THE MORPHOLOGY OF THE LUNGS AT THE EXPERIMENTAL ACUTE INJURY AND ITS PHARMACOCORRECTION

The study of lung morphology under the influence of various environmental factors is of great interest for various areas of medicine and biology. The study of pathological changes in the respiratory part of the lung of rats with aspiration acute injury and the action of pharmacological correction was carried out. Acetone was used as a damaging agent, and HyperHAES was used as a means of pharmacological correction, containing 7.2% NaCl solution in combination with 6% hydroxyethyl starch, as well as a liposomal form of N-acetylcysteine, which was administered to experimental animals once intravenously after induction of acute lung injury. The control group of animals received antibiotic therapy. The staining of the slides was carried out using hematoxylin and eosin. A quantitative assessment of the histological signs of lung tissue damage was carried out. As a result of the study of preparations of the lungs, the degree of pulmonary edema was established, as well as the anti-edema effect of pharmacological corrections. On the 6th day of the experiment, the anti-edematous effect was retained only after the introduction of N-acetylcysteine. Histological examination of the lungs showed generalized destruction of the organ architectonics in response to the impact of a damaging factor and its reduction under the influence of pharmacological corrections. In the control group, the signs of acute lung injury were most extensive. One day after the administration of the HyperHAEC solution, there were no hemorrhages in the histological picture of the lungs. In a quantitative assessment of the histological signs of acute lung injury, it was shown that the maximum positive effect from the administration of HyperHAES develops 24 hours after application. N-acetylcysteine primarily led to a decrease in leukocyte infiltration and prevented the development of a suppurative process. The lung-protective effect of N-acetylcysteine was realized in 24 hours from the moment of administration and persisted until the 6th day of the experiment. The use of pharmacological correction agents in acute lung injury was reflected in the picture of the lethality of the experimental animals. When HyperHAES was applied, 37.5% of animals died by day 6, in the group with N-acetylcysteine - 28.6%, while in the control group all animals died.

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The Impact of Oxidative Stress Levels on the Clinical Effectiveness of Sivelestat in Treating Acute Lung Injury: An Electron Spin Resonance Study

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0b013e3181bb80d4 ◽

2010 ◽

pp. 1

Author(s):

Shigekiyo Matsumoto ◽

Chihiro Shingu ◽

Hironori Koga ◽

Seigo Hidaka ◽

Koji Goto ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Electron Spin Resonance ◽

Lung Injury ◽

Electron Spin ◽

Clinical Effectiveness ◽

Electron Spin Resonance Study ◽

Spin Resonance ◽

The Impact ◽

Spin Resonance Study

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Colloidal gold particles as a new in vivo marker of early acute lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00078.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. L867-L878 ◽

Cited By ~ 53

Author(s):

Kai Heckel ◽

Rainer Kiefmann ◽

Martina Dörger ◽

Mechthild Stoeckelhuber ◽

Alwin E. Goetz

Keyword(s):

Electron Microscopy ◽

Acute Lung Injury ◽

Gas Exchange ◽

Lung Injury ◽

Colloidal Gold ◽

Microvascular Permeability ◽

Arterial Oxygen ◽

Control Group ◽

Gold Particles

Permeability of the endothelial barrier to large molecules plays a pivotal role in the manifestation of early acute lung injury. We present a novel and sensitive technique that brings microanatomical visualization and quantification of microvascular permeability in line. White New Zealand rabbits were anesthetized and ventilated mechanically. Rabbit serum albumin (RSA) was labeled with colloidal gold particles. We quantified macromolecular leakage of gold-labeled RSA and thickening of the gas exchange distance by electron microscopy, taking into account morphology of microvessels. The control group receiving a saline solution represented a normal gas exchange barrier without extravasation of gold-labeled albumin. Infusion of lipopolysaccharide (LPS) resulted in a significant displacement of gold-labeled albumin into pulmonary cells, the lung interstitium, and even the alveolar space. Correspondingly, intravital fluorescence microscopy and digital image analysis indicated thickening of width of alveolar septa. The findings were accompanied by a deterioration of alveolo-arterial oxygen difference, whereas wet/dry ratio and albumin concentration in the bronchoalveolar lavage fluid failed to detect that early stage of pulmonary edema. Inhibition of the nuclear enzyme poly(ADP-ribose) synthetase by 3-aminobenzamide prevented LPS-induced microvascular injury. To summarize: colloidal gold particles visualized by standard electron microscopy are a new and very sensitive in vivo marker of microvascular permeability in early acute lung injury. This technique enabling detailed microanatomical and quantitative pathophysiological characterization of edema formation can form the basis for evaluating novel treatment strategies against acute lung injury.

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Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of neutrophils

10.21203/rs.2.22090/v2 ◽

2020 ◽

Author(s):

Hongxia Mei ◽

Ying Tao ◽

Tianhao Zhang ◽

Feng Qi

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Rat Model ◽

Neutrophil Function ◽

Life Threatening ◽

Pulmonary Inflammatory Response ◽

Anti Inflammatory ◽

Factor Α ◽

The Impact

Abstract Background: Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of neutrophils that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the neutrophil function in a rat model of lipopolysaccharide (LPS)-induced ALI.Results: Treatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with neutrophil deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced neutrophils via the up-regulation of the ability of neutrophils to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the neutrophil respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated neutrophils, alleviating the damage of neutrophils to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of neutrophils. Conclusion: Our results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of neutrophils. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.

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Acute lung injury inhibition by juglone in LPS induced sepsis mouse model involves Sirt1 activation

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i5.14 ◽

2020 ◽

Vol 19 (5) ◽

pp. 1001-1007

Author(s):

Qiong Hu ◽

Chunai Yang ◽

Fenshuang Zheng ◽

Hongdan Duan ◽

Yangshan Fu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Mouse Model ◽

Inflammatory Cytokines ◽

Alveolar Epithelial Cells ◽

Control Group ◽

Western Blot Assay ◽

Edema Formation ◽

Sirt1 Expression ◽

Treatment Groups

Purpose: To investigate the effect of juglone on LPS induced lung injury in a mouse model and in TC 1cell line.Methods: Edema formation in lungs were measured by determination of lung wet/dry weight. Expressions of various proteins were assessed by western blot assay, while Sirt1 level was assessed using immunohistochemistry. Mice were randomly assigned to nine groups of 10 mice each: normal control, untreated and seven juglone treatment groups. Acute lung injury was induced in mice by injecting LPS (10 mg/kg) via intraperitoneal route (ip). The treatment groups were given 10, 20, 30, 40, 50, 60 and 100 μM of juglone, ip, respectively.Results: The levels of MMP-9, IL-6, IL-1β and iNOS were significantly higher in acute lung injury induced mice compared than the control group (p < 0.05). Treatment of the mice with juglone significantly decreased LPS-induced up-regulation of inflammatory cytokines in a dose-dependentmanner. The production of inflammatory cytokines was almost completely inhibited in the mice treated with 100 mg/kg dose of juglone, while treatment of the LPS-stimulated TC 1 cells with juglone upregulated the expression of Sirt1 mRNA. Down-regulation of Sirt1 expression by siRNA inhibited the effect of juglone on LPS-induced increase in inflammatory cytokine production.Conclusion: Juglone prevents lung injury in mice via up-regulation of Sirt1 expression. Therefore, juglone might be useful for the development of a treatment strategy for lung injury. Keywords: Inflammatory, Sirtuin, Edema, Cytokines, Lung injury, TC 1 lung alveolar epithelial cells, Sirt1

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A genetic variant of cortactin linked to acute lung injury impairs lamellipodia dynamics and endothelial wound healing

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00062.2015 ◽

2015 ◽

Vol 309 (9) ◽

pp. L983-L994 ◽

Cited By ~ 6

Author(s):

Sangwook Choi ◽

Sara M. Camp ◽

Arkaprava Dan ◽

Joe G. N. Garcia ◽

Steven M. Dudek ◽

...

Keyword(s):

Wound Healing ◽

Acute Lung Injury ◽

Lung Injury ◽

Regulatory Protein ◽

Actin Binding ◽

Gap Closure ◽

Sphingosine 1 Phosphate ◽

Endothelial Wound Healing ◽

Genetic Signatures ◽

The Impact

Inflammatory mediators released in acute lung injury (ALI) trigger the disruption of interendothelial junctions, leading to loss of vascular barrier function, protein-rich pulmonary edema, and severe hypoxemia. Genetic signatures that predict patient recovery or disease progression are poorly defined, but recent genetic screening of ALI patients has identified an association between lung inflammatory disease and a single nucleotide polymorphism (SNP) in the gene for the actin-binding and barrier-regulatory protein cortactin. This study investigated the impact of this disease-linked cortactin variant on wound healing processes that may contribute to endothelial barrier restoration. A microfabricated platform was used to quantify wound healing in terms of gap closure speed, lamellipodia dynamics, and cell velocity. Overexpression of wild-type cortactin in endothelial cells (ECs) improved directional cell motility and enhanced lamellipodial protrusion length, resulting in enhanced gap closure rates. By contrast, the cortactin SNP impaired wound closure and cell locomotion, consistent with the observed reduction in lamellipodial protrusion length and persistence. Overexpression of the cortactin SNP in lung ECs mitigated the barrier-enhancing activity of sphingosine 1-phosphate. These findings suggest that this common cortactin variant may functionally contribute to ALI predisposition by impeding endothelial wound healing.

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Effect of Thoracentesis on Intubated Patients with Acute Lung Injury

The American Surgeon ◽

10.1177/000313481608200321 ◽

2016 ◽

Vol 82 (3) ◽

pp. 266-270

Author(s):

Matthew B. Bloom ◽

Derek Serna-Gallegos ◽

Mark Ault ◽

Ahsan Khan ◽

Rex Chung ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Blood Gases ◽

Surgical Intensive Care Unit ◽

Surgical Intensive Care ◽

Mechanically Ventilated ◽

Arterial Blood ◽

Tertiary Center ◽

Before And After ◽

The Impact

Pleural effusions occur frequently in mechanically ventilated patients, but no consensus exists regarding the clinical benefit of effusion drainage. We sought to determine the impact of thoracentesis on gas exchange in patients with differing severities of acute lung injury (ALI). A retrospective analysis was conducted on therapeutic thoracenteses performed on intubated patients in an adult surgical intensive care unit of a tertiary center. Effusions judged by ultrasound to be 400 mL or larger were drained. Subjects were divided into groups based on their initial P:F ratios: normal >300, ALI 200 to 300, and acute respiratory distress syndrome (ARDS) <200. Baseline characteristics, physiologic variables, arterial blood gases, and ventilator settings before and after the intervention were analyzed. The primary end point was the change in measures of oxygenation. Significant improvements in P:F ratios (mean ± SD) were seen only in patients with ARDS (50.4 ± 38.5, P = 0.001) and ALI (90.6 ± 161.7, P = 0.022). Statistically significant improvement was observed in the pO2 (31.1, P = 0.005) and O2 saturation (4.1, P < 0.001) of the ARDS group. The volume of effusion removed did not correlate with changes in individual patient's oxygenation. These data support the role of therapeutic thoracentesis for intubated patients with abnormal P:F ratios.

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The impact of pretreatment with bolus dose of enteral glutamine on acute lung injury induced by oleic acid in rats

Journal of Anesthesia ◽

10.1007/s00540-013-1745-y ◽

2013 ◽

Vol 28 (3) ◽

pp. 354-362 ◽

Cited By ~ 5

Author(s):

A. Ebru Salman ◽

Fahri Yetişir ◽

Mehmet Kılıç ◽

Özkan Önal ◽

Ahmet Dostbil ◽

...

Keyword(s):

Acute Lung Injury ◽

Oleic Acid ◽

Lung Injury ◽

Bolus Dose ◽

The Impact

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Recent advances in genetic predisposition to clinical acute lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90269.2008 ◽

2009 ◽

Vol 296 (5) ◽

pp. L713-L725 ◽

Cited By ~ 79

Author(s):

Li Gao ◽

Kathleen C. Barnes

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Candidate Genes ◽

Genetic Variants ◽

Complex Traits ◽

Association Studies ◽

Genetic Association Studies ◽

Special Focus ◽

Disease Manifestation ◽

The Impact

It has been well established that acute lung injury (ALI), and the more severe presentation of acute respiratory distress syndrome (ARDS), constitute complex traits characterized by a multigenic and multifactorial etiology. Identification and validation of genetic variants contributing to disease susceptibility and severity has been hampered by the profound heterogeneity of the clinical phenotype and the role of environmental factors, which includes treatment, on outcome. The critical nature of ALI and ARDS, compounded by the impact of phenotypic heterogeneity, has rendered the amassing of sufficiently powered studies especially challenging. Nevertheless, progress has been made in the identification of genetic variants in select candidate genes, which has enhanced our understanding of the specific pathways involved in disease manifestation. Identification of novel candidate genes for which genetic association studies have confirmed a role in disease has been greatly aided by the powerful tool of high-throughput expression profiling. This article will review these studies to date, summarizing candidate genes associated with ALI and ARDS, acknowledging those that have been replicated in independent populations, with a special focus on the specific pathways for which candidate genes identified so far can be clustered.

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