Estimating oxygen diffusive conductances of gas-exchange systems: A stereological approach illustrated with the human placenta.

PubMed

Mayhew, Terry M

2014-01-01

For many organisms, respiratory gas exchange is a vital activity and different types of gas-exchange apparatus have evolved to meet individual needs. They include not only skin, gills, tracheal systems and lungs but also transient structures such as the chorioallantois of avian eggs and the placenta of eutherian mammals. The ability of these structures to allow passage of oxygen by passive diffusion can be expressed as a diffusive conductance (units: cm(3) O2 min(-1) kPa(-1)). Occasionally, the ability to estimate diffusive conductance by physiological techniques is compromised by the difficulty of obtaining O2 partial pressures on opposite sides of the tissue interface between the delivery medium (air, water, blood) and uptake medium (usually blood). An alternative strategy is to estimate a morphometric diffusive conductance by combining stereological estimates of key structural quantities (volumes, surface areas, membrane thicknesses) with complementary physicochemical data (O2-haemoglobin chemical reaction rates and Krogh's permeability coefficients). This approach has proved valuable in a variety of comparative studies on respiratory organs from diverse species. The underlying principles were formulated in pioneering studies on the pulmonary lung but are illustrated here by taking the human placenta as the gas exchanger. Copyright © 2012 Elsevier GmbH. All rights reserved.

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

Evolution of Air Breathing: Oxygen Homeostasis and the Transitions from Water to Land and Sky

PubMed Central

Hsia, Connie C. W.; Schmitz, Anke; Lambertz, Markus; Perry, Steven F.; Maina, John N.

2014-01-01

Life originated in anoxia, but many organisms came to depend upon oxygen for survival, independently evolving diverse respiratory systems for acquiring oxygen from the environment. Ambient oxygen tension (PO2) fluctuated through the ages in correlation with biodiversity and body size, enabling organisms to migrate from water to land and air and sometimes in the opposite direction. Habitat expansion compels the use of different gas exchangers, for example, skin, gills, tracheae, lungs, and their intermediate stages, that may coexist within the same species; coexistence may be temporally disjunct (e.g., larval gills vs. adult lungs) or simultaneous (e.g., skin, gills, and lungs in some salamanders). Disparate systems exhibit similar directions of adaptation: toward larger diffusion interfaces, thinner barriers, finer dynamic regulation, and reduced cost of breathing. Efficient respiratory gas exchange, coupled to downstream convective and diffusive resistances, comprise the “oxygen cascade”—step-down of PO2 that balances supply against toxicity. Here, we review the origin of oxygen homeostasis, a primal selection factor for all respiratory systems, which in turn function as gatekeepers of the cascade. Within an organism's lifespan, the respiratory apparatus adapts in various ways to upregulate oxygen uptake in hypoxia and restrict uptake in hyperoxia. In an evolutionary context, certain species also become adapted to environmental conditions or habitual organismic demands. We, therefore, survey the comparative anatomy and physiology of respiratory systems from invertebrates to vertebrates, water to air breathers, and terrestrial to aerial inhabitants. Through the evolutionary directions and variety of gas exchangers, their shared features and individual compromises may be appreciated. PMID:23720333

Evolution of air breathing: oxygen homeostasis and the transitions from water to land and sky.

PubMed

Hsia, Connie C W; Schmitz, Anke; Lambertz, Markus; Perry, Steven F; Maina, John N

2013-04-01

Life originated in anoxia, but many organisms came to depend upon oxygen for survival, independently evolving diverse respiratory systems for acquiring oxygen from the environment. Ambient oxygen tension (PO2) fluctuated through the ages in correlation with biodiversity and body size, enabling organisms to migrate from water to land and air and sometimes in the opposite direction. Habitat expansion compels the use of different gas exchangers, for example, skin, gills, tracheae, lungs, and their intermediate stages, that may coexist within the same species; coexistence may be temporally disjunct (e.g., larval gills vs. adult lungs) or simultaneous (e.g., skin, gills, and lungs in some salamanders). Disparate systems exhibit similar directions of adaptation: toward larger diffusion interfaces, thinner barriers, finer dynamic regulation, and reduced cost of breathing. Efficient respiratory gas exchange, coupled to downstream convective and diffusive resistances, comprise the "oxygen cascade"-step-down of PO2 that balances supply against toxicity. Here, we review the origin of oxygen homeostasis, a primal selection factor for all respiratory systems, which in turn function as gatekeepers of the cascade. Within an organism's lifespan, the respiratory apparatus adapts in various ways to upregulate oxygen uptake in hypoxia and restrict uptake in hyperoxia. In an evolutionary context, certain species also become adapted to environmental conditions or habitual organismic demands. We, therefore, survey the comparative anatomy and physiology of respiratory systems from invertebrates to vertebrates, water to air breathers, and terrestrial to aerial inhabitants. Through the evolutionary directions and variety of gas exchangers, their shared features and individual compromises may be appreciated.

Impact of hydrogel nanoparticle size and functionalization on in vivo behavior for lung imaging and therapeutics

PubMed Central

Liu, Yongjian; Ibricevic-Richardson, Aida; Cohen, Joel A.; Cohen, Jessica L.; Gunsten, Sean P.; Fréchet, Jean M. J.; Walter, Michael J.; Welch, Michael J.; Brody, Steven L.

2009-01-01

Polymer chemistry offers the possibility of synthesizing multifunctional nanoparticles which incorporate moieties that enhance diagnostic and therapeutic targeting of cargo delivery to the lung. However, since rules for predicting particle behavior following modification are not well defined, it is essential that probes for tracking fate in vivo are also included. Accordingly, we designed polyacrylamide-based hydrogel particles of differing sizes, functionalized with a nona-arginine cell-penetrating peptide (Arg9), and labeled with imaging components to assess lung retention and cellular uptake after intratracheal administration. Radiolabeled microparticles (1–5 µm diameter) and nanoparticles (20–40 nm diameter) without and with Arg9 showed diffuse airspace distribution by positron emission tomography imaging. Biodistribution studies revealed that particle clearance and extrapulmonary distribution was, in part, size dependent. Microparticles were rapidly cleared by mucociliary routes but unexpectedly, also through the circulation. In contrast, nanoparticles had prolonged lung retention enhanced by Arg9 and were significantly restricted to the lung. For all particle types, uptake was predominant in alveolar macrophages, and, to a lesser extent, lung epithelial cells. In general, particles did not induce local inflammatory responses, with the exception of microparticles bearing Arg9. Whereas microparticles may be advantageous for short-term applications, nano-sized particles constitute an efficient high-retention and non-inflammatory vehicle for the delivery of diagnostic imaging agents and therapeutics to lung airspaces and alveolar macrophages that can be enhanced by Arg9. Importantly, our results show that minor particle modifications may significantly impact in vivo behavior within the complex environments of the lung, underscoring the need for animal modeling. PMID:19852512

Lung inhomogeneities, inflation and [18F]2-fluoro-2-deoxy-D-glucose uptake rate in acute respiratory distress syndrome.

PubMed

Cressoni, Massimo; Chiumello, Davide; Chiurazzi, Chiara; Brioni, Matteo; Algieri, Ilaria; Gotti, Miriam; Nikolla, Klodiana; Massari, Dario; Cammaroto, Antonio; Colombo, Andrea; Cadringher, Paolo; Carlesso, Eleonora; Benti, Riccardo; Casati, Rosangela; Zito, Felicia; Gattinoni, Luciano

2016-01-01

The aim of the study was to determine the size and location of homogeneous inflamed/noninflamed and inhomogeneous inflamed/noninflamed lung compartments and their association with acute respiratory distress syndrome (ARDS) severity.In total, 20 ARDS patients underwent 5 and 45 cmH2O computed tomography (CT) scans to measure lung recruitability. [(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) uptake and lung inhomogeneities were quantified with a positron emission tomography-CT scan at 10 cmH2O. We defined four compartments with normal/abnormal [(18)F]FDG uptake and lung homogeneity.The homogeneous compartment with normal [(18)F]FDG uptake was primarily composed of well-inflated tissue (80±16%), double-sized in nondependent lung (32±27% versus 16±17%, p<0.0001) and decreased in size from mild, moderate to severe ARDS (33±14%, 26±20% and 5±9% of the total lung volume, respectively, p=0.05). The homogeneous compartment with high [(18)F]FDG uptake was similarly distributed between the dependent and nondependent lung. The inhomogeneous compartment with normal [(18)F]FDG uptake represented 4% of the lung volume. The inhomogeneous compartment with high [(18)F]FDG uptake was preferentially located in the dependent lung (21±10% versus 12±10%, p<0.0001), mostly at the open/closed interfaces and related to recruitability (r(2)=0.53, p<0.001).The homogeneous lung compartment with normal inflation and [(18)F]FDG uptake decreases with ARDS severity, while the inhomogeneous poorly/not inflated compartment increases. Most of the lung inhomogeneities are inflamed. A minor fraction of healthy tissue remains in severe ARDS. Copyright ©ERS 2016.

Nicotine transport in lung and non-lung epithelial cells.

PubMed

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

2017-11-01

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

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

Effect of hyperoxia on uptake and metabolism of 5-hydroxytryptamine and β-phenylethylamine in rat lung: a sex difference

PubMed Central

Ben-Harari, R.R.; Lanir, A.; Youdim, M.B.H.

1981-01-01

1 The uptake of 5-hydroxytryptamine (5—HT) and β-phenylethylamine (PEA) and their deamination by monoamine oxidase (MAO) were studied in perfused lung from male and female rats exposed to 100% O2 at 1 ATA for up to 60 h. 2 The uptake and metabolism of 5-HT in lungs from both male and female rats was not changed by exposure to O2. 3 The uptake and metabolism of PEA by lungs from male rats was unchanged. Uptake of PEA by lungs from female rats was inhibited 20% and 62% after 37 h and 50 h exposure respectively. 4 MAO activity, both in vitro and in perfused lung, was increased towards PEA after 35 h of hyperoxia. 5 Metabolism of PEA in perfused lung, measured over 30 min, was inhibited 52% after 50 h of O2 hyperoxia. 6 These results show that exposure to high concentrations of O2 damages lung, resulting in inhibition of uptake of PEA and consequently in inhibition of metabolism of PEA. 7 These results also indicate that, in lung from female rats, MAO-type B is more susceptible to changes in O2 tension than MAO type A. PMID:7236995

Gallium scintigraphic pattern in lung CMV infections

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

Ganz, W.I.; Cohen, D.; Mallin, W.

1994-05-01

Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patientsmore » without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.« less

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.

Differential Lung Uptake of 99mTc-HMPAO and 99mTc-Duramycin in the Chronic Hyperoxia Rat Model

PubMed Central

Clough, Anne V.; Audi, Said H.; Haworth, Steven T.; Roerig, David L.

2015-01-01

Noninvasive radionuclide imaging has the potential to identify and assess mechanisms involved in particular stages of lung injury which occur with acute respiratory distress syndrome, for example. Lung uptake of 99mTc-hexamethylpropyleneamine oxime (HMPAO) is reported to be partially dependent on the redox status of the lung tissue while 99mTc-duramycin, a new marker of cell injury, senses cell death via apoptosis and/or necrosis. Thus, we investigated changes in lung uptake of these agents in rat exposed to hyperoxia for prolonged periods, a common model of acute lung injury. Methods Male Sprague-Dawley rats were pre-exposed to either normoxia (21% O2) or hyperoxia (85% O2) for up to 21 days. For imaging, the rats were anesthetized, injected i.v. with either 99mTc-HMPAO or 99mTc-duramycin (37-74 MBq) and planar images were acquired using a high sensitivity modular gamma camera. Subsequently, 99mTc-macroagreggated albumin (37 MBq, diam=10-40 μm) was injected i.v., imaged, and used to define a lung region-of-interest. The lung to background ratio was used as a measure of lung uptake. Results Hyperoxia exposure resulted in a 74% increase in 99mTc-HMPAO lung uptake, which peaked at 7 days and persisted for the 21 days of exposure. 99mTc-duramycin lung uptake was also maximal at 7 days of exposure but decreased to near control levels by 21 days. The sustained elevation of 99mTc-HMPAO uptake suggests ongoing changes in lung redox status whereas cell death appears to have subsided by 21 days. Conclusion These results suggest the potential use of 99mTc-HMPAO and 99mTc-duramycin as redox and cell-death imaging biomarkers, respectively, for in vivo identification and assessment of different stages of lung injury. PMID:23086010

Pulmonary vascular clearance of harmful endogenous macromolecules in a porcine model of acute liver failure.

PubMed

Nedredal, Geir I; Elvevold, Kjetil; Chedid, Marcio F; Ytrebø, Lars M; Rose, Christopher F; Sen, Sambit; Smedsrød, Bård; Jalan, Rajiv; Revhaug, Arthur

2016-01-01

Pulmonary complications are common in acute liver failure (ALF). The role of the lungs in the uptake of harmful soluble endogenous macromolecules was evaluated in a porcine model of ALF induced by hepatic devascularization (n = 8) vs. controls (n = 8). In additional experiments, pulmonary uptake was investigated in healthy pigs. Fluorochrome-labeled modified albumin (MA) was applied to investigate the cellular uptake. As compared to controls, the ALF group displayed a 4-fold net increased lung uptake of hyaluronan, and 5-fold net increased uptake of both tissue plasminogen activator and lysosomal enzymes. Anatomical distribution experiments in healthy animals revealed that radiolabeled MA uptake (taken up by the same receptor as hyaluronan) was 53% by the liver, and 24% by the lungs. The lung uptake of LPS was 14% whereas 60% remained in the blood. Both fluorescence and electron microscopy revealed initial uptake of MA by pulmonary endothelial cells (PECs) with later translocation to pulmonary intravascular macrophages (PIMs). Moreover, the presence of PIMs was evident 10 min after injection. Systemic inflammatory markers such as leukopenia and increased serum TNF-α levels were evident after 20 min in the MA and LPS groups. Significant lung uptake of harmful soluble macromolecules compensated for the defect liver scavenger function in the ALF-group. Infusion of MA induced increased TNF-α serum levels and leukopenia, similar to the effect of the known inflammatory mediator LPS. These observations suggest a potential mechanism that may contribute to lung damage secondary to liver disease.

Lung diffusion testing

MedlinePlus

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

Positron Emission Tomography With 18F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome

PubMed Central

de Prost, Nicolas; Sasanelli, Myriam; Deux, Jean-François; Habibi, Anoosha; Razazi, Keyvan; Galactéros, Frédéric; Meignan, Michel; Maître, Bernard; Brun-Buisson, Christian; Itti, Emmanuel; Dessap, Armand Mekontso

2015-01-01

Abstract The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with 18F-fluorodeoxyglucose [18F-fluorodeoxyglucose (18F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS. Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with 18F-FDG emission scans for quantification of regional 18F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung 18F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed. Seventeen patients with ACS (mean age 28.3 ± 6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1–2.9] vs 0.8 [0.6–1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R2 = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6–11] vs 4 [3–6] days; P = 0.016). Lungs of patients with ACS exhibited higher 18F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower 18F-FDG uptake than lung bases, but higher 18F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung 18F-FDG uptake had longer ICU stay than others. PMID:25950690

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

Lieske, T.R.; Sunderrajan, E.V.; Passamonte, P.M.

A patient with chronic eosinophilic pneumonia was evaluated using bronchoalveolar lavage, technetium-99m glucoheptonate, and transbronchial lung biopsy. Bronchoalveolar lavage revealed 43 percent eosinophils and correlated well with results of transbronchial lung biopsy. Technetium-99m glucoheptonate lung imaging demonstrated intense parenchymal uptake. After eight weeks of corticosteroid therapy, the bronchoalveolar lavage eosinophil population and the technetium-99m glucoheptonate uptake had returned to normal. We suggest that bronchoalveolar lavage, with transbronchial lung biopsy, is a less invasive way than open lung biopsy to diagnose chronic eosinophilic pneumonia. The mechanism of uptake of technetium-99m glucoheptonate in this disorder remains to be defined.

Ontogenesis of uptake and deamination of 5-hydroxytryptamine, dopamine and beta-phenylethylamine in isolated perfused lung and lung homogenates from rats.

PubMed Central

Ben-Harari, R. R.; Youdim, M. B.

1981-01-01

1. Uptake of 5-hydroxytryptamine (5-HT) and beta-phenylethylamine (PEA) was studied in perfused lung from male rats between 10 and 70 days old. 2. Monoamine oxidase (MAO) activity towards 5-HT, PEA and dopamine was studied in homogenate preparations of lung from rats aged between 5 and 80 days. 3. Uptake of 5-HT (10 microM) decreased throughout the age range studied but uptake of PEA (50 microM) increased for the first 30 days and beyond this age it decreased. Metabolites formed for both amines reflected the changes in uptake. 4. MAO activity deaminating 5-HT is well developed by day 10 and reaches its maximum by day 40. For dopamine and PEA, MAO activity remained low until day 20, and the developed rapidly, reaching a maximum by day 40 for dopamine; activity towards PEA did not reach a maximum by day 80. 5. These results show that uptake and MAO activity changes with age and thus the lung responds like other tissues. 6. These results also demonstrate the independent development of uptake and MAO activity towards 5-HT, PEA and dopamine. PMID:7284689

In Vivo Detection of Hyperoxia-Induced Pulmonary Endothelial Cell Death Using 99mTc-Duramycin

PubMed Central

Audi, Said H.; Jacobs, Elizabeth R.; Zhao, Ming; Roerig, David L.; Haworth, Steven T.; Clough, Anne V.

2014-01-01

Introduction: 99mTc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury. Methods: Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained for caspase activation and endothelial and epithelial cells. Results: Lung DU uptake increased significantly (p < 0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r2 = 0.82, p = 0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48 hours. By 60 hours there was evidence of edema, and modest neutrophilic infiltrate. Conclusions: Rat lung DU uptake in vivo increased after just 48 hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo. PMID:25218023

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.

99mTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment

PubMed Central

Audi, Said H.; Clough, Anne V.; Haworth, Steven T.; Medhora, Meetha; Ranji, Mahsa; Densmore, John C.; Jacobs, Elizabeth R.

2016-01-01

99mTc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a pre-clinical marker of lung injury in two well-established rat models of human acute lung injury (ALI). Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 hours later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (Kf). For hyperoxia rats, HMPAO lung uptake increased after 24 hours (134%) and 48 hours (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 hours after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on Kf at 24 hours. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury. PMID:26974426

99MTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment.

PubMed

Audi, Said H; Clough, Anne V; Haworth, Steven T; Medhora, Meetha; Ranji, Mahsa; Densmore, John C; Jacobs, Elizabeth R

2016-10-01

Tc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a preclinical marker of lung injury in two well-established rat models of human acute lung injury (ALI).Rats were exposed to >95% O2 (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 h later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (Kf).For hyperoxia rats, HMPAO lung uptake increased after 24 h (134%) and 48 h (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 h after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on Kf at 24 h. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL, and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury.

Predicting Future Morphological Changes of Lesions from Radiotracer Uptake in 18F-FDG-PET Images

PubMed Central

Bagci, Ulas; Yao, Jianhua; Miller-Jaster, Kirsten; Chen, Xinjian; Mollura, Daniel J.

2013-01-01

We introduce a novel computational framework to enable automated identification of texture and shape features of lesions on 18F-FDG-PET images through a graph-based image segmentation method. The proposed framework predicts future morphological changes of lesions with high accuracy. The presented methodology has several benefits over conventional qualitative and semi-quantitative methods, due to its fully quantitative nature and high accuracy in each step of (i) detection, (ii) segmentation, and (iii) feature extraction. To evaluate our proposed computational framework, thirty patients received 2 18F-FDG-PET scans (60 scans total), at two different time points. Metastatic papillary renal cell carcinoma, cerebellar hemongioblastoma, non-small cell lung cancer, neurofibroma, lymphomatoid granulomatosis, lung neoplasm, neuroendocrine tumor, soft tissue thoracic mass, nonnecrotizing granulomatous inflammation, renal cell carcinoma with papillary and cystic features, diffuse large B-cell lymphoma, metastatic alveolar soft part sarcoma, and small cell lung cancer were included in this analysis. The radiotracer accumulation in patients' scans was automatically detected and segmented by the proposed segmentation algorithm. Delineated regions were used to extract shape and textural features, with the proposed adaptive feature extraction framework, as well as standardized uptake values (SUV) of uptake regions, to conduct a broad quantitative analysis. Evaluation of segmentation results indicates that our proposed segmentation algorithm has a mean dice similarity coefficient of 85.75±1.75%. We found that 28 of 68 extracted imaging features were correlated well with SUVmax (p<0.05), and some of the textural features (such as entropy and maximum probability) were superior in predicting morphological changes of radiotracer uptake regions longitudinally, compared to single intensity feature such as SUVmax. We also found that integrating textural features with SUV measurements significantly improves the prediction accuracy of morphological changes (Spearman correlation coefficient = 0.8715, p<2e-16). PMID:23431398

Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129

PubMed Central

Mugler, John P.; Altes, Talissa A.; Ruset, Iulian C.; Dregely, Isabel M.; Mata, Jaime F.; Miller, G. Wilson; Ketel, Stephen; Ketel, Jeffrey; Hersman, F. William; Ruppert, Kai

2010-01-01

Despite a myriad of technical advances in medical imaging, as well as the growing need to address the global impact of pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, on health and quality of life, it remains challenging to obtain in vivo regional depiction and quantification of the most basic physiological functions of the lung—gas delivery to the airspaces and gas uptake by the lung parenchyma and blood—in a manner suitable for routine application in humans. We report a method based on MRI of hyperpolarized xenon-129 that permits simultaneous observation of the 3D distributions of ventilation (gas delivery) and gas uptake, as well as quantification of regional gas uptake based on the associated ventilation. Subjects with lung disease showed variations in gas uptake that differed from those in ventilation in many regions, suggesting that gas uptake as measured by this technique reflects such features as underlying pathological alterations of lung tissue or of local blood flow. Furthermore, the ratio of the signal associated with gas uptake to that associated with ventilation was substantially altered in subjects with lung disease compared with healthy subjects. This MRI-based method provides a way to quantify relationships among gas delivery, exchange, and transport, and appears to have significant potential to provide more insight into lung disease. PMID:21098267

Effects of cardiac oscillations and lung volume on acinar gas mixing during apnea

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

Mackenzie, C.F.; Skacel, M.; Barnas, G.M.

1990-05-01

We evaluated the importance of cardiogenic gas mixing in the acini of 13 dogs during 2 min of apnea. 133Xe (1-2 mCi in 4 ml of saline) was injected into an alveolar region through an occluded pulmonary artery branch, and washout was measured by gamma scintillation scanning during continued occlusion or with blood flow reinstated. The monoexponential rate constant for Xe washout (XeW) was -0.4 +/- 0.08 (SE) min-1 at functional residual capacity (FRC) with no blood flow in the injected region. It decreased by more than half at lung volumes 500 ml above and 392 ml below FRC. Withmore » intact pulmonary blood flow, XeW was -1.0 +/- 0.08 (SE) min-1 at FRC, and it increased with decreasing lung volume. However, if calculated Xe uptake by the blood was subtracted from the XeW measured with blood flow intact, resulting values at FRC and at FRC + 500 ml were not different from XeW with no blood flow. Reasonable calculation of Xe blood uptake at 392 ml below FRC was not possible because airway closure, increased shunt, and other factors affect XeW. After death, no significant XeW could be measured, which suggests that XeW caused by molecular diffusion was small. We conclude that (1) the effect of heart motion on the lung parenchyma increases acinar gas mixing during apnea, (2) this effect diminishes above or below FRC, and (3) there is probably no direct effect of pulmonary vascular pulsatility on acinar gas mixing.« less

In vivo detection of hyperoxia-induced pulmonary endothelial cell death using (99m)Tc-duramycin.

PubMed

Audi, Said H; Jacobs, Elizabeth R; Zhao, Ming; Roerig, David L; Haworth, Steven T; Clough, Anne V

2015-01-01

(99m)Tc-duramycin, DU, is a SPECT biomarker of tissue injury identifying cell death. The objective of this study is to investigate the potential of DU imaging to quantify capillary endothelial cell death in rat lung injury resulting from hyperoxia exposure as a model of acute lung injury. Rats were exposed to room air (normoxic) or >98% O2 for 48 or 60 hours. DU was injected i.v. in anesthetized rats, scintigraphy images were acquired at steady-state, and lung DU uptake was quantified from the images. Post-mortem, the lungs were removed for histological studies. Sequential lung sections were immunostained for caspase activation and endothelial and epithelial cells. Lung DU uptake increased significantly (p<0.001) by 39% and 146% in 48-hr and 60-hr exposed rats, respectively, compared to normoxic rats. There was strong correlation (r(2)=0.82, p=0.005) between lung DU uptake and the number of cleaved caspase 3 (CC3) positive cells, and endothelial cells accounted for more than 50% of CC3 positive cells in the hyperoxic lungs. Histology revealed preserved lung morphology through 48 hours. By 60 hours there was evidence of edema, and modest neutrophilic infiltrate. Rat lung DU uptake in vivo increased after just 48 hours of >98% O2 exposure, prior to the onset of any substantial evidence of lung injury. These results suggest that apoptotic endothelial cells are the primary contributors to the enhanced DU lung uptake, and support the utility of DU imaging for detecting early endothelial cell death in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Ultrasound findings of diffuse metastasis of gastric signet-ring-cell carcinoma to the thyroid gland.

PubMed

Morita, Koji; Sakamoto, Takahiko; Ota, Shuji; Masugi, Hideo; Chikuta, Ikumi; Mashimo, Yamato; Edo, Naoki; Tokairin, Takuo; Seki, Nobuhiko; Ishikawa, Toshio

2017-01-01

It has been shown that metastases to the thyroid from extrathyroidal malignancies occur as solitary or multiple nodules, or may involve the whole thyroid gland diffusely. However, diffuse metastasis of gastric cancer to the thyroid is extremely rare. Here, we report a case of a 74-year-old woman with diffuse infiltration of gastric adenocarcinoma (signet-ring-cell carcinoma/poorly differentiated adenocarcinoma) cells in the thyroid. The pathological diagnosis was made based on upper gastrointestinal endoscopy with biopsy and fine-needle aspiration cytology of the thyroid. An 18F-FDG PET/CT revealed multiple lesions with increased uptake, including the bilateral thyroid gland. On thyroid ultrasound examination, diffuse enlargement with internal heterogeneity and hypoechoic reticular lines was observed. On color Doppler imaging, a blood-flow signal was not detected in these hypoechoic lines. These findings were similar to those of diffuse metastases caused by other primary cancers, such as lung cancer, as reported earlier. Therefore, the presence of hypoechoic reticular lines without blood-flow signals is probably common to diffuse thyroid metastasis from any origin and an important diagnostic finding. This is the first report to show detailed ultrasound findings of diffuse gastric cancer metastasis to the thyroid gland using color Doppler.

Ozone Uptake During Inspiratory Flow in a Model of the Larynx, Trachea and Primary Bronchial Bifurcation

PubMed Central

Padaki, Amit; Ultman, James S.; Borhan, Ali

2009-01-01

Three-dimensional simulations of the transport and uptake of a reactive gas such as O3 were compared between an idealized model of the larynx, trachea, and first bifurcation and a second “control” model in which the larynx was replaced by an equivalent, cylindrical, tube segment. The Navier-Stokes equations, Spalart-Allmaras turbulence equation, and convection-diffusion equation were implemented at conditions reflecting inhalation into an adult human lung. Simulation results were used to analyze axial velocity, turbulent viscosity, local fractional uptake, and regional uptake. Axial velocity data revealed a strong laryngeal jet with a reattachment point in the proximal trachea. Turbulent viscosity data indicated that jet turbulence occurred only at high Reynolds numbers and was attenuated by the first bifurcation. Local fractional uptake data affirmed hotspots previously reported at the first carina, and suggested additional hotspots at the glottal constriction and jet reattachment point in the proximal trachea. These laryngeal effects strongly depended on inlet Reynolds number, with maximal effects (approaching 15%) occurring at maximal inlet flow rates. While the increase in the regional uptake caused by the larynx subsided by the end of the model, the effect of the larynx on cumulative uptake persisted further downstream. These results suggest that with prolonged exposure to a reactive gas, entire regions of the larynx and proximal trachea could show signs of tissue injury. PMID:22949744

A hybrid multibreath wash-in wash-out lung function quantification scheme in human subjects using hyperpolarized 3 He MRI for simultaneous assessment of specific ventilation, alveolar oxygen tension, oxygen uptake, and air trapping.

PubMed

Hamedani, Hooman; Kadlecek, Stephen; Xin, Yi; Siddiqui, Sarmad; Gatens, Heather; Naji, Joseph; Ishii, Masaru; Cereda, Maurizio; Rossman, Milton; Rizi, Rahim

2017-08-01

To present a method for simultaneous acquisition of alveolar oxygen tension (P A O 2 ), specific ventilation (SV), and apparent diffusion coefficient (ADC) of hyperpolarized (HP) gas in the human lung, allowing reinterpretation of the P A O 2 and SV maps to produce a map of oxygen uptake (R). An imaging scheme was designed with a series of identical normoxic HP gas wash-in breaths to measure ADC, SV, P A O 2 , and R in less than 2 min. Signal dynamics were fit to an iterative recursive model that regionally solved for these parameters. This measurement was successfully performed in 12 subjects classified in three healthy, smoker, and chronic obstructive pulmonary disease (COPD) cohorts. The overall whole lung ADC, SV, P A O 2 , and R in healthy, smoker, and COPD subjects was 0.20 ± 0.03 cm 2 /s, 0.39 ± 0.06,113 ± 2 Torr, and 1.55 ± 0.35 Torr/s, respectively, in healthy subjects; 0.21 ± 0.03 cm 2 /s, 0.33 ± 0.06, 115.9 ± 4 Torr, and 0.97 ± 0.2 Torr/s, respectively, in smokers; and 0.25 ± 0.06 cm 2 /s, 0.23 ± 0.08, 114.8 ± 6.0Torr, and 0.94 ± 0.12 Torr/s, respectively, in subjects with COPD. Hetrogeneity of SV, P A O 2 , and R were indicators of both smoking-related changes and disease, and the severity of the disease correlated with the degree of this heterogeneity. Subjects with symptoms showed reduced oxygen uptake and specific ventilation. High-resolution, nearly coregistered and quantitative measures of lung function and structure were obtained with less than 1 L of HP gas. This hybrid multibreath technique produced measures of lung function that revealed clear differences among the cohorts and subjects and were confirmed by correlations with global lung measurements. Magn Reson Med 78:611-624, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

PubMed

Regier, M; Derlin, T; Schwarz, D; Laqmani, A; Henes, F O; Groth, M; Buhk, J-H; Kooijman, H; Adam, G

2012-10-01

To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm(2)) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV(mean)) and maximum (SUV(max)) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC(mean)) and minimum ADC (ADC(min)) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland-Altman and regression analysis were assessed. Data analysis revealed a significant inverse correlation of the ADC(min) and SUV(max) (r=-0.46; p=0.032). Testing the correlation of the ADC(min) and SUV(max) for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r=-0.47; p=0.03) and squamouscell carcinomas (r=-0.71; p=0.002), respectively. No significant correlation was found for the comparison of ADC(min) and SUV(mean) (r=-0.29; p=0.27), ADC(mean) vs. SUV(mean) (r=-0.28; p=0.31) or ADC(mean) vs. SUV(max) (r=-0.33; p=0.23). The κ-value of 0.88 indicated a good agreement between both observers. This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Working underground: Respiratory adaptations in the blind mole rat

PubMed Central

Widmer, Hans R.; Hoppeler, Hans; Nevo, Eviatar; Taylor, C. Richard; Weibel, Ewald R.

1997-01-01

Mole rats (Spalax ehrenbergi superspecies) perform the heavy work of digging their subterranean burrows in Israel under highly hypoxic/hypercapnic conditions. Unlike most other mammals, they can achieve high levels of metabolic rate under these conditions, while their metabolic rate at low work rates is depressed. We explored, by comparing mole rats with white rats, whether and how this is related to adaptations in the design of the respiratory system, which determines the transfer of O2 from the lung to muscle mitochondria. At the same body mass, mole rats were found to have a significantly smaller total skeletal muscle mass than ordinary white rats (−22%). In contrast, the fractional volume of muscle mitochondria was larger by 46%. As a consequence, both species had the same total amount of mitochondria and achieved, under normoxia, the same V̇O2max. Whereas the O2 transport capacity of the blood was not different, we found a larger capillary density (+31%) in the mole rat muscle, resulting in a reduced diffusion distance to mitochondria. The structural pulmonary diffusing capacity for O2 was greater in the mole rat (+44%), thus facilitating O2 uptake in hypoxia. We conclude that structural adaptations in lung and muscle tissue improve O2 diffusion conditions and serve to maintain high metabolic rates in hypoxia but have no consequences for achieving V̇O2max under normoxic conditions. PMID:9050905

PET/CT incidental detection of second tumor in patients investigated for pancreatic neoplasms.

PubMed

Moletta, Lucia; Bissoli, Sergio; Fantin, Alberto; Passuello, Nicola; Valmasoni, Michele; Sperti, Cosimo

2018-05-04

Positron Emission Tomography/computed tomography (PET/CT) is an imaging technique which has a role in the detection and staging malignancies (both in first diagnosis and follow-up). The finding of an unexpected region of FDG (Fluorodeoxyglucose) uptake can occur when performing whole-body FDG-PET, raising the possibility of a second primary tumor. The aim of this study was to evaluate our experience of second primary cancer incidentally discovered during PET/CT examination performed for pancreatic diseases, during the initial work-up or follow-up after surgical resection. In this study, a retrospective evaluation of a prospectively collected data base was performed. Three hundred ninety- nine patients with pancreatic pathology were evaluated by whole body PET/CT imaging from January 2004 to December 2014. Among them, 348 patients were scanned before surgical resection and 51 during the course of their follow-up (pancreatic cancer). Median follow-up time was 29 months (range 14-124). Fifty-six patients (14%) had incidental uptake of FDG in their organs: 31 patients had focal uptake and 25 showed diffuse with or without focal uptake. All patients with focal uptake were investigated, and invasive malignancy was diagnosed in 22 patients: 14 colon, 4 lung, 1 larynx, 1 urothelial, 1 breast cancer, and 1 colon metastasis from pancreatic cancer. Twenty patients underwent resection, and 6 endoscopic removal of colonic polyps. Three patients were not operated for advanced disease, and two patients did not show any pathology (PET/CT false positive). Of the 10 patients investigated for diffuse uptake, no malignancy was found; none of these patients developed a second cancer during the follow-up. As in other malignancies, unexpected FDG uptake can occur in patients having PET/CT investigation for pancreatic diseases. Focal uptake is likely to be a malignancy and deserves further investigations, although the stage and the poor prognosis of primary pancreatic cancer should be kept in mind. Some selected patients may benefit from the aggressive treatment of incidental lesions and show survival benefit.

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

Efficacy of /sup 67/Ga-scintigraphy in predicting the diagnostic yield of transbronchial lung biopsy in pulmonary sarcoidosis

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

Ackart, R.S.; Munzel, T.L.; Rodriguez, J.J.

1982-07-01

Nineteen consecutive patients with clinically suspected sarcoidosis underwent /sup 67/Ga-scintigraphy prior to transbronchial lung biopsy (TBLB) to determine if /sup 67/Ga uptake in lung parenchyma would increase the diagnostic yield of the biopsy procedure. Biopsies were obtained from the areas showing parenchymal uptake on the /sup 67/Ga scan in 13 of the 19 patients. In the six patients not demonstrating uptake of /sup 67/Ga in the lung parenchyma, biopsies were obtained at random from the right lower lobe. There was no correlation between /sup 67/Ga uptake in hilar nodes or pulmonary parenchyma tissue and the diagnostic yield from TBLB. Researchersmore » conclude that /sup 67/Ga scanning is neither efficacious nor cost-effective in predicting the diagnostic yield of TBLB in sarcoidosis.« less

Cost and effectiveness of lung lobectomy by video-assisted thoracic surgery for lung cancer

PubMed Central

Mafé, Juan J.; Planelles, Beatriz; Asensio, Santos; Cerezal, Jorge; Inda, María-del-Mar; Lacueva, Javier; Esteban, Maria-Dolores; Hernández, Luis; Martín, Concepción; Baschwitz, Benno

2017-01-01

Background Video-assisted thoracic surgery (VATS) emerged as a minimally invasive surgery for diseases in the field of thoracic surgery. We herein reviewed our experience on thoracoscopic lobectomy for early lung cancer and evaluated Health System use. Methods A cost-effectiveness study was performed comparing VATS vs. open thoracic surgery (OPEN) for lung cancer patients. Demographic data, tumor localization, dynamic pulmonary function tests [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusion capacity (DLCO) and maximal oxygen uptake (VO2max)], surgical approach, postoperative details, and complications were recorded and analyzed. Results One hundred seventeen patients underwent lung resection by VATS (n=42, 36%; age: 63±9 years old, 57% males) or OPEN (n=75, 64%; age: 61±11 years old, 73% males). Pulmonary function tests decreased just after surgery with a parallel increasing tendency during first 12 months. VATS group tended to recover FEV1 and FVC quicker with significantly less clinical and post-surgical complications (31% vs. 53%, P=0.015). Costs including surgery and associated hospital stay, complications and costs in the 12 months after surgery were significantly lower for VATS (P<0.05). Conclusions The VATS approach surgery allowed earlier recovery at a lower cost than OPEN with a better cost-effectiveness profile. PMID:28932560

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.

Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude.

PubMed

Faoro, Vitalie; Huez, Sandrine; Vanderpool, Rebecca; Groepenhoff, Herman; de Bisschop, Claire; Martinot, Jean-Benot; Lamotte, Michel; Pavelescu, Adriana; Guénard, Hervé; Naeije, Robert

2014-04-01

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation and arterial oxygen saturation, no excessive polycythemia, and lower pulmonary arterial pressures (Ppa) compared with other high-altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test, lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In Sherpas vs. lowlanders, arterial oxygen saturation was 86 ± 1 vs. 83 ± 2% (mean ± SE; P = nonsignificant), mPpa at rest 19 ± 1 vs. 23 ± 1 mmHg (P < 0.05), DL(CO) corrected for hemoglobin 61 ± 4 vs. 37 ± 2 ml · min(-1) · mmHg(-1) (P < 0.001), DL(NO) 226 ± 18 vs. 153 ± 9 ml · min(-1) · mmHg(-1) (P < 0.001), maximum oxygen uptake 32 ± 3 vs. 28 ± 1 ml · kg(-1) · min(-1) (P = nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs. 48 ± 2 (P < 0.001). Maximum oxygen uptake was correlated directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but with less pronounced pulmonary hypertension, lower ventilatory responses, and higher lung diffusing capacity.

Hyperpolarized 129Xe MRI of the Human Lung

PubMed Central

Mugler, John P.; Altes, Talissa A.

2012-01-01

By permitting direct visualization of the airspaces of the lung, MR imaging using hyperpolarized gases provides unique strategies for evaluating pulmonary structure and function. Although the vast majority of research in humans has been performed using hyperpolarized 3He, recent contraction in the supply of 3He and consequent increases in price have turned attention to the alternative agent, hyperpolarized 129Xe. Compared to 3He, 129Xe yields reduced signal due to its smaller magnetic moment. Nonetheless, taking advantage of advances in gas-polarization technology, recent studies in humans using techniques for measuring ventilation, diffusion, and partial pressure of oxygen have demonstrated results for hyperpolarized 129Xe comparable to those previously demonstrated using hyperpolarized 3He. In addition, xenon has the advantage of readily dissolving in lung tissue and blood following inhalation, which makes hyperpolarized 129Xe particularly attractive for exploring certain characteristics of lung function, such as gas exchange and uptake, which cannot be accessed using 3He. Preliminary results from methods for imaging 129Xe dissolved in the human lung suggest that these approaches will provide new opportunities for quantifying relationships among gas delivery, exchange, and transport, and thus show substantial potential to broaden our understanding of lung disease. Finally, recent changes in the commercial landscape of the hyperpolarized-gas field now make it possible for this innovative technology to move beyond the research lab. PMID:23355432

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

PubMed

Morris, Christopher J; Aljayyoussi, Ghaith; Mansour, Omar; Griffiths, Peter; Gumbleton, Mark

2017-12-01

Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection

PubMed Central

Minandri, Fabrizia; Imperi, Francesco; Frangipani, Emanuela; Bonchi, Carlo; Visaggio, Daniela; Facchini, Marcella; Pasquali, Paolo; Bragonzi, Alessandra

2016-01-01

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. Iron is essential for bacterial growth, and P. aeruginosa expresses multiple iron uptake systems, whose role in lung infection deserves further investigation. P. aeruginosa Fe3+ uptake systems include the pyoverdine and pyochelin siderophores and two systems for heme uptake, all of which are dependent on the TonB energy transducer. P. aeruginosa also has the FeoB transporter for Fe2+ acquisition. To assess the roles of individual iron uptake systems in P. aeruginosa lung infection, single and double deletion mutants were generated in P. aeruginosa PAO1 and characterized in vitro, using iron-poor media and human serum, and in vivo, using a mouse model of lung infection. The iron uptake-null mutant (tonB1 feoB) and the Fe3+ transport mutant (tonB1) did not grow aerobically under low-iron conditions and were avirulent in the mouse model. Conversely, the wild type and the feoB, hasR phuR (heme uptake), and pchD (pyochelin) mutants grew in vitro and caused 60 to 90% mortality in mice. The pyoverdine mutant (pvdA) and the siderophore-null mutant (pvdA pchD) grew aerobically in iron-poor media but not in human serum, and they caused low mortality in mice (10 to 20%). To differentiate the roles of pyoverdine in iron uptake and virulence regulation, a pvdA fpvR double mutant defective in pyoverdine production but expressing wild-type levels of pyoverdine-regulated virulence factors was generated. Deletion of fpvR in the pvdA background partially restored the lethal phenotype, indicating that pyoverdine contributes to the pathogenesis of P. aeruginosa lung infection by combining iron transport and virulence-inducing capabilities. PMID:27271740

Effects of lung ventilation–perfusion and muscle metabolism–perfusion heterogeneities on maximal O2 transport and utilization

PubMed Central

Cano, I; Roca, J; Wagner, P D

2015-01-01

Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation–perfusion and skeletal muscle metabolism–perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake ( and on mitochondrial (). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial () at sea level by 32 mmHg, but muscle by only 122 ml min−1 (–3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced by less than 1 mmHg and by 32 ml min−1 (–2.4%). Skeletal muscle heterogeneity led to a wide range of potential among muscle regions, a range that becomes narrower as increases, and in regions with a low ratio of metabolic capacity to blood flow, can exceed that of mixed muscle venous blood. For patients with severe COPD, peak was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of both in health and in diseases such as COPD if the extent for both lung ventilation–perfusion and tissue metabolism–perfusion heterogeneity is known. PMID:25640017

Lung uptake of /sup 99m/Tc--sulfur colloid in falciparum malaria: case report

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

Ziessman, H.A.

Increased lung uptake of /sup 99m/Tc-sulfur colloid was seen during liver scanning in a patient with falciparum malaria. This finding was due to the enhanced activity of the phagocytic cells of the reticuloendothelial system in the liver, spleen, and lung found in human and experimental malaria. Similar findings in other clinical situations and the relevant literature are reviewed.

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.

Quantification of Dynamic [18F]FDG Pet Studies in Acute Lung Injury.

PubMed

Grecchi, Elisabetta; Veronese, Mattia; Moresco, Rosa Maria; Bellani, Giacomo; Pesenti, Antonio; Messa, Cristina; Bertoldo, Alessandra

2016-02-01

This work aims to investigate lung glucose metabolism using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) positron emission tomography (PET) imaging in acute lung injury (ALI) patients. Eleven ALI patients and five healthy controls underwent a dynamic [(18)F]FDG PET/X-ray computed tomography (CT) scan. The standardized uptake values (SUV) and three different methods for the quantification of glucose metabolism (i.e., ratio, Patlak, and spectral analysis iterative filter, SAIF) were applied both at the region and the voxel levels. SUV reported a lower correlation than the ratio with the net tracer uptake. Patlak and SAIF analyses did not show any significant spatial or quantitative (R(2) > 0.80) difference. The additional information provided by SAIF showed that in lung inflammation, elevated tracer uptake is coupled with abnormal tracer exchanges within and between lung tissue compartments. Full kinetic modeling provides a multi-parametric description of glucose metabolism in the lungs. This allows characterizing the spatial distribution of lung inflammation as well as returning the functional state of the tissues.

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

PubMed

Abdeen, Nishard; Cross, Albert; Cron, Gregory; White, Steven; Rand, Thomas; Miller, David; Santyr, Giles

2006-08-01

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases. Copyright 2006 Wiley-Liss, Inc.

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

Correlation of the apparent diffusion coefficient and the standardized uptake value in neoplastic lesions: a meta-analysis.

PubMed

Shen, Guohua; Ma, Huan; Liu, Bin; Ren, Pengwei; Kuang, Anren

2017-12-01

Diffusion-weighted imaging and fluorine-18-fluorodeoxyglucose PET are increasingly being recognized as feasible oncological techniques. The apparent diffusion coefficient (ADC) measured by diffusion-weighted imaging and the standardized uptake value (SUV) from fluorine-18-fluorodeoxyglucose PET have similar clinical applications. The aim of this study was to assess the correlation between these two parameters in various cancers. Several major databases were searched for eligible studies. The correlation coefficient (ρ) values were pooled in a random-effects model. Begg's test was used to analyze the existence of publication bias and the sources of heterogeneity were explored in subgroup analyses on the basis of study design, diagnostic method, scanning modality, and tumor type. Thirty-five articles were accepted. The pooled ρ value of all of the accepted studies was -0.30 (95% confidence interval: -0.33 to -0.27), and notable heterogeneity was present (I=69.4%, P<0.001), which indicated a relatively weak negative correlation. The pooled ρ values were -0.26, -0.33, -0.32, and -0.33 for the SUVmax/ADCmean, SUVmax/ADCmin, SUVmean/ADCmean, and SUVmean/ADCmin relationships, respectively. The study design and diagnostic method were potential sources of heterogeneity. Lung cancer showed a stronger correlation (ρ=-0.42) than head and neck cancer (ρ=-0.27), cervical cancer (ρ=-0.21), and breast cancer (ρ=-0.23). A Begg's test indicated no significant publication bias among the accepted studies (P>0.05). The two functional parameters of ADC and SUV showed a very weak inverse correlation, which may contribute toward a sophisticated characterization of tumor biology. However, the findings require further validation with trials with large samples and different tumor types.

Pulmonary uptake in indium-111-antimyosin fab fragment imaging following human cardia transplantation

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

Folke, M.; Hesse, B.; Mortensen, S.A.

1994-02-01

Recent studies suggest that cardiac uptake of {sup 111}In-labeled antimyosin monoclonal antibody may be estimated semiquantitatively by calculating a heart-to-lung activity ratio, with pulmonary uptake serving as a reference region. The authors obtained 96 {sup 111}In-antimyosin scintigraphs to monitor rejection occurrence after heart transplantation in 26 patients. On five scintigraphs, the count rate density in ROIs over the lungs was markedly higher (mean 53% higher) than that in the immediately preceding and following scintigraphs, whereas the activity in the heart was essentially unchanged. Four of these scintigraphs coincided with ongoing pulmonary infection and the fifth with an occurrence of amore » high anti-CMV titer. The mechanism of apparent nonspecific antimyosin accumulation in the lungs is uncertain, although increased capillary permeability may be one possibility. Attention should be given to activity in the lungs if this activity is used as a reference in studies of {sup 111}In-antimyosin uptake in the heart. 15 refs., 3 figs., 1 tab.« less

SU-C-207A-07: Cumulative 18F-FDG Uptake Histogram Relative to Radiation Dose Volume Histogram of Lung After IMRT Or PSPT and Their Association with Radiation Pneumonitis

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

Shusharina, N; Choi, N; Bortfeld, T

2016-06-15

Purpose: To determine whether the difference in cumulative 18F-FDG uptake histogram of lung treated with either IMRT or PSPT is associated with radiation pneumonitis (RP) in patients with inoperable stage II and III NSCLC. Methods: We analyzed 24 patients from a prospective randomized trial to compare IMRT (n=12) with vs. PSPT (n=12) for inoperable NSCLC. All patients underwent PET-CT imaging between 35 and 88 days post-therapy. Post-treatment PET-CT was aligned with planning 4D CT to establish a voxel-to-voxel correspondence between post-treatment PET and planning dose images. 18F-FDG uptake as a function of radiation dose to normal lung was obtained formore » each patient. Distribution of the standard uptake value (SUV) was analyzed using a volume histogram method. The image quantitative characteristics and DVH measures were correlated with clinical symptoms of pneumonitis. Results: Patients with RP were present in both groups: 5 in the IMRT and 6 in the PSPT. The analysis of cumulative SUV histograms showed significantly higher relative volumes of the normal lung having higher SUV uptake in the PSPT patients for both symptomatic and asymptomatic cases (VSUV=2: 10% for IMRT vs 16% for proton RT and VSUV=1: 10% for IMRT vs 23% for proton RT). In addition, the SUV histograms for symptomatic cases in PSPT patients exhibited a significantly longer tail at the highest SUV. The absolute volume of the lung receiving the dose >70 Gy was larger in the PSPT patients. Conclusion: 18F-FDG uptake – radiation dose response correlates with RP in both groups of patients by means of the linear regression slope. SUV is higher for the PSPT patients for both symptomatic and asymptomatic cases. Higher uptake after PSPT patients is explained by larger volumes of the lung receiving high radiation dose.« less

Use of diffusion-weighted magnetic resonance imaging to distinguish between lung cancer and focal inflammatory lesions: a comparison of intravoxel incoherent motion derived parameters and apparent diffusion coefficient.

PubMed

Deng, Yu; Li, Xinchun; Lei, Yongxia; Liang, Changhong; Liu, Zaiyi

2016-11-01

Background Using imaging techniques to diagnose malignant and inflammatory lesions in the lung can be challenging. Purpose To compare intravoxel incoherent motion (IVIM) and apparent diffusion coefficient (ADC) magnetic resonance imaging (MRI) analysis in their ability to discriminate lung cancer from focal inflammatory lung lesions. Material and Methods Thirty-eight patients with lung masses were included: 30 lung cancers and eight inflammatory lesions. Patients were imaged with 3.0T MRI diffusion weighted imaging (DWI) using 10 b values (range, 0-1000 s/mm 2 ). Tissue diffusivity ( D), pseudo-diffusion coefficient ( D*), and perfusion fraction ( f) were calculated using segmented biexponential analysis. ADC (total) was calculated with monoexponential fitting of the DWI data. D, D*, f, and ADC were compared between lung cancer and inflammatory lung lesions. Receiver operating characteristic analysis was performed for all DWI parameters. Results The ADC was significantly higher for inflammatory lesions than for lung cancer ([1.21 ± 0.20] × 10 -3 mm 2 /s vs. [0.97 ± 0.15] × 10 -3 mm 2 /s; P = 0.004). By IVIM, f was found to be significantly higher in inflammatory lesions than lung cancer ([46.10 ± 12.92] % vs. [29.29 ± 10.89] %; P = 0.005). There was no difference in D and D* between lung cancer and inflammatory lesions ( P = 0.747 and 0.124, respectively). f showed comparable diagnostic performance with ADC in differentiating lung cancer from inflammatory lung lesions, with areas under the curve of 0.833 and 0.826, sensitivity 80.0% and 73.3%, and specificity 75.0% and 87.5%, respectively. Conclusion The IVIM parameter f value provides comparable diagnostic performance with ADC and could be used as a surrogate marker for differentiating lung cancer from inflammatory lesions.

Diffusion Limitations in Root Uptake of Cadmium and Zinc, But Not Nickel, and Resulting Bias in the Michaelis Constant1[W][OA

PubMed Central

Degryse, Fien; Shahbazi, Afsaneh; Verheyen, Liesbeth; Smolders, Erik

2012-01-01

It has long been recognized that diffusive boundary layers affect the determination of active transport parameters, but this has been largely overlooked in plant physiological research. We studied the short-term uptake of cadmium (Cd), zinc (Zn), and nickel (Ni) by spinach (Spinacia oleracea) and tomato (Lycopersicon esculentum) in solutions with or without metal complexes. At same free ion concentration, the presence of complexes, which enhance the diffusion flux, increased the uptake of Cd and Zn, whereas Ni uptake was unaffected. Competition effects of protons on Cd and Zn uptake were observed only at a very large degree of buffering, while competition of magnesium ions on Ni uptake was observed even in unbuffered solutions. These results strongly suggest that uptake of Cd and Zn is limited by diffusion of the free ion to the roots, except at very high degree of solution buffering, whereas Ni uptake is generally internalization limited. All results could be well described by a model that combined a diffusion equation with a competitive Michaelis-Menten equation. Direct uptake of the complex was estimated to be a major contribution only at millimolar concentrations of the complex or at very large ratios of complex to free ion concentration. The true Km for uptake of Cd2+ and Zn2+ was estimated at <5 nm, three orders of magnitude smaller than the Km measured in unbuffered solutions. Published Michaelis constants for plant uptake of Cd and Zn likely strongly overestimate physiological ones and should not be interpreted as an indicator of transporter affinity. PMID:22864584

3He Diffusion MRI of the Lung

PubMed Central

Conradi, Mark S.; Yablonskiy, Dmitriy A.; Woods, Jason C.; Gierada, David S.; Jacob, Richard E.; Chang, Yulin V.; Choong, Cliff K.; Sukstanskii, Alex L.; Tanoli, Tariq; Lefrak, Stephen S.; Cooper, Joel D.

2007-01-01

Rationale and Objectives MR imaging of the restricted diffusion of laser-polarized 3He gas provides unique insights into the changes in lung microstructure in emphysema. Results We discuss measurements of ventilation (spin density), mean diffusivity, and the anisotropy of diffusion, which yields the mean acinar airway radius. In addition, the use of spatially modulated longitudinal magnetization allows diffusion to be measured over longer distances and times, with sensitivity to collateral ventilation paths. Early results are also presented for spin density and diffusivity maps made with a perfluorinated inert gas, C3F8. Methods Techniques for purging and imaging excised lungs are discussed. PMID:16253852

Computed Tomography-Based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients With Mass-like Consolidation After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

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

Dunlap, Neal E.; Yang Wensha; McIntosh, Alyson

Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET)more » CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT.« less

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.

Uptake of 2, 4-Dichlorophenoxyacetic acid by Pseudomonas fluorescens

USGS Publications Warehouse

Wedemeyer, G.A.

1966-01-01

Factors influencing the uptake of the sodium salt of 2,4-dichlorophenoxyacetic acid (2,4-D), under conditions in which no net metabolism occurred, were investigated in an effort to determine both the significance of “nonmetabolic” uptake as a potential agent in reducing pesticide levels and the mechanisms involved. Uptake of 2,4-D was affected by pH, temperature, and the presence of other organic and inorganic compounds. Uptake was more pronounced at pH values less than 6, which implies that there may be some interaction between charged groups on the cell and the ionized carboxyl group of 2,4-D. Active transport, carriermediated diffusion, passive diffusion, and adsorption were considered as possible mechanisms. Though uptake was inhibited by glucose, sodium azide, and fluorodinitrobenzene (but not by uranylion), 2,4-D was not accumulated against a concentration gradient, a necessary consequence of an active transport system, nor was isotope counterflow found to occur. Thus, carrier-mediated diffusion was finally precluded, implying that uptake probably occurs by a two-step process: sorption onto the cell wall followed by passive diffusion into the cytoplasm.

Uptake of 2,4-dichlorophenoxyacetic acid by Pseudomonas fluorescens

USGS Publications Warehouse

Wedemeyer, Gary

1966-01-01

Factors influencing the uptake of the sodium salt of 2,4-dichlorophenoxyacetic acid (2,4-D), under conditions in which no net metabolism occurred, were investigated in an effort to determine both the significance of “non-metabolic” uptake as a potential agent in reducing pesticide levels and the mechanisms involved. Uptake of 2,4-D was affected by pH, temperature, and the presence of other organic and inorganic compounds. Uptake was more pronounced at pH values less than 6, which implies that there may be some interaction between charged groups on the cell and the ionized carboxyl group of 2,4-D. Active transport, carrier-mediated diffusion, passive diffusion, and adsorption were considered as possible mechanisms. Though uptake was inhibited by glucose, sodium azide, and fluorodinitrobenzene (but not by uranyl ion), 2,4-D was not accumulated against a concentration gradient, a necessary consequence of an active transport system, nor was isotope counterflow found to occur. Thus, carrier-mediated diffusion was finally precluded, implying that uptake probably occurs by a two-step process: sorption onto the cell wall followed by passive diffusion into the cytoplasm.

The Role of Collateral Paths in Long-Range Diffusion of 3He in Lungs

PubMed Central

Conradi, Mark S.; Yablonskiy, Dmitriy A.; Woods, Jason C.; Gierada, David S.; Bartel, Seth-Emil T.; Haywood, Susan E.; Menard, Christopher

2008-01-01

Rationale and Objectives The hyperpolarized 3He long-range diffusion coefficient (LRDC) in lungs is sensitive to changes in lung structure due to emphysema, reflecting the increase in collateral paths resulting from tissue destruction. However, no clear understanding of LRDC in healthy lungs has emerged. Here we compare LRDC measured in healthy lungs with computer simulations of diffusion along the airway tree with no collateral connections. Materials and Methods Computer simulations of diffusion of spatially modulated spin magnetization were performed in computer generated, symmetric-branching models of lungs and compared with existing LRDC measurements in canine and human lungs. Results The simulations predict LRDC values of order 0.001 cm2/s, approximately 20 times smaller than the measured LRDC. We consider and rule out possible mechanisms for LRDC not included in the simulations: incomplete breath hold, cardiac motion, and passage of dissolved 3He through airway walls. However, a very low density of small (micron) holes in the airways is shown to account for the observed LRDC. Conclusion It is proposed that LRDC in healthy lungs is determined by small collateral pathways. PMID:18486004

Diffuse Lung Disease in Biopsied Children 2 to 18 Years of Age. Application of the chILD Classification Scheme.

PubMed

Fan, Leland L; Dishop, Megan K; Galambos, Csaba; Askin, Frederic B; White, Frances V; Langston, Claire; Liptzin, Deborah R; Kroehl, Miranda E; Deutsch, Gail H; Young, Lisa R; Kurland, Geoffrey; Hagood, James; Dell, Sharon; Trapnell, Bruce C; Deterding, Robin R

2015-10-01

Children's Interstitial and Diffuse Lung Disease (chILD) is a heterogeneous group of disorders that is challenging to categorize. In previous study, a classification scheme was successfully applied to children 0 to 2 years of age who underwent lung biopsies for chILD. This classification scheme has not been evaluated in children 2 to 18 years of age. This multicenter interdisciplinary study sought to describe the spectrum of biopsy-proven chILD in North America and to apply a previously reported classification scheme in children 2 to 18 years of age. Mortality and risk factors for mortality were also assessed. Patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease from 12 North American institutions were included. Demographic and clinical data were collected and described. The lung biopsies were reviewed by pediatric lung pathologists with expertise in diffuse lung disease and were classified by the chILD classification scheme. Logistic regression was used to determine risk factors for mortality. A total of 191 cases were included in the final analysis. Number of biopsies varied by center (5-49 biopsies; mean, 15.8) and by age (2-18 yr; mean, 10.6 yr). The most common classification category in this cohort was Disorders of the Immunocompromised Host (40.8%), and the least common was Disorders of Infancy (4.7%). Immunocompromised patients suffered the highest mortality (52.8%). Additional associations with mortality included mechanical ventilation, worse clinical status at time of biopsy, tachypnea, hemoptysis, and crackles. Pulmonary hypertension was found to be a risk factor for mortality but only in the immunocompetent patients. In patients 2 to 18 years of age who underwent lung biopsies for diffuse lung disease, there were far fewer diagnoses prevalent in infancy and more overlap with adult diagnoses. Immunocompromised patients with diffuse lung disease who underwent lung biopsies had less than 50% survival at time of last follow-up.

Experimental investigation and numerical simulation of 3He gas diffusion in simple geometries: implications for analytical models of 3He MR lung morphometry.

PubMed

Parra-Robles, J; Ajraoui, S; Deppe, M H; Parnell, S R; Wild, J M

2010-06-01

Models of lung acinar geometry have been proposed to analytically describe the diffusion of (3)He in the lung (as measured with pulsed gradient spin echo (PGSE) methods) as a possible means of characterizing lung microstructure from measurement of the (3)He ADC. In this work, major limitations in these analytical models are highlighted in simple diffusion weighted experiments with (3)He in cylindrical models of known geometry. The findings are substantiated with numerical simulations based on the same geometry using finite difference representation of the Bloch-Torrey equation. The validity of the existing "cylinder model" is discussed in terms of the physical diffusion regimes experienced and the basic reliance of the cylinder model and other ADC-based approaches on a Gaussian diffusion behaviour is highlighted. The results presented here demonstrate that physical assumptions of the cylinder model are not valid for large diffusion gradient strengths (above approximately 15 mT/m), which are commonly used for (3)He ADC measurements in human lungs. (c) 2010 Elsevier Inc. All rights reserved.

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

Albumin nanocapsules containing fenretinide: pre-clinical evaluation of cytotoxic activity in experimental models of human non-small cell lung cancer.

PubMed

Pignatta, Sara; Orienti, Isabella; Falconi, Mirella; Teti, Gabriella; Arienti, Chiara; Medri, Laura; Zanoni, Michele; Carloni, Silvia; Zoli, Wainer; Amadori, Dino; Tesei, Anna

2015-02-01

The present study deals with the preparation of albumin nanocapsules containing fenretinide and their evaluation in experimental models of human non-small cell lung cancer. These nanocapsules showed enhanced antitumor activity with respect to free fenretinide due to the solubilization effect of albumin on the hydrophobic drug, known to improve bioavailability. The high expression of caveolin-1 on the A549 cell surface further enhanced the antitumor activity of the nanoencapsulated fenretinide. Caveolin-1 favored albumin uptake and improved the efficacy of the fenretinide-loaded albumin nanocapsules, especially in 3-D cultures where the densely packed 3-D structures impaired drug diffusibility and severely reduced the activity of the free drug. The efficacy of the fenretinide albumin nanocapsules was further confirmed in tumor xenograft models of A549 by the significant delay in tumor progression observed with respect to control after intravenous administration of the novel formulation. This study describes the preparation of fenretinide containing albumin nanocapsules and their evaluation in experimental models of non-small cell lung cancer, showing enhanced antitumor activity compared to free fenretinide. Copyright © 2015 Elsevier Inc. All rights reserved.

Technetium-99m-HMPAO as a marker of chemical and irradiation lung injury: Experimental and clinical investigations

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

Suga, Kazuyoshi; Uchisako, Hiromichi; Nishigauchi, Kazuya

1994-09-01

The authors evaluated the ability of {sup 99m}Tc-hexamethylpropyleneamine oxime ({sup 99m}Tc-HMPAO) to serve as a sensitive marker of lung injury. Two experiment rabbit models of minimal lung injury were designed using injections of a low dose (0.05 ml/kg) of oleic acid or 50 Gy of irradiation. In addition, they clinically investigated whether patients who received chemotherapy (n = 14) or radiotherapy (n = 13) for lung cancer showed high uptake of {sup 99m}Tc-HMPAO in the lungs. Despite the minimal endothelial lesions visualized by electron microscopy (edematous changes and blebbing), in both animal models, the lungs showed high uptake of {supmore » 99m}Tc-HMPAO, which occurred rapidly within 1 min after injection. Clinically, the mean lung-to-liver ratio of {sup 99m}Tc-HMPAO activity in the patients who received chemotherapy (0.649{+-}0.185, p < 0.01) was significantly higher than that of the controls (n = 16; 0.387{+-}0.108), and all 12 patients who received more than 30 Gy of irradiation showed abnormal uptake in the irradiated lungs, despite the lack of abnormal opacities on chest CT. These findings suggest that {sup 99m}Tc-HMPAO has the potential to be a sensitive marker of chemical and irradiation lung injury. 53 refs., 5 figs., 3 tabs.« less

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.

Comparative analysis of nitrite uptake and hemoglobin-nitrite reactions in erythrocytes: sorting out uptake mechanisms and oxygenation dependencies.

PubMed

Jensen, Frank B; Rohde, Sabina

2010-04-01

Nitrite uptake into red blood cells (RBCs) precedes its intracellular reactions with hemoglobin (Hb) that forms nitric oxide (NO) during hypoxia. We investigated the uptake of nitrite and its reactions with Hb at different oxygen saturations (So(2)), using RBCs with (carp and rabbit) and without (hagfish and lamprey) anion exchanger-1 (AE1) in the membrane, with the aim to unravel the mechanisms and oxygenation dependencies of nitrite transport. Added nitrite rapidly diffused into the RBCs until equilibrium. The distribution ratio of nitrite across the membrane agreed with that expected from HNO(2) diffusion and AE1-mediated facilitated NO(2)(-) diffusion. Participation of HNO(2) diffusion was emphasized by rapid transmembrane nitrite equilibration also in the natural AE1 knockouts. Following the equilibration, nitrite was consumed by reacting with Hb, which created a continued inward diffusion controlled by intracellular reaction rates. Changes in nitrite uptake with So(2), pH, or species were accordingly explained by corresponding changes in reaction rates. In carp, nitrite uptake rates increased linearly with decreasing So(2) over the entire So(2) range. In rabbit, nitrite uptake rates were highest at intermediate So(2), producing a bell-shaped relationship with So(2). Nitrite consumption increased approximately 10-fold with a 1 unit decrease in pH, as expected from the involvement of protons in the reactions with Hb. The reaction of nitrite with deoxyhemoglobin was favored over that with oxyhemoglobin at intermediate So(2). We propose a model for RBC nitrite uptake that involves both HNO(2) diffusion and AE1-mediated transport and that explains both the present and previous (sometimes puzzling) results.

Computerized scheme for detection of diffuse lung diseases on CR chest images

NASA Astrophysics Data System (ADS)

Pereira, Roberto R., Jr.; Shiraishi, Junji; Li, Feng; Li, Qiang; Doi, Kunio

2008-03-01

We have developed a new computer-aided diagnostic (CAD) scheme for detection of diffuse lung disease in computed radiographic (CR) chest images. One hundred ninety-four chest images (56 normals and 138 abnormals with diffuse lung diseases) were used. The 138 abnormal cases were classified into three levels of severity (34 mild, 60 moderate, and 44 severe) by an experienced chest radiologist with use of five different patterns, i.e., reticular, reticulonodular, nodular, air-space opacity, and emphysema. In our computerized scheme, the first moment of the power spectrum, the root-mean-square variation, and the average pixel value were determined for each region of interest (ROI), which was selected automatically in the lung fields. The average pixel value and its dependence on the location of the ROI were employed for identifying abnormal patterns due to air-space opacity or emphysema. A rule-based method was used for determining three levels of abnormality for each ROI (0: normal, 1: mild, 2: moderate, and 3: severe). The distinction between normal lungs and abnormal lungs with diffuse lung disease was determined based on the fractional number of abnormal ROIs by taking into account the severity of abnormalities. Preliminary results indicated that the area under the ROC curve was 0.889 for the 44 severe cases, 0.825 for the 104 severe and moderate cases, and 0.794 for all cases. We have identified a number of problems and reasons causing false positives on normal cases, and also false negatives on abnormal cases. In addition, we have discussed potential approaches for improvement of our CAD scheme. In conclusion, the CAD scheme for detection of diffuse lung diseases based on texture features extracted from CR chest images has the potential to assist radiologists in their interpretation of diffuse lung diseases.

Efficient zinc uptake is critical for the ability of Pseudomonas aeruginosa to express virulence traits and colonize the human lung.

PubMed

Mastropasqua, Maria Chiara; Lamont, Iain; Martin, Lois W; Reid, David W; D'Orazio, Melania; Battistoni, Andrea

2018-07-01

We have recently shown that Pseudomonas aeruginosa, an opportunistic pathogen that chronically infects the lungs of patients with cystic fibrosis (CF) and other forms of lung disease, is extremely efficient in recruiting zinc from the environment and that this capability is required for its ability to cause acute lung infections in mice. To verify that P. aeruginosa faces zinc shortage when colonizing the lungs of human patients, we analyzed the expression of three genes that are highly induced under conditions of zinc deficiency (zrmA, dksA2 and rpmE2), in bacteria in the sputum of patients with inflammatory lung disease. All three genes were expressed in all the analyzed sputum samples to a level much higher than that of bacteria grown in zinc-containing laboratory medium, supporting the hypothesis that P. aeruginosa is under zinc starvation during lung infections. We also found that the expression of several virulence traits that play a central role in the ability of P. aeruginosa to colonize the lung is affected by disruption of the most important zinc importing systems. Virulence features dependent on zinc intake include swarming and swimming motility and the ability to form biofilms. Furthermore, alterations in zinc assimilation interfere with the synthesis of the siderophore pyoverdine, suggesting that zinc recruitment could modulate iron uptake and affect siderophore-mediated cell signaling. Our results reveal that zinc uptake is likely to play a key role in the ability of P. aeruginosa to cause chronic lung infections and strongly modulates critical virulence traits of the pathogen. Taking into account the recent discovery that zinc uptake in P. aeruginosa is promoted by the release of a small molecular weight molecule showing high affinity for zinc, our data suggest novel and effective possibilities to control lung infections by these bacteria. Copyright © 2018 Elsevier GmbH. All rights reserved.

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

Vertebral Uptake of Tc-99m Macroaggregated Albumin (MAA) with SPECT/CT Occurring in Superior Vena Cava Obstruction.

PubMed

Karls, Shawn; Hassoun, Hani; Derbekyan, Vilma

2016-09-01

A 67-year-old male presented with dyspnea for which lung scintigraphy was ordered to rule out pulmonary embolus. Planar images demonstrated abnormal midline uptake of Tc-99m macroaggregated albumin, which SPECT/CT localized to several thoracic vertebrae. Thoracic vertebral uptake on perfusion lung scintigraphy was previously described on planar imaging. Radionuclide venography and contrast-enhanced CT subsequently demonstrated superior vena cava (SVC) obstruction with collateralization through the azygous/hemiazygous system and vertebral venous plexus. SPECT/CT differentiated residual esophageal/tracheal ventilation activity, a clinically insignificant finding, from vertebral uptake indicative of SVC obstruction, a potentially life-threatening condition.

Diffuse abdominal uptake of Ga-67 citrate in a patient with hypoproteinemia

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

Kim, E.K.; Gobuty, A.; Guiterrez, C.

1983-06-01

A 3-wk-old male, with abdominal distention and severe hypoproteinemia from poor nutrition, underwent a study that showed a persistent diffuse abdominal uptake of Ga-67 citrate, indicating pyogenic or tuberculous peritonitis. However, there were no corresponding clinical or laboratory findings. After a 1-wk course of hyperalimentation with albumin, furosemide, and protein, repeat radiographs showed reduction in bowel gas. It is suggested that hypoproteinemia should be considered as a possibility in the differential diagnosis when there is diffuse abdominal uptake of Ga-67 citrate, with careful clinical correlation. Possible mechanism of Ga-67 uptake in the peritoneal cavity is suggested.

Diffusion of Molecular Diagnostic Lung Cancer Tests: A Survey of German Oncologists

PubMed Central

Steffen, Julius Alexander

2014-01-01

This study was aimed at examining the diffusion of diagnostic lung cancer tests in Germany. It was motivated by the high potential of detecting and targeting oncogenic drivers. Recognizing that the diffusion of diagnostic tests is a conditio sine qua non for the success of personalized lung cancer therapies, this study analyzed the diffusion of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tests in Germany. Qualitative and quantitative research strategies were combined in a mixed-method design. A literature review and subsequent Key Opinion Leader interviews identified a set of qualitative factors driving the diffusion process, which were then translated into an online survey. The survey was conducted among a sample of 961 oncologists (11.34% response rate). The responses were analyzed in a multiple linear regression which identified six statistically significant factors driving the diffusion of molecular diagnostic lung cancer tests: reimbursement, attitude towards R&D, information self-assessment, perceived attitudes of colleagues, age and test-pathway strategies. Besides the important role of adequate reimbursement and relevant guidelines, the results of this study suggest that an increasing usage of test-pathway strategies, especially in an office-based setting, can increase the diffusion of molecular diagnostic lung cancer tests in the future. PMID:25562146

Fetal lung apparent diffusion coefficient measurement using diffusion-weighted MRI at 3 Tesla: Correlation with gestational age.

PubMed

Afacan, Onur; Gholipour, Ali; Mulkern, Robert V; Barnewolt, Carol E; Estroff, Judy A; Connolly, Susan A; Parad, Richard B; Bairdain, Sigrid; Warfield, Simon K

2016-12-01

To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T). Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated. When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks. We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655. © 2016 International Society for Magnetic Resonance in Medicine.

Diffuse abdominal gallium-67 citrate uptake in salmonella infections

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

Garty, I.; Koren, A.

1987-11-01

Two pediatric patients with salmonella infections (one with typhoid fever and the second with salmonella C2 gastroenteritis), had a diffuse abdominal uptake of Ga-67 citrate. The possible explanation for this finding is discussed. Salmonella infection should be included as a cause in the differential diagnosis of diffuse accumulation of Ga-67 citrate.

Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury

PubMed Central

Mondrinos, Mark J.; Knight, Linda C.; Kennedy, Paul A.; Wu, Jichuan; Kauffman, Matthew; Baker, Sandy T.; Wolfson, Marla R.

2015-01-01

Sepsis and sepsis-induced lung injury remain a leading cause of death in intensive care units. We identified protein kinase C-δ (PKCδ) as a critical regulator of the acute inflammatory response and demonstrated that PKCδ inhibition was lung-protective in a rodent sepsis model, suggesting that targeting PKCδ is a potential strategy for preserving pulmonary function in the setting of indirect lung injury. In this study, whole-body organ biodistribution and pulmonary cellular distribution of a transactivator of transcription (TAT)–conjugated PKCδ inhibitory peptide (PKCδ-TAT) was determined following intratracheal (IT) delivery in control and septic [cecal ligation and puncture (CLP)] rats to ascertain the impact of disease pathology on biodistribution and efficacy. There was negligible lung uptake of radiolabeled peptide upon intravenous delivery [<1% initial dose (ID)], whereas IT administration resulted in lung retention of >65% ID with minimal uptake in liver or kidney (<2% ID). IT delivery of a fluorescent-tagged (tetramethylrhodamine-PKCδ-TAT) peptide demonstrated uniform spatial distribution and cellular uptake throughout the peripheral lung. IT delivery of PKCδ-TAT at the time of CLP surgery significantly reduced PKCδ activation (tyrosine phosphorylation, nuclear translocation and cleavage) and acute lung inflammation, resulting in improved lung function and gas exchange. Importantly, peptide efficacy was similar when delivered at 4 hours post-CLP, demonstrating therapeutic relevance. Conversely, spatial lung distribution and efficacy were significantly impaired at 8 hours post-CLP, which corresponded to marked histopathological progression of lung injury. These studies establish a functional connection between peptide spatial distribution, inflammatory histopathology in the lung, and efficacy of this anti-inflammatory peptide. PMID:26243739

Synchronous diffuse large B-cell lymphoma of the stomach and small cell lung carcinoma: A case report.

PubMed

Li, Jia; Zhou, Changli; Liu, Wanqi; Sun, Xun; Meng, Xiangwei

2017-12-01

The synchronous occurrence of lung cancer in patients with gastric neoplasms is relatively uncommon, especially the cases of synchronous coexistence of small cell lung carcinoma and diffuse large B-cell lymphoma of the stomach. We encountered a case of synchronous primary small cell lung carcinoma and diffuse large B-cell lymphoma of the stomach. A 63-year-old patient with a 7.5 × 5.09 cm mass in the superior lobe of the right lung diagnosed with small cell lung cancer and synchronous diffuse large B-cell lymphoma of the stomach. The diseases were diagnosed by the pathological biopsy and immunohistochemical methods. As the patient received CHOP chemotherapy, pulmonary function deterioraed. Etoposide was added to the chemotherapy. However, after the first treatment, chest computed tomography showed that the mass in the superior lobe of the right lung had increased to 8.5 × 5.2 cm. This report draws attention to the fact that the treatment of synchronous tumors is a challenge. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Using satellite-derived optical thickness to assess the influence of clouds on terrestrial carbon uptake

Treesearch

S.J. Cheng; A.L. Steiner; D.Y. Hollinger; G. Bohrer; K.J. Nadelhoffer

2016-01-01

Clouds scatter direct solar radiation, generating diffuse radiation and altering the ratio of direct to diffuse light. If diffuse light increases plant canopy CO2 uptake, clouds may indirectly influence climate by altering the terrestrial carbon cycle. However, past research primarily uses proxies or qualitative categories of clouds to connect...

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.

Advances in modeling sorption and diffusion of moisture in porous reactive materials.

PubMed

Harley, Stephen J; Glascoe, Elizabeth A; Lewicki, James P; Maxwell, Robert S

2014-06-23

Water-vapor-uptake experiments were performed on a silica-filled poly(dimethylsiloxane) (PDMS) network and modeled by using two different approaches. The data was modeled by using established methods and the model parameters were used to predict moisture uptake in a sample. The predictions are reasonably good, but not outstanding; many of the shortcomings of the modeling are discussed. A high-fidelity modeling approach is derived and used to improve the modeling of moisture uptake and diffusion. Our modeling approach captures the physics and kinetics of diffusion and adsorption/desorption, simultaneously. It predicts uptake better than the established method; more importantly, it is also able to predict outgassing. The material used for these studies is a filled-PDMS network; physical interpretations concerning the sorption and diffusion of moisture in this network are discussed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sea-level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m.

PubMed

Wagner, P D; Simonson, T S; Wei, G; Wagner, H E; Wuren, T; Qin, G; Yan, M; Ge, R L

2015-11-01

What is the topic of this review? Recent developments link relatively lower hemoglobin concentration in Tibetans at high altitude to exercise capacity and components of oxygen transport. What advances does it highlight? Haemoglobin concentration (ranging from 15.2 to 22.9 g dl(-1) ) in Tibetan males was negatively associated with peak oxygen (O2 ) uptake per kilogram, cardiac output and muscle O2 diffusion conductance. Most variance in the peak O2 uptake per kilogram of Tibetan males was attributed to cardiac output, muscle diffusional conductance and arterial partial pressure of CO2 . The mechanisms underlying these differences in oxygen transport in Tibetans require additional analyses. Despite residence at >4000 m above sea level, many Tibetan highlanders, unlike Andean counterparts and lowlanders at altitude, exhibit haemoglobin concentration ([Hb]) within the typical sea-level range. Genetic adaptations in Tibetans are associated with this relatively low [Hb], yet the functional relevance of the lower [Hb] remains unknown. To address this, we examined each major step of the oxygen transport cascade [ventilation (VE), cardiac output (QT) and diffusional conductance in lung (DL) and muscle (DM)] in Tibetan males at maximal exercise on a cycle ergometer. Ranging from 15.2 to 22.9 g dl(-1) , [Hb] was negatively associated with peak O2 uptake per kilogram (r = -0.45, P < 0.05) and both cardiac output (QT/kg: r = -0.54, P < 0.02) and muscle O2 diffusion conductance (DM/kg: r = -0.44, P < 0.05) but not ventilation, arterial partial pressure of O2 or pulmonary diffusing capacity. Most variance in peak O2 uptake per kilogram was attributed to QT, DM and arterial partial pressure of CO2 (r(2)  = 0.90). In summary, lack of polycythaemia in Tibetans is associated with increased exercise capacity, which is explained by elevated cardiac, muscle and, to a small extent, ventilatory responses rather than pulmonary gas exchange. Whether lower [Hb] is the cause or result of these changes in O2 transport or is causally unrelated will require additional study. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Glucose Transporter-1 Distribution in Fibrotic Lung Disease

PubMed Central

Malide, Daniela; Yao, Jianhua; Nathan, Steven D.; Rosas, Ivan O.; Gahl, William A.; Moss, Joel; Gochuico, Bernadette R.

2013-01-01

Background: [18F]-2-fluoro-2-deoxyglucose (FDG)-PET scan uptake is increased in areas of fibrosis and honeycombing in patients with idiopathic pulmonary fibrosis (IPF). Glucose transporter-1 (Glut-1) is known to be the main transporter for FDG. There is a paucity of data regarding the distribution of Glut-1 and the cells responsible for FDG binding in fibrotic lung diseases. Methods: We applied immunofluorescence to localize Glut-1 in normal, IPF, and Hermansky-Pudlak syndrome (HPS) pulmonary fibrosis lung tissue specimens as well as an array of 19 different lung neoplasms. In addition, we investigated Glut-1 expression in inflammatory cells from BAL fluid (BALF) from healthy volunteers, subjects with IPF, and subjects with HPS pulmonary fibrosis. Results: In normal lung tissue, Glut-1 immunoreactivity was seen on the surface of erythrocytes. In tissue sections from fibrotic lung diseases (IPF and HPS pulmonary fibrosis), Glut-1 immunoreactivity was present on the surface of erythrocytes and inflammatory cells. BALF inflammatory cells from healthy control subjects showed no immunoreactivity; BALF cells from subjects with IPF and HPS pulmonary fibrosis showed Glut-1 immunoreactivity associated with neutrophils and alveolar macrophages. Conclusions: Glut-1 transporter expression in normal lung is limited to erythrocytes. In fibrotic lung, erythrocytes and inflammatory cells express Glut-1. Together, these data suggest that FDG-PET scan uptake in IPF could be explained by enhanced inflammatory and erythrocytes uptake due to neovascularization seen in IPF and not an upregulation of metabolic rate in pneumocytes. Thus, FDG-PET scan may detect inflammation and neovascularization in lung fibrosis. PMID:23699745

Point-particle method to compute diffusion-limited cellular uptake.

PubMed

Sozza, A; Piazza, F; Cencini, M; De Lillo, F; Boffetta, G

2018-02-01

We present an efficient point-particle approach to simulate reaction-diffusion processes of spherical absorbing particles in the diffusion-limited regime, as simple models of cellular uptake. The exact solution for a single absorber is used to calibrate the method, linking the numerical parameters to the physical particle radius and uptake rate. We study the configurations of multiple absorbers of increasing complexity to examine the performance of the method by comparing our simulations with available exact analytical or numerical results. We demonstrate the potential of the method to resolve the complex diffusive interactions, here quantified by the Sherwood number, measuring the uptake rate in terms of that of isolated absorbers. We implement the method in a pseudospectral solver that can be generalized to include fluid motion and fluid-particle interactions. As a test case of the presence of a flow, we consider the uptake rate by a particle in a linear shear flow. Overall, our method represents a powerful and flexible computational tool that can be employed to investigate many complex situations in biology, chemistry, and related sciences.

An exposure system for measuring nasal and lung uptake of vapors in rats

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

Dahl, A.R.; Brookins, L.K.; Gerde, P.

1995-12-01

Inhaled gases and vapors often produce biological damage in the nasal cavity and lower respiratory tract. The specific site within the respirator tract at which a gas or vapor is absorbed strongly influences the tissues at risk to potential toxic effects; to predict or to explain tissue or cell specific toxicity of inhaled gases or vapors, the sites at which they are absorbed must be known. The purpose of the work reported here was to develop a system for determining nose and lung absorption of vapors in rats, an animal commonly used in inhalation toxicity studies. In summary, the exposuremore » system described allows us to measure in the rate: (1) nasal absorption and desorption of vapors; (2) net lung uptake of vapors; and (3) the effects of changed breathing parameters on vapor uptake.« less

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

Levin, M.; McLeod, R.; Young, Q.

Pneumocystis pneumonia presented in a homosexual with fever, a normal chest radiograph, and pulmonary gallium uptake. Bronchial washings yielded Mycobaterium tuberculosis, but despite antituberculosis therapy he remained febrile, and gallium uptake in the lung increased. Subsequently, silver stain of transbronchial lung biopsy obtained 2 months earlier at the time that tuberculosis was diagnosed showed many Pneumocystis cysts in alveolar spaces. In contrast to Pneumocystis cysts in infected lung tissue from other humans, our patient's Pneumocystis cysts reacted more avidly with antiserum to rat Pneumocystis than with antiserum to human pneumocystis, raising the possibility that organisms that infect humans may havemore » varied surface antigenic properties.« less

Molecular mobility in the monolayers of foam films stabilized by porcine lung surfactant.

PubMed Central

Lalchev, Z I; Todorov, R K; Christova, Y T; Wilde, P J; Mackie, A R; Clark, D C

1996-01-01

Certain physical properties of a range of foam film types that are believed to exist in vivo in the lung have been investigated. The contribution of different lung surfactant components found in porcine lung surfactant to molecular surface diffusion in the plane of foam films has been investigated for the first time. The influence of the type and thickness of black foam films, temperature, electrolyte concentration, and extract composition on surface diffusion has been studied using the fluorescence recovery after photobleaching technique. Fluorescent phospholipid probe molecules in foam films stabilized by porcine lung surfactant samples or their hydrophobic extracts consisting of surfactant lipids and hydrophobic lung surfactant proteins, SP-B and SP-C, exhibited more rapid diffusion than observed in films of its principal lipid component alone, L-alpha-phosphatidylcholine dipalmitoyl. This effect appears to be due to contributions from minor lipid components present in the total surfactant lipid extracts. The minor lipid components influence the surface diffusion in foam films both by their negative charge and by lowering the phase transition temperature of lung surfactant samples. In contrast, the presence of high concentrations of the hydrophillic surfactant protein A (SP-A) and non-lung-surfactant proteins in the sample reduced the diffusion coefficient (D) of the lipid analog in the adsorbed layer of the films. Hysteresis behavior of D was observed during temperature cycling, with the cooling curve lying above the heating curve. However, in cases where some surface molecular aggregation and surface heterogeneity were observed during cooling, the films became more rigid and molecules at the interfaces became immobilized. The thickness, size, capillary pressure, configuration, and composition of foam films of lung surfactant prepared in vitro support their investigation as realistic structural analogs of the surface films that exist in vivo in the lung. Compared to other models currently in use, foam films provide new opportunities for studying the properties and function of physiologically important alveolar surface films. Images FIGURE 1 FIGURE 2 PMID:8913597

Do nanoparticles provide a new opportunity for diagnosis of distal airspace disease?

PubMed Central

Löndahl, Jakob; Jakobsson, Jonas KF; Broday, David M; Aaltonen, H Laura; Wollmer, Per

2017-01-01

There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4–1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide (DL,CO), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology. PMID:28053522

Do nanoparticles provide a new opportunity for diagnosis of distal airspace disease?

PubMed

Löndahl, Jakob; Jakobsson, Jonas Kf; Broday, David M; Aaltonen, H Laura; Wollmer, Per

There is a need for efficient techniques to assess abnormalities in the peripheral regions of the lungs, for example, for diagnosis of pulmonary emphysema. Considerable scientific efforts have been directed toward measuring lung morphology by studying recovery of inhaled micron-sized aerosol particles (0.4-1.5 µm). In contrast, it is suggested that the recovery of inhaled airborne nanoparticles may be more useful for diagnosis. The objective of this work is to provide a theoretical background for the use of nanoparticles in measuring lung morphology and to assess their applicability based on a review of the literature. Using nanoparticles for studying distal airspace dimensions is shown to have several advantages over other aerosol-based methods. 1) Nanoparticles deposit almost exclusively by diffusion, which allows a simpler breathing maneuver with minor artifacts from particle losses in the oropharyngeal and upper airways. 2) A higher breathing flow rate can be utilized, making it possible to rapidly inhale from residual volume to total lung capacity (TLC), thereby eliminating the need to determine the TLC before measurement. 3) Recent studies indicate better penetration of nanoparticles than micron-sized particles into poorly ventilated and diseased regions of the lungs; thus, a stronger signal from the abnormal parts is expected. 4) Changes in airspace dimensions have a larger impact on the recovery of nanoparticles. Compared to current diagnostic techniques with high specificity for morphometric changes of the lungs, computed tomography and magnetic resonance imaging with hyperpolarized gases, an aerosol-based method is likely to be less time consuming, considerably cheaper, simpler to use, and easier to interpret (providing a single value rather than an image that has to be analyzed). Compared to diagnosis by carbon monoxide ( D L,CO ), the uptake of nanoparticles in the lung is not affected by blood flow, hemoglobin concentration or alterations of the alveolar membranes, but relies only on lung morphology.

Diffuse reflectance spectra measured in vivo in human tissues during Photofrin-mediated pleural photodynamic therapy

NASA Astrophysics Data System (ADS)

Finlay, Jarod C.; Zhu, Timothy C.; Dimofte, Andreea; Friedberg, Joseph S.; Hahn, Stephen M.

2006-02-01

Optimal delivery of light in photodynamic therapy (PDT) requires not only optimal placement and power of light sources, but knowledge of the dynamics of light propagation in the tissue being treated and in the surrounding normal tissue, and of their respective accumulations of sensitizer. In an effort to quantify both tissue optical properties and sensitizer distribution, we have measured fluorescence emission and diffuse reflectance spectra at the surface of a variety of tissue types in the thoracic cavities of human patients. The patients studied here were enrolled in Phase II clinical trials of Photofrin-mediated PDT for the treatment of non-small cell lung cancer and cancers with pleural effusion. Patients were given Photofrin at dose of 2 mg per kg body weight 24 hours prior to treatment. Each patient received surgical resection of the affected lung and pleura. Patients received intracavity PDT at 630nm to a dose of 30 J/cm2, as determined by isotropic detectors sutured to the cavity walls. We measured the diffuse reflectance spectra before and after PDT in various positions within the cavity, including tumor, diaphragm, pericardium, skin, and chest wall muscle in 5 patients. The measurements we acquired using a specially designed fiber optic-based probe consisting of one fluorescence excitation fiber, one white light delivery fiber, and 9 detection fibers spaced at distances from 0.36 to 7.8 mm from the source, all of which are imaged via a spectrograph onto a CCD, allowing measurement of radially-resolved diffuse reflectance and fluorescence spectra. The light sources for these two measurements (a 403-nm diode laser and a halogen lamp, respectively) were blocked by computer-controlled shutters, allowing sequential fluorescence, reflectance, and background acquisition. The diffuse reflectance was analyzed to determine the absorption and scattering spectra of the tissue and from these, the concentration and oxygenation of hemoglobin and the local drug uptake. The total hemoglobin concentration in normal tissues varied from 50 to 300 µM, and the oxygen saturation was generally above 60%. One tumor measured exhibited higher hemoglobin concentration and lower saturation.

Uptake of reovirus serotype 1 by the lungs from the bloodstream is mediated by the viral hemagglutinin

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

Verdin, E.M.; Lynn, S.P.; Fields, B.N.

1988-02-01

The authors used the mammalian reoviruses to determine the molecular basis of the clearance of a virus from the bloodstream by specific organs. Reovirus serotypes 1 (T1) and 3 (T3) were radiolabeled with ({sup 35}S)methionine or {sup 125}I, and the viruses were injected intravenously into weanling rats. The distribution of radioactivity within the animals was determined at various times after the injection. Both viruses were cleared rapidly from the bloodstream and concentrated in different organs. Reovirus T1 was found predominantly in the lungs and liver, whereas T3 was found predominantly in the liver, with very little virus in the lungs.more » Using intertypic reassortants, they determined that the T1 S1 gene, which encodes the viral hemagglutinin ({sigma}1 protein), is responsible for the difference in uptake of T1 and T3 by the lungs. The genetic mapping was extended by using several approaches. (i) T1 subjected to limited proteolytic digestion with chymotrypsin was cleared efficiently by the lungs despite the removal of {sigma}3 and digestion of {mu}1C to {delta}. (ii) Uptake of T1 by the lungs was totally inhibited by incubation of T1 with an anti-{sigma}1 monoclonal antibody or its Fab fragment before injection. (iii) A reovirus T1 variant in the {sigma}1 protein was poorly taken up by the lungs. These data indicate that clearance of reovirus from the bloodstream by the lungs is dependent on the presence of the T1 or {sigma}1 protein.« less

DW MRI at 3.0 T versus FDG PET/CT for detection of malignant pulmonary tumors.

PubMed

Zhang, Jian; Cui, Long-Biao; Tang, Xing; Ren, Xin-Ling; Shi, Jie-Ran; Yang, Hai-Nan; Zhang, Yan; Li, Zhi-Kui; Wu, Chang-Gui; Jian, Wen; Zhao, Feng; Ti, Xin-Yu; Yin, Hong

2014-02-01

Emerging evidence suggests that diffusion-weighted magnetic resonance imaging (DW MRI) could be useful for tumor detection with N and M staging of lung cancer in place of fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). DW MRI at 3.0 T and FDG PET/CT were performed before therapy in 113 patients with pulmonary nodules. Mean apparent diffusion coefficient (ADC), maximal standardized uptake value (SUVmax ) and Ki-67 scores were assessed. Quantitatively, specificity and accuracy of ADC (91.7 and 92.9%, respectively) were significantly higher than those of SUVmax (66.7 and 77.9% respectively, p < 0.05), although sensitivity was not significantly different between them (93.5 and 83.1%, p > 0.05). Qualitatively, sensitivity, specificity and accuracy of DW MRI (96.1, 83.3 and 92.0%, respectively) were also not significantly different from that of FDG PET/CT (88.3, 83.3 and 86.7%, respectively, p > 0.05). Significant negative correlation was found between Ki-67 score and ADC (r = -0.66, p < 0.05), ADC and SUVmax (r = -0.37, p < 0.05), but not between Ki-67 score and SUVmax (r = -0.11, p > 0.05). In conclusion, quantitative and qualitative assessments for detection of malignant pulmonary tumors with DW MRI at 3.0 T are superior to those with FDG PET/CT. Furthermore, ADC could predict the malignancy of lung cancer. © 2013 UICC.

The effects of collagen-rich extracellular matrix on the intracellular delivery of glycol chitosan nanoparticles in human lung fibroblasts.

PubMed

Yhee, Ji Young; Yoon, Hong Yeol; Kim, Hyunjoon; Jeon, Sangmin; Hergert, Polla; Im, Jintaek; Panyam, Jayanth; Kim, Kwangmeyung; Nho, Richard Seonghun

2017-01-01

Recent progress in nanomedicine has shown a strong possibility of targeted therapy for obstinate chronic lung diseases including idiopathic pulmonary fibrosis (IPF). IPF is a fatal lung disease characterized by persistent fibrotic fibroblasts in response to type I collagen-rich extracellular matrix. As a pathological microenvironment is important in understanding the biological behavior of nanoparticles, in vitro cellular uptake of glycol chitosan nanoparticles (CNPs) in human lung fibroblasts was comparatively studied in the presence or absence of type I collagen matrix. Primary human lung fibroblasts from non-IPF and IPF patients (n=6/group) showed significantly increased cellular uptake of CNPs (>33.6-78.1 times) when they were cultured on collagen matrix. To elucidate the underlying mechanism of enhanced cellular delivery of CNPs in lung fibroblasts on collagen, cells were pretreated with chlorpromazine, genistein, and amiloride to inhibit clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis, respectively. Amiloride pretreatment remarkably reduced the cellular uptake of CNPs, suggesting that lung fibroblasts mainly utilize the macropinocytosis-dependent mechanism when interacted with collagen. In addition, the internalization of CNPs was predominantly suppressed by a phosphoinositide 3-kinase (PI3K) inhibitor in IPF fibroblasts, indicating that enhanced PI3K activity associated with late-stage macropinocytosis can be particularly important for the enhanced cellular delivery of CNPs in IPF fibroblasts. Our study strongly supports the concept that a pathological microenvironment which surrounds lung fibroblasts has a significant impact on the intracellular delivery of nanoparticles. Based on the property of enhanced intracellular delivery of CNPs when fibroblasts are made to interact with a collagen-rich matrix, we suggest that CNPs may have great potential as a drug-carrier system for targeting fibrotic lung fibroblasts.

The effects of collagen-rich extracellular matrix on the intracellular delivery of glycol chitosan nanoparticles in human lung fibroblasts

PubMed Central

Yhee, Ji Young; Yoon, Hong Yeol; Kim, Hyunjoon; Jeon, Sangmin; Hergert, Polla; Im, Jintaek; Panyam, Jayanth; Kim, Kwangmeyung; Nho, Richard Seonghun

2017-01-01

Recent progress in nanomedicine has shown a strong possibility of targeted therapy for obstinate chronic lung diseases including idiopathic pulmonary fibrosis (IPF). IPF is a fatal lung disease characterized by persistent fibrotic fibroblasts in response to type I collagen-rich extracellular matrix. As a pathological microenvironment is important in understanding the biological behavior of nanoparticles, in vitro cellular uptake of glycol chitosan nanoparticles (CNPs) in human lung fibroblasts was comparatively studied in the presence or absence of type I collagen matrix. Primary human lung fibroblasts from non-IPF and IPF patients (n=6/group) showed significantly increased cellular uptake of CNPs (>33.6–78.1 times) when they were cultured on collagen matrix. To elucidate the underlying mechanism of enhanced cellular delivery of CNPs in lung fibroblasts on collagen, cells were pretreated with chlorpromazine, genistein, and amiloride to inhibit clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis, respectively. Amiloride pretreatment remarkably reduced the cellular uptake of CNPs, suggesting that lung fibroblasts mainly utilize the macropinocytosis-dependent mechanism when interacted with collagen. In addition, the internalization of CNPs was predominantly suppressed by a phosphoinositide 3-kinase (PI3K) inhibitor in IPF fibroblasts, indicating that enhanced PI3K activity associated with late-stage macropinocytosis can be particularly important for the enhanced cellular delivery of CNPs in IPF fibroblasts. Our study strongly supports the concept that a pathological microenvironment which surrounds lung fibroblasts has a significant impact on the intracellular delivery of nanoparticles. Based on the property of enhanced intracellular delivery of CNPs when fibroblasts are made to interact with a collagen-rich matrix, we suggest that CNPs may have great potential as a drug-carrier system for targeting fibrotic lung fibroblasts. PMID:28860768

Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

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

Glowniak, J.V.; Turner, F.E.; Gray, L.L.

1989-07-01

Iodine-123 metaiodobenzylguanidine ((/sup 123/I)MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with (/sup 123/I)MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiacmore » transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy.« less

n-Hexane metabolism in occupationally exposed workers.

PubMed Central

Mutti, A; Falzoi, M; Lucertini, S; Arfini, G; Zignani, M; Lombardi, S; Franchini, I

1984-01-01

Lung uptake and excretion of n-hexane were studied in ten workers in a shoe factory. Simultaneous samples of inhaled and alveolar air were collected with the aid of a Rhan-Otis valve, personal samplers, and charcoal tubes. Alveolar excretion was monitored during a six hour postexposure period. Uptake was calculated from lung ventilation, the retention coefficient, and environmental concentrations. The amount of exhaled n-hexane was calculated from the decay curve. According to the experimental data, alveolar retention was about 25% of the inhaled n-hexane, corresponding to a lung uptake of about 17%. The postexposure alveolar excretion was about 10% of the total uptake. The main metabolites of n-hexane were identified and measured by capillary GC/MS in spot urine samples collected before, at the end, and 15 hours after the same working shift. Urinary concentrations were low, though related to n-hexane in the air. 2,5-Hexanedione in the end of shift samples gave the best estimate of overall exposure. About 3 mg/g creatinine of 2,5-hexanedione would correspond to about 50 ppm of n-hexane in the air (mean daily exposure). PMID:6498115

In vivo tomographic imaging of lung colonization of tumour in mouse with simultaneous fluorescence and X-ray CT.

PubMed

Zhang, Bin; Gao, Fuping; Wang, Mengjiao; Cao, Xu; Liu, Fei; Wang, Xin; Luo, Jianwen; Wang, Guangzhi; Bai, Jing

2014-01-01

Non-invasive in vivo imaging of diffuse and wide-spread colonization within the lungs, rather than distinct solid primary tumors, is still a challenging work. In this work, a lung colonization mouse model bearing A549 human lung tumor was simultaneously scanned by a dual-modality fluorescence molecular tomography (FMT) and X-ray computed tomography (CT) system in vivo. A two steps method which incorporates CT structural information into the FMT reconstruction procedure is employed to provide concurrent anatomical and functional information. By using the target-specific fluorescence agent, the fluorescence tomographic results show elevated fluorescence intensity deep within the lungs which is colonized with diffuse and wide-spread tumors. The results were confirmed with ex vivo fluorescence reflectance imaging and histological examination of the lung tissues. With FMT reconstruction combined with the CT information, the dual-modality FMT/micro-CT system is expected to offer sensitive and noninvasive imaging of diffuse tumor colonization within the lungs in vivo. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multilayer Spheroids To Quantify Drug Uptake and Diffusion in 3D

PubMed Central

2015-01-01

There is a need for new quantitative in vitro models of drug uptake and diffusion to help assess drug toxicity/efficacy as well as new more predictive models for drug discovery. We report a three-dimensional (3D) multilayer spheroid model and a new algorithm to quantitatively study uptake and inward diffusion of fluorescent calcein via gap junction intercellular communication (GJIC). When incubated with calcein-AM, a substrate of the efflux transporter P-glycoprotein (Pgp), spheroids from a variety of cell types accumulated calcein over time. Accumulation decreased in spheroids overexpressing Pgp (HEK-MDR) and was increased in the presence of Pgp inhibitors (verapamil, loperamide, cyclosporin A). Inward diffusion of calcein was negligible in spheroids that lacked GJIC (OVCAR-3, SK-OV-3) and was reduced in the presence of an inhibitor of GJIC (carbenoxolone). In addition to inhibiting Pgp, verapamil and loperamide, but not cyclosporin A, inhibited inward diffusion of calcein, suggesting that they also inhibit GJIC. The dose response curves of verapamil’s inhibition of Pgp and GJIC were similar (IC50: 8 μM). The method is amenable to many different cell types and may serve as a quantitative 3D model that more accurately replicates in vivo barriers to drug uptake and diffusion. PMID:24641346

Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome

PubMed Central

Güldner, Andreas; Braune, Anja; Ball, Lorenzo; Silva, Pedro L.; Samary, Cynthia; Insorsi, Angelo; Huhle, Robert; Rentzsch, Ines; Becker, Claudia; Oehme, Liane; Andreeff, Michael; Vidal Melo, Marcos F.; Winkler, Tilo; Pelosi, Paolo; Rocco, Patricia R. M.; Kotzerke, Jörg; de Abreu, Marcelo Gama

2016-01-01

Objective Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome. Design Laboratory investigation. Setting University-hospital research facility. Subjects Ten pigs (five per group; 34.7–49.9 kg) Interventions Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve driving pressure comparable with volutrauma (atelectrauma). The right (control) lung was kept on continuous positive airway pressure of 20 cm H2O, and Co2 was partially removed extracorporeally. Measurements and Main Results Regional lung aeration, specific [18F]fluorodeoxyglucose uptake rate, and perfusion were assessed using computed and positron emission tomography. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in the ventilated lung compared with atelectrauma (median [interquartile range], 0.017 [0.014–0.025] vs 0.013 min−1 [0.010–0.014min−1]; p < 0.01), mainly in central lung regions. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in ventilator-induced lung injury versus control lung (0.017 [0.014–0.025] vs 0.011 min−1 [0.010–0.016min−1]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood fraction at similar perfusion and increased normally as well as hyper-aerated lung compartments and tidal hyperaeration. Atelectrauma yielded higher poorly and nonaerated lung compartments, and tidal recruitment. Driving pressure increased in atelectrauma. Conclusions In this model of acute respiratory distress syndrome, volutrauma promoted higher lung inflammation than atelectrauma at comparable low tidal volume and lower driving pressure, suggesting that static stress and strain are major determinants of ventilator-induced lung injury. PMID:27035236

Directional Multi-scale Modeling of High-Resolution Computed Tomography (HRCT) Lung Images for Diffuse Lung Disease Classification

NASA Astrophysics Data System (ADS)

Vo, Kiet T.; Sowmya, Arcot

A directional multi-scale modeling scheme based on wavelet and contourlet transforms is employed to describe HRCT lung image textures for classifying four diffuse lung disease patterns: normal, emphysema, ground glass opacity (GGO) and honey-combing. Generalized Gaussian density parameters are used to represent the detail sub-band features obtained by wavelet and contourlet transforms. In addition, support vector machines (SVMs) with excellent performance in a variety of pattern classification problems are used as classifier. The method is tested on a collection of 89 slices from 38 patients, each slice of size 512x512, 16 bits/pixel in DICOM format. The dataset contains 70,000 ROIs of those slices marked by experienced radiologists. We employ this technique at different wavelet and contourlet transform scales for diffuse lung disease classification. The technique presented here has best overall sensitivity 93.40% and specificity 98.40%.

Role of collateral paths in long-range diffusion in lungs

PubMed Central

Bartel, Seth-Emil T.; Haywood, Susan E.; Woods, Jason C.; Chang, Yulin V.; Menard, Christopher; Yablonskiy, Dmitriy A.; Gierada, David S.; Conradi, Mark S.

2010-01-01

The long-range apparent diffusion coefficient (LRADC) of 3He gas in lungs, measured over times of several seconds and distances of 1–3 cm, probes the connections between the airways. Previous work has shown the LRADC to be small in health and substantially elevated in emphysema, reflecting tissue destruction, which is known to create collateral pathways. To better understand what controls LRADC, we report computer simulations and measurements of 3He gas diffusion in healthy lungs. The lung is generated with a random algorithm using well-defined rules, yielding a three-dimensional set of nodes or junctions, each connected by airways to one parent node and two daughters; airway dimensions are taken from published values. Spin magnetization in the simulated lung is modulated sinusoidally, and the diffusion equation is solved to 1,000 s. The modulated magnetization decays with a time constant corresponding to an LRADC of ~0.001 cm2/s, which is smaller by a factor of ~20 than the values in healthy lungs measured here and previously in vivo and in explanted lungs. It appears that collateral gas pathways, not present in the simulations, are functional in healthy lungs; they provide additional and more direct routes for long-range motion than the canonical airway tree. This is surprising, inasmuch as collateral ventilation is believed to be physiologically insignificant in healthy lungs. We discuss the effect on LRADC of small collateral connections through airway walls and rule out other possible mechanisms. The role of collateral paths is supported by measurements of smaller LRADC in pigs, where collateral ventilation is known to be smaller. PMID:18292298

The utility of electron microscopy in detecting asbestos fibers and particles in BALF in diffuse lung diseases.

PubMed

Kido, Takashi; Morimoto, Yasuo; Yatera, Kazuhiro; Ishimoto, Hiroshi; Ogoshi, Takaaki; Oda, Keishi; Yamasaki, Kei; Kawanami, Toshinori; Shimajiri, Shohei; Mukae, Hiroshi

2017-04-21

In patients with diffuse lung diseases, differentiating occupational lung diseases from other diseases is clinically important. However, the value of assessing asbestos and particles in bronchoalveolar lavage fluid (BALF) in diffuse lung diseases by electron microscopy (EM) remains unclear. We evaluated the utility of EM in detecting asbestos fibers and particles in patients with diffuse lung diseases. The BALF specimens of 107 patients with diffuse lung diseases were evaluated. First, detection of asbestos by EM and light microscopy (LM) were compared. Second, the detection of asbestos using surgically obtained lung tissues of 8 of 107 patients were compared with the results of EM and LM in BALF. Third, we compared the results of mineralogical components of particles in patients with (n = 48) and without (n = 59) a history of occupational exposure to inorganic dust. BALF asbestos were detected in 11 of 48 patients with a history of occupational exposure by EM; whereas asbestos as asbestos bodies (ABs) were detected in BALF in 4 of these 11 patients by LM. Eight of 107 patients in whom lung tissue samples were surgically obtained, EM detected BALF asbestos at a level of >1,000 fibers/ml in all three patients who had ABs in lung tissue samples by LM at a level of >1,000 fibers/g. The BALF asbestos concentration by EM and in lung tissue by LM were positively correlated. The particle fractions of iron and phosphorus were increased in patients with a history of occupational exposure and both correlated with a history of occupational exposure by a multiple regression analysis. EM using BALF seemed to be superior to LM using BALF and displayed a similar sensitivity to LM using surgically-obtained lung tissue samples in the detection of asbestos. Our results also suggest that detection of elements, such as iron and phosphorus in particles, is useful for evaluating occupational exposure. We conclude that the detection of asbestos and iron and phosphorus in particles in BALF by EM is very useful for the evaluation of occupational exposure.

Gas uptake and chemical aging of semisolid organic aerosol particles

PubMed Central

Shiraiwa, Manabu; Ammann, Markus; Koop, Thomas; Pöschl, Ulrich

2011-01-01

Organic substances can adopt an amorphous solid or semisolid state, influencing the rate of heterogeneous reactions and multiphase processes in atmospheric aerosols. Here we demonstrate how molecular diffusion in the condensed phase affects the gas uptake and chemical transformation of semisolid organic particles. Flow tube experiments show that the ozone uptake and oxidative aging of amorphous protein is kinetically limited by bulk diffusion. The reactive gas uptake exhibits a pronounced increase with relative humidity, which can be explained by a decrease of viscosity and increase of diffusivity due to hygroscopic water uptake transforming the amorphous organic matrix from a glassy to a semisolid state (moisture-induced phase transition). The reaction rate depends on the condensed phase diffusion coefficients of both the oxidant and the organic reactant molecules, which can be described by a kinetic multilayer flux model but not by the traditional resistor model approach of multiphase chemistry. The chemical lifetime of reactive compounds in atmospheric particles can increase from seconds to days as the rate of diffusion in semisolid phases can decrease by multiple orders of magnitude in response to low temperature or low relative humidity. The findings demonstrate that the occurrence and properties of amorphous semisolid phases challenge traditional views and require advanced formalisms for the description of organic particle formation and transformation in atmospheric models of aerosol effects on air quality, public health, and climate. PMID:21690350

Effect of Tumor Microenvironment on Selective Uptake of Boric Acid in HepG2 Human Hepatoma Cells.

PubMed

Bai, Yu-Chi; Hsia, Yu-Chun; Lin, Yu-Ting; Chen, Kuan-Hao; Chou, Fong-In; Yang, Chia-Min; Chuang, Yung-Jen

2017-11-01

Feasibility and efficacy of boric acid (BA)-mediated boron neutron capture therapy (BNCT) was first demonstrated by eliminating hepatocellular carcinoma (HCC) in a rat model. Furthermore, selective uptake of BA by liver tumor cells was shown in a rabbit model. To gain further insight, this study aimed to investigate the mechanisms of transportation and selective uptake of BA in HepG2 liver tumor cells. Transportation of BA in HepG2 cells was analyzed by time-course assays and by analyzing the rate of diffusion versus the concentration of BA. The effect of different tumor conditions on BA uptake was studied by treating HepG2 cells with 25 μg 10 B/ml BA under different concentrations of glucose, at different pH and in the presence of water-soluble cholesterol. HepG2 cells mainly uptake BA by simple diffusion. Cell membrane permeability may also contribute to tumor-specific uptake of BA. The selective uptake of BA was achieved primarily by diffusion, while other factors, such as low pH and increased membrane fluidity, which are hallmarks of HCC, might further enhance BA uptake. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Lung Hot Spot Without Corresponding Computed Tomography Abnormality on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography: Artifactual or Real, Iatrogenic or Pathologic?

PubMed

Liu, Yiyan

Focal lung uptake without corresponding lesions or abnormalities on computed tomography (CT) scan poses a dilemma in the interpretation of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). A limited number of case reports have previously suggested an artifactual or iatrogenic nature of the uptake. In the present study, 8 relevant cases were included within a retrospective search of the database. Medical records were reviewed for follow-up radiological and pathologic information. In 7 of 8 cases with focal increased FDG uptake but no corresponding lesions or abnormalities on CT scan, the lung hot spots were artifactual or iatrogenic upon follow-up diagnostic chest CT or repeated PET/CT or both the scans. Microemboli were most likely a potential cause of the pulmonary uptake, with or without partial paravenous injection. One case in the series had a real pulmonary lesion demonstrated on follow-up PET/CT scans and on surgical pathology, although the initial integrated CT and follow-up diagnostic chest CT scans revealed negative findings to demonstrate pulmonary abnormalities corresponding to the hot spot on the PET scan. In conclusion, the finding of a lung hot spot in the absence of anatomical abnormality on FDG PET/CT was most likely artifactual or iatrogenic, but it might also represent a real pulmonary lesion. Nonvisualization of anatomical abnormality could be because of its small size and position directly overlying a segmental vessel. Further image follow-up is necessary and important to clarify the nature of the uptake. Copyright © 2017 Elsevier Inc. All rights reserved.

Gallium-67 activity in bronchoalveolar lavage fluid in sarcoidosis

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

Trauth, H.A.; Heimes, K.; Schubotz, R.

1986-01-01

Roentgenograms and gallium-67 scans and gallium-67 counts of BAL fluid samples, together with differential cell counts, have proved to be useful in assessing activity and lung involvement in sarcoidosis. In active pulmonary sarcoidosis gallium-67 scans are usually positive. Quantitation of gallium-67 uptake in lung scans, however, may be difficult. Because gallium-67 uptake and cell counts in BAL fluid may be correlated, we set out to investigate gallium-67 activity in BAL fluid recovered from patient of different groups. Sixteen patients with recently diagnosed and untreated sarcoidosis, nine patients with healthy lungs, and five patients with CFA were studied. Gallium-67 uptake ofmore » the lung, gallium-67 activity in the lavage fluid, SACE and LACE levels, and alpha 1-AT activity were measured. Significantly more gallium-67 activity was found in BAL fluid from sarcoidosis patients than in that from CFA patients (alpha = .001) or patients with healthy lungs (alpha = .001). Gallium-67 activity in BAL fluid could be well correlated with the number of lymphocytes in BAL fluid, but poorly with the number of macrophages. Subjects with increased levels of SACE or serum alpha 1-AT showed higher lavage gallium-67 activity than did normals, but no correlation could be established. High gallium-67 activity in lavage fluid may be correlated with acute sarcoidosis or physiological deterioration; low activity denotes change for the better. The results show that gallium-67 counts in BAL fluid reflects the intensity of gallium-67 uptake and thus of activity of pulmonary sarcoidosis.« less

Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung.

PubMed

Groneberg, D A; Eynott, P R; Döring, F; Dinh, Q Thai; Oates, T; Barnes, P J; Chung, K F; Daniel, H; Fischer, A

2002-01-01

Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the beta-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics.

Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung

PubMed Central

Groneberg, D; Eynott, P; Doring, F; Thai, D; Oates, T; Barnes, P; Chung, K; Daniel, H; Fischer, A

2002-01-01

Background: Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Methods: Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the ß-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. Results: PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative D-Ala-L-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. Conclusions: These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics. PMID:11809991

Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients.

PubMed

Mazzuco, Adriana; Medeiros, Wladimir Musetti; Sperling, Milena Pelosi Rizk; de Souza, Aline Soares; Alencar, Maria Clara Noman; Arbex, Flávio Ferlin; Neder, José Alberto; Arena, Ross; Borghi-Silva, Audrey

2015-01-01

In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); however, it is unknown if static lung volumes and lung diffusion capacity negatively impacts HRV responses. We investigated whether impairment of static lung volumes and lung diffusion capacity could be related to HRV indices in patients with moderate to severe COPD. Sixteen sedentary males with COPD were enrolled in this study. Resting blood gases, static lung volumes, and lung diffusion capacity for carbon monoxide (DLCO) were measured. The RR interval (RRi) was registered in the supine, standing, and seated positions (10 minutes each) and during 4 minutes of a respiratory sinus arrhythmia maneuver (M-RSA). Delta changes (Δsupine-standing and Δsupine-M-RSA) of the standard deviation of normal RRi, low frequency (LF, normalized units [nu]) and high frequency (HF [nu]), SD1, SD2, alpha1, alpha2, and approximate entropy (ApEn) indices were calculated. HF, LF, SD1, SD2, and alpha1 deltas significantly correlated with forced expiratory volume in 1 second, DLCO, airway resistance, residual volume, inspiratory capacity/total lung capacity ratio, and residual volume/total lung capacity ratio. Significant and moderate associations were also observed between LF/HF ratio versus total gas volume (%), r=0.53; LF/HF ratio versus residual volume, %, r=0.52; and HF versus total gas volume (%), r=-0.53 (P<0.05). Linear regression analysis revealed that ΔRRi supine-M-RSA was independently related to DLCO (r=-0.77, r (2)=0.43, P<0.05). Responses of HRV indices were more prominent during M-RSA in moderate to severe COPD. Moreover, greater lung function impairment was related to poorer heart rate dynamics. Finally, impaired lung diffusion capacity was related to an altered parasympathetic response in these patients.

Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders

PubMed Central

Kaarteenaho, Riitta; Kinnula, Vuokko L.

2011-01-01

It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal. PMID:21637367

Relaxation and diffusion of perfluorocarbon gas mixtures with oxygen for lung MRI

NASA Astrophysics Data System (ADS)

Chang, Yulin V.; Conradi, Mark S.

2006-08-01

We report measurements of free diffusivity D0 and relaxation times T1 and T2 for pure C 2F 6 and C 3F 8 and their mixtures with oxygen. A simplified relaxation theory is presented and used to fit the data. The results enable spatially localized relaxation time measurements to determine the local gas concentration in lung MR images, so the free diffusivity D0 is then known. Comparison of the measured diffusion to D0 will express the extent of diffusion restriction and allow the local surface-to-volume ratio to be found.

Morphological Pulmonary Diffusion Capacity for Oxygen of Burmese Pythons (Python molurus): a Comparison of Animals in Healthy Condition and with Different Pulmonary Infections.

PubMed

Starck, J M; Weimer, I; Aupperle, H; Müller, K; Marschang, R E; Kiefer, I; Pees, M

2015-11-01

A qualitative and quantitative morphological study of the pulmonary exchange capacity of healthy and diseased Burmese pythons (Python molurus) was carried out in order to test the hypothesis that the high morphological excess capacity for oxygen exchange in the lungs of these snakes is one of the reasons why pathological processes extend throughout the lung parenchyma and impair major parts of the lungs before clinical signs of respiratory disease become apparent. Twenty-four Burmese pythons (12 healthy and 12 diseased) were included in the study. A stereology-based approach was used to quantify the lung parenchyma using computed tomography. Light microscopy was used to quantify tissue compartments and the respiratory exchange surface, and transmission electron microscopy was used to measure the thickness of the diffusion barrier. The morphological diffusion capacity for oxygen of the lungs and the anatomical diffusion factor were calculated. The calculated anatomical diffusion capacity was compared with published values for oxygen consumption of healthy snakes, and the degree to which the exchange capacity can be obstructed before normal physiological function is impaired was estimated. Heterogeneous pulmonary infections result in graded morphological transformations of pulmonary parenchyma involving lymphocyte migration into the connective tissue and thickening of the septal connective tissue, increasing thickness of the diffusion barrier and increasing transformation of the pulmonary epithelium into a columnar pseudostratified or stratified epithelium. The transformed epithelium developed by hyperplasia of ciliated cells arising from the tip of the faveolar septa and by hyperplasia of type II pneumocytes. These results support the idea that the lungs have a remarkable overcapacity for oxygen consumption and that the development of pulmonary disease continuously reduces the capacity for oxygen consumption. However, due to the overcapacity of the lungs, this reduction does not result in clinical signs and disease can progress unrecognized for an extended period. Copyright © 2015 Elsevier Ltd. All rights reserved.

Removal of 5-hydroxytryptamine in the pulmonary circulation of rat isolated lungs

PubMed Central

Alabaster, Valerie A.; Bakhle, Y. S.

1970-01-01

1. Rat isolated lungs perfused via the pulmonary artery with Krebs solution removed 92% of the 5-hydroxytryptamine (5-HT) infused through it. This degree of removal was independent of concentration in the range from 5 to 100 g/ml. 2. The removal of 5-HT by the lungs was inhibited by amitriptyline and desmethylimipramine (10-6-10-5M). 3. The monoamine oxidase inhibitors, mebanazine and iproniazid (10-6-10-5M), inhibited the initial removal slightly, but their main effect was to preserve the 5-HT taken up and this 5-HT slowly reappeared in the effluent from the lungs. Tranylcypromine (5 × 10-7-10-6M) showed a combination of amitriptyline-like and mebanazine-like effects on the 5-HT removal in rat lung. 4. Experiments with 3H-5-HT showed that although under normal conditions only 10% of the radioactivity appeared in the lung effluent as 5-HT within the first 5 min, the rest of radioactivity administered could be recovered in the effluent over 50 min as a metabolite, probably 5-hydroxyindoleacetic acid. 5. The following amines were without effect on the removal of 5-HT by rat lungs: noradrenaline (6 × 10-7M), normetanephrine (5 × 10-6M), metaraminol (10-6M), reserpine (10-6-10-5M) and phenoxybenzamine (10-5M). 6. We conclude that the removal of 5-HT by rat lungs involves a process of uptake and metabolism rather than one of uptake and storage, but this process is not the catecholamine Uptake2. The cells involved in this process might be either capillary endothelial cells or septal cells. PMID:5497795

A NOVEL TECHNIQUE FOR QUANTITATIVE ESTIMATION OF UPTAKE OF DIESEL EXHAUST PARTICLES BY LUNG CELLS

EPA Science Inventory

While airborne particulates like diesel exhaust particulates (DEP) exert significant toxicological effects on lungs, quantitative estimation of accumulation of DEP inside lung cells has not been reported due to a lack of an accurate and quantitative technique for this purpose. I...

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.

PubMed

Quaife, Samantha L; Ruparel, Mamta; Beeken, Rebecca J; McEwen, Andy; Isitt, John; Nolan, Gary; Sennett, Karen; Baldwin, David R; Duffy, Stephen W; Janes, Samuel M; Wardle, Jane

2016-04-20

Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number: ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015.

Solubility of indium-tin oxide in simulated lung and gastric fluids: Pathways for human intake.

PubMed

Andersen, Jens Christian Østergård; Cropp, Alastair; Paradise, Diane Caroline

2017-02-01

From being a metal with very limited natural distribution, indium (In) has recently become disseminated throughout the human society. Little is known of how In compounds behave in the natural environment, but recent medical studies link exposure to In compounds to elevated risk of respiratory disorders. Animal tests suggest that exposure may lead to more widespread damage in the body, notably the liver, kidneys and spleen. In this paper, we investigate the solubility of the most widely used In compound, indium-tin oxide (ITO) in simulated lung and gastric fluids in order to better understand the potential pathways for metals to be introduced into the bloodstream. Our results show significant potential for release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal fluid) and digestive tract, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree) is very low. Our study confirms that ITO is likely to remain as solid particles in the upper parts of the lungs, but that particles are likely to slowly dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung, this environment is likely to provide the major route for uptake of In and Sn from inhaled ITO nano- and microparticles. Although dissolution through digestion may also lead to some uptake, the much shorter residence time is likely to lead to much lower risk of uptake. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

PubMed

Sarduy, M R; García, I; Coca, M A; Perera, A; Torres, L A; Valenzuela, C M; Baladrón, I; Solares, M; Reyes, V; Hernández, I; Perera, Y; Martínez, Y M; Molina, L; González, Y M; Ancízar, J A; Prats, A; González, L; Casacó, C A; Acevedo, B E; López-Saura, P A; Alonso, D F; Gómez, R; Perea-Rodríguez, S E

2015-05-12

We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens. Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.

Variation in Extracellular Detoxification Is a Link to Different Carcinogenicity among Chromates in Rodent and Human Lungs.

PubMed

Krawic, Casey; Luczak, Michal W; Zhitkovich, Anatoly

2017-09-18

Inhalation of soluble chromium(VI) is firmly linked with higher risks of lung cancer in humans. However, comparative studies in rats have found a high lung tumorigenicity for moderately soluble chromates but no tumors for highly soluble chromates. These major species differences remain unexplained. We investigated the impact of extracellular reducers on responses of human and rat lung epithelial cells to different Cr(VI) forms. Extracellular reduction of Cr(VI) is a detoxification process, and rat and human lung lining fluids contain different concentrations of ascorbate and glutathione. We found that reduction of chromate anions in simulated lung fluids was principally driven by ascorbate with only minimal contribution from glutathione. The addition of 500 μM ascorbate (∼rat lung fluid concentration) to culture media strongly inhibited cellular uptake of chromate anions and completely prevented their cytotoxicity even at otherwise lethal doses. While proportionally less effective, 50 μM extracellular ascorbate (∼human lung fluid concentration) also decreased uptake of chromate anions and their cytotoxicity. In comparison to chromate anions, uptake and cytotoxicity of respirable particles of moderately soluble CaCrO 4 and SrCrO 4 were much less sensitive to suppression by extracellular ascorbate, especially during early exposure times and in primary bronchial cells. In the absence of extracellular ascorbate, chromate anions and CaCrO 4 /SrCrO 4 particles produced overall similar levels of DNA double-stranded breaks, with less soluble particles exhibiting a slower rate of breakage. Our results indicate that a gradual extracellular dissolution and a rapid internalization of calcium chromate and strontium chromate particles makes them resistant to detoxification outside the cells, which is extremely effective for chromate anions in the rat lung fluid. The detoxification potential of the human lung fluid is significant but much lower and insufficient to provide a threshold-type dose dependence for soluble chromates.

Pulmonary uptake of morphine (M)

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

Roerig, D.L.; Bunke, S.S.; Kotrly, K.J.

Previously the authors reported less than 5% of M was taken up during the first pass through the human lung. The low uptake of this basic lipophilic amine was further investigated in a single pass isolated perfused rat lung (IPL) in comparison to uptake of radiolabelled H/sub 2/O, antipyrine (A), aminopyrine (AM), nicotine (N) and phenylethylamine (P). The IPL was perfused for 5 min with each drug (5nmol/ml) and effluent collected in 10 sec fractions. Pulmonary extraction was calculated using indocyanine green dye as a non-extractable reference indicator. Accumulation of all compounds in the IPL reached an apparent equilibrium withinmore » 4 min. At equilibrium lung/perfusate conc. ratios for H/sub 2/O, A, AM, N, P and M were 1.04, 0.84, 0.85, 1.44, 2.57 and 1.13 respectively. The time course of M uptake differed from the other compounds since initial extraction of M was low (23%) compared to 75%, 53%, 35%, 82% and 86% for H/sub 2/O, A, AM, N and P respectively. Also, the half time to equilibrium for M was longer (50 sec) compared to 18, 21, 26, 19 and 22 sec for H/sub 2/O, A, AM, N and P respectively. The low initial pulmonary extraction of M compared to these compounds followed by greater M extraction during the remainder of drug infusion suggests uptake mechanisms for M different than the flow limited uptake for water and other basic amine drugs.« less

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

Extraosseus uptake of F-18 fluoride in the primary malignancy and cerebral metastasis in a case of non-small-cell lung cancer.

PubMed

Li, Yuxin; Tafti, Bashir A; Shaba, Wisam; Berenji, Gholam R

2011-07-01

A 68-year-old man with history of heavy smoking was admitted for increasing falls during the past 4 weeks. Chest x-ray revealed a right upper lobe mass. Biopsy demonstrated poorly differentiated non-small-cell carcinoma. F-18 fluoride positron emission tomography/computer tomography (PET/CT) was performed to evaluate bone metastasis. Review of the sectional PET images demonstrated extraosseous fluoride uptake in the primary lung mass, as well as ring-shaped fluoride uptake in the cerebral metastatic lesion. Neither of these lesions demonstrated calcifications on CT images. The patient received radiation treatment of the brain metastasis after F-18 fluoride PET/CT study.

Deposition of ultrafine (nano) particles in the human lung.

PubMed

Asgharian, Bahman; Price, Owen T

2007-10-01

Increased production of industrial devices constructed with nanostructured materials raises the possibility of environmental and occupational human exposure with consequent adverse health effects. Ultrafine (nano) particles are suspected of having increased toxicity due to their size characteristics that serve as carrier transports. For this reason, it is critical to refine and improve existing deposition models in the nano-size range. A mathematical model of nanoparticle transport by airflow convection, axial diffusion, and convective mixing (dispersion) was developed in realistic stochastically generated asymmetric human lung geometries. The cross-sectional averaged convective-diffusion equation was solved analytically to find closed-form solutions for particle concentration and losses per lung airway. Airway losses were combined to find lobar, regional, and total lung deposition. Axial transport by diffusion and dispersion was found to have an effect on particle deposition. The primary impact was in the pulmonary region of the lung for particles larger than 10 nm in diameter. Particles below 10 nm in diameter were effectively removed from the inhaled air in the tracheobronchial region with little or no penetration into the pulmonary region. Significant variation in deposition was observed when different asymmetric lung geometries were used. Lobar deposition was found to be highest in the left lower lobe. Good agreement was found between predicted depositions of ultrafine (nano) particles with measurements in the literature. The approach used in the proposed model is recommended for more realistic assessment of regional deposition of diffusion-dominated particles in the lung, as it provides a means to more accurately relate exposure and dose to lung injury and other biological responses.

Isopycnal mixing by mesoscale eddies significantly impacts oceanic anthropogenic carbon uptake

NASA Astrophysics Data System (ADS)

Gnanadesikan, Anand; Pradal, Marie-Aude; Abernathey, Ryan

2015-06-01

Anthropogenic carbon dioxide uptake varies across Earth System Models for reasons that have remained obscure. When varied within a single model, the lateral eddy mixing coefficient ARedi produces a range of uptake similar to the modeled range. The highest uptake, resulting from a simulation with a constant ARedi of 2400 m2/s, simulates 15% more historical carbon uptake than a model with ARedi = 400 m2/s. A sudden doubling in carbon dioxide produces a 21% range in carbon uptake across the models. Two spatially dependent representations of ARedi produce uptake that lies in the middle of the range of constant values despite predicting very large values in the subtropical gyres. One-dimensional diffusive models of the type used for integrated assessments can be fit to the simulations, with ARedi accounting for a substantial fraction of the effective vertical diffusion. Such models, however, mask significant regional changes in stratification and biological carbon storage.

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.

Wolf in Sheep's Clothing: Primary Lung Cancer Mimicking Benign Entities.

PubMed

Snoeckx, Annemie; Dendooven, Amélie; Carp, Laurens; Desbuquoit, Damien; Spinhoven, Maarten J; Lauwers, Patrick; Van Schil, Paul E; van Meerbeeck, Jan P; Parizel, Paul M

2017-10-01

Lung cancer is the most common cancer worldwide. On imaging, it typically presents as mass or nodule. Recognition of these typical cases is often straightforward, whereas diagnosis of uncommon manifestations of primary lung cancer is far more challenging. Lung cancer can mimic a variety of benign entities, including pneumonia, lung abscess, postinfectious scarring, atelectasis, a mediastinal mass, emphysema and granulomatous diseases. Correlation with previous history, clinical and biochemical parameters is necessary in the assessment of these cases, but often aspecific and inconclusive. Whereas 18 F-fluorodeoxyglucose ( 18 F-FDG) Positron Emission Tomography is the cornerstone in staging of lung cancer, its role in diagnosis of these uncommon manifestations is less straightforward since benign entities can present with increased 18 F-FDG-uptake and, on the other hand, a number of these uncommon lung cancer manifestations do not exhibit increased uptake. Chest Computed Tomography (CT) is the imaging modality of choice for both lesion detection and characterization. In this pictorial review we present the wide imaging spectrum of CT-findings as well as radiologic-pathologic correlation of these uncommon lung cancer manifestations. Knowledge of the many faces of lung cancer is crucial for early diagnosis and subsequent treatment. A multidisciplinary approach in these cases is mandatory. Copyright © 2017 Elsevier B.V. All rights reserved.

Localization of lung fields in HRCT images using a deep convolution neural network

NASA Astrophysics Data System (ADS)

Kumar, Abhishek; Agarwala, Sunita; Dhara, Ashis Kumar; Mukhopadhyay, Sudipta; Nandi, Debashis; Garg, Mandeep; Khandelwal, Niranjan; Kalra, Naveen

2018-02-01

Lung field segmentation is a prerequisite step for the development of a computer-aided diagnosis system for interstitial lung diseases observed in chest HRCT images. Conventional methods of lung field segmentation rely on a large gray value contrast between lung fields and surrounding tissues. These methods fail on lung HRCT images with dense and diffused pathology. An efficient prepro- cessing could improve the accuracy of segmentation of pathological lung field in HRCT images. In this paper, a convolution neural network is used for localization of lung fields in HRCT images. The proposed method provides an optimal bounding box enclosing the lung fields irrespective of the presence of diffuse pathology. The performance of the proposed algorithm is validated on 330 lung HRCT images obtained from MedGift database on ZF and VGG networks. The model achieves a mean average precision of 0.94 with ZF net and a slightly better performance giving a mean average precision of 0.95 in case of VGG net.

The Rate and Clinical Significance of Incidental Thyroid Uptake as Detected by Gallium-68 DOTATATE Positron Emission Tomography/Computed Tomography

PubMed Central

Nockel, Pavel; Millo, Corina; Keutgen, Xavier; Klubo-Gwiezdzinska, Joanna; Shell, Jasmine; Patel, Dhaval; Nilubol, Naris; Herscovitch, Peter; Sadowski, Samira M.

2016-01-01

Background: Gallium-68 (Ga-68) DOTATATE is a radiolabeled peptide–imaging modality that targets the somatostatin receptor (SSTR), especially subtype 2 (SSTR2). Benign and malignant thyroid tumors have been observed to express SSTR. The aim of this study was to evaluate the frequency and clinical significance of incidental atypical thyroid uptake as detected by Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT). Methods: A retrospective analysis was conducted of a prospective study in which 237 patients underwent Ga-68 DOTATATE PET/CT as part of a work-up for metastatic and unknown primary neuroendocrine tumors. The types of uptake in the thyroid gland (focal/diffuse) and maximum standardized uptake value (SUVmax) levels were evaluated and compared with the background uptake in the liver and salivary glands. Results: Of 237 patients, 26 (11%) had atypical thyroid uptake as detected by Ga-68 DOTATATE PET/CT. There were no significant clinical or biochemical variables associated with atypical thyroid uptake. Fourteen (54%) patients had positive focal uptake, and 12 (46%) patients had diffuse uptake. Of the 14 patients with atypical focal uptake, 10 (71%) had thyroid nodules on the corresponding side, as detected by anatomic imaging. Three of 10 patients (21%) were found to have papillary thyroid cancer, and seven (70%) had adenomatoid nodules. Of the 12 patients with diffuse increased uptake, six (50%) had a history of hypothyroidism, five (42%) had chronic lymphocytic thyroiditis, and one (8%) had nontoxic multinodular goiter. Conclusions: Patients with an incidental focal abnormal thyroid uptake on Ga-68 DOTATATE PET/CT scan should have further clinical evaluation to exclude a diagnosis of thyroid cancer. PMID:27094616

Diffusion-weighted magnetic resonance imaging for assessment of lung lesions: repeatability of the apparent diffusion coefficient measurement.

PubMed

Bernardin, L; Douglas, N H M; Collins, D J; Giles, S L; O'Flynn, E A M; Orton, M; deSouza, N M

2014-02-01

To establish repeatability of apparent diffusion coefficients (ADCs) acquired from free-breathing diffusion-weighted magnetic resonance imaging (DW-MRI) in malignant lung lesions and investigate effects of lesion size, location and respiratory motion. Thirty-six malignant lung lesions (eight patients) were examined twice (1- to 5-h interval) using T1-weighted, T2-weighted and axial single-shot echo-planar DW-MRI (b = 100, 500, 800 s/mm(2)) during free-breathing. Regions of interest around target lesions on computed b = 800 s/mm(2) images by two independent observers yielded ADC values from maps (pixel-by-pixel fitting using all b values and a mono-exponential decay model). Intra- and inter-observer repeatability was assessed per lesion, per patient and by lesion size (> or <2 cm) or location. ADCs were similar between observers (mean ± SD, 1.15 ± 0.28 × 10(-3) mm(2)/s, observer 1; 1.15 ± 0.29 × 10(-3) mm(2)/s, observer 2). Intra-observer coefficients of variation of the mean [median] ADC per lesion and per patient were 11% [11.4%], 5.7% [5.7%] for observer 1 and 9.2% [9.5%], 3.9% [4.7%] for observer 2 respectively; inter-observer values were 8.9% [9.3%] (per lesion) and 3.0% [3.7%] (per patient). Inter-observer coefficient of variation (CoV) was greater for lesions <2 cm (n = 20) compared with >2 cm (n = 16) (10.8% vs 6.5% ADCmean, 11.3% vs 6.7% ADCmedian) and for mid (n = 14) vs apical (n = 9) or lower zone (n = 13) lesions (13.9%, 2.7%, 3.8% respectively ADCmean; 14.2%, 2.8%, 4.7% respectively ADCmedian). Free-breathing DW-MRI of whole lung achieves good intra- and inter-observer repeatability of ADC measurements in malignant lung tumours. • Diffusion-weighted MRI of the lung can be satisfactorily acquired during free-breathing • DW-MRI demonstrates high contrast between primary and metastatic lesions and normal lung • Apparent diffusion coefficient (ADC) measurements in lung tumours are repeatable and reliable • ADC offers potential in assessing response in lung metastases in clinical trials.

Monosaccharide uptake by erythrocytes of the embryonic and adult chicken.

PubMed

Ingermann, R L; Stock, M K; Metcalfe, J; Bissonnette, J M

1985-01-01

Rates of monosaccharide uptake by adult and 10-18 day old embryonic chicken erythrocytes were quantitated. The rate of carrier-mediated, stereospecific transport decreased 28% from day 10 to day 14 of incubation and was unchanged thereafter. At no time, however, did the rate of carrier-mediated transport by embryonic erythrocytes differ significantly from that of the adult cells. The rate of transfer by simple diffusion was 3-5 fold faster in embryonic than in adult erythrocytes. Uptake by simple diffusion decreased slightly as the embryo developed. Chronic hyperoxic incubation (70% O2) had little influence on total monosaccharide uptake by embryonic erythrocytes.

Uptake of the antileishmania drug tafenoquine follows a sterol-dependent diffusion process in Leishmania.

PubMed

Manzano, José Ignacio; Carvalho, Luis; García-Hernández, Raquel; Poveda, José Antonio; Ferragut, José Antonio; Castanys, Santiago; Gamarro, Francisco

2011-11-01

The present study was designed to elucidate the mechanism of tafenoquine uptake in Leishmania and its sterol dependence. Because tafenoquine is a fluorescent compound, spectrofluorimetric analysis allowed us to monitor its uptake by Leishmania promastigotes and intracellular amastigotes, and to evaluate the effect of temperature, energy and H+ gradient on drug entry. The influence of sterols on tafenoquine uptake in Leishmania parasites was determined in experiments using sterol-depleting agents such as methyl-β-cyclodextrin or cholesterol oxidase. Tafenoquine exhibited fast entry kinetics into Leishmania in an energy-independent, but pH- and temperature-dependent, non-saturable process. Furthermore, sterol depletion decreased tafenoquine uptake. These findings suggest that Leishmania takes up tafenoquine by a diffusion process and that decreases in membrane sterol content may induce a decrease in drug uptake.

Plants may alter competition by modifying nutrient bioavailability in rhizosphere: a modeling approach.

PubMed

Raynaud, Xavier; Jaillard, Benoît; Leadley, Paul W

2008-01-01

Plants modify nutrient availability by releasing chemicals in the rhizosphere. This change in availability induced by roots (bioavailability) is known to improve nutrient uptake by individual plants releasing such compounds. Can this bioavailability alter plant competition for nutrients and under what conditions? To address these questions, we have developed a model of nutrient competition between plant species based on mechanistic descriptions of nutrient diffusion, plant exudation, and plant uptake. The model was parameterized using data of the effects of root citrate exudation on phosphorus availability. We performed a sensitivity analysis for key parameters to test the generality of these effects. Our simulations suggest the following. (1) Nutrient uptake depends on the number of roots when nutrients and exudates diffuse little, because individual roots are nearly independent in terms of nutrient supply. In this case, bioavailability profits only species with exudates. (2) Competition for nutrients depends on the spatial arrangement of roots when nutrients diffuse little but exudates diffuse widely. (3) Competition for nutrients depends on the nutrient uptake capacity of roots when nutrients and exudates diffuse widely. In this case, bioavailability profits all species. Mechanisms controlling competition for bioavailable nutrients appear to be diverse and strongly depend on soil, nutrient, and plant properties.

[Function of alveoles as a result of evolutionary development of respiratory system in mammals].

PubMed

Ivanov, K P

2013-01-01

Reaction of hemoglobin oxygenation is known to occur for 40 femtoseconds (40 x 10(-15) s). However, the process of oxygen diffusion to hemoglobin under physiologic conditions decelerated this reaction approximately billion times. In mammalian lungs, blood is moving at a high rate and in a relatively high amount. The human lung mass is as low as 600 g, but the complete cardiac output approaches 6 1/min. In rat, from 20 to 40 ml of blood is passed for q min through the lung whose mass is about 1.5 g. Such blood flow rate is possible, as in lungs of high animals there exists a dense network of relatively large microvessels with diameter from 20 to 40 microm and more. In spite of a large volume and a high blood flow rate hampering oxygen diffusion, the complete blood oxygenation occurs in lung alveoli. This is due to peculiar mechanisms that facilitate markedly the oxygen diffusion and that developed in alveoli of mammals in the course of many million years of evolution of their respiratory system. Thus, alveolus is not a bubble with air, but a complex tool of fight with inertness of diffusion. It is interesting that in lungs of the low vertebrates, neither such system of blood vessels nor alveoli exist, and their blood flow rate is much lower than in mammals.

A high 18F-FDOPA uptake is associated with a slow growth rate in diffuse Grade II-III gliomas.

PubMed

Isal, Sibel; Gauchotte, Guillaume; Rech, Fabien; Blonski, Marie; Planel, Sophie; Chawki, Mohammad B; Karcher, Gilles; Marie, Pierre-Yves; Taillandier, Luc; Verger, Antoine

2018-04-01

In diffuse Grade II-III gliomas, a high 3,4-dihydroxy-6-( 18 F)-fluoro-L-phenylalanine ( 18 F-FDOPA) positron emission tomography (PET) uptake, with a standardized uptake value (SUV max )/contralateral brain tissue ratio greater than 1.8, was previously found to be consistently associated with the presence of an isocitrate dehydrogenase (IDH) mutation, whereas this mutation is typically associated with a better prognosis. This pilot study was aimed to ascertain the prognostic value of this high 18 F-FDOPA uptake in diffuse Grade II-III gliomas with regard to the velocity of diameter expansion (VDE), which represents an established landmark of better prognosis when below 4 mm per year. 20 patients (42 ± 10 years, 10 female) with newly-diagnosed diffuse Grade II-III gliomas (17 with IDH mutation) were retrospectively included. All had a 18 F-FDOPA PET, quantified with SUV max ratio, along with a serial MRI enabling VDE determination. SUV max ratio was above 1.8 in 5 patients (25%) all of whom had a VDE <4 mm/year (100%) and IDH mutation (100%). Moreover, a SUV max ratio above 1.8 was associated with higher rates of VDE <4 mm/year in the overall population (45 vs 0%, p = 0.04) and also in the subgroup of patients with IDH mutation (45 vs 0%, p = 0.10). This pilot study shows that in diffuse Grade II-III gliomas, a high 18 F-FDOPA uptake would be predictive of low tumour growth, with a different prognostic significance than IDH mutation. Advances in knowledge: 18 F-FDOPA PET in a single session imaging could have prognostic value in initial diagnosis of diffuse Grade II-III gliomas.

A new approach to assess COPD by identifying lung function break-points

PubMed Central

Eriksson, Göran; Jarenbäck, Linnea; Peterson, Stefan; Ankerst, Jaro; Bjermer, Leif; Tufvesson, Ellen

2015-01-01

Purpose COPD is a progressive disease, which can take different routes, leading to great heterogeneity. The aim of the post-hoc analysis reported here was to perform continuous analyses of advanced lung function measurements, using linear and nonlinear regressions. Patients and methods Fifty-one COPD patients with mild to very severe disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 41 healthy smokers were investigated post-bronchodilation by flow-volume spirometry, body plethysmography, diffusion capacity testing, and impulse oscillometry. The relationship between COPD severity, based on forced expiratory volume in 1 second (FEV1), and different lung function parameters was analyzed by flexible nonparametric method, linear regression, and segmented linear regression with break-points. Results Most lung function parameters were nonlinear in relation to spirometric severity. Parameters related to volume (residual volume, functional residual capacity, total lung capacity, diffusion capacity [diffusion capacity of the lung for carbon monoxide], diffusion capacity of the lung for carbon monoxide/alveolar volume) and reactance (reactance area and reactance at 5Hz) were segmented with break-points at 60%–70% of FEV1. FEV1/forced vital capacity (FVC) and resonance frequency had break-points around 80% of FEV1, while many resistance parameters had break-points below 40%. The slopes in percent predicted differed; resistance at 5 Hz minus resistance at 20 Hz had a linear slope change of −5.3 per unit FEV1, while residual volume had no slope change above and −3.3 change per unit FEV1 below its break-point of 61%. Conclusion Continuous analyses of different lung function parameters over the spirometric COPD severity range gave valuable information additional to categorical analyses. Parameters related to volume, diffusion capacity, and reactance showed break-points around 65% of FEV1, indicating that air trapping starts to dominate in moderate COPD (FEV1 =50%–80%). This may have an impact on the patient’s management plan and selection of patients and/or outcomes in clinical research. PMID:26508849

[Peak oxygen uptake during the six-minute walk test in diffuse interstitial lung disease and pulmonary hypertension].

PubMed

Blanco, Isabel; Villaquirán, Claudio; Valera, José Luis; Molina-Molina, María; Xaubet, Antoni; Rodríguez-Roisin, Robert; Barberà, Joan A; Roca, Josep

2010-03-01

The six-minute walk test (6MWT) is widely used in evaluating diffuse interstitial lung disease (ILD) and pulmonary hypertension (PH). However, their physiological determining factors have not been well defined. To evaluate the physiological changes that occur in ILD and PH during the 6MWT, and compare them with the cardiopulmonary exercise test (CPET). Thirteen patients with ILD and 14 with PH were studied using the 6MWT and CPET on an ergometer cycle. The respiratory variables were recorded by means of telemetry during the 6MWT. Oxygen consumption (VO(2)), respiratory and heart rate reached a plateau from minute 3 of the 6MWT in both diseases. The VO(2) did not differ from the peak value in the CPET (14+/-2 and 15+/-2 ml/kg/min, respectively, in ILD; 16+/-6 and 16+/-6 ml/kg/min, in PH). The arterial oxygen saturation decreased in both diseases, although it was more marked in ILD (-12+/-5%, p<0,01). The ventilatory equivalent for CO(2) (V(E)/VCO(2)) in PH during the 6MWT was strongly associated with functional class (FC) (85+/-14 in FC III-IV, 44+/-6 in FC I-II; p<0,001). The 6MWT in ILD and PH behaves like a maximal effort test, with similar VO(2) to the CPET, demonstrating a limit in oxygen transport capacity. Monitoring using telemetry during the 6MWT may be useful for the clinical evaluation of patients with ILD or PH. Copyright 2009 SEPAR. Published by Elsevier Espana. All rights reserved.

Swelling mechanism of urea cross-linked starch-lignin films in water.

PubMed

Sarwono, Ariyanti; Man, Zakaria; Bustam, M Azmi; Subbarao, Duvvuri; Idris, Alamin; Muhammad, Nawshad; Khan, Amir Sada; Ullah, Zahoor

2018-06-01

Coating fertilizer particles with thin films is a possibility to control fertilizer release rates. It is observed that novel urea cross-linked starch-lignin composite thin films, prepared by solution casting, swell on coming into contact with water due to the increase in volume by water uptake by diffusion. The effect of lignin content, varied from 0% to 20% in steps of 5% at three different temperatures (25°C, 35°C and 45°C), on swelling of the film was investigated. By gravimetric analysis, the equilibrium water uptake and diffusion coefficient decrease with lignin content, indicating that the addition of lignin increases the hydrophobicity of the films. When temperature increases, the diffusion coefficient and the amount of water absorbed tend to increase. Assuming that swelling of the thin film is by water uptake by diffusion, the diffusion coefficient is estimated. The estimated diffusion coefficient decreases from 4.3 to 2.1 × 10 -7  cm 2 /s at 25°C, from 5.3 to 2.9 × 10 -7  cm 2 /s at 35°C and from 6.2 to 3.8 × 10 -7  cm 2 /s at 45°C depending on the lignin content. Activation energy for the increase in diffusion coefficient with temperature is observed to be 16.55 kJ/mol. An empirical model of water uptake as a function of percentage of lignin and temperature was also developed based on Fick's law.

Relationship between pretreatment FDG-PET and diffusion-weighted MRI biomarkers in diffuse large B-cell lymphoma

PubMed Central

de Jong, Antoinette; Kwee, Thomas C; de Klerk, John MH; Adam, Judit A; de Keizer, Bart; Fijnheer, Rob; Kersten, Marie José; Ludwig, Inge; Jauw, Yvonne WS; Zijlstra, Josée M; den Bos, Indra C Pieters - Van; Stoker, Jaap; Hoekstra, Otto S; Nievelstein, Rutger AJ

2014-01-01

The purpose of this study was to determine the correlation between the 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) and the diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Pretreatment FDG-PET and diffusion-weighted MRI of 21 patients with histologically proven DLBCL were prospectively analyzed. In each patient, maximum, mean and peak standardized uptake value (SUV) was measured in the lesion with visually highest FDG uptake and in the largest lesion. Mean ADC (ADCmean, calculated with b-values of 0 and 1000 s/mm2) was measured in the same lesions. Correlations between FDG-PET metrics (SUVmax, SUVmean, SUVpeak) and ADCmean were assessed using Pearson’s correlation coefficients. In the lesions with visually highest FDG uptake, no significant correlations were found between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.498, P=0.609 and P=0.595, respectively). In the largest lesions, there were no significant correlations either between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.992, P=0.843 and P=0.894, respectively). The results of this study indicate that the glycolytic rate as measured by FDG-PET and changes in water compartmentalization and water diffusion as measured by the ADC are independent biological phenomena in newly diagnosed DLBCL. Further studies are warranted to assess the complementary roles of these different imaging biomarkers in the evaluation and follow-up of DLBCL. PMID:24795837

Enhanced Heme Function and Mitochondrial Respiration Promote the Progression of Lung Cancer Cells

PubMed Central

Alam, Md Maksudul; Shah, Ajit; Cao, Thai M.; Sullivan, Laura A.; Brekken, Rolf; Zhang, Li

2013-01-01

Lung cancer is the leading cause of cancer-related mortality, and about 85% of the cases are non-small-cell lung cancer (NSCLC). Importantly, recent advance in cancer research suggests that altering cancer cell bioenergetics can provide an effective way to target such advanced cancer cells that have acquired mutations in multiple cellular regulators. This study aims to identify bioenergetic alterations in lung cancer cells by directly measuring and comparing key metabolic activities in a pair of cell lines representing normal and NSCLC cells developed from the same patient. We found that the rates of oxygen consumption and heme biosynthesis were intensified in NSCLC cells. Additionally, the NSCLC cells exhibited substantially increased levels in an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins HRG1 and HCP1 that are involved in heme uptake, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. Several types of human tumor xenografts also displayed increased levels of such proteins. Furthermore, we found that lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. In contrast, lowering heme degradation does not have an effect on lung cancer cells. These results show that increased heme flux and function are a key feature of NSCLC cells. Further, increased generation and supply of heme and oxygen-utilizing hemoproteins in cancer cells will lead to intensified oxygen consumption and cellular energy production by mitochondrial respiration, which would fuel cancer cell proliferation and progression. The results show that inhibiting heme and respiratory function can effectively arrest the progression of lung cancer cells. Hence, understanding heme function can positively impact on research in lung cancer biology and therapeutics. PMID:23704904

Applicability of avidin protein coated mesoporous silica nanoparticles as drug carriers in the lung

NASA Astrophysics Data System (ADS)

van Rijt, S. H.; Bölükbas, D. A.; Argyo, C.; Wipplinger, K.; Naureen, M.; Datz, S.; Eickelberg, O.; Meiners, S.; Bein, T.; Schmid, O.; Stoeger, T.

2016-04-01

Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery.Mesoporous silica nanoparticles (MSNs) exhibit unique drug delivery properties and are thus considered as promising candidates for next generation nano-medicines. In particular, inhalation into the lungs represents a direct, non-invasive delivery route for treating lung disease. To assess MSN biocompatibility in the lung, we investigated the bioresponse of avidin-coated MSNs (MSN-AVI), as well as aminated (uncoated) MSNs, after direct application into the lungs of mice. We quantified MSN distribution, clearance rate, cell-specific uptake, and inflammatory responses to MSNs within one week after instillation. We show that amine-functionalized (MSN-NH2) particles are not taken up by lung epithelial cells, but induced a prolonged inflammatory response in the lung and macrophage cell death. In contrast, MSN-AVI co-localized with alveolar epithelial type 1 and type 2 cells in the lung in the absence of sustained inflammatory responses or cell death, and showed preferential epithelial cell uptake in in vitro co-cultures. Further, MSN-AVI particles demonstrated uniform particle distribution in mouse lungs and slow clearance rates. Thus, we provide evidence that avidin functionalized MSNs (MSN-AVI) have the potential to serve as versatile biocompatible drug carriers for lung-specific drug delivery. Electronic supplementary information (ESI) available: Synthesis of MSN particles. Characterisation of MSN particles (Fig. S1 and S2), DLS measurements of MSNs over time, lymphocyte and PMN cell count after MSN exposure (Fig. S3). Toxicity in BAL cytospins controls, phalloidin staining on BAL cytospins of MSN-NH2 exposed mice (Fig. S4), nanoparticle distribution in lung cryo-slices of Balb/c mice exposed to 100 μg MSNs (Fig. S5). Balb/c mice cryo-slices exposed to MSN-AVI for 1 or 7 days, co-stained with alveolar epithelial cell type 1 marker or with alveolar epithelial cell type 2 marker (Fig. S6), DiD selective labeling in a co-culture set-up (Fig. S7). See DOI: 10.1039/c5nr04119h

[A novel compound heterozygous mutation in ABCA3 gene in a child with diffuse parenchymal lung disease].

PubMed

Bao, Y M; Liu, X L; Liu, X L; Chen, J H; Zheng, Y J

2017-11-02

Objective: To summarize the clinical characteristics of the diffuse parenchymal lung diseases in a child caused by a novel compound heterozygous ABCA3 mutation and explore the association between the phenotype and ABCA3 mutation. Method: The clinical material of a patient diagnosed with diffuse parenchymal lung disease with ABCA3 mutation in December 2016 in Shenzhen Children's Hospital was analyzed. The information about ABCA3 gene mutation updated before April, 2017 was searched and collected from the gene databases (including 1000Genomes, HGMD, EXAC) and the literatures (including Wanfang Chinese database and Pubmed). Result: The girl was one year and nine months old. She presented with chronic cough, tachypnea, cyanosis and failure to thrive since she was one year and three months old. Her condition gradually deteriorated after she was empirically treated. Physical examination showed malnutrition, tachypnea and clubbed-fingers. Her high resolution computed tomography (HRCT) revealed diffused ground-glass opacities, thickened interlobular septum, and multiple subpleural small air-filled lung cysts. The second generation sequencing study identified a novel compound heterozygous mutation (c.1755delC+c.2890G>A) in her ABCA3 gene, which derived respectively from her parents and has not been reported in the database and the literatures mentioned above. Conclusion: c.1755delC+c.2890G>A is a new kind of compound heterozygous mutation in ABCA3, which can cause children's diffuse parenchymal lung disease. Its phenotype is related to its genotype.

Abdominal and hepatic uptake of /sup 99m/Tc-pyrophosphate in neonatal necrotizing enterocolitis

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

Caride, V.J.; Touloukian, R.J.; Ablow, R.C.

1981-04-01

Abdominal /sup 99m/Tc-pyrophosphate (/sup 99m/Tc-PYP) scans were obtained in 15 neonates: 12 with neonatal necrotizing enterocolitis (NEC), two with osteomyelitis, and one with myocarditis. Ten of the babies with NEC had at least one positive scan; of these 10 studies, seven (Group A) showed both diffuse abdominal uptake and localized hepatic activity, two (Group B) showed abdominal uptake and questionable hepatic uptake, and one (Group C) demonstrated diffuse abdominal uptake only. The other two babies with NEC had normal scans (Group D). All NEC patients had normal scans. A patient with myocarditis had hepatic uptake of /sup 99m/Tc-PYP while themore » abdominal scan in the two infants with osteomyelitis was normal. These preliminary observations suggest that further study of a relationship between abdominal scan findings and the course of NEC is warranted.« less

Tc-99m colloid lung uptake in a rare case of toxoplasmosis with liver involvement

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

Garty, I.; Tal, I.; Kaynan, A.

1984-06-01

Intensive lung accumulation of colloid (Tc-99m phytate) was demonstrated in a child suffering from acquired toxoplasmosis with a rare manifestation of severe liver damage. The possible mechanism and clinical importance of colloid lung concentration in this case is briefly discussed, including a review of the literature on this subject.

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

Morais, J.; Carrier, L.; Gariepy, G.

Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed.

Nitrate Utilization by the Diatom Skeletonema costatum

PubMed Central

Serra, Juan L.; Llama, Maria J.; Cadenas, Eduardo

1978-01-01

Nitrate uptake has been studied in nitrogen-deficient cells of the marine diatom Skeletonema costatum. When these cells are incubated in the presence of nitrate, this ion is quickly taken up from the medium, and nitrite is excreted by the cells. Nitrite is excreted following classical saturation kinetics, its rate being independent of nitrate concentration in the incubation medium for nitrate concentration values higher than 3 micromolar. Nitrate uptake shows mixed-transfer kinetics, which can be attributed to the simultaneous contributions of mediated and diffusion transfer. Cycloheximide and p-hydroxymercuribenzoate inhibit the carrier-mediated contribution to nitrate uptake, without affecting the diffusion component. When cells are preincubated with nitrate, the net nitrogen uptake is increased. PMID:16660652

Radiological and Pathological Correlation in Anti-MDA5 Antibody-positive Interstitial Lung Disease: Rapidly Progressive Perilobular Opacities and Diffuse Alveolar Damage.

PubMed

Chino, Haruka; Sekine, Akimasa; Baba, Tomohisa; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Itoh, Harumi; Sato, Shinji; Suzuki, Yasuo; Ogura, Takashi

2016-01-01

We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD). Rapidly progressive perilobular opacities may be characteristic of RP-ILD with anti-MDA5 antibody and DAD.

Novel mucus-penetrating liposomes as a potential oral drug delivery system: preparation, in vitro characterization, and enhanced cellular uptake

PubMed Central

Li, Xiuying; Chen, Dan; Le, Chaoyi; Zhu, Chunliu; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

2011-01-01

Background The aim of this study was to investigate the intestinal mucus-penetrating properties and intestinal cellular uptake of two types of liposomes modified by Pluronic F127 (PF127). Methods The two types of liposomes, ie, PF127-inlaid liposomes and PF127-adsorbed liposomes, were prepared by a thin-film hydration method followed by extrusion, in which coumarin 6 was loaded as a fluorescence marker. A modified Franz diffusion cell mounted with the intestinal mucus of rats was used to study the diffusion characteristics of the two types of PF127 liposomes. Cell uptake studies were conducted in Caco-2 cells and analyzed using confocal laser scanning microcopy as well as flow cytometry. Results The diffusion efficiency of the two types of PF127-modified liposomes through intestinal rat mucus was 5–7-fold higher than that of unmodified liposomes. Compared with unmodified liposomes, PF127-inlaid liposomes showed significantly higher cellular uptake of courmarin 6. PF127-adsorbed liposomes showed a lower cellular uptake. Moreover, and interestingly, the two types of PF127-modified liposomes showed different cellular uptake mechanisms in Caco-2 cells. Conclusion PF127-inlaid liposomes with improved intestinal mucus-penetrating ability and enhanced cellular uptake might be a potential carrier candidate for oral drug delivery. PMID:22163166

Primary Sjögren's syndrome with diffuse cystic lung changes developed systemic lupus erythematosus: a case report and literature review.

PubMed

Liu, Xiao; Li, Hao; Yin, Yunhong; Ma, Dedong; Qu, Yiqing

2017-05-23

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that can occur as a unique existence (primary Sjögren's syndrome) or merge with other systemic diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis or systemic sclerosis (secondary Sjögren's syndrome). Data on the two diseases occurrence order are inadequate. Primary Sjögren's syndrome (pSS) may relatively uncommonly lead to diffuse cystic lung changes. We represent a female who was diagnosed pSS with diffuse cystic lung alterations developed SLE two years later. SS was diagnosed on account of the existence of dryness of eye and mouth, Schirmer's test, biopsy of the minor salivary glands of her lip, positive anti-SSA and anti-SSB antibody in the serum. Chest computed tomography image showed bilateral diffuse cystic changes with a wide variation in cyst size and distribution. SLE was finally diagnosed based on bilateral lower limb skin rash, gonarthritis and omarthritis, low level of complement, antinuclear antibody 1:640 and positive antibodies to double-stranded DNA. Improvement was achieved with therapy of corticosteroids, hydroxychloroquine and antibiotics. This report provides us clinical, diagnosis and treatment perception of SS-onset SLE as patient presenting diffuse cystic lung changes.

Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds.

PubMed

Wagner, T; Page, J; Burniston, M; Skillen, A; Ross, J C; Manwani, R; McCool, D; Hawkins, P N; Wechalekar, Ashutosh D

2018-07-01

18 F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18 F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. Seventeen patients with proven cardiac amyloidosis underwent 18 F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123 I-serum amyloid P component (SAP). 18 F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUV mean ) were produced. All 17 patients showed 18 F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123 I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18 F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123 I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. 18 F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18 F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL.

Diffuse consolidation form of bronchoalveolar carcinoma.

PubMed

Khalil, Kanwal Fatima; Saeed, Waseem; Zill-e-Hamayun

2010-03-01

This case report describes a patient with diffuse consolidation form of bronchoalveolar carcinoma (BAC) which is a rare type of adenocarcinoma of lung. He was diagnosed on the basis of findings on X-ray and high resolution CT(HRCT) chest later confirmed by open lung biopsy and immuno-histochemical staining. Only supportive treatment could be provided and the patient expired during the subsequent month of follow-up. Traditionally, diffuse consolidation is the radiological presentation in only 20% of patients with bronchoalveolar carcinoma.

The Value of PET/CT in Detecting Bone Marrow Involvement in Patients With Follicular Lymphoma.

PubMed

Perry, Chava; Lerman, Hedva; Joffe, Erel; Sarid, Nadav; Amit, Odelia; Avivi, Irit; Kesler, Mikhail; Ben-Ezra, Jonathan; Even-Sapir, Einat; Herishanu, Yair

2016-03-01

Follicular lymphoma (FL) is the 2nd most common type of lymphoma diagnosed in the Western World. Bone marrow (BM) involvement is an adverse prognostic factor in FL, routinely assessed by an arbitrary biopsy of the iliac crest. This study was aimed to investigate the role of positron emission tomography/computed tomography (PET/CT) in identifying BM involvement by FL. In this retrospective, single-center study we reviewed the records of consecutive patients with FL at diagnosis or relapse who underwent staging/restaging workup visual assessment of BM uptake was categorized as either normal, diffusely increased, or focally increased. Quantitative BM fluorine-18-fluro-deoxyglucose (FDG) uptake was measured using mean standardized uptake value (BM-SUVmean). The diagnosis of BM involvement was based on either BM histological findings or disappearance of increased uptake at end-treatment PET/CT in patients who responded to treatment. Sixty eight cases with FL were included. Sixteen (23.5%) had BM involvement, 13 (19.1%) had a biopsy proven involvement, and 3 (4.4%) had a negative BM biopsy, but increased medullary uptake that normalized post-treatment. BM FDG uptake in these patients was diffuse in 8 (50%) and focal in 8 (50%). Focal increased uptake was indicative of BM involvement; however, diffuse uptake was associated with 17 false positive cases (32.7%). Overall, visual assessment of BM involvement had a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 48.5%. On a quantitative assessment, BM-SUVmean was significantly higher in patients with BM involvement (SUVmean of 3.7 [1.7-6] vs 1.4 [0.4-2.65], P < 0.001). On receiver operator curve (ROC) analysis, BM-SUVmean > 2.7 had a PPV of 100% for BM involvement (sensitivity of 68%), while BM-SUVmean < 1.7 had an NPV of 100% (specificity of 73%). Visual assessment of PET/CT is appropriate for ruling out BM involvement by FL. Although focal increased uptake indicates marrow involvement, diffuse uptake is nonspecific. SUV measurement improves PET/CT diagnostic accuracy, identifying additional 19% of patients with BM involvement that would have been otherwise missed.

Spermidine-mediated poly(lactic-co-glycolic acid) nanoparticles containing fluorofenidone for the treatment of idiopathic pulmonary fibrosis

PubMed Central

Tang, Jing; Li, Jianming; Li, Guo; Zhang, Haitao; Wang, Ling; Li, Dai; Ding, Jinsong

2017-01-01

Idiopathic pulmonary fibrosis is a progressive, fatal lung disease with poor survival. The advances made in deciphering this disease have led to the approval of different antifibrotic molecules, such as pirfenidone and nintedanib. An increasing number of studies with particles (liposomes, nanoparticles [NPs], microspheres, nanopolymersomes, and nanoliposomes) modified with different functional groups have demonstrated improvement in lung-targeted drug delivery. In the present study, we prepared, characterized, and evaluated spermidine (Spd)-modified poly(lactic-co-glycolic acid) (PLGA) NPs as carriers for fluorofenidone (AKF) to improve the antifibrotic efficacy of this drug in the lung. Spd-AKF-PLGA NPs were prepared and functionalized by modified solvent evaporation with Spd and polyethylene glycol (PEG)-PLGA groups. The size of Spd-AKF-PLGA NPs was 172.5±4.3 nm. AKF release from NPs was shown to fit the Higuchi model. A549 cellular uptake of an Spd–coumarin (Cou)-6-PLGA NP group was found to be almost twice as high as that of the Cou-6-PLGA NP group. Free Spd and difluoromethylornithine (DFMO) were preincubated in A549 cells to prove uptake of Spd-Cou-6-PLGA NPs via a polyamine-transport system. As a result, the uptake of Spd-Cou-6-PLGA NPs significantly decreased with increased Spd concentrations in incubation. At higher Spd concentrations of 50 and 500 µM, uptake of Spd-Cou-6-PLGA NPs reduced 0.34- and 0.49-fold from that without Spd pretreatment. After pretreatment with DFMO for 36 hours, cellular uptake of Spd-Cou-6-PLGA NPs reached 1.26-fold compared to the untreated DFMO group. In a biodistribution study, the drug-targeting index of Spd-AKF-PLGA NPs in the lung was 3.62- and 4.66-fold that of AKF-PLGA NPs and AKF solution, respectively. This suggested that Spd-AKF-PLGA NPs accumulated effectively in the lung. Lung-histopathology changes and collagen deposition were observed by H&E staining and Masson staining in an efficacy study. In the Spd-AKF-PLGA NP group, damage was further improved compared to the AKF-PLGA NP group and AKF-solution group. The results indicated that Spd-AKF-PLGA NPs are able to be effective nanocarriers for anti–pulmonary fibrosis therapy. PMID:28932114

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

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

Forstrom, L.A.; Loken, M.K.; Cook, A.

1981-04-01

Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6more » mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.« less

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

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

Forstrom, L.A.; Loken, M.K.; Cook, A.

1981-04-01

Indium-111-labelled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labelling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6more » mCi of In-111 leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.« less

Inter- and intraobserver agreement of ADC measurements of lung cancer in free breathing, breath-hold and respiratory triggered diffusion-weighted MRI.

PubMed

Cui, Lei; Yin, Jian-Bing; Hu, Chun-Hong; Gong, Shen-Chu; Xu, Jun-Feng; Yang, Ju-Shun

2016-01-01

To prospectively evaluate the inter- and intraobserver agreement of apparent diffusion coefficient (ADC) measurements in free breathing, breath-hold, and respiratory triggered diffusion-weighted imaging (DWI) of lung cancer. Twenty-two patients with lung cancer (tumor size >2cm) underwent DWIs (3.0T) in three imaging methods. Lesion ADCs were measured twice by both of the two independent observers and compared. No statistical significance was found among methods, though respiratory-triggered DWI tended to have higher ADCs than breath-hold DWI. Great inter- and intraobserver agreement was shown. ADCs had good inter- and intraobserver agreement in all three DWI methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Nanodiamond internalization in cells and the cell uptake mechanism

NASA Astrophysics Data System (ADS)

Perevedentseva, E.; Hong, S.-F.; Huang, K.-J.; Chiang, I.-T.; Lee, C.-Y.; Tseng, Y.-T.; Cheng, C.-L.

2013-08-01

Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.

Exercise-induced oxyhaemoglobin desaturation, ventilatory limitation and lung diffusing capacity in women during and after exercise.

PubMed

Walls, Justin; Maskrey, Michael; Wood-Baker, Richard; Stedman, Wade

2002-06-01

Arterial haemoglobin saturation during exercise in healthy young women [eight subjects mean (SEM) age 20.8 (1.8) years] was measured to confirm the theory that young women experience exercise-induced arterial hypoxaemia (EIAH) at a lower relative percentage of maximal oxygen uptake (VO(2max)) than has been documented in their male counterparts. To determine if flow limitation [the percentage of the tidal volume ( V(T)) that met or exceeded the boundary established by multiple maximal expiratory manoeuvres] and/or post-exercise lung diffusing capacity are linked to EIAH in women, and to investigate the influence of exercise intensity and duration on post-exercise carbon monoxide lung diffusing capacity ( D(L, CO)), these parameters were measured during and after three exercise tests (incremental test until exhaustion, 5 km run and 5 km run with sprint). All subjects experienced physiologically significant EIAH (a fall of more than 3% in oxygen saturation of arterial blood from levels at rest) and seven subjects experienced flow limitation during the VO(2max) protocol [mean (SD) 12.2 (8.8)% of V(T)]. Even though there was no significant relationship between aerobic capacity and the degree of flow limitation ( r=0.33, P>0.05), the flow limitation was related to absolute ventilation in the subjects studied ( r=0.82, P<0.05). There was no significant relationship between decrements in post exercise D(L, CO) and EIAH ( r=0.05, P>0.05), however there was a strong correlation between the extent of flow limitation (% of V(T)) and EIAH ( r=0.71). Significant decreases in D(L, CO) lasted for up to 16 h after each of the exercise tests ( P<0.05) and lasted for a further 8 h after the maximal test ( P<0.05). Exercise intensity was the main contributing factor to the observed decreases in post-exercise D(L, CO) with the percentage of VO(2max) attained during the various tests being significantly related to the fall in D(L, CO) for 1, 2, 3, 16 and 24 h after exercise ( P<0.05). As the appearance of flow limitation closely coincided with the appearance of EIAH, the results from the present study suggest that flow limitation is a contributing factor to EIAH in women although the exact mechanism remains unclear.

European survey on the usefulness of /sup 67/Ga lung scans in assessing sarcoidosis. Experience in 14 research centers in seven different countries

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

Rizzato, G.; Blasi, A.

1986-01-01

Fifty-eight contributors from 12 European and 2 American sarcoidosis centers have collaborated in a survey to define many questions concerning the use of /sup 67/Ga lung scan in sarcoidosis. The new quantitative scoring methods based on digital evaluation seem better in detecting lung activity. In 20.1% of untreated patients, the /sup 67/Ga lung scan appeared to be the only noninvasive method with which clinical activity could be detected. /sup 67/Ga scans may be useful in guiding lung biopsy and in choosing pulmonary segments for BAL. Of 382 patients studied during follow-up (154 patients with three to nine scans at intervalsmore » of 2 to 12 months), the /sup 67/Ga scan was far more sensitive than chest radiography, both in detecting improvement and in foreseeing relapses. Steroid therapy appears to suppress ACE levels more than /sup 67/Ga uptake, and /sup 67/Ga uptake more than the alveolitis detectable by BAL. Gallium-67 uptake rebounds to positivity occur in about 40% of patients after steroid discontinuation and in about 20% of patients after steroid reduction to daily doses of 10 mg or less of prednisone. The /sup 67/Ga dose of 1.5 mCi seems appropriate for clinical purposes and is recommended for the subjective scoring method in order to reduce the cost and the radiation burden.« less

Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications.

PubMed

Volkow, Nora D; Fowler, Joanna S; Wang, Gene-Jack; Shumay, Elena; Telang, Frank; Thanos, Peter K; Alexoff, David

2010-12-07

Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [(11)C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [(11)C]d-methamphetamine was 30% higher for African Americans than Caucasians (p<0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

Hybrid [¹⁸F]-FDG PET/MRI including non-Gaussian diffusion-weighted imaging (DWI): preliminary results in non-small cell lung cancer (NSCLC).

PubMed

Heusch, Philipp; Köhler, Jens; Wittsack, Hans-Joerg; Heusner, Till A; Buchbender, Christian; Poeppel, Thorsten D; Nensa, Felix; Wetter, Axel; Gauler, Thomas; Hartung, Verena; Lanzman, Rotem S

2013-11-01

To assess the feasibility of non-Gaussian DWI as part of a FDG-PET/MRI protocol in patients with histologically proven non-small cell lung cancer. 15 consecutive patients with histologically proven NSCLC (mean age 61 ± 11 years) were included in this study and underwent whole-body FDG-PET/MRI following whole-body FDG-PET/CT. As part of the whole-body FDG-PET/MRI protocol, an EPI-sequence with 5 b-values (0, 100, 500, 1000 and 2000 s/mm(2)) was acquired for DWI of the thorax during free-breathing. Volume of interest (VOI) measurements were performed to determine the maximum and mean standardized uptake value (SUV(max); SUV(mean)). A region of interest (ROI) was manually drawn around the tumor on b=0 images and then transferred to the corresponding parameter maps to assess ADC(mono), D(app) and K(app). To assess the goodness of the mathematical fit R(2) was calculated for monoexponential and non-Gaussian analysis. Spearman's correlation coefficients were calculated to compare SUV values and diffusion coefficients. A Student's t-test was performed to compare the monoexponential and non-Gaussian diffusion fitting (R(2)). T staging was equal between FDG-PET/CT and FDG-PET/MRI in 12 of 15 patients. For NSCLC, mean ADC(mono) was 2.11 ± 1.24 × 10(-3) mm(2)/s, Dapp was 2.46 ± 1.29 × 10(-3) mm(2)/s and mean Kapp was 0.70 ± 0.21. The non-Gaussian diffusion analysis (R(2)=0.98) provided a significantly better mathematical fitting to the DWI signal decay than the monoexponetial analysis (R(2)=0.96) (p<0.001). SUV(max) and SUV(mean) of NSCLC was 13.5 ± 7.6 and 7.9 ± 4.3 for FDG-PET/MRI. ADC(mono) as well as Dapp exhibited a significant inverse correlation with the SUV(max) (ADC(mono): R=-0.67; p<0.01; Dapp: R=-0.69; p<0.01) as well as with SUV(mean) assessed by FDG-PET/MRI (ADC(mono): R=-0.66; p<0.01; Dapp: R=-0.69; p<0.01). Furthermore, Kapp exhibited a significant correlation with SUV(max) (R=0.72; p<0.05) and SUV(mean) as assessed by FDG-PET/MRI (R=0.71; p<0.005). Simultaneous PET and non-Gaussian diffusion acquisitions are feasible. Non-Gaussian diffusion parameters show a good correlation with SUV and might provide additional information beyond monoexponential ADC, especially as non-Gaussian diffusion exhibits better mathematical fitting to the decay of the diffusion signal than monoexponential DWI. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

On the mechanism of Cr (VI)-induced carcinogenesis: dose dependence of uptake and cellular responses.

PubMed

Liu, K; Husler, J; Ye, J; Leonard, S S; Cutler, D; Chen, F; Wang, S; Zhang, Z; Ding, M; Wang, L; Shi, X

2001-06-01

Cr (VI) compounds are widely used industrial chemicals and are recognized human carcinogens. The mechanisms of carcinogenesis associated with these compounds remain to be investigated. The present study focused on dose-dependence of Cr (VI)-induced uptake and cellular responses. The results show that Cr (VI) is able to enter the cells (human lung epithelial cell line A549) at low concentration (< 10 microM) and that the Cr (VI) uptake appears to be a combination of saturable transport and passive diffusion. Electron spin resonance (ESR) trapping measurements showed that upon stimulation with Cr (VI), A549 cells were able to generate reactive oxygen species (ROS). The amount of ROS generated depended on the Cr (VI) concentration. ROS generation involved NADPH-dependent flavoenzymes. Cr (VI) affected the following cellular parameters in a dose-dependent manner, (a) activation of nuclear transcription factors NF-kappaB, and p53, (b) DNA damage, (c) induction of cell apoptosis, and (d) inhibition of cell proliferation. The activation of transcription factors was assessed by electrophoretic mobility shift assay and western blot analysis, DNA damage by single cell gel electrophoresis assay, cell apoptosis by DNA fragmentation assay, and cell proliferation by a non-radioactive ELISA kit. At the concentration range used in the present study, no thresholds were found in all of these cell responses to Cr (VI). The results may guide further research to better understand and evaluate the risk of Cr (VI)-induced carcinogenesis at low levels of exposure.

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

PubMed Central

Sarduy, M R; García, I; Coca, M A; Perera, A; Torres, L A; Valenzuela, C M; Baladrón, I; Solares, M; Reyes, V; Hernández, I; Perera, Y; Martínez, Y M; Molina, L; González, Y M; Ancízar, J A; Prats, A; González, L; Casacó, C A; Acevedo, B E; López-Saura, P A; Alonso, D F; Gómez, R; Perea-Rodríguez, S E

2015-01-01

Background: We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose. Methods: Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry. Results: Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens. Conclusion: Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies. PMID:25880012

Polarized Helium to Image the Lung

NASA Astrophysics Data System (ADS)

Leduc, Michèle; Nacher, Pierre Jean

2005-05-01

The main findings of the european PHIL project (Polarised Helium to Image the Lung) are reported. State of the art optical pumping techniques for polarising 3He gas are described. MRI methodological improvements allow dynamical ventilation images with a good resolution, ultimately limited by gas diffusion. Diffusion imaging appears as a robust method of lung diagnosis. A discussion of the potential advantage of low field MRI is presented. Selected PHIL results for emphysema are given, with the perspectives that this joint work opens up for the future of respiratory medicine.

Tumour exosome integrins determine organotropic metastasis

PubMed Central

Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Mark, Milica Tesic; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E.; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M.; Dumont-Cole, Vanessa D.; Kramer, Kimberly; Wexler, Leonard H.; Narendran, Aru; Schwartz, Gary K.; Healey, John H.; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H.; Grandgenett, Paul M.; Hollingsworth, Michael A.; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K.; Jarnagin, William R.; Brady, Mary S.; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J.; Bissell, Mina J.; Garcia, Benjamin A.; Kang, Yibin; Rajasekhar, Vinagolu K.; Ghajar, Cyrus M.; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

2015-01-01

Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. PMID:26524530

Tumour exosome integrins determine organotropic metastasis

DOE PAGES

Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; ...

2015-10-28

Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. In this paper, we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α 6β 4 and α 6β 1 weremore » associated with lung metastasis, while exosomal integrin α vβ 5 was linked to liver metastasis. Targeting the integrins α 6β 4 and α vβ 5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. In conclusion, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.« less

Tumour exosome integrins determine organotropic metastasis

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

Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long

Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. In this paper, we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α 6β 4 and α 6β 1 weremore » associated with lung metastasis, while exosomal integrin α vβ 5 was linked to liver metastasis. Targeting the integrins α 6β 4 and α vβ 5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. In conclusion, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.« less

Tumour exosome integrins determine organotropic metastasis.

PubMed

Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David

2015-11-19

Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

[A case of lung cancer producing granulocyte colony-stimulating factor with a significantly high uptake in the bones observed by a FDG-PET scan].

PubMed

Hidaka, Dai; Koshizuka, Hiroaki; Hiyama, Junichiro; Nakatsubo, Seita; Ikeda, Koutarou; Hayashi, Akihiro; Fujii, Akiko; Sawamoto, Ryouko; Misumi, Yukihiro; Miyagawa, Yousuke

2009-03-01

A 57-year-old man complaining of right shoulder pain was admitted. Chest enhanced CT scanning showed a mass shadow in the right upper lobe with chest wall invasion. The laboratory data on admission showed marked leukocytosis. A CT-guided lung biopsy was performed, and a histological examination of the biopsy specimen showed a spindle cell type pleomorphic carcinoma. Immunohistochemistry staining using an anti-granulocyte colony-stimulating factor (G-CSF) monoclonal antibody demonstrated many tumor cells containing G-CSF as well as an increased level of serum G-CSF. The diagnosis was determined to be lung cancer producing G-CSF. FDG-PET scanning showed a significantly high uptake in the right upper field and the bones throughout the body. After chemoradiation therapy, the patient underwent a right upper lobectomy with a chest wall resection. Since then, the leukocytosis and the high level of serum G-CSF normalized and the high uptake in the bones disappeared in the FDG-PET scan.

Cerebral Metastases of Lung Cancer Mimicking Multiple Ischaemic Lesions - A Case Report and Review of Literature.

PubMed

Zacharzewska-Gondek, Anna; Maksymowicz, Hanna; Szymczyk, Małgorzata; Sąsiadek, Marek; Bladowska, Joanna

2017-01-01

Restricted diffusion that is found on magnetic resonance diffusion-weighted imaging (DWI) typically indicates acute ischaemic stroke. However, restricted diffusion can also occur in other diseases, like metastatic brain tumours, which we describe in this case report. A 57-year-old male, with a diagnosis of small-cell cancer of the right lung (microcellular anaplastic carcinoma), was admitted with focal neurological symptoms. Initial brain MRI revealed multiple, disseminated lesions that were hyperintense on T2-weighted images and did not enhance after contrast administration; notably, some lesions manifested restricted diffusion on DWI images. Based on these findings, disseminated ischaemic lesions were diagnosed. On follow-up MRI that was performed after 2 weeks, we observed enlargement of the lesions; there were multiple, disseminated, sharply outlined, contrast-enhancing, oval foci with persistent restriction of diffusion. We diagnosed the lesions as disseminated brain metastases due to lung cancer. To our knowledge, this is the first description of a patient with brain metastases that were characterised by restricted diffusion and no contrast enhancement. Multiple, disseminated brain lesions, that are characterised by restricted diffusion on DWI, typically indicate acute or hyperacute ischemic infarcts; however, they can also be due to hypercellular metastases, even if no contrast enhancement is observed. This latter possibility should be considered particularly in patients with cancer.

An unusual case of diffuse large B-cell lymphoma involving the vulva evaluated by 18F-FDG PET/CT.

PubMed

Treglia, Giorgio; Paone, Gaetano; Perriard, Ulrike; Ceriani, Luca; Giovanella, Luca

2014-10-01

We describe an unusual case of diffuse large B-cell lymphoma involving the vulva detected and staged by F-FDG PET/CT. An 83-year-old female patient with history of endometrial carcinoma underwent F-FDG PET/CT for follow-up. PET/CT detected an area of increased F-FDG uptake corresponding to a vulvar nodule; moderate and diffuse F-FDG uptake in the bone marrow was also evident. Based on these PET/CT findings, the patient underwent biopsy of the vulvar nodule. Histology demonstrated the presence of a diffuse large B-cell lymphoma of the vulva. Bone marrow biopsy was positive for lymphoid infiltration.

Metabolism of phenylethylamine in rat isolated perfused lung: evidence for monoamine oxidase 'type B' in lung.

PubMed Central

Bakhle, Y S; Youdim, M B

1976-01-01

Phenylethylamine is inactivated in a single passage through rat lung tissue by a process of uptake and deamination by a monoamine oxidase 'type B'. This enzyme is particularly susceptible to inhibition by deprenil and less sensitive to clorgyline. The monoamine oxidase of the lung, like that of other rat tissues, can be differentiated into 'type A' and 'type B' which appear to operate independently in the organized tissue. PMID:1252659

DMT1 EXPRESSION IS INCREASED IN THE LUNG OF HYPOTRANSFERRINEMIC MICE

EPA Science Inventory

Despite a lack of transferrin, hypotransferrinemic (Hp) mice demonstrate an accumulation of iron in peripheral organs including the lungs. One potential candidate for such transferrin-independent uptake of iron is divalent metal transporter-1 (DMT1), an established iron transport...

Cigarette smoking and pulmonary diffusion defects in rheumatoid arthritis.

PubMed

Westedt, M L; Hazes, J M; Breedveld, F C; Sterk, P J; Dijkman, J H

1998-01-01

The pathogenesis of lung disease in rheumatoid arthritis (RA) has still to be defined. Risk factors associated with lung involvement in RA were investigated by means of pulmonary function studies in 40 RA patients without apparent lung disease. A decreased carbon monoxide (CO) diffusion capacity indicative of interstitial lung disease (ILD) was the main pulmonary function defect found in the first 20 patients. The occurrence was associated with current cigarette smoking. This association was confirmed in a case control study performed subsequently. These data suggest that ILD in RA is stimulated by smoking and provide an additional argument that modification of smoking behaviour in RA patients might lead to less severe complications.

Uptake of L-nicotine and of 6-hydroxy-L-nicotine by Arthrobacter nicotinovorans and by Escherichia coli is mediated by facilitated diffusion and not by passive diffusion or active transport.

PubMed

Ganas, Petra; Brandsch, Roderich

2009-06-01

The mechanism by which l-nicotine is taken up by bacteria that are able to grow on it is unknown. Nicotine degradation by Arthrobacter nicotinovorans, a Gram-positive soil bacterium, is linked to the presence of the catabolic megaplasmid pAO1. l-[(14)C]Nicotine uptake assays with A. nicotinovorans showed transport of nicotine across the cell membrane to be energy-independent and saturable with a K(m) of 6.2+/-0.1 microM and a V(max) of 0.70+/-0.08 micromol min(-1) (mg protein)(-1). This is in accord with a mechanism of facilitated diffusion, driven by the nicotine concentration gradient. Nicotine uptake was coupled to its intracellular degradation, and an A. nicotinovorans strain unable to degrade nicotine (pAO1(-)) showed no nicotine import. However, when the nicotine dehydrogenase genes were expressed in this strain, import of l-[(14)C]nicotine took place. A. nicotinovorans pAO1(-) and Escherichia coli were also unable to import 6-hydroxy-l-nicotine, but expression of the 6-hydroxy-l-nicotine oxidase gene allowed both bacteria to take up this compound. l-Nicotine uptake was inhibited by d-nicotine, 6-hydroxy-l-nicotine and 2-amino-l-nicotine, which may indicate transport of these nicotine derivatives by a common permease. Attempts to correlate nicotine uptake with pAO1 genes possessing similarity to amino acid transporters failed. In contrast to the situation at the blood-brain barrier, nicotine transport across the cell membrane by these bacteria was not by passive diffusion or active transport but by facilitated diffusion.

Development of an integrated sensor module for a non-invasive respiratory monitoring system

NASA Astrophysics Data System (ADS)

Kang, Seok-Won; Chang, Keun-Shik

2013-09-01

A respiratory monitoring system has been developed for analyzing the carbon dioxide (CO2) and oxygen (O2) concentrations in the expired air using gas sensors. The data can be used to estimate some medical conditions, including diffusion capability of the lung membrane, oxygen uptake, and carbon dioxide output. For this purpose, a 3-way valve derived from a servomotor was developed, which operates synchronously with human respiratory signals. In particular, the breath analysis system includes an integrated sensor module for valve control, data acquisition through the O2 and CO2 sensors, and respiratory rate monitoring, as well as software dedicated to analysis of respiratory gasses. In addition, an approximation technique for experimental data based on Haar-wavelet-based decomposition is explored to remove noise as well as to reduce the file size of data for long-term monitoring.

Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: what 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report.

PubMed

Cistaro, A; Pazè, F; Durando, S; Cogoni, M; Faletti, R; Vesco, S; Vallero, S; Quartuccio, N; Treglia, G; Ramenghi, U

2014-01-01

A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A (18)F-FDG-PET/CT scan showed many areas of intense (18)F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the (18)F-FDG-PET/CT scan showed a complete metabolic response. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Diffusion of small molecules into medaka embryos improved by electroporation

PubMed Central

2013-01-01

Background Diffusion of small molecules into fish embryos is essential for many experimental procedures in developmental biology and toxicology. Since we observed a weak uptake of lithium into medaka eggs we started a detailed analysis of its diffusion properties using small fluorescent molecules. Results Contrary to our expectations, not the rigid outer chorion but instead membrane systems surrounding the embryo/yolk turned out to be the limiting factor for diffusion into medaka eggs. The consequence is a bi-phasic uptake of small molecules first reaching the pervitelline space with a diffusion half-time in the range of a few minutes. This is followed by a slow second phase (half-time in the range of several hours) during which accumulation in the embryo/yolk takes place. Treatment with detergents improved the uptake, but strongly affected the internal distribution of the molecules. Testing electroporation we could establish conditions to overcome the diffusion barrier. Applying this method to lithium chloride we observed anterior truncations in medaka embryos in agreement with its proposed activation of Wnt signalling. Conclusions The diffusion of small molecules into medaka embryos is slow, caused by membrane systems underneath the chorion. These results have important implications for pharmacologic/toxicologic techniques like the fish embryo test, which therefore require extended incubation times in order to reach sufficient concentrations in the embryos. PMID:23815821

Characterization of the Lung Parenchyma Using Ultrasound Multiple Scattering.

PubMed

Mohanty, Kaustav; Blackwell, John; Egan, Thomas; Muller, Marie

2017-05-01

The purpose of the study described here was to showcase the application of ultrasound to quantitative characterization of the micro-architecture of the lung parenchyma to predict the extent of pulmonary edema. The lung parenchyma is a highly complex and diffusive medium for which ultrasound techniques have remained qualitative. The approach presented here is based on ultrasound multiple scattering and exploits the complexity of ultrasound propagation in the lung structure. The experimental setup consisted of a linear transducer array with an 8-MHz central frequency placed in contact with the lung surface. The diffusion constant D and transport mean free path L* of the lung parenchyma were estimated by separating the incoherent and coherent intensities in the near field and measuring the growth of the incoherent diffusive halo over time. Significant differences were observed between the L* values obtained in healthy and edematous rat lungs in vivo. In the control rat lung, L* was found to be 332 μm (±48.8 μm), whereas in the edematous lung, it was 1040 μm (±90 μm). The reproducibility of the measurements of L* and D was tested in vivo and in phantoms made of melamine sponge with varying air volume fractions. Two-dimensional finite difference time domain numerical simulations were carried out on rabbit lung histology images with varying degrees of lung collapse. Significant correlations were observed between air volume fraction and L* in simulation (r = -0.9542, p < 0.0117) and sponge phantom (r = -0.9932, p < 0.0068) experiments. Ex vivo measurements of a rat lung in which edema was simulated by adding phosphate-buffered saline revealed a linear relationship between the fluid volume fraction and L*. These results illustrate the potential of methods based on ultrasound multiple scattering for the quantitative characterization of the lung parenchyma. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy.

PubMed

Iftikhar, Imran H; Alghothani, Lana; Sardi, Alejandro; Berkowitz, David; Musani, Ali I

2017-07-01

Transbronchial lung cryobiopsy is increasingly being used for the assessment of diffuse parenchymal lung diseases. Several studies have shown larger biopsy samples and higher yields compared with conventional transbronchial biopsies. However, the higher risk of bleeding and other complications has raised concerns for widespread use of this modality. To study the diagnostic accuracy and safety profile of transbronchial lung cryobiopsy and compare with video-assisted thoracoscopic surgery (VATS) by reviewing available evidence from the literature. Medline and PubMed were searched from inception until December 2016. Data on diagnostic performance were abstracted by constructing two-by-two contingency tables for each study. Data on a priori selected safety outcomes were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of transbronchial lung cryobiopsy were 83.7% (76.9-88.8%), 87% (85-89%), and 57% (40-73%), respectively. The pooled diagnostic yield, pooled sensitivity, and pooled specificity of VATS were 92.7% (87.6-95.8%), 91.0% (89-92%), and 58% (31-81%), respectively. The incidence of grade 2 (moderate to severe) endobronchial bleeding after transbronchial lung cryobiopsy and of post-procedural pneumothorax was 4.9% (2.2-10.7%) and 9.5% (5.9-14.9%), respectively. Although the diagnostic test accuracy measures of transbronchial lung cryobiopsy lag behind those of VATS, with an acceptable safety profile and potential cost savings, the former could be considered as an alternative in the evaluation of patients with diffuse parenchymal lung diseases.

Possible role of ammonia on the deposition, retention, and absorption of nicotine in humans while smoking.

PubMed

Seeman, Jeffrey I

2007-03-01

This perspective presents an overview of the properties of tobacco smoke aerosol and the possible effect of ammonia on the deposition location, retention and the amount and rate of nicotine absorption during cigarette smoking. Three main mechanisms describe the absorption of smoke constituents: (A) gas-phase constituents deposit directly; (B) particles deposit and the constituents then diffuse through the particle into the biological buffer and then into the tissue; and (C) particulate phase constituents evaporate from the particles and then deposit from the gas phase. Nicotine from smoking deposits and is absorbed predominately in the lungs. When particles deposit on the lung-blood interfaces, nicotine is absorbed rapidly, regardless of the acid-base nature of the particles. This is due to the buffering capacity of the lung-blood interfaces and the small mass of nicotine per puff distributed over a large number of particles depositing onto a huge lung surface. The composition of both tobacco smoke aerosol particles and the gas phase are time dependent. Ammonia in mainstream smoke evaporates faster from particles than nicotine. It is, therefore, unlikely that ammonia can significantly affect the volatility of MS smoke nicotine from particles in the smoke aerosol. It is certain that no single measurement of tobacco or of smoke, especially one made under equilibrium conditions, can adequately characterize the time-dependent properties of mainstream smoke aerosol. Thus, the fraction of nonprotonated freebase nicotine in trapped, aged smoke particulate matter has not been shown to be a useful predictor of the amount or total rate of nicotine uptake in human smokers. Similarly, "smoke pH" and "pHeff" are not useful practical parameters for providing understanding or predictability of tobacco smoke chemistry or nicotine bioavailability.

Impact of Computer-Aided CT and PET Analysis on Non-invasive T Staging in Patients with Lung Cancer and Atelectasis.

PubMed

Flechsig, Paul; Rastgoo, Ramin; Kratochwil, Clemens; Martin, Ole; Holland-Letz, Tim; Harms, Alexander; Kauczor, Hans-Ulrich; Haberkorn, Uwe; Giesel, Frederik L

2018-04-20

Tumor delineation within an atelectasis in lung cancer patients is not always accurate. When T staging is done by integrated 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG)-positron emission tomography (PET)/X-ray computer tomography (CT), tumors of neuroendocrine differentiation and slowly growing tumors can present with reduced FDG uptake, thus aggravating an exact T staging. In order to further exhaust information derived from [ 18 F]FDG-PET/CT, we evaluated the impact of CT density and maximum standardized uptake value (SUVmax) for the classification of different tumor subtypes within a surrounding atelectasis, as well as possible cutoff values for the differentiation between the primary tumor and atelectatic lung tissue. Seventy-two patients with histologically proven lung cancer and adjacent atelectasis were investigated. Non-contrast-enhanced [ 18 F]FDG-PET/CT was performed within 2 weeks before surgery/biopsy. Boundaries of the primary within the atelectasis were determined visually on the basis of [ 18 F]FDG uptake; CT density was quantified manually within each primary and each atelectasis. CT density of the primary (36.4 Hounsfield units (HU) ± 6.2) was significantly higher compared to that of atelectatic lung (24.3 HU ± 8.3; p < 0.01), irrespective of the histological subtype. The discrimination between different malignant tumors using density analysis failed. SUVmax was increased in squamous cell carcinomas compared to adenocarcinomas. Irrespective of the malignant subtype, a possible cutoff value of 24 HU may help to exclude the presence of a primary in lesions below 24 HU, whereas a density above a threshold of 40 HU can help to exclude atelectatic lung. Density measurements in patients with lung cancer and surrounding atelectasis may help to delineate the primary tumor, irrespective of the specific lung cancer subtype. This could improve T staging and radiation treatment planning (RTP) without additional application of a contrast agent in CT, or an additional magnetic resonance imaging (MRI), even in cases of lung tumors of neuroendocrine differentiation or in slowly growing tumors with less avidity to [ 18 F]FDG.

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.

Evaluation of a low-carbohydrate diet-based preparation protocol without fasting for cardiac PET/MR imaging.

PubMed

Nensa, Felix; Tezgah, E; Schweins, K; Goebel, J; Heusch, P; Nassenstein, K; Schlosser, T; Poeppel, T D

2017-06-01

Assessment of increased glucose uptake in inflammatory or malignant myocardial disease using PET/MRI relies on uptake suppression in normal myocardium. We evaluated the efficacy of a ≥24 hours high-fat, low-carbohydrate, and protein-permitted diet (HFLCPP) in combination with unfractionated heparin for suppression of "physiologic" myocardial glucose uptake. PET/MRI was successfully performed in 89 patients. HFLCPP was started ≥24 hours prior to PET/MRI. All patients received i.v. injection of unfractionated heparin (50 IU·kg -1 ) 15 minutes prior to FDG administration. Left ventricular FDG uptake was visually evaluated by two readers. Diffuse myocardial uptake exceeding liver uptake, isolated uptake in the lateral wall, or diffuse uptake in the entire circumference of the heart base were defined as failed suppression. Homogeneous myocardial uptake below liver uptake with/without focal uptake was defined as successful suppression. Success rate was 84%. Suppression was unsuccessful in 14 patients. No significant influence of gender (P = .40) or age (P = .21) was found. However, insufficient suppression was more common in patients younger than 45 years (20% vs 7%). PET/MR imaging completion rate was >97%. A HFLCPP diet in combination with unfractionated heparin was successfully implemented for cardiac PET/MRI and resulted in a sufficient suppression of myocardial FDG uptake in 84% of patients.

Interstitial diffusion and the relationship between compartment modelling and multi-scale spatial-temporal modelling of (18)F-FLT tumour uptake dynamics.

PubMed

Liu, Dan; Chalkidou, Anastasia; Landau, David B; Marsden, Paul K; Fenwick, John D

2014-09-07

Tumour cell proliferation can be imaged via positron emission tomography of the radiotracer 3'-deoxy-3'-18F-fluorothymidine (18F-FLT). Conceptually, the number of proliferating cells might be expected to correlate more closely with the kinetics of 18F-FLT uptake than with uptake at a fixed time. Radiotracer uptake kinetics are standardly visualized using parametric maps of compartment model fits to time-activity-curves (TACs) of individual voxels. However the relationship between the underlying spatiotemporal accumulation of FLT and the kinetics described by compartment models has not yet been explored. In this work tumour tracer uptake is simulated using a mechanistic spatial-temporal model based on a convection-diffusion-reaction equation solved via the finite difference method. The model describes a chain of processes: the flow of FLT between the spatially heterogeneous tumour vasculature and interstitium; diffusion and convection of FLT within the interstitium; transport of FLT into cells; and intracellular phosphorylation. Using values of model parameters estimated from the biological literature, simulated FLT TACs are generated with shapes and magnitudes similar to those seen clinically. Results show that the kinetics of the spatial-temporal model can be recovered accurately by fitting a 3-tissue compartment model to FLT TACs simulated for those tumours or tumour sub-volumes that can be viewed as approximately closed, for which tracer diffusion throughout the interstitium makes only a small fractional change to the quantity of FLT they contain. For a single PET voxel of width 2.5-5 mm we show that this condition is roughly equivalent to requiring that the relative difference in tracer uptake between the voxel and its neighbours is much less than one.

Correlation of iodine uptake and perfusion parameters between dual-energy CT imaging and first-pass dual-input perfusion CT in lung cancer.

PubMed

Chen, Xiaoliang; Xu, Yanyan; Duan, Jianghui; Li, Chuandong; Sun, Hongliang; Wang, Wu

2017-07-01

To investigate the potential relationship between perfusion parameters from first-pass dual-input perfusion computed tomography (DI-PCT) and iodine uptake levels estimated from dual-energy CT (DE-CT).The pre-experimental part of this study included a dynamic DE-CT protocol in 15 patients to evaluate peak arterial enhancement of lung cancer based on time-attenuation curves, and the scan time of DE-CT was determined. In the prospective part of the study, 28 lung cancer patients underwent whole-volume perfusion CT and single-source DE-CT using 320-row CT. Pulmonary flow (PF, mL/min/100 mL), aortic flow (AF, mL/min/100 mL), and a perfusion index (PI = PF/[PF + AF]) were automatically generated by in-house commercial software using the dual-input maximum slope method for DI-PCT. For the dual-energy CT data, iodine uptake was estimated by the difference (λ) and the slope (λHU). λ was defined as the difference of CT values between 40 and 70 KeV monochromatic images in lung lesions. λHU was calculated by the following equation: λHU = |λ/(70 - 40)|. The DI-PCT and DE-CT parameters were analyzed by Pearson/Spearman correlation analysis, respectively.All subjects were pathologically proved as lung cancer patients (including 16 squamous cell carcinoma, 8 adenocarcinoma, and 4 small cell lung cancer) by surgery or CT-guided biopsy. Interobserver reproducibility in DI-PCT (PF, AF, PI) and DE-CT (λ, λHU) were relatively good to excellent (intraclass correlation coefficient [ICC]Inter = 0.8726-0.9255, ICCInter = 0.8179-0.8842; ICCInter = 0.8881-0.9177, ICCInter = 0.9820-0.9970, ICCInter = 0.9780-0.9971, respectively). Correlation coefficient between λ and AF, and PF were as follows: 0.589 (P < .01) and 0.383 (P < .05). Correlation coefficient between λHU and AF, and PF were as follows: 0.564 (P < .01) and 0.388 (P < .05).Both the single-source DE-CT and dual-input CT perfusion analysis method can be applied to assess blood supply of lung cancer patients. Preliminary results demonstrated that the iodine uptake relevant parameters derived from DE-CT significantly correlated with perfusion parameters derived from DI-PCT.

Designing for diffusion: how can we increase uptake of cancer communication innovations?

PubMed

Dearing, James W; Kreuter, Matthew W

2010-12-01

The best innovations in cancer communication do not necessarily achieve uptake by researchers, public health and clinical practitioners, and policy makers. This paper describes design activities that can be applied and combined for the purpose of spreading effective cancer communication innovations. A previously developed Push-Pull-Infrastructure Model is used to organize and highlight the types of activities that can be deployed during the design phase of innovations. Scientific literature about the diffusion of innovations, knowledge utilization, marketing, public health, and our experiences in working to spread effective practices, programs, and policies are used for this purpose. Attempts to broaden the reach, quicken the uptake, and facilitate the use of cancer communication innovations can apply design activities to increase the likelihood of diffusion. Some simple design activities hold considerable promise for improving dissemination and subsequent diffusion. Augmenting current dissemination practices with evidence-based concepts from diffusion science, marketing science, and knowledge utilization hold promise for improving results by eliciting greater market pull. Inventors and change agencies seeking to spread cancer communication innovations can experience more success by explicit consideration of design activities that reflect an expanded version of the Push-Pull-Infrastructure Model. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Designing for Diffusion: How Can We Increase Uptake of Cancer Communication Innovations?

PubMed Central

Dearing, James W.; Kreuter, Matthew W.

2010-01-01

Objective The best innovations in cancer communication do not necessarily achieve uptake by researchers, public health and clinical practitioners, and policy makers. This paper describes design activities that can be applied and combined for the purpose of spreading effective cancer communication innovations. Methods A previously developed Push-Pull-Infrastructure Model is used to organize and highlight the types of activities that can be deployed during the design phase of innovations. Scientific literature about the diffusion of innovations, knowledge utilization, marketing, public health, and our experiences in working to spread effective practices, programs, and policies are used for this purpose. Results Attempts to broaden the reach, quicken the uptake, and facilitate the use of cancer communication innovations can apply design activities to increase the likelihood of diffusion. Some simple design activities hold considerable promise for improving dissemination and subsequent diffusion. Conclusion Augmenting current dissemination practices with evidence-based concepts from diffusion science, marketing science, and knowledge utilization hold promise for improving results by eliciting greater market pull. Practice Implications Inventors and change agencies seeking to spread cancer communication innovations can experience more success by explicit consideration of design activities that reflect an expanded version of the Push-Pull-Infrastructure Model. PMID:21067884

Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ.

PubMed

Samén, Erik; Lu, Li; Mulder, Jan; Thorell, Jan-Olov; Damberg, Peter; Tegnebratt, Tetyana; Holmgren, Lars; Rundqvist, Helene; Stone-Elander, Sharon

2014-03-26

Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ. (R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse. A heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands. The results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development.

Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ

PubMed Central

2014-01-01

Background Vascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ. Methods (R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse. Results A heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands. Conclusion The results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development. PMID:24670127

Spirometry, Static Lung Volumes, and Diffusing Capacity.

PubMed

Vaz Fragoso, Carlos A; Cain, Hilary C; Casaburi, Richard; Lee, Patty J; Iannone, Lynne; Leo-Summers, Linda S; Van Ness, Peter H

2017-09-01

Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry ( n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver ( n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity ( n = 2,508). Using multivariable linear regression, adjusted least-squares means (adj LS Means) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adj LS Means were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal ( n = 1,251), restrictive pattern ( n = 663), and air-flow obstruction (mild, [ n = 128]; moderate, [ n = 150]; and severe, [ n = 394]). Relative to normal spirometry, restrictive-pattern had lower adj LS Means for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity ( P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adj LS Means for FRC and RV ( P < .001). However, only mild and moderate air-flow obstruction had higher adj LS Means for TLC ( P < .001), while only moderate and severe air-flow obstruction had higher adj LS Means for RV/TLC ( P < .001) and lower adj LS Means for hemoglobin-adjusted single-breath diffusing capacity ( P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction ( P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction ( P < .001), thus opposing the increased FRC ( P < .001). Finally, P values were similar whether adj LS Means were height-cubed standardized. A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity). Copyright © 2017 by Daedalus Enterprises.

Bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions

DOE PAGES

Powell, Joshua D.; Hutchison, Janine R.; Hess, Becky M.; ...

2015-07-30

Aims: To better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems. Methods and Results: We evaluated the kinetics of uptake, germination and proliferation of B. anthracis Sterne spores in association with human primary lung epithelial cells, Calu-3, and A549 cell lines. We also analyzed the influence of various cell culture media formulations related to spore germination. Conclusions: We found negligible spore uptake by epithelial cells, but germination and proliferation of spores in the extracellular environment was evident, and was appreciably higher in A549 and Calu-3 cultures than in primary epithelial cells. Additionally, ourmore » results revealed spores in association with primary cells submerged in cell culture media germinated 1 h« less

ECT imaging with Tc(V)-99m dimercaptosuccinic acid useful to detect lung metastases of osteosarcoma

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

Ohta, H.; Ishii, M.; Yoshizumi, M.

1985-01-01

ECT imaging, using Tc(V)-99m dimercaptosuccinic acid (Tc(V)-DMS) was performed in two patients with lung metastasis of osteosarcoma, and the results were compared with those of CT scan. Clear accumulation of Tc(V)-DMS was recognized in all cases in the same area that CT scans demonstrated. Tc(V)-DMS was labeled under optimal pH 8, had very low SnCl/sub 2/ concentrations, an equilibrium between a stable form and a dissociated form of anion TcO/sub 4/(3-) structurally similar to PO/sub 4/(3-), and was postulated for tumor uptake. Considering this proposed mechanism for Tc(V)-DMS uptake by tumor cells, ECT imaging using this tracer could be ofmore » use in the early detection of lung metastasis of osteosarcoma.« less

Size-related bioconcentration kinetics of hydrophobic chemicals in fish

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

Sijm, D.T.H.M.; Linde, A. van der

1994-12-31

Uptake and elimination of hydrophobic chemicals by fish can be regarded as passive diffusive transport processes. Diffusion coefficients, lipid/water partitioning, diffusion pathlenghts, concentration gradients and surface exchange areas are key parameters describing this bioconcentration distribution process. In the present study two of these parameters were studied: the influence of lipid/water partitioning was studied by using hydrophobic chemicals of different hydrophobicity, and the surface exchange area by using different sizes of fish. By using one species of fish it was assumed that all other parameters were kept constant. Seven age classes of fish were exposed to a series of hydrophobic, formore » five days, which was followed by a deputation phase lasting up to 6 months. Bioconcentration parameters, such as uptake and elimination rate constants, and bioconcentration factors were determined. Uptake of the hydrophobic compounds was compared to that of oxygen. Uptake and elimination rates were compared to weight and estimated (gill) exchange areas. The role of weight and its implications for extrapolations of bioconcentration parameters to other species and sizes will be discussed.« less

Rifampicin Lipid-Polymer hybrid nanoparticles (LIPOMER) for enhanced Peyer's patch uptake.

PubMed

Bachhav, Sagar S; Dighe, Vikas D; Kotak, Darsheen; Devarajan, Padma V

2017-10-30

The oral uptake of intact nanocarriers through Peyer's patches is an important uptake pathway. We report Rifampicin Lipid-Polymer hybrid nanoparticles (RIF-LIPOMER) using glyceryl monostearate as lipid and the mucoadhesive polymer, Gantrez, with the objective of balancing hydrophobicity and mucoadhesion for enhanced Peyer's patch uptake. RIF-LIPOMER was optimized for size, hydrophobicity, and mucoadhesion using Box-Behnken. Designed RIF-LIPOMER (RIF-LIPO-120) exhibited average particle size in the range 300-400nm with drug loading >12%. DSC and XRD confirmed complete amorphization. Contact angle and mucoadhesion force revealed that RIF-LIPO-120 exhibited greater hydrophobicity and lower mucoadhesion compared to Gantrez nanoparticles (RIF-GzNP). Comparative uptake of fluorescent labelled RIF-LIPO-120 and RIF-GzNP, through Peyer's patch following intraduodenal administration in rats, revealed the high accumulation of RIF-GzNP at the villi border, and high Peyer's patch uptake of RIF-LIPO-120. Furthermore, lower accumulation of RIF-LIPO-120 in the liver, compared to RIF-GzNP, suggested bypass of the portal circulation and lymphatic uptake through Peyer's patches. Significantly higher lung: plasma concentration ratio exhibited by RIF-LIPO-120 compared to RIF-GzNP confirmed the same (p<0.05). Our study demonstrated that optimization of hydrophobicity and mucoadhesion of nanoparticles could favor Peyer's patch uptake, which in turn could enable enhanced drug accumulation in the lungs with advantage in the therapy of pulmonary afflictions. Copyright © 2017 Elsevier B.V. All rights reserved.

Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

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

Volkow, N.D.; Fowler, J.; Volkow, N.D.

2010-12-01

Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [{sup 11}C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight {approx}1246 g), livermore » (23%; weight {approx}1677 g) and intermediate in brain (10%; weight {approx}1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [{sup 11}C]d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.« less

Distribution and Pharmacokinetics of Methamphetamine in the Human Body: Clinical Implications

PubMed Central

Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Shumay, Elena; Telang, Frank; Thanos, Peter K.; Alexoff, David

2010-01-01

Background Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Methods Positron Emission Tomography (PET) was used in conjunction with [11C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Results Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight ∼1246 g), liver (23%; weight ∼1677 g) and intermediate in brain (10%; weight ∼1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7–16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22–50 minutes). Lung accumulation of [11C]d-methamphetamine was 30% higher for African Americans than Caucasians (p<0.05) but did not differ in other organs. Conclusions The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans. PMID:21151866

Livestock vaccine adoption among poor farmers in Bolivia: remembering innovation diffusion theory.

PubMed

Heffernan, Claire; Thomson, Kim; Nielsen, Louise

2008-05-02

The paper explores the low uptake of livestock vaccination among poor farming communities in Bolivia utilising core elements of the original innovation diffusion theory. Contrary to the recent literature, we found that vaccination behaviour was strongly linked to social and cultural, rather than economic, drivers. While membership in a group increased uptake, the 'hot' and 'cold' distinctions which dictate health versus illness within Andean cosmology also played a role, with vaccination viewed as a means of addressing underlying imbalances. We concluded that uptake of livestock vaccination was unlikely to improve without knowledge transfer that acknowledges local epistemologies for livestock disease.

Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles.

PubMed

Yuan, Xue; Xie, Qian; Su, Keyu; Li, Zhijie; Dong, Dong; Wu, Baojian

2017-01-01

Arenobufagin (ABG) is a major active component of toad venom, a traditional Chinese medicine used for cancer therapy. However, poor aqueous solubility limits its pharmacological studies in vivo due to administration difficulties. In this study, we aimed to develop a polymeric nanomicelle (PN) system to enhance the solubility of ABG for effective intravenous delivery. ABG-loaded PNs (ABG-PNs) were prepared with methoxy poly (ethylene glycol)-block-poly (d,l-lactic-co-glycolic acid) (mPEG-PLGA) using the solvent-diffusion technique. The obtained ABG-PNs were 105 nm in size with a small polydispersity index of 0.08. The entrapment efficiency and drug loading were 71.9% and 4.58%, respectively. Cellular uptake of ABG-PNs was controlled by specific clathrin-mediated endocytosis. In addition, ABG-PNs showed improved drug pharmacokinetics with an increased area under the curve value (a 1.73-fold increase) and a decreased elimination clearance (37.8% decrease). The nanomicelles showed increased drug concentrations in the liver and lung. In contrast, drug concentrations in both heart and brain were decreased. Moreover, the nanomicelles enhanced the anticancer effect of the pure drug probably via increased cellular uptake of drug molecules. In conclusion, the mPEG-PLGA-based nanomicelle system is a satisfactory carrier for the systemic delivery of ABG.

Multiphase chemical kinetics of OH radical uptake by molecular organic markers of biomass burning aerosols: humidity and temperature dependence, surface reaction, and bulk diffusion.

PubMed

Arangio, Andrea M; Slade, Jonathan H; Berkemeier, Thomas; Pöschl, Ulrich; Knopf, Daniel A; Shiraiwa, Manabu

2015-05-14

Multiphase reactions of OH radicals are among the most important pathways of chemical aging of organic aerosols in the atmosphere. Reactive uptake of OH by organic compounds has been observed in a number of studies, but the kinetics of mass transport and chemical reaction are still not fully understood. Here we apply the kinetic multilayer model of gas-particle interactions (KM-GAP) to experimental data from OH exposure studies of levoglucosan and abietic acid, which serve as surrogates and molecular markers of biomass burning aerosol (BBA). The model accounts for gas-phase diffusion within a cylindrical coated-wall flow tube, reversible adsorption of OH, surface-bulk exchange, bulk diffusion, and chemical reactions at the surface and in the bulk of the condensed phase. The nonlinear dependence of OH uptake coefficients on reactant concentrations and time can be reproduced by KM-GAP. We find that the bulk diffusion coefficient of the organic molecules is approximately 10(-16) cm(2) s(-1), reflecting an amorphous semisolid state of the organic substrates. The OH uptake is governed by reaction at or near the surface and can be kinetically limited by surface-bulk exchange or bulk diffusion of the organic reactants. Estimates of the chemical half-life of levoglucosan in 200 nm particles in a biomass burning plume increase from 1 day at high relative humidity to 1 week under dry conditions. In BBA particles transported to the free troposphere, the chemical half-life of levoglucosan can exceed 1 month due to slow bulk diffusion in a glassy matrix at low temperature.

Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Solomon, Melani; Schuchman, Edward H; Muro, Silvia

2017-07-05

Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Biodistribution of 99mTc-MAA on SPECT/CT performed for 90Y radioembolization therapy planning: a pictorial review.

PubMed

Bailey, J J; Dewaraja, Y; Hubers, D; Srinivasa, R N; Frey, K A

2017-10-01

To evaluate the frequency of 99mTc-MAA uptake in extrahepatic organs during 90Y radioembolization therapy planning. This retrospective case series of 70 subjects who underwent 99mTc-MAA hepatic artery perfusion studies between January 2014 and July 2016 for 90Y radioembolization therapy planning at our institution involved direct image review for all subjects, with endpoints recorded: lung shunt fraction, extrahepatic radiotracer uptake, time from MAA injection to imaging. Combined planar and SPECT/CT imaging findings in the 70 subjects demonstrated lung shunt fraction measurements of less than 10% in 53 (76%) subjects and greater than 10% in 17 (24%) subjects. All patients demonstrated renal cortical uptake, 23 (33%) demonstrated salivary gland uptake, 23 (33%) demonstrated thyroid uptake, and 32 (46%) demonstrated gastric mucosal uptake, with significant overlap between these groups. The range of elapsed times between MAA injection and initial imaging was 41-138 min, with a mean of 92 min. There was no correlation between time to imaging and the presence of extrahepatic radiotracer uptake at any site. During hepatic artery perfusion scanning for 90Y radioembolization therapy planning, extrahepatic uptake is common, particularly in the kidney, salivary gland, thyroid and gastric mucosa, and is hypothesized to result from breakdown of 99mTc-MAA over time. Given the breakdown to smaller aggregates and ultimately pertechnetate, this should not be a contraindication to actual Y-90 microsphere therapy. Although we found no correlation between time to imaging and extrahepatic uptake, most of our injection to imaging times were relatively short.

Lung injury induced by secondhand smoke exposure detected with hyperpolarized helium-3 diffusion MR.

PubMed

Wang, Chengbo; Mugler, John P; de Lange, Eduard E; Patrie, James T; Mata, Jaime F; Altes, Talissa A

2014-01-01

To determine whether helium-3 diffusion MR can detect the changes in the lungs of healthy nonsmoking individuals who were regularly exposed to secondhand smoke. Three groups were studied (age: 59 ± 9 years): 23 smokers, 37 exposure-to-secondhand-smoke subjects, and 29 control subjects. We measured helium-3 diffusion values at diffusion times from 0.23 to 1.97 s. One-way analysis of variance revealed that the mean area under the helium-3 diffusion curves (ADC AUC) of the smokers was significantly elevated compared with the controls and to the exposure-to-secondhand-smoke subjects (P < 0.001 both). No difference between the mean ADC AUC of the exposure-to-secondhand-smoke subjects and that of the controls was found (P = 0.115). However, application of a receiver operator characteristic-derived rule to classify subjects as either a "control" or a "smoker," based on ADC AUC, revealed that 30% (11/37) of the exposure-to-secondhand subjects were classified as "smokers" indicating an elevation of the ADC AUC. Using helium-3 diffusion MR, elevated ADC values were detected in 30% of nonsmoking healthy subjects who had been regularly exposed to secondhand smoke, supporting the concept that, in susceptible individuals, secondhand smoke causes mild lung damage. Copyright © 2013 Wiley Periodicals, Inc.

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.

Contribution of CT quantified emphysema, air trapping and airway wall thickness on pulmonary function in male smokers with and without COPD.

PubMed

Mohamed Hoesein, Firdaus A A; de Jong, Pim A; Lammers, Jan-Willem J; Mali, Willem P Th M; Mets, Onno M; Schmidt, Michael; de Koning, Harry J; Aalst, Carlijn van der; Oudkerk, Matthijs; Vliegenthart, Rozemarijn; Ginneken, Bram van; van Rikxoort, Eva M; Zanen, Pieter

2014-09-01

Emphysema, airway wall thickening and air trapping are associated with chronic obstructive pulmonary disease (COPD). All three can be quantified by computed tomography (CT) of the chest. The goal of the current study is to determine the relative contribution of CT derived parameters on spirometry, lung volume and lung diffusion testing. Emphysema, airway wall thickening and air trapping were quantified automatically on CT in 1,138 male smokers with and without COPD. Emphysema was quantified by the percentage of voxels below -950 Hounsfield Units (HU), airway wall thickness by the square root of wall area for a theoretical airway with 10 mm lumen perimeter (Pi10) and air trapping by the ratio of mean lung density at expiration and inspiration (E/I-ratio). Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were obtained. Standardized regression coefficients (β) were used to analyze the relative contribution of CT changes to pulmonary function measures. The independent contribution of the three CT measures differed per lung function parameter. For the FEV1 airway wall thickness was the most contributing structural lung change (β = -0.46), while for the FEV1/FVC this was emphysema (β = -0.55). For the residual volume (RV) air trapping was most contributing (β = -0.35). Lung diffusion capacity was most influenced by emphysema (β = -0.42). In a cohort of smokers with and without COPD the effect of different CT changes varies per lung function measure and therefore emphysema, airway wall thickness and air trapping need to be taken in account.

Differentiation of Central Lung Cancer from Atelectasis: Comparison of Diffusion-Weighted MRI with PET/CT

PubMed Central

Yang, Rui-Meng; Li, Long; Wei, Xin-Hua; Guo, Yong-Mei; Huang, Yun-Hai; Lai, Li-Sha; Chen, A-Mei; Liu, Guo-Shun; Xiong, Wei-Feng; Luo, Liang-Ping; Jiang, Xin-Qing

2013-01-01

Objective Prospectively assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis. Materials and Methods 38 consecutive lung cancer patients (26 males, 12 females; age range: 28–71 years; mean age: 49 years) who were referred for thoracic MR imaging examinations were enrolled. MR examinations were performed using a 1.5-T clinical scanner and scanning sequences of T1WI, T2WI, and DWI. Cancers and atelectasis were measured by mapping of the apparent diffusion coefficients (ADCs) obtained with a b-value of 500 s/mm2. Results PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm2/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both). Conclusions DW-MR imaging provides valuable information not obtained by conventional MR and may be useful for differentiation of central lung carcinoma from atelectasis. Future developments may allow DW-MR imaging to be used as an alternative to PET-CT in imaging of patients with lung cancer. PMID:23593186

A Simplified Model of Moisture Transport in Hydrophilic Porous Media With Applications to Pharmaceutical Tablets.

PubMed

Klinzing, Gerard R; Zavaliangos, Antonios

2016-08-01

This work establishes a predictive model that explicitly recognizes microstructural parameters in the description of the overall mass uptake and local gradients of moisture into tablets. Model equations were formulated based on local tablet geometry to describe the transient uptake of moisture. An analytical solution to a simplified set of model equations was solved to predict the overall mass uptake and moisture gradients with the tablets. The analytical solution takes into account individual diffusion mechanisms in different scales of porosity and diffusion into the solid phase. The time constant of mass uptake was found to be a function of several key material properties, such as tablet relative density, pore tortuosity, and equilibrium moisture content of the material. The predictions of the model are in excellent agreement with experimental results for microcrystalline cellulose tablets without the need for parameter fitting. The model presented provides a new method to analyze the transient uptake of moisture into hydrophilic materials with the knowledge of only a few fundamental material and microstructural parameters. In addition, the model allows for quick and insightful predictions of moisture diffusion for a variety of practical applications including pharmaceutical tablets, porous polymer systems, or cementitious materials. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Contribution of sediment fluxes and transformations to the summer nitrogen budget of an Upper Mississippi River backwater system

USGS Publications Warehouse

James, W.F.; Richardson, W.B.; Soballe, D.M.

2008-01-01

Routing nitrate through backwaters of regulated floodplain rivers to increase retention could decrease loading to nitrogen (N)-sensitive coastal regions. Sediment core determinations of N flux were combined with inflow-outflow fluxes to develop mass balance approximations of N uptake and transformations in a flow-controlled backwater of the Upper Mississippi River (USA). Inflow was the dominant nitrate source (>95%) versus nitrification and varied as a function of source water concentration since flow was constant. Nitrate uptake length increased linearly, while uptake velocity decreased linearly, with increasing inflow concentration to 2 mg l-1, indicating limitation of N uptake by loading. N saturation at higher inflow concentration coincided with maximum uptake capacity, 40% uptake efficiency, and an uptake length 2 times greater than the length of the backwater. Nitrate diffusion and denitrification in sediment accounted for 27% of the backwater nitrate retention, indicating that assimilation by other biota or denitrification on other substrates were the dominant uptake mechanisms. Ammonium export from the backwater was driven by diffusive efflux from the sediment. Ammonium increased from near zero at the inflow to a maximum mid-lake, then declined slightly toward the outflow due to uptake during transport. Ammonium export was small compared to nitrate retention. ?? 2007 Springer Science+Business Media B.V.

High-Resolution Computed Tomography and Pulmonary Function Findings of Occupational Arsenic Exposure in Workers.

PubMed

Ergün, Recai; Evcik, Ender; Ergün, Dilek; Ergan, Begüm; Özkan, Esin; Gündüz, Özge

2017-05-05

The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.

Comparison of Positron Emission Tomography Using 2-[18F]-fluoro-2-deoxy-D-glucose and 3-deoxy-3-[18F]-fluorothymidine in Lung Cancer Imaging

PubMed Central

Wang, Fu-Li; Tan, Ye-Ying; Gu, Xiang-Min; Li, Tian-Ran; Lu, Guang-Ming; Liu, Gang; Huo, Tian-Long

2016-01-01

Background: The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography (CT) imaging results remains a significant challenge. The 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[18F]-fluorothymidine (18F-FLT) in lung cancer PET/CT imaging. Methods: The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established (n = 12), and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values (SUVs), and Ki-67 proliferation marker expression were investigated. Results: The cell-tracer binding ratio for the A549 cells using the 18F-FDG was greater than the ratio using 18F-FLT (P < 0.05). The Ki-67 expression showed a significant positive correlation with the 18F-FLT binding ratio (r = 0.824, P < 0.01). The tumor-to-nontumor uptake ratio of 18F-FDG imaging in xenografts was higher than that of 18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of 18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of 18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of 18F-FDG and 18F-FLT (r = 0.658, P < 0.05 and r = 0.724, P < 0.01, respectively). Conclusions: The 18F-FDG uptake ratio is higher than that of 18F-FLT in A549 cells at the cellular level. 18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs. PMID:27958224

Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

PubMed

Cruces, Pablo; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Díaz, Franco

2013-11-01

The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI. © 2013 John Wiley & Sons Ltd.

POLUTE. Forest Air Pollutant Uptake Model

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

Murphy, C.E. Jr.; Sinclair, T.R.

1992-02-13

POLUTE is a computer model designed to estimate the uptake of air pollutants by forests. The model utilizes submodels to describe atmospheric diffusion immediately above and within the canopy, and into the sink areas within or on the trees. The program implementing the model is general and can be used, with only minor changes, for any gaseous pollutant. The model provides an estimate describing the response of the vegetarian-atmosphere system to the environment as related to three types of processes: atmospheric diffusion, diffusion near and inside the absorbing plant, and the physical and chemical processes at the sink on ormore » within the plant.« less

Characteristics of elderly patients with COPD and newly diagnosed lung cancer, and factors associated with treatment decision.

PubMed

Qin, Jianwen; Li, Guangsheng; Zhou, Jingmin

2016-01-01

To investigate the clinical features, diagnosis, and treatment status of elderly patients with chronic obstructive pulmonary disease (COPD) complicated with lung cancer. This was a retrospective study of 206 patients aged >60 years with COPD and newly diagnosed lung cancer at the Tianjin Chest Hospital Respiratory Centre between September 2008 and September 2013. Lung function, radiology, and clinical data were retrieved. Among all patients, 57% (117/206) were hospitalized due to acute COPD aggravation, 47% (96/206) had COPD grade III or IV, 95% (195/206), showed diffusion dysfunction in pulmonary function examination, 90% (185/206) had a history of smoking, and 26% (54/206) were treated with inhaled corticosteroids for COPD treatment. Ninety-eight patients suffered from squamous carcinoma, 73 from adenocarcinoma, and 35 from small-cell carcinoma. Clinical staging was I in 36 patients, II in 47 patients, III in 78 patients, and IV in 45 patients. Initial treatments were surgery in 59 patients, chemotherapy in 30 patients, and no treatment in 117 patients. Multivariate analysis showed that age (P<0.001), COPD grades (P=0.01), clinical staging (P<0.001), and pulmonary diffusion function (P=0.007) were independent factors associated with patients with COPD being given treatments for lung cancer. Younger patients with lower COPD grades, earlier lung cancer stage, and better pulmonary diffusion function are more likely to receive treatments.

Random Walk Simulation of the MRI Apparent Diffusion Coefficient in a Geometrical Model of the Acinar Tree

PubMed Central

Pérez-Sánchez, José M.; Rodríguez, Ignacio; Ruiz-Cabello, Jesús

2009-01-01

Abstract Apparent diffusion coefficient (ADC) measurement in the lung using gas magnetic resonance imaging is a promising technique with potential for reflecting changes in lung microstructure. Despite some recent impressive human applications, full interpretation of ADC measures remains an elusive goal, due to a lack of detailed knowledge about the structure dependency of ADC. In an attempt to fill this gap we have performed random walk simulations in a three-dimensional geometrical model of the lung acinus, the distal alveolated sections of the lung tree accounting for ∼90% of the total lung volume. Simulations were carried out adjusting model parameters after published morphological data for the rat peripheral airway system, which predict an ADC behavior as microstructure changes with lung inflation in partial agreement with measured ADCs at different airway pressures. The approach used to relate experimental ADCs to lung microstructural changes does not make any assumption about the cause of the changes, so it could be applied to other scenarios such as chronic obstructive pulmonary disease, lung development, etc. The work presented here predicts numerically for the first time ADC values measured in the lung from independent morphological measures of lung microstructure taken at different inflation stages during the breath cycle. PMID:19619480

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

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.

Nonlinear Porous Diffusion Modeling of Hydrophilic Ionic Agrochemicals in Astomatous Plant Cuticle Aqueous Pores: A Mechanistic Approach.

PubMed

Tredenick, Eloise C; Farrell, Troy W; Forster, W Alison; Psaltis, Steven T P

2017-01-01

The agricultural industry requires improved efficacy of sprays being applied to crops and weeds in order to reduce their environmental impact and deliver improved financial returns. Enhanced foliar uptake is one means of improving efficacy. The plant leaf cuticle is known to be the main barrier to diffusion of agrochemicals within the leaf. The usefulness of a mathematical model to simulate uptake of agrochemicals in plant cuticles has been noted previously in the literature, as the results of each uptake experiment are specific to each formulation of active ingredient, plant species and environmental conditions. In this work we develop a mathematical model and numerical simulation for the uptake of hydrophilic ionic agrochemicals through aqueous pores in plant cuticles. We propose a novel, nonlinear, porous diffusion model for ionic agrochemicals in isolated cuticles, which extends simple diffusion through the incorporation of parameters capable of simulating: plant species variations, evaporation of surface droplet solutions, ion binding effects on the cuticle surface and swelling of the aqueous pores with water. We validate our theoretical results against appropriate experimental data, discuss the key sensitivities in the model and relate theoretical predictions to appropriate physical mechanisms. Major influencing factors have been found to be cuticle structure, including tortuosity and density of the aqueous pores, and to a lesser extent humidity and cuticle surface ion binding effects.

Nonlinear Porous Diffusion Modeling of Hydrophilic Ionic Agrochemicals in Astomatous Plant Cuticle Aqueous Pores: A Mechanistic Approach

PubMed Central

Tredenick, Eloise C.; Farrell, Troy W.; Forster, W. Alison; Psaltis, Steven T. P.

2017-01-01

The agricultural industry requires improved efficacy of sprays being applied to crops and weeds in order to reduce their environmental impact and deliver improved financial returns. Enhanced foliar uptake is one means of improving efficacy. The plant leaf cuticle is known to be the main barrier to diffusion of agrochemicals within the leaf. The usefulness of a mathematical model to simulate uptake of agrochemicals in plant cuticles has been noted previously in the literature, as the results of each uptake experiment are specific to each formulation of active ingredient, plant species and environmental conditions. In this work we develop a mathematical model and numerical simulation for the uptake of hydrophilic ionic agrochemicals through aqueous pores in plant cuticles. We propose a novel, nonlinear, porous diffusion model for ionic agrochemicals in isolated cuticles, which extends simple diffusion through the incorporation of parameters capable of simulating: plant species variations, evaporation of surface droplet solutions, ion binding effects on the cuticle surface and swelling of the aqueous pores with water. We validate our theoretical results against appropriate experimental data, discuss the key sensitivities in the model and relate theoretical predictions to appropriate physical mechanisms. Major influencing factors have been found to be cuticle structure, including tortuosity and density of the aqueous pores, and to a lesser extent humidity and cuticle surface ion binding effects. PMID:28539930

Respiratory factors in the uptake and excretion of anesthetics. 1965.

PubMed

Epstein, R M; Papper, E M

1998-01-01

We have considered some of the ways in which respiration can affect the gas exchange process. The simplest relationships are purely physical and relate to the speed with which the lung and tissues can be filled or emptied. More complex relationships involve a consideration of the interplay between blood and gas in the lung and the effects of gas exchange on respiratory volumes themselves. Finally, some examples of the importance of physiologic alteration produced by, and producing respiratory shifts during, gas uptake processes were presented briefly. The detailed interpretation of gas exchange phenomena demands more quantitative information of this sort, concerning not only the respiratory but the circulatory and tissue level variations affecting uptake during anesthesia. Nevertheless, understanding of the principles and application of such data as are available can go far toward removing the handicaps of empirical practice from the day-to-day administration of anesthetic agents to human beings.

The Cytotoxicity and Genotoxicity of Hexavalent Chromium in Steller Sea Lion Lung Fibroblasts Compared to Human Lung Fibroblasts

PubMed Central

Wise, John Pierce; Wise, Sandra S.; Holmes, Amie L.; LaCerte, Carolyne; Shaffiey, Fariba; Aboueissa, AbouEl-Makarim

2010-01-01

In this study we directly compared soluble and particulate chromate cytotoxicity and genotoxicity in human (Homo sapiens) and sea lion (Eumetopias jubatus) lung fibroblasts. Our results show that hexavalent chromium induces increased cell death and chromosome damage in both human and sea lion cells with increasing intracellular chromium ion levels. The data further indicate that both sodium chromate and lead chromate are less cytotoxic and genotoxic to sea lion cells than human cells, based on administered dose. Differences in chromium ion uptake explained some but not all of the reduced amounts of sodium chromate-induced cell death. By contrast, uptake differences could explain the differences in sodium chromate-induced chromosome damage and particulate chromate-induced toxicity. Altogether they indicate that while hexavalent chromium induces similar toxic effects in sea lion and human cells, there are different mechanisms underlying the toxic outcomes. PMID:20211760

Diffuse Parenchymal Diseases Associated With Aluminum Use and Primary Aluminum Production

PubMed Central

2014-01-01

Aluminum use and primary aluminum production results in the generation of various particles, fumes, gases, and airborne materials with the potential for inducing a wide range of lung pathology. Nevertheless, the presence of diffuse parenchymal or interstitial lung disease related to these processes remains controversial. The relatively uncommon occurrence of interstitial lung diseases in aluminum-exposed workers—despite the extensive industrial use of aluminum—the potential for concurrent exposure to other fibrogenic fibers, and the previous use of inhaled aluminum powder for the prevention of silicosis without apparent adverse respiratory effects are some of the reasons for this continuing controversy. Specific aluminum-induced parenchymal diseases described in the literature, including existing evidence of interstitial lung diseases, associated with primary aluminum production are reviewed. PMID:24806728

Lung hilar Ga-67 uptake in patients with lymphoma following chemotherapy.

PubMed

Gunay, Emel Ceylan; Salanci, Bilge Volkan; Barista, Ibrahim; Caner, Biray

2004-07-01

Scintigraphic characteristics of lung hilar Ga-67 uptake (HU) and their relationship with the etiology (benign vs. malignant) of the hilar lesions in lymphoma patients following chemotherapy were retrospectively investigated. A total of 161 lymphoma patients were included in the study. The presence/absence of HU and if present, symmetry/asymmetry and intensity of HU (on the basis of a 3 scale grading system) were visually and semiquantitatively assessed on transaxial sections of thorax Ga-67 SPECT. By drawing ROIs over right and left hilum, asymmetry index (AI%) was also calculated. HU was categorized as benign or malignant depending on the radiological correlation and clinical follow-up. In the malignant group, the majority of patients (85.7%) had grade 2 or grade 3 uptake and all had asymmetric pattern. However, in the benign group, grade 1 uptake was more common (66%) and was mainly symmetric (94.6%) in appearance. AI% in the malignant group (73.7 +/- 36.6) was significantly higher than in the benign group (5.7 +/- 4.9) confirming the marked asymmetry in malignant patients.

[Solitary Peripheral Pulmonary Squamous Cell Papilloma;Diagnostic Significance of 18F-fluorodeoxyglucose Positron Emission Tomography Findings].

PubMed

Hayashi, Tetsuya; Tachibana, Syuichi; Nakao, Keiichi; Tokitsu, Kosuke; Morita, Takuya; Kishima, Genichi

2017-04-01

The patient was a 79-year-old woman who had received enucleation of right pulmonary papilloma 7 years earlier. She experienced bloody sputum and was therefore referred to our hospital. Chest computed tomography revealed a mass shadow(21 mm) in the right upper lobe (S2). By bronchoscopy, there was no bulging lesion in the visible range. SCC and CEA increased to 6.4 ng/ml and 6.42 ng/ml, respectively. Whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased FDG uptake in the region of the right-lung mass shadow (maximum standardized uptake value 12.95). Since malignancy could not be ruled out, a wedge resection was performed. The post-operative histopathologic diagnosis was squamous cell papilloma. Our literature review showed 12 out of 14 cases with solitary papilloma of the peripheral lung to have increased FDG uptake. Ki-67 positive cells were confirmed in the basal layers of the epithelium, and active cell proliferation of the papilloma is likely to be a cause of increased FDG uptake.

Mathematical Description of the Uptake of Hydrocarbons in Jet Fuel into the Stratum Corneum of Human Volunteers

PubMed Central

Kim, David; Farthing, Matthew W.; Miller, Cass T.; Nylander-French, Leena A.

2008-01-01

The objective of this research was to develop a mathematical description of uptake of aromatic and aliphatic hydrocarbons into the stratum corneum of human skin in vivo. A simple description based on Fick’s Laws of diffusion was used to predict the spatiotemporal variation of naphthalene, 1- and 2-methylnaphthalene, undecane, and dodecane in the stratum corneum of human volunteers. The estimated values of the diffusion coefficients for each chemical were comparable to values predicted using in vitro skin systems and biomonitoring studies. These results demonstrate the value of measuring dermal exposure using the tape-strip technique and the importance of quantifying of dermal uptake. PMID:18423910

Discussion on the alteration of FDG uptake by the breast according to the menstrual cycle in 18F-FDG PET/CT

NASA Astrophysics Data System (ADS)

Park, H. H.; Park, M. S.; Lee, C. H.; Cho, J. H.; Dong, K. R.; Chung, W. K.

2012-09-01

18F-FDG (fluorodeoxyglucose) PET (positron emission tomography)/CT (computed tomography) is a useful modality for identifying high-glucose-consuming cells, such as cancer cells, by the glucose metabolism of FDG. FDG is taken up by cancer and inflammatory cells, but occasionally there is also some FDG uptake by normal tissues as a result of their individual physiological characteristics. In particular, in fertile females, unusual FDG uptake in the breast changes according to the stages in the menstrual cycle, which can adversely affect a diagnosis. Therefore, this study examined the change in breast FDG uptake in the menstrual cycle on 18F-FDG PET/CT. One hundred and sixty females (34±3.5 years old), who had not undergone a gynecologic anamnesis and had a regular menstrual cycle over the previous 6 months, were examined from March 2010 to February 2011. The subjects were divided into the following four groups (each with 40 patients): flow phase, proliferative phase, ovulatory phase and secretory phase using Pregnancy Calculator Ver. 0.14 and history taking. Discovery Ste was used as the PET/CT. The standardized uptake values (SUVs) on the accumulated region on the breast were analyzed, and three nuclear medicine specialists performed a blind test. The SUVs on the breast were the flow phase (1.64±0.25), proliferative phase (0.93±0.28), ovulatory phase (1.66±0.26) and secretory phase (1.77±0.28). A high uptake value was observed in the secretory, flow and ovulatory phases. The FDG accumulation of the breast was divided into the following three grades compared with the lung and liver by gross analysis: the breast uptake was equal to the lung (Grade I), between the lung and liver (Grade II) and equal to or greater than the liver (Grade III). These results showed a high uptake value in the secretory, flow and ovulatory phases. In fertile females, the FDG uptake of the breast showed changes according to the menstrual cycle, which can be used to improve the diagnosis of breast disease. Therefore, the false-negative findings of breast disease can be reduced by performing an examination at the appropriate period through history taking and considering the individual menstrual cycle.

Water Uptake Behavior and Young Modulus Prediction of Composites Based on Treated Sisal Fibers and Poly(Lactic Acid)

PubMed Central

Orue, Ander; Eceiza, Arantxa; Peña-Rodriguez, Cristina; Arbelaiz, Aitor

2016-01-01

The main aim of this work was to study the effect of sisal fiber surface treatments on water uptake behavior of composites based on untreated and treated fibers. For this purpose, sisal fibers were treated with different chemical treatments. All surface treatments delayed the water absorption of fibers only for a short time of period. No significant differences were observed in water uptake profiles of composites based on fibers with different surface treatments. After water uptake period, tensile strength and Young modulus values of sisal fiber/poly(lactic acid) (PLA) composites were decreased. On the other hand, composites based on NaOH + silane treated fibers showed the lowest diffusion coefficient values, suggesting that this treatment seemed to be the most effective treatment to reduce water diffusion rate into the composites. Finally, Young modulus values of composites, before water uptake period, were predicted using different micromechanical models and were compared with experimental data. PMID:28773524

The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles

PubMed Central

Cho, Eun Chul; Zhang, Qiang; Xia, Younan

2011-01-01

In vitro experiments typically measure the uptake of nanoparticles by exposing cells at the bottom of a culture plate to a suspension of nanoparticles, which is assumed to be well-dispersed. However, nanoparticles can sediment and this means the concentration of particles on the cell surface and those actually taken up by the cells may be higher than the initial bulk concentration. Here we use upright and inverted cell culture configurations to show that cellular uptake of gold nanoparticles depends on the sedimentation and diffusion velocities of the nanoparticles and is independent of size, shape, density, surface coating and initial concentration of the nanoparticles. Generally more nanoparticles are taken up in the upright configuration than the inverted one and nanoparticles that sediment faster showed greater differences in uptake between the two configurations. Our results suggest that cellular uptake of nanoparticles is sensitive to the way cells are positioned and sedimentation need to be considered when performing in vitro studies for large and heavy nanoparticles. PMID:21516092

Transfection efficiency and uptake process of polyplexes in human lung endothelial cells: a comparative study in non-polarized and polarized cells.

PubMed

Mennesson, Eric; Erbacher, Patrick; Piller, Véronique; Kieda, Claudine; Midoux, Patrick; Pichon, Chantal

2005-06-01

Following systemic administration, polyplexes must cross the endothelium barrier to deliver genes to the target cells underneath. To design an efficient gene delivery system into lung epithelium, we evaluated capture and transfection efficiencies of DNA complexed with either Jet-PEI (PEI-polyplexes) or histidylated polylysine (His-polyplexes) in human lung microvascular endothelial cells (HLMEC) and tracheal epithelial cells. After optimizing growth conditions to obtain a tight HLMEC monolayer, we characterized uptake of polyplexes by flow cytometry and evaluated their transfection efficiency. Polyplexes were formulated as small particles. YOYO-labelled plasmid fluorescence intensity and luciferase activity were used as readouts for uptake and gene expression, respectively. PEI-polyplexes were more efficiently taken up than His-polyplexes by both non-polarized (2-fold) and polarized HLMEC (10-fold). They were mainly internalized by a clathrin-dependent pathway whatever the cell state. In non-polarized cells, His-polyplexes entered also mainly via a clathrin-dependent pathway but with an involvement of cholesterol. The cell polarization decreased this way and a clathrin-independent pathway became predominant. PEI-polyplexes transfected more efficiently HLMEC than His-polyplexes (10(7) vs. 10(5) relative light units (RLU)/mg of proteins) with a more pronounced difference in polarized cells. In contrast, no negative effect of the cell polarization was observed with tracheal epithelial cells in which both polyplexes had comparable efficiency. We show that the efficiency of polyplex uptake by HLMEC and their internalization mechanism are polymer-dependent. By contrast with His-polyplexes, the HLMEC polarization has little influence on the uptake process and on the transfection efficiency of PEI-polyplexes. Copyright (c) 2005 John Wiley & Sons, Ltd.

Repeatability of FDG PET/CT metrics assessed in free breathing and deep inspiration breath hold in lung cancer patients.

PubMed

Nygård, Lotte; Aznar, Marianne C; Fischer, Barbara M; Persson, Gitte F; Christensen, Charlotte B; Andersen, Flemming L; Josipovic, Mirjana; Langer, Seppo W; Kjær, Andreas; Vogelius, Ivan R; Bentzen, Søren M

2018-01-01

We measured the repeatability of FDG PET/CT uptake metrics when acquiring scans in free breathing (FB) conditions compared with deep inspiration breath hold (DIBH) for locally advanced lung cancer. Twenty patients were enrolled in this prospective study. Two FDG PET/CT scans per patient were conducted few days apart and in two breathing conditions (FB and DIBH). This resulted in four scans per patient. Up to four FDG PET avid lesions per patient were contoured. The following FDG metrics were measured in all lesions and in all four scans: Standardized uptake value (SUV) peak , SUV max , SUV mean , metabolic tumor volume (MTV) and total lesion glycolysis (TLG), based on an isocontur of 50% of SUV max . FDG PET avid volumes were delineated by a nuclear medicine physician. The gross tumor volumes (GTV) were contoured on the corresponding CT scans. Nineteen patients were available for analysis. Test-retest standard deviations of FDG uptake metrics in FB and DIBH were: SUV peak FB/DIBH: 16.2%/16.5%; SUV max : 18.2%/22.1%; SUV mean : 18.3%/22.1%; TLG: 32.4%/40.5%. DIBH compared to FB resulted in higher values with mean differences in SUV max of 12.6%, SUV peak 4.4% and SUV mean 11.9%. MTV, TLG and GTV were all significantly smaller on day 1 in DIBH compared to FB. However, the differences between metrics under FB and DIBH were in all cases smaller than 1 SD of the day to day repeatability. FDG acquisition in DIBH does not have a clinically relevant impact on the uptake metrics and does not improve the test-retest repeatability of FDG uptake metrics in lung cancer patients.

Challenges in pulmonary fibrosis · 3: Cystic lung disease

PubMed Central

Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

2007-01-01

Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID:17726170

Altered carnitine transport in pressure-overload hypertrophied rat hearts

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

O'Rourke, B.; Foster, K.; Reibel, D.K.

1986-03-01

The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L-/sup 14/C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 ..mu..M carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. Themore » reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 ..mu..M carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart.« less

DIVALENT METAL TRANSPORTER-1 REGULATION BY IRON AND VANADIUM MODULATES HYDROGEN PEROXIDE-INDUCED DNA DAMAGE IN LUNG CELLS

EPA Science Inventory

The divalent metal transporter-1 (DMT1) participates in the detoxification of metals that can damage lung epithelium. Elevated iron levels increase the expression of DMT1 in bronchial epithelial cells stimulating its uptake and storage in ferritin, thus making iron unavailable t...

Lung tumor segmentation in PET images using graph cuts.

PubMed

Ballangan, Cherry; Wang, Xiuying; Fulham, Michael; Eberl, Stefan; Feng, David Dagan

2013-03-01

The aim of segmentation of tumor regions in positron emission tomography (PET) is to provide more accurate measurements of tumor size and extension into adjacent structures, than is possible with visual assessment alone and hence improve patient management decisions. We propose a segmentation energy function for the graph cuts technique to improve lung tumor segmentation with PET. Our segmentation energy is based on an analysis of the tumor voxels in PET images combined with a standardized uptake value (SUV) cost function and a monotonic downhill SUV feature. The monotonic downhill feature avoids segmentation leakage into surrounding tissues with similar or higher PET tracer uptake than the tumor and the SUV cost function improves the boundary definition and also addresses situations where the lung tumor is heterogeneous. We evaluated the method in 42 clinical PET volumes from patients with non-small cell lung cancer (NSCLC). Our method improves segmentation and performs better than region growing approaches, the watershed technique, fuzzy-c-means, region-based active contour and tumor customized downhill. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

PubMed

Holtfreter, Birte; Richter, Stefanie; Kocher, Thomas; Dörr, Marcus; Völzke, Henry; Ittermann, Till; Obst, Anne; Schäper, Christoph; John, Ulrich; Meisel, Peter; Grotevendt, Anne; Felix, Stephan B; Ewert, Ralf; Gläser, Sven

2013-12-01

This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases.

Lung diffusion capacity in children with respiratory symptoms and untreated GERD.

PubMed

Mirić, Mirjana; Turkalj, Mirjana; Nogalo, Boro; Erceg, Damir; Perica, Marija; Plavec, Davor

2014-05-12

Gastroesophageal reflux disease (GERD) is associated with many respiratory disorders, among which, chronic cough, laryngitis, and asthma are among the most common. We investigated lung function, including gas diffusion capacity, in children with poor asthma control or chronic laryngitis with untreated GERD. A total of 71 children, aged 6-17 years, with chronic respiratory and other symptoms suggestive for GERD, were enrolled and divided into 2 groups: chronic laryngitis and asthma. Participants underwent 24-hour pH monitoring and lung function assessment, measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCO), and fraction of exhaled nitric oxide (FENO) measurement. 24-hour pH monitoring was positive for GERD in 92.1% of preselected children with asthma and 90.1% of children with chronic recurrent laryngitis. All flows (PEF, MEF75, MEF50, and MEF25) were significantly lower in the asthma group, while FENO and DLCO were significantly lower in the laryngitis group. A significant inverse relationship was found between DLCO and all reflux indexes in the laryngitis group. Each unit change of Johnson-DeMeester score and Boix-Ochoa score increased the odds for significantly lower DLCO in laryngitis patients by 3.9% and 5.5%, respectively. In children with uncontrolled asthma and chronic laryngitis, the regurgitation of gastric contents due to GERD contributes to poor asthma control and aggravation of chronic laryngitis. Despite having normal lung function, the gas diffusion capacity should be controlled in patients with GERD and chronic laryngitis, and it might be the very first abnormality in distal airways.

IDH mutation is paradoxically associated with higher 18F-FDOPA PET uptake in diffuse grade II and grade III gliomas.

PubMed

Verger, A; Metellus, Ph; Sala, Q; Colin, C; Bialecki, E; Taieb, D; Chinot, O; Figarella-Branger, D; Guedj, E

2017-08-01

The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and 18 F-FDOPA uptake on PET in newly diagnosed gliomas. A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone 18 F-FDOPA PET at an initial stage before surgery and histological diagnosis. 18 F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). Patients with IDH mutation showed higher 18 F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). This study showed paradoxically higher 18 F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of 18 F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation.

Uptake of PAHs into polyoxymethylene and application to oil-soot (lampblack)-impacted soil samples.

PubMed

Hong, Lei; Luthy, Richard G

2008-05-01

Polyoxymethylene (POM) is a polymeric material used increasingly in passive sampling of hydrophobic organic contaminants such as PAHs and PCBs in soils and sediments. In this study, we examined the sorption behavior of 12 PAH compounds to POM and observed linear isotherms spanning two orders of magnitude of aqueous concentrations. Uptake kinetic studies performed in batch systems for up to 54 d with two different volume ratios of POM-to-aqueous phase were evaluated with coupled diffusion and mass transfer models to simulate the movement of PAHs during the uptake process and to assess the physicochemical properties and experimental conditions that control uptake rates. Diffusion coefficients of PAHs in POM were estimated to be well correlated with diffusants' molecular weights as D(POM) proportional, variant(MW)(-3), descending from 2.3 x 10(-10) cm(2) s(-1) for naphthalene to 7.0 x 10(-11) cm(2) s(-1) for pyrene. The uptake rates for PAHs with log K(ow)<5.8 were controlled by the POM phase and the hydrophobicity of PAH compounds. For more hydrophobic PAH compounds, the aqueous boundary layer played an increasingly important role in determining the overall mass transfer rate. The POM partitioning technique was demonstrated to agree well with two other procedures for measuring PAH soil-water distribution coefficients in oil-soot (lampblack) containing soil samples.

Comparison of measurement methods for benzene and toluene

NASA Astrophysics Data System (ADS)

Wideqvist, U.; Vesely, V.; Johansson, C.; Potter, A.; Brorström-Lundén, E.; Sjöberg, K.; Jonsson, T.

Diffusive sampling and active (pumped) sampling (tubes filled with Tenax TA or Carbopack B) were compared with an automatic BTX instrument (Chrompack, GC/FID) for measurements of benzene and toluene. The measurements were made during differing pollution levels and different weather conditions at a roof-top site and in a densely trafficked street canyon in Stockholm, Sweden. The BTX instrument was used as the reference method for comparison with the other methods. Considering all data the Perkin-Elmer diffusive samplers, containing Tenax TA and assuming a constant uptake rate of 0.406 cm3 min-1, showed about 30% higher benzene values compared to the BTX instrument. This discrepancy may be explained by a dose-dependent uptake rate with higher uptake rates at lower dose as suggested by laboratory experiments presented in the literature. After correction by applying the relationship between uptake rate and dose as suggested by Roche et al. (Atmos. Environ. 33 (1999) 1905), the two methods agreed almost perfectly. For toluene there was much better agreement between the two methods. No sign of a dose-dependent uptake could be seen. The mean concentrations and 95% confidence intervals of all toluene measurements (67 values) were (10.80±1.6) μg m -3 for diffusive sampling and (11.3±1.6) μg m -3 for the BTX instrument, respectively. The overall ratio between the concentrations obtained using diffusive sampling and the BTX instrument was 0.91±0.07 (95% confidence interval). Tenax TA was found to be equal to Carbopack B for measuring benzene and toluene in this concentration range, although it has been proposed not to be optimal for benzene. There was also good agreement between the active samplers and the BTX instrument.

Use of Inert Gases to Study the Interaction of Blood Flow and Diffusion during Passive Absorption from the Gastrointestinal Tract of the Rat

PubMed Central

Levitt, Michael D.; Levitt, David G.

1973-01-01

Measurement of the relative absorption rates of inert gases (H2, He, CH4, SF6, and 133Xe) was used to investigate the interaction between diffusion and blood flow during passive absorption from the stomach, small bowel, and colon of the rat. If uptake is blood flow limited, the gases should be absorbed in proportion to their solubilities in blood, but if diffusion limited, uptake should be proportional to the diffusion rate of the gases in mucosal tissues. The observed absorption data were fitted to a series of models of interaction between perfusion and diffusion. A simple model accurately predicted the absorption rates of the gases from all segments of bowel. In this model, gas is absorbed into two distinct blood flows: one which flows in proximity to the lumen and completely equilibrates with the lumen, and a second which is sufficiently rapid and distant from the lumen that its gas uptake is entirely diffusion limited. The fraction of the total absorption attributable to the equilibrating flow can be readily calculated and equalled 93%, 77%, and 33% for the small bowel, colon, and stomach, respectively. Thus the rate of passive absorption of gases from the small bowel is limited almost entirely by the blood flow to the mucosa, and absorption from the stomach is largely limited by the diffusion rate of the gases. The flow which equilibrates with the lumen can be quantitated, and this flow may provide a useful measure of “effective” mucosal blood flow. Images PMID:4719667

Diffusion and cellular uptake of drugs in live cells studied with surface-enhanced Raman scattering probes

NASA Astrophysics Data System (ADS)

Bálint, Štefan; Rao, Satish; Sánchez, Mónica Marro; Huntošová, Veronika; Miškovský, Pavol; Petrov, Dmitri

2010-03-01

An understanding of the mechanisms of drug diffusion and uptake through cellular membranes is critical for elucidating drug action and in the development of effective drug delivery systems. We study these processes for emodin, a potential anticancer drug, in live cancer cells using surface-enhanced Raman scattering. Micrometer-sized silica beads covered by nanosized silver colloids are passively embedded into the cell and used as sensors of the drug. We demonstrate that the technique offers distinct advantages: the possibility to study the kinetics of drug diffusion through the cellular membrane toward specific cell organelles, the detection of lower drug concentrations compared to fluorescence techniques, and less damage imparted on the cell.

POLUTE; forest air pollutant uptake model. [IBM360,370; CSMP

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

Murphy, C.E.

POLUTE is a computer model designed to estimate the uptake of air pollutants by forests. The model utilizes submodels to describe atmospheric diffusion immediately above and within the canopy, and into the sink areas within or on the trees. The program implementing the model is general and can be used, with only minor changes, for any gaseous pollutant. The model provides an estimate describing the response of the vegetarian-atmosphere system to the environment as related to three types of processes: atmospheric diffusion, diffusion near and inside the absorbing plant, and the physical and chemical processes at the sink on ormore » within the plant.IBM360,370; CSMP; OS/370.« less

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

99mTc-zolmitriptan: radiolabeling, molecular modeling, biodistribution and gamma scintigraphy as a hopeful radiopharmaceutical for lung nuclear imaging.

PubMed

Rashed, H M; Marzook, F A; Farag, H

2016-12-01

Lung imaging radiopharmaceuticals are helpful agents for measuring pulmonary blood flow and allow detection of pulmonary embolism and lung cancer. The goal of this study was to develop a novel potential radiopharmaceutical for lung imaging. Zolmitriptan (a selective serotonin receptor agonist) was successfully labeled with 99m Tc via direct labeling method under reductive conditions studying different factors affecting the labeling efficiency. 99m Tc-zolmitriptan was obtained with a maximum labeling yield of 92.5 ± 0.61 % and in vitro stability up to 24 h. Molecular modeling was done to predict the structure of 99m Tc-zolmitriptan and ensure that radiolabeling did not affect binding ability of zolmitriptan to its receptor. Biodistribution studies showed that maximum lung uptake of 99m Tc-zolmitriptan was 23.89 ± 1.2 % injected dose/g tissue at 15 min post-injection and retention in lungs remained high up to 1 h, whereas the clearance from mice appeared to proceed mainly via the renal pathway. Scintigraphic images confirmed the biodistribution results showing a high resolution lung image with low accumulation of radioactivity in other organs except kidneys and urinary bladder. 99m Tc-zolmitriptan is not a blood product and so it is more safe than the currently available 99m Tc-MAA, and its lung uptake is higher than that of the recently discovered 123 I-IPMPD, 99m Tc(CO) 5 I and 99m Tc-DHPM. So, 99m Tc-zolmitriptan could be used as a hopeful radiopharmaceutical for lung scintigraphic imaging.

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.

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils.

PubMed

Camp, Jeremy V; Bagci, Ulas; Chu, Yong-Kyu; Squier, Brendan; Fraig, Mostafa; Uriarte, Silvia M; Guo, Haixun; Mollura, Daniel J; Jonsson, Colleen B

2015-09-01

Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virus-infected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [(18)F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. Severe influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure and death. Well-developed animal models that mimic human disease are essential to understanding the complex relationships of the microenvironment, organ, and system in controlling virus replication, inflammation, and disease progression. Employing the ferret model of H1N1pdm virus infection, we used live imaging and comprehensive histological analyses to address specific hypotheses regarding spatial and temporal relationships that occur during the progression of infection and inflammation. We show the general invasion of neutrophils at the organ level (lung) but also a distinct pattern of localized accumulation within the microenvironment at the site of infection. Moreover, we show that these responses were biphasic within the lung. Finally, live imaging revealed an early and sustained host metabolic response at sites of infection that may reflect damage and repair of tissues in the lungs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

PubMed Central

Camp, Jeremy V.; Bagci, Ulas; Chu, Yong-Kyu; Squier, Brendan; Fraig, Mostafa; Uriarte, Silvia M.; Guo, Haixun; Mollura, Daniel J.

2015-01-01

ABSTRACT Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virus-infected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [18F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. IMPORTANCE Severe influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure and death. Well-developed animal models that mimic human disease are essential to understanding the complex relationships of the microenvironment, organ, and system in controlling virus replication, inflammation, and disease progression. Employing the ferret model of H1N1pdm virus infection, we used live imaging and comprehensive histological analyses to address specific hypotheses regarding spatial and temporal relationships that occur during the progression of infection and inflammation. We show the general invasion of neutrophils at the organ level (lung) but also a distinct pattern of localized accumulation within the microenvironment at the site of infection. Moreover, we show that these responses were biphasic within the lung. Finally, live imaging revealed an early and sustained host metabolic response at sites of infection that may reflect damage and repair of tissues in the lungs. PMID:26063430

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

Powell, Joshua D.; Hutchison, Janine R.; Hess, Becky M.

Aims: To better understand the parameters that govern spore dissemination after lung exposure using in vitro cell systems. Methods and Results: We evaluated the kinetics of uptake, germination and proliferation of B. anthracis Sterne spores in association with human primary lung epithelial cells, Calu-3, and A549 cell lines. We also analyzed the influence of various cell culture media formulations related to spore germination. Conclusions: We found negligible spore uptake by epithelial cells, but germination and proliferation of spores in the extracellular environment was evident, and was appreciably higher in A549 and Calu-3 cultures than in primary epithelial cells. Additionally, ourmore » results revealed spores in association with primary cells submerged in cell culture media germinated 1 h« less

Modeling and Uncertainty Quantification of Vapor Sorption and Diffusion in Heterogeneous Polymers

DOE PAGES

Sun, Yunwei; Harley, Stephen J.; Glascoe, Elizabeth A.

2015-08-13

A high-fidelity model of kinetic and equilibrium sorption and diffusion is developed and exercised. The gas-diffusion model is coupled with a triple-sorption mechanism: Henry’s law absorption, Langmuir adsorption, and pooling or clustering of molecules at higher partial pressures. Sorption experiments are conducted and span a range of relative humidities (0-95%) and temperatures (30-60°C). Kinetic and equilibrium sorption properties and effective diffusivity are determined by minimizing the absolute difference between measured and modeled uptakes. Uncertainty quantification and sensitivity analysis methods are described and exercised herein to demonstrate the capability of this modeling approach. Water uptake in silica-filled and unfilled poly(dimethylsiloxane) networksmore » is investigated; however, the model is versatile enough to be used with a wide range of materials and vapors.« less

[Modern Views on Children's Interstitial Lung Disease].

PubMed

Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

2015-01-01

Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.

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

Imbriano, L.J.; Mandel, P.R.; Cordaro, A.F.

The value of Ga-67 scanning to detect acute infectious lung disease has been described. We present a patient who apparently improved both clinically and radiographically after acute Legionnaires' pneumonia. Five months later a relapse developed. During his relapse the pulmonary uptake of Ga-67 and the appearance of chest x-rays were disparate. We suggest that pulmonary Ga-67 uptake may be a more sensitive indicator of the resolution of pneumonia than is chest radiography. Therapeutic success may be assumed when pulmonary Ga-67 uptake is absent.

Hybrid atomistic simulation of fluid uptake in a deformable solid

NASA Astrophysics Data System (ADS)

Moghadam, Mahyar M.; Rickman, J. M.

2014-01-01

Fluid imbibition via diffusion in a deformable solid results in solid stresses that may, in turn, alter subsequent fluid uptake. To examine this interplay between diffusional and elastic fields, we employed a hybrid Monte Carlo-molecular dynamics scheme to model the coupling of a fluid reservoir to a deformable solid, and then simulated the resulting fluid permeation into the solid. By monitoring the instantaneous structure factor and solid dimensions, we were able to determine the compositional strain associated with imbibition, and the diffusion coefficient in the Fickian regime was obtained from the time dependence of the fluid uptake. Finally, for large, mobile fluid atoms, a non-Fickian regime was highlighted and possible mechanisms for this behavior were identified.

Lung cancer biology: a genetic and genomic perspective.

PubMed

Sánchez-Céspedes, M

2009-05-01

Lung cancer is the leading cause of death due to cancer in most western countries and, as tobacco consumption is not significantly decreasing worldwide, will remain so in the coming decades. Thus, in addition to preventing uptake and encouraging cessation of the smoking habit, it is important to invest in understanding the biology of this type of cancer. Of particular interest are the recent efforts directed towards characterising the entire set of gene alterations in lung cancer. The present review describes the catalogue of known genetic alterations in lung cancer, their biological role and their use in clinical management.

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.

Evaluation of the Outcome of Lung Nodules Missed on 18F-FDG PET/MRI Compared with 18F-FDG PET/CT in Patients with Known Malignancies.

PubMed

Sawicki, Lino M; Grueneisen, Johannes; Buchbender, Christian; Schaarschmidt, Benedikt M; Gomez, Benedikt; Ruhlmann, Verena; Umutlu, Lale; Antoch, Gerald; Heusch, Philipp

2016-01-01

The lower detection rate of (18)F-FDG PET/MRI than (18)F-FDG PET/CT regarding small lung nodules should be considered in the staging of malignant tumors. The purpose of this study was to evaluate the outcome of these small lung nodules missed by (18)F-FDG PET/MRI. Fifty-one oncologic patients (mean age ± SD, 56.6 ± 14.0 y; 29 women, 22 men; tumor stages, I [n = 7], II [n = 7], III [n = 9], IV [n = 28]) who underwent (18)F-FDG PET/CT and subsequent (18)F-FDG PET/MRI on the same day were retrospectively enrolled. Images were analyzed by 2 interpreters in random order and separate sessions with a minimum of 4 wk apart. A maximum of 10 lung nodules was identified for each patient on baseline imaging. The presence, size, and presence of focal tracer uptake was noted for each lung nodule detected on (18)F-FDG PET/CT and (18)F-FDG PET/MRI using a postcontrast T1-weighted 3-dimensional gradient echo volume-interpolated breath-hold examination sequence with fat suppression as morphologic dataset. Follow-up CT or (18)F-FDG PET/CT (mean time to follow-up, 11 mo; range, 3-35 mo) was used as a reference standard to define each missed nodule as benign or malignant based on changes in size and potential new tracer uptake. Nodule-to-nodule comparison between baseline and follow-up was performed using descriptive statistics. Out of 134 lung nodules found on (18)F-FDG PET/CT, (18)F-FDG PET/MRI detected 92 nodules. Accordingly, 42 lung nodules (average size ± SD, 3.9 ± 1.3 mm; range, 2-7 mm) were missed by (18)F-FDG PET/MRI. None of the missed lung nodules presented with focal tracer uptake on baseline imaging or follow-up (18)F-FDG PET/CT. Thirty-three out of 42 missed lung nodules (78.6%) in 26 patients were rated benign, whereas 9 nodules (21.4%) in 4 patients were rated malignant. As a result, 1 patient required upstaging from tumor stage I to IV. Although most small lung nodules missed on (18)F-FDG PET/MRI were found to be benign, there was a relevant number of undetected metastases. However, in patients with advanced tumor stages the clinical impact remains controversial as upstaging is usually more relevant in lower stages. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Pleural plaques and their effect on lung function in Libby vermiculite miners.

PubMed

Clark, Kathleen A; Flynn, J Jay; Goodman, Julie E; Zu, Ke; Karmaus, Wilfried J J; Mohr, Lawrence C

2014-09-01

Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners. The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure. Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function. Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

Modeling the effect of glutamate diffusion and uptake on NMDA and non-NMDA receptor saturation.

PubMed Central

Holmes, W R

1995-01-01

One- and two-dimensional models of glutamate diffusion, uptake, and binding in the synaptic cleft were developed to determine if the release of single vesicles of glutamate would saturate NMDA and non-NMDA receptors. Ranges of parameter values were used in the simulations to determine the conditions when saturation could occur. Single vesicles of glutamate did not saturate NMDA receptors unless diffusion was very slow and the number of glutamate molecules in a vesicle was large. However, the release of eight vesicles at 400 Hz caused NMDA receptor saturation for all parameter values tested. Glutamate uptake was found to reduce NMDA receptor saturation, but the effect was smaller than that of changes in the diffusion coefficient or in the number of glutamate molecules in a vesicle. Non-NMDA receptors were not saturated unless diffusion was very slow and the number of glutamate molecules in a vesicle was large. The release of eight vesicles at 400 Hz caused significant non-NMDA receptor desensitization. The results suggest that NMDA and non-NMDA receptors are not saturated by single vesicles of glutamate under usual conditions, and that tetanic input, of the type typically used to induce long-term potentiation, will increase calcium influx by increasing receptor binding as well as by reducing voltage-dependent block of NMDA receptors. Images FIGURE 1 PMID:8580317

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

Accelerated Analyte Uptake on Single Beads in Microliter-scale Batch Separations using Acoustic Streaming: Plutonium Uptake by Anion Exchange for Analysis by Mass Spectrometry

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

Paxton, Walter F.; O'Hara, Matthew J.; Peper, Shane M.

2008-06-01

The use of acoustic streaming as a non-contact mixing platform to accelerate mass transport-limited diffusion processes in small volume heterogeneous reactions has been investigated. Single bead anion exchange of plutonium at nanomolar and sub-picomolar concentrations in 20 microliter liquid volumes was used to demonstrate the effect of acoustic mixing. Pu uptake rates on individual ~760 micrometer diameter AG 1x4 anion exchange resin beads were determined using acoustic mixing and compared with Pu uptake rates achieved by static diffusion alone. An 82 MHz surface acoustic wave (SAW) device was placed in contact with the underside of a 384-well microplate containing flat-bottomedmore » semiconical wells. Acoustic energy was coupled into the solution in the well, inducing acoustic streaming. Pu uptake rates were determined by the plutonium remaining in solution after specific elapsed time intervals, using liquid scintillation counting (LSC) for nanomolar concentrations and thermal ionization mass spectrometry (TIMS) analysis for the sub-picomolar concentration experiments. It was found that this small batch uptake reaction could be accelerated by a factor of about five-fold or more, depending on the acoustic power applied.« less

Is non-attenuation-corrected PET inferior to body attenuation-corrected PET or PET/CT in lung cancer?

NASA Astrophysics Data System (ADS)

Maintas, Dimitris; Houzard, Claire; Ksyar, Rachid; Mognetti, Thomas; Maintas, Catherine; Scheiber, Christian; Itti, Roland

2006-12-01

It is considered that one of the great strengths of PET imaging is the ability to correct for body attenuation. This enables better lesion uptake quantification and quality of PET images. The aim of this work is to compare the sensitivity of non-attenuation-corrected (NAC) PET images, the gamma photons (GPAC) and CT attenuation-corrected (CTAC) images in detecting and staging of lung cancer. We have studied 66 patients undergoing PET/CT examinations for detecting and staging NSC lung cancer. The patients were injected with 18-FDG; 5 MBq/kg under fasting conditions and examination was started 60 min later. Transmission data were acquired by a spiral CT X-ray tube and by gamma photons emitting Cs-137l source and were used for the patient body attenuation correction without correction for respiratory motion. In 55 of 66 patients we performed both attenuation correction procedures and in 11 patients only CT attenuation correction. In seven patients with solitary nodules PET was negative and in 59 patients with lung cancer PET/CT was positive for pulmonary or other localization. In the group of 55 patients we found 165 areas of focal increased 18-FDG uptake in NAC, 165 in CTAC and 164 in GPAC PET images.In the patients with only CTAC we found 58 areas of increased 18-FDG uptake on NAC and 58 areas lesions on CTAC. In the patients with positive PET we found 223 areas of focal increased uptake in NAC and 223 areas in CTAC images. The sensitivity of NAC was equal to the sensitivity of CTAC and GPAC images. The visualization of peripheral lesions was better in NAC images and the lesions were better localized in attenuation-corrected images. In three lesions of the thorax the localization was better in GPAC and fused images than in CTAC images.

Diffusional limits to the consumption of atmospheric methane by soils

USGS Publications Warehouse

Striegl, Robert G.

1993-01-01

Net transport of atmospheric gases into and out of soil systems is primarily controlled by diffusion along gas partial pressure gradients. Gas fluxes between soil and the atmosphere can therefore be estimated by a generalization of the equation for ordinary gaseous diffusion in porous unsaturated media. Consumption of CH4 by methylotrophic bacteria in the top several centimeters of soil causes the uptake of atmospheric CH4 by aerated soils. The capacity of the methylotrophs to consume CH4 commonly exceeds the potential of CH4 to diffuse from the atmosphere to the consumers. The maximum rate of uptake of atmospheric CH4 by soil is, therefore, limited by diffusion and can be calculated from soil physical properties and the CH4 concentration gradient. The CH4 concentration versus depth profile is theoretically described by the equation for gaseous diffusion with homogeneous chemical reaction in porous unsaturated media. This allows for calculation of the in situ rate of CH4 consumption within specified depth intervals.

Cost minimization analysis and utility of pretreatment and posttreatment total body iodine-131 scans in patients with thyroid carcinoma.

PubMed

Grigsby, P

1998-03-01

The purpose of this study was to evaluate the utility of posttreatment total body iodine-131 (I-131) scans. The records of 63 consecutive patients with thyroid carcinoma treated with surgery and postoperative I-131 were reviewed. Patients underwent a postoperative diagnostic total body I-131 scan. Subsequently, patients received therapeutic administration of I-131. Posttreatment total body I-131 scans were performed. The postoperative diagnostic total body I-131 scans revealed uptake in the neck in all 63 patients and also demonstrated lung and mediastinal uptake in 7 patients with known sites of metastatic disease. The posttreatment total body I-131 scans also revealed neck uptake in all patients and demonstrated uptake in the lung and mediastinum in those with known metastasis to those sites. Additional foci of neck uptake were revealed on the posttreatment total body I-131 scans in six patients. Stepwise logistic regression was performed to identify prognostic factors predictive of additional foci of uptake on the posttreatment total body I-131 scans compared with the pretreatment diagnostic total body I-131 scans. Variables found to correlate significantly with additional uptake on the posttreatment total body I-131 scans were tumor size > or = 2 cm, follicular histology, and multifocal disease. Posttreatment total body I-131 scans yielded additional information in only 10% (6 of 63) of the study patient population treated with postoperative I-131 for thyroid carcinoma. Therefore, the cost, and the associated inconvenience to the patient, of performing a posttreatment total body I-131 scan can be eliminated for most patients.

Mechanisms of Ocean Heat Uptake

NASA Astrophysics Data System (ADS)

Garuba, Oluwayemi

An important parameter for the climate response to increased greenhouse gases or other radiative forcing is the speed at which heat anomalies propagate downward in the ocean. Ocean heat uptake occurs through passive advection/diffusion of surface heat anomalies and through the redistribution of existing temperature gradients due to circulation changes. Atlantic meridional overturning circulation (AMOC) weakens in a warming climate and this should slow the downward heat advection (compared to a case in which the circulation is unchanged). However, weakening AMOC also causes a deep warming through the redistributive effect, thus increasing the downward rate of heat propagation compared to unchanging circulation. Total heat uptake depends on the combined effect of these two mechanisms. Passive tracers in a perturbed CO2 quadrupling experiments are used to investigate the effect of passive advection and redistribution of temperature anomalies. A new passive tracer formulation is used to separate ocean heat uptake into contributions due to redistribution and passive advection-diffusion of surface heating during an ocean model experiment with abrupt increase in surface temperature. The spatial pattern and mechanisms of each component are examined. With further experiments, the effects of surface wind, salinity and temperature changes in changing circulation and the resulting effect on redistribution in the individual basins are isolated. Analysis of the passive advection and propagation path of the tracer show that the Southern ocean dominates heat uptake, largely through vertical and horizontal diffusion. Vertical diffusion transports the tracer across isopycnals down to about 1000m in 100 years in the Southern ocean. Advection is more important in the subtropical cells and in the Atlantic high latitudes, both with a short time scale of about 20 years. The shallow subtropical cells transport the tracer down to about 500m along isopycnal surfaces, below this vertical diffusion takes over transport in the tropics; in the Atlantic, the MOC transports heat as deep 2000m in about 30 years. Redistributive surface heat uptake alters the total amount surface heat uptake among the basins. Compared to the passive-only heat uptake, which is about the same among the basins, redistribution nearly doubles the surface heat input into the Atlantic but makes smaller increases in the Indian and Pacific oceans for a net global increase of about 25%, in the perturbation experiment with winds unchanged. The passive and redistributive heat uptake components are further distributed among the basins through the global conveyor belt. The Pacific gains twice the surface heat input into it through lateral transport from the other two basins, as a result, the Atlantic and Pacific gain similar amounts of heat even though surface heat input is in the Atlantic is much bigger. Of this heat transport, most of the passive component comes from the Indian and the redistributive component comes from the Atlantic. Different surface forcing perturbation gives different circulation change pattern and as a result yield different redistributive uptake. Ocean heat uptake is more sensitive to wind forcing perturbation than to thermohaline forcing perturbation. About 2% reduction in subtropical cells transport and southern ocean transport, in the wind-change perturbation experiment, resulted in about 10% reduction in the global ocean heat uptake of wind-unchanged experiment. The AMOC weakened by about 35% and resulted in a 25% increase in passive heat uptake in the wind-unchanged experiment. Surface winds weakening reduces heat uptake by warming the reservoir surface temperatures, while MOC weakening increases heat input by a cooling reservoir surface temperatures. Thermohaline forcing perturbation is combination of salinity and temperature perturbations, both weaken the AMOC, however, they have opposite redistributive effects. Ocean surface freshening gives positive redistributive effect, while surface temperature increase gives negative redistributive effect on heat uptake. The salinity effect dominates the redistributive effect for thermohaline perturbation.

Deep neural network convolution (NNC) for three-class classification of diffuse lung disease opacities in high-resolution CT (HRCT): consolidation, ground-glass opacity (GGO), and normal opacity

NASA Astrophysics Data System (ADS)

Hashimoto, Noriaki; Suzuki, Kenji; Liu, Junchi; Hirano, Yasushi; MacMahon, Heber; Kido, Shoji

2018-02-01

Consolidation and ground-glass opacity (GGO) are two major types of opacities associated with diffuse lung diseases. Accurate detection and classification of such opacities are crucially important in the diagnosis of lung diseases, but the process is subjective, and suffers from interobserver variability. Our study purpose was to develop a deep neural network convolution (NNC) system for distinguishing among consolidation, GGO, and normal lung tissue in high-resolution CT (HRCT). We developed ensemble of two deep NNC models, each of which was composed of neural network regression (NNR) with an input layer, a convolution layer, a fully-connected hidden layer, and a fully-connected output layer followed by a thresholding layer. The output layer of each NNC provided a map for the likelihood of being each corresponding lung opacity of interest. The two NNC models in the ensemble were connected in a class-selection layer. We trained our NNC ensemble with pairs of input 2D axial slices and "teaching" probability maps for the corresponding lung opacity, which were obtained by combining three radiologists' annotations. We randomly selected 10 and 40 slices from HRCT scans of 172 patients for each class as a training and test set, respectively. Our NNC ensemble achieved an area under the receiver-operating-characteristic (ROC) curve (AUC) of 0.981 and 0.958 in distinction of consolidation and GGO, respectively, from normal opacity, yielding a classification accuracy of 93.3% among 3 classes. Thus, our deep-NNC-based system for classifying diffuse lung diseases achieved high accuracies for classification of consolidation, GGO, and normal opacity.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two cases.

PubMed

García-Fontán, Eva; Blanco Ramos, Montserrat; García, Jose Soro; Carrasco, Rommel; Cañizares, Miguel Ángel; González Piñeiro, Ana

2018-05-19

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder characterized by a proliferation of neuroendocrine cells within the lung. It is classically described as a disease with persistent cough, dyspnea and wheezing in non-smoker middle aged females. CT of the chest reveals diffuse air trapping with mosaic pattern. We present two cases of DIPNECH that were sent to our department to perform a lung biopsy with the diagnostic suspicion of diffuse interstitial disease. Both cases were women with a history of chronic cough and moderate effort dyspnea. The aim of this paper is that physicians take into account this diagnostic entity before treating as an asthmatic a patient with these characteristics, not forgetting that they are prenoplastic lesions. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Including carrier-mediated transport in oral uptake prediction of nutrients and pharmaceuticals in humans.

PubMed

O'Connor, Isabel A; Veltman, Karin; Huijbregts, Mark A J; Ragas, Ad M J; Russel, Frans G M; Hendriks, A Jan

2014-11-01

Most toxicokinetic models consider passive diffusion as the only mechanism when modeling the oral uptake of chemicals. However, the overall uptake of nutrients and xenobiotics, such as pharmaceuticals and environmental pollutants, can be increased by influx transport proteins. We incorporated carrier-mediated transport into a one-compartment toxicokinetic model originally developed for passive diffusion only. The predictions were compared with measured oral uptake efficiencies of nutrients and pharmaceuticals, i.e. the fraction of the chemical reaching systemic circulation. Including carrier-mediated uptake improved model predictions for hydrophilic nutrients (RMSE=10% vs. 56%, Coefficient of Efficiency CoE=0.5 vs. -9.6) and for pharmaceuticals (RMSE=21% vs. 28% and CoE=-0.4 vs. -1.1). However, the negative CoE for pharmaceuticals indicates that further improvements are needed. Most important in this respect is a more accurate estimation of vMAX and KM as well as the determination of the amount of expressed and functional transport proteins both in vivo and in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Mass Conservation in Modeling Moisture Diffusion in Multi-Layer Carbon Composite Structures

NASA Technical Reports Server (NTRS)

Nurge, Mark A.; Youngquist, Robert C.; Starr, Stanley O.

2009-01-01

Moisture diffusion in multi-layer carbon composite structures is difficult to model using finite difference methods due to the discontinuity in concentrations between adjacent layers of differing materials. Applying a mass conserving approach at these boundaries proved to be effective at accurately predicting moisture uptake for a sample exposed to a fixed temperature and relative humidity. Details of the model developed are presented and compared with actual moisture uptake data gathered over 130 days from a graphite epoxy composite sandwich coupon with a Rohacell foam core.

Transbronchial cryobiopsy for diffuse parenchymal lung disease: a state-of-the-art review of procedural techniques, current evidence, and future challenges.

PubMed

Lentz, Robert J; Argento, A Christine; Colby, Thomas V; Rickman, Otis B; Maldonado, Fabien

2017-07-01

Transbronchial lung biopsy with a cryoprobe, or cryobiopsy, is a promising new bronchoscopic biopsy technique capable of obtaining larger and better-preserved samples than previously possible using traditional biopsy forceps. Over two dozen case series and several small randomized trials are now available describing experiences with this technique, largely for the diagnosis of diffuse parenchymal lung disease (DPLD), in which the reported diagnostic yield is typically 70% to 80%. Cryobiopsy technique varies widely between centers and this predominantly single center-based retrospective literature heterogeneously defines diagnostic yield and complications, limiting the degree to which this technique can be compared between centers or to surgical lung biopsy (SLB). This review explores the broad range of cryobiopsy techniques currently in use, their rationale, the current state of the literature, and suggestions for the direction of future study into this promising but unproven procedure.

[Comparative study of respiratory exchanging surfaces in birds and mammals].

PubMed

Jammes, Y

1975-01-01

Anatomical studies of the respiratory apparatus of birds show evidences for a gas exchanging tubular system (parabronchi and air capillaries); these exchanging structures are entirely dissociated from the ventilatory drive acting on the air sacs. A "cross-current" gas exchanging system (perpendicular disposition of air and blood capillaries) allow a good wash-out of carbon dioxide (PaCO2 lower than PECO2). The great efficiency of this lung is allowed by its very large diffusive surface (ASa) and by the high values of lung specific oxygen diffusing capacity (DO2/ASa) and of O2 extraction coefficient in inspired air. The ventilatory pattern of birds is characterized by a greater tidal volume and a smaller respiratory frequency than in mammals of same weight. Respiratory centers of birds receive afferences from lung stretch receptors, CO2-sensitive lung receptors and arterial chemoreceptors.

Preferential reduction of quadriceps over respiratory muscle strength and bulk after lung transplantation for cystic fibrosis.

PubMed

Pinet, C; Scillia, P; Cassart, M; Lamotte, M; Knoop, C; Mélot, C; Estenne, M

2004-09-01

In the absence of complications, recipients of lung transplants for cystic fibrosis have normal pulmonary function but the impact of the procedure on the strength and bulk of respiratory and limb muscles has not been studied. Twelve stable patients who had undergone lung transplantation for cystic fibrosis 48 months earlier (range 8-95) and 12 normal subjects matched for age, height, and sex were studied. The following parameters were measured: standard lung function, peak oxygen uptake by cycle ergometry, diaphragm surface area by computed tomographic (CT) scanning, diaphragm and abdominal muscle thickness by ultrasonography, twitch transdiaphragmatic and gastric pressures, quadriceps isokinetic strength, and quadriceps cross section by CT scanning, and lean body mass. Diaphragm mass was computed from diaphragm surface area and thickness. Twitch transdiaphragmatic and gastric pressures, diaphragm mass, and abdominal muscle thickness were similar in the two groups but quadriceps strength and cross section were decreased by nearly 30% in the patients. Patients had preserved quadriceps strength per unit cross section but reduced quadriceps cross section per unit lean body mass. The cumulative dose of corticosteroids was an independent predictor of quadriceps atrophy. Peak oxygen uptake showed positive correlations with quadriceps strength and cross section in the two groups, but peak oxygen uptake per unit quadriceps strength or cross section was reduced in the patient group. The diaphragm and abdominal muscles have preserved strength and bulk in patients transplanted for cystic fibrosis but the quadriceps is weak due to muscle atrophy. This atrophy is caused in part by corticosteroid therapy and correlates with the reduction in exercise capacity.

/sup 99m/Tc-fibrinogen scanning in adult respiratory distress syndrome

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

Quinn, D.A.; Carvalho, A.C.; Geller, E.

1987-01-01

Fibrin is often seen occluding the lung vessels of patients dying from ARDS and is surrounded by regions of lung necrosis. To learn if we could observe increased or focal fibrin deposition and assess the kinetics of plasma fibrinogen turnover during severe acute respiratory failure, we injected technetium 99m-labeled human purified fibrinogen (Tc-HF) and used gamma camera scanning for as long as 12 h in 13 sequential patients as soon as possible after ICU admission. The fibrinogen uptake rates were determined by calculating the lung:heart radioactivity ratios at each time point. Slopes of the lung:heart ratio versus time were comparedmore » between ARDS and mild acute respiratory failure (ARF). The slope of the lung:heart Tc-HF ratio of the 9 patients with ARDS (2.9 +/- 0.4 units) was markedly higher (p less than 0.02) than the slope of the 4 patients with mild ARF (1.1 +/- 0.4) and the 3 patients studied 5 to 9 months after recovery from respiratory failure (0.7 +/- 0.07). In the 1 patient with ARDS and the 2 patients with mild ARF studied both during acute lung injury and after recovery, the lung:heart Tc-HF ratio had decreased at recovery. To compare the pulmonary uptake of Tc-HF to /sup 99m/Tc-labeled human serum albumin (Tc-HSA), 5 patients were injected with 10 mCi of Tc-HSA, and scanning of the thorax was performed with a similar sequential imaging protocol 24 h after conclusion of the Tc-HF study.« less

Bronchoscopic lung biopsy using noninvasive ventilatory support: case series and review of literature of NIV-assisted bronchoscopy.

PubMed

Agarwal, Ritesh; Khan, Ajmal; Aggarwal, Ashutosh N; Gupta, Dheeraj

2012-11-01

Fiberoptic bronchoscopy and lung biopsy are important diagnostic tools in patients with diffuse pulmonary infiltrates. However, these patients often have hypoxemic respiratory failure that makes this procedure hazardous. Noninvasive ventilation (NIV) has been shown to improve oxygenation in hypoxemic patients. To report the efficacy and safety of an innovative technique of NIV-assisted bronchoscopic lung biopsy in a small case-series of hypoxemic subjects with diffuse parenchymal infiltrates; also to systematically review the literature on NIV-assisted bronchoscopy. Subjects with bilateral diffuse parenchymal infiltrates and P(aO(2))/F(IO(2)) < 200 mm Hg underwent bronchoscopic lung biopsy under NIV support. NIV was initiated 10 min before the procedure and continued for 30 min after the procedure. The primary outcomes were performance of successful procedure and episodes of decline in S(pO(2)) < 90%. Secondary end points were the change in the respiratory and hemodynamic parameters during the procedure and occurrence of complications such as pneumothorax, hemorrhage, and endotracheal intubation. Six subjects, with a mean ± SD age of 44.5 ± 11.6 years, were included in the study. The median (interquartile range [IQR]) P(aO(2))/F(IO(2)) prior to lung biopsy was 164.5 mm Hg (146.3-176.3 mm Hg), and the median (IQR) inspiratory and expiratory positive airway pressures were 14 cm H(2)O (12-15 cm H(2)O) and 5 cm H(2)O. Fiberoptic bronchoscopy was well tolerated and all subjects maintained S(pO(2)) > 92% during the procedure. One subject required endotracheal intubation due to hemoptysis. A definite diagnosis was obtained in 5 of the 6 subjects. A repeat procedure was performed in one subject, which again yielded no diagnosis. No other periprocedural complications were encountered. NIV-assisted bronchoscopic lung biopsy is a novel method for obtaining diagnosis in hypoxemic patients with diffuse lung infiltrates. However, this approach should be reserved for centers with extensive experience in NIV. More studies are required to define the utility of this approach.

Oceanic Uptake of Oxygen During Deep Convection Events Through Diffusive and Bubble-Mediated Gas Exchange

NASA Astrophysics Data System (ADS)

Sun, Daoxun; Ito, Takamitsu; Bracco, Annalisa

2017-10-01

The concentration of dissolved oxygen (O2) plays fundamental roles in diverse chemical and biological processes throughout the oceans. The balance between the physical supply and the biological consumption controls the O2 level of the interior ocean, and the O2 supply to the deep waters can only occur through deep convection in the polar oceans. We develop a theoretical framework describing the oceanic O2 uptake during open-ocean deep convection events and test it against a suite of numerical sensitivity experiments. Our framework allows for two predictions, confirmed by the numerical simulations. First, both the duration and the intensity of the wintertime cooling contribute to the total O2 uptake for a given buoyancy loss. Stronger cooling leads to deeper convection and the oxygenation can reach down to deeper depths. Longer duration of the cooling period increases the total amount of O2 uptake over the convective season. Second, the bubble-mediated influx of O2 tends to weaken the diffusive influx by shifting the air-sea disequilibrium of O2 toward supersaturation. The degree of compensation between the diffusive and bubble-mediated gas exchange depends on the dimensionless number measuring the relative strength of oceanic vertical mixing and the gas transfer velocity. Strong convective mixing, which may occur under strong cooling, reduces the degree of compensation so that the two components of gas exchange together drive exceptionally strong oceanic O2 uptake.

Guava (Psidium guajava) leaf powder: novel adsorbent for removal of methylene blue from aqueous solutions.

PubMed

Ponnusami, V; Vikram, S; Srivastava, S N

2008-03-21

Batch sorption experiments were carried out using a novel adsorbent, guava leaf powder (GLP), for the removal of methylene blue (MB) from aqueous solutions. Potential of GLP for adsorption of MB from aqueous solution was found to be excellent. Effects of process parameters pH, adsorbent dosage, concentration, particle size and temperature were studied. Temperature-concentration interaction effect on dye uptake was studied and a quadratic model was proposed to predict dye uptake in terms of concentration, time and temperature. The model conforms closely to the experimental data. The model was used to find optimum temperature and concentration that result in maximum dye uptake. Langmuir model represent the experimental data well. Maximum dye uptake was found to be 295mg/g, indicating that GLP can be used as an excellent low-cost adsorbent. Pseudo-first-order, pseudo-second order and intraparticle diffusion models were tested. From experimental data it was found that adsorption of MB onto GLP follow pseudo second order kinetics. External diffusion and intraparticle diffusion play roles in adsorption process. Free energy of adsorption (DeltaG degrees ), enthalpy change (DeltaH degrees ) and entropy change (DeltaS degrees ) were calculated to predict the nature of adsorption. Adsorption in packed bed was also evaluated.

Intracellular dynamics and fate of polystyrene nanoparticles in A549 Lung epithelial cells monitored by image (cross-) correlation spectroscopy and single particle tracking.

PubMed

Deville, Sarah; Penjweini, Rozhin; Smisdom, Nick; Notelaers, Kristof; Nelissen, Inge; Hooyberghs, Jef; Ameloot, Marcel

2015-10-01

Novel insights in nanoparticle (NP) uptake routes of cells, their intracellular trafficking and subcellular targeting can be obtained through the investigation of their temporal and spatial behavior. In this work, we present the application of image (cross-) correlation spectroscopy (IC(C)S) and single particle tracking (SPT) to monitor the intracellular dynamics of polystyrene (PS) NPs in the human lung carcinoma A549 cell line. The ensemble kinetic behavior of NPs inside the cell was characterized by temporal and spatiotemporal image correlation spectroscopy (TICS and STICS). Moreover, a more direct interpretation of the diffusion and flow detected in the NP motion was obtained by SPT by monitoring individual NPs. Both techniques demonstrate that the PS NP transport in A549 cells is mainly dependent on microtubule-assisted transport. By applying spatiotemporal image cross-correlation spectroscopy (STICCS), the correlated motions of NPs with the early endosomes, late endosomes and lysosomes are identified. PS NPs were equally distributed among the endolysosomal compartment during the time interval of the experiments. The cotransport of the NPs with the lysosomes is significantly larger compared to the other cell organelles. In the present study we show that the complementarity of ICS-based techniques and SPT enables a consistent elaborate model of the complex behavior of NPs inside biological systems. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Prediction of therapeutic response in steroid-treated pulmonary sarcoidosis. Evaluation of clinical parameters, bronchoalveolar lavage, gallium-67 lung scanning, and serum angiotensin-converting enzyme levels

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

Hollinger, W.M.; Staton, G.W. Jr.; Fajman, W.A.

1985-07-01

To find a pretreatment predictor of steroid responsiveness in pulmonary sarcoidosis the authors studied 21 patients before and after steroid treatment by clinical evaluation, pulmonary function tests, bronchoalveolar lavage (BAL), gallium-67 lung scan, and serum angiotensin-converting enzyme (SACE) level. Although clinical score, forced vital capacity (FVC), BAL percent lymphocytes (% lymphs), quantitated gallium-67 lung uptake, and SACE levels all improved with therapy, only the pretreatment BAL % lymphs correlated with the improvement in FVC (r = 0.47, p less than 0.05). Pretreatment BAL % lymphs of greater than or equal to 35% predicted improvement in FVC of 10/11 patients, whereasmore » among 10 patients with BAL % lymphs less than 35%, 5 patients improved and 5 deteriorated. Clinical score, pulmonary function parameters, quantitated gallium-67 lung uptake, and SACE level used alone, in combination with BAL % lymphs or in combination with each other, did not improve this predictive value. The authors conclude that steroid therapy improves a number of clinical and laboratory parameters in sarcoidosis, but only the pretreatment BAL % lymphs are useful in predicting therapeutic responsiveness.« less

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.

Diffusion of D-glucose measured in the cytosol of a single astrocyte.

PubMed

Kreft, Marko; Lukšič, Miha; Zorec, Tomaž M; Prebil, Mateja; Zorec, Robert

2013-04-01

Astrocytes interact with neurons and endothelial cells and may mediate exchange of metabolites between capillaries and nerve terminals. In the present study, we investigated intracellular glucose diffusion in purified astrocytes after local glucose uptake. We used a fluorescence resonance energy transfer (FRET)-based nano sensor to monitor the time dependence of the intracellular glucose concentration at specific positions within the cell. We observed a delay in onset and kinetics in regions away from the glucose uptake compared with the region where we locally super-fused astrocytes with the D-glucose-rich solution. We propose a mathematical model of glucose diffusion in astrocytes. The analysis showed that after gradual uptake of glucose, the locally increased intracellular glucose concentration is rapidly spread throughout the cytosol with an apparent diffusion coefficient (D app) of (2.38 ± 0.41) × 10(-10) m(2) s(-1) (at 22-24 °C). Considering that the diffusion coefficient of D-glucose in water is D = 6.7 × 10(-10) m(2) s(-1) (at 24 °C), D app determined in astrocytes indicates that the cytosolic tortuosity, which hinders glucose molecules, is approximately three times higher than in aqueous solution. We conclude that the value of D app for glucose measured in purified rat astrocytes is consistent with the view that cytosolic diffusion may allow glucose and glucose metabolites to traverse from the endothelial cells at the blood-brain barrier to neurons and neighboring astrocytes.

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

Levy, H.M.; Smith, R.

Two cases of thalassemia major are presented in which bone scintigraphy demonstrated diffuse hepatic uptake of Tc-99m diphosphonate. Although abnormal splenic and renal uptake of Tc-99m phosphates has been reported in patients with thalassemia major, hepatic uptake has not been reported previously. This scintigraphic finding is presumably due to increased iron deposition in the liver, resulting from increased iron turnover and retention in these patients and from multiple previous blood transfusions.

Improved iodine radiolabels for monoclonal antibody therapy.

PubMed

Stein, Rhona; Govindan, Serengulam V; Mattes, M Jules; Chen, Susan; Reed, Linda; Newsome, Guy; McBride, Bill J; Griffiths, Gary L; Hansen, Hans J; Goldenberg, David M

2003-01-01

A major disadvantage of (131)iodine (I)-labeled monoclonal antibodies (MAbs) for radioimmunotherapy has been the rapid diffusion of iodotyrosine from target cells after internalization and catabolism of the radioiodinated MAbs. We recently reported that a radioiodinated, diethylenetriaminepentaacetic acid-appended peptide, designated immunomedics' residualizing peptide 1 (IMP-R1), was a residualizing iodine label that overcame many of the limitations that had impeded the development of residualizing iodine for clinical use. To determine the factors governing the therapeutic index of the labeled MAb, as well as the factors required for production of radioiodinated MAb in high yield and with high specific activity, variations in the peptide structure of IMP-R1 were evaluated. A series of radioiodinated, diethylenetriaminepentaacetic acid-appended peptide moieties (IMP-R1 through IMP-R8) that differed in overall hydrophilicity and charge were compared. Radioiodinations of the peptides followed by conjugations to disulfide-reduced RS7 (an anti-epithelial glycoprotein-1 MAb) furnished radioimmunoconjugates in good overall incorporations, with immunoreactivities comparable to that of directly radioiodinated RS7. Specific activities of up to 8 mCi/mg and yields > 80% have been achieved. In vitro processing experiments showed marked increases in radioiodine retention with all of the adducts; radioiodine retention at 45 h was up to 86% greater in cells than with directly iodinated RS7. Each of the (125)I-peptide-RS7 conjugates was compared with (131)I-RS7 (labeled by the chloramine-T method) in paired-label biodistribution studies in nude mice bearing human lung tumor xenografts. All of the residualizing substrates exhibited significantly enhanced retention in tumor in comparison to directly radioiodinated RS7, but the nontarget uptakes differed significantly among the residualizing labels. The best labels were IMP-R4 and IMP-R8, showing superior tumor-to-non-tumor ratios by virtue of high tumor uptake and retention and low normal organ uptake, as well as superior radiochemical properties. The therapeutic efficacy of (131)I-IMP-R4-RS7 was compared with that of conventionally (131)I-labeled RS7 and (90)yttrium-RS7 in the nude mice lung cancer model. The therapeutic efficacy of (131)I-IMP-R4-RS7 and (90)yttrium-RS7 were equivalent, and both agents yielded significantly improved control of tumor growth compared with conventional (131)I-labeled RS7.

Introduction and uptake of new medical technologies in the Australian health care system: a qualitative study.

PubMed

Gallego, Gisselle; Casey, Robert; Norman, Richard; Goodall, Stephen

2011-10-01

The aim of this study was to explore the views and perceptions of stakeholders about the current national health technology assessment process conducted by the Medical Services Advisory Committee (MSAC) and its role in the uptake and diffusion of new medical technologies in Australia. Data collection occurred over a nine month period (August 2008-April 2009). Twenty in-depth, semi-structured interviews were conducted with individuals from four stakeholders groups: (i) MSAC members and evaluators, (ii) academic and health technology assessment experts, (iii) medical industry representatives and (iv) medical specialists. Interviews were digitally recorded, transcribed verbatim and coded using a constant comparative method. Respondents expressed a consensus opinion that the MSAC process is generally fair and transparent, and has been increasingly so over time. The process was described as "flexible" and "intuitive" yet also "idiosyncratic" due to the nature of the technologies being appraised. Approval by MSAC was generally reported to be increasingly important once a technology becomes more widely used. While successful MSAC approval was felt to be important for widespread distribution of a new technology, it was viewed more as a "facilitator of the uptake of new technologies" as opposed to a primary "driver" of technology uptake. Instead, other factors were identified as providing the actual impetus for the uptake of new technologies, with MSAC approval and reimbursement eventually helping facilitate more widespread diffusion. MSAC's decision making process is perceived as fair but with room for improvement. Its role in the uptake and diffusion of new medical technologies in Australia is limited. MSAC does not act as a barrier to significant market penetration of new procedures and medical technologies. However reimbursement is a trigger for increased use. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Transbronchial biopsies safely diagnose amyloid lung disease

PubMed Central

Govender, Praveen; Keyes, Colleen M.; Hankinson, Elizabeth A.; O’Hara, Carl J.; Sanchorawala, Vaishali; Berk, John L.

2018-01-01

Background Autopsy identifies lung involvement in 58–92% of patients with the most prevalent forms of systemic amyloidoses. In the absence of lung biopsies, amyloid lung disease often goes unrecognized. Report of a death following transbronchial biopsies in a patient with systemic amyloidosis cautioned against the procedure in this patient cohort. We reviewed our experience with transbronchial biopsies in patients with amyloidosis to determine the safety and utility of bronchoscopic lung biopsies. Methods We identified patients referred to the Amyloidosis Center at Boston Medical Center with lung amyloidosis diagnosed by transbronchial lung biopsies (TBBX). Amyloid typing was determined by immunohistochemistry or mass spectrometry. Standard end organ assessments, including pulmonary function test (PFT) and chest tomography (CT) imaging, and extra-thoracic biopsies established the extent of disease. Results Twenty-five (21.7%) of 115 patients with lung amyloidosis were diagnosed by TBBX. PFT classified 33.3% with restrictive physiology, 28.6% with obstructive disease, and 9.5% mixed physiology; 9.5% exhibited isolated diffusion defects while 19% had normal pulmonary testing. Two view chest or CT imaging identified focal opacities in 52% of cases and diffuse interstitial disease in 48%. Amyloid type and disease extent included 68% systemic AL disease, 16% localized (lung limited) AL disease, 12% ATTR disease, and 4% AA amyloidosis. Fluoroscopy was not used during biopsy. No procedure complications were reported. Conclusions Our case series of 25 patients supports the use of bronchoscopic transbronchial biopsies for diagnosis of parenchymal lung amyloidosis. Normal PFTs do not rule out the histologic presence of amyloid lung disease. PMID:28393574

Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study.

PubMed

Walsh, Simon L F; Wells, Athol U; Desai, Sujal R; Poletti, Venerino; Piciucchi, Sara; Dubini, Alessandra; Nunes, Hilario; Valeyre, Dominique; Brillet, Pierre Y; Kambouchner, Marianne; Morais, António; Pereira, José M; Moura, Conceição Souto; Grutters, Jan C; van den Heuvel, Daniel A; van Es, Hendrik W; van Oosterhout, Matthijs F; Seldenrijk, Cornelis A; Bendstrup, Elisabeth; Rasmussen, Finn; Madsen, Line B; Gooptu, Bibek; Pomplun, Sabine; Taniguchi, Hiroyuki; Fukuoka, Junya; Johkoh, Takeshi; Nicholson, Andrew G; Sayer, Charlie; Edmunds, Lilian; Jacob, Joseph; Kokosi, Maria A; Myers, Jeffrey L; Flaherty, Kevin R; Hansell, David M

2016-07-01

Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease. We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis. 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (κ=0·50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (κw=0·71 [IQR 0·64-0·77]) and connective tissue disease-related interstitial lung disease (κw=0·73 [0·68-0·78]); moderate for non-specific interstitial pneumonia (NSIP; κw=0·42 [0·37-0·49]); and fair for hypersensitivity pneumonitis (κw=0·29 [0·24-0·40]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinician's diagnosis of this disease in five of seven MDTMs, and radiologist's diagnosis of IPF in four of seven MDTMs. Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease. National Institute of Health Research, Imperial College London. Copyright © 2016 Elsevier Ltd. All rights reserved.

TC-99m MIBI SPECT imaging in patients with lung carcinoma: is it a functional probe of multidrug resistance genes?

PubMed

Ak, Ilknur; Gülbaş, Zafer; Ocak, Suna; Kaya, Eser; Alataş, Füsun; Vardareli, Erkan; Metintaş, Muzaffer

2007-01-01

Multidrug-resistance (MDR) phenotype concerns altered membrane transport that results in lower cell concentrations of cytotoxic drug in many cancer types, including lung cancer, and is related to the overexpression of a variety of proteins that act as adenosine triphosphate-dependent extrusion pumps. Tc-99m Sestamibi (MIBI) is a transport substrate for P-glycoprotein (Pgp) pump. In this study, we assessed the uptake and clearance of technetium-99m-2-hexakis 2-methoxyisobutylisonitrile (Tc-99m MIBI) from the tumor and its correlation with messenger RNA (mRNA) levels of Pgp, MDR-associated protein (MRP1), and lung resistance protein (LRP) in lung carcinoma. This study was carried out on 19 patients (mean age, 60.1 +/- 2.07 years) with advanced-stage lung carcinoma. The tumor samples obtained by bronchoscopy were assessed to estimate the levels of Pgp, MRP1, and LRP expression on mRNA level by quantitative real-time reverse-transcription polymerase chain reaction. Tc-99m MIBI chest imaging was performed 15 and 180 minutes after injection of 740 MBq Tc-99m MIBI. The early (T/Be) and delayed (T/Bd) Tc-99m MIBI uptakes and washout rate (WR) of Tc-99m MIBI from the tumor were measured. No correlation was found between the T/Be Tc-99m MIBI uptake of tumors (T/Be) and the levels of Pgp mRNA, MRP1 mRNA, and LRP mRNA by reverse-transcription polymerase chain reaction. There was a correlation between the mean T/Bd Tc-99m MIBI uptake and Pgp expression of the tumors (P = 0.001, Spearman rho = - 0.702). There was a correlation between the WR of Tc-99m MIBI from the tumor and Pgp expression of the tumor (P = 0.000, Spearman rho = 0.875). Washout rate of Tc-99m MIBI was not related to the levels of MRP1 mRNA (P = 0.93, Spearman rho = 0.02) or LRP mRNA (P = 0.47, Spearman rho = 0.177). Increased WR of Tc-99m MIBI is related in Pgp over expression of the tumor. Tc-99m MIBI single photon emission computed tomography imaging may be a functional probe of overexpression of Pgp in patients with lung carcinoma. However, Tc-99m MIBI single photon emission computed tomography imaging cannot be used to identify the MDR involved in the MRP1 or LRP in these patients.

Dynamic OCT monitoring and quantification of light penetration enhancement for normal, benign and cancerous human lung tissues at different concentrations of glycerol

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

Shu-wen Tan; Ying Jin; Hui Yu

2013-10-31

We have evaluated the dynamic effects of the analyte diffusion on the 1/e light penetration depths of normal, benign and cancerous human lung tissue in vitro, as well as have monitored and quantified the dynamic change in the light penetration depths of the mentioned human lung tissue after application of 25 % and 50 % glycerol solution, respectively. The light penetration depths of the analyte diffusion in the lung tissue are measured using the Fourierdomain optical coherence tomography (FD-OCT). Experimental results show that the application of glycerol as a chemical agent can significantly enhance light penetration depths into the humanmore » normal lung (NL), lung benign granulomatosis (LBG) and lung squamous cell carcinoma (LSCC) tissue. In-depth transport of the glycerol molecules in the NL, LBG and LSCC tissue at a lower glycerol concentration (25 %) are faster than those at a higher glycerol concentration (50 %), and the 1/e light penetration depths at a lower glycerol concentration (25 %) are smaller than those at a higher glycerol concentration (50 %), respectively. Their differences in the maximal 1/e light penetration depths of the NL, LBG and LSCC tissue at a higher and a lower glycerol concentrations were only 8.8 %, 6.8 % and 4.7 %, respectively. (biophotonics)« less

Nonlinear histogram binning for quantitative analysis of lung tissue fibrosis in high-resolution CT data

NASA Astrophysics Data System (ADS)

Zavaletta, Vanessa A.; Bartholmai, Brian J.; Robb, Richard A.

2007-03-01

Diffuse lung diseases, such as idiopathic pulmonary fibrosis (IPF), can be characterized and quantified by analysis of volumetric high resolution CT scans of the lungs. These data sets typically have dimensions of 512 x 512 x 400. It is too subjective and labor intensive for a radiologist to analyze each slice and quantify regional abnormalities manually. Thus, computer aided techniques are necessary, particularly texture analysis techniques which classify various lung tissue types. Second and higher order statistics which relate the spatial variation of the intensity values are good discriminatory features for various textures. The intensity values in lung CT scans range between [-1024, 1024]. Calculation of second order statistics on this range is too computationally intensive so the data is typically binned between 16 or 32 gray levels. There are more effective ways of binning the gray level range to improve classification. An optimal and very efficient way to nonlinearly bin the histogram is to use a dynamic programming algorithm. The objective of this paper is to show that nonlinear binning using dynamic programming is computationally efficient and improves the discriminatory power of the second and higher order statistics for more accurate quantification of diffuse lung disease.

Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

PubMed Central

Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

2012-01-01

Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

A simple model of the effect of ocean ventilation on ocean heat uptake

NASA Astrophysics Data System (ADS)

Nadiga, Balu; Urban, Nathan

2017-11-01

Transport of water from the surface mixed layer into the ocean interior is achieved, in large part, by the process of ventilation-a process associated with outcropping isopycnals. Starting from such a configuration of outcropping isopycnals, we derive a simple model of the effect of ventilation on ocean uptake of anomalous radiative forcing. This model can be seen as an improvement of the popular anomaly-diffusing class of energy balance models (AD-EBM) that are routinely employed to analyze and emulate the warming response of both observed and simulated Earth system. We demonstrate that neither multi-layer, nor continuous-diffusion AD-EBM variants can properly represent both surface-warming and the vertical distribution of ocean heat uptake. The new model overcomes this deficiency. The simplicity of the models notwithstanding, the analysis presented and the necessity of the modification is indicative of the role played by processes related to the down-welling branch of global ocean circulation in shaping the vertical distribution of ocean heat uptake.

Copper uptake by the water hyacinth. [Eichornia crassipes

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

Lee, T.A.; Hardy, J.K.

1987-01-01

Factors affecting Cu/sup +2/ uptake by the water hyacinth (Eichornia crassipes) were examined. Two phases of copper uptake were observed throughout the uptake range (1-1000 mg/1). An initial rapid uptake phase of 4 hours followed by a slower, near linear uptake phase extending past 48 hours was observed. Stirring the solution enhanced uptake, suggesting copper removal is partially diffusion limited. Variations in pH over the range of 3 to 10 did not significantly affect uptake. Increasing the root mass of the plant increased the amount of copper taken up. As solution volume was increased more copper was removed. The presencemore » of complexing agents during the uptake phase reduced copper uptake. The inability of complexing agents to recover all copper initially removed by a plant suggests a migration to sites within the plant.« less

Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease.

PubMed

Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

2017-01-01

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 ( 67 Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67 Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.

Pulmonary Hypertension in Parenchymal Lung Disease

PubMed Central

Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.

2012-01-01

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

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.

[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.

Transporters, channels, or simple diffusion? Dogmas, atypical roles and complexity in transport systems.

PubMed

Conde, Artur; Diallinas, George; Chaumont, François; Chaves, Manuela; Gerós, Hernâni

2010-06-01

The recent breakthrough discoveries of transport systems assigned with atypical functions provide evidence for complexity in membrane transport biochemistry. Some channels are far from being simple pores creating hydrophilic passages for solutes and can, unexpectedly, act as enzymes, or mediate high-affinity uptake, and some transporters are surprisingly able to function as sensors, channels or even enzymes. Furthermore, numerous transport studies have demonstrated complex multiphasic uptake kinetics for organic and mineral nutrients. The biphasic kinetics of glucose uptake in Saccharomyces cerevisiae, a result of several genetically distinct uptake systems operating simultaneously, is a classical example that is a subject of continuous debate. In contrast, some transporters display biphasic kinetics, being bona fidae dual-affinity transporters, their kinetic properties often modulated by post-translational regulation. Also, aquaporins have recently been reported to exhibit diverse transport properties and can behave as highly adapted, multifunctional channels, transporting solutes such as CO(2), hydrogen peroxide, urea, ammonia, glycerol, polyols, carbamides, purines and pyrimidines, metalloids, glycine, and lactic acid, rather than being simple water pores. The present review provides an overview on some atypical functions displayed by transporter proteins and discusses how this novel knowledge on cellular uptake systems may be related to complex multiphasic uptake kinetics often seen in a wide variety of living organisms and the intriguing diffusive uptake of sugars and other solutes. Copyright 2009 Elsevier Ltd. All rights reserved.

(18)F-FDG uptake predicts diagnostic yield of transbronchial biopsy in peripheral lung cancer.

PubMed

Umeda, Yukihiro; Demura, Yoshiki; Anzai, Masaki; Matsuoka, Hiroki; Araya, Tomoyuki; Nishitsuji, Masaru; Nishi, Koichi; Tsuchida, Tatsuro; Sumida, Yasuyuki; Morikawa, Miwa; Ameshima, Shingo; Ishizaki, Takeshi; Kasahara, Kazuo; Ishizuka, Tamotsu

2014-07-01

Recent advances in endobronchial ultrasonography with a guide sheath (EBUS-GS) have enabled better visualization of distal airways, while virtual bronchoscopic navigation (VBN) has been shown useful as a guide to navigate the bronchoscope. However, indications for utilizing VBN and EBUS-GS are not always clear. To clarify indications for a bronchoscopic examination using VBN and EBUS-GS, we evaluated factors that predict the diagnostic yield of a transbronchial biopsy (TBB) procedure for peripheral lung cancer (PLC) lesions. We retrospectively reviewed the charts of 194 patients with 201 PLC lesions (≤3cm mean diameter), and analyzed the association of diagnostic yield of TBB with [(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron emission tomography and chest computed tomography (CT) findings. The diagnostic yield of TBB using VBN and EBUS-GS was 66.7%. High maximum standardized uptake value (SUVmax), positive bronchus sign, and ground-glass opacity component shown on CT were all significant predictors of diagnostic yield, while multivariate analysis showed only high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign as significant predictors. Diagnostic yield was higher for PLC lesions with high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign (84.6%) than for those with SUVmax <2.8 and negative bronchus sign (33.3%). High (18)F-FDG uptake was also correlated with tumor invasiveness. High (18)F-FDG uptake predicted the diagnostic yield of TBB using VBN and EBUS-GS for PLC lesions. (18)F-FDG uptake and bronchus sign may indicate for the accurate application of bronchoscopy with those modalities for diagnosing PLC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Epithelial organic cation transporters ensure pH-dependent drug absorption in the airway.

PubMed

Horvath, Gabor; Schmid, Nathalie; Fragoso, Miryam A; Schmid, Andreas; Conner, Gregory E; Salathe, Matthias; Wanner, Adam

2007-01-01

Most inhaled beta(2)-adrenergic agonist and anticholinergic bronchodilators have low lipid solubility because of their transient or permanent positive net charge at physiologic pH. Airway absorption of these cationic drugs is incompletely understood. We examined carrier-mediated mechanisms of cationic drug uptake by human airway epithelia. Airway tissues and epithelial cells, obtained from lung donors without preexisting lung disease, were evaluated for organic cation transporter expression by quantitative RT-PCR and immunofluorescence. For in vitro functional studies on primary airway epithelial cells, uptake of the cationic fluorophore 4-[4-(dimethylamino)-styryl]-N-methylpyridinium (ASP+) was characterized. Quantitative RT-PCR analysis demonstrated high mRNA levels for two polyspecific organic cation/carnitine transporters, OCTN1 and OCTN2, in human airway epithelia. Immunofluorescence of human airway sections confirmed OCTN1/2 protein expression, with a predominant localization to the apical portion of epithelial cells. Primary airway epithelial cells showed a carrier-mediated, temperature-sensitive and saturable uptake of ASP(+). Seventy-five to eighty percent of ASP(+) uptake was inhibited by L-carnitine, an OCTN2-carried zwitterion. The uptake was pH dependent, with approximately 3-fold lower rates at acidic (pH 5.7) than at alkaline (pH 8.2) extracellular pH. Albuterol and formoterol inhibited ASP(+) uptake, suggesting that all these molecules are carried by the same transport mechanism. These findings demonstrate the existence and functional role of a pH-dependent organic cation uptake machinery, namely OCTN1 and OCTN2, in human airway epithelia. We suggest that epithelial OCTN1/2 are involved in the delivery of inhaled cationic bronchodilators to the airway tissue.

Neural Networks for Nodal Staging of Non–Small Cell Lung Cancer with FDG PET and CT: Importance of Combining Uptake Values and Sizes of Nodes and Primary Tumor

PubMed Central

Vesselle, Hubert J.

2014-01-01

Purpose To evaluate the effect of adding lymph node size to three previously explored artificial neural network (ANN) input parameters (primary tumor maximum standardized uptake value or tumor uptake, tumor size, and nodal uptake at N1, N2, and N3 stations) in the structure of the ANN. The goal was to allow the resulting ANN structure to relate lymph node uptake for size to primary tumor uptake for size in the determination of the status of nodes as human readers do. Materials and Methods This prospective study was approved by the institutional review board, and informed consent was obtained from all participants. The authors developed a back-propagation ANN with one hidden layer and eight processing units. The data set used to train the network included node and tumor size and uptake from 133 patients with non–small cell lung cancer with surgically proved N status. Statistical analysis was performed with the paired t test. Results The ANN correctly predicted the N stage in 99.2% of cases, compared with 72.4% for the expert reader (P < .001). In categorization of N0 and N1 versus N2 and N3 disease, the ANN performed with 99.2% accuracy versus 92.2% for the expert reader (P < .001). Conclusion The ANN is 99.2% accurate in predicting surgical-pathologic nodal status with use of four fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)–derived parameters. Malignant and benign inflammatory lymph nodes have overlapping appearances at FDG PET/CT but can be differentiated by ANNs when the crucial input of node size is used. © RSNA, 2013 Online supplemental material is available for this article. PMID:24056403

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.

Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice.

PubMed

Zarogoulidis, Paul; Kerenidi, Theodora; Huang, Haidong; Kontakiotis, Theodoros; Tremma, Ourania; Porpodis, Konstantinos; Kalianos, Anastasios; Rapti, Ageliki; Foroulis, Christoforos; Zissimopoulos, Athanasios; Courcoutsakis, Nikolaos; Zarogoulidis, Konstantinos

2012-12-01

Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages. Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society. There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010). The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.

Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

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

Line, B.R.; Hunninghake, G.W.; Keogh, B.A.

1981-04-01

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, we studied 41 patients with this disorder and correlated estimates of pulmonary 67Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of 67Ga accumulation in the lung compared with control subjects, only weak correlations (r lessmore » than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of 67Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because 67Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.« less

The change of longitudinal relaxation rate in oxygen enhanced pulmonary MRI depends on age and BMI but not diffusing capacity of carbon monoxide in healthy never-smokers.

PubMed

Kindvall, Simon Sven Ivan; Diaz, Sandra; Svensson, Jonas; Wollmer, Per; Olsson, Lars E

2017-01-01

Oxygen enhanced pulmonary MRI is a promising modality for functional lung studies and has been applied to a wide range of pulmonary conditions. The purpose of this study was to characterize the oxygen enhancement effect in the lungs of healthy, never-smokers, in light of a previously established relationship between oxygen enhancement and diffusing capacity of carbon monoxide in the lung (DL,CO) in patients with lung disease. In 30 healthy never-smoking volunteers, an inversion recovery with gradient echo read-out (Snapshot-FLASH) was used to quantify the difference in longitudinal relaxation rate, while breathing air and 100% oxygen, ΔR1, at 1.5 Tesla. Measurements were performed under multiple tidal inspiration breath-holds. In single parameter linear models, ΔR1 exhibit a significant correlation with age (p = 0.003) and BMI (p = 0.0004), but not DL,CO (p = 0.33). Stepwise linear regression of ΔR1 yields an optimized model including an age-BMI interaction term. In this healthy, never-smoking cohort, age and BMI are both predictors of the change in MRI longitudinal relaxation rate when breathing oxygen. However, DL,CO does not show a significant correlation with the oxygen enhancement. This is possibly because oxygen transfer in the lung is not diffusion limited at rest in healthy individuals. This work stresses the importance of using a physiological model to understand results from oxygen enhanced MRI.

High expression of neutral endopeptidase in idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells.

PubMed

Cohen, A J; King, T E; Gilman, L B; Magill-Solc, C; Miller, Y E

1998-11-01

Idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells (IDHPNC) is a clinicopathological entity characterized by a diffuse hyperplasia of neuroendocrine cells involving distal bronchi and bronchioles. The pathogenesis of this syndrome remains unknown. The hyperplastic neuroendocrine (NE) cells contain multiple neuropeptides, including the bombesinlike peptides (BLP), which are likely important in the pathogenesis of the disorder by stimulating proliferation of fibroblasts in a paracrine fashion and the NE cells themselves in an autocrine manner. Neutral endopeptidase (NEP) is a cell-surface enzyme that hydrolyzes BLP and other bioactive peptides. Low or undetectable NEP is present in many primary lung cancers and cell lines. Low NEP expression could increase neuropeptide-induced autocrine effects by increasing local levels of neuropeptides. We hypothesized that IDHPNC was associated with low or absent NEP expression. NEP expression was assayed in patients with IDHPNC (n = 3) and was compared with expression in patients with idiopathic pulmonary fibrosis (n = 5), hypersensitivity pneumonitis (n = 5), and normal lung (n = 4) using immunohistochemistry, ELISA, activity assay, and Western blot analysis. By these assays, NEP expression was highest in lungs affected by IDHPNC. NEP mRNA, as assessed in IDHPNC lung tissue by RT-PCR, was the expected size and free of mutation between bp 238-2437. Therefore, IDHPNC is unlikely to be the result of a defect in NEP expression. The apparent increase in NEP expression in lung tissue from patients with IDHPNC may reflect a compensatory increase that partly counteracts abundant neuropeptides, including BLP, present in this disorder.

Are there sex differences in the capillary blood volume and diffusing capacity response to exercise?

PubMed

Bouwsema, Melissa M; Tedjasaputra, Vincent; Stickland, Michael K

2017-03-01

Previous work suggests that women may exhibit a greater respiratory limitation in exercise compared with height-matched men. Diffusion capacity (Dl CO ) increases with incremental exercise, and the smaller lungs of women may limit membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) in response to the increased oxygen demand. We hypothesized that women would have lower Dl CO , Dl CO relative to cardiac output (Dl CO /Q̇), Dm, Vc, and pulmonary transit time, secondary to lower Vc at peak exercise. Sixteen women (112 ± 12% predicted relative V̇o 2peak ) and sixteen men (118 ± 22% predicted relative V̇o 2peak ) were matched for height and weight. Hemoglobin-corrected diffusing capacity (Dl CO ), Vc, and Dm were determined via the multiple-[Formula: see text] Dl CO technique at rest and during incremental exercise up to 90% of V̇o 2peak Both groups increased Dl CO , Vc, and Dm with exercise intensity, but women had 20% lower Dl CO ( P < 0.001), 18% lower Vc ( P = 0.002), and 22% lower Dm ( P < 0.001) compared with men across all workloads, and neither group exhibited a plateau in Vc. When expressed relative to alveolar volume (Va), the between-sex difference was eliminated. The drop in Dl CO /Q̇ was proportionally less in women than men, and mean pulmonary transit time did not drop below 0.3 s in either group. Women demonstrate consistently lower Dl CO , Vc, and Dm compared with height-matched men during exercise; however, these differences disappear with correction for lung size. These results suggest that after differences in lung volume are accounted for there is no intrinsic sex difference in the Dl CO , Vc, or Dm response to exercise. NEW & NOTEWORTHY Women demonstrate lower diffusing capacity-to-cardiac output ratio (Dl CO /Q̇), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) compared with height-matched men during exercise. However, these differences disappear after correction for lung size. The drop in Dl CO /Q̇ was proportionally less in women, and pulmonary transit time did not drop below 0.3 s in either group. After differences in lung volume are accounted for, there is no intrinsic sex difference in Dl CO , Vc, or Dm response to exercise. Copyright © 2017 the American Physiological Society.

Contrasting Diffusion Patterns for PC and Mobile Videos: A User-Centric View of the Influencing Factors

ERIC Educational Resources Information Center

Wu, Baixue

2010-01-01

As both computer and mobile phone reach nearly ubiquity in the U.S. market, the slow uptake of mobile video, in contrast to the thriving usage of PC-based video, warrants a deeper understanding of user-oriented factors contributing to the two diffusion paths. Unlike the majority of existing diffusion research practices, the dissertation…

Crosstalk between the equilibrative nucleoside transporter ENT2 and alveolar Adora2b adenosine receptors dampens acute lung injury

PubMed Central

Eckle, Tobias; Hughes, Kelly; Ehrentraut, Heidi; Brodsky, Kelley S.; Rosenberger, Peter; Choi, Doo-Sup; Ravid, Katya; Weng, Tingting; Xia, Yang; Blackburn, Michael R.; Eltzschig, Holger K.

2013-01-01

The signaling molecule adenosine has been implicated in attenuating acute lung injury (ALI). Adenosine signaling is terminated by its uptake through equilibrative nucleoside transporters (ENTs). We hypothesized that ENT-dependent adenosine uptake could be targeted to enhance adenosine-mediated lung protection. To address this hypothesis, we exposed mice to high-pressure mechanical ventilation to induce ALI. Initial studies demonstrated time-dependent repression of ENT1 and ENT2 transcript and protein levels during ALI. To examine the contention that ENT repression represents an endogenous adaptive response, we performed functional studies with the ENT inhibitor dipyridamole. Dipyridamole treatment (1 mg/kg; EC50=10 μM) was associated with significant increases in ALI survival time (277 vs. 395 min; P<0.05). Subsequent studies in gene-targeted mice for Ent1 or Ent2 revealed a selective phenotype in Ent2−/− mice, including attenuated pulmonary edema and improved gas exchange during ALI in conjunction with elevated adenosine levels in the bronchoalveolar fluid. Furthermore, studies in genetic models for adenosine receptors implicated the A2B adenosine receptor (Adora2b) in mediating ENT-dependent lung protection. Notably, dipyridamole-dependent attenuation of lung inflammation was abolished in mice with alveolar epithelial Adora2b gene deletion. Our newly identified crosstalk pathway between ENT2 and alveolar epithelial Adora2b in lung protection during ALI opens possibilities for combined therapies targeted to this protein set.—Eckle, T., Hughes, K., Ehrentraut, H., Brodsky, K. S., Rosenberger, P., Choi, D.-S., Ravid, K., Weng, T., Xia, Y., Blackburn, M. R., Eltzschig, H. K. Crosstalk between the equilibrative nucleoside transporter ENT2 and alveolar Adora2b adenosine receptors dampens acute lung injury. PMID:23603835

Metabolic effects of pulmonary obstruction on myocardial functioning: a pilot study using multiple time-point 18F-FDG-PET imaging.

PubMed

Choi, Grace G; Han, Yuchi; Weston, Brian; Ciftci, Esra; Werner, Thomas J; Torigian, Drew; Salavati, Ali; Alavi, Abass

2015-01-01

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the right ventricle (RV) of patients with chronic obstructive pulmonary disease (COPD) and to characterize the variability of 18F-FDG uptake in the RV at different time points following radiotracer administration using PET/computerized tomography (CT). Impaired RV systolic function, RV hypertrophy, and RV dilation are associated with increases in mean pulmonary arterial pressure in patients with COPD. Metabolic changes in the RV using 18F-FDG-PET images 2 and 3 h after tracer injection have not yet been investigated. Twenty-five patients with clinical suspicion of lung cancer underwent 18F-FDG-PET/CT imaging at 1, 2, and 3 h after tracer injection. Standardized uptake values (SUVs) and volumes of RV were recorded from transaxial sections to quantify the metabolic activity. The SUV of RV was higher in patients with COPD stages 1-3 as compared with that in patients with COPD stage 0. RV SUV was inversely correlated with FEV1/FVC pack-years of smoking at 1 h after 18F-FDG injection. In the majority of patients, 18F-FDG activity in RV decreased over time. There was no significant difference in the RV myocardial free wall and chamber volume on the basis of COPD status. The severity of lung obstruction and pack-years of smoking correlate with the level of 18F-FDG uptake in the RV myocardium, suggesting that there may be metabolic changes in the RV associated with lung obstruction that can be detected noninvasively using 18F-FDG-PET/CT. Multiple time-point images of the RV did not yield any additional value in this study.

Pharmacological evaluation of an [(123)I] labelled imidazopyridine-3-acetamide for the study of benzodiazepine receptors.

PubMed

Mattner, Filomena; Mardon, Karine; Loc'h, Christian; Katsifis, Andrew

2006-06-13

In vitro binding of the iodinated imidazopyridine, N',N'-dimethyl-6-methyl-(4'-[(123)I]iodophenyl)imidazo[1,2-a]pyridine-3-acetamide [(123)I]IZOL to benzodiazepine binding sites on brain cortex, adrenal and kidney membranes is reported. Saturation experiments showed that [(123)I]IZOL, bound to a single class of binding site (n(H)=0.99) on adrenal and kidney mitochondrial membranes with a moderate affinity (K(d)=30 nM). The density of binding sites was 22+/-6 and 1.2+/-0.4 pmol/mg protein on adrenal and kidney membranes, respectively. No specific binding was observed in mitochondrial-synaptosomal membranes of brain cortex. In biodistribution studies in rats, the highest uptake of [(123)I]IZOL was found 30 min post injection in adrenals (7.5% ID/g), followed by heart, kidney, lung (1% ID/g) and brain (0.12% ID/g), consistent with the distribution of peripheral benzodiazepine binding sites. Pre-administration of unlabelled IZOL and the specific PBBS drugs, PK 11195 and Ro 5-4864 significantly reduced the uptake of [(123)I]IZOL by 30% (p<0.05) in olfactory bulbs and by 51-86% (p<0.01) in kidney, lungs, heart and adrenals, while it increased by 30% to 50% (p<0.01) in the rest of the brain and the blood. Diazepam, a mixed CBR-PBBS drug, inhibited the uptake in kidney, lungs, heart, adrenals and olfactory bulbs by 32% to 44% (p<0.01) but with no effect on brain uptake and in blood concentration. Flumazenil, a central benzodiazepine drug and haloperidol (dopamine antagonist/sigma receptor drug) displayed no effect in [(123)I]IZOL in peripheral organs and in the brain. [(123)I]IZOL may deserve further development for imaging selectively peripheral benzodiazepine binding sites.

Colloid Adenocarcinoma of the Lung: CT and PET/CT Findings in Seven Patients.

PubMed

Kim, Han Kyul; Han, Joungho; Franks, Teri J; Lee, Kyung Soo; Kim, Tae Jung; Choi, Joon Young; Zo, Jaeil

2018-05-24

We aimed to assess CT and 18 F-FDG PET/CT findings of colloid adenocarcinoma of the lung in seven patients. From 2010 to 2017, seven patients with surgically proven colloid adenocarcinoma of the lung were identified. CT (both enhanced and unenhanced) and PET/CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed. In all cases except one, tumors showed low attenuation on unenhanced CT scans, ranging in attenuation from -16.5 to 20.7 HU (median, 9.2 HU). After contrast medium injection, enhancement was scant, so net enhancement ranged from 0.4 to 29.0 HU (median, 4.1 HU). All tumors had a lobulated contour. Stippled calcifications within the tumor were seen in one patient. The maximum standardized uptake value of tumors on PET/CT ranged from 1.5 to 4.5 (median, 3.5). In six of seven patients, FDG accumulation was seen in the tumor walls (n = 3, curvilinear uptake) or in both the tumor walls and tumor septa (n = 3, crisscross uptake). Six patients were alive without recurrence after a median follow-up period of 2.3 years (range, 2 months to 5 years). In one patient, who was alive at follow-up 4 years after imaging and had received adjuvant concurrent chemoradiation therapy after lobectomy, recurrent disease was detected 6 months after completion of the therapy. On CT, pulmonary colloid adenocarcinomas present as lobulated homogeneously low-attenuation tumors. At PET, curvilinear or crisscross FDG uptake is seen within the tumor where tumor cells are lining the walls or septal structures.

Exploring the cellular and tissue uptake of nanomaterials in a range of biological samples using multimodal nonlinear optical microscopy

NASA Astrophysics Data System (ADS)

Johnston, Helinor J.; Mouras, Rabah; Brown, David M.; Elfick, Alistair; Stone, Vicki

2015-12-01

The uptake of nanomaterials (NMs) by cells is critical in determining their potential biological impact, whether beneficial or detrimental. Thus, investigation of NM internalization by cells is a common consideration in hazard and efficacy studies. There are currently a number of approaches that are routinely used to investigate NM-cell interactions, each of which have their own advantages and limitations. Ideally, imaging modalities used to investigate NM uptake by cells should not require the NM to be labelled (e.g. with fluorophores) to facilitate its detection. We present a multimodal imaging approach employing a combination of label-free microscopies that can be used to investigate NM-cell interactions. Coherent anti-Stokes Raman scattering microscopy was used in combination with either two-photon photoluminescence or four-wave mixing (FWM) to visualize the uptake of gold or titanium dioxide NMs respectively. Live and fixed cell imaging revealed that NMs were internalized by J774 macrophage and C3A hepatocyte cell lines (15-31 μg ml-1). Sprague Dawley rats were exposed to NMs (intratracheal instillation, 62 μg) and NMs were detected in blood and lung leucocytes, lung and liver tissue, demonstrating that NMs could translocate from the exposure site. Obtained data illustrate that multimodal nonlinear optical microscopy may help overcome current challenges in the assessment of NM cellular uptake and biodistribution. It is therefore a powerful tool that can be used to investigate unlabelled NM cellular and tissue uptake in three dimensions, requires minimal sample preparation, and is applicable to live and fixed cells.

Boron absorption imaging in rat lung colon adenocarcinoma metastases

NASA Astrophysics Data System (ADS)

Altieri, S.; Bortolussi, S.; Bruschi, P.; Fossati, F.; Vittor, K.; Nano, R.; Facoetti, A.; Chiari, P.; Bakeine, J.; Clerici, A.; Ferrari, C.; Salvucci, O.

2006-05-01

Given the encouraging results from our previous work on the clinical application of BNCT on non-resectable, chemotherapy resistant liver metastases, we explore the possibility to extend our technique to lung metastases. A fundamental requirement for BNCT is achieving higher 10B concentrations in the metastases compared to those in healthy tissue. For this reason we developed a rat model with lung metastases in order to study the temporal distribution of 10B concentration in tissues and tumoral cells. Rats with induced lung metastases from colon adenocarcinoma were sacrificed two hours after intraperitoneal Boronphenylalanine infusion. The lungs were harvested, frozen in liquid nitrogen and subsequently histological sections underwent neutron autoradiography in the nuclear reactor Triga Mark II, University of Pavia. Our findings demonstrate higher Boron uptake in tumoral nodules compared to healthy lung parenchyma 2 hours after Boronphenylalanine infusion.

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

Study on kinetics of glucose uptake by some species of plankton

NASA Astrophysics Data System (ADS)

Li, Wenquan; Wang, Xian; Zhang, Yaohua

1993-03-01

The rates of glucose uptake by some species of plankton were determined by3H-glucose tracer method. Experimental results indicated that the observed glucose uptake at natural seawater concentrations by Platymonas subcordiformis and Brachionus plicatilis was principally a metabolic process fitted with the Michaelis-Menten equation in the range of adaptive temperatures. Heterotrophic uptake by Platymonas subcordiformis was mainly dependent on diffusion at high glucose levels. The uptake by Brachionus plicatilis showed active transport even at high glucose levels, indicating its high heterotrophic activity. The uptake rate by Artemia salina was lower, and its V m/K ratio was lower than those of the other two species of plankton.

SU-F-T-130: [18F]-FDG Uptake Dose Response in Lung Correlates Linearly with Proton Therapy Dose

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

Kim, D; Titt, U; Mirkovic, D

2016-06-15

Purpose: Analysis of clinical outcomes in lung cancer patients treated with protons using 18F-FDG uptake in lung as a measure of dose response. Methods: A test case lung cancer patient was selected in an unbiased way. The test patient’s treatment planning and post treatment positron emission tomography (PET) were collected from picture archiving and communication system at the UT M.D. Anderson Cancer Center. Average computerized tomography scan was registered with post PET/CT through both rigid and deformable registrations for selected region of interest (ROI) via VelocityAI imaging informatics software. For the voxels in the ROI, a system that extracts themore » Standard Uptake Value (SUV) from PET was developed, and the corresponding relative biological effectiveness (RBE) weighted (both variable and constant) dose was computed using the Monte Carlo (MC) methods. The treatment planning system (TPS) dose was also obtained. Using histogram analysis, the voxel average normalized SUV vs. 3 different doses was obtained and linear regression fit was performed. Results: From the registration process, there were some regions that showed significant artifacts near the diaphragm and heart region, which yielded poor r-squared values when the linear regression fit was performed on normalized SUV vs. dose. Excluding these values, TPS fit yielded mean r-squared value of 0.79 (range 0.61–0.95), constant RBE fit yielded 0.79 (range 0.52–0.94), and variable RBE fit yielded 0.80 (range 0.52–0.94). Conclusion: A system that extracts SUV from PET to correlate between normalized SUV and various dose calculations was developed. A linear relation between normalized SUV and all three different doses was found.« less

Fluorodeoxyglucose positron emission tomography for detection of tumor recurrence following radiofrequency ablation in retrospective cohort of stage I lung cancer.

PubMed

Wang, Yingbing; Lanuti, Michael; Bernheim, Adam; Shepard, Jo-Anne O; Sharma, Amita

2018-05-03

The goal of this study was to define patterns for tumor recurrence on PET following RFA, compare time to imaging recurrence by PET versus CT, evaluate whether pre-treatment tumor uptake predicts recurrence and propose an optimal post-RFA surveillance strategy. A retrospective cohort study was performed of biopsy confirmed primary stage I lung cancers treated with RFA. FDG PET and near contemporaneous diagnostic CT imaging pre-ablation, within 30 days post-ablation, and beyond 6 months were independently and retrospectively evaluated for features supportive of recurrence. Time to imaging recurrence by PET (TTR_PET) and by CT (TTR_CT) were determined and compared. FDG avidity of untreated tumors was compared between recurrent and non-recurrent groups. Thirteen recurrences after 72 RFA treatments were confirmed by diagnostic CT. All recurrences were associated with focally intense and increasing FDG uptake beyond 6 months (sensitivity 100%; specificity 98.5%). Mean TTR_PET was 14 months compared to mean TTR_CT of 17 months (not statistically significant). Normalized SUVmax and total lesions glycolysis of lung cancers that recurred after RFA was 4.0 and 6.0, respectively compared to 2.8 and 5.0, respectively for cancers that did not recur (p = .068). A pattern of focally intense and increasing FDG PET uptake has high sensitivity and specificity for detecting recurrent lung cancer following RFA. Surveillance after RFA should include a contrast enhanced diagnostic CT at 1 month to diagnose procedural complications, PET at 6 months as a post-treatment metabolic baseline (with diagnostic CT if PET is abnormal) and alternating diagnostic CTs or PET every 6 months for 2 years.

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

Pharmacology of radioiodinated hexadecenoic acid--a myocardial imaging agent.

PubMed

Sun, Q X; Zhang, J; Ji, Q M; Wang, Y C; Xie, D F; Hua, R L; He, W Y; Shi, X C; Li, Y J; Jiang, C J

1984-04-01

123I- and 131I-labeled hexadecenoic acid (IHDA, radiochemical purity over 92%, dissolved in 6% bovine serum albumin solution) was investigated in vivo. ICR mice were administered IHDA via the tail vein. Maximum myocardial uptake (27.3 +/- 5.1%) was reached about 0.5 min after the injection. The ratio of uptake in the heart to that in the lungs was 2.3, to that in liver 1.5 and to that in other organs 2.4 to 6.4. The dog myocardium was visualized distinctly within 3-5 min with a gamma camera after i.v. 131I-IHDA, and not interfered with by activities in the lungs, liver and other organs. The low blood levels at 20 min had little effect on the quality of the heart images.

Postmortem endogenous ethanol production and diffusion from the lung due to aspiration of wood chip dust in the work place.

PubMed

Furumiya, Junichi; Nishimura, Hiroyuki; Nakanishi, Akinori; Hashimoto, Yoshiaki

2011-07-01

We report an autopsy case of postmortem ethanol diffusion into the cardiac blood after aspiration of wood chips, although antemortem ethanol consumption was not evident. A man in his twenties, who was loading a truck with small wood chips in a hot, humid storehouse, was accidentally buried in a heap of chips. At the time the body was discovered, 20 h after the accident, rectal temperature was 36°C. Autopsy showed the cause of death to be asphyxia due to obstruction of the airway by aspiration of wood chips. The ethanol and n-propanol levels were significantly higher in the lungs (left, 0.603 and 0.009 mg/g; right, 0.571 and 0.006 mg/g) than in other tissues. A significant difference in ethanol concentration was observed between the left cardiac blood (0.243 mg/g) and the right femoral blood (0.042 mg/g). Low levels of ethanol and n-propanol were detected in the stomach contents (0.105 and 0.001 mg/g, respectively). In order to determine whether aspiration of wood chips affects postmortem ethanol production in the lung, we measured the ethanol and n-propanol levels of homogenized rabbit lung tissue incubated with autoclaved or non-autoclaved wood chips. Levels of ethanol and n-propanol were significantly higher in the homogenates incubated with non-autoclaved chips for 24h. The results of this animal experiment suggested that the ethanol detected in the lung was produced by putrefactive bacteria within the wood chips. After death, the ethanol produced endogenously in the lung appears to have diffused and affected the ethanol concentration of the left cardiac blood. 2011 Elsevier Ireland Ltd. All rights reserved.

Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

PubMed Central

Wolf, Michael S.; Chadha, Ashley D.; Carroll, Clinton M.; Borinstein, Scott C.

2014-01-01

Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. PMID:25434733

How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion

PubMed Central

Kell, Douglas B.; Oliver, Stephen G.

2014-01-01

One approach to experimental science involves creating hypotheses, then testing them by varying one or more independent variables, and assessing the effects of this variation on the processes of interest. We use this strategy to compare the intellectual status and available evidence for two models or views of mechanisms of transmembrane drug transport into intact biological cells. One (BDII) asserts that lipoidal phospholipid Bilayer Diffusion Is Important, while a second (PBIN) proposes that in normal intact cells Phospholipid Bilayer diffusion Is Negligible (i.e., may be neglected quantitatively), because evolution selected against it, and with transmembrane drug transport being effected by genetically encoded proteinaceous carriers or pores, whose “natural” biological roles, and substrates are based in intermediary metabolism. Despite a recent review elsewhere, we can find no evidence able to support BDII as we can find no experiments in intact cells in which phospholipid bilayer diffusion was either varied independently or measured directly (although there are many papers where it was inferred by seeing a covariation of other dependent variables). By contrast, we find an abundance of evidence showing cases in which changes in the activities of named and genetically identified transporters led to measurable changes in the rate or extent of drug uptake. PBIN also has considerable predictive power, and accounts readily for the large differences in drug uptake between tissues, cells and species, in accounting for the metabolite-likeness of marketed drugs, in pharmacogenomics, and in providing a straightforward explanation for the late-stage appearance of toxicity and of lack of efficacy during drug discovery programmes despite macroscopically adequate pharmacokinetics. Consequently, the view that Phospholipid Bilayer diffusion Is Negligible (PBIN) provides a starting hypothesis for assessing cellular drug uptake that is much better supported by the available evidence, and is both more productive and more predictive. PMID:25400580

Pulmonary function tests do not predict mortality in patients undergoing continuous-flow left ventricular assist device implantation.

PubMed

Bedzra, Edo K S; Dardas, Todd F; Cheng, Richard K; Pal, Jay D; Mahr, Claudius; Smith, Jason W; Shively, Kent; Masri, S Carolina; Levy, Wayne C; Mokadam, Nahush A

2017-12-01

To investigate the effect of pulmonary function testing on outcomes after continuous flow left ventricular assist device implantation. A total of 263 and 239 patients, respectively, had tests of forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide preoperatively for left ventricular assist device implantations between July 2005 and September 2015. Kaplan-Meier analysis and multivariable Cox regressions were performed to evaluate mortality. Patients were analyzed in a single cohort and across 5 groups. Postoperative intensive care unit and hospital lengths of stay were evaluated with negative binomial regressions. There is no association of forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide with survival and no difference in mortality at 1 and 3 years between the groups (log rank P = .841 and .713, respectively). Greater values in either parameter were associated with decreased hospital lengths of stay. Only diffusing capacity of the lungs for carbon monoxide was associated with increased intensive care unit length of stay in the group analysis (P = .001). Ventilator times, postoperative pneumonia, reintubation, and tracheostomy rates were similar across the groups. Forced expiratory volume in 1 second and diffusing capacity of the lungs for carbon monoxide are not associated with operative or long-term mortality in patients undergoing continuous flow left ventricular assist device implantation. These findings suggest that these abnormal pulmonary function tests alone should not preclude mechanical circulatory support candidacy. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Incidental lung volume reduction following fulminant pulmonary hemorrhage in a patient with severe emphysema.

PubMed

Hetzel, Juergen; Spengler, Werner; Horger, Marius; Boeckeler, Michael

2015-06-01

Endoscopic lung volume reduction is an emerging technique meant to improve lung function parameters, quality of life, and exercise tolerance in patients with severe lung emphysema. This is the first report of lung volume reduction by autologous blood in a patient with non-bullous lung emphysema. A 74-year-old woman with heterogeneous lung emphysema developed accidentally diffuse lobar bleeding immediately after valve placement. Due to persistent hemorrhage, the valves had to be removed shortly thereafter. Despite extraction of the valves, respiratory function of the patient improved rapidly indicated also by a drop in the COPD assessment test questionnaire, 3 months later. This was consistent with both improvement of lung function tests and six-minute walking test.

Coupled elasticity–diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles

PubMed Central

Wang, Jizeng; Li, Long

2015-01-01

Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity–diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand–receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand–receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake. PMID:25411410

The effect of tissue structure and soil chemistry on trace element uptake in fossils

NASA Astrophysics Data System (ADS)

Hinz, Emily A.; Kohn, Matthew J.

2010-06-01

Trace element profiles for common divalent cations (Sr, Zn, Ba), rare-earth elements (REE), Y, U, and Th were measured in fossil bones and teeth from the c. 25 ka Merrell locality, Montana, USA, by using laser-ablation ICP-MS. Multiple traverses in teeth were transformed into 2-D trace element maps for visualizing structural influences on trace element uptake. Trace element compositions of different soils from the fossil site were also analyzed by solution ICP-MS, employing progressive leaches that included distilled H 2O, 0.1 M acetic acid, and microwave digestion in concentrated HCl-HNO 3. In teeth, trace element uptake in enamel is 2-4 orders of magnitude slower than in dentine, forming an effective trace element barrier. Uptake in dentine parallel to the dentine-enamel interface is enhanced by at least 2 orders of magnitude compared to transverse, causing trace element "plumes" down the tooth core. In bone, U, Ba and Sr are nearly homogeneous, implying diffusivities ˜5 orders of magnitude faster than in enamel and virtually complete equilibration with host soils. In contrast all REE show strong depletions inward, with stepwise linear segments in log-normal or inverse complementary error function plots; these data require a multi-medium diffusion model, with about 2 orders of magnitude difference in slowest vs. fastest diffusivities. Differences in REE diffusivities in bone (slow) vs. dentine (fast) reflect different partition coefficients ( Kd's). Although acid leaches and bulk digestion of soils yield comparable fossil-soil Kd's among different elements, natural solutions are expected to be neutral to slightly basic. Distilled H 2O leachates instead reveal radically different Kd's in bone for REE than for U-Sr-Ba, suggest orders of magnitude lower effective diffusivities for REE, and readily explain steep vs. flat profiles for REE vs. U-Sr-Ba, respectively. Differences among REE Kd's and diffusivities may explain inward changes in Ce anomalies. Acid washes and bulk soil compositions yield misleading Kd's for many trace elements, especially the REE, and H 2O-leaches are preferred. Patterns of trace element distributions indicate diagenetic alteration at all scales, including enamel, and challenge the use of trace elements in paleodietary studies.

Gallium-positive Lyme disease myocarditis

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

Alpert, L.I.; Welch, P.; Fisher, N.

1985-09-01

In the course of a work-up for fever of unknown origin associated with intermittent arrhythmias, a gallium scan was performed which revealed diffuse myocardial uptake. The diagnosis of Lyme disease myocarditis subsequently was confirmed by serologic titers. One month following recovery from the acute illness, the abnormal myocardial uptake completely resolved.

Urinary Tobacco Smoke Constituent Biomarkers for Assessing Risk of Lung Cancer

PubMed Central

Yuan, Jian-Min; Butler, Lesley M.; Stepanov, Irina; Hecht, Stephen S.

2014-01-01

Tobacco constituent biomarkers are metabolites of specific compounds present in tobacco or tobacco smoke. Highly reliable analytical methods, based mainly on mass spectrometry, have been developed for quantitation of these biomarkers in both urine and blood specimens. There is substantial inter-individual variation in smoking-related lung cancer risk that is determined in part by individual variability in the uptake and metabolism of tobacco smoke carcinogens. Thus, by incorporating these biomarkers in epidemiological studies we can potentially obtain a more valid and precise measure of in vivo carcinogen dose than by using self-reported smoking history, ultimately improving the estimation of smoking-related lung cancer risk. Indeed, we have demonstrated this by using a prospective study design comparing biomarker levels in urine samples collected from smokers many years prior to their development of cancer, versus those in their smoking counterparts without a cancer diagnosis. The following urinary metabolites were associated with lung cancer risk, independent of smoking intensity and duration: cotinine plus its glucuronide, a biomarker of nicotine uptake; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), a biomarker of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); and r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a biomarker of polycyclic aromatic hydrocarbons (PAH). These results provide several possible new directions for using tobacco smoke constituent biomarkers in lung cancer prevention, including improved lung cancer risk assessment, intermediate outcome determination in prevention trials and regulation of tobacco products. PMID:24408916

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.

An improved procedure for reconstitution of the uncoupling protein and in-depth analysis of H+/OH- transport.

PubMed

Winkler, E; Klingenberg, M

1992-07-01

An improved procedure for reincorporation of isolated uncoupling protein (UCP) from brown adipose tissue into phospholipid vesicles is reported and H+ uptake in K(+)-driven exchange diffusion quantitatively analyzed. UCP is isolated and reconstituted with medium-length linear-chain alkyl polyoxyethylene. In the critical step of vesicle formation, the stepwise removal of the detergent by polystyrene beads is applied. Vesicles are generated in the presence of solutes and buffers to be internalized which are then removed by gel filtration. The internal volume is about 4 microliters/mg phospholipid with a vesicle diameter of 100 nm. One vesicle contains, on average, six molecules UCP. The best results are obtained with purified egg yolk phosphatidylcholine. Addition of PtdEtn, PtdSer decreases the vesicle size and, still more, H(+)-transport activity by UCP. Asolectin completely inactivates UCP. K(+)-gradient-driven H+ uptake is 80% inhibited by external GTP and 95% by internal plus external GTP. When H+ transport is recorded externally by a pH electrode and internally by pyranine, the kinetics show no delay resulting from intervening membrane-bound H+ pools. Total H+ uptake after addition of carbonylcyanine m-chlorophenylhydrazone (CCCP) and valinomycin corresponds to the diffusion between H+ and K+ and is unchanged by GTP. The linear correlation of H(+)-transport inhibition to GTP binding demonstrates that all UCP molecules incorporated are equally active. The exchange diffusion between H+ uptake and K+ efflux is demonstrated using a K+ electrode and 86Rb measurements. Recording delta psi using 3,3'-diispropylthiadicarbocyanine shows a rapid generation of delta psi on valinomycin addition, which decreases only slightly with H+ uptake, even after addition of CCCP or gramicidin. The delta psi collapses only after addition of external K+. By demonstrating that valinomycin-induced K+ and H+ fluxes reflect relaxation into the diffusion equilibrium state, the transport rate of UCP can be evaluated as a first-order rate, VH+/CH+, in which the rate, VH+, is related to H(+)-uptake capacity, CH+. This allows quantitative comparison of transport rates independently of the variable CH+. The dependence on delta psi of H+ transport is measured by varying external K+ concentration. A virtually linear relation of the rate to the K(+)-diffusion potential is observed, although the capacity is only slightly changed. The linear VH+/delta psi relationship resembles an open-channel type of transport, but is discussed in terms of a low-activation-barrier type of carrier mechanism, in contrast to the log (VH+/delta psi) relation found for the ADP/ATP carrier with high activation barriers.

Effects of the oestrous cycle and exogenous ovarian steroids on metabolism of beta-phenylethylamine in rat lung.

PubMed Central

Bakhle, Y. S.; Ben-Harari, R. R.

1979-01-01

1 Metabolism of [14C]-beta-phenylethylamine (PEN), a substrate for monoamine oxidase-B (MAO-B), was measured in lung homogenates and in perfused lungs during the 4 day oestrous cycle of the rat. 2 Metabolism in vitro was high during met-oestrus and di-oestrus and low during pro-oestrus and oestrus; this variation in activity correlated with changes in Vmax of the enzyme without changes in Km. 3 PEN metabolism in lung homogenates was also altered by treatment of rats with 17 beta-oestradiol but not by progesterone treatment. 4 Metabolism of [14C]-PEN in perfused lungs was the same during either pro-oestrus or met-oestrus. Uptake of [14C]-PEN in perfused lung measured directly was also the same at these two stages. 5 These results demonstrate that in lungs MAO-B activity was affected by endogenous changes in steroid level but that such changes in enzymic activity were not reflected in the metabolic properties of whole lung. PMID:574038

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

Postmortem CT investigation of air/gas distribution in the lungs and gastrointestinal tracts of newborn infants: a serial case study with regard to still- and live birth.

PubMed

Michiue, Tomomi; Ishikawa, Takaki; Kawamoto, Osamu; Sogawa, Nozomi; Oritani, Shigeki; Maeda, Hitoshi

2013-03-10

Flotation tests on the lungs and gastrointestinal tract to investigate aeration are classic procedures to examine the life of a newborn after birth; however, there are arguments about the reliability. The present study investigated serial forensic autopsy cases of newborn infants without marked decomposition (n=4) with regard to air/gas distribution in the lungs and gastrointestinal tracts by means of postmortem CT (PM-CT) as well as macromorphology and histology, compared with intrauterine and aborted fetuses (n=3). No gas was detected in the lungs or gastrointestinal tracts in all of three intrauterine fetal deaths. Gas was diffusely detected in the lungs of a newborn fatality attributed to smothering after birth; however, two neonatal fatalities had poor lung gas contents due to marked congestion with edema and diffuse atelectasis. In a case of unsuccessful cardiopulmonary resuscitation following possible birth asphyxia, pulmonary aeration was evidently localized on CT morphology, despite a larger amount of bowel gas, and was also uneven in histology, showing a membranous immunostaining pattern of pulmonary surfactant on the intra-alveolar surfaces of expanded alveoli. The combined use of PM-CT is useful to demonstrate air/gas distributions in the lungs and gastrointestinal tract for interpretation of spontaneous breathing after birth in newborn fatalities. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Is it better to include necrosis in apparent diffusion coefficient (ADC) measurements? The necrosis/wall ADC ratio to differentiate malignant and benign necrotic lung lesions: Preliminary results.

PubMed

Karaman, Adem; Durur-Subasi, Irmak; Alper, Fatih; Durur-Karakaya, Afak; Subasi, Mahmut; Akgun, Metin

2017-10-01

To determine whether the use of necrosis/wall apparent diffusion coefficient (ADC) ratios in the differentiation of necrotic lung lesions is more reliable than measuring the wall alone. In this retrospective study, a total of 76 patients (54 males and 22 females, 71% vs. 29%, with a mean age of 53 ± 18 years, range, 18-84) were enrolled, 33 of whom had lung carcinoma and 43 had a benign necrotic lung lesion. A 3T scanner was used. The calculation of the necrosis/wall ADC ratio was based on ADC values measured from necrosis and the wall of the lesions by diffusion-weighted imaging (DWI). Statistical analyses were performed with the independent samples t-test and receiver operating characteristic analysis. Intraobserver and interobserver reliability were calculated for ADC values of wall and necrosis. The mean necrosis/wall ADC ratio was 1.67 ± 0.23 for malignant lesions and 0.75 ± 0.19 for benign lung lesions (P < 0.001). To estimate malignancy the area under the curve (AUC) values for necrosis ADC, wall ADC, and the necrosis/wall ADC ratio were 0.720, 0.073, and 0.997, respectively. A wall/necrosis ADC ratio cutoff value of 1.12 demonstrated a 100% sensitivity and 98% specificity in the estimation of malignancy. Positive predictive value was 100%, and negative predictive value 98% and diagnostic accuracy 99%. There was a good intraobserver and interobserver reliability for wall and necrosis. The necrosis/wall ADC ratio appears to be a reliable and promising tool for discriminating lung carcinoma from benign necrotic lung lesions than measuring the wall alone. 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1001-1006. © 2017 International Society for Magnetic Resonance in Medicine.

NMR studies and applications of perfluorocarbon gases

NASA Astrophysics Data System (ADS)

Chang, Yulin

Hyperpolarized 3He has been very successful in magnetic resonance imaging (MRI) of the lungs. It provides ways to study the physiological properties of the lungs and lung function. However, the high costs of the polarizing apparatus and the complicated polarizing procedure are preventing this technique from being clinically used routinely. Recent developments have shown that several fluorinated gases have the potential to replace 3He in some of its applications. This thesis presents some preliminary results of human excised lung imaging using C2F6 and C3F8. These two fluorinated gases were able to yield images with good signal-to-noise ratio and reasonable resolutions in a 1.5 T magnet. Using diffusion MRI of these two gases can distinguish emphysematous lungs from healthy ones. An important application of these gases would be to determine local lung surface-to-volume (S/V) ratio in vivo, which requires the unrestricted (free) diffusivity in each pixel to be known. We present data in this thesis which allow free diffusivities to be calculated from the relaxation time T1. Samples of pure C 2F6 and C3F8 at different pressures and in mixtures with oxygen at different concentrations were made. Measurements were done at two different magnetic fields and temperature was regulated to study the temperature dependence over a small range. These two gases were also used in studies of carbon-block filters, where the strong adsorption of the gases to the high surface-area carbon is beneficial. A brief review of our work on mouse lung imaging using hyperpolarized 3He is presented in Appendix A; Appendix B is a study of the longitudinal spin magnetization in the presence of a strong magnetic field gradient; the construction of the pulsed field gradient waveform measurement coils and some experimental results using these coils are contained in Appendix C.

Uptake of DNA by cancer cells without a transfection reagent.

PubMed

Kong, Yanping; Zhang, Xianbo; Zhao, Yongliang; Xue, Yanfang; Zhang, Ye

2017-01-21

Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis. Their uptake of DNAs might be different from normal cells; they may take in DNAs directly from the environment. In this report, we studied the uptake of DNAs in cancer cells without a transfection reagent. A group of DNA fragments were prepared with PCR and labeled with isotope phosphorous-32 to test their uptake by Huh 7 (liver cancer) and THLE3 (normal liver cells) after incubation overnight by counting radioactivity of the cells' genomic DNA. Multiple cell lines including breast cancer and lung cancer were tested with the same method. DNA molecules were also labeled with fluorescence to test the location in the cells using a kit of "label it fluorescence in situ hybridization (FISH)" from Mirus (USA). The data demonstrated that hepatocellular carcinoma cells possess the ability to take in large DNA fragments directly without a transfection reagent whereas normal liver cells cannot. Huh7 and MDA-MB231 cells displayed a significantly higher Rhodamine density in the cytoplasmic phagosomes and this suggests that the mechanism of uptake of large DNA by cancer cells is likely endocytosis. The efficacy of uptake is related to the DNA's size. Some cell lines of lung cancer and breast cancer also showed similar uptake of DNA. In the present study, we have revealed the evidence that some cancer cells, but not nontumorigenic cells, can take DNA fragments directly from the environment without the aid of the transfecting reagent.

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.

Systematic investigation on the validity of partition model dosimetry for 90Y radioembolization using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Aziz Hashikin, Nurul Ab; Yeong, Chai-Hong; Guatelli, Susanna; Jeet Abdullah, Basri Johan; Ng, Kwan-Hoong; Malaroda, Alessandra; Rosenfeld, Anatoly; Perkins, Alan Christopher

2017-09-01

We aimed to investigate the validity of the partition model (PM) in estimating the absorbed doses to liver tumour ({{D}T} ), normal liver tissue ({{D}NL} ) and lungs ({{D}L} ), when cross-fire irradiations between these compartments are being considered. MIRD-5 phantom incorporated with various treatment parameters, i.e. tumour involvement (TI), tumour-to-normal liver uptake ratio (T/N) and lung shunting (LS), were simulated using the Geant4 Monte Carlo (MC) toolkit. 108 track histories were generated for each combination of the three parameters to obtain the absorbed dose per activity uptake in each compartment (DT{{AT}} , DNL{{ANL}} , and DL{{AL}} ). The administered activities, A were estimated using PM, so as to achieve either limiting doses to normal liver, DNLlim or lungs, ~DLlim (70 or 30 Gy, respectively). Using these administered activities, the activity uptake in each compartment ({{A}T} , {{A}NL} , and {{A}L} ) was estimated and multiplied with the absorbed dose per activity uptake attained using the MC simulations, to obtain the actual dose received by each compartment. PM overestimated {{D}L} by 11.7% in all cases, due to the escaped particles from the lungs. {{D}T} and {{D}NL} by MC were largely affected by T/N, which were not considered by PM due to cross-fire exclusion at the tumour-normal liver boundary. These have resulted in the overestimation of {{D}T} by up to 8% and underestimation of {{D}NL} by as high as  -78%, by PM. When DNLlim was estimated via PM, the MC simulations showed significantly higher {{D}NL} for cases with higher T/N, and LS  ⩽  10%. All {{D}L} and {{D}T} by MC were overestimated by PM, thus DLlim were never exceeded. PM leads to inaccurate dose estimations due to the exclusion of cross-fire irradiation, i.e. between the tumour and normal liver tissue. Caution should be taken for cases with higher TI and T/N, and lower LS, as they contribute to major underestimation of {{D}NL} . For {{D}L} , a different correction factor for dose calculation may be used for improved accuracy.

[Lung is also involved in juvenile dermatomyositis].

PubMed

Pouessel, G; Thumerelle, C; Nève, V; Santangelo, T; Flammarion, S; Pruvot, I; Tillie-Leblond, I; Deschildre, A

2014-07-01

Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children. Lung involvement in inflammatory myopathies is well described in adults, involving mostly interstitial lung disease, aspiration pneumonia and alveolar hypoventilation. We propose to describe its specificities in children. Pulmonary involvement may be asymptomatic and therefore must be systematically screened for. In case of clinical or functional respiratory abnormality, a chest computed tomographic (CT) scan is necessary. In children, a decrease of respiratory muscle strength seems common and should be systematically and specifically searched for by non-invasive and reproducible tests (sniff test). Interstitial lung disease usually associates restrictive functional defect, impairment of carbon monoxide diffusion and interstitial lung disease on CT scan. As in adults, the first-line treatment of juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant forms require corticosteroid bolus or adjuvant immunosuppressive drugs (methotrexate or cyclosporine). There is no consensus in pediatrics for the treatment of diffuse interstitial lung disease. Complications of treatment, including prolonged steroid therapy, are frequent and therefore a careful assessment of the treatments risk-benefit ratio is necessary, especially in growing children. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Glycerol uptake is by passive diffusion in the heart but by facilitated transport in RBCs at high glycerol levels in cold acclimated rainbow smelt (Osmerus mordax).

PubMed

Clow, Kathy A; Driedzic, William R

2012-04-15

Rainbow smelt (Osmerus mordax) is a small fish that accumulates glycerol at low winter seawater temperatures. In laboratory-held fish, glycerol concentration typically reaches 225 mM in plasma and in all cells. Glycerol uptake by the heart and red blood cells (RBCs) was assessed by tracking [(14)C(U)]glycerol into the acid-soluble pool. In fish acclimated to 9-10°C a decrease in perfusion/incubation temperature from 8 to 1°C resulted in a decrease in glycerol uptake with a Q(10) of 3.2 in heart and 2.4 in RBCs. Acclimation to ∼1.5°C did not result in an adaptive enhancement of glycerol uptake as rates were unchanged in heart and RBCs. Glycerol uptake at 1°C was by passive diffusion in heart as evidenced by a linear relationship between glycerol uptake and extracellular glycerol concentration and a lack of inhibition by phloretin. In contrast, in RBCs, glycerol uptake with respect to glycerol concentration showed two linear relationships with a transition point around 50 mM extracellular glycerol. The slope of the second phase was much steeper and eliminated with the inclusion of phloretin. In RBCs from Atlantic salmon (Salmo salar), a related species that does not accumulate glycerol, glycerol uptake showed only a single linear curve and was not inhibited by phloretin. The data imply a strong facilitated component to glycerol uptake in rainbow smelt RBCs at high glycerol concentrations. We propose this is related to cyclic changes in RBC glycerol content involving a loss of glycerol at the gill and a reaccumulation during passage through the liver.

Optical tracer size differences allow quantitation of active pumping rate versus Stokes-Einstein diffusion in lymphatic transport

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Marra, Kayla; Gunn, Jason R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-10-01

Lymphatic uptake of interstitially administered agents occurs by passive convective-diffusive inflow driven by interstitial concentration and pressure, while the downstream lymphatic transport is facilitated by active propulsive contractions of lymphatic vessel walls. Near-infrared fluorescence imaging in mice was used to measure these central components of lymphatic transport for the first time, using two different-sized molecules-methylene blue (MB) and fluorescence-labeled antibody immunoglobulin G (IgG)-IRDye 680RD. This work confirms the hypothesis that lymphatic passive inflow and active propulsion rates can be separated based upon the relative differences in Stokes-Einstein diffusion coefficient. This coefficient specifically affects the passive-diffusive uptake when the interstitial volume and pressure are constant. Parameters such as mean time-to-peak signal, overall fluorescence signal intensities, and number of active peristaltic pulses, were estimated from temporal imaging data. While the mean time to attain peak signal representative of diffusion-dominated flow in the lymph vessels was 0.6±0.2 min for MB and 8±6 min for IgG, showing a size dependence, the active propulsion rates were 3.4±0.8 pulses/min and 3.3±0.5 pulses/min, respectively, appearing size independent. The propulsion rates for both dyes decreased with clearance from the interstitial injection-site, indicating intrinsic control of the smooth muscles in response to interstitial pressure. This approach to size-comparative agent flow imaging of lymphatic function can enable noninvasive characterization of diseases related to uptake and flow in lymph networks.

Influence of substrate diffusion on degradation of dibenzofuran and 3-chlorodibenzofuran by attached and suspended bacteria.

PubMed Central

Harms, H; Zehnder, A J

1994-01-01

Dibenzofuran uptake-associated kinetic parameters of suspended and attached Sphingomonas sp. strain HH19k cells were compared. The suspended cells were studied in a batch system, whereas glass beads in percolated columns were used as the solid support for attached cells. The maximum specific activities of cells in the two systems were the same. The apparent half-maximum uptake rate-associated concentrations (Kt') of attached cells, however, were considerably greater than those of suspended cells and depended on cell density and on percolation velocity. A mathematical model was developed to explain the observed differences in terms of substrate transport to the cells. This model was based on the assumptions that the intrinsic half-maximum uptake rate-associated concentration (Kt) was unchanged and that deviations of Kt' from Kt resulted from the stereometry and the hydrodynamics around the cells. Our calculations showed that (i) diffusion to suspended cells and to single attached cells is efficient and therefore only slightly affects Kt'; (ii) diffusion to cells located on crowded surfaces is considerably lower than that to single attached cells and greatly increases Kt', which depends on the cell density; (iii) the convective-diffusive transport to attached cells that occurs in a percolated column is influenced by the liquid flow and results in dependency of Kt' on the flow rate; and (iv) higher specific affinity of cells correlates with higher susceptibility to diffusion limitation. Properties of the experimental system which limited quantitative proof of exclusively transport-controlled variations of Kt' are discussed. PMID:8085817

Terminate Lung Cancer (TLC) Study - A mixed-methods population approach to increase lung cancer screening awareness and low-dose computed tomography in Eastern Kentucky

PubMed Central

Cardarelli, Roberto; Reese, David; Roper, Karen L.; Cardarelli, Kathryn; Feltner, Frances J.; Studts, Jamie L.; Knight, Jennifer R.; Armstrong, Debra; Weaver, Anthony; Shaffer, Dana

2017-01-01

For low dose CT lung cancer screening to be effective in curbing disease mortality, efforts are needed to overcome barriers to awareness and facilitate uptake of the current evidence-based screening guidelines. A sequential mixed-methods approach was employed to design a screening campaign utilizing messages developed from community focus groups, followed by implementation of the outreach campaign intervention in two high-risk Kentucky regions. This study reports on rates of awareness and screening in intervention regions, as compared to a control region. PMID:27866066

Lung ultrasound for the diagnosis of community-acquired pneumonia in children.

PubMed

Stadler, Jacob A M; Andronikou, Savvas; Zar, Heather J

2017-10-01

Ultrasound (US) has been proposed as an alternative first-line imaging modality to diagnose community-acquired pneumonia in children. Lung US has the potential benefits over chest radiography of being radiation free, subject to fewer regulatory requirements, relatively lower cost and with immediate bedside availability of results. However, the uptake of lung US into clinical practice has been slow and it is not yet included in clinical guidelines for community-acquired pneumonia in children. The aim of this review is to give an overview of the equipment and techniques used to perform lung US in children with suspected pneumonia and the interpretation of relevant sonographic findings. We also summarise the current evidence of diagnostic accuracy and reliability of lung US compared to alternative imaging modalities in children and critically consider the strengths and limitations of lung US for use in children presenting with suspected community-acquired pneumonia.

Repeatability of Quantitative Whole-Body 18F-FDG PET/CT Uptake Measures as Function of Uptake Interval and Lesion Selection in Non-Small Cell Lung Cancer Patients.

PubMed

Kramer, Gerbrand Maria; Frings, Virginie; Hoetjes, Nikie; Hoekstra, Otto S; Smit, Egbert F; de Langen, Adrianus Johannes; Boellaard, Ronald

2016-09-01

Change in (18)F-FDG uptake may predict response to anticancer treatment. The PERCIST suggest a threshold of 30% change in SUV to define partial response and progressive disease. Evidence underlying these thresholds consists of mixed stand-alone PET and PET/CT data with variable uptake intervals and no consensus on the number of lesions to be assessed. Additionally, there is increasing interest in alternative (18)F-FDG uptake measures such as metabolically active tumor volume and total lesion glycolysis (TLG). The aim of this study was to comprehensively investigate the repeatability of various quantitative whole-body (18)F-FDG metrics in non-small cell lung cancer (NSCLC) patients as a function of tracer uptake interval and lesion selection strategies. Eleven NSCLC patients, with at least 1 intrathoracic lesion 3 cm or greater, underwent double baseline whole-body (18)F-FDG PET/CT scans at 60 and 90 min after injection within 3 d. All (18)F-FDG-avid tumors were delineated with an 50% threshold of SUVpeak adapted for local background. SUVmax, SUVmean, SUVpeak, TLG, metabolically active tumor volume, and tumor-to-blood and -liver ratios were evaluated, as well as the influence of lesion selection and 2 methods for correction of uptake time differences. The best repeatability was found using the SUV metrics of the averaged PERCIST target lesions (repeatability coefficients < 10%). The correlation between test and retest scans was strong for all uptake measures at either uptake interval (intraclass correlation coefficient > 0.97 and R(2) > 0.98). There were no significant differences in repeatability between data obtained 60 and 90 min after injection. When only PERCIST-defined target lesions were included (n = 34), repeatability improved for all uptake values. Normalization to liver or blood uptake or glucose correction did not improve repeatability. However, after correction for uptake time the correlation of SUV measures and TLG between the 60- and 90-min data significantly improved without affecting test-retest performance. This study suggests that a 15% change of SUVmean/SUVpeak at 60 min after injection can be used to assess response in advanced NSCLC patients if up to 5 PERCIST target lesions are assessed. Lower thresholds could be used in averaged PERCIST target lesions (<10%). © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

An analytical procedure for the determination of aluminum used in antiperspirants on human skin in Franz™ diffusion cell.

PubMed

Guillard, Olivier; Fauconneau, Bernard; Favreau, Frédéric; Marrauld, Annie; Pineau, Alain

2012-04-01

A local case report of hyperaluminemia (aluminum concentration: 3.88 µmol/L) in a woman using an aluminum-containing antiperspirant for 4 years raises the question of possible transdermal uptake of aluminum salt as a future public health problem. Prior to studying the transdermal uptake of three commercialized cosmetic formulas, an analytical assay of aluminum (Al) in chlorohydrate form (ACH) by Zeeman Electrothermal Atomic Absorption Spectrophotometer (ZEAAS) in a clean room was optimized and validated. This analysis was performed with different media on human skin using a Franz(™) diffusion cell. The detection and quantification limits were set at ≤ 3 µg/L. Precision analysis as within-run (n = 12) and between-run (n = 15-68 days) yield CV ≤ 6%. The high analytic sensitivity (2-3 µg/L) and low variability should allow an in vitro study of the transdermal uptake of ACH.

Spectrally resolved visualization of fluorescent dyes permeating into skin

NASA Astrophysics Data System (ADS)

Maeder, Ulf; Bergmann, Thorsten; Beer, Sebastian; Burg, Jan Michael; Schmidts, Thomas; Runkel, Frank; Fiebich, Martin

2012-03-01

We present a spectrally resolved confocal imaging approach to qualitatively asses the overall uptake and the penetration depth of fluorescent dyes into biological tissue. We use a confocal microscope with a spectral resolution of 5 nm to measure porcine skin tissue after performing a Franz-Diffusion experiment with a submicron emulsion enriched with the fluorescent dye Nile Red. The evaluation uses linear unmixing of the dye and the tissue autofluorescence spectra. The results are combined with a manual segmentation of the skin's epidermis and dermis layers to assess the penetration behavior additionally to the overall uptake. The diffusion experiments, performed for 3h and 24h, show a 3-fold increased dye uptake in the epidermis and dermis for the 24h samples. As the method is based on spectral information it does not face the problem of superimposed dye and tissue spectra and therefore is more precise compared to intensity based evaluation methods.

Striatal dopamine neurotransmission: regulation of release and uptake

PubMed Central

Sulzer, David; Cragg, Stephanie J.; Rice, Margaret E.

2016-01-01

Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved. We discuss the role of DA uptake in restricting the sphere of influence of DA and in temporal accumulation of extracellular DA levels upon successive action potentials. The tonic discharge activity of DA neurons may be translated into a tonic extracellular DA level, whereas their bursting activity can generate discrete extracellular DA transients. PMID:27141430

Pulmonary Abscess as a Complication of Transbronchial Lung Cryobiopsy.

PubMed

Skalski, Joseph H; Kern, Ryan M; Midthun, David E; Edell, Eric S; Maldonado, Fabien

2016-01-01

We present the case of a 49-year-old man who developed pulmonary abscess as a complication of transbronchial lung cryobiopsy. He had been receiving prednisone therapy, but otherwise had no specific risk factors for lung abscess. Cryobiopsy is a novel technique for obtaining peripheral lung parenchymal tissue for the evaluation of diffuse parenchymal lung diseases. Cryobiopsy is being increasingly proposed as an alternative to surgical lung biopsy or conventional bronchoscopic transbronchial forceps biopsy, but the safety profile of the procedure has not been fully appreciated. Pulmonary abscess has been rarely reported as a complication of other bronchoscopic procedures such as endobronchial ultrasound-guided needle biopsy, however, to our knowledge this is the first reported case of pulmonary abscess complicating peripheral lung cryobiopsy.

Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics

PubMed Central

Schlosser, Kenny; Taha, Mohamad; Stewart, Duncan J.

2018-01-01

There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, p<0.05). Mimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of miRNA-based drug candidates. PMID:29507615

Membrane transport of amino acid enantiomers in protoscoleces of Echinococcus granulosus (Cestoda).

PubMed

Allen, J T; Arme, C

1991-02-01

Protoscoleces of Echinococcus granulosus absorb both L- and D-alanine. Concentration ratios exceed 1 with values for D-alanine exceeding those for the L-isomer, suggesting that both are absorbed by active mechanisms. Uptake of both isomers involves both diffusion and carrier-mediated components. Values for the diffusion component (Kd) for L- and D-alanine were 0.21 and 0.38 nmol mg-1 protein/1.5 min mM-1 respectively, and values for Kt, the transport constants, 0.17 mM and 0.21 mM respectively. Uptake of both isomers was inhibited competitively by a number of other amino acids.

Synergistic Skin Penetration Enhancer and Nanoemulsion Formulations Promote the Human Epidermal Permeation of Caffeine and Naproxen.

PubMed

Abd, Eman; Namjoshi, Sarika; Mohammed, Yousuf H; Roberts, Michael S; Grice, Jeffrey E

2016-01-01

We examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterized oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum (SC), as well as the uptake of product components into the SC were measured. The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous control solutions. Caffeine maximum flux enhancement was associated with a synergistic increase in both caffeine SC solubility and skin diffusivity, whereas a formulation-increased solubility in the SC was the dominant determinant for increased naproxen fluxes. Enhancements in SC solubility were related to the uptake of the formulation excipients containing the active compounds into the SC. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into the SC with impacts on SC solubility and diffusivity.

Microdialysis of Soil P: A means to mimic root uptake?

NASA Astrophysics Data System (ADS)

Schack-Kirschner, Helmer; Demand, Dominic; Lang, Friederike

2017-04-01

Standard procedures to assess P availability in soils are based on batch experiments with various extractants. However, in most soils P nutrition is less limited by bulk stocks but by slow diffusion of phosphate through the soil solution. More comparable to the root's approach is to strip phosphate locally from the solid phase by lowering the soil-solution concentration, which can be achieved by establishing an infinite diffusional sink, such as DGT. An alternative diffusive sampling technique is microdialysis (MD), well established in pharmacokinetics. Briefly, this method uses miniaturized flow-through probes where the perfusate gets in diffusive contact to the external solution by a semipermeable membrane. Important aspects of P supply to roots resemble MD sampling. This is not only the mostly diffusive transport, but also an elongated capillary tube-like geometry of absorption. The diameter of typical commercial MD probes is around 500μm. One additional inherent feature of microdialysis is the possibility to release low-molecular substances from the perfusate by diffusion into the matrix, such as carboxylates. However, microdialysis has yet not been used for P in soils. We tested microdialysis in topsoils of an acid beech forest, of an unfertilized grassland and of a fertilized crop site. Three perfusates have been used: 1 mM KNO3, electrolyte + 0.1 mM citric acid, and electrolyte + 1 mM citric acid. We observed rates of uptake into the probes in a range between 1.5*10-15 and 6.7*10-14 mol s-1cm-1 in case of no citrate addition. Surprisingly, these uptake rates were mostly independent of the bulk stocks. Citrate addition increased P yields only in the higher concentration but not in the forest soil. The order of magnitude of MD uptake rates from the soil samples matched root-length related uptake rates from other studies. The micro-radial citrate release in MD reflects the processes controlling phosphate mobilization in the rhizosphere better than measurements based on "flooding" of soil samples with citric acid in batch experiments. Important challenges in MD with phosphate are small volumes of dialysate with extremely low concentrations and a high variability of results due to soil heterogeneity and between-probe variability. We conclude that MD is a promising tool to complement existing P-analytical procedures, especially when spatial aspects or the release of mobilizing substances are in focus.

Brain abscess mimicking lung cancer metastases; a case report.

PubMed

Asano, Michiko; Fujimoto, Nobukazu; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kimura, Fumiaki; Kishimoto, Takumi

2013-01-01

A 76-year-old woman came to us because of staggering, fever, dysarthria, and appetite loss. Magnetic resonance imaging (MRI) of the brain revealed multiple masses with surrounding edema. Chest X-ray and computed tomography demonstrated a mass-like lesion in the left lung and left pleural effusion. Lung cancer and multiple brain metastases were suspected. However, the brain lesions demonstrated a high intensity through diffusion-weighted MRI. The finding was an important key to differentiate brain abscesses from lung cancer metastases. Copyright © 2013 Elsevier Inc. All rights reserved.

G4-Tetra DNA Duplex Induce Lung Cancer Cell Apoptosis in A549 Cells

NASA Astrophysics Data System (ADS)

Xu, Xiaobo; Zhao, YiZhuo; Lu, Hu; Fu, Cuiping; Li, Xiao; Jiang, Liyan; Li, Shanqun

2016-10-01

The specific DNA is typically impermeable to the plasma membrane due to its natural characters, but DNA tetra structures (DTNs) can be readily uptake by cells in the absence of transfection agents, providing a new strategy to deliver DNA drugs. In this research, the delivery efficiency of tetrahedral DNA nanostructures was measured on adenocarcinomic human alveolar basal epithelial (A549) cells via delivering AS1411 (G4). The DNA tetra-AS1411 complex was rapidly and abundantly uptake by A549 cells, and the induced apoptosis was enhanced. Furthermore, biodistribution in mouse proved the rapid clearance from non-targeted organs in vivo. This study improved the understanding of potential function in DNA-based drug delivery and proved that DTNs-AS1411 could be potentially useful for the treatment of lung cancer.

A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment.

PubMed

Alberti, Diego; Protti, Nicoletta; Toppino, Antonio; Deagostino, Annamaria; Lanzardo, Stefania; Bortolussi, Silva; Altieri, Saverio; Voena, Claudia; Chiarle, Roberto; Geninatti Crich, Simonetta; Aime, Silvio

2015-04-01

This study aims at developing an innovative theranostic approach for lung tumor and metastases treatment, based on Boron Neutron Capture Therapy (BNCT). It relies on to the use of low density lipoproteins (LDL) as carriers able to maximize the selective uptake of boron atoms in tumor cells and, at the same time, to quantify the in vivo boron distribution by magnetic resonance imaging (MRI). Tumor cells uptake was initially assessed by ICP-MS and MRI on four types of tumor (TUBO, B16-F10, MCF-7, A549) and one healthy (N-MUG) cell lines. Lung metastases were generated by intravenous injection of a Her2+ breast cancer cell line (i.e. TUBO) in BALB/c mice and transgenic EML4-ALK mice were used as primary tumor model. After neutron irradiation, tumor growth was followed for 30-40 days by MRI. Tumor masses of boron treated mice increased markedly slowly than the control group. From the clinical editor: In this article, the authors described an improvement to existing boron neutron capture therapy. The dual MRI/BNCT agent, carried by LDLs, was able to maximize the selective uptake of boron in tumor cells, and, at the same time, quantify boron distribution in tumor and in other tissues using MRI. Subsequent in vitro and in vivo experiments showed tumor cell killing after neutron irradiation. Copyright © 2015 Elsevier Inc. All rights reserved.

Gallium-67 scanning to stage the alveolitis of sarcoidosis: correlation with clinical studies, pulmonary function studies, and bronchoalveolar lavage

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

Line, B.R.; Hunninghake, G.W.; Keogh, B.A.

1981-04-01

Current concepts of the pathogenesis of sarcoidosis suggest that the alveolitis of this disorder is related to increased numbers of mononuclear phagocytes and activated T-lymphocytes within the lung. To determine if 67Ga scanning, a procedure commonly used in the evaluation of inflammation, would be useful in staging the alveolitis of sarcoidosis, researchers studied 41 patients with this disorder and correlated estimates of pulmonary /sup 67/Ga accumulation with clinical, roentgenographic, physiologic, and bronchoalveolar lavage studies in these patients. Although 65% of patients with sarcoidosis showed increased amounts of /sup 67/Ga accumulation in the lung compared with control subjects, only weak correlationsmore » (r less than +/- 0.42, all comparisons) were found between the degree of gallium uptake and the clinical, roentgenographic, or physiologic data. In contrast, there was a strong correlation of /sup 67/Ga uptake and the number of lymphocytes and T-lymphocytes recovered from the lungs of these patients by bronchoalveolar lavage (p less than 0.0001, r greater than or equal to 0.67, both comparisons). This data suggested that gallium uptake reflects the intensity of the T-lymphocytes mediated component of the alveolitis in sarcoidosis. Because /sup 67/Ga scans are noninvasive, simple to perform, and widely available, they should prove useful to stage the activity of sarcoidosis and to make decisions regarding therapy directed against the alveolitis of the disease.« less

When obesity and chronic obstructive pulmonary disease collide. Physiological and clinical consequences.

PubMed

O'Donnell, Denis E; Ciavaglia, Casey E; Neder, J Alberto

2014-05-01

In many parts of the world, the prevalence of both chronic obstructive pulmonary disease (COPD) and obesity is increasing at an alarming rate. Such patients tend to have greater respiratory symptoms, more severe restriction of daily activities, poorer health-related quality of life, and greater health care use than their nonobese counterparts. Physiologically, increasing weight gain is associated with lung volume reduction effects in both health and disease, and this should be considered when interpreting common pulmonary function tests where lung volume is the denominator, such as FEV1/FVC and the ratio of diffusing capacity of carbon monoxide to alveolar volume, or indeed when evaluating the physiological consequences of emphysema in obese individuals. Contrary to expectation, the presence of mild to moderate obesity in COPD appears to have little deleterious effect on respiratory mechanics and muscle function, exertional dyspnea, and peak symptom-limited oxygen uptake during cardiopulmonary exercise testing. Thus, in evaluating obese patients with COPD reporting activity restriction, additional nonpulmonary factors, such as increased metabolic loading, cardiocirculatory impairment, and musculoskeletal abnormalities, should be considered. Care should be taken to recognize the presence of obstructive sleep apnea in obese patients with COPD, as effective treatment of the former condition likely conveys an important survival advantage. Finally, morbid obesity in COPD presents significant challenges to effective management, given the combined effects of erosion of the ventilatory reserve and serious metabolic and cardiovascular comorbidities that collectively predispose to an increased risk of death from respiratory failure.

Maximizing tumour exposure to anti-neuropilin-1 antibody requires saturation of non-tumour tissue antigenic sinks in mice

PubMed Central

Bumbaca, Daniela; Xiang, Hong; Boswell, C Andrew; Port, Ruediger E; Stainton, Shannon L; Mundo, Eduardo E; Ulufatu, Sheila; Bagri, Anil; Theil, Frank-Peter; Fielder, Paul J; Khawli, Leslie A; Shen, Ben-Quan

2012-01-01

BACKGROUND AND PURPOSE Neuropilin-1 (NRP1) is a VEGF receptor that is widely expressed in normal tissues and is involved in tumour angiogenesis. MNRP1685A is a rodent and primate cross-binding human monoclonal antibody against NRP1 that exhibits inhibition of tumour growth in NPR1-expressing preclinical models. However, widespread NRP1 expression in normal tissues may affect MNRP1685A tumour uptake. The objective of this study was to assess MNRP1685A biodistribution in tumour-bearing mice to understand the relationships between dose, non-tumour tissue uptake and tumour uptake. EXPERIMENTAL APPROACH Non-tumour-bearing mice were given unlabelled MNRP1685A at 10 mg·kg−1. Tumour-bearing mice were given 111In-labelled MNRP1685A along with increasing amounts of unlabelled antibody. Blood and tissues were collected from all animals to determine drug concentration (unlabelled) or radioactivity level (radiolabelled). Some animals were imaged using single photon emission computed tomography – X-ray computed tomography. KEY RESULTS MNRP1685A displayed faster serum clearance than pertuzumab, indicating that target binding affected MNRP1685A clearance. I.v. administration of 111In-labelled MNRP1685A to tumour-bearing mice yielded minimal radioactivity in the plasma and tumour, but high levels in the lungs and liver. Co-administration of unlabelled MNRP1685A with the radiolabelled antibody was able to competitively block lungs and liver radioactivity uptake in a dose-dependent manner while augmenting plasma and tumour radioactivity levels. CONCLUSIONS AND IMPLICATIONS These results indicate that saturation of non-tumour tissue uptake is required in order to achieve tumour uptake and acceptable exposure to antibody. Utilization of a rodent and primate cross-binding antibody allows for translation of these results to clinical settings. PMID:22074316

GFPT2-expressing cancer-associated fibroblasts mediate metabolic reprogramming in human lung adenocarcinoma.

PubMed

Zhang, Weiruo; Bouchard, Gina; Yu, Alice; Shafiq, Majid; Jamali, Mehran; Shrager, Joseph B; Ayers, Kelsey; Bakr, Shaimaa; Gentles, Andrew J; Diehn, Maximilian; Quon, Andrew; West, Robert B; Nair, Viswam; van de Rijn, Matt; Napel, Sandy; Plevritis, Sylvia K

2018-05-14

Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC). Next, we identified genes correlated to glucose uptake that were predominately overexpressed in a single cell-type comprising the tumor microenvironment. For SCC, most of these genes were expressed by malignant cells, whereas in AD they were predominately expressed by stromal cells, particularly cancer-associated fibroblasts (CAFs). Among these AD genes correlated to glucose uptake, we focused on Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2), which codes for the Glutamine-Fructose-6-Phosphate Aminotransferase 2 (GFAT2), a rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which is responsible for glycosylation. GFPT2 was predictive of glucose uptake independent of GLUT1, the primary glucose transporter, and was prognostically significant at both gene and protein level. We confirmed that normal fibroblasts transformed to CAF-like cells, following TGF-β treatment, upregulated HBP genes, including GFPT2, with less change in genes driving glycolysis, pentose phosphate pathway and TCA cycle. Our work provides new evidence of histology-specific tumor-stromal properties associated with glucose uptake in NSCLC and identifies GFPT2 as a critical regulator of tumor metabolic reprogramming in AD. Copyright ©2018, American Association for Cancer Research.

Innovation Diffusion: Implications for Evaluation

ERIC Educational Resources Information Center

Ashley, Shena R.

2009-01-01

Whether looking at the spread and adoption of an intervention across a community, across multiple units, or within a single unit, an understanding of diffusion theory can help evaluators uncover patterns and impacts that might otherwise be overlooked. The theory alerts evaluators to examine why uptake of an intervention appeared different in…

Application of the diffusive gradients in thin films technique for available potassium measurement in agricultural soils: effects of competing cations on potassium uptake by the resin gel.

PubMed

Zhang, Yulin; Mason, Sean; McNeill, Ann; McLaughlin, Michael J

2014-09-09

The utilization of Amberlite (IRP-69 ion-exchange resin, 100-500 wet mesh) as the binding phase in the diffusive gradients in thin films (DGT) technique has shown potential to improve the assessment of plant-available K in soils. The binding phase has recently been optimized by using a mixed Amberlite and ferrihydrite (MAF) gel which results in linear K uptake over extended deployment periods and in solutions with higher K concentrations. As restriction of K uptake by Ca on the Amberlite based resin gel has been previously proposed, potential competing effects of Ca(2+), Mg(2+) and NH(4+) on K uptake by the MAF gel were investigated. These cations had no effect on K elution efficiency which was 85%. However, K uptake by the MAF gel was restricted in the presence of competing cations in solution. Consequently, the diffusion coefficient of K decreased in the presence of cations compared to previous studies but was stable at 1.12×10(-5)cm(2)s(-1) at 25°C regardless of cation concentrations. Uptake of K by the DGT device was affected by the presence of excessive Ca in more than 30% of twenty typical Australian agricultural soils. However, this problem could be circumvented by using a shorter deployment time than the normal 24 h. Moderate correlation of concentrations of K extracted by DGT with Colwell K (extracted by NaHCO(3), R(2)=0.69) and NH4OAc K (R(2)=0.61) indicates that DGT measures a different pool of K in soils than that measured by the standard extractants used. In addition, the MAF gel has the ability to measure Ca and Mg simultaneously. Copyright © 2014 Elsevier B.V. All rights reserved.

Safety Study of SEA-CD40 in Cancer Patients

ClinicalTrials.gov

2018-06-21

Cancer; Carcinoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Hematologic Malignancies; Hodgkin Disease; Lymphoma; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Melanoma; Neoplasms; Neoplasm Metastasis; Neoplasms, Head and Neck; Neoplasms, Squamous Cell; Non-Small Cell Lung Cancer; Non-Small Cell Lung Cancer Metastatic; Non-small Cell Carcinoma; Squamous Cell Cancer; Squamous Cell Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Neoplasm; Lymphoma, Non-Hodgkin

Influence of extrinsic operational parameters on salt diffusion during ultrasound assisted meat curing.

PubMed

Inguglia, Elena S; Zhang, Zhihang; Burgess, Catherine; Kerry, Joseph P; Tiwari, Brijesh K

2018-02-01

The present study investigated the effect of geometric parameters of the ultrasound instrument during meat salting in order to enhance salt diffusion and salt distribution in pork meat on a lab scale. The effects of probe size (∅2.5 and 1.3cm) and of different distances between the transducer and the meat sample (0.3, 0.5, and 0.8cm) on NaCl diffusion were investigated. Changes in the moisture content and NaCl gain were used to evaluate salt distribution and diffusion in the samples, parallel and perpendicular to ultrasound propagation direction. Results showed that 0.3cm was the most efficient distance between the probe and the sample to ensure a higher salt diffusion rate. A distance of 0.5cm was however considered as a trade-off distance to ensure salt diffusion and maintenance of meat quality parameters. The enhancement of salt diffusion by ultrasound was observed to decrease with increased horizontal distance from the probe. This study is of valuable importance for meat processing industries willing to apply new technologies on a larger scale and with defined operational standards. The data suggest that the geometric parameters of ultrasound systems can have strong influence on the efficiency of ultrasonic enhancement of NaCl uptake in meat and can be a crucial element in determining salt uptake during meat processing. Copyright © 2017 Elsevier B.V. All rights reserved.

Reduced xenon diffusion for quantitative lung study--the role of SF(6)

NASA Technical Reports Server (NTRS)

Mair, R. W.; Hoffmann, D.; Sheth, S. A.; Wong, G. P.; Butler, J. P.; Patz, S.; Topulos, G. P.; Walsworth, R. L.

2000-01-01

The large diffusion coefficients of gases result in significant spin motion during the application of gradient pulses that typically last a few milliseconds in most NMR experiments. In restricted environments, such as the lung, this rapid gas diffusion can lead to violations of the narrow pulse approximation, a basic assumption of the standard Stejskal-Tanner NMR method of diffusion measurement. We therefore investigated the effect of a common, biologically inert buffer gas, sulfur hexafluoride (SF(6)), on (129)Xe NMR and diffusion. We found that the contribution of SF(6) to (129)Xe T(1) relaxation in a 1:1 xenon/oxygen mixture is negligible up to 2 bar of SF(6) at standard temperature. We also measured the contribution of SF(6) gas to (129)Xe T(2) relaxation, and found it to scale inversely with pressure, with this contribution approximately equal to 1 s for 1 bar SF(6) pressure and standard temperature. Finally, we found the coefficient of (129)Xe diffusion through SF(6) to be approximately 4.6 x 10(-6) m(2)s(-1) for 1 bar pressure of SF(6) and standard temperature, which is only 1.2 times smaller than the (129)Xe self diffusion coefficient for 1 bar (129)Xe pressure and standard temperature. From these measurements we conclude that SF(6) will not sufficiently reduce (129)Xe diffusion to allow accurate surface-area/volume ratio measurements in human alveoli using time-dependent gas diffusion NMR.

Proangiogenic and Profibrotic Markers in Pulmonary Sarcoidosis.

PubMed

Tuleta, I; Biener, L; Pizarro, C; Nickenig, G; Skowasch, D

2018-04-21

The aim of our study was to determine the blood levels of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2, and platelet-derived growth factor (PDGF)-AB in different stages of pulmonary sarcoidosis. There were 92 patients in sarcoidosis stages I + II, III, and IV enrolled into the study. All the patients underwent lung diffusing capacity and blood sampling. We found that VEGF levels differed significantly between the stage groups with the peak VEGF concentrations in stage III. TGF-β1 levels were similar in stages I + II and III, and tended to be lower in stage IV. The analysis of the subgroups showed increased VEGF and FGF-2, and reduced TGF-β1 concentration in stages I + II patients with relevantly reduced lung diffusing capacity or increased sarcoidosis activity compared to patients with normal lung diffusing capacity or inactive sarcoidosis. A tendency towards increased VEGF, PDGF-AB and TGF-β1 levels was observed in the analogical subgroup analysis within the stage III. We conclude that proangiogenic VEGF, and profibrotic FGF-2 and PDGF-AB may contribute to the progression of sarcoidosis, whereas TGF-β1, with its dual anti-inflammatory and profibrotic actions, may play a dichotomous protective or deleterious role. Reduced diffusing capacity and active sarcoidosis are associated with an unfavorable constellation of the markers studied, which predicts a progressive disease course.

Coupled elasticity-diffusion model for the effects of cytoskeleton deformation on cellular uptake of cylindrical nanoparticles.

PubMed

Wang, Jizeng; Li, Long

2015-01-06

Molecular dynamic simulations and experiments have recently demonstrated how cylindrical nanoparticles (CNPs) with large aspect ratios penetrate animal cells and inevitably deform cytoskeletons. Thus, a coupled elasticity-diffusion model was adopted to elucidate this interesting biological phenomenon by considering the effects of elastic deformations of cytoskeleton and membrane, ligand-receptor binding and receptor diffusion. The mechanism by which the binding energy drives the CNPs with different orientations to enter host cells was explored. This mechanism involved overcoming the resistance caused by cytoskeleton and membrane deformations and the change in configurational entropy of the ligand-receptor bonds and free receptors. Results showed that deformation of the cytoskeleton significantly influenced the engulfing process by effectively slowing down and even hindering the entry of the CNPs. Additionally, the engulfing depth was determined quantitatively. CNPs preferred or tended to vertically attack target cells until they were stuck in the cytoskeleton as implied by the speed of vertically oriented CNPs that showed much faster initial engulfing speeds than horizontally oriented CNPs. These results elucidated the most recent molecular dynamics simulations and experimental observations on the cellular uptake of carbon nanotubes and phagocytosis of filamentous Escherichia coli bacteria. The most efficient engulfment showed the stiffness-dependent optimal radius of the CNPs. Cytoskeleton stiffness exhibited more significant influence on the optimal sizes of the vertical uptake than the horizontal uptake. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Cold tuberculous abscess identified by FDG PET.

PubMed

Yago, Yuzo; Yukihiro, Masashi; Kuroki, Hirofumi; Katsuragawa, Yuzo; Kubota, Kazuo

2005-09-01

We report FDG PET of two cases of cold abscess due to Mycobacterium tuberculosis. Case 1 had colon cancer; FDG PET showed high FDG uptake in the colon lesion and low uptake in the inguinal lesion. The latter was a tuberculous cold abscess confirmed by CT/MRI and biopsy. Case 2 received radiotherapy for lung cancer and presented with suspected vertebral metastasis. Further studies revealed tuberculosis of the vertebra and a tuberculous cold abscess in the iliopsoas muscle. FDG PET showed moderate uptake in the third lumbar spine and low uptake in the abscess center of iliopsoas lesion. Both tuberculous cold abscesses showed moderate FDG uptake in the capsule and low uptake in the center. These features are unique compared with non-tuberculous abscess and typical tuberculosis lesions, which are characterized by high FDG uptake. Pathologically, tuberculous cold abscess is not accompanied by active inflammatory reaction. Our findings suggested that the FDG uptake by tuberculous lesion varies according to the grade of inflammatory activity. The new diagnostic features of tuberculous cold abscess may be useful in the evaluation of such lesions by FDG PET.

Feasibility of assessing [(18)F]FDG lung metabolism with late dynamic PET imaging.

PubMed

Laffon, Eric; de Clermont, Henri; Vernejoux, Jean-Marc; Jougon, Jacques; Marthan, Roger

2011-04-01

The aim of this work was to non-invasively establish the feasibility of assessing 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) lung metabolism with the use of a late dynamic positron emission tomograpy (PET) acquisition, i.e., beyond 2 h after injection. The present method has been probed in 11 patients without any respiratory disease, under fasting conditions, by assessing mean values of (18)F-FDG lung metabolism. A kinetic model analysis has been implemented on a simple calculation sheet. An arbitrary (population based) input function has been used in each individual, which was obtained from literature data. In the healthy lung, no (18)F-FDG release was found, and the mean values (±SD) of the (18)F-FDG uptake rate constant and of the fraction of the free tracer in blood and interstitial volume were: K = 0.0016 min(-1) (±0.0005), and F = 0.18 (±0.10), respectively. These results were in very close agreement with literature data that were obtained by both three-compartment model analysis and Patlak graphical analysis (gold standards), and that used an invasive blood sampling. Furthermore, K and the standard uptake value index have been compared. We conclude that assessing lung metabolism of (18)F-FDG in humans with the use of late dynamic PET imaging is feasible. The arbitrary input function of this non-invasive feasibility study could be replaced in further experiments by an input function obtained by arterial sampling. It is suggested that this method may prove useful to quantify (18)F-FDG lung metabolism under pathological conditions.

Protection by Inhaled Hydrogen Therapy in a Rat Model of Acute Lung Injury can be Tracked in vivo Using Molecular Imaging.

PubMed

Audi, Said H; Jacobs, Elizabeth R; Zhang, Xiao; Camara, Amadou K S; Zhao, Ming; Medhora, Meetha M; Rizzo, Benjamin; Clough, Anne V

2017-10-01

Inhaled hydrogen gas (H2) provides protection in rat models of human acute lung injury (ALI). We previously reported that biomarker imaging can detect oxidative stress and endothelial cell death in vivo in a rat model of ALI. Our objective was to evaluate the ability of Tc-hexamethylpropyleneamineoxime (HMPAO) and Tc-duramycin to track the effectiveness of H2 therapy in vivo in the hyperoxia rat model of ALI. Rats were exposed to room air (normoxia), 98% O2 + 2% N2 (hyperoxia) or 98% O2 + 2% H2 (hyperoxia+H2) for up to 60 h. In vivo scintigraphy images were acquired following injection of Tc-HMPAO or Tc-duramycin. For hyperoxia rats, Tc-HMPAO and Tc-duramycin lung uptake increased in a time-dependent manner, reaching a maximum increase of 270% and 150% at 60 h, respectively. These increases were reduced to 120% and 70%, respectively, in hyperoxia+H2 rats. Hyperoxia exposure increased glutathione content in lung homogenate (36%) more than hyperoxia+H2 (21%), consistent with increases measured in Tc-HMPAO lung uptake. In 60-h hyperoxia rats, pleural effusion, which was undetectable in normoxia rats, averaged 9.3 gram/rat, and lung tissue 3-nitrotyrosine expression increased by 790%. Increases were reduced by 69% and 59%, respectively, in 60-h hyperoxia+H2 rats. This study detects and tracks the anti-oxidant and anti-apoptotic properties of H2 therapy in vivo after as early as 24 h of hyperoxia exposure. The results suggest the potential utility of these SPECT biomarkers for in vivo assessment of key cellular pathways in the pathogenesis of ALI and for monitoring responses to therapies.

Prediction of methyl mercury uptake by rice plants ( Oryza sativa L.) using the diffusive gradient in thin films technique.

PubMed

Liu, Jinling; Feng, Xinbin; Qiu, Guangle; Anderson, Christopher W N; Yao, Heng

2012-10-16

Rice consumption is the primary pathway for methyl mercury (MeHg) exposure at inland mercury (Hg) mining areas of SW China. Mechanistic information on MeHg accumulation in rice is, however, limited. The process of MeHg exchange between paddy soil and rice plants predominantly occurs in pore water. The detection of bioavailable MeHg in pore water is therefore important to predict MeHg uptake by rice plants ( Oryza sativa L.). This study investigated MeHg dynamics and spatial MeHg trends in pore water during the rice growing season using the diffusive gradient in thin films (DGT) technique and tested the ability of DGT to predict MeHg uptake by rice. The MeHg uptake flux from soil to rice plants via roots was significantly correlated with the DGT-measured MeHg flux (R = 0.853, p < 0.01). Our study implies that DGT can predict the bioavailability of MeHg in rice paddy soil and that the DGT method can provide quantitative description of the rate of uptake of this bioavailable MeHg. The DGT technique is demonstrated as a useful indicator of the likely ecotoxicological risk that might be apparent where paddy rice is grown in MeHg contaminated soil.

Adenosine uptake by the isolated epithelium of guine pig jejunum.

PubMed

Kolassa, N; Stengg, R; Turnheim, K

1977-10-01

The uptake of [8-14C]adenosine by the isolated epithelium of guinea pig jejunum was faster than that of inosine, hypoxanthine, or adenine. The initial velocity of adenosine uptake from both the luminal and the antiluminal side of the epithelium exhibited saturation kinetics. The apparent Km, V, and passive permeability of luminal adenosine uptake were all lower than the corresponding values of antiluminal uptake. p-Nitrobenzyl-thioguanosine inhibited adenosine uptake from both the luminal and the antiluminal side, whilst hexobendine decreased the uptake only from the antiluminal side of the epithelium. The results suggest that adenosine enters the intestinal epithelium by a carrier-mediated process in addition to passive diffusion. The antiluminal transport system for adenosine seems similar to that of other tissues with respect to hexobendine inhibition; the luminal transport mechanism, however, exhibits different properties, being insensitive to hexobendine.

The influence of hepatic transport on the distribution volumes and mean residence time of drug in the body and the accuracy of estimating these parameters by the traditional pharmacokinetic calculations.

PubMed

Berezhkovskiy, Leonid M

2011-11-01

The influence of hepatic uptake and efflux, which includes passive diffusion and transporter-mediated component, on drug distribution volumes [steady-state volume of distribution (V(ss)) and terminal volume of distribution (V(β))], mean residence time (MRT), clearance, and terminal half-life is considered using a simplified physiologically based pharmacokinetic model. To account for hepatic uptake, liver is treated as two-compartmental unit with drug transfer from extracellular water into hepatocytes. The exactly calculated distribution volumes and MRT are compared with that obtained by the traditional equations based on the assumption of central elimination. It was found that V(ss) may increase more than 10-fold and V(β) more than 100-fold due to the contribution of transporter-mediated uptake. The terminal half-life may be substantially shortened (more than 100-fold) due to transporters. It may also decrease significantly due to the increase of intrinsic hepatic clearance (CL(int)), whereas hepatic clearance has already reached saturation (and stays close to the possible maximum value). It is shown that in case of transporter-mediated uptake of compound into hepatocytes, in the absence of efflux and passive diffusion (unidirectional uptake), hepatic clearance is independent of CL(int) and is determined by hepatic blood flow and uptake rate constant. The effects of transporter-mediated uptake are mostly pronounced for hydrophilic acidic compounds and moderately lipophilic neutral compounds. For basic compounds and lipophilic neutral compounds the change of distribution volumes due to transporters is rather unlikely. It was found that the traditional equations provide very accurate values of V(ss), V(β), and MRT in the absence of transporter action even for very low rates of passive diffusion. On the other hand, the traditional equations fail to provide the correct values of these parameters when the increase of distribution volumes due to transporters takes place, and actually yield the values substantially smaller than the true ones (up to an order of magnitude for V(ss) and MRT, and three orders of magnitude for V(β)). Copyright © 2011 Wiley-Liss, Inc.

Quantitative Evaluation of Segmentation- and Atlas-Based Attenuation Correction for PET/MR on Pediatric Patients.

PubMed

Bezrukov, Ilja; Schmidt, Holger; Gatidis, Sergios; Mantlik, Frédéric; Schäfer, Jürgen F; Schwenzer, Nina; Pichler, Bernd J

2015-07-01

Pediatric imaging is regarded as a key application for combined PET/MR imaging systems. Because existing MR-based attenuation-correction methods were not designed specifically for pediatric patients, we assessed the impact of 2 potentially influential factors: inter- and intrapatient variability of attenuation coefficients and anatomic variability. Furthermore, we evaluated the quantification accuracy of 3 methods for MR-based attenuation correction without (SEGbase) and with bone prediction using an adult and a pediatric atlas (SEGwBONEad and SEGwBONEpe, respectively) on PET data of pediatric patients. The variability of attenuation coefficients between and within pediatric (5-17 y, n = 17) and adult (27-66 y, n = 16) patient collectives was assessed on volumes of interest (VOIs) in CT datasets for different tissue types. Anatomic variability was assessed on SEGwBONEad/pe attenuation maps by computing mean differences to CT-based attenuation maps for regions of bone tissue, lungs, and soft tissue. PET quantification was evaluated on VOIs with physiologic uptake and on 80% isocontour VOIs with elevated uptake in the thorax and abdomen/pelvis. Inter- and intrapatient variability of the bias was assessed for each VOI group and method. Statistically significant differences in mean VOI Hounsfield unit values and linear attenuation coefficients between adult and pediatric collectives were found in the lungs and femur. The prediction of attenuation maps using the pediatric atlas showed a reduced error in bone tissue and better delineation of bone structure. Evaluation of PET quantification accuracy showed statistically significant mean errors in mean standardized uptake values of -14% ± 5% and -23% ± 6% in bone marrow and femur-adjacent VOIs with physiologic uptake for SEGbase, which could be reduced to 0% ± 4% and -1% ± 5% using SEGwBONEpe attenuation maps. Bias in soft-tissue VOIs was less than 5% for all methods. Lung VOIs showed high SDs in the range of 15% for all methods. For VOIs with elevated uptake, mean and SD were less than 5% except in the thorax. The use of a dedicated atlas for the pediatric patient collective resulted in improved attenuation map prediction in osseous regions and reduced interpatient bias variation in femur-adjacent VOIs. For the lungs, in which intrapatient variation was higher for the pediatric collective, a patient- or group-specific attenuation coefficient might improve attenuation map accuracy. Mean errors of -14% and -23% in bone marrow and femur-adjacent VOIs can affect PET quantification in these regions when bone tissue is ignored. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Catecholamine transport in isolated lung parenchyma of pig

PubMed Central

Goldie, Roy G.; Paterson, James W.

1982-01-01

1 Lung parenchyma strips of the pig incubated at 37°C with [3H]-(-)-noradrenaline ([3H]-NA) or [3H]-(±)-isoprenaline ([3H]-Iso), accumulated radioactivity via saturable, high affinity uptake processes. Apparent saturation constants (Km) for [3H]-NA and [3H]-Iso were 1.34 × 10-6 M and 1.63 × 10-6 M respectively, while apparent transport maxima (Vmax) were 4.86 and 1.63 × 10-9 mol min-1 g-1 respectively. 2 Cellular accumulation of radioactivity from radiolabelled catecholamines was greatly reduced by lowering the temperature to 7°C, pretreatment with ouabain (100 μM), phentolamine (15 μM) or phenoxybenzamine (80 μM). However, accumulation of radioactivity derived from (3H]-NA was inhibited selectively by cocaine (10 μM) and desipramine (1 μM), while normetanephrine (80 μM) and 3-O-methylisoprenaline (50 μM) caused much greater reductions in cellular radioactivity from [3H]-Iso than from (3H]-NA. Taken together with information from kinetic studies, the results indicate that these amines are transported by separate uptake processes. 3 Cocaine (50 μM) which selectively reduced [3H]-NA transport, had no significant effect on the sensitivity (EC50) of isolated parenchyma lung strips of the pig to the contractile effects of cumulative concentrations of NA. The catechol-O-methyl transferase (COMT) inhibitor, U-0521 (60 μM), also failed to alter the potency of NA, while normetanephrine (80 μM) caused a 2 fold decrease in potency. 4 Phentolamine (15 μM), which reduced the cellular accumulation of radioactivity derived from [3H]-Iso by 64%, caused a small potentiation of Iso-induced relaxations of porcine lung strips. Normetanephrine (80 μM) and 3-O-methylisoprenaline (50 μM), which also depressed the accumulation of cellular radioactivity from [3H]-Iso by > 50%, caused rightward shifts in Iso concentration-effect curves as a result of β-adrenoceptor blockade. In sharp contrast, cortisol (80 μM) and U-0521 (60 μM), which caused smaller reductions in the cellular accumulation of radioactivity derived from [3H]-Iso, both caused an approximately 9 fold potentiation of responses to Iso in isolated lung strips. 5 The results indicate that the major sites of uptake and metabolism of NA in porcine parenchyma strip are remote from α-adrenoceptors mediating NA-induced contraction. Similarly, some major sites of uptake of Iso are remote from β-adrenoceptors mediating Iso-induced relaxation. However, β-adrenoceptors are apparently in close proximity to a compartment containing COMT activity. PMID:7104521

Novel algorithm to identify and differentiate specific digital signature of breath sound in patients with diffuse parenchymal lung disease.

PubMed

Bhattacharyya, Parthasarathi; Mondal, Ashok; Dey, Rana; Saha, Dipanjan; Saha, Goutam

2015-05-01

Auscultation is an important part of the clinical examination of different lung diseases. Objective analysis of lung sounds based on underlying characteristics and its subsequent automatic interpretations may help a clinical practice. We collected the breath sounds from 8 normal subjects and 20 diffuse parenchymal lung disease (DPLD) patients using a newly developed instrument and then filtered off the heart sounds using a novel technology. The collected sounds were thereafter analysed digitally on several characteristics as dynamical complexity, texture information and regularity index to find and define their unique digital signatures for differentiating normality and abnormality. For convenience of testing, these characteristic signatures of normal and DPLD lung sounds were transformed into coloured visual representations. The predictive power of these images has been validated by six independent observers that include three physicians. The proposed method gives a classification accuracy of 100% for composite features for both the normal as well as lung sound signals from DPLD patients. When tested by independent observers on the visually transformed images, the positive predictive value to diagnose the normality and DPLD remained 100%. The lung sounds from the normal and DPLD subjects could be differentiated and expressed according to their digital signatures. On visual transformation to coloured images, they retain 100% predictive power. This technique may assist physicians to diagnose DPLD from visual images bearing the digital signature of the condition. © 2015 Asian Pacific Society of Respirology.

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

Correlation of dopaminergic terminal dysfunction and microstructural abnormalities of the basal ganglia and the olfactory tract in Parkinson's disease.

PubMed

Scherfler, Christoph; Esterhammer, Regina; Nocker, Michael; Mahlknecht, Philipp; Stockner, Heike; Warwitz, Boris; Spielberger, Sabine; Pinter, Bernadette; Donnemiller, Eveline; Decristoforo, Clemens; Virgolini, Irene; Schocke, Michael; Poewe, Werner; Seppi, Klaus

2013-10-01

Signal abnormalities of the substantia nigra and the olfactory tract detected either by diffusion tensor imaging, including measurements of mean diffusivity, a parameter of brain tissue integrity, and fractional anisotropy, a parameter of neuronal fibre integrity, or transcranial sonography, were recently reported in the early stages of Parkinson's disease. In this study, changes in the nigral and olfactory diffusion tensor signal, as well as nigral echogenicity, were correlated with clinical scales of motor disability, odour function and putaminal dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron emission tomography in early and advanced stages of Parkinson's disease. Diffusion tensor imaging, transcranial sonography and positron emission tomography were performed on 16 patients with Parkinson's disease (mean disease duration 3.7 ± 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched healthy control subjects. Odour function was measured by the standardized Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant, mean nigral echogenicity, mean diffusivity and fractional anisotropy values of the substantia nigra and the olfactory tract were identified by region of interest analysis. When compared with the healthy control group, the Parkinson's disease group showed significant signal changes in the caudate and putamen by 6-[(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P < 0.05). Regional mean diffusivity values of the substantia nigra and the olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations were also found between nigral mean diffusivity values and the Unified Parkinson's Disease Rating Scale motor score (r = -0.48, P < 0.01) and between mean putaminal 6-[(18)F] fluorolevodopa uptake and the total odour score (r = 0.58; P < 0.05) as well as the Unified Parkinson's Disease Rating Scale motor score (r = -0.53, P < 0.05). This study reports a significant association between increased mean diffusivity signal and decreased 6-[(18)F] fluorolevodopa uptake, indicating that microstructural degradation of the substantia nigra and the olfactory tract parallels progression of putaminal dopaminergic dysfunction in Parkinson's disease. Since increases in nigral mean diffusivity signal also correlated with motor dysfunction, diffusion tensor imaging may serve as a surrogate marker for disease progression in future studies of putative disease modifying therapies.

Use of a chemical equilibrium model to describe surface properties and uptake of cadmium, strontium, and lead by Chlorella (UTEX 252)

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

Hassett, J.M.

1988-01-01

Metal-aquatic biota interactions are important in both natural and engineered systems. In this study, the uptake of cadmium, strontium and lead by the unicellular green alga Chlorella (UTEX 252) was investigated. Variables included metal concentration, pH, and ionic strength. Data gathered included dry weights (mg/l), cell counts (cells/ml), electrophoretic mobilities (EPMs, {mu}m/sec/V/cm) of metal-free and metal-exposed cells, and metal uptake - difference in concentration in filtrate of cell-metal and cell-free metal solutions. Derived data included cell volumes and surface area, uptake on a {mu}M/m{sup 2} basis, {zeta}-potentials, diffuse layer potentials and charge densities. Typical uptake values were 1.1, 5.2, andmore » 6 {mu}M/m{sup 2} for Cd, Pb, and Sr, respectively, from solutions of pH 6, ionic strength 0.02M, and metal concentration 10{sup {minus}4} M. Cell EPMs were insensitive to metal; under certain conditions, however, (pM > 4, pH > 8), cadmium exposed cells exhibited a reversal in surface charge from negative to positive. The chemical equilibrium model MINEQL1 + STANFORD was used to model algal surface properties and metal uptake. Input data included site pK, density, and {Delta}pK, estimated from EPM-pH data. The model described surface properties of Chlorella (UTEX 252) as judged by a close fit of {zeta}-potentials and model-derived diffuse layer potentials. Metal uptake was modelled by adjusting site density and/or metal-surface site equilibrium constants. Attempts to model surface properties and metal uptake simultaneously were not successful.« less

Mapping trace element distribution in fossil teeth and bone with LA-ICP-MS

NASA Astrophysics Data System (ADS)

Hinz, E. A.; Kohn, M. J.

2009-12-01

Trace element profiles were measured in fossil bones and teeth from the late Pleistocene (c. 25 ka) Merrell locality, Montana, USA, by using laser-ablation ICP-MS. Laser-ablation ICP-MS can collect element counts along predefined tracks on a sample’s surface using a constant ablation speed allowing for rapid spatial sampling of element distribution. Key elements analyzed included common divalent cations (e.g. Sr, Zn, Ba), a suite of REE (La, Ce, Nd, Sm, Eu, Yb), and U, in addition to Ca for composition normalization and standardization. In teeth, characteristic diffusion penetration distances for all trace elements are at least a factor of 4 greater in traverses parallel to the dentine-enamel interface (parallel to the growth axis of the tooth) than perpendicular to the interface. Multiple parallel traverses in sections parallel and perpendicular to the tooth growth axis were transformed into trace element maps, and illustrate greater uptake of all trace elements along the central axis of dentine compared to areas closer to enamel, or within the enamel itself. Traverses in bone extending from the external surface, through the thickness of cortical bone and several mm into trabecular bone show major differences in trace element uptake compared to teeth: U and Sr are homogeneous, whereas all REE show a kinked profile with high concentrations on outer surfaces that decrease by several orders of magnitude within a few mm inward. The Eu anomaly increases uniformly from the outer edge of bone inward, whereas the Ce anomaly decreases slightly. These observations point to major structural anisotropies in trace element transport and uptake during fossilization, yet transport and uptake of U and REE are not resolvably different. In contrast, transport and uptake of U in bone must proceed orders of magnitude faster than REE as U is homogeneous whereas REE exhibit strong gradients. The kinked REE profiles in bone unequivocally indicate differential transport rates, consistent with a double-medium diffusion model in which microdomains with slow diffusivities are bounded by fast-diffusing pathways.

Respiratory gating enhances imaging of pulmonary nodules and measurement of tracer uptake in FDG PET/CT.

PubMed

Werner, Matthias K; Parker, J Anthony; Kolodny, Gerald M; English, Jeffrey R; Palmer, Matthew R

2009-12-01

The aim of this study was to evaluate prospectively the effects of respiratory gating during FDG PET/CT on the determination of lesion size and the measurement of tracer uptake in patients with pulmonary nodules in a clinical setting. Eighteen patients with known pulmonary nodules (nine women, nine men; mean age, 61.4 years) underwent conventional FDG PET/CT and respiratory-gated PET acquisitions during their scheduled staging examinations. Maximum, minimum, and average standardized uptake values (SUVs) and lesion size and volume were determined with and without respiratory gating. The results were then compared using the two-tailed Student's t test and the nonparametric Wilcoxon's test to assess the effects of respiratory gating on PET acquisitions. Respiratory gating reduced the measured area of lung lesions by 15.5%, the axial dimension by 10.3%, and the volume by 44.5% (p = 0.014, p = 0.007, and p = 0.025, respectively). The lesion volumes in gated studies were closer to those assessed by standard CT (difference decreased by 126.6%, p = 0.025). Respiratory gating increased the measured maximum SUV by 22.4% and average SUV by 13.3% (p < 0.001 and p = 0.002). Our findings suggest that the use of PET respiratory gating in PET/CT results in lesion volumes closer to those assessed by CT and improved measurements of tracer uptake for lesions in the lungs.

[Lung volume reduction surgery for emphysema and bullous pulmonary emphysema].

PubMed

Le Pimpec-Barthes, F; Das Neves-Pereira, J-C; Cazes, A; Arame, A; Grima, R; Hubsch, J-P; Zukerman, C; Hernigou, A; Badia, A; Bagan, P; Delclaux, C; Dusser, D; Riquet, M

2012-04-01

The improvement of respiratory symptoms for emphysematous patients by surgery is a concept that has evolved over time. Initially used for giant bullae, this surgery was then applied to patients with diffuse microbullous emphysema. The physiological and pathological concepts underlying these surgical procedures are the same in both cases: improve respiratory performance by reducing the high intrapleural pressure. The functional benefit of lung volume reduction surgery (LVRS) in the severe diffuse emphysema has been validated by the National Emphysema Treatment Trial (NETT) and the later studies which allowed to identify prognostic factors. The quality of the clinical, morphological and functional data made it possible to develop recommendations now widely used in current practice. Surgery for giant bullae occurring on little or moderately emphysematous lung is often a simpler approach but also requires specialised support to optimize its results. Copyright © 2012 Elsevier Masson SAS. 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.

Impairment of pulmonary diffusion correlates with hypoxemic burden in central sleep apnea heart failure patients.

PubMed

Fox, Henrik; Koerber, Britta; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf

2017-09-01

Central sleep apnea (CSA) and Cheyne-Stokes respiration (CSR) are highly prevalent in heart failure (HF) and are linked to increased mortality. Impaired pulmonary diffusion capacity [DLCO] and [KCO]) have been suggested to play a key role in CSA-CSR pathophysiology. This study investigated the relationship between HF, CSR, DLCO and KCO in well-characterized HF patients. This prospective study included HF patients with CSR, all patients underwent full overnight polysomnography (PSG) and lung function testing. A total of 100 patients were included (age 70.7±9.7years, 95% male, body mass index 28.9±5.3kg/m 2 , left ventricular ejection fraction 33.5±7.7%, New York Heart Association class III 65%. DLCO and oxygenation were significantly correlated with hypoxemic burden (p<0.05). Mean oxygen saturation, oxygen desaturation, C-reactive protein level and pH were significantly associated with CSA-CSR severity (p<0.05). The finding that lung diffusion capacity is significantly associated with hypoxemic burden in HF patients with CSA-CSR highlights the important of lung function in HF patients. Copyright © 2017. Published by Elsevier B.V.

Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling

NASA Astrophysics Data System (ADS)

Khakinejad, Mahdiar; Ghassabi Kondalaji, Samaneh; Donohoe, Gregory C.; Valentine, Stephen J.

2016-03-01

Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M - 2H]2- ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M - 3H]3- ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M - 2H]2- ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M - 3H]3- ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively-charged ions is presented.

Deposition in the distal parts of the bovine respiratory tract: assessment of equipment suitable for drug inhalation.

PubMed

Genicot, B; Votion, D; Munsters, K; Close, R; Lindsey, J K; Lekeux, P

1996-03-30

The efficiency of equipment suitable for the inhalation of drugs by calves was assessed in six animals which inhaled radioisotopically labelled particles while suffering from reversible diffuse bronchoconstriction induced experimentally with 5-hydroxytryptamine and while they were breathing normally. Respiratory rates and data from pulmonary function tests and scintiscans were recorded during both investigations. After the first investigation, a mean (se) wash-out period of 9.8 (3.2) days was allowed. Under diffuse bronchoconstriction, the respiratory rate, the oscillatory resistance and the compliance of the respiratory system reached 282.1 (22.0), 161.1 (10.8) and 68.8 (2.7) per cent of their respective baseline values. When the calves were breathing normally these parameters did not change over time. The ratios (Cp/Ct) of the counts of gamma-disintegrations in the peripheral part (Cp) of the lungs and in the total lung area (Ct) were not significantly different when comparing the results from the two investigations. The ratios of Cp/Ct in the left lungs did not differ significantly from those in the right lungs.

Automated Synthesis of 18F-Fluoropropoxytryptophan for Amino Acid Transporter System Imaging

PubMed Central

Shih, I-Hong; Duan, Xu-Dong; Kong, Fan-Lin; Williams, Michael D.; Zhang, Yin-Han; Yang, David J.

2014-01-01

Objective. This study was to develop a cGMP grade of [18F]fluoropropoxytryptophan (18F-FTP) to assess tryptophan transporters using an automated synthesizer. Methods. Tosylpropoxytryptophan (Ts-TP) was reacted with K18F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of 18F-FTP and 18F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with 18F-FTP and 18F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv). Results. Radio-TLC and HPLC analyses of 18F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of 18F-FTP and 18F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that 18F-FTP had less tumor uptake than 18F-FDG in prostate cancer model. However, 18F-FTP had more uptake than 18F-FDG in small cell lung cancer model. Conclusion. 18F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by 18F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response. PMID:25136592

Automated synthesis of 18F-fluoropropoxytryptophan for amino acid transporter system imaging.

PubMed

Shih, I-Hong; Duan, Xu-Dong; Kong, Fan-Lin; Williams, Michael D; Yang, Kevin; Zhang, Yin-Han; Yang, David J

2014-01-01

This study was to develop a cGMP grade of [(18)F]fluoropropoxytryptophan ((18)F-FTP) to assess tryptophan transporters using an automated synthesizer. Tosylpropoxytryptophan (Ts-TP) was reacted with K(18)F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of (18)F-FTP and (18)F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with (18)F-FTP and (18)F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv). Radio-TLC and HPLC analyses of (18)F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that (18)F-FTP had less tumor uptake than (18)F-FDG in prostate cancer model. However, (18)F-FTP had more uptake than (18)F-FDG in small cell lung cancer model. (18)F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.

Nepheline rock dust pneumoconiosis. A report of 2 cases

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

Olscamp, G.; Herman, S.J.; Weisbrod, G.L.

1982-01-01

Two cases of nepheline rock dust pneumoconiosis are presented. Radiologically, this is seen as a diffuse increase in interstitial lung markings, lymphadenopathy, air-space disease, and atelectasis secondary to extrinsic compression by enlarged hilar lymph nodes. Major differential diagnoses include carcinoma of the lung, sarcoidosis, and interstitial lung disease caused by other inorganic dusts. Nepheline rock dust pneumoconiosis should be considered when the above radiological changes are observed and an occupational exposure to inorganic dust is documented.

Nepheline rock dust pneumoconiosis: a report of 2 cases

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

Olscamp, G.; Herman, S.J.; Weisbrod, G.L.

1982-01-01

Two cases of nepheline rock dust pneumoconiosis are presented. Radiologically, this is seen as a diffuse increase in interstitial lung markings, lymphadenopathy air-space disease, and atelectasis secondary to extrinsic compression by enlarged hilar lymph nodes. Major differential diagnoses include carcinoma of the lung, sarcoidosis, and interstitial lung disease caused by other inorganic dusts. Nepheline rock dust pneumoconiosis should be considered when the above radiological changes are observed and an occupational exposure to inorganic dust is documented.

Enhancing the Sensitivity of Fluorescence Bronchoscopy for Early Lung Cancer Detection Using a Fluorescent Deoxyglucose Analog

DTIC Science & Technology

2013-11-01

overexpression of glucose transporters ( Gluts ) and the increased activity of mitochondria- bound hexokinases in tumors (5, 6). Since 1976, 2-(fluorine-18...glucose transport through the cell membrane via Gluts has been reported as an important factor in the increase of FDG uptake in malignant tumors (5). In...capabilities of bronchoscopy without substantially increasing cost. Although there has been no work evaluating the use of 2-NBDG for lung cancer

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.

Decreases in maximal oxygen uptake following long-duration spaceflight: Role of convective and diffusive O2 transport mechanisms.

PubMed

Ade, C J; Broxterman, R M; Moore, A D; Barstow, T J

2017-04-01

We have previously predicted that the decrease in maximal oxygen uptake (V̇o 2max ) that accompanies time in microgravity reflects decrements in both convective and diffusive O 2 transport to the mitochondria of the contracting myocytes. The aim of this investigation was therefore to quantify the relative changes in convective O 2 transport (Q̇o 2 ) and O 2 diffusing capacity (Do 2 ) following long-duration spaceflight. In nine astronauts, resting hemoglobin concentration ([Hb]), V̇o 2max , maximal cardiac output (Q̇ Tmax ), and differences in arterial and venous O 2 contents ([Formula: see text]-[Formula: see text]) were obtained retrospectively for International Space Station Increments 19-33 (April 2009-November 2012). Q̇o 2 and Do 2 were calculated from these variables via integration of Fick's Principle of Mass Conservation and Fick's Law of Diffusion. V̇o 2max significantly decreased from pre- to postflight (-53.9 ± 45.5%, P = 0.008). The significant decrease in Q̇ Tmax (-7.8 ± 9.1%, P = 0.05), despite an unchanged [Hb], resulted in a significantly decreased Q̇o 2 (-11.4 ± 10.5%, P = 0.02). Do 2 significantly decreased from pre- to postflight by -27.5 ± 24.5% ( P = 0.04), as did the peak [Formula: see text]-[Formula: see text] (-9.2 ± 7.5%, P = 0.007). With the use of linear regression analysis, changes in V̇o 2max were significantly correlated with changes in Do 2 ( R 2  = 0.47; P = 0.04). These data suggest that spaceflight decreases both convective and diffusive O 2 transport. These results have practical implications for future long-duration space missions and highlight the need to resolve the specific mechanisms underlying these spaceflight-induced changes along the O 2 transport pathway. NEW & NOTEWORTHY Long-duration spaceflight elicited a significant decrease in maximal oxygen uptake. Given the adverse physiological adaptations to microgravity along the O 2 transport pathway that have been reported, an integrative approach to the determinants of postflight maximal oxygen uptake is needed. We demonstrate that both convective and diffusive oxygen transport are decreased following ~6 mo International Space Station missions. Copyright © 2017 the American Physiological Society.

Need-based activation of ammonium uptake in Escherichia coli

PubMed Central

Kim, Minsu; Zhang, Zhongge; Okano, Hiroyuki; Yan, Dalai; Groisman, Alexander; Hwa, Terence

2012-01-01

The efficient sequestration of nutrients is vital for the growth and survival of microorganisms. Some nutrients, such as CO2 and NH3, are readily diffusible across the cell membrane. The large membrane permeability of these nutrients obviates the need of transporters when the ambient level is high. When the ambient level is low, however, maintaining a high intracellular nutrient level against passive back diffusion is both challenging and costly. Here, we study the delicate management of ammonium (NH4+/NH3) sequestration by E. coli cells using microfluidic chemostats. We find that as the ambient ammonium concentration is reduced, E. coli cells first maximize their ability to assimilate the gaseous NH3 diffusing into the cytoplasm and then abruptly activate ammonium transport. The onset of transport varies under different growth conditions, but always occurring just as needed to maintain growth. Quantitative modeling of known interactions reveals an integral feedback mechanism by which this need-based uptake strategy is implemented. This novel strategy ensures that the expensive cost of upholding the internal ammonium concentration against back diffusion is kept at a minimum. PMID:23010999

Role of Mutant CFTR in Hypersusceptibility of Cystic Fibrosis Patients to Lung Infections

NASA Astrophysics Data System (ADS)

Pier, Gerald B.; Grout, Martha; Zaidi, Tanweer S.; Olsen, John C.; Johnson, Larry G.; Yankaskas, James R.; Goldberg, Joanna B.

1996-01-01

Cystic fibrosis (CF) patients are hypersusceptible to chronic Pseudomonas aeruginosa lung infections. Cultured human airway epithelial cells expressing the ΔF508 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) were defective in uptake of P. aeruginosa compared with cells expressing the wild-type allele. Pseudomonas aeruginosa lipopolysaccharide (LPS)-core oligosaccharide was identified as the bacterial ligand for epithelial cell ingestion; exogenous oligosaccharide inhibited bacterial ingestion in a neonatal mouse model, resulting in increased amounts of bacteria in the lungs. CFTR may contribute to a host-defense mechanism that is important for clearance of P. aeruginosa from the respiratory tract.

Chest Computed Tomographic Image Screening for Cystic Lung Diseases in Patients with Spontaneous Pneumothorax Is Cost Effective

PubMed Central

Langenderfer, Dale; McCormack, Francis X.; Schauer, Daniel P.; Eckman, Mark H.

2017-01-01

Rationale: Patients without a known history of lung disease presenting with a spontaneous pneumothorax are generally diagnosed as having primary spontaneous pneumothorax. However, occult diffuse cystic lung diseases such as Birt-Hogg-Dubé syndrome (BHD), lymphangioleiomyomatosis (LAM), and pulmonary Langerhans cell histiocytosis (PLCH) can also first present with a spontaneous pneumothorax, and their early identification by high-resolution computed tomographic (HRCT) chest imaging has implications for subsequent management. Objectives: The objective of our study was to evaluate the cost-effectiveness of HRCT chest imaging to facilitate early diagnosis of LAM, BHD, and PLCH. Methods: We constructed a Markov state-transition model to assess the cost-effectiveness of screening HRCT to facilitate early diagnosis of diffuse cystic lung diseases in patients presenting with an apparent primary spontaneous pneumothorax. Baseline data for prevalence of BHD, LAM, and PLCH and rates of recurrent pneumothoraces in each of these diseases were derived from the literature. Costs were extracted from 2014 Medicare data. We compared a strategy of HRCT screening followed by pleurodesis in patients with LAM, BHD, or PLCH versus conventional management with no HRCT screening. Measurements and Main Results: In our base case analysis, screening for the presence of BHD, LAM, or PLCH in patients presenting with a spontaneous pneumothorax was cost effective, with a marginal cost-effectiveness ratio of $1,427 per quality-adjusted life-year gained. Sensitivity analysis showed that screening HRCT remained cost effective for diffuse cystic lung diseases prevalence as low as 0.01%. Conclusions: HRCT image screening for BHD, LAM, and PLCH in patients with apparent primary spontaneous pneumothorax is cost effective. Clinicians should consider performing a screening HRCT in patients presenting with apparent primary spontaneous pneumothorax. PMID:27737563

Chest Computed Tomographic Image Screening for Cystic Lung Diseases in Patients with Spontaneous Pneumothorax Is Cost Effective.

PubMed

Gupta, Nishant; Langenderfer, Dale; McCormack, Francis X; Schauer, Daniel P; Eckman, Mark H

2017-01-01

Patients without a known history of lung disease presenting with a spontaneous pneumothorax are generally diagnosed as having primary spontaneous pneumothorax. However, occult diffuse cystic lung diseases such as Birt-Hogg-Dubé syndrome (BHD), lymphangioleiomyomatosis (LAM), and pulmonary Langerhans cell histiocytosis (PLCH) can also first present with a spontaneous pneumothorax, and their early identification by high-resolution computed tomographic (HRCT) chest imaging has implications for subsequent management. The objective of our study was to evaluate the cost-effectiveness of HRCT chest imaging to facilitate early diagnosis of LAM, BHD, and PLCH. We constructed a Markov state-transition model to assess the cost-effectiveness of screening HRCT to facilitate early diagnosis of diffuse cystic lung diseases in patients presenting with an apparent primary spontaneous pneumothorax. Baseline data for prevalence of BHD, LAM, and PLCH and rates of recurrent pneumothoraces in each of these diseases were derived from the literature. Costs were extracted from 2014 Medicare data. We compared a strategy of HRCT screening followed by pleurodesis in patients with LAM, BHD, or PLCH versus conventional management with no HRCT screening. In our base case analysis, screening for the presence of BHD, LAM, or PLCH in patients presenting with a spontaneous pneumothorax was cost effective, with a marginal cost-effectiveness ratio of $1,427 per quality-adjusted life-year gained. Sensitivity analysis showed that screening HRCT remained cost effective for diffuse cystic lung diseases prevalence as low as 0.01%. HRCT image screening for BHD, LAM, and PLCH in patients with apparent primary spontaneous pneumothorax is cost effective. Clinicians should consider performing a screening HRCT in patients presenting with apparent primary spontaneous pneumothorax.

Effect of CO2 absorption on ion and water mobility in an anion exchange membrane

NASA Astrophysics Data System (ADS)

Peng, Jing; Roy, Asa L.; Greenbaum, Steve G.; Zawodzinski, Thomas A.

2018-03-01

We report the measured water uptake, density, ionic conductivity and water transport properties in Tokuyama A201 membrane in OH-, HCO3- and Cl- forms. The water uptake of the AEM varies with anion type in the order λ(OH-) > λ(HCO3-) > λ(Cl-) for samples equilibrated with the same water vapor activity (aw). The conductivity of the AEM is reduced by absorption of CO2. Pulsed-field gradient nuclear magnetic resonance (PFG-NMR) measurements were utilized to characterize the diffusivity of water and HCO3- ion. The anion diffusion coefficient and membrane conductivity are used to probe the applicability of the Nernst-Einstein equation in these AEMs.

Management of the Patient with Aggressive and Resistant Papillary Thyroid Carcinoma

PubMed Central

Miftari, Rame; Topçiu, Valdete; Nura, Adem; Haxhibeqiri, Valdete

2016-01-01

Purpose: Papillary carcinoma is the most frequent type of thyroid cancer and was considered the most benign of all thyroid carcinomas, with a low risk of distant metastases. However, there are some variants of papillary thyroid carcinoma that have affinity to spread in many organs, such as: lymph nodes, lungs and bones. Aim: The aim of this study was presentation of a case with papillary carcinoma of the thyroid gland, very persistent and resistant in treatment with I 131. Material and results: A man 56 years old were diagnosed with papillary carcinoma of thyroid gland. He underwent a surgical removal of the tumor and right lobe of thyroid gland. With histopathology examination, were confirmed follicular variant of papillary carcinoma pT4. Two weeks later he underwent total thyroidectomy and was treated with 100 mCi of J 131. Six months later, the value of thyroglobulin was found elevated above upper measured limits (more than 500 ng/ml). Patient underwent surgical removal of 10 metastatic lymph nodes in the left side of the neck and has been treated with 145 mCi of radioiodine I 131. The examination after 5 months shows elevation of thyroglobulin, more than 20000 ng/ml and focally uptake of J 131 in the left lung. Patient was treated once again with 150 mCi radioiodine J 131. Whole body scintigraphy was registered focal uptake of radioiodine in the middle of the left collarbone. After a month, patient refers the enlargement of the lymph node in the right side of the neck. Currently patient is being treated with kinase inhibitor drug sorafenib and ibandronate. We have identified first positive response in treatment. Enlarged lymph node in the neck was reduced and the patient began feeling better. Conclusion: This study suggests that some subtypes of papillary thyroid carcinoma appear to have more aggressive biological course. Subtypes of papillary thyroid carcinoma such as diffuse sclerosing carcinoma, tall cell or columnar cell and insular variants, appears to have more aggressive biological course and need early detection and other kind of treatment. PMID:27703298

Three-dimensional visualization of morphology and ventilation procedure (air flow and diffusion) of a subdivision of the acinus using synchrotron radiation microtomography of the human lung specimens

NASA Astrophysics Data System (ADS)

Shimizu, Kenji; Ikura, Hirohiko; Ikezoe, Junpei; Nagareda, Tomofumi; Yagi, Naoto; Umetani, Keiji; Imai, Yutaka

2004-04-01

We have previously reported a synchrotron radiation (SR) microtomography system constructed at the bending magnet beamline at the SPring-8. This system has been applied to the lungs obtained at autopsy and inflated and fixed by Heitzman"s method. Normal lung and lung specimens with two different types of pathologic processes (fibrosis and emphysema) were included. Serial SR microtomographic images were stacked to yield the isotropic volumetric data with high-resolution (12 μm3 in voxel size). Within the air spaces of a subdivision of the acinus, each voxel is segmented three-dimensionally using a region growing algorithm ("rolling ball algorithm"). For each voxel within the segmented air spaces, two types of voxel coding have been performed: single-seeded (SS) coding and boundary-seeded (BS) coding, in which the minimum distance from an initial point as the only seed point and all object boundary voxels as a seed set were calculated and assigned as the code values to each voxel, respectively. With these two codes, combinations of surface rendering and volume rendering techniques were applied to visualize three-dimensional morphology of a subdivision of the acinus. Furthermore, sequentially filling process of air into a subdivision of the acinus was simulated under several conditions to visualize the ventilation procedure (air flow and diffusion). A subdivision of the acinus was reconstructed three-dimensionally, demonstrating the normal architecture of the human lung. Significant differences in appearance of ventilation procedure were observed between normal and two pathologic processes due to the alteration of the lung architecture. Three-dimensional reconstruction of the microstructure of a subdivision of the acinus and visualization of the ventilation procedure (air flow and diffusion) with SR microtomography would offer a new approach to study the morphology, physiology, and pathophysiology of the human respiratory system.

The Influence of Type 1 Diabetes Mellitus on Pulmonary Function and Exercise Capacity - Results from the Study of Health in Pomerania (SHIP).

PubMed

Stubbe, Beate; Schipf, Sabine; Schäper, Christoph; Felix, Stephan B; Steveling, Antje; Nauck, Matthias; Völzke, Henry; Wallaschofski, Henri; Friedrich, Nele; Ewert, Ralf; Ittermann, Till; Gläser, Sven

2017-01-01

Background: Diabetes mellitus Type 1 (T1DM) is associated with metabolic and microvascular diseases as part of a multi-organ and multi-systemic disorder. The dense network of capillary vessels in the lungs may change during the course of the development of microangiopathy. The connective tissue as well as alveoli may be subjected to non-enzymatic glycosylation of proteins which may in turn affect pulmonary function. Previous studies investigating lung function in patients with type 1 diabetes have only been performed on small numbers of patients. Our study is based on population data of the Study of Health in Pomerania (SHIP). Objective: To investigate the influence of metabolic control on pulmonary system function and to establish a decreased pulmonary system function as a late complication of T1DM in a population based setting. Methods: The study is a case matched study with multiple controls based on participants with T1DM (SHIP-DM-1, n=73) and non-diabetics (SHIP-1, n=292) from the population based study of Pomerania. Data on lung function and exercise performance stratified by age, sex, body mass index and smoking habits in participants with T1DM and without diabetes were matched. Results: Participants with T1DM showed a significantly lower total lung capacity, residual volume and forced vital capacity. The transfer factor for carbon monoxide, the maximum power output and oxygen uptake during exercise were significantly decreased in comparison to the general population without diabetes. Conclusion: The pattern of abnormal pulmonary function as observed in the present study with a reduction in lung volume parameters and reduced oxygen uptake in participants with T1DM suggests a restrictive type of lung disease caused by an intrinsic lung tissue derangement as well as pulmonary microangiopathy. © Georg Thieme Verlag KG Stuttgart · New York.

Use of metaiodobenzylguanidine (MIBG) in pneumology.

PubMed

Giordano, A; Calcagni, M L; Rossi, B; Rufini, V; Fuso, L; Valente, S; Pistelli, R; Franceschini, R; Troncone, L

1995-12-01

Norepinephrine (NE) is one of the many biologically active substances that are metabolized by the lung. The norepinephrine uptake in the lung has been widely investigated in animal studies in order to detect abnormalities of the endothelial cells. 131I- or 123I-labelled metaiodobenzylguanidine (MIBG) is a radioactive tracer that shares several metabolic pathways with NE; it has been used instead NE or both in animal and in human studies for the same purposes. It has been definitely demonstrated that MIBG lung uptake following intravenous administration is a reliable marker of minimal endothelial cell lesions and it allows one to investigate several conditions involving damage to the lung vasculature such as adult respiratory distress syndrome, post-actinic lung fibrosis or chemotherapic lung toxicity. MIBG could also potentially be used as a tracer of the neuroadrenergic system of the airways, once it has been deposited in the whole branches of the bronchial tree. With this in mind we evaluated the feasibility of the administration of MIBG in radioaerosol form. We first performed a chromatographic study on [123I]MIBG aliquots aerosolized for variable lengths of time (2-30 minutes). Radiochemical purity was always over 96%, thus demonstrating that aerosolization does not significantly modify the stability of the tracer. We then compared both the lung clearance curves and the scintigraphic images in two groups of normal subjects who respectively underwent [123I]MIBG and 99mTc-DTPA radioaerosol dynamic scintigraphy. We found that MIBG clearance to be significantly lower than that of DTPA (135 +/- 32 minutes versus 69 +/- 27 minutes, p < 0.01), probably due to its being trapped in the adrenergic nerve endings of the airways. The pulmonary distribution of both tracers was homogeneous, as demonstrated by the correspondence of the values for the aerosol penetration index in both groups of subjects. Such results warrant further research and pharmacologic tests.

Dual Tracer PET Imaging (68Ga-DOTATATE and 18F-FDG) Features in Pulmonary Carcinoid: Correlation with Tumor Proliferation Index.

PubMed

Bhatkar, Dhiraj; Utpat, Ketaki; Basu, Sandip; Joshi, Jyotsna M

2017-01-01

Pulmonary carcinoid tumors are rare group of lung neoplasms representing 1% of all the lung tumors. The typical bronchial carcinoids showed higher and more selective uptake of 68 Ga-DOTATATE than of 18 F-FDG on PET-CT. The Ki-67(MIB-1), a tumor proliferation index is a prognostic marker in neuroendocrine tumors for estimating tumor progression. Atypical carcinoids have higher Ki-67 index and have an increased propensity to metastasize as compared to typical ones. 68 Ga-DOTATATE PET imaging along with Ki-67 can be correlated for better management of patients with neuroendocrine tumors. We describe the dual tracer imaging features in a patient of pulmonary carcinoid with avid 68 Ga-DOTATATE and minimal 18 FDG ( 18 Flurodeoxyglucose) uptake diagnosed on the basis of imaging and bronchoscopic biopsy and its correlation with tumor proliferation index.

Glossosoma nigrior (Trichoptera: Glossosomatidae) respiration in moving fluid.

PubMed

Morris, Mark W L; Hondzo, Miki

2013-08-15

Laboratory measurements of dissolved oxygen (DO) uptake by Glossosoma nigrior Banks were conducted in a sealed, recirculating flume under variable fluid flow velocities. Measurements were performed in similar water temperatures, DO concentrations and fluid flow velocities to field conditions in the stream where the larvae were obtained. Total oxygen uptake by both cased larvae and corresponding cases without larvae were quantified. An increased fluid flow velocity corresponded to an increased larval DO uptake rate. Oxygen uptake by the larval cases alone was not as sensitive to changes in the Peclet (Pe) number, the dimensionless ratio of advective to diffusive DO transport, as uptake by larvae themselves. The flux of DO to larvae and their cases was up to seven times larger in a moving fluid in comparison to non-moving fluid conditions in the proximity of larvae for 087, larvae typically remained in their cases. This indicates that oxygen delivery to the larvae at low Pe is insufficient to satisfy the respiratory demands of cased larvae.

Application of ET-Kyoto solution in clinical lung transplantation.

PubMed

Omasa, Mitsugu; Hasegawa, Seiki; Bando, Toru; Hanaoka, Nobuharu; Yoshimura, Takashi; Nakamura, Takayuki; Wada, Hiromi

2004-01-01

We have developed a new organ preservation solution called extracellular-type trehalose-containing Kyoto (ET-Kyoto) solution. ET-Kyoto solution has been applied in clinical lung transplantation. The patient was a 49-year-old woman with diffuse panbronchiolitis. She underwent bilateral lobar lung transplantation from living donors. Each lobe was flushed with ET-Kyoto solution. After reperfusion, PaO(2) with inhalation of 100% oxygen was more than 500 Torr. Posttransplantation course was uneventful. Despite the relatively short ischemic time of this case report, ET-Kyoto solution may be feasible and safely applied in clinical lung transplantation.

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

A novel paclitaxel-loaded poly(d,l-lactide-co-glycolide)-Tween 80 copolymer nanoparticle overcoming multidrug resistance for lung cancer treatment

PubMed Central

Yuan, Xun; Ji, Wenxiang; Chen, Si; Bao, Yuling; Tan, Songwei; Lu, Shun; Wu, Kongming; Chu, Qian

2016-01-01

Drug resistance has become a main obstacle for the effective treatment of lung cancer. To address this problem, a novel biocompatible nanoscale package, poly(d,l-lactide-co-glycolide)-Tween 80, was designed and synthesized to overcome paclitaxel (PTX) resistance in a PTX-resistant human lung cancer cell line. The poly(d,l-lactide-co-glycolide) (PLGA)-Tween 80 nanoparticles (NPs) could efficiently load PTX and release the drug gradually. There was an increased level of uptake of PLGA-Tween 80 in PTX-resistant lung cancer cell line A549/T, which achieved a significantly higher level of cytotoxicity than both PLGA NP formulation and Taxol®. The in vivo antitumor efficacy also showed that PLGA-Tween 80 NP was more effective than Taxol®, indicating that PLGA-Tween 80 copolymer was a promising carrier for PTX in resistant lung cancer. PMID:27307727

Lung cancer disparities and African-Americans.

PubMed

Sin, Mo-Kyung

2017-07-01

African-Americans, as historically disadvantaged minorities, have more advanced stages of cancer when diagnosed, lower survival rates, and lower rates of accessing timely care than do Caucasians. Lung cancer incidence and mortality, in particular, are high among African-Americans. The U.S. Preventive Services Task Force recently released an evidence-based lung cancer screening technology called low-dose computerized tomography. High-risk African-Americans might benefit greatly from such screening but not many are aware of this technology. Public health nurses can play a key role in increasing awareness of the technology among African-American communities and encouraging qualified African-Americans to obtain screening. This study discusses issues with lung cancer and smoking among African-Americans, a recently released evidence-based lung cancer screening technology, and implications for public health nurses to enhance uptake of the new screening technology among high-risk African-Americans. © 2017 Wiley Periodicals, Inc.

RADIOAUTOGRAPHIC DEMONSTRATION OF 5-HYDROXYTRYPTAMINE-3H UPTAKE BY PULMONARY ENDOTHELIAL CELLS

PubMed Central

Strum, Judy M.; Junod, Alain F.

1972-01-01

The lung is able to rapidly remove 5-hydroxytryptamme (5-HT) from the circulation by a Na+-dependent transport mechanism. In order to identify the sites of uptake, radioautographic studies were done on rat lungs which had been isolated and perfused with 5-HT-3H and 0 5 mM iproniazid, a monoamine oxidase inhibitor. In control experiments 10-4 M imipramine was added to the perfusate to inhibit the membrane transport of 5-HT At the light microscope level, silver grains were seen concentrated near capillaries and in the endothelium of large vessels From electron microscope radioautographs a semiquantitative grain count was made and 90% of the silver grains were observed over capillary endothelial cells. The grains were found over the nucleus and cytoplasm of the cell and shewed no preferential association with any particular cytoplasmic inclusion bodies, organelles, or vesicles Other cell types were unlabeled except for a few mast cells, certain vascular smooth muscle cells, and one nerve ending. This radioautographic demonstration of the cell type responsible for the rapid removal of 5-HT from the lung circulation clearly establishes the existence of a new metabolic role for pulmonary endothelial cells. PMID:5044755

Endotoxin reduces specific pulmonary uptake of radiolabeled monoclonal antibody to angiotensin-converting enzyme

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

Muzykantov, V.R.; Puchnina, E.A.; Atochina, E.N.

The biodistribution of radiolabeled monoclonal antibody (Mab) to angiotensin-converting enzyme (ACE) was examined in normal and endotoxin-treated rats. Endotoxin administration at a dose of 4 mg/kg induced mild or middle pulmonary edema. The ACE activity in lung homogenate remained virtually unchanged, while the activity of serum ACE increased 15 hr after endotoxin infusion. In normal rats, anti-ACE Mab accumulates specifically in the lung after i.v. injection. Endotoxin injection induces reduction of specific pulmonary uptake of this antibody. Even in non-edematous endotoxemia, the accumulation of anti-ACE Mab antibody (Mab 9B9) decreased from 19.02 to 11.91% of ID/g of tissue without anymore » change in accumulation of control nonspecific IgG. The antibody distribution in other organs and its blood level were almost the same as in the control. In a case of endotoxemia accompanied by increased microvascular permeability, the lung accumulation of Mab 9B9 was reduced to 9.17% of ID/g of tissue, while the accumulation of nonspecific IgG increased to 1.44% versus 0.89% in the control.« less

Consistency of metabolic tumor volume of non-small-cell lung cancer primary tumor measured using 18F-FDG PET/CT at two different tracer uptake times.

PubMed

Liu, Haiping; Chen, Ping; Wroblewski, Kristen; Hou, Peng; Zhang, Chen-Peng; Jiang, Yulei; Pu, Yonglin

2016-01-01

The objective of this study was to test the hypothesis that the metabolic tumor volume (MTV) of primary non-small-cell lung cancer is not sensitive to differences in F-fluorodeoxyglucose (F-FDG) uptake time, and to compare this consistency of MTV measurements with that of standardized uptake value (SUV) and total lesion glycolysis (TLG). Under Institutional Review Board approval, 134 consecutive patients with histologically proven non-small-cell lung cancer underwent F-FDG PET/computed tomography scanning at about 1 h (early) and 2 h (delayed) after intravenous injection of F-FDG. MTV, SUV, and TLG of the primary tumor were all measured. Student's t-test and Wilcoxon's signed-rank test for paired data were used to compare MTV, SUV, and TLG between the two scans. The intraclass correlation coefficient (ICC) was used to assess agreement in PET parameters between the two scans and between the measurements made by two observers. MTV was not significantly different (P=0.17) between the two scans. However, SUVmax, SUVmean, SUVpeak, and TLG increased significantly from the early to the delayed scans (P<0.0001 for all). The median percentage change between the two scans in MTV (1.65%) was smaller than in SUVmax (11.76%), SUVmean(10.57%), SUVpeak(13.51%), and TLG (14.34%); the ICC of MTV (0.996) was greater than that of SUVmax (0.933), SUVmean (0.952), SUVpeak (0.928), and TLG (0.982). Interobserver agreement between the two radiologists was excellent for MTV, SUV, and TLG on both scans (ICC: 0.934-0.999). MTV is not sensitive to common clinical variations in F-FDG uptake time, its consistency is greater than that of SUVmax, SUVmean, SUVpeak, and TLG, and it has excellent interobserver agreement.

Correlation of {sup 18}F-FDG Avid Volumes on Pre–Radiation Therapy and Post–Radiation Therapy FDG PET Scans in Recurrent Lung Cancer

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

Shusharina, Nadya, E-mail: nshusharina@partners.org; Cho, Joseph; Sharp, Gregory C.

2014-05-01

Purpose: To investigate the spatial correlation between high uptake regions of 2-deoxy-2-[{sup 18}F]-fluoro-D-glucose positron emission tomography ({sup 18}F-FDG PET) before and after therapy in recurrent lung cancer. Methods and Materials: We enrolled 106 patients with inoperable lung cancer into a prospective study whose primary objectives were to determine first, the earliest time point when the maximum decrease in FDG uptake representing the maximum metabolic response (MMR) is attainable and second, the optimum cutoff value of MMR based on its predicted tumor control probability, sensitivity, and specificity. Of those patients, 61 completed the required 4 serial {sup 18}F-FDG PET examinations aftermore » therapy. Nineteen of 61 patients experienced local recurrence at the primary tumor and underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were defined by use of an isocontour at ≥50% of maximum standard uptake value (SUV{sub max}) (≥50% of SUV{sub max}) with correction for heterogeneity. The VOI on posttherapy images were defined at ≥80% of SUV{sub max}. The VOI of pretherapy and posttherapy {sup 18}F-FDG PET images were correlated for the extent of overlap. Results: The size of VOI at pretherapy images was on average 25.7% (range, 8.8%-56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49-0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10 days, 3 months, and 6 months, respectively. The residual uptake originated from the pretherapy VOI in 15 of 17 cases. Conclusions: VOI defined by the SUV{sub max}-≥50% isocontour may be a biological target volume for escalated radiation dose.« less

18F-FDG PET/CT Can Predict Development of Thyroiditis due to Immunotherapy for Lung Cancer.

PubMed

Eshghi, Naghmehossadat; Garland, Linda; Nia, Emily Saghar; Betancourt, Robert; Krupinski, Elizabeth; Kuo, Phillip H

2018-03-29

Objective: For patients undergoing immunotherapy with nivolumab for lung cancer, determine if increased 18 F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism. Secondarily, determine if 18 F-FDG uptake in the thyroid gland correlates with administered cycles of nivolumab. Materials and Methods: Retrospective chart review over 2 years found 18 lung cancer patients treated with nivolumab and with 18 F-FDG PET/CT scans pre- and during therapy. Standardized uptake value (SUV) mean and maximum and total lesion glycolysis (TLG) of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver and spleen. Patients obtained monthly thyroid testing. PET/CT parameters were analyzed by unpaired t-test for differences between two groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab received was also tested. Results: Six of eighteen patients developed hypothyroidism. T-test comparing the two groups (patients who developed hypothyroidism and those who did not) demonstrated significant differences in SUVmean ( P = 0.04), SUV max ( P = 0.04) and TLG ( P = 0.02) of the thyroid gland. Two of four patients who developed thyroiditis and had increased 18 F-FDG uptake in the thyroid gland, had normal TSH at time of follow-up 18 F-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) compared to patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver or spleen. Conclusion: 18 F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Prognostic Value of Bone Marrow Tracer Uptake Pattern in Baseline PET Scans in Hodgkin Lymphoma: Results from an International Collaborative Study.

PubMed

Zwarthoed, Colette; El-Galaly, Tarec Cristoffer; Canepari, Maria; Ouvrier, Matthieu John; Viotti, Julien; Ettaiche, Marc; Viviani, Simonetta; Rigacci, Luigi; Trentin, Livio; Rusconi, Chiara; Luminari, Stefano; Cantonetti, Maria; Bolis, Silvia; Borra, Anna; Darcourt, Jacques; Salvi, Flavia; Subocz, Edyta; Tajer, Joanna; Kulikowski, Waldemar; Malkowski, Bogdan; Zaucha, Jan Maciej; Gallamini, Andrea

2017-08-01

PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of different patterns of bone marrow (BM) 18 F-FDG uptake in HL. Methods: One hundred eighty newly diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) courses with 18 F-FDG PET, enrolled in 2 international studies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD × 4-6 cycles and involved-field radiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET + ), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (>liver) diffuse uptake (dPET + ) and 89 (48.4%) showed no or faint (≤liver) BM uptake (nPET + ). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET + , in 1 of 53 (1.9%) for dPET + , and in 5 of 89 (5.6%) for nPET + dPET + was correlated with younger age, higher frequency of bulky disease, lower hemoglobin levels, higher leukocyte counts, and similar diffuse uptake in the spleen. Patients with pure dPET + had a 3-y progression-free survival identical to patients without any 18 F-FDG uptake (82.9% and 82.2%, respectively, P = 0.918). However, patients with fPET+ (either unifocal or multifocal) had a 3-y progression-free survival significantly inferior to patients with dPET+ and nPET+ (66.7% and 82.5%, respectively, P = 0.03). The κ values for interobserver agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. Conclusion: We confirmed that 18 F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal 18 F-FDG BM uptake should be considered as a harbinger of HL. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Lung damage and pulmonary uptake of serotonin in intact dogs

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

Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.

1985-06-01

The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of (/sup 3/H)serotonin and the extravascular volume accessible to (/sup 14/C)antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as withmore » embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.« less

Designing herbicide formulation characteristics to maximize efficacy and minimize rice injury in paddy environments.

PubMed

Cryer, S A; Mann, R K; Erhardt-Zabik, S; Keeney, F N; Handy, P R

2001-06-01

Mathematical descriptors, coupled with experimental observations, are used to quantify differential uptake of an experimental herbicide in Japonica and Indica rice (Oryza sativa, non-target) and barnyardgrass (Echinochloa crus-galli, target). Partitioning, degradation, plant uptake and metabolism are described using mass-balance conservation equations in the form of kinetic approximations. Estimated environmental concentrations, governed by the pesticide formulation, are described using superimposed analytical solutions for the one-dimensional diffusion equation in spherical coordinates and by a finite difference representation of the two-dimensional diffusion equation in Cartesian coordinates. Formulation attributes from granules include active ingredient release rates, particle sizes, pesticide loading, and granule spacing. The diffusion model for pesticide transport is coupled with the compartment model to follow the fate and transport of a pesticide from its initial application location to various environmental matrices of interest. Formulation effects, partitioning and degradation in the various environmental matrices, differential plant uptake and metabolism, and dose-response information for plants are accounted for. This novel model provides a mechanism for selecting formulation delivery systems that optimize specific attributes (such as weed control or the therapeutic index) for risk-assessment procedures. In this report we describe how this methodology was used to explore the factors affecting herbicide efficacy and to define an optimal release rate for a granule formulation.

Effect of Pore Clogging on Kinetics of Lead Uptake by Clinoptilolite.

PubMed

Inglezakis; Diamandis; Loizidou; Grigoropoulou

1999-07-01

The kinetics of lead-sodium ion exchange using pretreated natural clinoptilolite are investigated, more specifically the influence of agitation (0, 210, and 650 rpm) on the limiting step of the overall process, for particle sizes of 0.63-0.8 and 0.8-1 mm at ambient temperature and initial lead solutions of 500 mg l-1 without pH adjustment. The isotopic exchange model is found to fit the ion exchange process. Particle diffusion is shown to be the controlling step for both particle sizes under agitation, while in the absence of agitation film diffusion is shown to control. The ion exchange process effective diffusion coefficients are calculated and found to depend strongly on particle size in the case of agitation at 210 rpm and only slightly on particle size at 650 rpm. Lead uptake rates are higher for smaller particles only at rigorous agitation, while at mild agitation the results are reversed. These facts are due to partial clogging of the pores of the mineral during the grinding process. This is verified through comparison of lead uptake rates for two samples of the same particle size, one of which is rigorously washed for a certain time before being exposed to the ion exchange. Copyright 1999 Academic Press.

Quantitative diffusion and swelling kinetic measurements using large-angle interferometric refractometry.

PubMed

Saunders, John E; Chen, Hao; Brauer, Chris; Clayton, McGregor; Chen, Weijian; Barnes, Jack A; Loock, Hans-Peter

2015-12-07

The uptake and release of sorbates into films and coatings is typically accompanied by changes of the films' refractive index and thickness. We provide a comprehensive model to calculate the concentration of the sorbate from the average refractive index and the film thickness, and validate the model experimentally. The mass fraction of the analyte partitioned into a film is described quantitatively by the Lorentz-Lorenz equation and the Clausius-Mosotti equation. To validate the model, the uptake kinetics of water and other solvents into SU-8 films (d = 40-45 μm) were explored. Large-angle interferometric refractometry measurements can be used to characterize films that are between 15 μm to 150 μm thick and, Fourier analysis, is used to determine independently the thickness, the average refractive index and the refractive index at the film-substrate interface at one-second time intervals. From these values the mass fraction of water in SU-8 was calculated. The kinetics were best described by two independent uptake processes having different rates. Each process followed one-dimensional Fickian diffusion kinetics with diffusion coefficients for water into SU-8 photoresist film of 5.67 × 10(-9) cm(2) s(-1) and 61.2 × 10(-9) cm(2) s(-1).

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.

Direct quantitation of thoracic gallium-67 uptake in sarcoidosis

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

Bourguet, P.; Delaval, P.; Herry, J.Y.

1986-10-01

A method of direct quantitation of /sup 67/Ga uptake in the lung is described. The attenuation coefficient requires calculation and is obtained simply for each patient by transmission using a planar radionuclide source. The validity of the method was tested with a phantom (error less than 10%). Forty-three patients with pulmonary and/or mediastinal sarcoidosis were classified. The different groups of patients as defined clinically and radiographically (controls, nonactive, and active sarcoidosis) were well-differentiated (p less than 0.001).

Prostate-Specific Membrane Antigen Expression in Adrenocortical Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Aggarwal, Sameer; Passah, Averilicia; Behera, Abhishek; Arora, Geetanjali; Bal, Chandrasekhar; Tripathi, Madhavi

2018-06-01

We present here a case of metastatic adrenocortical carcinoma with bilateral lung nodules. The patient had been treated with mitotane therapy initially and then was later referred for chemotherapy. There was progression of disease noted on the F-FDG PET/CT. Ga prostate-specific membrane antigen (PSMA) PET/CT was planned to explore the possibility of future treatment with Lu-DKFZ-PSMA-617. It revealed peripheral increased uptake of Ga-HBED-CC-PSMA equal to liver uptake.

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

Acute pleurisy in sarcoidosis.

PubMed Central

Gardiner, I T; Uff, J S

1978-01-01

A 47-year-old white man with sarcoidosis presented with a six-week history of acute painful pleurisy. On auscultation a loud pleural rub was heard at the left base together with bilateral basal crepitations. The chest radiograph showed hilar enlargement as well as diffuse lung shadowing. A lung biopsy showed the presence of numerous epithelioid and giant-cell granulomata, particularly subpleurally. A patchy interstitial pneumonia was also present. He was given a six-month course of prednisolone, and lung function returned to normal. Images PMID:644534

Cadmium and Zn availability as affected by pH manipulation and its assessment by soil extraction, DGT and indicator plants.

PubMed

Muhammad, Iqbal; Puschenreiter, Markus; Wenzel, Walter W

2012-02-01

Manipulation of soil pH by soil additives and / or rhizosphere processes may enhance the efficiency of metal phytoextraction. Here we report on the effect of nitric acid additions to four polluted soils on Cd and Zn concentrations in soil solution (C(soln)) and 0.005M Ca(NO(3))(2) extracts, and related changes in the diffusive fluxes and resupply of the metals as assessed by diffusive gradients in thin films (DGT). The responses of these chemical indicators of bioavailability were compared to metal uptake in two indicator plant species, common dandelion (Taraxacum officinale F.H. Wigg) and narrow leaf plantain (Plantago lanceolata L.) grown for 75days in a pot experiment. Lowering soil pH increased C(soln), the 0.005M Ca(NO(3))(2)-soluble fractions and the DGT-measured Cd and Zn concentrations (C(DGT)) in the experimental soils. This was associated with enhanced uptake of Cd and Zn on soils acidified to pH 4.5 whereas plants did not survive at pH 3.5. Toxicity along with decreased kinetics of metal resupply (calculated by the 2D DIFS model) in the strong acidification treatment suggests that moderate acidification is more appropriate to enhance the phytoextraction process. Each of the chemical indicators of bioavailability predicted well (R(2)>0.70) the Cd and Zn concentrations in plantain shoots but due to metal toxicity not for dandelion. Concentration factors, i.e. the ratio between metal concentrations in shoots and in soil solution (CF) indicate that Cd and Zn uptake in plantain was not limited by diffusion which may explain that DGT did not perform better than C(soln). However, DGT is expected to predict plant uptake better in diffusion-limited conditions such as in the rhizosphere of metal-accumulating phytoextraction crops. Copyright © 2011 Elsevier B.V. All rights reserved.

Surgical lung biopsy in transplant patients with diffuse lung disease: how much worse when the lung is the graft?

PubMed

Bertolotti, Alejandro; Defranchi, Sebastián; Vigliano, Carlos; Haberman, Diego; Favaloro, Roberto

2013-07-01

There are no data that compare the clinical presentation and results of surgical lung biopsy (SLB) for diffuse lung disease (DLD) in lung transplant patients, in contrast to individuals with other type of solid organ grafts. Our objective was to compare the clinical picture, radiologic pattern, pathology results, and outcomes of SLB for DLD in these two subsets of patients. We retrospectively reviewed the clinical records of transplant patients undergoing SLB for DLD at our institution between 2004 and 2011. Patients with lung transplants and those with other transplants were compared. During the study period, 1,232 solid organ transplants were done at our institution. Of these, 49 patients (4%) had DLD that needed SLB for diagnosis, and 24 of these patients had a lung transplant. Dyspnea and a radiologic reticular pattern were more frequent in lung transplant patients, 21 of 24 vs 11 of 25 (p = 0.001) and 14 of 24 vs 7 of 25 (p = 0.03), respectively. Although postoperative complications and in-hospital deaths were more common in lung transplant patients, the differences were not statistically significant. Having the SLB performed for diagnosis, as opposed to being conducted for DLD that did not improve on medical treatment, had a protective effect on multivariate analysis (hazard ratio, 0.39; 95% confidence interval, 0.16 to 0.96; p = 0.042). A prior lung transplant was the only independent predictor of survival (hazard ratio, 4.62; 95% confidence interval, 1.53 to 13.92, p = 0.006). It is relatively uncommon for a solid organ transplant patient with DLD to require a SLB. Clinical and radiologic presentation differ in patients with lung transplants compared with other transplants. Postoperative outcomes are not significantly different between the groups. SLB performed early in the course of the disease might be beneficial. Having a lung transplant is a significant negative predictor of survival. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

A Pilot Study Treatment of Malignant Tumors Using [18F] Fluorodeoxyglucose (FDG)

ClinicalTrials.gov

2018-05-08

Radiosensitive Stage IV Solid and Hematological Tumors With High FDG Uptake Not Responding to Standard of Care; Lung Cancer, Head and Neck Cancer, Breast Cancer, Gastric Cancer, Pancreatic Cancer, Colon Cancer, Lymphomas, Sarcomas, Etc

Contribution of aerial hyphae of Aspergillus oryzae to respiration in a model solid-state fermentation system.

PubMed

Rahardjo, Yovita S P; Weber, Frans J; le Comte, E Paul; Tramper, Johannes; Rinzema, Arjen

2002-06-05

Oxygen transfer is for two reasons a major concern in scale-up and process control in industrial application of aerobic fungal solid-state fermentation (SSF): 1) heat production is proportional to oxygen uptake and it is well known that heat removal is one of the main problems in scaled-up fermenters, and 2) oxygen supply to the mycelium on the surface of or inside the substrate particles may be hampered by diffusion limitation. This article gives the first experimental evidence that aerial hyphae are important for fungal respiration in SSF. In cultures of A. oryzae on a wheat-flour model substrate, aerial hyphae contributed up to 75% of the oxygen uptake rate by the fungus. This is due to the fact that A. oryzae forms very abundant aerial mycelium and diffusion of oxygen in the gas-filled pores of the aerial hyphae layer is rapid. It means that diffusion limitation in the densely packed mycelium layer that is formed closer to the substrate surface and that has liquid-filled pores is much less important for A. oryzae than was previously reported for R. oligosporus and C. minitans. It also means that the overall oxygen uptake rate for A. oryzae is much higher than the oxygen uptake rate that can be predicted in the densely packed mycelium layer for R. oligosporus and C. minitans. This would imply that cooling problems become more pronounced. Therefore, it is very important to clarify the physiological role of aerial hyphae in SSF. Copyright 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 78: 539-544, 2002.

Diffusive gradient in thin FILMS (DGT) compared with soil solution and labile uranium fraction for predicting uranium bioavailability to ryegrass.

PubMed

Duquène, L; Vandenhove, H; Tack, F; Van Hees, M; Wannijn, J

2010-02-01

The usefulness of uranium concentration in soil solution or recovered by selective extraction as unequivocal bioavailability indices for uranium uptake by plants is still unclear. The aim of the present study was to test if the uranium concentration measured by the diffusive gradient in thin films (DGT) technique is a relevant substitute for plant uranium availability in comparison to uranium concentration in the soil solution or uranium recovered by ammonium acetate. Ryegrass (Lolium perenne L. var. Melvina) is grown in greenhouse on a range of uranium spiked soils. The DGT-recovered uranium concentration (C(DGT)) was correlated with uranium concentration in the soil solution or with uranium recovered by ammonium acetate extraction. Plant uptake was better predicted by the summed soil solution concentrations of UO(2)(2+), uranyl carbonate complexes and UO(2)PO(4)(-). The DGT technique did not provide significant advantages over conventional methods to predict uranium uptake by plants. Copyright 2009 Elsevier Ltd. All rights reserved.

Postural variation of pulmonary diffusing capacity as a marker of lung microangiopathy in Indian patients with type 2 diabetes mellitus.

PubMed

Kumar, Avinash; Bade, Geetanjali; Trivedi, Anjali; Jyotsna, Viveka P; Talwar, Anjana

2016-01-01

Diabetes mellitus (DM) is characterized by the presence of chronic hyperglycemia and formation of advanced glycation end products (AGEs). Interaction between AGE and its receptor leads to endothelial damage and microangiopathy. This study was undertaken to investigate the possibility of using a postural variation of diffusing capacity as an early marker of lung microangiopathy and its correlation with the level of adhesion molecules, HbA1c, duration of diabetes, and insulin resistance in type 2 DM (T2DM) patients with and without microangiopathy. Forty patients having T2DM without any microangiopathy (n = 20) as well as with microangiopathy (n = 20), and 22 age and sex matched healthy controls were enrolled in this cross-sectional study. Measurement of lung volumes and capacities were done. DLco was measured in sitting and supine position. Levels of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, fasting glucose, and insulin were estimated in plasma of the patients and compared with controls. Restrictive type of ventilatory change was observed in DM patients. Diffusing capacity (% predicted) in the supine position (P < 0.0001), postural change in DLco (P < 0.0001), and coefficient of diffusion were significantly less in DM patients as compared to controls. Plasma levels of VCAM-1 were significantly higher in DM patients without microangiopathy and negatively correlated (r = -0.4054, P = 0.0094) with Δ DLco in all diabetic subjects. All patients had significantly higher insulin resistance. Lack of postural increase in diffusing capacity in type 2 diabetic patients along with increased VCAM-1 levels could reflect the presence of an early microangiopathy of the small pulmonary vessels.

[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.

WE-FG-206-07: Assessing the Lung Function of Patients with Non-Small Cell Lung Cancer Using Hyperpolarized Xenon-129 Dissolved-Phase MRI

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

Qing, K; Mugler, J; Chen, Q

Purpose: Hyperpolarized xenon-129 dissolved-phase MRI is the first imaging technique that allows 3-dimensional regional mapping of ventilation and gas uptake by tissue and blood the in human lung. Multiple outcome measures can be produced from this method. Existing studies in subjects with major lung diseases compared to healthy controls demonstrated high sensitivities of this method to pulmonary physiological factors including ventilation, alveolar tissue density, surface-to-volume ratio, pulmonary perfusion and gas-blood barrier thickness. The purpose of this study is to evaluate the utility of this new imaging tool to assess the lung function in patients with non-small cell lung cancer (NSCLC).more » Methods: Ten healthy controls (age: 63±10) and five patients (age: 62±13) with NSCLC underwent the xenon-129 dissolved-phase MRI, pulmonary function test (PFT) and CT for clinical purpose. Three outcome measures were produced from xenon-129 dissolved-phase MRI, including ventilation defect fraction (Vdef%) reflecting the airflow obstruction, tissue-to-gas ratio reflecting lung tissue density, and RBC-to-tissue ratio reflecting pulmonary perfusion and gas exchange. Results: Compared to healthy controls, patients with NSCLC showed more ventilation defects (NSCLC: 22±6%; control: 40±18%; P=0.01), lower tissue-to-gas (NSCLC: 0.82±0.31%; control: 1.07±0.13%; P=0.05) and RBC-to-tissue ratios (NSCLC: 0.82±0.31%; control: 1.07±0.13%; P=0.01). Maps for ventilation and gas uptake by tissue and blood were highly heterogeneous in the lungs of patients. Vdef% and RBC-to-tissue ratios in all 15 subjects correlated with corresponding global lung functional measures from PFT: FEV1/FVC (R=−0.91, P<0.001) and DLCO % predicted (R=0.54, P=0.03), respectively. The tissue-to-gas ratios correlated with tissue density (HU) measured by CT (R=0.88, P<0.001). Conclusion: With the unique ability to provide detailed information about lung function including ventilation, tissue density, perfusion and gas exchange with 3D resolution, hyperpolarized xenon-129 dissolved-phase MRI has high potential to be used as an important reference for radiotherapy treatment planning and for evaluating the side effects of the treatment. Receive research support and funding from Siemens.« less

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer.

PubMed

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-09-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer

PubMed Central

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-01-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib. PMID:28794368

Quantitative assessment of lung ventilation and microstructure in an animal model of idiopathic pulmonary fibrosis using hyperpolarized gas MRI.

PubMed

Stephen, Michael J; Emami, Kiarash; Woodburn, John M; Chia, Elaine; Kadlecek, Stephen; Zhu, Jianliang; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R; Rossman, Milton

2010-11-01

The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). Preliminary results suggest that quantitative (3)He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

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.

Carrier-mediated uptake of nobiletin, a citrus polymethoxyflavonoid, in human intestinal Caco-2 cells.

PubMed

Kimura, Osamu; Ohta, Chiho; Koga, Nobuyuki; Haraguchi, Koichi; Kato, Yoshihisa; Endo, Tetsuya

2014-07-01

The mechanism of intestinal absorption of nobiletin (NBL) was investigated using Caco-2 cells. The uptake of NBL from the apical membranes of Caco-2 cells was rapid and temperature-dependent and the presence of metabolic inhibitors, NaN3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone, did not cause a decrease in NBL uptake. The relationship between the initial uptake of NBL and its concentration was saturable, suggesting the involvement of a carrier-mediated process. The Km and uptake clearance (Vmax/Km) values for NBL were 50.6 and 168.1μl/mg protein/min, respectively. This clearance value was about 9-fold greater than that of the non-saturable uptake clearance (Kd: 18.5μl/mg protein/min). The presence of structurally similar compounds, such as quercetin and luteolin, competitively inhibited NBL uptake. These results suggest that uptake of NBL from the apical membranes of Caco-2 cells is mainly mediated by an energy-independent facilitated diffusion process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multifunctional Micelles Dually Responsive to Hypoxia and Singlet Oxygen: Enhanced Photodynamic Therapy via Interactively Triggered Photosensitizer Delivery.

PubMed

Li, Juanjuan; Meng, Xuan; Deng, Jian; Lu, Di; Zhang, Xin; Chen, Yanrui; Zhu, Jundong; Fan, Aiping; Ding, Dan; Kong, Deling; Wang, Zheng; Zhao, Yanjun

2018-05-23

Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT's antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.

Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD.

PubMed

Jones, Joshua H; Zelt, Joel T; Hirai, Daniel M; Diniz, Camilla V; Zaza, Aida; O'Donnell, Denis E; Neder, J Alberto

2017-04-01

There is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV 1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation ([Formula: see text]E)/CO 2 output ([Formula: see text]CO 2 ) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake ([Formula: see text]O 2 ), higher [Formula: see text]E/[Formula: see text]CO 2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak [Formula: see text]O 2 and worse dyspnea were found in patients with higher [Formula: see text]E/[Formula: see text]CO 2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-[Formula: see text]O 2 exercise (p < 0.05). Higher [Formula: see text]E/[Formula: see text]CO 2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = -0.72) and blunted changes in PBF from rest to exercise (r = -0.69) (p < 0.01). Ventilation "wasted" in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (D L CO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

Response assessment of stereotactic body radiation therapy using dynamic contrast-enhanced integrated MR-PET in non-small cell lung cancer patients.

PubMed

Huang, Yu-Sen; Chen, Jenny Ling-Yu; Hsu, Feng-Ming; Huang, Jei-Yie; Ko, Wei-Chun; Chen, Yi-Chang; Jaw, Fu-Shan; Yen, Ruoh-Fang; Chang, Yeun-Chung

2018-01-01

To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, K trans , k ep , v e , v p , and iAUC 60 . Chest computed tomography (CT) was performed at 3 months after SBRT. SBRT treatment led to tumor changes including significant decreases in the SUV max (-61%, P < 0.001), K trans mean (-72%, P = 0.005), K trans standard deviation (SD; -85%, P = 0.046), k ep mean (-53%, P = 0.014), k ep SD (-63%, P = 0.001), and v p SD (-58%, P = 0.002). The PET SUV max was correlated with the MR k ep mean (P = 0.002) and k ep SD (P < 0.001). The percentage reduction in K trans mean (P < 0.001) and k ep mean (P = 0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUV max > 10 (P = 0.083). In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199. © 2017 International Society for Magnetic Resonance in Medicine.

Arterial Carboxyhemoglobin Measurement Is Useful for Evaluating Pulmonary Inflammation in Subjects with Interstitial Lung Disease

PubMed Central

Hara, Yu; Shinkai, Masaharu; Kanoh, Soichiro; Fujikura, Yuji; K. Rubin, Bruce; Kawana, Akihiko; Kaneko, Takeshi

2017-01-01

Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, high-resolution CT (HRCT) findings, and the uptake in gallium-67 (67Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5±0.5%, (B) 2.1±0.5%, (C) 1.2±0.4%, and (D) 1.7±0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4±0.5% vs. 1.1±0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation. PMID:28321059

Uptake and output of various forms of choline by organs of the conscious chronically catheterized sheep.

PubMed Central

Robinson, B S; Snoswell, A M; Runciman, W B; Upton, R N

1984-01-01

The net uptake and output of plasma unesterified choline, glycerophosphocholine, phosphocholine and lipid choline by organs of the conscious chronically catheterized sheep were measured. There was significant production of plasma unesterified choline by the upper- and lower-body regions and the alimentary tract and uptake by the liver, lungs and kidneys. The upper- and lower-body regions drained by the venae cavae provided the bulk (about 82%) of the total body venous return of plasma unesterified choline. Production of plasma unesterified choline by the alimentary tract was approximately balanced by the plasma unesterified choline taken up by the liver, and was almost equal to the amount of choline secreted in the bile. There was a considerable amount of glycerophosphocholine in the liver and there was production of plasma glycerophosphocholine by the liver and uptake by the lungs and kidneys. Glycerophosphocholine was higher in the plasma of sheep than in that of rats. Plasma phosphocholine was produced by the alimentary tract and kidneys. There was production of plasma lipid choline by the upper- and lower-body regions drained by the venae cavae. The results suggest that the sheep synthesizes substantial amounts of choline in ectrahepatic tissues and has the capacity for extensive retention and recycling of bile choline. These observations, coupled with a slow turnover of the endogenous choline body pool, explain the low requirement of sheep for dietary choline in contrast with non-ruminant species. PMID:6696739

Effect of specific activity on cardiac uptake of iodine-123-MIBG.

PubMed

Farahati, J; Bier, D; Scheubeck, M; Lassmann, M; Schelper, L F; Grelle, I; Hanscheid, H; Biko, J; Graefe, K H; Reiners, C

1997-03-01

Radioiodinated meta-iodobenzylguanidine (MIBG), an analog of norepinephrine, has been used to assess myocardial sympathetic innervation. Recent in vivo studies predict enhanced cardiac uptake of this radiopharmaceutical with high specific activity. To clarify the effect of specific activity on cardiac uptake of radioiodinated MIBG, the distribution and kinetics of no-carrier-added [123I]MIBG (> or = 7.4 TBq/mumol) were compared with those of commercial [123I]MIBG (approximately 74 MBq/mumol) in three healthy volunteers by serial imaging and blood sampling. Higher specific activity result in higher uptake of radioiodinated MIBG in all volunteers in the heart (p < 0.05) and liver (p < 0.05) but not in the lung (p = 0.26). Due to rapid deiodination, a more pronounced accumulation of radioactivity was present in plasma after no-carrier-added MIBG than commercial [123I]MIBG, resulting in higher background and thyroid activity after administration of the former. Calculated heart-to-liver (p = 0.96) and heart-to-lung (p = 0.42) count ratios in all volunteers revealed no significant improvement in cardiac imaging with no-carrier-added [123I]MIBG compared to commercial [123I]MIBG. This study highlights the appreciably higher in vivo deiodination of no-carrier-added [123I]MIBG compared to commercial preparation of [123I]MIBG in humans. Cardiac images acquired with no-carrier-added [123I]MIBG do not seem to be superior to those obtained with commercial MIBG.

Effect of specific activity on neuroblastoma uptake of I-123-meta-iodobenzylguanidine in nude mice xenografted with SK-N-SH cells.

PubMed

Farahati, J; Coenen, H; Dutschka, K; Stuben, G; Knuhmann, K; Budach, W; Kremens, B; Reiners, C

1997-01-01

The effect of specific activity of meta[I-123]iodobenzylguanidine ([I-123]MIBG) on neuroblastoma uptake was studied in a nude mouse model (NMRI nu/nu) xenografted subcutaneously with SK-N-SH cells. Groups of eight animals received [I-123]MIBG intravenously with a specific activity of greater than or equal to 260 GBq/mu mol (no-carrier-added), 3.7 GBq/mu mol, 37 MBq/mu mol, and 0.37 MBq/mu mol, respectively. All animals in the group injected with 0.37 MBq/mu mol died immediately after the injection. Al 4 and 24 h, there was no significant effect of specific activity on tumor uptake of [I-123]MIBG in the different groups. The uptake of non-tumor tissue was in general lower with 37 MBq/mu mol compared to higher specific activities. The differences in blood, heart, liver, spleen and lungs were statistically significant at 24 h, whereas at 4 h significant differences were only present in the heart, liver and lungs. The results suggest that for the treatment of children with neuroblastoma a lower specific activity of radioiodinated MIBG may minimize the radiation exposure to non-tumor tissue but not to the tumor. Higher mass of MIBG >0.5 mu mol/g, however, is considered as lethal dose in our nude mice model and corresponding doses may cause toxic side effects in human.

Association of adult respiratory distress syndrome (ARDS) with thoracic irradiation (RT)

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

Byhardt, R.W.; Abrams, R.; Almagro, U.

1988-12-01

The authors report two cases of apparent adult respiratory distress syndrome (ARDS) following limited thoracic irradiation for lung cancer. Respiratory failure followed rapidly after irradiation with diffuse bilateral infiltrates, both in and out of the irradiated volume along with progressive hypoxemia unresponsive to oxygen management. Other potential causes of lung injury such as lymphangitic tumor, cardiac failure, and infections were excluded by both premortem and postmortem examination. Autopsy findings in both irradiated and unirradiated volumes of lung were consistent with hyaline membrane changes. The possible relationship between radiation therapy to limited lung volumes and the development of adult respiratory distressmore » syndrome is discussed.« less

High resolution multidetector CT aided tissue analysis and quantification of lung fibrosis

NASA Astrophysics Data System (ADS)

Zavaletta, Vanessa A.; Karwoski, Ronald A.; Bartholmai, Brian; Robb, Richard A.

2006-03-01

Idiopathic pulmonary fibrosis (IPF, also known as Idiopathic Usual Interstitial Pneumontis, pathologically) is a progressive diffuse lung disease which has a median survival rate of less than four years with a prevalence of 15-20/100,000 in the United States. Global function changes are measured by pulmonary function tests and the diagnosis and extent of pulmonary structural changes are typically assessed by acquiring two-dimensional high resolution CT (HRCT) images. The acquisition and analysis of volumetric high resolution Multi-Detector CT (MDCT) images with nearly isotropic pixels offers the potential to measure both lung function and structure. This paper presents a new approach to three dimensional lung image analysis and classification of normal and abnormal structures in lungs with IPF.

Mathematical modelling of the uptake and transport of salt in plant roots.

PubMed

Foster, Kylie J; Miklavcic, Stanley J

2013-11-07

In this paper, we present and discuss a mathematical model of ion uptake and transport in roots of plants. The underlying physical model of transport is based on the mechanisms of forced diffusion and convection. The model can take account of local variations in effective ion and water permeabilities across the major tissue regions of plant roots, represented through a discretized coupled system of governing equations including mass balance, forced diffusion, convection and electric potential. We present simulation results of an exploration of the consequent enormous parameter space. Among our findings we identify the electric potential as a major factor affecting ion transport across, and accumulation in, root tissues. We also find that under conditions of a constant but realistic level of bulk soil salt concentration and plant-soil hydraulic pressure, diffusion plays a significant role even when convection by the water transpiration stream is operating. Crown Copyright © 2013 Published by Elsevier Ltd. All rights reserved.

Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo.

PubMed

Gullbrand, Sarah E; Peterson, Joshua; Mastropolo, Rosemarie; Roberts, Timothy T; Lawrence, James P; Glennon, Joseph C; DiRisio, Darryl J; Ledet, Eric H

2015-05-01

The intervertebral disc primarily relies on trans-endplate diffusion for the uptake of nutrients and the clearance of byproducts. In degenerative discs, diffusion is often diminished by endplate sclerosis and reduced proteoglycan content. Mechanical loading-induced convection has the potential to augment diffusion and enhance net transport into the disc. The ability of convection to augment disc transport is controversial and has not been demonstrated in vivo. To determine if loading-induced convection can enhance small molecule transport into the intervertebral disc in vivo. Net transport was quantified via postcontrast enhanced magnetic resonance imaging (MRI) into the discs of the New Zealand white rabbit lumbar spine subjected to in vivo cyclic low rate loading. Animals were administered the MRI contrast agent gadodiamide intravenously and subjected to in vivo low rate loading (0.5 Hz, 200 N) via a custom external loading apparatus for either 2.5, 5, 10, 15, or 20 minutes. Animals were then euthanized and the lumbar spines imaged using postcontrast enhanced MRI. The T1 constants in the nucleus, annulus, and cartilage endplates were quantified as a measure of gadodiamide transport into the loaded discs compared with the adjacent unloaded discs. Microcomputed tomography was used to quantify subchondral bone density. Low rate loading caused the rapid uptake and clearance of gadodiamide in the nucleus compared with unloaded discs, which exhibited a slower rate of uptake. Relative to unloaded discs, low rate loading caused a maximum increase in transport into the nucleus of 16.8% after 5 minutes of loading. Low rate loading increased the concentration of gadodiamide in the cartilage endplates at each time point compared with unloaded levels. Results from this study indicate that forced convection accelerated small molecule uptake and clearance in the disc induced by low rate mechanical loading. Low rate loading may, therefore, be therapeutic to the disc as it may enhance the nutrient uptake and waste product clearance. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of Ergothioneine on Acute Lung Injury and Inflammation in Cytokine Insufflated Rats

PubMed Central

Repine, John E.; Elkins, Nancy D.

2012-01-01

Objective The Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), is a highly-fatal, diffuse non-cardiogenic edematous lung disorder. The pathogenesis of ARDS is unknown but lung inflammation and lung oxidative stress are likely contributing factors. Since no specific pharmacologic intervention exists for ARDS, our objective was to determine the effect of treatment with ergothioneine---a safe agent with multiple anti-inflammatory and antioxidant properties on the development of lung injury and inflammation in rats insufflated with cytokines found in lung lavages of ARDS patients. Method Sprague-Dawley rats (3-10/group) were given 15 mg/kg or 150 mg/kg L-ergothioneine intravenously 1 hour before or 18 hours after cytokine (IL-1 and IFNγ) insufflation. Lung injury (lavage LDH levels) and lung inflammation (lavage neutrophil numbers) were measured 24 hours after cytokine insufflation. Results Ergothioneine pre- and post- treatment generally decreased lung injury and lung inflammation in cytokine insufflated rats. Conclusion Ergothioneine should be considered for additional testing as a potential therapy for treating and preventing ARDS. PMID:22197759

Significant suppression of myocardial (18)F-fluorodeoxyglucose uptake using 24-h carbohydrate restriction and a low-carbohydrate, high-fat diet.

PubMed

Kobayashi, Yasuhiro; Kumita, Shin-ichiro; Fukushima, Yoshimitsu; Ishihara, Keiichi; Suda, Masaya; Sakurai, Minoru

2013-11-01

(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a useful tool for evaluating inflammation. Because, myocardial-FDG uptake occurs with diverse physiology, it should be suppressed during evaluation of myocardial inflammation by FDG-PET/CT. Diets inducing fat-based metabolism, such as a low-carbohydrate, high-fat diet (LCHF), are used in uptake-suppression protocols. However, a complete suppression of myocardial-FDG uptake has not been established. Hence, we assessed the efficacy of 24-h carbohydrate restriction along with an LCHF diet compared to that of the conventional protocol in suppressing myocardial-FDG uptake and also compared fat and glucose metabolism between these protocols. Fourteen healthy volunteers agreed to undergo >24-h carbohydrate restriction (glucose, <10g) and drank an LCHF beverage an hour before FDG administration. A scan performed under conventional fasting protocol served as the control. The maximal standardized uptake values (SUVmax) of the left ventricular (LV) myocardium, and left atrium lumen (blood pool), liver, and lung fields as background, were measured. Blood sugar, free fatty acids (FFAs), insulin, and triglyceride concentrations were measured just before FDG injection and compared between the 2 protocols. Global LV myocardial uptake was significantly lower with the diet-preparation protocol (SUVmax 1.31 [1.15-1.49] vs. 2.98 [1.76-6.43], p=0.001). Target-to-background ratios [myocardium-to-blood ratio (MBR), myocardium-to-lung ratio (MLR), and myocardium-to-liver ratio (MLvR)] were also significantly lower with the diet-preparation protocol [MBR: 0.75 (0.68-0.84) vs. 1.63 (0.98-4.09), p<0.001; MLR: 1.87 (1.53-2.47) vs. 4.54 (2.53-12.78), p=0.004; MLvR: 0.48 (0.44-0.56) vs. 1.11 (0.63-2.32), p=0.002]. Only insulin levels were significantly different between the subjects in each protocol group (11.3 [6.2-15.1] vs. 3.9 [2.9-6.2]). Carbohydrate restriction together with an LCHF supplement administered 1h before FDG significantly suppressed myocardial-FDG uptake. FFAs and insulin might not directly affect myocardial-FDG uptake. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Mechanically triggered solute uptake in soft contact lenses.

PubMed

Tavazzi, Silvia; Ferraro, Lorenzo; Fagnola, Matteo; Cozza, Federica; Farris, Stefano; Bonetti, Simone; Simonutti, Roberto; Borghesi, Alessandro

2015-06-01

Molecular arrangement plays a role in the diffusion of water and solutes across soft contact lenses. In particular, the uptake of solutes in hydrated contact lenses can occur as long as free water is available for diffusion. In this work, we investigated the effect of mechanical vibrations of low frequency (200 Hz) on the solute uptake. Hyaluronan, a polysaccharide of ophthalmic use, was taken as example of solute of interest. For a specific water-hydrated hydrogel material, differential scanning calorimetry experiments showed that a large fraction of the hydration water accounted for loosely-bound water, both before and after one week of daily-wear of the lenses. The size (of the order of magnitude of few hundreds of nanometers) of hyaluronan in aqueous solution was found to be less than the size of the pores of the lens observed by scanning electron microscopy. However, solute uptake in already-hydrated lenses was negligible by simple immersion, while a significant increase occurred under mechanical vibrations of 200 Hz, thus providing experimental evidence of mechanically triggered enhanced solute uptake, which is attributed to the release of interfacial loosely-bound water. Also other materials were taken into consideration. However, the effectiveness of mechanical vibrations for hyaluronan uptake is restricted to lenses containing interfacial loosely-bound water. Indeed, loosely-bound water is expected to be bound to the polymer with bonding energies of the order of magnitude of 10-100 J/g, which are compatible with the energy input supplied by the vibrations. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessing trace element diffusion models in fossil and sub-fossil bone

NASA Astrophysics Data System (ADS)

Suarez, C. A.; Kohn, M. J.

2012-12-01

Three different diffusion models have been proposed to explain trace element uptake during fossilization of bone: diffusion-adsorption (DA), diffusion-recrystallization (DR), and double-medium diffusion (DMD). Theoretically, differences in trace element profiles, particularly the rare earth elements (REE) and U, can discriminate among these possibilities. In this study, we tested which model best explains natural samples by analyzing trace element profiles in natural bone using laser-ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS). Fossil bones ranging in age from a few ka to over 100 Ma were analyzed along traverses from the outer cortical edge to the inner marrow cavity margin. Forty major, minor and trace elements were analyzed, notably Ca, P, transition metals, Sr, Ba, REE, U, Th and Pb. Spatial and analytical resolutions were ~10 μm and ~100 ppb respectively. Many specimens show commonly observed exponential decreases in REE from the outer edge and marrow cavity, with relatively homogeneous U distributions. Yet, most significantly, specimens from American Falls (last interglacial) and Duck Point (last glacial maximum) show distinctive U plateaus adjacent to the outer and inner cortical bone margins. Whereas exponential profiles can be produced by different uptake processes, such plateaus are diagnostic of a DR mechanism. Our work is consistent with recent investigation of trace element diffusivities in modern fresh and deproteinated bone. These studies show similar diffusion rates for REE and U, so the profound disparity in U vs. REE profiles in most fossils cannot result solely from differences in volume diffusion within the context of DA and DMD. Rather, as a recrystallization front propagates into bone, the bone appears to encode changing soil water compositions with earlier vs. later compositions reflected in the bone margin vs. interior. Soil water U concentrations apparently remain nearly fixed during fossilization, whereas REE are rapidly stripped from the surrounding matrix, leading to nearly homogeneous U vs. steep REE profiles. However in our Pleistocene bones (American Falls and Duck Point), changes to U concentrations on the bone margin reveal more complex changes to boundary compositions, and eliminate both DA and DMD (alone) as the dominant mechanisms of trace element uptake. Our work reconciles disparate zoning patterns observed in fossil bone, and simplifies interpretations of soil or sediment water chemistry, but complicates U-series dating of fossils.

Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

PubMed Central

Kumari, Mandavi; Sachar, Sumedha; Saxena, Rajiv K.

2012-01-01

Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells. PMID:22384094

Spontaneous pneumothorax in diffuse cystic lung diseases.

PubMed

Cooley, Joseph; Lee, Yun Chor Gary; Gupta, Nishant

2017-07-01

Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders with varying pathophysiologic mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In this article, we review the epidemiology, clinical features, and management DCLD-associated spontaneous pneumothorax, with a focus on lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, and pulmonary Langerhans cell histiocytosis. DCLDs are responsible for approximately 10% of apparent primary spontaneous pneumothoraces. Computed tomography screening for DCLDs (Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis) following the first spontaneous pneumothorax has recently been shown to be cost-effective and can help facilitate early diagnosis of the underlying disorders. Patients with DCLD-associated spontaneous pneumothorax have a very high rate of recurrence, and thus pleurodesis should be considered following the first episode of spontaneous pneumothorax in these patients, rather than waiting for a recurrent episode. Prior pleurodesis is not a contraindication to future lung transplant. Although DCLDs are uncommon, spontaneous pneumothorax is often the sentinel event that provides an opportunity for diagnosis. By understanding the burden and implications of pneumothoraces in DCLDs, clinicians can facilitate early diagnosis and appropriate management of the underlying disorders.

Helium-3 MR q-space imaging with radial acquisition and iterative highly constrained back-projection.

PubMed

O'Halloran, Rafael L; Holmes, James H; Wu, Yu-Chien; Alexander, Andrew; Fain, Sean B

2010-01-01

An undersampled diffusion-weighted stack-of-stars acquisition is combined with iterative highly constrained back-projection to perform hyperpolarized helium-3 MR q-space imaging with combined regional correction of radiofrequency- and T1-related signal loss in a single breath-held scan. The technique is tested in computer simulations and phantom experiments and demonstrated in a healthy human volunteer with whole-lung coverage in a 13-sec breath-hold. Measures of lung microstructure at three different lung volumes are evaluated using inhaled gas volumes of 500 mL, 1000 mL, and 1500 mL to demonstrate feasibility. Phantom results demonstrate that the proposed technique is in agreement with theoretical values, as well as with a fully sampled two-dimensional Cartesian acquisition. Results from the volunteer study demonstrate that the root mean squared diffusion distance increased significantly from the 500-mL volume to the 1000-mL volume. This technique represents the first demonstration of a spatially resolved hyperpolarized helium-3 q-space imaging technique and shows promise for microstructural evaluation of lung disease in three dimensions. Copyright (c) 2009 Wiley-Liss, Inc.

Uptake of VOC by sunflower

NASA Astrophysics Data System (ADS)

Folkers, A.; Miebach, M.; Kleist, E.; Wildt, J.

2003-04-01

To study potential VOC uptake by plants we exposed sunflower (Helianthus annuus) to different VOC in continuously stirred tank reactors. For many VOC like methanol, ethanol, acetone, methylvinylketone, isoprene or limonene no uptake was detectable within the accuracy of our analytic set up. Other VOC like hexanal, octanal, (E)-3-hexenol and nopinone were taken up by sunflower. The uptake was related to stomatal aperture. Obviously, these VOC enter the plants through stomata. In case of hexanal, octanal, and (E)-3-hexenol the uptake was only limited by stomatal aperture implying that these VOC are rapidly metabolised. For nopinone the uptake seems to be limited by a slow metabolization. Estimations of deposition velocities showed that dry deposition of these compounds cannot be neglected as sink if diffusion through stomata is the limiting step for dry deposition. In such cases the lifetime with respect to dry deposiotion is comparable to the lifetime with respect to oxidation by hydroxyl radicals.

Pulmonary ventilation-perfusion mismatch: a novel hypothesis for how diving vertebrates may avoid the bends.

PubMed

Garcia Párraga, Daniel; Moore, Michael; Fahlman, Andreas

2018-04-25

Hydrostatic lung compression in diving marine mammals, with collapsing alveoli blocking gas exchange at depth, has been the main theoretical basis for limiting N 2 uptake and avoiding gas emboli (GE) as they ascend. However, studies of beached and bycaught cetaceans and sea turtles imply that air-breathing marine vertebrates may, under unusual circumstances, develop GE that result in decompression sickness (DCS) symptoms. Theoretical modelling of tissue and blood gas dynamics of breath-hold divers suggests that changes in perfusion and blood flow distribution may also play a significant role. The results from the modelling work suggest that our current understanding of diving physiology in many species is poor, as the models predict blood and tissue N 2 levels that would result in severe DCS symptoms (chokes, paralysis and death) in a large fraction of natural dive profiles. In this review, we combine published results from marine mammals and turtles to propose alternative mechanisms for how marine vertebrates control gas exchange in the lung, through management of the pulmonary distribution of alveolar ventilation ([Formula: see text]) and cardiac output/lung perfusion ([Formula: see text]), varying the level of [Formula: see text] in different regions of the lung. Man-made disturbances, causing stress, could alter the [Formula: see text] mismatch level in the lung, resulting in an abnormally elevated uptake of N 2 , increasing the risk for GE. Our hypothesis provides avenues for new areas of research, offers an explanation for how sonar exposure may alter physiology causing GE and provides a new mechanism for how air-breathing marine vertebrates usually avoid the diving-related problems observed in human divers. © 2018 The Authors.

The cell line NCl-H441 is a useful in vitro model for transport studies of human distal lung epithelial barrier.

PubMed

Salomon, Johanna J; Muchitsch, Viktoria E; Gausterer, Julia C; Schwagerus, Elena; Huwer, Hanno; Daum, Nicole; Lehr, Claus-Michael; Ehrhardt, Carsten

2014-03-03

The lack of a well characterized, continuously growing in vitro model of human distal lung epithelial phenotype constitutes a serious limitation in the area of inhalation biopharmaceutics, particularly in the context of transepithelial transport studies. Here, we investigated if a human lung adenocarcinoma cell line, NCl-H441, has potential to serve as an in vitro model of human distal lung epithelium. The development of barrier properties was studied by immunocytochemistry (ICC) against the junction proteins zonula occludens protein 1 (ZO-1) and E-cadherin and measurement of transepithelial electrical resistance (TEER). Moreover, transport studies with the paracellular marker compounds fluorescein sodium and fluorescein isothiocyanate (FITC)-labeled dextrans of molecular weights ranging from 4 to 70 kDa were carried out. The expression of P-glycoprotein (P-gp; ABCB1) and organic cation transporters (OCT/Ns; SLC22A1-A5) was investigated by ICC and immunoblot. P-gp function was assessed by monolayer release and bidirectional transport studies using rhodamine 123 (Rh123) and the inhibitors verapamil and LY335979. Uptake of 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP(+)) was measured, in order to assess organic cation transporter function in vitro. Furthermore, the inhibitory potential of several organic cations on ASP(+) uptake was studied. NCl-H441 cells, when grown under liquid-covered conditions, formed confluent, electrically tight monolayers with peak TEER values of approximately 1000 Ω·cm(2), after 8-12 days in culture. These monolayers were able to differentiate paracellularly transported substrates according to their molecular weight. Presence of P-gp, OCT1, OCT2, OCT3, OCTN1, and OCTN2 was confirmed by Western blot and ICC and was similar to data from freshly isolated human alveolar epithelial cells in primary culture. Rh123 release from NCI-H441 monolayers was time-dependent and showed low, albeit significant attenuation by both inhibitors. In transport studies, Rh123 exhibited net secretion, which again was inhibitable by bona fide P-gp modulators. The uptake of ASP(+) was time- and temperature-dependent with Km = 881.2 ± 195.3 μM and Vmax = 2.07 ± 0.26 nmol/min/mg protein. TEA, amantadine, quinidine, and verapamil significantly inhibited ASP(+) uptake into NCl-H441 cells, whereas the effect of d- and l-carnitine and ergothioneine, two OCTN substrates, was less pronounced. NCl-H441 cells are the first cell line of human distal lung epithelial origin with the ability to form monolayers with appreciable barrier properties. Moreover, drug transporter expression and activity in NCl-H441 cells was consistent with what has been reported for human alveolar epithelial cells in primary culture.

Maximizing tumour exposure to anti-neuropilin-1 antibody requires saturation of non-tumour tissue antigenic sinks in mice.

PubMed

Bumbaca, Daniela; Xiang, Hong; Boswell, C Andrew; Port, Ruediger E; Stainton, Shannon L; Mundo, Eduardo E; Ulufatu, Sheila; Bagri, Anil; Theil, Frank-Peter; Fielder, Paul J; Khawli, Leslie A; Shen, Ben-Quan

2012-05-01

Neuropilin-1 (NRP1) is a VEGF receptor that is widely expressed in normal tissues and is involved in tumour angiogenesis. MNRP1685A is a rodent and primate cross-binding human monoclonal antibody against NRP1 that exhibits inhibition of tumour growth in NPR1-expressing preclinical models. However, widespread NRP1 expression in normal tissues may affect MNRP1685A tumour uptake. The objective of this study was to assess MNRP1685A biodistribution in tumour-bearing mice to understand the relationships between dose, non-tumour tissue uptake and tumour uptake. Non-tumour-bearing mice were given unlabelled MNRP1685A at 10 mg·kg(-1) . Tumour-bearing mice were given (111) In-labelled MNRP1685A along with increasing amounts of unlabelled antibody. Blood and tissues were collected from all animals to determine drug concentration (unlabelled) or radioactivity level (radiolabelled). Some animals were imaged using single photon emission computed tomography - X-ray computed tomography. MNRP1685A displayed faster serum clearance than pertuzumab, indicating that target binding affected MNRP1685A clearance. I.v. administration of (111) In-labelled MNRP1685A to tumour-bearing mice yielded minimal radioactivity in the plasma and tumour, but high levels in the lungs and liver. Co-administration of unlabelled MNRP1685A with the radiolabelled antibody was able to competitively block lungs and liver radioactivity uptake in a dose-dependent manner while augmenting plasma and tumour radioactivity levels. These results indicate that saturation of non-tumour tissue uptake is required in order to achieve tumour uptake and acceptable exposure to antibody. Utilization of a rodent and primate cross-binding antibody allows for translation of these results to clinical settings. © 2011 Genentech Inc. British Journal of Pharmacology © 2011 The British Pharmacological Society.

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.

BioFVM: an efficient, parallelized diffusive transport solver for 3-D biological simulations

PubMed Central

Ghaffarizadeh, Ahmadreza; Friedman, Samuel H.; Macklin, Paul

2016-01-01

Motivation: Computational models of multicellular systems require solving systems of PDEs for release, uptake, decay and diffusion of multiple substrates in 3D, particularly when incorporating the impact of drugs, growth substrates and signaling factors on cell receptors and subcellular systems biology. Results: We introduce BioFVM, a diffusive transport solver tailored to biological problems. BioFVM can simulate release and uptake of many substrates by cell and bulk sources, diffusion and decay in large 3D domains. It has been parallelized with OpenMP, allowing efficient simulations on desktop workstations or single supercomputer nodes. The code is stable even for large time steps, with linear computational cost scalings. Solutions are first-order accurate in time and second-order accurate in space. The code can be run by itself or as part of a larger simulator. Availability and implementation: BioFVM is written in C ++ with parallelization in OpenMP. It is maintained and available for download at http://BioFVM.MathCancer.org and http://BioFVM.sf.net under the Apache License (v2.0). Contact: paul.macklin@usc.edu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26656933

The effect of aging and cardiorespiratory fitness on the lung diffusing capacity response to exercise in healthy humans.

PubMed

Coffman, Kirsten E; Carlson, Alex R; Miller, Andrew D; Johnson, Bruce D; Taylor, Bryan J

2017-06-01

Aging is associated with deterioration in the structure and function of the pulmonary circulation. We characterized the lung diffusing capacity for carbon monoxide (DL CO ), alveolar-capillary membrane conductance (Dm CO ), and pulmonary-capillary blood volume (Vc) response to discontinuous incremental exercise at 25, 50, 75, and 90% of peak work (W peak ) in four groups: 1 ) Young [27 ± 3 yr, maximal oxygen consumption (V̇o 2max ): 110 ± 18% age predicted]; 2) Young Highly Fit (27 ± 3 yr, V̇o 2max : 147 ± 8% age predicted); 3 ) Old (69 ± 5 yr, V̇o 2max : 116 ± 13% age predicted); and 4 ) Old Highly Fit (65 ± 5 yr, V̇o 2max : 162 ± 18% age predicted). At rest and at 90% W peak , DL CO , Dm CO , and Vc were decreased with age. At 90% W peak , DL CO , Dm CO , and Vc were greater in Old Highly Fit vs. Old adults. The slope of the DL CO -cardiac output (Q̇) relationship from rest to end exercise at 90% W peak was not different between Young, Young Highly Fit, Old, and Old Highly Fit (1.35 vs. 1.44 vs. 1.10 vs. 1.35 ml CO ·mmHg -1 ·liter blood -1 , P = 0.388), with no evidence of a plateau in this relationship during exercise; this was also true for Dm CO -Q̇ and Vc-Q̇. V̇o 2max was positively correlated with 1 ) DL CO , Dm CO , and Vc at rest; and 2 ) the rest to end exercise change in DL CO , Dm CO , and Vc. In conclusion, these data suggest that despite the age-associated deterioration in the structure and function of the pulmonary circulation, expansion of the pulmonary capillary network does not become limited during exercise in healthy individuals regardless of age or cardiorespiratory fitness level. NEW & NOTEWORTHY Healthy aging is a crucial area of research. This article details how differences in age and cardiorespiratory fitness level affect lung diffusing capacity, particularly during high-intensity exercise. We conclude that highly fit older adults do not experience a limit in lung diffusing capacity during high-intensity exercise. Interestingly, however, we found that highly fit older individuals demonstrate greater values of lung diffusing capacity during high-intensity exercise than their less fit age-matched counterparts. Copyright © 2017 the American Physiological Society.

Surgical lung biopsy to diagnose Behcet's vasculitis with adult respiratory distress syndrome.

PubMed

Vydyula, Ravikanth; Allred, Charles; Huartado, Mariana; Mina, Bushra

2014-10-01

A 34-year-old female presented with fever and abdominal pain. Past medical history includes Crohn's and Behcet's disease. Examination revealed multiple skin ulcerations, oral aphthae, and bilateral coarse rales. She developed respiratory distress with diffuse bilateral alveolar infiltrates on chest radiograph requiring intubation. PaO2/FiO2 ratio was 132. The chest computed tomography revealed extensive nodular and patchy ground-glass opacities. Bronchoalveolar lavage demonstrated a predominance of neutrophils. Methylprednisolone 60 mg every 6 h and broad-spectrum antimicrobials were initiated. No infectious etiologies were identified. Surgical lung biopsy demonstrated diffuse alveolar damage (DAD) mixed with lymphocytic and necrotizing vasculitis with multiple small infarcts and thrombi consistent with Behcet's vasculitis. As she improved, steroids were tapered and discharged home on oral cyclophosphamide. Pulmonary involvement in Behcet's is unusual and commonly manifests as pulmonary artery aneurysms, thrombosis, infarction, and hemorrhage. Lung biopsy findings demonstrating DAD are consistent with the clinical diagnosis of adult respiratory distress syndrome. The additional findings of necrotizing vasculitis and infarcts may have led to DAD.

Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

PubMed

Mukhopadhyay, Sanjay; Parambil, Joseph G

2012-10-01

Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

DUODENAL CYTOCHROME B: A NOVEL FERRIREDUCTASE IN AIRWAY EPITHELIAL CELLS

EPA Science Inventory

Catalytically active iron in the lung causes oxidative stress and promotes microbial growth that can be limited by intracellular sequestration of iron within ferritin. Because cellular iron uptake requires membrane ferrireductase activity that in the gut can be provided by duoden...

ACTIVATION OF EGF RECEPTOR IN RATS EXPOSED TO ROFA

EPA Science Inventory

Despite a lack of transferrin, hypotransferrinemic (Hp) mice demonstrate an accumulation of iron in peripheral organs including the lungs. One potential candidate for such transferrin-independent uptake of iron is DMT1, an established transporter of iron. We tested the hypothesis...

Increased vital and total lung capacities in Tibetan compared to Han residents of Lhasa (3,658 m).

PubMed

Droma, T; McCullough, R G; McCullough, R E; Zhuang, J G; Cymerman, A; Sun, S F; Sutton, J R; Moore, L G

1991-11-01

Larger chest dimensions and lung volumes have been reported for Andean high-altitude natives compared with sea-level residents and implicated in raising lung diffusing capacity. Studies conducted in Nepal suggested that lifelong Himalayan residents did not have enlarged chest dimensions. To determine if high-altitude Himalayans (Tibetans) had larger lung volumes than acclimatized newcomers (Han "Chinese"), we studied 38 Tibetan and 43 Han residents of Lhasa, Tibet Autonomous Region, China (elevation 3,658 m) matched for age, height, weight, and smoking history. The Tibetan compared with the Han subjects had a larger total lung capacity [6.80 +/- 0.19 (mean +/- SEM) vs 6.24 +/- 0.18 l BTPS, P less than 0.05], vital capacity (5.00 +/- 0.08 vs 4.51 +/- 0.10 1 BTPS, P less than 0.05), and tended to have a greater residual volume (1.86 +/- 0.12 vs 1.56 +/- 0.09 1 BTPS, P less than 0.06). Chest circumference was greater in the Tibetan than the Han subjects (85 +/- 1 vs 82 +/- 1 cm, P less than 0.05) and correlated with vital capacity in each group as well as in the two groups combined (r = 0.69, P less than 0.05). Han who had migrated to high altitude as children (less than or equal to 5 years old, n = 6) compared to Han adult migrants (greater than or equal to 18 years old, n = 26) were shorter but had similar lung volumes and capacities when normalized for body size. The Tibetans' vital capacity and total lung capacity in relation to body size were similar to values reported previously for lifelong residents of high altitude in South and North America. Thus, Tibetans, like North and South American high-altitude residents, have larger lung volumes. This may be important for raising lung diffusing capacity and preserving arterial oxygen saturation during exercise.

[The respiratory effects of smoking].

PubMed

Peiffer, G; Underner, M; Perriot, J

2018-06-01

A marked increase in the morbidity and mortality of a large number of broncho-pulmonary diseases has been documented in relation to smoking. The influence of tobacco smoking on various respiratory conditions. is discussed: incidence, severity or natural history modification of some respiratory illnesses: obstructive lung diseases (COPD, asthma), lung cancer, bacterial, viral respiratory infections, with the impact of smoking on tuberculosis. Finally, the relationship of tobacco with diffuse interstitial lung disease: protective role of smoking (controversial in sarcoidosis, real in hypersensitivity pneumonitis). The benefits of smoking cessation are described. Copyright © 2018. Published by Elsevier Masson SAS.

Viscous organic aerosol particles in the upper troposphere: diffusivity-controlled water uptake and ice nucleation?

DOE PAGES

Lienhard, D. M.; Huisman, A. J.; Krieger, U. K.; ...

2015-01-01

New measurements of water diffusion in secondary organic aerosol (SOA) material produced by oxidation of α-pinene and in a number of organic/inorganic model mixtures (3-methylbutane-1,2,3-tricarboxylic acid (3-MBTCA), levoglucosan, levoglucosan/NH 4HSO 4, raffinose) are presented. These indicate that water diffusion coefficients are determined by several properties of the aerosol substance and cannot be inferred from the glass transition temperature or bouncing properties. Our results suggest that water diffusion in SOA particles is faster than often assumed and imposes no significant kinetic limitation on water uptake and release at temperatures above 220 K. The fast diffusion of water suggests that heterogeneous icemore » nucleation on a glassy core is very unlikely in these systems. At temperatures below 220 K, model simulations of SOA particles suggest that heterogeneous ice nucleation may occur in the immersion mode on glassy cores which remain embedded in a liquid shell when experiencing fast updraft velocities. The particles absorb significant quantities of water during these updrafts which plasticize their outer layers such that these layers equilibrate readily with the gas phase humidity before the homogeneous ice nucleation threshold is reached. Glass formation is thus unlikely to restrict homogeneous ice nucleation. Only under most extreme conditions near the very high tropical tropopause may the homogeneous ice nucleation rate coefficient be reduced as a consequence of slow condensed-phase water diffusion. Since the differences between the behavior limited or non limited by diffusion are small even at the very high tropical tropopause, condensed-phase water diffusivity is unlikely to have significant consequences on the direct climatic effects of SOA particles under tropospheric conditions.« less

Optimization of CT image reconstruction algorithms for the lung tissue research consortium (LTRC)

NASA Astrophysics Data System (ADS)

McCollough, Cynthia; Zhang, Jie; Bruesewitz, Michael; Bartholmai, Brian

2006-03-01

To create a repository of clinical data, CT images and tissue samples and to more clearly understand the pathogenetic features of pulmonary fibrosis and emphysema, the National Heart, Lung, and Blood Institute (NHLBI) launched a cooperative effort known as the Lung Tissue Resource Consortium (LTRC). The CT images for the LTRC effort must contain accurate CT numbers in order to characterize tissues, and must have high-spatial resolution to show fine anatomic structures. This study was performed to optimize the CT image reconstruction algorithms to achieve these criteria. Quantitative analyses of phantom and clinical images were conducted. The ACR CT accreditation phantom containing five regions of distinct CT attenuations (CT numbers of approximately -1000 HU, -80 HU, 0 HU, 130 HU and 900 HU), and a high-contrast spatial resolution test pattern, was scanned using CT systems from two manufacturers (General Electric (GE) Healthcare and Siemens Medical Solutions). Phantom images were reconstructed using all relevant reconstruction algorithms. Mean CT numbers and image noise (standard deviation) were measured and compared for the five materials. Clinical high-resolution chest CT images acquired on a GE CT system for a patient with diffuse lung disease were reconstructed using BONE and STANDARD algorithms and evaluated by a thoracic radiologist in terms of image quality and disease extent. The clinical BONE images were processed with a 3 x 3 x 3 median filter to simulate a thicker slice reconstructed in smoother algorithms, which have traditionally been proven to provide an accurate estimation of emphysema extent in the lungs. Using a threshold technique, the volume of emphysema (defined as the percentage of lung voxels having a CT number lower than -950 HU) was computed for the STANDARD, BONE, and BONE filtered. The CT numbers measured in the ACR CT Phantom images were accurate for all reconstruction kernels for both manufacturers. As expected, visual evaluation of the spatial resolution bar patterns demonstrated that the BONE (GE) and B46f (Siemens) showed higher spatial resolution compared to the STANDARD (GE) or B30f (Siemens) reconstruction algorithms typically used for routine body CT imaging. Only the sharper images were deemed clinically acceptable for the evaluation of diffuse lung disease (e.g. emphysema). Quantitative analyses of the extent of emphysema in patient data showed the percent volumes above the -950 HU threshold as 9.4% for the BONE reconstruction, 5.9% for the STANDARD reconstruction, and 4.7% for the BONE filtered images. Contrary to the practice of using standard resolution CT images for the quantitation of diffuse lung disease, these data demonstrate that a single sharp reconstruction (BONE/B46f) should be used for both the qualitative and quantitative evaluation of diffuse lung disease. The sharper reconstruction images, which are required for diagnostic interpretation, provide accurate CT numbers over the range of -1000 to +900 HU and preserve the fidelity of small structures in the reconstructed images. A filtered version of the sharper images can be accurately substituted for images reconstructed with smoother kernels for comparison to previously published results.

Lung volumes: measurement, clinical use, and coding.

PubMed

Flesch, Judd D; Dine, C Jessica

2012-08-01

Measurement of lung volumes is an integral part of complete pulmonary function testing. Some lung volumes can be measured during spirometry; however, measurement of the residual volume (RV), functional residual capacity (FRC), and total lung capacity (TLC) requires special techniques. FRC is typically measured by one of three methods. Body plethysmography uses Boyle's Law to determine lung volumes, whereas inert gas dilution and nitrogen washout use dilution properties of gases. After determination of FRC, expiratory reserve volume and inspiratory vital capacity are measured, which allows the calculation of the RV and TLC. Lung volumes are commonly used for the diagnosis of restriction. In obstructive lung disease, they are used to assess for hyperinflation. Changes in lung volumes can also be seen in a number of other clinical conditions. Reimbursement for measurement of lung volumes requires knowledge of current procedural terminology (CPT) codes, relevant indications, and an appropriate level of physician supervision. Because of recent efforts to eliminate payment inefficiencies, the 10 previous CPT codes for lung volumes, airway resistance, and diffusing capacity have been bundled into four new CPT codes.

Folic acid-CdTe quantum dot conjugates and their applications for cancer cell targeting

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

Suriamoorthy, Preethi; Zhang, Xing; Hao, Guiyang

2010-12-01

In this study, we report the preparation,luminescence, and targeting properties of folic acid- CdTe quantum dot conjugates. Water-soluble CdTe quantum dots were synthesized and conjugated with folic acid using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide chemistry. The in-fluence of folic acid on the luminescence properties of CdTe quantum dots was investigated, and no energy transfer between them was observed. To investigate the efficiency of folic acid-CdTe nanoconjugates for tumor targeting, pure CdTe quantum dots and folic acid-coated CdTe quantum dots were incubated with human naso- pharyngeal epidermal carcinoma cell line with positive expressing folic acid receptors (KB cells) and lung cancer cells without expressionmore » of folic acid receptors (A549 cells). For the cancer cells with positive folate receptors (KB cells), the uptake for CdTe quantum dots is very low, but for folic acid-CdTe nanoconjugates, the uptake is very high. For the lung cancer cells without folate receptors (A549 cells), the uptake for folic acid- CdTe nanoconjugates is also very low. The results indicate that folic acid is an effective targeting molecule for tumor cells with overexpressed folate receptors.« less

Modeling of photon migration in the human lung using a finite volume solver

NASA Astrophysics Data System (ADS)

Sikorski, Zbigniew; Furmanczyk, Michal; Przekwas, Andrzej J.

2006-02-01

The application of the frequency domain and steady-state diffusive optical spectroscopy (DOS) and steady-state near infrared spectroscopy (NIRS) to diagnosis of the human lung injury challenges many elements of these techniques. These include the DOS/NIRS instrument performance and accurate models of light transport in heterogeneous thorax tissue. The thorax tissue not only consists of different media (e.g. chest wall with ribs, lungs) but its optical properties also vary with time due to respiration and changes in thorax geometry with contusion (e.g. pneumothorax or hemothorax). This paper presents a finite volume solver developed to model photon migration in the diffusion approximation in heterogeneous complex 3D tissues. The code applies boundary conditions that account for Fresnel reflections. We propose an effective diffusion coefficient for the void volumes (pneumothorax) based on the assumption of the Lambertian diffusion of photons entering the pleural cavity and accounting for the local pleural cavity thickness. The code has been validated using the MCML Monte Carlo code as a benchmark. The code environment enables a semi-automatic preparation of 3D computational geometry from medical images and its rapid automatic meshing. We present the application of the code to analysis/optimization of the hybrid DOS/NIRS/ultrasound technique in which ultrasound provides data on the localization of thorax tissue boundaries. The code effectiveness (3D complex case computation takes 1 second) enables its use to quantitatively relate detected light signal to absorption and reduced scattering coefficients that are indicators of the pulmonary physiologic state (hemoglobin concentration and oxygenation).

Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias.

PubMed

Barisione, Giovanni; Brusasco, Claudia; Garlaschi, Alessandro; Baroffio, Michele; Brusasco, Vito

2016-05-01

Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO. Copyright © 2016 the American Physiological Society.

A model for estimating air-pollutant uptake by forests: calculation of absorption of sulfur dioxide from dispersed sources

Treesearch

C. E., Jr. Murphy; T. R. Sinclair; K. R. Knoerr

1977-01-01

The computer model presented in this paper is designed to estimate the uptake of air pollutants by forests. The model utilizes submodels to describe atmospheric diffusion immediately above and within the canopy, and into the sink areas within or on the trees. The program implementing the model is general and can be used with only minor changes for any gaseous pollutant...

Cognitive and brain structural changes in a lung cancer population.

PubMed

Simó, Marta; Root, James C; Vaquero, Lucía; Ripollés, Pablo; Jové, Josep; Ahles, Tim; Navarro, Arturo; Cardenal, Felipe; Bruna, Jordi; Rodríguez-Fornells, Antoni

2015-01-01

No study has examined structural brain changes specifically associated with chemotherapy in a lung cancer population. The aim of this cross-sectional study was to assess differences in brain structure between small-cell lung cancer patients (C+) following chemotherapy, non-small-cell lung cancer patients (C-) before chemotherapy and healthy controls (HC). Twenty-eight small-cell lung cancer patients underwent a neuropsychological assessment and a structural magnetic resonance imaging, including T1-weighted and diffusion tensor imaging to examine gray matter density and white matter (WM) integrity, respectively, 1 month following completion of platinum-based chemotherapy. This group was compared with 20 age and education-matched non-small-cell lung cancer patients before receiving chemotherapy and 20 HC. Both C+ and C- groups exhibited cognitive impairment compared with the HC group. The C+ group performed significantly worse than HC in verbal fluency and visuospatial subtests; C- performed significantly worse than both C+ and HC in verbal memory. Voxel-based morphometry analysis revealed lower gray matter density in the insula and parahippocampal gyrus bilaterally, and left anterior cingulate cortex in C+ compared with HC. Diffusion tensor imaging indices showed focal decreased WM integrity in left cingulum and bilateral inferior longitudinal fasciculus in the C+ group and more widespread decreased integrity in the C- group compared with the HC group. This study demonstrates that lung cancer patients exhibit cognitive impairment before and after chemotherapy. Before the treatment, C- showed verbal memory deficits as well as a widespread WM damage. Following treatment, the C+ group performed exhibited lower visuospatial and verbal fluency abilities, together with structural gray matter and WM differences in bilateral regions integrating the paralimbic system.

Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

2007-09-01

Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

[Combined pulmonary fibrosis and emphysema (CPFE)--limitation of usual lung function test and challenge at practice].

PubMed

Takai, Daiya

2014-12-01

Spirometry and the flow-volume curve test are commonly performed lung function tests. However, a unique clinical entity occasionally shows almost normal data in these tests, and is therefore missed on screening tests. The clinical entity of combined pulmonary emphysema and pulmdoary fibrosis was recognized and documented in the 90's in Japan, the USA, and Europe. Typical emphysema shows obstructive disorders, and pulmonary fibrosis shows restrictive disorders. Thus, the combination of both should lead to a combined disorder pattern in lung function tests, but this is not the case. In 2005, Cottin reported and redefined this combination of emphysema and fibrosis of the lung as "Combined Pulmonary Fibrosis and Emphysema" (CPFE). The patients are typically heavily smoking males who show an almost normal lung function. The upper lobe of these patients usually shows severe emphysema, which contributes to a static volume and a late phase in the forced volume test. On the other hand their lower lobe shows fibrotic change. The fibrotic portion contributes to early phase flow in the flow-volume curve. These mechanisms are a reason for the normal pattern appearance in lung function tests in CPFE patients. As a matter of course, these patients have damaged upper and lower lobes: their diffusing capacity of the lung shows a low performance, their saturation of blood hemoglobin decreases soon after light exercise, and their KL-6 (a blood marker of pulmonary fibrosis) usually shows a high value. They are considered a high risk group regarding complications of post-surgical treatment. Thus, when medical technologists identify suspicious cases, they should advise doctors to add diffusing capacity and KL-6 tests. (Review).

Diverse bone scan abnormalitites in "shin splints".

PubMed

Spencer, R P; Levinson, E D; Baldwin, R D; Sziklas, J J; Witek, J T; Rosenberg, R

1979-12-01

Four young patients who presented with pain over the anterior compartment of the legs, gave a recent athletic history suggesting stress fractures. Although radiographs were initially normal in all four cases, the bone scintigrams were positive. The individual findings, however, were quite different. In one there was a single focal area of increased radioactivity in each of the tibias; the second patient had uneven uptake of radiotracer and several foci of accumulation in the fibulas; the third showed diffuse linear tibial uptake suggesting periosteal lesions; and the fourth case revealed uptake in the lateral malleolus and in bones of the foot.

Advance care planning uptake among patients with severe lung disease: a randomised patient preference trial of a nurse-led, facilitated advance care planning intervention.

PubMed

Sinclair, Craig; Auret, Kirsten Anne; Evans, Sharon Frances; Williamson, Fiona; Dormer, Siobhan; Wilkinson, Anne; Greeve, Kim; Koay, Audrey; Price, Dot; Brims, Fraser

2017-02-24

Advance care planning (ACP) clarifies goals for future care if a patient becomes unable to communicate their own preferences. However, ACP uptake is low, with discussions often occurring late. This study assessed whether a systematic nurse-led ACP intervention increases ACP in patients with advanced respiratory disease. A multicentre open-label randomised controlled trial with preference arm. Metropolitan teaching hospital and a rural healthcare network. 149 participants with respiratory malignancy, chronic obstructive pulmonary disease or interstitial lung disease. Nurse facilitators offered facilitated ACP discussions, prompted further discussions with doctors and loved ones, and assisted participants to appoint a substitute medical decision-maker (SDM) and complete an advance directive (AD). The primary measure was formal (AD or SDM) or informal (discussion with doctor) ACP uptake assessed by self-report (6 months) and medical notes audit. Secondary measures were the factors predicting baseline readiness to undertake ACP, and factors predicting postintervention ACP uptake in the intervention arm. At 6 months, formal ACP uptake was significantly higher (p<0.001) in the intervention arm (54/106, 51%), compared with usual care (6/43, 14%). ACP discussions with doctors were also significantly higher (p<0.005) in the intervention arm (76/106, 72%) compared with usual care (20/43, 47%). Those with a strong preference for the intervention were more likely to complete formal ACP documents than those randomly allocated. Increased symptom burden and preference for the intervention predicted later ACP uptake. Social support was positively associated with ACP discussion with loved ones, but negatively associated with discussion with doctors. Nurse-led facilitated ACP is acceptable to patients with advanced respiratory disease and effective in increasing ACP discussions and completion of formal documents. Awareness of symptom burden, readiness to engage in ACP and relevant psychosocial factors may facilitate effective tailoring of ACP interventions and achieve greater uptake. ACTRN12614000255684. 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/.

Herniated Thoracic Spleen Mimicking Lung Metastasis on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT in a Patient With Prostate Cancer.

PubMed

Malik, Dharmender; Basher, Rajender K; Sood, Apurva; Devana, Sudheer Kumar; Bhattacharya, Anish; Mittal, Bhagwant Rai

2017-06-01

We report a case of clinically asymptomatic patient of prostate cancer who was previously subjected to radical prostatectomy presenting with a rising serum prostate-specific antigen level of 6.6 ng/mL. Whole-body PET/CT with Ga-labeled prostate-specific membrane antigen ligand was performed to assess for disease recurrence, which revealed an intense tracer uptake in a soft tissue mass in left hemithorax mimicking lung metastasis; which later turned out to be splenic tissue.

[Henoch-Schönlein Purpura with lung abscess].

PubMed

Nakazawa, Junji; Watanabe, Atsushi; Nakajima, Tomohiro; Mishina, Taijiro; Miyajima, Masahiro; Higami, Tetsuya

2013-09-01

A 72-year-old man had underwent left lower lobectomy for squamous cell carcinoma in our hospital in 2008. Postoperative stage was I A (T1N0M0). In 2010, follow-up chest computed tomography (CT) images showed similar cavitary nodules in segments 2 and 8 of the right lung with positive uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) images. Physical examination, blood tests, and levels of serum tumor markers showed no abnormality. Transbronchial lung biopsy revealed the absence of malignant cells. Segment 8 of the right lower lobe with the nodule was partially resected, and pathological examination demonstrated lung abscess. He was discharged but was hospitalized in another hospital for purpuric rash, fever, and arthralgia. Microscopic albuminuria was noted, and renal biopsy revealed nephritis with immunoglobulin A( IgA)deposition. He was made a diagnosis of Henoch-Schönlein purpura. Oral steroid therapy( prednisolone 60 mg/d) was initiated, resulting in the improvement of symptoms and disapearance of the cavitary nodule in the right lung segment 2.

Bilateral pneumothorax, lung cavitations, and pleural empyema in a cocaine addict.

PubMed

Solaini, Leonardo; Solini, Leonardo; Gourgiotis, Stavros; Salemis, Nikolaos S; Koukis, Ioannis

2008-12-01

A case of bilateral pneumothorax, lung cavitations, and pleural empyema in a cocaine user is described. The patient was treated by left tube thoracostomy and right lower lobectomy. The postoperative course was uneventful. Six months later, the patient remains asymptomatic. The pathology examination of the specimen revealed infected bronchiectasis, interstitial desquamative pneumonia, diffuse alveolar damage, subsegmental arterial thrombosis, and consequent areas of pulmonary infarction.

Mechanism of uptake of nitrosoureas by L5178Y lymphoblasts in vitro.

PubMed

Begleiter, A; Lam, H P; Goldenberg, G J

1977-04-01

The mechanism of uptake of nitrosoureas by L5178Y cells in vitro was investigated. A time course of the uptake of radioactivity on incubation of L5178Y lymphoblast with [14C]-1,3-bis(2-chloroethyl)-1-nitrosourea was linear for 30 min and then entered a plateau phase; it was markedly temperature dependent. A similar time course for cells incubated with [14C]ethylene-labeled 1-(2-chlorethyl)-3-cyclohexyl-1-nitrosourea reached equilibrium rapidly, was temperature independent, and resulted in a relatively low level of uptake of radioactivity. However, cells treated with 3-[cyclohexyl-14C]-1-(2-chlorethyl)-1-nitrosourea had a time course that was linear for 30 min, resulted in much higher levels of uptake of radioactivity, and was strongly temperature dependent. These findings, at least for 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, suggest that some drug decomposition precedes uptake. The percentage of radioactivity found in the cell sap fraction was at least 85% of total cell activity when cells were incubated with any of the three 14C-labeled nitrosoureas. Furthermore, thin-layer chromatography of the cell sap fraction revealed the presence of free intact drug. These findings indicate that intracellular uptake of intact nitrosoureas occurred. A time course of uptake of intact 1,3-bis(2-chloroethyl)-1-nitrosourea reached equilibrium rapidly with cell/medium distribution ratios of 0.2 to 0.6 and was temperature independent. The addition of excess unlabeled 1,3-bis(2-chlorethyl)-1-nitrosourea or 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea had no effect on uptake of [14C]-1,3-bis(2-chloroethyl)-1-nitrosourea, These findings suggest that uptake of intact 1,3-bis(2-chloroethyl)-1-nitrosourea was by passive diffusion. A time course of the uptake of intact 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea with either [14C]ethylene- or ring-labeled drug rapidly reached equilibrium, was temperature independent, and attained a cell/medium ratio greater than unity. Uptake of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was sodium independent and was unaffected by the metabolic inhibitors (sodium fluoride, sodium cyanide, or 2,4-dinitrophenol) or by urea, a potential physiological competitor. Furthermore, addition of unlabeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea or 1,3-bis(2-chlorethyl)-1-nitrosourea had no effect on uptake of labeled 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. These findings suggest that uptake of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea also occurs by passive diffusion.

SUPEROXIDE-DEPENDENT IRON UPTAKE: A NEW ROLE FOR ANION EXCHANGE PROTEIN 2

EPA Science Inventory

Lung cells import iron across the plasma membrane as ferrous (Fe2+) ion by incompletely understood mechanisms. We tested the hypothesis that human bronchial epithelial (HBE) cells import non-transferrin-bound iron (NTBI) using superoxide-dependent ferri-reductase activity involvi...

Macrophages phagocytose nonopsonized silica particles using a unique microtubule-dependent pathway

PubMed Central

Gilberti, Renée M.; Knecht, David A.

2015-01-01

Silica inhalation leads to the development of the chronic lung disease silicosis. Macrophages are killed by uptake of nonopsonized silica particles, and this is believed to play a critical role in the etiology of silicosis. However, the mechanism of nonopsonized-particle uptake is not well understood. We compared the molecular events associated with nonopsonized- and opsonized-particle phagocytosis. Both Rac and RhoA GTPases are activated upon nonopsonized-particle exposure, whereas opsonized particles activate either Rac or RhoA. All types of particles quickly generate a PI(3,4,5)P3 and F-actin response at the particle attachment site. After formation of a phagosome, the events related to endolysosome-to-phagosome fusion do not significantly differ between the pathways. Inhibitors of tyrosine kinases, actin polymerization, and the phosphatidylinositol cascade prevent opsonized- and nonopsonized-particle uptake similarly. Inhibition of silica particle uptake prevents silica-induced cell death. Microtubule depolymerization abolished uptake of complement-opsonized and nonopsonized particles but not Ab-opsonized particles. Of interest, regrowth of microtubules allowed uptake of new nonopsonized particles but not ones bound to cells in the absence of microtubules. Although complement-mediated uptake requires macrophages to be PMA-primed, untreated cells phagocytose nonopsonized silica and latex. Thus it appears that nonopsonized-particle uptake is accomplished by a pathway with unique characteristics. PMID:25428990

Biodistribution of a positron-emitting suicide inactivator of monoamine oxidase, carbon-11 pargyline, in mice and a rabbit

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

Ishiwata, K.; Ido, T.; Yanai, K.

Carbon-11 (/sup 11/C) pargyline, which is a suicide inactivator of Type B monoamine oxidase (MAO), was synthesized by the reaction of N-demethylpargyline with /sup 11/CH/sub 3/l. Biodistribution was investigated in mice, and positron tomographic images of the heart and lung in a rabbit were obtained. The distribution of /sup 11/C after administration of (/sup 11/C)pargyline was measured in several organs and blood at various time intervals. After 30 min its concentrations in the organs were constant. Subcellular distribution studies in the brain, lung, liver, and kidney showed that 59-70% of the /sup 11/C became acid-insoluble and 9-33% was present inmore » the crude mitochondrial fraction at 60 min after injection. The uptakes of the /sup 11/C in each organ except for the kidney and spleen seemed to correlate with the in vitro enzymatic activity of Type B MAO. At high loading dose a nonspecific uptake was observed.« less

[Lung diffusion capacity and quality of life 6 months after discharge from the ICU among survivors of acute respiratory distress syndrome due to influenza A H1N1].

PubMed

Quispe-Laime, A M; Fiore, C; González-Ros, M N; Bettini, J E; Rolfo, V E; Campagne, C G; Barberio, P A

2012-01-01

An evaluation is made of lung function and quality of life 6 months after discharge from the Intensive Care Unit (ICU) among survivors of acute respiratory distress syndrome (ARDS) due to pandemic 2009 influenza A H1N1, based on studies of lung function and the EQ-5D health questionnaire. Case series. The ICU of Dr. Leónidas Lucero Acute Cases Municipal Hospital, Bahía Blanca, Argentina. PATIENTS discharged from the ICU who had been admitted with ARDS in 2009 due to influenza A H1N1. Eleven patients were studied. Seven were positive for influenza H1N1 and four were negative. The mean age was 37±9.5 years, and 73% were males. Quality of life, as measured by the EQ-5D, showed changes in the 5 components in all patients, particularly in the pain/discomfort dimension 1.55±0.52; health status (EQ%health) was 70%±24. The indices adjusted for Argentina were Time Trade Off (TTO) 0.903±0.085 and Visual Analog Scale (VAS) 0.827±0.153. In all patients, spirometry and the study of pulmonary diffusion (DLCO) showed values of >80%. There was no correlation between lung diffusion and quality of life (%DLCO and EQ%health). A correlation was observed between quality of life and TTO (EQ%health and TTO), and between quality of life and the VAS score (EQ%health and VAS). Although the sample is small, our results suggest that patients with ARDS due to influenza A H1N1 evaluated 6 months after discharge from the ICU show no deterioration of lung function, and the impact on quality of life is moderate-in contrast to the situation found in patients with ARDS of other etiologies. Copyright © 2011 Elsevier España, S.L. and SEMICYUC. All rights reserved.

[Phylogeny of gas exchange systems].

PubMed

Jürgens, K D; Gros, G

2002-04-01

Several systems of gas transport have developed during evolution, all of which are able to sufficiently supply oxygen to the tissues and eliminate the CO2 produced by the metabolism, in spite of great distances between the environment and the individual cells of the tissues. Almost all these systems utilize a combination of convection and diffusion steps. Convection achieves an efficient transport of gas over large distances, but requires energy and cannot occur across tissue barriers. Diffusion, on the other hand, achieves gas transport across barriers, but requires optimization of diffusion paths and diffusion areas. When two convectional gas flows are linked via a diffusional barrier (gas/fluid in the case of the avian lung, fluid/fluid in the case of gills), the directions in which the respective convectional movements pass each other are important determinants of gas exchange efficiency (concurrent, countercurrent and cross-current systems). The tracheal respiration found in insects has the advantage of circumventing the convective gas transport step in the blood, thereby avoiding the high energy expenditure of circulatory systems. This is made possible by a system of tracheae, ending in tracheoles, that reaches from the body surface to every cell within the body. The last step of gas transfer in these animals occurs by diffusion from the tracheoles ("air capillaries") to the mitochondria of cells. The disadvantage is that the tracheal system occupies a substantial fraction of body volume and that, due to limited mechanical stability of tracheal walls, this system would not be able to operate under conditions of high hydrostatic pressures, i. e. in large animals. Respiration in an "open" system, i. e. direct exposure of the diffusional barrier to the environmental air, eliminates the problem of bringing the oxygen to the barrier by convection, as is necessary in the avian and mammalian lung, in the insects' tracheal system and in the gills. An open system is found in the respiration via the skin, which is of significance in some amphibians, but is limited by the thickness of the skin that constitutes a substantial diffusion path for O2 and CO2. The thick skin, on the other hand, provides mechanical protection as well as flexibility for the animals' body and helps avoid massive water loss via the body surface. The gills of fishes, in contrast, exhibit rather short diffusion distances, are located in a mechanically protected space, and the problem of water loss does not exist. The flows of blood and water occur in opposite direction (countercurrent flow) and this situation makes an arterial PO2 approaching the environmental PO2 possible. A major disadvantage is constituted by the environmental medium since water contains little O2 compared to air and, to compensate this, much energy is expended to maintain a high flow rate of water through the gills. In the mammalian lung ("pool system"), the presence of a dead space and the rhythmic ventilation that replaces only a small fraction of the gas volume of the lung per breath, are responsible for an arterial PO2 (2/3 of the atmospheric PO2) that cannot reach the expiratory PO2. However, an advantage of this feature is the constantly high alveolar and arterial PCO2, which provides a highly effective H(+) buffer system in the entire body. The apparent disadvantage of the mammalian lung is avoided by the avian lung, which uses an extended system of airways to establish continuous equilibration of a part of the capillary blood with fresh air (cross current system), during inspiration as well as during expiration. In this system, arterial PO2 can significantly exceed expiratory PO2. A disadvantage here is the enormous amount of space taken up by the avian lung, in animals of 1 kg body weight three times as much as taken up by the mammalian lung. All respiratory exchange systems considered here exhibit high degrees of optimization - yet follow highly diverse construction principles. There is no such thing as an ideal gas exchange system. The system that has evolved in each species depends to an impressive extent on environmental conditions, on body build and size, on the animal's patterns of movement and on its energy consumption.