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Pulmonary Pharmacology & Therapeutics

Matea Cedilak, Mihailo Banjanac, Daniela Belamarić, Andrea Paravić Radičević, Ivan Faraho, Krunoslav Ilić, Snježana Čužić, Ines Glojnarić, Vesna Eraković Haber, Martina Bosnar
Idiopathic pulmonary fibrosis (IPF) is a complex lung disease with incompletely understood pathophysiology. Effectiveness of available medicines is limited and the need for new and improved therapies remains. Due to complexity of the disease, it is difficult to develop predictable in vitro models. In this study we have described precision-cut lung slices (PCLS) prepared from bleomycin treated mice as an in vitro model for testing of novel compounds with antifibrotic activity. We have shown that PCLS during in vitro incubation retain characteristics of bleomycin model with increased expression of fibrosis related genes ACTA2 (α-smooth muscle actin), COL1A1 (collagen 1), FN1 (fibronectin 1), MMP12 (matrix metalloproteinase 12) and TIMP1 (tissue inhibitor of metalloproteinases)...
February 15, 2019: Pulmonary Pharmacology & Therapeutics
Louis-Philippe Boulet, Julie Turmel
In the general population, particularly in individuals with asthma, cough is a common symptom, often reported after exertion, although regular exercise may be associated with a reduction in the prevalence of cough. In athletes, exercise-induced cough is also a particularly frequent symptom. The main etiologies of cough in athletes are somewhat similar to non-athletes, including asthma/airway hyperresponsiveness, upper airways disorders such as allergic or non-allergic rhinitis, and exercise-induced laryngeal obstruction, although these conditions are more frequently observed in athletes...
February 13, 2019: Pulmonary Pharmacology & Therapeutics
Stuart B Mazzone, Michael J Farrell
Cough is an important protective mechanism for clearing the airways but becomes a troublesome, and often difficult to treat, symptom in respiratory disease. Although cough can be produced as a reflex in response to the presence of irritants within the airways, emerging research demonstrates an unappreciated complexity in the peripheral and central neural systems that regulate cough. This complexity includes multiple primary sensory neurons that can induce or facilitate reflex coughing, different ascending central circuits in the brain that contribute to cough sensory discrimination and the perception of the urge-to-cough, and several descending brain systems for inducing, facilitating and inhibiting cough responses...
February 11, 2019: Pulmonary Pharmacology & Therapeutics
Xiaojie Zhu, Ying Kong, Qi Liu, Yayuan Lu, Han Xing, Xiaoyu Lu, Yue Yang, Jiaqiu Xu, Ning Li, Di Zhao, Xijing Chen, Yang Lu
Pulmonary delivery of anti-cancer drugs in the form of nanoparticulate dry powders is considered a promising modality for treating lung cancer. However, it is not known whether the pharmacodynamics and pharmacokinetics of nano-preparations are altered after co-spray drying. In this study, we compared the physicochemical property, anti-cancer activity, tumor targeting and pharmacokinetic behavior of docetaxel-loaded folic acid-conjugated liposomes (LPs-DTX-FA) with those of dry powder prepared by co-spray-drying LPs-DTX-FA...
February 7, 2019: Pulmonary Pharmacology & Therapeutics
Richard Douglas Turner
Cough is a prominent symptom of pulmonary tuberculosis (TB), one of the oldest and most prevalent infectious diseases. Coughing probably has a pivotal role in transmission of the causative organism Mycobacterium tuberculosis. Despite this, little research to date has addressed this subject. Current knowledge of the mechanisms of cough in TB and how exactly coughing patterns predict infectiousness is scant, but this is changing. This overview summarises the existing evidence for the infectiousness of cough in TB, clinical correlates, and possible causes of cough in TB...
February 1, 2019: Pulmonary Pharmacology & Therapeutics
Yufeng Yao, Hui Li, Xinwen Da, Zhuhan He, Bo Tang, Yong Li, Changqing Hu, Chengqi Xu, Qiuyun Chen, Qing K Wang
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a life-threatening disease without effective therapies. PAH is associated with a progressive increase in pulmonary vascular resistance and irreversible pulmonary vascular remodeling. SUMO1 (small ubiquitin-related modifier 1) can bind to target proteins and lead to protein SUMOylation, an important post-translational modification with a key role in many diseases. However, the contribution of SUMO1 to PAH remains to be fully characterized...
January 28, 2019: Pulmonary Pharmacology & Therapeutics
Jyotshna Mandal, Michael Roth, Eleni Papakonstantinou, Lei Fang, Spasenija Savic, Michael Tamm, Daiana Stolz
PURPOSE: Adrenomedullin (AM) is a pluripotent peptide hormone with contradictory effects in human health and disease. In chronic inflammatory lung diseases, such as asthma and COPD, AM has been shown to inhibit inflammation and cell proliferation. In the present study, we aimed to investigate the effect of AM on pro-angiogenic and pro-inflammatory cytokines in asthma and COPD. PATIENTS AND METHODS: Serum levels of pro-AM were measured in patients with asthma, COPD and matched controls...
January 25, 2019: Pulmonary Pharmacology & Therapeutics
Eugen Javor, Sanja Popović Grle
The role of intravenous (IV) or nebulised magnesium sulphate (MgSO4 ) in the treatment of severe acute asthma in adults is unclear. A controversy exists regarding its efficacy. In children MgSO4 has a more evident clinical effect, but the child population has not been considered in this work. The applicability of the results from randomized clinical trials (RCTs) involving MgSO4 in adult population is questioned in the optimal treatment of asthma exacerbations. According to the newest guidelines from the Global Initiative for Asthma (GINA), optimal treatment in the emergency department (ED) is based on short-acting beta2 -agonists (SABA), oral or IV corticosteroids (CS), short acting muscarinic antagonists (SAMA) and the controlled oxygen therapy...
January 17, 2019: Pulmonary Pharmacology & Therapeutics
Vasilios Tzilas, Evangelos Bouros, Ilianna Barbayianni, Thodoris Karampitsakos, Sofia Kourtidou, Maria Ntassiou, Ioanna Ninou, Vassilis Aidinis, Demosthenes Bouros, Argyris Tzouvelekis
BACKGROUND: Vitamin D (VitD) is a steroid hormone with cytoprotective and anti-inflammatory properties. Epidemiological studies have suggested a link between VitD deficiency and risk of development of chronic lung diseases. Its role in lung fibrosis is largely unknown. The aim of our study was to investigate the role of VitD in experimental and human lung fibrosis. METHODS: VitD (25-OH-D3, 2 μg/kg) was orally administered from day 3-day 13 following bleomycin-challenge, in 8-10 weeks-old C57/BL6 mice...
January 16, 2019: Pulmonary Pharmacology & Therapeutics
E Nigro, P Stiuso, M G Matera, M L Monaco, M Caraglia, M Maniscalco, F Perrotta, G Mazzarella, A Daniele, A Bianco
Adiponectin (Acrp30) plays an important role in energy metabolism and inflammation. Recently, in vivo serum Acrp30 levels have been reported to be correlated to risk of developing several types of cancers such as lung cancer, and in vitro studies have demonstrated a role for Acrp30 in the control of cell proliferation and survival. However, the molecular effects of Acrp30 on lung cancer have not yet been clearly defined. In the present study, we investigated the effects of different concentrations of Acrp30 on the A549 human alveolar epithelial cell line, an in vitro model of lung adenocarcinoma...
January 14, 2019: Pulmonary Pharmacology & Therapeutics
Mario Gehlen, Jose Carlos Fraga, Sergio Luis Amantea, Nadya P Silveira, Jane Kulczynski, Eliane Roesch, Kalyana G Portal, Paulo R Sanches
BACKGROUND AND OBJECTIVES: Adjunctive intrapleural fibrinolytic is an option to treat empyema at fibrinopurulent stage, but there is controversy about which should be use. Our objective is to evaluate the action of alteplase and/or desoxyribonuclease at physical and chemical properties in vitro pus derived from an experimental induced empyema in rats. METHODS: Streptococcus pneumoniae was introduced into the pleural cavity by thoracentesis through pleural pressure monitor...
January 12, 2019: Pulmonary Pharmacology & Therapeutics
Peilin Xie, Zhen Zheng, Lihua Jiang, Songwei Wu
The present study sought to determine the pharmacological effects of penehyclidine, an anticholinergic agent, on the angiogenic capacity of pulmonary microvascular endothelial cells (PMVECs). In vitro Matrigel network formation assay, cell proliferation assay, cell-matrix adhesion assay, and wound-healing assay were performed in PMVECs with or without exposure to penehyclidine or, in some cases, glycopyrrolate or acetylcholine, over a concentration range. In addition, the phosphorylation state of Akt and ERK, as well as the endogenous level of mTOR and RICTOR were examined in PMVECs by Western blot following the cells exposure to penehyclidine or, for some proteins, glycopyrrolate or acetylcholine...
January 11, 2019: Pulmonary Pharmacology & Therapeutics
Lei Jiang, Qing Jiang, Songlin Yang, Shicong Huang, Xiaoli Han, Jun Duan, Shangha Pan, Mingyan Zhao, Shuliang Guo
GYY4137, a slow-releasing hydrogen sulfide (H2 S) donor, has been reported to exert anti-inflammatory activity and protect against sepsis. Heme oxygenase-1 (HO-1) is an important anti-inflammatory heat shock protein and plays a similar effect on sepsis. This study investigated the role of GYY4137 in acute lung injury (ALI) via HO-1 regulation. Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide (LPS) and the mechanism of anti-inflammatory effects of GYY4137 was investigated in mice and RAW264...
December 31, 2018: Pulmonary Pharmacology & Therapeutics
Fernanda Blasina, Lucía Vaamonde, Fernando Silvera, Gonzalo Solla, Juan Andrés Abin-Carriquiry, Carmen Gutiérrez, Pilar Beltramo, Irene García, Miguel Martell
Persistent pulmonary hypertension of the newborn (PPHN) is a complex pathology resulting from a failure of the post-natal reduction in pulmonary vascular resistance leading to hypoxemia. The standard therapy is inhaled Nitric Oxide (NO) improving oxygenation but its availability is limited, especially in hospitals with restricted financial resources. We evaluated the efficacy and safety of a new device generating NO (TAS + PLUS), in an experimental piglet models of pulmonary hypertension (PH), and we later tested its application in a pilot study of newborn patients suffering from PPHN...
December 7, 2018: Pulmonary Pharmacology & Therapeutics
Jinyan Ye, Minqiang Guan, Yao Lu, Dan Zhang, Chengye Li, Caicun Zhou
The main goal of this study was to evaluate the effects of arbutin (AR) on lipopolysaccharide (LPS)-induced lung injury. A lung injury rat model was established by intravenous LPS administration. We found that levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in both serum and lung tissue were significant increased after LPS challenge. In addition, pathological conditions were examined in rat lungs, and it was demonstrated that AR-pretreatment reduced LPS-induced malondialdehyde (MDA) levels and increased LPS-induced superoxide dismutase (SOD) activity...
December 5, 2018: Pulmonary Pharmacology & Therapeutics
S Fraňová, I Kazimierová, L Pappová, M Molitorisová, M Jošková, M Šutovská
INTRODUCTION: Mucoactive agent, erdosteine, besides mucolytic activity, is characterized by many other pharmacodynamic properties which could be beneficial in the management of inflammatory conditions. BACKGROUND: s: Using guinea pig experimental model of allergic inflammation, we evaluated the ability of erdosteine to modulate airway defence mechanisms and inflammation after 10 days (10 mg/kg/day) administration. METHODS: In vivo changes in specific airway resistance and amplitude of tracheal contraction were estimated to evaluate the bronchodilatory effect...
November 28, 2018: Pulmonary Pharmacology & Therapeutics
Li-Bo Zhang, Min He
BACKGROUND: Over the years, mesenchymal stromal (stem) cells (MSCs) have been pre-clinically applied in the treatment of variety kinds of diseases including asthma and chronic lung diseases. Aim of the current study was to systematically review and to conduct meta-analysis on the published studies of MSC treatment in asthma animal models. METHODS: Publications on the MSC and asthma treatment was thoroughly searched in the electronic databases. Statistical analysis was then performed using the Comprehensive Meta-Analysis software (Version 3)...
November 26, 2018: Pulmonary Pharmacology & Therapeutics
Carlo Lombardi, Diego Bagnasco, Cristiano Caruso, Mariella D'Amato, Francesco Menzella, Manlio Milanese, Gianenrico Senna, Giorgio Walter Canonica, Giovanni Passalacqua
Mepolizumab (anti IL-5, monoclonal antibody) is commercially available in Italy since more than one year for the treatment of severe hypereosinophilic asthma. Its efficacy and safety were evaluated in several regulatory trials. The characteristics of this drug in real life began to be assessed only recently. We describe herein the drop-out rate observed with mepolizumab in real life, because this datum can indirectly reflect the safety and tolerability aspects. The demographic and clinical data of patients receiving mepolizumab for severe asthma were collected, and the number and reasons for discontinuation of the treatment were analyzed...
February 2019: Pulmonary Pharmacology & Therapeutics
Rafael J Hernández Zenteno, Danitza Fernández Lara, Alejandra Ramírez Venegas, Raúl H Sansores, Justino Regalado Pineda, Fernando Flores Trujillo, José Rogelio Pérez Padilla, Maria Gabriela Matera, Mario Cazzola
BACKGROUND: Quitting smoking is key for patients with Chronic Obstructive Pulmonary Disease (COPD). Standard recommendations for quitting smoking are implemented for COPD as well. Varenicline Tartrate (VT) is the most effective drug to help quit smoking, but few studies have analysed its effectiveness. AIM OF THE STUDY: To determine the Abstinence Rate (AR) at 12 months, in COPD and non-COPD smokers. METHODS: Observational study in 31 COPD (post bronchodilator-BD FEV1 /FVC <0...
December 2018: Pulmonary Pharmacology & Therapeutics
Zhen Ma, Cungang Zhao, Qi Chen, Chenhuan Yu, Huanhuan Zhang, Zhimin Zhang, Wenhai Huang, Zhengrong Shen
BACKGROUND: Idiopathic pulmonary fibrosis is a lethal fibrosing interstitial pneumonia characterized by progressive worsening of dyspnea and lung function with poor prognosis. Since pirfenidone was approved for IPF treatment, the search for more effective candidates has been greatly intensified. METHODS: In this study, the antifibrotic effects and mechanisms of compound PBD-617, the ideal candidate discovered in our previous work, were investigated on transforming growth factor-β1 (TGF-β1)-induced human embryonic lung fibroblasts (HELF) and on bleomycin (BLM)-induced pulmonary fibrotic rats...
December 2018: Pulmonary Pharmacology & Therapeutics
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