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Molecular Imaging and Biology Apr 2019Foreign body reactions elicit granulomatous inflammation composed of reactive macrophages. We hypothesized that [I]iodo-DPA-713 single-photon emission computed...
PURPOSE
Foreign body reactions elicit granulomatous inflammation composed of reactive macrophages. We hypothesized that [I]iodo-DPA-713 single-photon emission computed tomography (SPECT), a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by phagocytes, could be used to detect foreign body reactions in a murine model.
PROCEDURES
C57BL/6 mice intratracheally inoculated with dextran beads, which developed foreign body lesions, were imaged after injection of [I]iodo-DPA-713 or DPA-713-IRDye800CW using SPECT and optical imaging, respectively.
RESULTS
Foreign body lesions were clearly observed in the lungs of the dextran-treated mice on computer tomography imaging and demonstrated significantly higher [I]iodo-DPA-713 uptake compared with control animals (p < 0.01). Ex vivo studies demonstrated granulomatous reactions in the lungs of dextran-treated mice and localization of DPA-713-IRDye800CW at the diseased sites confirming the imaging findings.
CONCLUSION
Radioiodinated DPA-713 may be used as a noninvasive biomarker for the detection of pulmonary foreign body reactions.
Topics: Acetamides; Animals; Female; Foreign-Body Reaction; Iodine Radioisotopes; Lung; Mice, Inbred C57BL; Optical Imaging; Pyrazoles; Pyrimidines; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
PubMed: 29987615
DOI: 10.1007/s11307-018-1249-0 -
Particle and Fibre Toxicology Nov 2013Several properties of multi-walled carbon nanotubes (MWCNT) have the potential to affect their bioactivity. This study examined the in vitro and in vivo outcomes of the...
BACKGROUND
Several properties of multi-walled carbon nanotubes (MWCNT) have the potential to affect their bioactivity. This study examined the in vitro and in vivo outcomes of the influence of diameter, length, purification and carboxylation (in vitro testing only) of MWCNT.
METHODS
Three original 'as received' MWCNT that varied in size (diameter and length) were purified and functionalized by carboxylation. The resulting MWCNT were characterized and examined for cytotoxicity and inflammasome activation in vitro using THP-1 cells and primary alveolar macrophages from C57BL/6 mice. Oropharyngeal aspiration administration was used to deliver original MWCNT and in vivo bioactivity and lung retention was examined at 1 and 7 days.
RESULTS
Studies with THP-1 macrophages demonstrated that increased length or diameter corresponded with increased bioactivity as measured by inflammasome activation. Purification had little effect on the original MWCNT, and functionalization completely eliminated bioactivity. Similar results were obtained using alveolar macrophages isolated from C57BL/6 mice. The in vivo studies demonstrated that all three original MWCNT caused similar neutrophil influx at one day, but increasing length or diameter resulted in the lavaged cells to release more inflammatory cytokines (IL-6, TNF-α, and IL-1β) ex vivo. Seven-day histology revealed that, consistent with the in vitro results, increasing width or length of MWCNT caused more severe pathology with the longest MWCNT causing the most severe inflammation. In addition, the same two larger MWCNT were retained more in the lung at 7 days.
CONCLUSIONS
Taken together, the results indicated that in vitro and in vivo bioactivity of MWCNT increased with diameter and length. Purification had no significant modifying effect from the original MWCNT. Functionalization by carboxylation completely eliminated the bioactive potential of the MWCNT regardless of size in in vitro testing.
Topics: Animals; Bronchoalveolar Lavage Fluid; Carrier Proteins; Cell Line; Cytokines; Humans; In Vitro Techniques; Inflammasomes; Inflammation; Lung; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Molecular Weight; NLR Family, Pyrin Domain-Containing 3 Protein; Nanotubes, Carbon
PubMed: 24225053
DOI: 10.1186/1743-8977-10-57 -
Medicine Nov 2019Evaluating the efficacy and safety of low molecular weight heparin (LMWH) for patients with chronic obstructive pulmonary disease (COPD) and respiratory failure (RF) is...
Efficacy of low molecular weight heparin for chronic obstructive pulmonary disease and respiratory failure: A protocol of systematic review of randomized controlled trials.
BACKGROUND
Evaluating the efficacy and safety of low molecular weight heparin (LMWH) for patients with chronic obstructive pulmonary disease (COPD) and respiratory failure (RF) is a major purpose of this study.
METHODS
The following electronic databases will be comprehensively retrieved from the inception to July 1, 2019: Cochrane Library, PUBMED, EMBASE, Google Scholar, Web of Science, Allied and Complementary Medicine Database, WANGFANG, and China National Knowledge Infrastructure without language restrictions. All randomized controlled trials related to LMWH for COPD and RF will be included. Two authors will carry out study selection, data collection, and risk of bias assessment independently.
RESULTS
This study will systematically explore the efficacy and safety of LMWH for COPD and RF. The primary outcome is lung function. The secondary outcomes are severity of dyspnea on exertion, quality of life, body mass index, airflow obstruction; and any expected and unexpected adverse events.
CONCLUSION
The findings of this study will provide evidence to judge whether LMWH is an effective treatment for patients with COPD and RF.
PROSPERO REGISTRATION NUMBER
PROSPERO CRD42019 139631.
Topics: Body Mass Index; Dyspnea; Heparin, Low-Molecular-Weight; Humans; Lung; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Respiratory Insufficiency; Systematic Reviews as Topic; Treatment Outcome
PubMed: 31770219
DOI: 10.1097/MD.0000000000018051 -
Journal of Applied Physiology... May 2020Disorders of the fractality of an airway tree and a vessel tree have been studied in pulmonary diseases. Here we successfully applied Mishima's D to the bronchial...
Disorders of the fractality of an airway tree and a vessel tree have been studied in pulmonary diseases. Here we successfully applied Mishima's D to the bronchial minimal inner cross-sectional area (iCSA) measured in multidetector computed tomography (MDCT) images of chronic obstructive pulmonary disease (COPD) and non-COPD smokers ( = 162), by defining D in the following formula: log(≥) = -D × log + c, where is a certain iCSA value, (≥) is the number of airway branches having iCSA greater than or equal to , and c is a constant. Mathematically, this D of iCSA was associated with the expected reduction ratio of iCSA at bifurcations, which can be estimated by 2. This D of iCSA also correlated weakly with the box-counting fractal dimension and Weibel's reduction ratio over airway generations, which indicated that the airway tree was not a perfect fractal object and that the branch bifurcation was asymmetric. The D of iCSA showed positive correlations with lung function measurements of airflow limitation in study participants. In addition, D of iCSA representing the periphery showed an association with future body mass index reduction, most likely as an indicator of energy efficacy for breathing as predicted by Hess-Murray's law. D of iCSA may be helpful to understanding the pathogenesis of obstructive lung diseases. An airway tree is a fractal object. We showed that the distribution of minimal inner cross-sectional area (iCSA) of airway branches can be expressed by a fractal index, D, of minimal iCSA. This D was correlated with airflow limitation and future body mass index reduction in chronic obstructive pulmonary disease patients, as predicted by Hess-Murray's law.
Topics: Body Mass Index; Bronchi; Fractals; Humans; Lung; Pulmonary Disease, Chronic Obstructive
PubMed: 32240020
DOI: 10.1152/japplphysiol.00461.2019 -
Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus.Carbohydrate Polymers May 2021Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world....
Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world. Although a vaccine has recently been approved, there are currently few effective therapeutics to fight its associated disease in humans, COVID-19. SARS-CoV-2 and the related severe acute respiratory syndrome (SARS-CoV-1), and Middle East respiratory syndrome (MERS-CoV) result from zoonotic respiratory viruses that have bats as the primary host and an as yet unknown secondary host. While each of these viruses has different protein-based cell-surface receptors, each rely on the glycosaminoglycan, heparan sulfate as a co-receptor. In this study we compare, for the first time, differences and similarities in the structure of heparan sulfate in human and bat lungs. Furthermore, we show that the spike glycoprotein of COVID-19 binds 3.5 times stronger to human lung heparan sulfate than bat lung heparan sulfate.
Topics: Animals; Chiroptera; Female; Heparitin Sulfate; Humans; Lung; Male; Molecular Structure; Molecular Weight; Protein Binding; Receptors, Virus; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 33712145
DOI: 10.1016/j.carbpol.2021.117797 -
Saudi Medical Journal Jun 2019Diffuse alveolar hemorrhage is an uncommon and often fatal condition in children that is characterized by distinct histopathological etiologies. Herein, we discuss the...
Diffuse alveolar hemorrhage is an uncommon and often fatal condition in children that is characterized by distinct histopathological etiologies. Herein, we discuss the case of an 11-year-old girl who presented with acute worsening of hypoxia and left-sided chest pain. The patient had lung biopsy-proven idiopathic pulmonary capillaritis and was being treated with prednisolone every alternate day, azathioprine, and hydroxychloroquine. A contrast-computed tomography (CT) scan of the chest showed an acute left lower-lobe pulmonary embolism. Negative results were obtained on a test for thrombophilia. In children, pulmonary embolism with anti-neutrophil cytoplasmic antibody-negative idiopathic pulmonary capillaritis is a rare clinical condition. The exact cause of thrombus formation in this case is unknown; however, obesity, immobility, and chronic systemic corticosteroid therapy probably played a role.
Topics: Acute Disease; Antibodies, Antineutrophil Cytoplasmic; Capillaries; Chest Pain; Child; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hydroxychloroquine; Hypoxia; Lung; Lung Diseases; Mercaptopurine; Prednisolone; Pulmonary Alveoli; Pulmonary Embolism; Treatment Outcome; Vasculitis
PubMed: 31219497
DOI: 10.15537/smj.2019.6.24210 -
International Journal of Clinical and... 2015In infants, pleuropulmonary blastoma is a rare but aggressive tumor. The typical histopathological presentation includes the aggregation of malignant primitive small...
In infants, pleuropulmonary blastoma is a rare but aggressive tumor. The typical histopathological presentation includes the aggregation of malignant primitive small cells, usually observed in sheets. So as to provide proper and timely treatment, the differential diagnosis includes pulmonary blastoma, sarcomatoid mesothelioma, fetal rhabdomyoma, synovial sarcoma, and primitive neuroectodermal tumor. Herein, we will present one male pediatric patient with pleuropulmonary blastoma. The patient was a 4-month-old male infant, who had a prolonged cough and dyspnea for 4 months that was complicated by cyanosis for 3 days. A physical examination revealed a solid mass in the right lung that was sized 9.0 × 6.0 × 4.0 cm and had a grayish-white cross section. The boundary between the mass and lung tissue was clear; the mass already occupied a great portion of the lung. A microscopic examination suggested that the tumor was composed of round or orbicular-ovate primitive fetal cells. The cells were medium sized, having little cytoplasm, but had a clearly visualized nucleolus and active karyokinesis. The tumor mass was biphasic, namely, fasciculated sarcoma (composed of spindle-shaped cells and short spindle-shaped cells) and malignant fibrous histiocytoma containing well-differentiated cartilage islands or cartilaginous nodes. Immunohistochemistry was performed for further detection: vimentin (+), S-100 protein (+), CK (AE1/AE3), EMA and TTF-1 in residual epithelial components (+), NSE (focal +), SMA (mesenchymal cells, focal +), CD99 (weak +), Bcl-2 (weak +), desmin (-), myoglobin (-), calretinin (-), calponin (-), FLI (-), MyoD-1 (-), and CD34 (-). Pleuropulmonary blastoma is extremely rare but highly aggressive neoplasm in children. Its typical histopathological presentation is the aggregation of primitive malignant small cells. Combining imaging and histopathological examinations and clinical data should help in determining the diagnosis of pleural pulmonary blastoma.
Topics: Biomarkers, Tumor; Humans; Infant; Lung; Lung Neoplasms; Male; Pulmonary Blastoma
PubMed: 26722577
DOI: No ID Found -
American Journal of Physiology. Lung... Mar 2000The polyamines putrescine, spermidine (SPD), and spermine are a family of low-molecular-weight organic cations essential for cell growth and differentiation and other...
The polyamines putrescine, spermidine (SPD), and spermine are a family of low-molecular-weight organic cations essential for cell growth and differentiation and other aspects of signal transduction. Hypoxic pulmonary vascular remodeling is accompanied by depressed lung polyamine synthesis and markedly augmented polyamine uptake. Cell types in which hypoxia induces polyamine transport in intact lung have not been delineated. Accordingly, rat lung and rat main pulmonary arterial explants were incubated with [(14)C]SPD in either normoxic (21% O(2)) or hypoxic (2% O(2)) environments for 24 h. Autoradiographic evaluation confirmed previous studies showing that, in normoxia, alveolar epithelial cells are dominant sites of polyamine uptake. In contrast, hypoxia was accompanied by prominent localization of [(14)C]SPD in conduit, muscularized, and partially muscularized pulmonary arteries, which was not evident in normoxic lung tissue. Hypoxic main pulmonary arterial explants also exhibited substantial increases in [(14)C]SPD uptake relative to control explants, and autoradiography revealed that enhanced uptake was most evident in the medial layer. Main pulmonary arterial explants denuded of endothelium failed to increase polyamine transport in hypoxia. Conversely, medium conditioned by endothelial cells cultured in hypoxic, but not in normoxic, environments enabled hypoxic transport induction in denuded arterial explants. These findings in arterial explants were recapitulated in rat cultured main pulmonary artery cells, including the enhancing effect of a soluble endothelium-derived factor(s) on hypoxic induction of [(14)C]SPD uptake in smooth muscle cells. Viewed collectively, these results show in intact lung tissue that hypoxia enhances polyamine transport in pulmonary artery smooth muscle by a mechanism requiring elaboration of an unknown factor(s) from endothelial cells.
Topics: Animals; Biological Transport; Culture Media; Hypoxia; In Vitro Techniques; Lung; Male; Muscle, Smooth, Vascular; Polyamines; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Reference Values; Spermidine; Tissue Distribution
PubMed: 10710534
DOI: 10.1152/ajplung.2000.278.3.L610 -
The Journal of Thoracic and... Feb 2016Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during...
OBJECTIVES
Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight.
METHODS
In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF.
RESULTS
After in vivo induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups.
CONCLUSIONS
In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity.
Topics: Animals; Feasibility Studies; Hemofiltration; In Vitro Techniques; Lung; Lung Compliance; Models, Animal; Nitroglycerin; Organ Size; Perfusion; Pressure; Pulmonary Circulation; Pulmonary Edema; Respiration; Swine; Time Factors; Vasodilator Agents
PubMed: 26219590
DOI: 10.1016/j.jtcvs.2015.06.046 -
Molecules (Basel, Switzerland) Jul 2020The use of humidifier disinfectant (HD) has been determined to be associated with lung injuries (HDLI) in Korea. Although HD brands containing polyhexamethylene...
The use of humidifier disinfectant (HD) has been determined to be associated with lung injuries (HDLI) in Korea. Although HD brands containing polyhexamethylene guanidine (PHMG) oligomers have been found to cause more HDLI compared to brands containing other disinfectants, the physicochemical properties of PHMG have been poorly defined. We aimed to quantify the PHMG dissolved in HD brands, characterize the number-average () and weight-average () molecular masses, and identify the polymerization degree of PHMG. Analysis of the PHMG oligomers was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) operated in positive-ion reflectron mode. Eight brands of HD containing PHMG were identified. The PHMG concentrations in these brands ranged from 160 to 37,200 ppm (mean = 3100.9 ppm). Concentration was a significant variable among and within HD brands. The degree of PHMG oligomerization fell within the range of two to four. The averages of and were 517.2 g/mol (range: 422-613 g/mol) and 537.3 g/mol (range: 441.0-678.0 g/mol), respectively. Based on the average molecular weight and the degree of polymerization, the PHMG examined here could be regarded as oligomers, which may be associated with the highest proportion of HDLI being caused by PHMG.
Topics: Disinfectants; Equipment Contamination; Guanidines; Humans; Humidifiers; Lung; Lung Injury; Molecular Weight; Polymerization; Republic of Korea; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 32708129
DOI: 10.3390/molecules25143301