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https://www.readbyqxmd.com/read/28721208/new-perspectives-on-the-regulation-of-type-ii-inflammation-in-asthma
#1
REVIEW
Mireya Becerra-Díaz, Marsha Wills-Karp, Nicola M Heller
Asthma is a chronic inflammatory disease of the lungs which has been thought to arise as a result of inappropriately directed T helper type-2 (Th2) immune responses of the lungs to otherwise innocuous inhaled antigens. Current asthma therapeutics are directed towards the amelioration of downstream consequences of type-2 immune responses (i.e. β-agonists) or broad-spectrum immunosuppression (i.e. corticosteroids). However, few approaches to date have been focused on the primary prevention of immune deviation...
2017: F1000Research
https://www.readbyqxmd.com/read/28721202/defining-the-inflammatory-signature-of-human-lung-explant-tissue-in-the-presence-and-absence-of-glucocorticoid
#2
Tracy L Rimington, Emily Hodge, Charlotte K Billington, Sangita Bhaker, Binaya K C, Iain Kilty, Scott Jelinsky, Ian P Hall, Ian Sayers
BACKGROUND:  Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help study the mechanisms underlying inflammatory responses and which can provide a tool to aid drug discovery for inflammatory respiratory diseases such as asthma and COPD. METHOD:  Parenchymal lung tissue from 6 individual donors was dissected and cultured with two pro-inflammatory stimuli, lipopolysaccharide (LPS) (1 µg/ml) and interleukin-1 beta (IL-1β) (10 ng/ml) in the presence or absence of dexamethasone (1 µM)...
2017: F1000Research
https://www.readbyqxmd.com/read/28720675/the-effect-of-nebulizer-position-on-aerosolized-epoprostenol-delivery-in-an-adult-lung-model
#3
Allison C Anderson, Meagan N Dubosky, Kelly A Fiorino, Vanessa Quintana, Carl A Kaplan, David L Vines
BACKGROUND: Aerosolized epoprostenol is an alternative for inhaled nitric oxide in the management of pulmonary arterial hypertension and possibly acute hypoxemia. Our objective was to determine differences in drug deposition based on different nebulizer positions in the ventilator circuit, using a vibrating mesh nebulizer. METHODS: An 8.0-mm inner diameter endotracheal tube (ETT) was connected to a training test lung, compliance of 30 mL/cm H2O, with a collecting filter placed at the ETT-test lung junction...
July 18, 2017: Respiratory Care
https://www.readbyqxmd.com/read/28720405/persistent-cognitive-and-morphological-alterations-induced-by-repeated-exposure-of-adolescent-rats-to-the-abused-inhalant-toluene
#4
K M Braunscheidel, J T Gass, P J Mulholland, S B Floresco, J J Woodward
While thepsychoactive inhalant toluene causes behavioral effects similarto those produced by other drugs of abuse, the persistent behavioral and anatomical abnormalities induced by toluene exposure are not well known. To mimic human "binge-like" inhalant intoxication, adolescent, male Sprague-Dawley rats were exposed to toluene vapor (57000 ppm) twice daily for five consecutive days. These rats remained in their home cages until adulthood (P60), when they were trained in operant boxes to respond to a palatable food reward and then challenged with several different cognitive tasks...
July 15, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28718908/death-from-butane-inhalation-abuse-in-teenagers-two-new-case-studies-and-review-of-the-literature
#5
Véronique Alunni, Yvan Gaillard, François Castier, Marie-Dominique Piercecchi-Marti, Gérald Quatrehomme
The ready availability of butane makes butane abuse frequent. Fatalities are rare. This study presents two cases of death by butane overdose. The postmortem analyses were carried out using headspace gas chromatography-mass spectrometry. It revealed femoral blood butane concentrations of 18 and 22 mg/L, respectively, as well as specific combinations of adjuvants in each victim. In one of the victims, brain and fatty tissue also contained butane, pointing to chronic consumption. The originality of this study is to show that the identification of specific combinations of adjuvants can be helpful for identifying the brand of deodorant used...
July 18, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28718049/good-things-in-small-packages-an-innovative-delivery-approach-for-inhaled-insulin
#6
James B Fink, Lisa Molloy, John S Patton, Valdecir Castor Galindo-Filho, Jacqueline de Melo Barcelar, Luciana Alcoforado, Simone Cristina Soares Brandão, Armèle Dornelas de Andrade
PURPOSE: The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3-6 μm particle size distribution. METHODS: In silico modeling with computational fluid dynamics (CFD) and in vitro testing of device components were assessed using an Alberta idealized adult airway (Copley, UK) to optimize mouthpiece and aerosol path design for dose delivered distal to the trachea...
July 17, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28717881/a-retrospective-comparison-of-inhaled-milrinone-and-iloprost-in-post-bypass-pulmonary-hypertension
#7
Kassiani Theodoraki, Apostolos Thanopoulos, Panagiota Rellia, Evangelos Leontiadis, Dimitrios Zarkalis, Konstantinos Perreas, Theophani Antoniou
During cardiac operations, weaning from cardiopulmonary bypass (CPB) may prove challenging as a result of superimposed acute right ventricular dysfunction in the setting of elevated pulmonary vascular resistance (PVR). The aim of this study was to retrospectively evaluate the effect of inhaled milrinone versus inhaled iloprost in patients with persistent pulmonary hypertension following discontinuation of CPB. Eighteen patients with elevated PVR post-bypass were administered inhaled milrinone at a cumulative dose of 50 μg kg(-1)...
July 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28713018/effect-of-increased-surface-hydrophobicity-via-drug-conjugation-on-the-clearance-of-inhaled-pegylated-polylysine-dendrimers
#8
Shadabul Haque, Victoria M McLeod, Seth Jones, Sandy Fung, Michael Whittaker, Michelle McIntosh, Colin Pouton, David J Owen, Christopher J H Porter, Lisa M Kaminskas
PEGylated polylysine dendrimers are attractive and well tolerated inhalable drug delivery platforms that have the potential to control the release, absorption kinetics and lung retention time of conjugated drugs. The clinical application of these systems though, would likely require partial substitution of surface PEG groups with drug molecules that are anticipated to alter their lung clearance kinetics and clearance pathways. In the current study, we therefore evaluated the impact of increased surface hydrophobicity via substitution of 50% surface PEG groups with a model hydrophobic drug (α-carboxyl OtButylated methotrexate) on the lung clearance of a Generation 5 PEGylated polylysine dendrimer in rats...
July 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28709902/duration-of-fever-and-other-symptoms-after-the-inhalation-of-laninamivir-octanoate-hydrate-comparison-of-the-2011-12-to-2015-16-japanese-influenza-seasons
#9
Hideyuki Ikematsu, Naoki Kawai, Norio Iwaki, Seizaburo Kashiwagi
The duration of fever and symptoms after laninamivir octanoate hydrate (laninamivir) inhalation were investigated in the Japanese 2015/16 influenza season, and the results were compared with those of the 2011/12 to 2014/15 seasons. A total of 1068 patients were evaluated for the duration of fever and symptoms in the five studied seasons. The influenza types/subtypes were 125 A(H1N1)pdm09 (62.2%), 17 A(H3N2) (8.5%), and 59 B (29.4%) in the 2015/16 season. The median durations of fever were 40.0, 41.0, and 47...
July 11, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28709466/effects-of-inhaled-hypertonic-7-saline-on-lung-function-test-in-preschool-children-with-cystic-fibrosis-results-of-a-crossover-randomized-clinical-trial
#10
Raffaella Nenna, Fabio Midulla, Caterina Lambiase, Giovanna De Castro, Anna Maria Zicari, Luciana Indinnimeo, Giuseppe Cimino, Patrizia Troiani, Serena Quattrucci, Giancarlo Tancredi
BACKGROUND: This crossover, randomized, double-blind study (conducted over a 32-week period) was performed to determine, in clinically stable Cystic fibrosis (CF) preschool children: the effects of 7% inhaled hypertonic saline on spirometry and interrupter resistance technique (Rint), and the possible side effects. METHODS: Twelve CF children (6M, mean age ± SD: 5.7 ± 0.8 yrs) were enrolled and randomly assigned to receive hypertonic saline (HS-4 ml 7% sodium chloride), or normal saline (NS-0...
July 15, 2017: Italian Journal of Pediatrics
https://www.readbyqxmd.com/read/28708443/regulatory-approaches-and-considerations-in-establishing-bioequivalence-of-inhaled-compounds
#11
Irvin Mayers, Mohit Bhutani
To be considered bioequivalent to their branded counterparts, generic drugs must meet the standards for bioequivalence (BE) described by the regulatory agencies. While BE of generic inhalational drugs can be evaluated using a similar approach as that for oral dosage from products or drugs that are delivered systemically, the approach is insufficient to address the complexities of inhalational products (e.g., localized site of action, device-patient interface). Therefore, more considerations are needed and caution should be applied when evaluating BE of inhaled compounds...
July 14, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28708440/model-calculations-of-regional-deposition-and-disposition-for-single-doses-of-inhaled-liposomal-and-dry-powder-ciprofloxacin
#12
Andrew R Martin, Warren H Finlay
BACKGROUND: Model predictions of regional deposition in the respiratory tract are useful in assessing factors that influence the effectiveness of aerosol delivery. Regional deposition models have previously been coupled with models of mucous production and clearance to estimate initial concentrations of drug deposited in the airway surface liquid (ASL) lining tracheobronchial airways. METHODS: Established models of regional deposition and ASL volumes were used to provide input to a new model evaluating the disposition of drug resulting from dissolution or release, absorption, and mucociliary clearance...
July 14, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28706334/an-evaluation-of-impact-of-educational-interventions-on-the-technique-of-use-of-metered-dose-inhaler-by-patients
#13
Avadhi Nirajkumar Purohit, P P Patel, A M Gandhi, M K Desai
OBJECTIVES: The objective of this study is to evaluate the impact of two educational interventions that are demonstration versus pictorial Leaflet in patients using metered-dose inhaler (MDI). MATERIALS AND METHODS: This interventional study was done in patients who were prescribed drugs through MDI at Tuberculosis and Chest Department. The patients were enrolled in Group A or Group B as per random number table method. The method of use of MDI was assessed using a checklist based on the technique described in the WHO Guide to good prescribing...
March 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28702798/the-differential-absorption-of-a-series-of-p-glycoprotein-substrates-in-isolated-perfused-lungs-from-mdr1a-1b-genetic-knockout-mice-can-be-attributed-to-distinct-physico-chemical-properties-an-insight-into-predicting-transporter-mediated-pulmonary-specific
#14
Daniel F Price, Chris N Luscombe, Peter J Eddershaw, Chris D Edwards, Mark Gumbleton
PURPOSE: To examine if pulmonary P-glycoprotein (P-gp) is functional in an intact lung; impeding the pulmonary absorption and increasing lung retention of P-gp substrates administered into the airways. Using calculated physico-chemical properties alone build a predictive Quantitative Structure-Activity Relationship (QSAR) model distinguishing whether a substrate's pulmonary absorption would be limited by P-gp or not. METHODS: A panel of 18 P-gp substrates were administered into the airways of an isolated perfused mouse lung (IPML) model derived from Mdr1a/Mdr1b knockout mice...
July 12, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28701014/-spacer-aerosol-therapy-through-space-and-time
#15
Thomas Voshaar, Peter Haidl, Rolf Michael Clös
Aim of the literature review Within this review, results of a literature analysis on the application of spacers with pressurized metered dose inhalers (pMDI) are described and evaluated. Methods Next to an extensive revision on effects of spacers, the impacts of current guidelines and the conditions for product authorisations on the use of spacers are described which result from the interplay of characteristics from dose inhalers with a spacer. Results Spacers are generally useful to avoid coordination problems concerning the actuation of a pMDI at the beginning of an inhalation...
July 2017: Pneumologie
https://www.readbyqxmd.com/read/28698801/tak1-inhibition-attenuates-both-inflammation-and-fibrosis-in-experimental-pneumoconiosis
#16
Jie Li, Chao Liang, Zong-Kang Zhang, Xiaohua Pan, Songlin Peng, Wing-Sze Lee, Aiping Lu, Zhixiu Lin, Ge Zhang, Wing-Nang Leung, Bao-Ting Zhang
Pneumoconiosis, caused by inhalation of mineral dusts, is a major occupational disease worldwide. Currently, there are no effective drugs owing to a lack of potential therapeutic targets during either the inflammation or fibrosis molecular events in pneumoconiosis. Here, we performed microarrays to identify aberrantly expressed genes in the above molecular events in vitro and found a hub gene transforming growth factor-β-activated kinase 1 (TAK1), which was highly expressed and activated in pneumoconiosis patients as well as silica-exposed rats with experimental pneumoconiosis...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28698321/factors-associated-with-non-persistence-to-oral-and-inhaled-antiviral-therapies-for-seasonal-influenza-a-secondary-analysis-of-a-double-blind-multicentre-randomised-clinical-trial
#17
Remi Flicoteaux, Camelia Protopopescu, Annick Tibi, Thierry Blanchon, Sylvie Van Der Werf, Xavier Duval, Anne Mosnier, Cécile Charlois-Ou, Bruno Lina, Catherine Leport, Sylvie Chevret
OBJECTIVES: We aimed to evaluate and compare non-adherence to oral and inhaled antiviral therapies prescribed of a randomised clinical trial in outpatients with influenza A infection. DESIGN: A parallel, three-arm, double-blinded trial randomly allocated antiviral therapies twice daily for 5 days: (1) oral oseltamivir plus inhaled zanamivir (arm OZ); (2) oseltamivir plus inhaled placebo (arm Opz); or (3) oral placebo plus inhaled zanamivir (arm poZ). Analysis of non-adherence was a secondary objective of the trial...
July 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28696894/preference-of-aerosolized-pirfenidone-to-oral-intake-an-experimental-model-of-pulmonary-fibrosis-by-paraquat
#18
Rokhsana Rasooli, Hamid Rajaian, Abbas Pardakhty, Ali Mandegary
BACKGROUND: Inhalation drug delivery is a fast, effective, and safe route of delivering medication directly to the lungs. Thanks to the large surface area and highly vascularized epithelium in lung, pulmonary drug delivery has been considered as an effective route to deliver drugs to the systemic circulation. Pirfenidone (PF), an oral antifibrotic agent, has been shown to slow down the progression of the lung fibrosis. Inhalation or intrapulmonary delivery of PF appears to be a good alternative to optimize drug delivery and minimize the dosage, adverse and nonspecific effects...
July 11, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28696794/the-effects-of-asthma-medications-on-reactive-oxygen-species-production-in-human-monocytes
#19
Ming-Kai Tsai, Yi-Ching Lin, Ming-Yii Huang, Min-Sheng Lee, Chang-Hung Kuo, Po-Lin Kuo, Ching-Hsiung Lin, Chih-Hsing Hung
OBJECTIVE: Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promote the reactive oxygen species (ROS) production leading to airway inflammation, hyper-responsiveness and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long acting β2 agonists (LABAs; salmeterol and formoterol) and a new extra-LABA (indacaterol)...
July 11, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28696235/evaluation-of-combination-drug-therapy-for-treatment-of-antibiotic-resistant-inhalation-anthrax-in-a-murine-model
#20
H S Heine, S V Shadomy, A E Boyer, L Chuvala, R Riggins, A Kesterson, J Myrick, J Craig, M G Candela, J R Barr, K Hendricks, W A Bower, H Walke, G L Drusano
Bacillus anthracis is considered a likely agent to be used as a bioweapon and use of a strain resistance to the first-line antimicrobial treatments is a concern. We determined treatment efficacy against a ciprofloxacin-resistant (C(r)) strain of B. anthracis (C(r) Ames) in a murine inhalational anthrax model. Ten groups of 46 BALB/c mice were exposed by inhalation to 7-35 LD50 of B. anthracis C(r) Ames spores. Commencing at 36 hours (h) post-exposure, groups were administered intraperitoneal doses of sterile water for injections (SWI) and ciprofloxacinalone (control groups), or ciprofloxacin combined with two antimicrobials including meropenem/linezolid, meropenem/clindamycin, meropenem/rifampin, meropenem/doxycycline, penicillin/linezolid, penicillin/doxycycline, rifampin/linezolid, or rifampin/clindamycin at appropriate dosing intervals(6 or 12 hours) for the respective antibiotics...
July 10, 2017: Antimicrobial Agents and Chemotherapy
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