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Protective lung strategy

Chris Durkin, Travis Schisler, Jens Lohser
PURPOSE OF REVIEW: Despite marked improvements in perioperative outcomes, esophagectomy continues to be a high-risk operation associated with significant morbidity and mortality. Progress has been achieved through evidence-based changes in preoperative optimization, intraoperative ventilation strategies, fluid therapy, and analgesia, as well as expedited postoperative recovery pathways. This review will summarize the recent literature on the anesthetic management of patients undergoing esophageal resection...
October 18, 2016: Current Opinion in Anaesthesiology
Adam J N Raymakers, Natalie McCormick, Carlo A Marra, J Mark Fitzgerald, Don Sin, Larry D Lynd
Inhaled corticosteroids (ICS) are commonly prescribed to COPD patients, particularly those with more advanced stages of the disease. These patients are also at increased risk of lung cancer. A systematic review was undertaken to identify studies that examined the association between lung cancer risk and ICS therapy in COPD patients. The search strategy was created in MEDLINE and extended to EMBASE as well as other relevant databases. Both randomized controlled trials (RCTs) and observational studies were considered for inclusion...
October 19, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
You Jin Jang, Moon Jung Back, Zhicheng Fu, Joo Hyun Lee, Jong Hoon Won, Hae Chan Ha, Hae Kyung Lee, Ji Min Jang, Jong Min Choi, Dae Kyong Kim
Acute lung injury (ALI) is a respiratory failure disease and the major source of mortality in the critically ill patients. The main pathological changes involved in ALI include the excessive recruitment and activation of neutrophils by increased pro-inflammatory mediators. However, any specific therapy for ALI has not been developed. The objective of this study was to investigate protective effects of parthenolide, a sesquiterpene lactone produced in feverfew, on LPS-induced lung injury. In the present study, parthenolide treatment reduced infiltration of inflammatory cells, airway permeability and production of pro-inflammatory cytokines in LPS-induced ALI mouse model...
October 18, 2016: Archives of Pharmacal Research
Wook-Jin Chung
Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome...
September 2016: Journal of Hypertension
Elisabet Cuyàs, Almudena Pérez-Sánchez, Vicente Micol, Javier A Menendez, Joaquim Bosch-Barrera
The signal transducer and activator of transcription 3 (STAT3) has been suggested to play a prominent role in mediating non-small-cell lung cancer (NSCLC) resistance to some tyrosine kinase inhibitor (TKI)-mediated therapies. Using a model of anaplastic lymphoma kinase gene (ALK)-translocated NSCLC with acquired resistance to the ALK TKI crizotinib, but lacking amplifications or mutations in the kinase domain of ALK, we herein present evidence that STAT3 activation is a novel mechanism of crizotinib resistance that involves the upregulation of immune escape and epithelial to mesenchymal transition (EMT) signaling pathways...
October 18, 2016: Cell Cycle
Luciana P Tavares, Mauro M Teixeira, Cristiana C Garcia
Influenza A virus (IAV) is a relevant respiratory tract pathogen leading to a great number of deaths and hospitalizations worldwide. Secondary bacterial infections are a very common cause of IAV associated morbidity and mortality. The robust inflammatory response that follows infection is important for the control of virus proliferation but is also associated with lung damage, morbidity and death. The role of the different components of immune response underlying protection or disease during IAV infection is not completely elucidated...
October 15, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Q Lv
OBJECTIVE: In order to seek an effective strategy for clinical treatment of acute lung injury (ALI), we are committed to explore the effect of combination therapy of glucocorticoid and hyaluronic acid on acute lung injury caused by an endotoxin (LPS) and its mechanism. MATERIALS AND METHODS: Adult male Sprague-Dawley (SD) rats were divided randomly into 5 groups: normal group (n=8); LPS group (n=8); dexamethasone +LPS group (DXMS group, n=8); hyaluronic acid+ LPS group (HA group, n=8); dexamethasone +hyaluronic acid +LPS group (DXMS+HA group, n=8)...
September 2016: European Review for Medical and Pharmacological Sciences
Anne Lorenz, Vinay Pawar, Susanne Häussler, Siegfried Weiss
Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies...
October 12, 2016: FEBS Letters
Erik Tenland, Gisela Håkansson, Nader Alaridah, Nataliya Lutay, Anna Rönnholm, Oskar Hallgren, Gunilla Westergren-Thorsson, Gabriela Godaly
Mycobacterium bovis bacilli Calmette-Guerin (BCG) is used as a benchmark to compare the immunogenicity of new vaccines against tuberculosis. This live vaccine is administered intradermal, but several new studies show that changing the route to mucosal immunisation represents an improved strategy. We analysed the immunomodulatory functions of BCG on human neutrophils and primary airway epithelial cells (AECs), as the early events of mucosal immune activation are unclear. Neutrophils and the primary epithelial cells were found to express the IL-17A receptor subunit IL-17RA, while the expression of IL-17RE was only observed on epithelial cells...
2016: PloS One
Hesham Fathy Hassan Hassan, Ahmed Mohamed Mansour, Amira Morad Hussein Abo-Youssef, Bakheet E M Elsadek, Basim Anwar Shehata Messiha
Currently, the outcomes of conventional chemotherapeutic approaches are unsatisfactory. Clinical application of nanoparticles seems promising. We aim to evaluate the possible antitumor activity of zinc oxide nanoparticles (ZnONPs) as a chemotherapeutic approach in in vitro and in vivo experimental models. An in vitro study was performed on three different cell lines, namely human hepatocellular carcinoma (HEPG2), human prostate cancer (PC3), and none-small cell lung cancer (A549) cell lines. An in vivo study using diethylnitrosamine (DENA)-induced HCC in adult male Wistar rats was conducted to investigate the potential antitumor activity of ZnONPs in HCC and the possible underlying mechanisms...
October 8, 2016: Clinical and Experimental Pharmacology & Physiology
Takeshi Shiraishi, Akinori Iwasaki
The most frequent cause of death within a year after lung transplantation is infectious complications, which shifts to chronic allograft rejection or chronic lung allograft dysfunction(CLAD) thereafter. It is no doubt that minimization of the dose of immunosuppression within the acceptable therapeutic range is a best strategy to avoid infectious complications however, adequate dose of immunosuppressant is mandatory to protect lung allografts from acute or chronic rejection. Carefully balanced therapy of immunosuppression and infection control is extremely important for patient's long term survival after lung transplantation...
October 2016: Kyobu Geka. the Japanese Journal of Thoracic Surgery
René H M Raeven, Jolanda Brummelman, Larissa van der Maas, Wichard Tilstra, Jeroen L A Pennings, Wanda G H Han, Cécile A C M van Els, Elly van Riet, Gideon F A Kersten, Bernard Metz
Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B...
2016: PloS One
Yawei Wang, Haiyan Zhang, Jisheng Li, Xiuwen Wang
An acquired T798M gatekeeper mutation in human epidermal growth factor receptor 2 (HER2) kinase can cause drug resistance to anti-HER2 chemotherapy drugs in lung cancer. Previously, the reversible pan-kinase inhibitor Staurosporine has been found to selectively inhibit the HER2 T798M mutant over wild-type kinase, suggesting that the Staurosporine scaffold is potentially to develop mutant-selective inhibitors. Here, we systematically evaluated the chemical space of Staurosporine scaffold-based compounds in response to HER2 T798M mutation at structural, energetic and molecular levels by using an integrated analysis strategy...
October 1, 2016: Chemistry & Biodiversity
Jialing Pan, Tingting Xu, Fengli Xu, Yali Zhang, Zhiguo Liu, Wenbo Chen, Weitao Fu, Yuanrong Dai, Yunjie Zhao, Jianpeng Feng, Guang Liang
Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. Resveratrol and curcumin are proven to have potent anti-inflammatory efficacy, but their clinical application is limited by their metabolic instability. Here, a series of resveratrol and the Mono-carbonyl analogs of curcumin (MCAs) hybrids were designed and synthesized by efficient aldol construction strategy, and then screened for anti-inflammatory activities in vitro and in vivo. The results showed that the majority of analogs effectively inhibited the LPS-induced production of IL-6 and TNF-α...
September 10, 2016: European Journal of Medicinal Chemistry
Santiago Uranga, Dessislava Marinova, Carlos Martin, Nacho Aguilo
Despite global coverage of intradermal BCG vaccination, tuberculosis remains one of the most prevalent infectious diseases in the world. Preclinical data have encouraged pulmonary tuberculosis vaccines as a promising strategy to prevent pulmonary disease, which is responsible for transmission. In this work, we describe the methodology used to demonstrate in the mouse model the benefits of intranasal BCG vaccination when compared to subcutaneous. Our data revealed greater protective efficacy following intranasal BCG administration...
2016: Journal of Visualized Experiments: JoVE
Yu-Li Chen, Tsong-Long Hwang, Huang-Ping Yu, Jia-You Fang, Kowit Yu Chong, Yao-Wen Chang, Chun-Yu Chen, Hsuan-Wu Yang, Wen-Yi Chang, Pei-Wen Hsieh
Acute lung injury (ALI) is a severe respiratory disease with high mortality rates worldwide. Recent reports suggest that human neutrophil elastase (HNE) plays a key role in the inflammatory response that is characteristic of ALI, which indicates that the development of HNE inhibitors could be an efficient treatment strategy. In the current study, an enzyme-based screening assay was used to identify effective HNE inhibitors from a number of traditional Chinese medicines (TCMs). Among them, a water extract of Ilex kaushue (IKWE) effectively inhibited HNE activity (IC50, 11...
September 29, 2016: Scientific Reports
Akinobu Kamei, Geli Gao, Geoffrey Neale, Lip Nam Loh, Peter Vogel, Paul G Thomas, Elaine I Tuomanen, Peter J Murray
Infection is the single greatest threat to survival during cancer chemotherapy because of depletion of bone marrow-derived immune cells. Phagocytes, especially neutrophils, are key effectors in immunity to extracellular pathogens, which has limited the development of new approaches to protect patients with cancer and chemotherapy-induced neutropenia. Using a model of vaccine-induced protection against lethal Pseudomonas aeruginosa pneumonia in the setting of chemotherapy-induced neutropenia, we found a population of resident lung macrophages in the immunized lung that mediated protection in the absence of neutrophils, bone marrow-derived monocytes, or antibodies...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Hannah A Scarborough, Barbara A Helfrich, Matias Casas-Selves, Alwin Schuller, Shaun E Grosskurth, Jihye Kim, Aik-Choon Tan, Daniel C Chan, Zhiyong Zhang, Vadym Zaberezhnyy, Paul A Bunn, James DeGregori
PURPOSE: The emergence of EGFR-inhibitors such as gefitinib, erlotinib and osimertinib has provided novel treatment opportunities in EGFR-driven non-small cell lung cancer (NSCLC). However, most patients with EGFR-driven cancers treated with these inhibitors eventually relapse. Recent efforts have identified the canonical Wnt pathway as a mechanism of protection from EGFR-inhibition and that inhibiting tankyrase, a key player in this pathway, is a potential therapeutic strategy for the treatment of EGFR-driven tumors...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Dang-Dang Xu, Yun-Liang Deng, Cheng-Yu Li, Yi Lin, Hong-Wu Tang
The world health organization figures show prostate cancer in developed countries has been the second primary cause of cancer mortality following lung cancer for the men. So, early and sensitive diagnosis of cancer is very important before it spreads out to the other organs of the body. It is well-known that prostate-specific antigen (PSA) is the most specific and efficient tumor marker for the diagnosis of prostate cancer. Herein, we successfully fabricated core-shell composite fluorescent nanoparticle Ag@SiO2@SiO2-RuBpy which provide a photoluminescence enhancement of up to ~3-fold when the separation distance between the surface of silver core and the center of the third RuBpy doped silica shell is about 10nm...
September 12, 2016: Biosensors & Bioelectronics
Wook-Jin Chung
Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome...
September 2016: Journal of Hypertension
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