPK signaling.

PubMed

Zhang, Zhiguo; Xiang, Lihua; Bai, Dong; Wang, Wenlai; Li, Yan; Pan, Jinghua; Liu, Hong; Wang, Shaojun; Xiao, Gary Guishan; Ju, Dahong

2014-12-12

The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats were subjected to either ovariectomy or a sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX) or RDE by oral gavage or with 17β-estradiol (E2) subcutaneously. After treatments, the bone mineral density (BMD), the three-dimensional bone architecture of the alveolar bone and the plasma biomarkers of bone turnover were analyzed to assess bone metabolism, and the histomorphometry of the alveolar bone was observed. Microarrays were used to evaluate gene expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of genes was further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using real-time quantitative RT-PCR (qRT-PCR). Our results showed that RDE inhibited alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 207 genes and downregulated expression levels of 176 genes in the alveolar bone. The IPA showed that several genes had the potential to code for proteins that were involved in the Wnt/β-catenin signaling pathway (Wnt7a, Fzd2, Tcf3, Spp1, Frzb, Sfrp2 and Sfrp4) and the p38 MAPK signaling pathway (Il1rn and Mapk14). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may be involved in the reduced abnormal bone remodeling, which is associated with the modulation of the Wnt/β-catenin and the p38 MAPK signaling pathways via gene regulation.