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Cell and Tissue Research Mar 2017The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing... (Review)
Review
The study of the structural basis of gas exchange function in the lung depends on the availability of quantitative information that concerns the structures establishing contact between the air in the alveoli and the blood in the alveolar capillaries, which can be entered into physiological equations for predicting oxygen uptake. This information is provided by morphometric studies involving stereological methods and allows estimates of the pulmonary diffusing capacity of the human lung that agree, in experimental studies, with the maximal oxygen consumption. The basis for this "machine lung" structure lies in the complex design of the cells building an extensive air-blood barrier with minimal cell mass.
Topics: Animals; Diffusion; Gases; Humans; Lung
PubMed: 27981379
DOI: 10.1007/s00441-016-2541-4 -
Toxicology Mechanisms and Methods Mar 2013Carbon nanotubes (CNTs) have been a subject of intensive research for a wide range of applications. However, because of their extremely small size and light weight, CNTs... (Review)
Review
Carbon nanotubes (CNTs) have been a subject of intensive research for a wide range of applications. However, because of their extremely small size and light weight, CNTs are readily inhaled into human lungs resulting in increased rates of pulmonary disorders, most notably fibrosis. Several studies have demonstrated the fibrogenic effects of CNTs given their ability to translocate into the surrounding areas in the lung causing granulomatous lesions and interstitial and sub-pleural fibrosis. However, the mechanisms underlying the disease process remain obscure due to the lack of understanding of the cellular interactions and molecular targets involved. Interestingly, certain physicochemical properties of CNTs have been shown to affect their respiratory toxicity, thereby becoming significant determinants of fibrogenesis. CNT-induced fibrosis involves a multitude of cell types and is characterized by the early onset of inflammation, oxidative stress and accumulation of extracellular matrix. Increased reactive oxygen species activate various cytokine/growth factor signaling cascades resulting in increased expression of inflammatory and fibrotic genes. Profibrotic growth factors and cytokines contribute directly to fibroblast proliferation and collagen production. Given the role of multiple players during the pathogenesis of CNT-induced fibrosis, the objective of this review is to summarize the key findings and discuss major cellular and molecular events governing pulmonary fibrosis. We also discuss the physicochemical properties of CNTs and their effects on pulmonary toxicities as well as various biological factors contributing to the development of fibrosis.
Topics: Animals; Blood-Air Barrier; Capillary Permeability; DNA Damage; Humans; Inflammation Mediators; Lung; Nanotubes, Carbon; Oxidative Stress; Pneumonia; Pulmonary Fibrosis; Reactive Oxygen Species; Risk Assessment; Signal Transduction
PubMed: 23194015
DOI: 10.3109/15376516.2012.753967 -
American Journal of Physiology. Lung... Aug 2011Hyaluronan (HA) has diverse functions in normal lung homeostasis and pulmonary disease. HA constitutes the major glycosaminoglycan in lung tissue, with HA degradation... (Review)
Review
Hyaluronan (HA) has diverse functions in normal lung homeostasis and pulmonary disease. HA constitutes the major glycosaminoglycan in lung tissue, with HA degradation products, produced by hyaluronidase enzymes and reactive oxygen species, being implicated in several lung diseases, including acute lung injury, asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. The differential activities of HA and its degradation products are due, in part, to regulation of multiple HA-binding proteins, including cluster of differentiation 44 (CD44), Toll-like receptor 4 (TLR4), HA-binding protein 2 (HABP2), and receptor for HA-mediated motility (RHAMM). Recent research indicates that exogenous administration of high-molecular-weight HA can serve as a novel therapeutic intervention for lung diseases, including lipopolysaccharide (LPS)-induced acute lung injury, sepsis/ventilator-induced lung injury, and airway hyperreactivity. This review focuses on the regulatory role of HA and HA-binding proteins in lung pathology and discusses the capacity of HA to augment and inhibit various lung diseases.
Topics: Acute Lung Injury; Animals; Bronchial Hyperreactivity; Bronchitis; Chronic Disease; Extracellular Matrix Proteins; Glucuronosyltransferase; Humans; Hyaluronan Receptors; Hyaluronan Synthases; Hyaluronic Acid; Lipopolysaccharides; Lung; Lung Diseases; Molecular Weight; Protein Isoforms; Pulmonary Emphysema; Reactive Oxygen Species; Toll-Like Receptor 4; Ventilator-Induced Lung Injury
PubMed: 21571904
DOI: 10.1152/ajplung.00071.2010 -
Chinese Medical Journal May 2018Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation,... (Review)
Review
OBJECTIVE
Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.
DATA SOURCES
This review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."
STUDY SELECTION
The original articles and reviews including the topics were the primary references.
RESULTS
Based on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.
CONCLUSIONS
At present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.
Topics: Acute Lung Injury; Animals; Chlorine; Halogens; Humans; Lung; Respiratory Distress Syndrome
PubMed: 29722341
DOI: 10.4103/0366-6999.231515 -
Respiration; International Review of... 2014Pulmonary disease has been the primary target of inhaled therapeutics for over 50 years. During that period, increasing interest has arisen in the use of this route of... (Review)
Review
Pulmonary disease has been the primary target of inhaled therapeutics for over 50 years. During that period, increasing interest has arisen in the use of this route of administration to gain access to the systemic circulation for the treatment of a number of diseases beyond the airways. In order to effectively employ this route, the barriers to transport from the lungs following deposition of aerosols must be considered, including the nature of the disease (whether proximal, as in pulmonary hypertension, or distal, as in diabetes). Delivery to the systemic circulation begins with the efficiency of aerosol generation and subsequent deposition in the airways and proceeds to the influence of mechanisms of clearance, including absorption, metabolism, and mucociliary and cell-mediated transport, on the residence time of the drugs in the lungs. The nature of the drug (small or large molecules/low or high molecular weight), susceptibility to degradation and general physicochemical properties play a role in the chemistry of its formulation, physics of aerosol delivery and biology of disposition.
Topics: Administration, Inhalation; Aerosols; Drug Delivery Systems; Humans; Lung; Mucociliary Clearance; Respiratory Transport
PubMed: 25277464
DOI: 10.1159/000367852 -
Carbohydrate Research Jul 2021The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral... (Review)
Review
The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral drugs have found to be unsuccessful in the treatment of COVID-19 patients. The demand for efficient antiviral drugs has created a huge burden on physicians and health workers. Plasma therapy seems to be less accomplishable due to insufficient donors to donate plasma and low recovery rate from viral infection. Repurposing of antivirals has been evolved as a suitable strategy in the current treatment and preventive measures. The concept of drug repurposing represents new experimental approaches for effective therapeutic benefits. Besides, SARS-CoV-2 exhibits several complications such as lung damage, blood clot formation, respiratory illness and organ failures in most of the patients. Based on the accumulation of data, sulfated marine polysaccharides have exerted successful inhibition of virus entry, attachment and replication with known or unknown possible mechanisms against deadly animal and human viruses so far. Since the virus entry into the host cells is the key process, the prevention of such entry mechanism makes any antiviral strategy effective. Enveloped viruses are more sensitive to polyanions than non-enveloped viruses. Besides, the viral infection caused by RNA virus types embarks severe oxidative stress in the human body that leads to malfunction of tissues and organs. In this context, polysaccharides play a very significant role in providing shielding effect against the virus due to their polyanionic rich features and a molecular weight that hinders their reactive surface glycoproteins. Significantly the functional groups especially sulfate, sulfate pattern and addition, uronic acids, monosaccharides, glycosidic linkage and high molecular weight have greater influence in the antiviral activity. Moreover, they are very good antioxidants that can reduce the free radical generation and provokes intracellular antioxidant enzymes. Additionally, polysaccharides enable a host-virus immune response, activate phagocytosis and stimulate interferon systems. Therefore, polysaccharides can be used as candidate drugs, adjuvants in vaccines or combination with other antivirals, antioxidants and immune-activating nutritional supplements and antiviral materials in healthcare products to prevent SARS-CoV-2 infection.
Topics: Anticoagulants; Antiviral Agents; Blood Platelets; COVID-19; Humans; Immunologic Factors; Lung; Phaeophyceae; Polysaccharides; Pulmonary Embolism; Respiratory Insufficiency; Rhodophyta; SARS-CoV-2; Sulfuric Acid Esters; Virus Attachment; Virus Internalization; COVID-19 Drug Treatment
PubMed: 34015720
DOI: 10.1016/j.carres.2021.108326 -
Journal of Anatomy Jul 2020We examined the morphology of the lungs of five species of high-altitude resident ducks from Lake Titicaca in the Peruvian Andes (yellow-billed pintail [Anas georgica],...
We examined the morphology of the lungs of five species of high-altitude resident ducks from Lake Titicaca in the Peruvian Andes (yellow-billed pintail [Anas georgica], cinnamon teal [Anas cyanoptera orinomus], puna teal [Anas puna], speckled teal [Anas flavirostris oxyptera], and ruddy duck [Oxyura jamaicensis ferruginea]) and compared them with those of the high-altitude migratory bar-headed goose (Anser indicus) and the low-altitude migratory barnacle goose (Branta leucopsis). We then determined the relationship between mass-specific lung volume, the volume densities of the component parts of the lung, and previously reported hypoxia-induced increases in pulmonary O extraction. We found that the mass-specific lung volumes and the mass-specific volume of the exchange tissue were larger in the lungs of high-altitude resident birds. The bar-headed goose had a mass-specific lung volume that fell between those of the low-altitude species and the high-altitude residents, but a mass-specific volume of exchange tissue that was not significantly different than that of the high-altitude residents. The data suggest that the mass-specific volume of the lung may increase with evolutionary time spent at altitude. We found an inverse relationship between the percentage increase in pulmonary O extraction and the percentage increase in ventilation across species that was independent of the volume density of the exchange tissue, at least for the resident Andean birds.
Topics: Altitude; Animals; Ducks; Flight, Animal; Geese; Lung; Oxygen Consumption; Respiration
PubMed: 32173858
DOI: 10.1111/joa.13180 -
Biomolecules Apr 2022Hyaluronic acid (HA) is a major component of the extracellular matrix. It is synthesized by hyaluronan synthases (HAS) into high-molecular-weight chains (HMW-HA) that... (Review)
Review
Hyaluronic acid (HA) is a major component of the extracellular matrix. It is synthesized by hyaluronan synthases (HAS) into high-molecular-weight chains (HMW-HA) that exhibit anti-inflammatory and immunomodulatory functions. In damaged, infected, and/or inflamed tissues, HMW-HA are degraded by hyaluronidases (HYAL) or reactive oxygen species (ROS) to give rise to low-molecular-weight HAs (LMW-HAs) that are potent pro-inflammatory molecules. Therefore, the size of HA regulates the balance of anti- or pro-inflammatory functions. The activities of HA depend also on its interactions with hyaladherins. HA synthesis, degradation, and activities through HA/receptors interactions define the hyaluronasome. In this review, a short overview of the role of high and low-molecular-weight HA polymers in the lungs is provided. The involvement of LMW-HA in pulmonary innate immunity via the activation of neutrophils, macrophages, dendritic cells, and epithelial cells is described to highlight LMW-HA as a therapeutic target in inflammatory respiratory diseases. Finally, the possibilities to counter LMW-HA's deleterious effects in the lungs are discussed.
Topics: Hyaluronan Receptors; Hyaluronic Acid; Immunity, Innate; Lung; Molecular Weight
PubMed: 35625586
DOI: 10.3390/biom12050658 -
Clinical Biochemistry Oct 2014Metabonomics is a powerful and promising analytic tool that allows assessment of global low-molecular-weight metabolites in biological systems. It has a great potential... (Review)
Review
OBJECTIVES
Metabonomics is a powerful and promising analytic tool that allows assessment of global low-molecular-weight metabolites in biological systems. It has a great potential for identifying useful biomarkers for early diagnosis, prognosis and assessment of therapeutic interventions in clinical practice. The aim of this review is to provide a brief summary of the recent advances in UPLC-based metabonomic approach for biomarker discovery in a variety of diseases, and to discuss their significance in clinical chemistry.
DESIGN AND METHODS
All the available information on UPLC-based metabonomic applications for discovering biomarkers of diseases were collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Springer, Google Scholar, etc.).
RESULTS
Metabonomics has been used in clinical chemistry to identify and evaluate potential biomarkers and therapeutic targets in various diseases affecting the liver (hepatocarcinoma and liver cirrhosis), lung (lung cancer and pneumonia), gastrointestinal tract (colorectal cancer) and urogenital tract (prostate cancer, ovarian cancer and chronic kidney disease), as well as metabolic diseases (diabetes) and neuropsychiatric disorders (Alzheimer's disease and schizophrenia), etc.
CONCLUSIONS
The information provided highlights the potential value of determination of endogenous low-molecular-weight metabolites and the advantages and potential drawbacks of the application of UPLC-based metabonomics in clinical setting.
Topics: Biomarkers; Biomedical Research; Chemistry, Clinical; Chromatography, High Pressure Liquid; Diagnosis; Humans; Mass Spectrometry; Metabolomics; Molecular Targeted Therapy; Molecular Weight
PubMed: 25087975
DOI: 10.1016/j.clinbiochem.2014.07.019 -
Molecular Imaging and Biology Feb 2022Molecular imaging has provided unparalleled opportunities to monitor disease processes, although tools for evaluating infection remain limited. Coronavirus disease...
PURPOSE
Molecular imaging has provided unparalleled opportunities to monitor disease processes, although tools for evaluating infection remain limited. Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by lung injury that we sought to model. Activated macrophages/phagocytes have an important role in lung injury, which is responsible for subsequent respiratory failure and death. We performed pulmonary PET/CT with I-iodo-DPA-713, a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by activated macrophages cells, to evaluate the local immune response in a hamster model of SARS-CoV-2 infection.
PROCEDURES
Pulmonary I-iodo-DPA-713 PET/CT was performed in SARS-CoV-2-infected golden Syrian hamsters. CT images were quantified using a custom-built lung segmentation tool. Studies with DPA-713-IRDye680LT and a fluorescent analog of DPA-713 as well as histopathology and flow cytometry were performed on post-mortem tissues.
RESULTS
Infected hamsters were imaged at the peak of inflammatory lung disease (7 days post-infection). Quantitative CT analysis was successful for all scans and demonstrated worse pulmonary disease in male versus female animals (P < 0.01). Increased I-iodo-DPA-713 PET activity co-localized with the pneumonic lesions. Additionally, higher pulmonary I-iodo-DPA-713 PET activity was noted in male versus female hamsters (P = 0.02). DPA-713-IRDye680LT also localized to the pneumonic lesions. Flow cytometry demonstrated a higher percentage of myeloid and CD11b + cells (macrophages, phagocytes) in male versus female lung tissues (P = 0.02).
CONCLUSION
I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, I-Iodo-DPA-713 PET could serve as a noninvasive, clinically translatable approach to monitor SARS-CoV-2-associated pulmonary inflammation and expedite the development of novel therapeutics for COVID-19.
Topics: Acetamides; Animals; COVID-19; Chlorocebus aethiops; Cricetinae; Disease Models, Animal; Iodine Radioisotopes; Lung; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Pyrazoles; Pyrimidines; SARS-CoV-2; Vero Cells
PubMed: 34424479
DOI: 10.1007/s11307-021-01638-5