scholarly journals Method for Pulmonary Administration Using Negative Pressure Generated by Inspiration in Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 200 ◽  
Author(s):  
Yuki Oiso ◽  
Tomomi Akita ◽  
Daiki Kato ◽  
Chikamasa Yamashita
Keyword(s):  
Lung Injury ◽  
Negative Pressure ◽  
Drug Distribution ◽  
Pulmonary Delivery ◽  
Chronic Obstructive ◽  
Clinical Tests ◽  
Obstructive Pulmonary Disease ◽  
Pulmonary Administration ◽  
Pressure Method ◽  
All Trans Retinoic Acid

When developing inhaled medicines for respiratory diseases, such as chronic obstructive pulmonary disease, drugs need to be administered by pulmonary delivery to animals in non-clinical tests. Common methods require application of pressure during administration, and it may cause lung injury, so we focused on the inhalation of liquid medicines by mice themselves. This study aimed to evaluate a negative pressure method of pulmonary administration in mice by self-inhalation. First, to confirm the accuracy of delivery of liquid medicines into lungs and the potential for lung injury, Institute of Cancer Research (ICR) mice received methylene blue tetrahydrate or saline by the negative pressure method. We assessed drug distribution and usefulness of this method by administering porcine pancreatic elastase and all-trans-retinoic acid (ATRA) to mice. Consequently, we confirmed good distribution of the dye and no injury such as disruption of blood flow or destruction of alveoli in lungs of mice. Following production of the murine emphysema model, the mean linear intercept (Lm) was calculated as 78 ± 4 μm. Moreover, a significant therapeutic effect of administration of the ATRA was confirmed. These results suggest that this negative pressure method of administration may be useful for pulmonary administration in non-clinical tests.

scholarly journals The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection against lung injury

2017 ◽  
Vol 312 (2) ◽  
pp. L155-L162 ◽  
Author(s):  
Hailin Zhao ◽  
Shiori Eguchi ◽  
Azeem Alam ◽  
Daqing Ma
Keyword(s):  
Lung Injury ◽  
Therapeutic Potential ◽  
Antioxidant Response ◽  
Protective Role ◽  
Chronic Obstructive ◽  
Related Factor ◽  
Nuclear Factor ◽  
Obstructive Pulmonary Disease ◽  
Antioxidant Response Elements

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that upregulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. Activation of Nrf2 has been shown to be protective against lung injury. In the lung, diverse stimuli including environmental oxidants, medicinal agents, and pathogens can activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2-antioxidant pathway has been shown to be important in the protection against various lung injuries including acute lung injury/acute respiratory distress syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and allergy and was widely examined for new therapeutic targets. The present review explores the protective role of Nrf-2 against lung injury and the therapeutic potential in targeting Nrf-2.

scholarly journals Atrial Fibrillation after Inhalational Lung Injury: A Troubling Complication of a Rare Problem

2012 ◽  
Vol 2012 ◽  
pp. 1-3
Author(s):  
Ragesh Panikkath ◽  
Kenneth Nugent ◽  
Alejandro Perez-Verdia
Keyword(s):  
Atrial Fibrillation ◽  
Lung Injury ◽  
Lung Diseases ◽  
Myocardial Injury ◽  
Antiarrhythmic Drugs ◽  
Structural Changes ◽  
Structural Heart Disease ◽  
Chronic Obstructive ◽  
Medical Problems ◽  
Obstructive Pulmonary Disease

Atrial fibrillation (AF) has been associated with lung diseases like pneumonia and chronic obstructive pulmonary disease but has only infrequently been associated with inhalational lung injury. We report two cases of resistant AF, which developed in young healthy manual laborers shortly after inhalational lung injury due to massive quantity of pesticides and anhydrous ammonia, respectively. They had no evidence of valvular or structural heart disease and did not have any previous medical problems. The AF was resistant to antiarrhythmic drugs and required pulmonary vein isolation in first patient and possibly the second patient who is currently being evaluated for this procedure. These arrhythmias may reflect direct myocardial injury during and after exposure. Alternatively, multiple mechanisms can cause atrial fibrillation in lung diseases, including hypoxemia, acidemia, inflammatory mediators, and structural changes in the atria and ventricle, and these could lead to AF in inhalational lung injury cases. AF needs to be excluded when patients present with palpitations after inhalational lung injury, especially since, if unrecognized, AF may lead to complications, like thromboembolic phenomenon and tachycardiomyopathy.

Asthma und COPD: Bronchodilatation durch nasale High-Flow-Therapie

2020 ◽  
Vol 8 (4) ◽  
pp. 210-211
Author(s):  
Peter Haidl
Keyword(s):  
Pulmonary Delivery ◽  
Air Entrainment ◽  
Forced Expiratory Volume ◽  
Nasal Cannula ◽  
Dose Titration ◽  
Dose Inhaler ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Moderate Asthma ◽  
Bronchodilator Response

Background: There has been increasing interest in transnasal pulmonary aerosol administration, but the dose-response relationship has not been reported. Objectives: To determine the accumulative bronchodilator dose at which patients with stable mild-to-moderate asthma and chronic obstructive pulmonary disease (COPD) achieve similar spirometry responses before and after bronchodilator tests using albuterol via a metered dose inhaler with a valved holding chamber (MDI + VHC). Method: Adult patients who met ATS/ERS criteria for bronchodilator responses in pulmonary function laboratory were recruited and consented to participate. After a washout period, patients received escalating doubling dosages (0.5, 1, 2, and 4 mg) of albuterol in a total volume of 2 mL delivered by vibrating mesh nebulizer via a nasal cannula at 37 °C with a flow rate of 15–20 L/min using a Venturi air entrainment device. Spirometry was measured at baseline and after each dose. Titration was stopped when an additional forced expiratory volume in 1 second (FEV1) improvement was < 5%. Results: 42 patients (16 males) with stable mild-to-moderate asthma (n = 29) and COPD (n = 13) were enrolled. FEV1 increment after a cumulative dose of 1.5 mg of albuterol via nasal cannula at 15–20 L/min was similar to 4 actuations of MDI + VHC (0.34 ± 0.18 vs. 0.34 ± 0.12 L, p = 0.878). Using ATS/ERS criteria of the bronchodilator test, 33.3% (14/42) and 69% (29/42) of patients responded to 0.5 and 1.5 mg of albuterol, respectively. Conclusions: With a nasal cannula at 15–20 L/min, transnasal pulmonary delivery of 1.5 mg albuterol resulted in similar bronchodilator response as 4 actuations of MDI + VHC.

scholarly journals Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Yang Sun ◽  
Sachiko Ito ◽  
Naomi Nishio ◽  
Yuriko Tanaka ◽  
Nana Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lung Injury ◽  
Respiratory Diseases ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Chronic Obstructive ◽  
Oxygen Species ◽  
Obstructive Pulmonary Disease ◽  
Pulmonary Damage ◽  
Adverse Environmental Conditions

Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2αin GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury.

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