Dstl Porton Down

Salisbury, United Kingdom

Dstl Porton Down

Salisbury, United Kingdom
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Cornes S.P.,University of Oxford | Sambrook M.R.,Dstl Porton Down | Beer P.D.,University of Oxford
Chemical Communications | Year: 2017

Alpha-cyclodextrin based anion receptors functionalised with pendant arms containing halogen and hydrogen bond donor motifs display selective association of perrhenate in aqueous media at neutral pH. NMR and ITC anion binding investigations reveal the halogen bonding receptor to be the superior host. © The Royal Society of Chemistry.

Mumford H.,Dstl Porton Down | Docx C.J.,Dstl Porton Down | Price M.E.,Dstl Porton Down | Green A.C.,Dstl Porton Down | And 2 more authors.
Chemico-Biological Interactions | Year: 2013

Potent organophosphorous (OP) agents, such as VX, are hazardous by absorption through the skin and are resistant to conventional pharmacological antidotal treatments. The residence time of a stoichiometric bioscavenger, human butyrylcholinesterase (huBuChE), in the plasma more closely matches that of VX than do the residence times of conventional therapy drugs (oxime, anti-muscarinic, anticonvulsant). Intramuscular (i.m.) huBuChE afforded almost complete protection when administered prior to the onset of observable cholinergic signs of VX poisoning, but once signs of poisoning became evident the efficacy of i.m. huBuChE decreased. A combination of nerve agent therapy drugs (oxime, anti-muscarinic, anticonvulsant) with huBuChE (i.m.) protected 100% (8/8) of guinea-pigs from a lethal dose of VX (0.74 mg/kg) to 48 h, even when administered on signs of poisoning. Survival was presumed to be due to immediate alleviation of the cholinergic crisis by the conventional pharmacological treatment drugs, in conjunction with bioscavenger that prevented further absorbed agent reaching the AChE targets. Evidence to support this proposed mechanism of action was obtained from PKPD experiments in which multiple blood samples and microdialysate samples were collected from individual conscious ambulatory animals. Plasma concentrations of intramuscularly- administered atropine, diazepam and HI-6 reached a peak within 15 min and were eliminated rapidly within 4 h. Plasma concentrations of huBuChE administered by the i.m. route took approximately 24 h to reach a peak, but were well-maintained over the subsequent 7 days. Thus, the pharmacological therapy rapidly treated the initial signs of poisoning, whilst the bioscavenger provided prolonged protection by neutralising further nerve agent entering the bloodstream and preventing it from reaching the target organs. © 2012 Elsevier Ireland Ltd. All rights reserved.

Kirkman E.,Dstl Porton Down | Watts S.,Dstl Porton Down
Journal of the Royal Army Medical Corps | Year: 2014

The Combat Casualty Care research programme is an integrated suite of projects designed to address Defence Medical Services' research needs for casualty care. The programme covers a broad spectrum of topics ranging from the pathophysiological and immunological impact of military relevant injuries to the effects of these disturbances on the response to early treatment. Dstl Porton Down has a long history of studying military injuries and has developed models, both in vivo and physical, to address the research needs. The work is conducted in close collaboration with clinical colleagues at the Royal Centre for Defence Medicine who have direct experience of the clinical issues faced by combat casualties and insights into the potential clinical implications of emerging strategies. This article reviews progress in research areas spanning forward resuscitation, with a particular focus on blast-related injuries, trauma coagulopathy, effects of drugs on the response to haemorrhage and deployed research. A significant 'value added' component has been the underpinning of higher degrees for seconded military clinicians at Dstl Porton Down who have made a valuable contribution to the overall programme. © Crown copyright 2014.

Biosensors are desired for the detection of a wide range of analytes in various scenarios, for example environmental monitoring for biological threats, from toxins to viruses and bacteria. Ideally a single sensor will be capable of simultaneous multianalyte detection. The varying nature, and in particular disparate size, of such a variety of analytes poses a significant challenge in the development of effective high-confidence instruments. Many existing biosensors employ functionalized flow cells in which spatially defined arrays of surface-immobilized recognition elements, such as antibodies, specifically capture their analyte of interest. To function optimally, arrays should provide equivalent responses for equivalent events across their active area. Experimental data obtained using a grating coupled surface plasmon resonance (GC-SPR) instrument, the BIAcore Flexchip, have revealed differences in response behaviors between proteinaceous and particulate analytes. In particular, the magnitude of responses seen with Bacillus anthracis spores appears to be influenced by shear and gravitational effects while those from soluble proteins are more uniform. We have explored this dependence to understand its fundamental impact on the successful implementation of multianalyte environmental biological detection systems. © Published 2012 by the American Chemical Society.

Lindsay C.D.,Dstl Porton Down | Griffiths G.D.,Dstl Porton Down
Human and Experimental Toxicology | Year: 2013

Staphylococcal enterotoxin B (SEB) is of concern to military and civilian populations as a bioterrorism threat agent. It is a highly potent toxin produced by Staphylococcus aureus and is stable in storage and under aerosolisation; it is able to produce prolonged highly incapacitating illness at very low-inhaled doses and death at elevated doses. Concerns regarding SEB are compounded by the lack of effective medical countermeasures for mass treatment of affected populations. This article considers the mechanism of action of SEB, the availability of appropriate experimental models for evaluating the efficacy of candidate medical countermeasures with particular reference to the need to realistically model SEB responses in man and the availability of candidate countermeasures (with an emphasis on commercial off-the-shelf options). The proposed in vitro approaches would be in keeping with Dstl's commitment to reduction, refinement and replacement of animal models in biomedical research, particularly in relation to identifying valid alternatives to the use of nonhuman primates in experimental studies. © 2013 The Author(s).

Garner J.,Dstl Porton Down | Watts S.,Dstl Porton Down | Parry C.,Dstl Porton Down | Bird J.,Dstl Porton Down | And 2 more authors.
Annals of Surgery | Year: 2010

Objective: To determine the effects of primary blast injury (PBI) on survival and the physiological response to resuscitation after hemorrhagic shock. Background: Air-blast injury is a significant clinical problem that can reduce blood oxygenation and modify the response to hemorrhage. PBI has specific physiological effects that have not been fully accounted for in resuscitation strategies. Permissive hypotension is a widely adopted strategy in trauma resuscitation. However, the choice of resuscitation strategy requires a full understanding of the mechanisms of injury and their physiological consequences. Methods: Terminally anesthetized pigs were divided into 4 groups and subjected to either air-blast injury (B) or no blast (S). All received a controlled hemorrhage of 30% blood volume and resuscitation with 0.9% saline to a normotensive (Normot, systolic blood pressure 110 mm Hg) or hypotensive (Hypot, 80 mm Hg) end point for up to 8 hours. (n = 6 in each B and n = 8 in each S subgroup). Results: Survival time was significantly shorter with Hypot (P < 0.0001 Peto log rank). The effect was in the animals subjected to B (P = 0.0005) (mean survival time [95% CI]; BNormot 422 [313-531] vs. BHypot137 [94-181] min), but not those given S (P = 0.06) (SNormot 480 [all survived] vs. SHypot 352 [210-494] min). PBI exacerbated a profound metabolic acidosis during Hypot, possibly due to an overwhelming compromise in tissue oxygen delivery. Conclusions: Prolonged hypotensive resuscitation is not compatible with survival after primary blast. Casualties most likely to be in this category are those injured by blast in confined spaces or by enhanced blast weapons. The risk of rebleeding associated with normotensive resuscitation needs to be balanced with the metabolic derangement associated with hypotensive resuscitation. © 2010 Lippincott Williams & Wilkins.

Laws T.R.,Dstl Porton Down | Clark G.,Dstl Porton Down | D'Elia R.V.,Dstl Porton Down
Infection and Immunity | Year: 2013

Differential Role for Interleukin-6 during Francisella tularensis Infection with Virulent and Vaccine Strains Thomas R. Laws, Graeme Clark, Riccardo V. D'Elia Dstl Porton Down, Wiltshire, United Kingdom © 2013, American Society for Microbiology. All Rights Reserved.

Sigle D.O.,University of Cambridge | Perkins E.,Dstl Porton Down | Baumberg J.J.,University of Cambridge | Mahajan S.,University of Cambridge
Journal of Physical Chemistry Letters | Year: 2013

Surface-enhanced Raman scattering (SERS) with deep-UV excitation is of particular interest because a large variety of biomolecules such as amino acids exhibit electronic transitions in the UV spectral range and resonant excitation dramatically increases the cross section of the associated vibrational modes. Despite its potential, UV-SERS is still little-explored. We present a novel straightforward scalable route to fabricate aluminum nanovoids for reproducible SERS in the deep-UV without the need of expensive lithographic techniques. We adopt a modified template stripping method utilizing a soluble template and self-assembled polymer spheres to create nanopatterned aluminum films. We observe high surface enhancement of approximately 6 orders of magnitude, with excitation in the deep-UV (244 nm) on structures optimized for this wavelength. This work thus enables sensitive detection of organics and biomolecules, normally nonresonant at visible wavelengths, with deep-UV surface-enhanced resonant Raman scattering on reproducible and scalable substrates. © 2013 American Chemical Society.

Sambrook M.R.,Dstl Porton Down | Notman S.,Dstl Porton Down
Chemical Society Reviews | Year: 2013

Supramolecular chemistry presents many possible avenues for the mitigation of the effects of chemical warfare agents (CWAs), including sensing, catalysis and sequestration. To-date, efforts in this field both to study fundamental interactions between CWAs and to design and exploit host systems remain sporadic. In this tutorial review the non-covalent recognition of CWAs is considered from first principles, including taking inspiration from enzymatic systems, and gaps in fundamental knowledge are indicated. Examples of synthetic systems developed for the recognition of CWAs are discussed with a focus on the supramolecular complexation behaviour and non-covalent approaches rather than on the proposed applications. © 2013 The Royal Society of Chemistry.

Findlay J.S.,Dstl Porton Down | Ulaeto D.,Dstl Porton Down
Journal of General Virology | Year: 2015

Viruses are obligate intracellular pathogens which rely on the cell’s machinery to produce the energy and macromolecules required for replication. Infection is associated with a modified metabolic profile and one pathway which can be modified is glycolysis. In this study, we investigated if the glycolysis pathway is required for alphavirus replication. Pre-treatment of Vero cells with three different glycolysis inhibitors (2-deoxyglucose, lonidamine and oxamate) resulted in a significant reduction (but not abrogation) of Semliki Forest virus and Sindbis virus replication, but not of the unrelated virus, vaccinia virus. Reduced virus yield was not associated with any significant cytotoxic effect and delayed treatment up to 3 h post-infection still resulted in a significant reduction. This suggested that glycolysis is required for optimal replication of alphaviruses by supporting post-entry life cycle steps. © 2015 The Authors.

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