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El-Sherbiny I.M.,Center for Materials Science | El-Shibiny A.,Biomedical Science | Salih E.,Center for Materials Science
Journal of Photochemistry and Photobiology B: Biology | Year: 2016

This study reports the photo-induced green synthesis and antimicrobial assessment of poly(ϵ-caprolactone)/curcumin/grape leaf extract-Ag hybrid nanoparticles (PCL/Cur/GLE-Ag NPs). PCL/Cur/GLE NPs were synthesized via emulsion-solvent evaporation in the presence of PVA as a capping agent, then used as active nano-supports for the green synthesis and stabilization of AgNPs on their surfaces. Both Cur and GLE were selected and incorporated into the PCL nano-supports due to their reported promising antimicrobial activity that would further enhance that of the synthesized AgNPs. The developed PCL/Cur/GLE NPs and PCL/Cur/GLE-Ag hybrid NPs were characterized using UV-visible spectrophotometry, high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). HRTEM images showed that the PCL/Cur/GLE NPs are monodispersed and spherical with size of about 270 nm, and the AgNPs were formed mainly on their surfaces with average size in the range 10-30 nm. The synthesized AgNPs were found to be crystalline as shown by XRD patterns with fcc phase oriented along the (111), (200), (220) and (311) planes. The antimicrobial characteristics of the newly developed NPs were investigated against gram-positive and gram-negative bacteria in addition to two fungal strains. The results demonstrated that the PCL/Cur/GLE-Ag hybrid NPs have a potential antimicrobial activity against pathogenic bacterial species and could be considered as an alternative antibacterial agent. © 2016 Elsevier B.V. All rights reserved.


Kirkman E.,Biomedical science | Watts S.,Biomedical science | Cooper G.,Biomedical science
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Blast injuries are an increasing problem in both military and civilian practice. Primary blast injury to the lungs (blast lung) is found in a clinically significant proportion of casualties from explosions even in an open environment, and in a high proportion of severely injured casualties following explosions in confined spaces. Blast casualties also commonly suffer secondary and tertiary blast injuries resulting in significant blood loss. The presence of hypoxaemia owing to blast lung complicates the process of fluid resuscitation. Consequently, prolonged hypotensive resuscitation was found to be incompatible with survival after combined blast lung and haemorrhage. This article describes studies addressing new forward resuscitation strategies involving a hybrid blood pressure profile (initially hypotensive followed later by normotensive resuscitation) and the use of supplemental oxygen to increase survival and reduce physiological deterioration during prolonged resuscitation. Surprisingly, hypertonic saline dextran was found to be inferior to normal saline after combined blast injury and haemorrhage. New strategies have therefore been developed to address the needs of blast-injured casualties and are likely to be particularly useful under circumstances of enforced delayed evacuation to surgical care. © 2011 The Royal Society.


Kirkman E.,Biomedical science | Watts S.,Biomedical science
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Lung injuries, predominantly arising from blast exposure, are a clinical problem in a significant minority of current military casualties. This special feature consists of a series of articles on lung injury. This first article examines the mechanism of the response to blast lung (primary blast injury to the lung). Subsequent articles examine the incidence of blast lung, clinical consequences and current concepts of treatment, computer (in silico) modelling of lung injury and finally chemical injuries to the lungs. Blast lung is caused by a shock wave generated by an explosion causing widespread damage in the lungs, leading to intrapulmonary haemorrhage. This, and the ensuing inflammatory response in the lung, leads to a compromise in pulmonary gas exchange and hypoxia that can worsen over several hours. There is also a characteristic cardio-respiratory effect mediated via an autonomic reflex causing apnoea (or rapid shallow breathing), bradycardia and hypotension (the latter possibly also due to the release of nitric oxide). An understanding of this response, and the way it modifies other reflexes, can help the development of new treatment strategies for this condition and for the way it influences the patient's response to concomitant injuries. © 2011 The Royal Society.


Thomas R.J.,Biomedical science
Bioengineered Bugs | Year: 2010

The specter of intentional release of pathogenic microbes and their toxins is a real threat. This article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. The minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the Galβ1-4GlcNAc structure. The botulinum toxin serotypes A-F bind to a low number of gangliosides (GT1b, GQ1b, GD1a and GD1b) hence it should be possible to determine the minimal structure for binding. The minimal disaccharide sequence of GalNAcβ1-4Gal found in the gangliosides asialo-GM1 and asialo-GM2 is required for adhesion for many respiratory pathogens. Although a number of adhesins have been identified in bacterial biothreat agents such as Yersinia pestis, Bacillus anthracis, Francisella tularensis, Brucella species and Burkholderia pseudomallei, specific information regarding their in vivo expression during pneumonic infection is lacking. Limited oligosaccharide inhibition studies indicate the potential of GalNAcβ1-4Gal, GalNAcβ-3Gal and the hydrophobic compound, para-nitrophenol as starting points for the rational design of generic antiadhesion compounds. A cocktail of multivalent oligosaccharides based on the minimal binding structures of identified adhesions would offer the best candidates for anti-adhesion therapy. © 2010 Landes Bioscience.


Oyston P.,Biomedical science | Robinson K.,University of Nottingham
Journal of Medical Microbiology | Year: 2012

Vaccine development has played a hugely important role in combating infectious disease. Despite this success, there is still a great need for new vaccines and these are emerging far more slowly than we would wish. Despite the massive expansion in understanding of immune responses to infection, research is often hindered by a lack of understanding of the immune responses required specifically for protection, or by a lack of approved adjuvants and delivery systems to induce the required responses. In addition, the financial commitment required to license new vaccines is significant, and the more lucrative markets are often not those with the greatest need. In this review, we discuss many of the hurdles that new vaccines must overcome in order to reduce morbidity and mortality, and some of the initiatives that are being attempted to supply new vaccines to those that need them most. © 2012 Crown Dstl.


Williamson E.D.,Biomedical science | Oyston P.C.F.,Biomedical science
Journal of Medical Microbiology | Year: 2012

Plague is an ancient, serious, infectious disease which is still endemic in regions of the modern world and is a potential biothreat agent. This paper discusses the natural history of the bacterium and its evolution into a flea-vectored bacterium able to transmit bubonic plague. It reviews the incidence of plague in the modern world and charts the history of vaccines which have been used to protect against the flea-vectored disease, which erupts as bubonic plague. Current approaches to vaccine development to protect against pneumonic, as well as bubonic, plague are also reviewed. The considerable challenges in achieving a vaccine which is licensed for human use and which will comprehensively protect against this serious human pathogen are assessed. © 2012 Crown copyright Dstl.


Oyston P.C.F.,Biomedical science | Williamson E.D.,Biomedical science
Expert Review of Anti-Infective Therapy | Year: 2013

Plague has been a scourge of mankind for centuries, and outbreaks continue to the present day. The virulence mechanisms employed by the etiological agent Yersinia pestis are reviewed in the context of the available prophylactic and therapeutic strategies for plague. Although antibiotics are available, resistance is emerging in this dangerous pathogen. Therapeutics used in the clinic are discussed and innovative approaches to the design and development of new therapeutic compounds are reviewed. Currently there is no licensed vaccine available for prevention of plague in the USA or western Europe, although both live attenuated strains and killed whole-cell extracts have been used historically. Live strains are still approved for human use in some PTs of the world, such as the former Soviet Union, but poor safety profiles render them unaccePTable to many countries. The development of safe, effective next-generation vaccines, including the recombinant subunit vaccine currently used in clinical trials is discussed. © 2013 Informa UK Ltd.


D'Elia R.V.,Biomedical science | Laws T.R.,Biomedical science | Carter A.,Biomedical science | Lukaszewski R.,Biomedical science | Clark G.C.,Biomedical science
Antimicrobial Agents and Chemotherapy | Year: 2013

Antibiotic efficacy is greatly enhanced the earlier it is administered following infection with a bacterial pathogen. However, in a clinical setting antibiotic treatment usually commences following the onset of symptoms, which in some cases (e.g., biothreat agents) may be too late. In a BALB/c murine intranasal model of infection for Francisella tularensis SCHU S4 infection, we demonstrate during a time course experiment that proinflammatory cytokines and the damage-associated molecular pattern HMGB1 were not significantly elevated above naive levels in tissue or sera until 72 h postinfection. HMGB1 was identified as a potential therapeutic target that could extend the window of opportunity for the treatment of tularemia with antibiotics. Antibodies to HMGB1 were administered in conjunction with a delayed/suboptimal levofloxacin treatment of F. tularensis. We found in the intranasal model of infection that treatment with anti-HMGB1 antibody, compared to an isotype IgY control antibody, conferred a significant survival benefit and decreased bacterial loads in the spleen and liver but not the lung (primary loci of infection) 4 days into infection. We also observed an increase in the production of gamma interferon in all tested organs. These data demonstrate that treatment with anti-HMGB1 antibody is beneficial in enhancing the effectiveness of current antibiotics in treating tularemia. Strategies of this type, involving antibiotics in combination with immunomodulatory drugs, are likely to be essential for the development of a postexposure therapeutic for intracellular pathogens. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Delia R.V.,Biomedical science | Harrison K.,Biomedical science | Oyston P.C.,Biomedical science | Lukaszewski R.A.,Biomedical science | Clark G.C.,Biomedical science
Clinical and Vaccine Immunology | Year: 2013

Inflammation is the bodýs first line of defense against infection or injury, responding to challenges by activating innate and adaptive responses. Microbes have evolved a diverse range of strategies to avoid triggering inflammatory responses. However, some pathogens, such as the influenza virus and the Gram-negative bacterium Francisella tularensis, do trigger life-threatening "cytokine storms" in the host which can result in significant pathology and ultimately death. For these diseases, it has been proposed that downregulating inflammatory immune responses may improve outcome. We review some of the current candidates for treatment of cytokine storms which may prove useful in the clinic in the future and compare them to more traditional therapeutic candidates that target the pathogen rather than the host response. © 2013, American Society for Microbiology.


De Almeida Mello J.,Biomedical science | Van Durme T.,Catholic University of Leuven | MacQ J.,Catholic University of Leuven | Declercq A.,Catholic University of Leuven
BMC Public Health | Year: 2012

Background: Older people usually prefer staying at home rather than going into residential care. The Belgian National Institute for Health and Disability Insurance wishes to invest in home care by financing innovative projects that effectively help older people to stay at home longer. In this study protocol we describe the evaluation of 34 home care projects. These projects are clustered according to the type of their main intervention such as case management, night care, occupational therapy at home and psychological/psychosocial support. The main goal of this study is to identify which types of projects have the most effect in delaying institutionalization of frail older persons. Methods/design. This is a longitudinal intervention study based on a quasi-experimental design. Researchers use three comparison strategies to evaluate intervention - comparison among different types of projects, comparisons between older persons in the projects and older persons not benefiting from a project but who are still at home and between older persons in the projects and older persons who are already institutionalized. Projects are asked to include clients who are frail and at risk of institutionalization. In the study we use internationally validated instruments such as the interRAI Home Care instrument, the WHO-QOL-8 and the Zarit Burden Interview-12. These instruments are filled out at baseline, at exit from the project and 6 months after baseline. Additionally, caregivers have to do a follow-up every 6 months until exit from the project. Criteria to exit the cohort will be institutionalization longer than 3 months and death. The main analysis in the study consists of the calculation of incidence rates, cumulative incidence rates and hazard rates of definitive institutionalization through survival analyses for each type of project. Discussion. This research will provide knowledge on the functional status of frail older persons who are still living at home. This is important information to identify determinants of risk for institutionalization. The identification of effective home care projects in delaying institutionalization will be useful to inform and empower home care providers, policy and related decision makers to manage and improve home care services. © 2012 De Almeida Mello et al.; licensee BioMed Central Ltd.

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