July 31, 2013

Control of neutrophil inflammation at mucosal surfaces by secreted epithelial products

MINI REVIEW ARTICLE

Front. Immunol., 31 July 2013 | doi: 10.3389/fimmu.2013.00220

Control of neutrophil inflammation at mucosal surfaces by secreted epithelial products

Rose L. Szabady* and Beth A. McCormick
  • Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
The human intestine is a large and delicately balanced organ, responsible for efficiently absorbing nutrients and selectively eliminating disease-causing pathogens. The gut architecture consists of a single layer of epithelial cells that forms a barrier against the food antigens and resident microbiota within the lumen. This barrier is augmented by a thick layer of mucus on the luminal side and an underlying lamina propria containing a resident population of immune cells. Attempted breaches of the intestinal barrier by pathogenic bacteria result in the rapid induction of a coordinated innate immune response that includes release of antimicrobial peptides, activation of pattern recognition receptors, and recruitment of various immune cells. In recent years, the role of epithelial cells in initiating this immune response has been increasingly appreciated. In particular, epithelial cells are responsible for the release of a variety of factors that attract neutrophils, the body’s trained bacterial killers. In this review we will highlight recent research that details a new understanding of how epithelial cells directionally secrete specific compounds at distinct stages of the inflammatory response in order to coordinate the immune response to intestinal microbes. In addition to their importance during the response to infection, evidence suggests that dysregulation of these pathways may contribute to pathologic inflammation during inflammatory bowel disease. Therefore, a continued understanding of the mechanisms by which epithelial cells control neutrophil migration into the intestine will have tremendous benefits in both the understanding of biological processes and the identification of potential therapeutic targets.
Keywords: hepoxilin, eicosanoids, neutrophil migration, Salmonella, intestinal inflammation, lipoxygenase, MRP2, lipid chemoattractant
Citation: Szabady RL and McCormick BA (2013) Control of neutrophil inflammation at mucosal surfaces by secreted epithelial products. Front. Immunol. 4:220. doi: 10.3389/fimmu.2013.00220
Received: 20 May 2013; Paper pending published: 12 June 2013;
Accepted: 15 July 2013; Published online: 31 July 2013.
Edited by:
Rajaraman D. Eri, University of Tasmania, Australia
Reviewed by:
Joseph N. Blattman, University of Washington, USA
George Hajishengallis, University of Pennsylvania, USA
Copyright: © 2013 Szabady and McCormick. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Rose L. Szabady, Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, 368 Plantation Street, AS8-2010, Worcester, MA 01604, USA e-mail: rose.szabady@umassmed.edu

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Factors associated with change in exacerbation frequency in COPD

Open Access
Research

Factors associated with change in exacerbation frequency in COPD

Gavin C Donaldson, Hanna Müllerova, Nicholas Locantore, John R Hurst, Peter MA Calverley, Jorgen Vestbo, Antonio Anzueto and Jadwiga A Wedzicha
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Respiratory Research 2013, 14:79 doi:10.1186/1465-9921-14-79
Published: 30 July 2013

Abstract (provisional)

Background

Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.

Methods

1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly. Exacerbations were defined by health care utilisation. Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.
Findings: Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE. More severe disease was associated with changing from IE to FE and less severe disease from FE to IE. Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.

Conclusion

No parameter clearly predicts an imminent change in exacerbation frequency category.
Trial registration: SCO104960, clinicaltrials.gov identifier NCT00292552

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

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Vaccine adjuvants: mode of action

REVIEW ARTICLE

Front. Immunol., 31 July 2013 | doi: 10.3389/fimmu.2013.00214

Vaccine adjuvants: mode of action

Ennio De Gregorio1, Elena Caproni1 and Jeffrey B. Ulmer2*
  • 1Novartis Vaccines and Diagnostics Inc., Siena, Italy
  • 2Novartis Vaccines and Diagnostics Inc., Cambridge, MA, USA
Vaccines were first introduced more than 200 years ago and have since played a key role in the reduction of morbidity and mortality caused by infectious diseases. Many of the safest and most effective vaccines in use today are based on attenuated live viruses, as they mimic a live infection without causing disease. However, it is not always practical to take this approach, such as when it may not be safe to do so (e.g., for viruses that cause chronic infections such as HIV) or may not be feasible to manufacture (e.g., for viruses that do not grow well in cell culture such as HCV). In addition, it may preferable in some cases to target immune responses toward specific antigens from the pathogen, rather than the entirety of the genome. In these cases, subunit vaccines consisting of antigens purified from the pathogen or produced by recombinant DNA technology are being developed. However, highly purified proteins are typically not inherently immunogenic, as they usually lack the means to directly stimulate the innate immune system, and often require the addition of adjuvants to enhance vaccine potency. Despite more than a century of human use, only a few adjuvants are licensed today. However many adjuvants have been tested in humans and are in advanced stages of development. Much of the early work on adjuvants discovery and development was empirical producing safe and effective products, but without a clear understanding of how they worked. Recent insight into the functioning of the innate immune system has demonstrated its important role in triggering and shaping the adaptive immune response to vaccines.
Keywords: adjuvant, vaccine, human, innate immunity, toll-like receptor
Citation: De Gregorio E, Caproni E and Ulmer JB (2013) Vaccine adjuvants: mode of action.Front. Immunol. 4:214. doi: 10.3389/fimmu.2013.00214
Received: 05 April 2013; Paper pending published: 29 April 2013;
Accepted: 12 July 2013; Published online: 31 July 2013.
Edited by:
Volker Gerdts, Vaccine and Infectious Disease Organization-InterVac, Canada
Reviewed by:
Rae Ritchie, Bioscience Vaccines, Inc., USA
Volker Gerdts, Vaccine and Infectious Disease Organization-InterVac, Canada
Copyright: © 2013 De Gregorio, Caproni and Ulmer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jeffrey B. Ulmer, Novartis Vaccines and Diagnostics, Inc., 350 Massachusetts Avenue, Cambridge, MA 02139, USA e-mail: jeffrey.ulmer@novartis.com

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Asymptomatic Preclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease 



Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 406927, 5 pages
http://dx.doi.org/10.1155/2013/406927
Clinical Study

Asymptomatic Preclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease

Juan Chen,1 YongHong Shi,2 XiaoPing Wang,3 Heqing Huang,1 and Dana Ascherman4
1Rheumatology Department of the First Hospital of Xiamen University, Zhen Hai Road No. 55, Xiamen 361003, China
2Pulmonary Department of the First Hospital of Xiamen University, Zhen Hai Road No. 55, Xiamen 361003, China
3Radiology Department of the First Hospital of Xiamen University, Zhen Hai Road No. 55, Xiamen 361003, China
4University of Miami School of Medicine, Miami, FL 33136, USA
Received 2 May 2013; Revised 29 June 2013; Accepted 11 July 2013
Academic Editor: Guixiu Shi
Copyright © 2013 Juan Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective. Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and a significant cause of morbidity and mortality. The objective of this study was to define high-resolution chest CT (HRCT) and pulmonary function test (PFT) abnormalities capable of identifying asymptomatic, preclinical forms of RA-ILD that may represent precursors to more severe fibrotic lung disease. Methods. We analyzed chest HRCTs in consecutively enrolled RA patients and subsequently classified these individuals as RA-ILD or RA-no ILD based on the presence/absence of ground glass opacification, septal thickening, reticulation, traction bronchiectasis, and/or honeycombing. Coexisting PFT abnormalities (reductions in percent predicted FEV1, FVC, TLC, and/or DLCO) were also used to further characterize occult respiratory defects. Results. 61% (63/103) of RA patients were classified as RA-ILD based on HRCT and PFT abnormalities, while 39% (40/103) were designated as RA-no ILD. 57/63 RA-ILD patients lacked symptoms of significant dyspnea or cough at the time of HRCT and PFT assessment. Compared with RA-no ILD, RA-ILD patients were older and had longer disease duration, higher articular disease activity, and more significant PFT abnormalities.Conclusion. HRCT represents an effective tool to detect occult/asymptomatic ILD that is highly prevalent in our unselected, university-based cohort of RA patients.
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July 30, 2013

Trends in the use of antiasthmatic medications in Morocco (1999–2010)

Open Access
Research

Trends in the use of antiasthmatic medications in Morocco (1999–2010)

Imane Ghanname1*, Samir Ahid1, Ghizlane Berrada1, Abdelmjid Belaiche2, Mohamed Hassar1 and Yahya Cherrah1
Author Affiliations
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SpringerPlus 2013, 2:82 doi:10.1186/2193-1801-2-82
Published: 5 March 2013

Abstract

Background

Asthma is a big public health problem in Morocco. The drug therapy existing in Morocco is currently insufficient because of the low purchasing power and the low health insurance coverage available to the average citizen in Morocco. In this study we evaluated the consumption of antiasthmatics in Morocco during the period 1999–2010, the classes of used drugs and the generics’ market share.

Methods

We used sales data from the Moroccan subsidiaries of the IMS Health “Intercontinental Marketing Service”. The consumption volume was converted to Defined Daily Doses (DDDs).

Results

During 1999–2010, antiasthmatics’s consumption increased from 3.91 to 14.47 DDD per 1000 inhabitants per day. In 2010, the association Beta-2-mimetic-Glucocorticosteroids were the most consumed (8.53 DDD/1000 Inhabitants/day) followed by the short-acting inhaled Beta-2-mimetic (4 DDD/1000 Inhabitants/day) and inhaled Glucocorticosteroids alone accounted for 1.13 DDD/1000 Inhabitants/day. The largest consumption share in volume was held by the short-acting inhaled Beta-2-mimetic (42%) followed by the combination Beta-2-mimetic-Glucocorticosteroids (38%). Between 1999 and 2010, the market for generic antiasthmatics increased from 1.84 to 2.18 DDD/1000 Inhabitants/day. The ratio of the monthly average cost of treatment to the minimum wage in Morocco decreased from 10.8% in 1999 to 7.11% in 2010.

Conclusion

Antiasthmatics’ consumption in Morocco has undergone significant changes between 1999 and 2010. However, the availability of these drugs expressed as the Average Monthly Expenditure/Guaranteed Minimum Wage ratio improved. Despite this, the use of antiasmathics in Morocco remains low.
Keywords: 
Antiasthmatic; Average monthly expenditure; Consumption; Defined Daily Dose (DDD); Morocco
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Role of Computerized Physician Order Entry Usability in the Reduction of Prescribing Errors

Role of Computerized Physician Order Entry Usability in the Reduction of Prescribing Errors
Hamid Reza Peikari, PhD1, Mohamad Shanudin Zakaria, PhD1, Norjaya M. Yasin, PhD1, Mahmood Hussain Shah, PhD2, Abdelbary Elhissi, BSc, PhD3
1Graduate School of Business, Universiti Kebangsaan Malaysia, Bangi, Malaysia; 2Lancashire Business School and 3School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objectives: Some hospitals have implemented computerized physician order entry (CPOE) systems to reduce the medical error rates. However, research in this area has been very limited, especially regarding the impact of CPOE use on the reduction of prescribing errors. Moreover, the past studies have dealt with the overall impact of CPOE on the reduction of broadly termed "medical errors", and they have not specified which medical errors have been reduced by CPOE. Furthermore, the majority of the past research in this field has been either qualitative or has not used robust empirical techniques. This research examined the impacts of usability of CPOE systems on the reduction of doctors' prescribing errors. Methods: One hundred and sixty-six questionnaires were used for quantitative data analyses. Since the data was not normally distributed, partial least square path modelling−as the second generation of multivariate data analyses−was applied to analyze data. Results: It was found that the ease of use of the system and information quality can significantly reduce prescribing errors. Moreover, the user interface consistency and system error prevention have a significant positive impact on the perceived ease of use. More than 50% of the respondents believed that CPOE reduces the likelihood of drug allergy, drug interaction, and drug dosing errors thus improving patient safety. Conclusions: Prescribing errors in terms of drug allergy, drug interaction, and drug dosing errors are reduced if the CPOE is not error-prone and easy to use, if the user interface is consistent, and if it provides quality information to doctors.
Healthcare Informatics Research 2013 Jun; 19(02) 93-101 
Keyword : Medical, Usability, Health Informatics, CPOE

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