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https://www.readbyqxmd.com/read/27936238/trehalose-6-phosphate-mediated-toxicity-determines-essentiality-of-otsb2-in-mycobacterium-tuberculosis-in-vitro-and-in-mice
#1
Jan Korte, Marina Alber, Carolina M Trujillo, Karl Syson, Hendrik Koliwer-Brandl, René Deenen, Karl Köhrer, Michael A DeJesus, Travis Hartman, William R Jacobs, Stephen Bornemann, Thomas R Ioerger, Sabine Ehrt, Rainer Kalscheuer
Trehalose biosynthesis is considered an attractive target for the development of antimicrobials against fungal, helminthic and bacterial pathogens including Mycobacterium tuberculosis. The most common biosynthetic route involves trehalose-6-phosphate (T6P) synthase OtsA and T6P phosphatase OtsB that generate trehalose from ADP/UDP-glucose and glucose-6-phosphate. In order to assess the drug target potential of T6P phosphatase, we generated a conditional mutant of M. tuberculosis allowing the regulated gene silencing of the T6P phosphatase gene otsB2...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27933955/biphenyl-pyridazinone-derivatives-as-inhaled-pde4-inhibitors-structural-biology-and-structure-activity-relationships
#2
Jordi Gràcia, Maria Antonia Buil, Jordi Castro, Peter Eichhorn, Manel Ferrer, Amadeu Gavaldà, Begoña Hernández, Victor Segarra, Martin D Lehner, Imma Moreno, Lluís Pagès, Richard S Roberts, Jordi Serrat, Sara Sevilla, Joan Taltavull, Miriam Andrés, Judit Cabedo, Dolors Vilella, Elena Calama, Carla Carcasona, Montserrat Miralpeix
Cyclic nucleotide cAMP is a ubiquitous secondary messenger involved in a plethora of cellular responses to biological agents involving activation of adenylyl cyclase. Its intracellular levels are tightly controlled by a family of cyclic nucleotide degrading enzymes, the PDEs. In recent years, cyclic nucleotide phosphodiesterase type 4 (PDE4) has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases, particularly in the management of asthma and COPD. Here we describe our efforts to discover novel, highly potent inhaled inhibitors of PDE4...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27916621/point-should-inhaled-antibiotic-therapy-be-routinely-used-for-the-treatment-of-bacterial-lower-respiratory-tract-infections-in-the-icu-setting-yes
#3
EDITORIAL
Richard G Wunderink
Routine use of aerosolized antibiotics is the most rational approach to the current treatment dilemmas for severe hospital-acquired pneumonia (HAP) requiring endotracheal intubation or ventilator-associated pneumonia (VAP). The two main issues for HAP/VAP are inappropriate initial therapy and ineffective therapy for multidrug resistant (MDR) pathogens, particularly gram negative bacilli such as Pseudomonas aeruginosa and Acinetobacter species. The emergence of extended spectrum beta-lactamases (ESBL) and carbapenem resistance in Enterobacteriaceae (CRE) have made even common pathogens such as Escherichia coli difficult to treat...
November 22, 2016: Chest
https://www.readbyqxmd.com/read/27898235/postexposure-prophylaxis-after-possible-anthrax-exposure-adherence-and-adverse-events
#4
Leisha D Nolen, Rita M Traxler, Grishma A Kharod, Pallavi A Kache, Stefan Katharios-Lanwermeyer, Katherine A Hendricks, Sean V Shadomy, William A Bower, Dana Meaney-Delman, Henry T Walke
Anthrax postexposure prophylaxis (PEP) was recommended to 42 people after a laboratory incident that involved potential aerosolization of Bacillus anthracis spores in 2 laboratories at the Centers for Disease Control and Prevention in 2014. At least 31 (74%) individuals who initiated PEP did not complete either the recommended 60 days of antimicrobial therapy or the 3-dose vaccine regimen. Among the 29 that discontinued the antimicrobial component of PEP, most (38%) individuals discontinued PEP because of their low perceived risk of infection; 9 (31%) individuals discontinued prophylaxis due to PEP-related minor adverse events, and 10% cited both low risk and adverse events as their reason for discontinuation...
November 29, 2016: Health Security
https://www.readbyqxmd.com/read/27890714/a-randomized-trial-of-the-amikacin-fosfomycin-inhalation-system-for-the-adjunctive-therapy-of-gram-negative-ventilator-associated-pneumonia-iasis-trial
#5
Marin H Kollef, Jean-Damien Ricard, Damien Roux, Bruno Francois, Eleni Ischaki, Zsolt Rozgonyi, Thierry Boulain, Zsolt Ivanyi, Gál János, Denis Garot, Firas Koura, Epaminondas Zakynthinos, George Dimopoulos, Antonio Torres, Wayne Danker, A Bruce Montgomery
BACKGROUND: Clinical failures in ventilator-associated pneumonia (VAP) caused by Gram-negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. METHODS: We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of Gram-negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if <10 days) via the investigational eFlow Inline System (PARI GmbH, Germany)...
November 24, 2016: Chest
https://www.readbyqxmd.com/read/27866986/modelling-of-in-vitro-and-in-vivo-performance-of-aerosol-emitted-from-different-vibrating-mesh-nebulisers-in-non-invasive-ventilation-circuit
#6
Hoda Rabea, Ahmed M A Ali, Randa Salah Eldin, Maha M Abdelrahman, Amira S A Said, Mohamed E Abdelrahim
Substituting nebulisers by another in non-invasive ventilation circuit (NIV) involves many process variables which must be adjusted to ensure patient optimum therapy. However, there is a doubt when nebulisers use the same technology. Data mining technology based on artificial neural networks and genetic algorithms were used here to model in-vitro inhalation process and predict bioavailability from inhaled doses delivered by three different vibrating mesh nebulisers (VMNs) in NIV. Modelling of data indicated that in-vitro performance of VMNs was dependent mainly on fine particle fraction, mass median aerodynamic diameter (MMAD), total emitted dose (TED) and to lesser extent on nebuliser type...
November 17, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27866296/intranasal-curcumin-inhibits-pulmonary-fibrosis-by-modulating-matrix-metalloproteinase-9-mmp-9-in-ovalbumin-induced-chronic-asthma
#7
Preeti S Chauhan, D Dash, Rashmi Singh
Pulmonary fibrosis is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been found effective in allergic asthma. To study the effect of intranasal curcumin on airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21 (after sensitization) for 5 weeks (twice/week)...
November 19, 2016: Inflammation
https://www.readbyqxmd.com/read/27863827/-assessment-of-physicians-and-nurses-knowledge-and-practices-of-aerosol-therapy
#8
N Eychenne, A Jaouadi, D Macquart de Terline, A Fratta, S Laribe-Caget, O Steichen, C Fernandez, M Antignac
INTRODUCTION: Aerosol therapy is an efficient, but complex procedure. National and international practice guidelines are regularly updated. However, only a few studies have assessed the application of guidelines by users. The aim of this study is to assess the knowledge and practices of physicians and nurses regarding these guidelines. METHODS: Two self-administered questionnaires were designed by a working team and presented to physicians and nurses of four university hospitals in Paris...
November 15, 2016: Revue des Maladies Respiratoires
https://www.readbyqxmd.com/read/27852893/philip-morris-research-on-precursors-to-the-modern-e-cigarette-since-1990
#9
Lauren M Dutra, Rachel Grana, Stanton A Glantz
BACKGROUND: Use of electronic cigarettes (e-cigarettes) is increasing rapidly. Chinese pharmacist Hon Lik is frequently cited as inventing the modern e-cigarette in 2003. However, tobacco companies have developed electronic nicotine delivery systems since at least 1963. METHODS: We searched the University of California San Francisco Truth (formerly Legacy) Tobacco Industry Documents beginning with the terms 'electric cigarette' and 'electronic cigarettes', 'e-cigarette', 'smokeless cigarettes', 'nicotine aerosol', 'tobacco aerosol', and 'vaping' and then expanded the search using snowball sampling...
November 15, 2016: Tobacco Control
https://www.readbyqxmd.com/read/27850320/681-aerosolized-amikacin-as-adjunctive-therapy-of-vap-caused-by-mdr-gnb
#10
Chang Liu, Jianguo Li, Zhiyong Peng
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27846726/-new-technologies-for-in-vivo-cancer-diagnostics
#11
L Hernychova, D Coufalová, E Michalova, R Nenutil, B Vojtěšek
BACKGROUND: The treatment of oncological diseases is based on the combination of surgery, representing the key step for the removal of the tumor tissue, radiotherapy, chemotherapy, and hormone therapy. However, the surgery is often accompanied by issue of determining the boundaries of the tumor. Prior the operation, the surgeon has information on preoperative findings, which indicate the location and extent of the tumor, but does not specify a clear boundary between the tumor and healthy tissue...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/27834151/in-vitro-and-in-vivo-performance-of-novel-spray-dried-andrographolide-loaded-scleroglucan-based-formulation-for-dry-powder-inhaler
#12
Ashwin J Mali, C Bothiraja, Ravindra R Purohit, Atmaram P Pawar
Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity...
November 9, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27809794/alternative-pre-approved-and-novel-therapies-for-the-treatment-of-anthrax
#13
REVIEW
Breanne M Head, Ethan Rubinstein, Adrienne F A Meyers
BACKGROUND: Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death...
November 3, 2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27806553/a-survey-of-acute-q-fever-among-patients-with-brucellosis-like-and-atypical-pneumonia-symptoms-who-are-referred-to-qaemshahr-razi-hospital-in-northern-iran-2014-2015
#14
Roya Ghasemian, Ehsan Mostafavi, Saber Esmaeili, Narges Najafi, Sara Arabsheybani
INTRODUCTION: Coxiella burnetii is the etiologic agent of the zoonotic disease of Q fever which causes lots of morbidities and mortalities every year. The main route of human infection is inhalation of contaminated aerosols; however, consumption of contaminated dairy products is the second cause. Mazandaran province is one of the main livestock centers of the country and consumption of raw dairy in the region is quite common. There isn't any data about Q fever incidence in this region...
August 26, 2016: Global Journal of Health Science
https://www.readbyqxmd.com/read/27804854/aerosol-delivery-devices-for-the-treatment-of-adult-patients-in-acute-and-critical-care
#15
Arzu Ari, James B Fink
Aerosolized medications are commonly used for the treatment of patients with pulmonary diseases in acute care. While there are many drug/device combinations available on the market, new devices have been developed in the past few years. Due to differences in their operation, performance and requirements for proper use, it is important to know how to use these aerosol devices effectively during inhalation therapy both in ambulatory and acute settings. This paper reviews aerosol devices used for the treatment of patients with an emphasis on acute and critical care...
October 28, 2016: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/27795380/pharmacodynamics-of-aerosolized-fosfomycin-and-amikacin-against-resistant-clinical-isolates-of-pseudomonas-aeruginosa-and-klebsiella-pneumoniae-in-a-hollow-fiber-infection-model-experimental-basis-for-combination-therapy
#16
Fekade Bruck Sime, Adam Johnson, Sarah Whalley, Anahi Santoyo-Castelazo, A Bruce Montgomery, Kathie Ann Walters, Jeffrey Lipman, William W Hope, Jason A Roberts
There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia, caused by multi-drug resistant pathogens. A combination formulation of amikacin/fosfomycin is currently undergoing clinical testing although the exposure response-relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs 16 mg/L; 64 mg/L) and Klebsiella pneumoniae (MICs 2 mg/L; 64 mg/L) using the dynamic hollow-fiber infection model over 7-days...
October 24, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27779664/inhalation-of-inactivated%C3%A2-mycobacterium%C3%A2-phlei-prevents-asthma%C3%A2-mediated-airway-hyperresponsiveness-and-airway-eosinophilia-in-mice-by-reducing-il%C3%A2-5-and-il%C3%A2-13-levels
#17
Moyu Ming, Zhixi Luo, Shengqiu Lv, Chaoqian Li
The present study aimed to investigate whether inhalation of inactivated‑Mycobacterium phlei could prevent airway hyperresponsiveness and airway eosinophilia. A total of 24 male Balb/c mice were randomly divided into three groups: Normal control group (group A), asthma model group (group B) and the intervention group (group C), (8 mice/group). Group A mice were sensitized and with challenged saline and group B with ovalbumin (OVA). Group C mice were administered with aerosol Mycobacterium phlei once daily prior to the allergen challenge...
October 19, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27776446/inhaled-phage-therapy-a-promising-and-challenging-approach-to-treat-bacterial-respiratory-infections
#18
Elsa Bodier-Montagutelli, Eric Morello, Guillaume l'Hostis, Antoine Guillon, Emilie Dalloneau, Renaud Respaud, Nikita Pallaoro, Hélène Blois, Laurent Vecellio, Jérôme Gabard, Nathalie Heuzé-Vourc'h
Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context...
October 25, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27769520/combined-local-pulmonary-and-systemic-delivery-of-at2r-gene-by-modified-tat-peptide-nanoparticles-attenuates-both-murine-and-human-lung-carcinoma-xenografts-in-mice
#19
Susumu Ishiguro, Nabil A Alhakamy, Deepthi Uppalapati, Jennifer Delzeit, Cory J Berkland, Masaaki Tamura
To evaluate the potential of cell-penetrating peptide-based delivery of apoptosis-inducer gene in cancer therapy, a modified HIV-1 TAT peptide (dimerized TAT peptide, dTAT) was studied. The dTAT and plasmid DNA (pDNA) complexes (dTAT-pDNA) were condensed using calcium chloride (dTAT-pDNA-Ca(2+)). This simple nonviral formulation approach showed high levels of gene expression in vitro without any cytotoxicity. In mouse studies, a single intratracheal (IT) aerosol spray or 2 intravenous (IV) injections of the dTAT, apoptosis-inducer gene, angiotensin II type 2 receptor (AT2R), and Ca(2+) complexes (dTAT-pAT2R-Ca(2+)) significantly attenuated the acutely growing mouse Lewis lung carcinoma allografts in mouse lungs...
October 18, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27751218/-effect-of-obesity-on-treatment-outcome-of-asthma-predictive-index-positive-infants-and-young-children-with-wheezing
#20
Bo Chen, Shuai Feng, Xiao-Wen Yin
OBJECTIVE: To study the effect of obesity on the treatment outcome of asthma predictive index (API)-positive infants and young children with wheezing. METHODS: A total of 208 API-positive infants and young children with wheezing were enrolled. According to the Kaup index, the patients were divided into an obese group (n=93) and a non-obese group (n=115). The patients were given multimodality therapy in an acute episode of wheezing and aerosol inhalation of inhaled corticosteroid (ICS) budesonide suspension in the remission stage...
October 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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