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Medical Countermeasures (medical + countermeasure)
Selected AbstractsTools for planning and coordinating development of medical countermeasures in the public sectorDRUG DEVELOPMENT RESEARCH, Issue 4 2009Ian Manger Abstract In spite of significant increases in biodefense spending in the 7 years since the 2001 anthrax attacks, the United States may not yet be fully prepared to respond effectively to many potential biothreats. The principal reasons appear to be that: (1) the problem is extremely complex, and the metrics for success are often unclear; (2) although the US Congress has allocated substantial resources for this effort, these funds are insufficient for the task as initially conceived, i.e., "one drug for each bug;" and (3) there is insufficient coordination among the many agencies working to achieve the goal of protecting the nation from biothreats. In the last few years, much of the biodefense community has come to recognize that an approach that focuses on developing and stockpiling a medical countermeasure (MCM) for each possible biothreat agent is unachievable for reasons of cost, time, and the sheer diversity of emerging threats. Promising alternative models are emerging, including broad spectrum and technology platform approaches, but the requisite cross-agency planning and coordination, although improving, is still problematic. We have developed a set of software tools and methods for using them that could support the desired coordination and that could also provide for more rapid, comprehensive, and shared identification of key enabling technologies for accomplishing the development of effective medical countermeasures in time to counter or prevent a biothreat. The tools and methods could also make possible a collaborative public-private partnership for the development of MCM, which many believe is critical to success. Drug Dev Res 70:327,334, 2009 © 2009 Wiley-Liss, Inc. [source] Putative role of proteolysis and in,ammatory response in the toxicity of nerve and blister chemical warfare agents: implications for multi-threat medical countermeasures,JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2003F. M. Cowan Abstract Despite the contrasts in chemistry and toxicity, for blister and nerve chemical warfare agents there may be some analogous proteolytic and in,ammatory mediators and pathological pathways that can be pharmacological targets for a single-drug multi-threat medical countermeasure. The dermal,epidermal separation caused by proteases and bullous diseases compared with that observed following exposure to the blister agent sulfur mustard (2,2,-dichlorodiethyl sul,de) has fostered the hypothesis that sulfur mustard vesication involves proteolysis and in,ammation. In conjunction with the paramount toxicological event of cholinergic crisis that causes acute toxicity and precipitates neuronal degeneration, both anaphylactoid reactions and pathological proteolytic activity have been reported in nerve-agent-intoxicated animals. Two classes of drugs already have demonstrated multi-threat activity for both nerve and blister agents. Serine protease inhibitors can prolong the survival of animals intoxicated with the nerve agent soman and can also protect against vesication caused by the blister agent sulfur mustard. Poly (ADP-ribose) polymerase (PARP) inhibitors can reduce both soman-induced neuronal degeneration and sulfur-mustard-induced epidermal necrosis. Protease and PARP inhibitors, like many of the other countermeasures for blister and nerve agents, have potent primary or secondary anti-in,ammatory pharmacology. Accordingly, we hypothesize that drugs with anti-in,ammatory actions against either nerve or blister agent might also display multi-threat ef,cacy for the in,ammatory pathogenesis of both classes of chemical warfare agent. Published in 2003 by John Wiley & Sons, Ltd. [source] Developing medical countermeasures: from BioShield to BARDADRUG DEVELOPMENT RESEARCH, Issue 4 2009Jonathan B. TuckerArticle first published online: 12 JUN 200 Abstract The U.S. Congress passed the Project BioShield Act in 2004 to create market incentives for the private sector to develop medical countermeasures (MCMs) against high-priority chemical, biological, radiological, and nuclear threats. Two years later, Congress patched recognized gaps in the BioShield legislation by adopting the Pandemic and All-Hazards Preparedness Act of 2006, which established the Biomedical Advanced Research and Development Authority (BARDA) within the Department of Health and Human Services (DHHS). BARDA provides financial and managerial support for companies developing MCMs. This article examines U.S. government efforts in the MCM field and prospects for the future. Drug Dev Res 70:224,233, 2009. © 2009 Wiley-Liss, Inc. [source] Tools for planning and coordinating development of medical countermeasures in the public sectorDRUG DEVELOPMENT RESEARCH, Issue 4 2009Ian Manger Abstract In spite of significant increases in biodefense spending in the 7 years since the 2001 anthrax attacks, the United States may not yet be fully prepared to respond effectively to many potential biothreats. The principal reasons appear to be that: (1) the problem is extremely complex, and the metrics for success are often unclear; (2) although the US Congress has allocated substantial resources for this effort, these funds are insufficient for the task as initially conceived, i.e., "one drug for each bug;" and (3) there is insufficient coordination among the many agencies working to achieve the goal of protecting the nation from biothreats. In the last few years, much of the biodefense community has come to recognize that an approach that focuses on developing and stockpiling a medical countermeasure (MCM) for each possible biothreat agent is unachievable for reasons of cost, time, and the sheer diversity of emerging threats. Promising alternative models are emerging, including broad spectrum and technology platform approaches, but the requisite cross-agency planning and coordination, although improving, is still problematic. We have developed a set of software tools and methods for using them that could support the desired coordination and that could also provide for more rapid, comprehensive, and shared identification of key enabling technologies for accomplishing the development of effective medical countermeasures in time to counter or prevent a biothreat. The tools and methods could also make possible a collaborative public-private partnership for the development of MCM, which many believe is critical to success. Drug Dev Res 70:327,334, 2009 © 2009 Wiley-Liss, Inc. [source] Experimental respiratory anthrax infection in the common marmoset (Callithrix jacchus)INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2008Mark S. Lever Summary Inhalational anthrax is a rare but potentially fatal infection in man. The common marmoset (Callithrix jacchus) was evaluated as a small non-human primate (NHP) model of inhalational anthrax infection, as an alternative to larger NHP species. The marmoset was found to be susceptible to inhalational exposure to Bacillus anthracis Ames strain. The pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. The calculated LD50 for B. anthracis Ames strain in the marmoset was 1.47 × 103 colony-forming units, compared with a published LD50 of 5.5 × 104 spores in the rhesus macaque and 4.13 × 103 spores in the cynomolgus macaque. This suggests that the common marmoset is an appropriate alternative NHP and will be used for the evaluation of medical countermeasures against respiratory anthrax infection. [source] A novel approach to assessing percutaneous VX poisoning in the conscious guinea-pig,JOURNAL OF APPLIED TOXICOLOGY, Issue 5 2008Helen Mumford Abstract Nerve agents like VX (S-2-diisopropylaminoethyl-O-ethyl-methylphosphonothiolate) are potent irreversible acetylcholinesterase (AChE) inhibitors. Following percutaneous nerve agent exposure there is a slower rate of absorption, later onset and longer duration of signs of poisoning. Relatively little is known about the physiological effects of percutaneously applied nerve agent in unanaesthetised laboratory animals. Heart rate (ECG), brain electrical activity (EEG), body temperature, locomotor activity and clinical signs were monitored following percutaneous application of VX to conscious guinea-pigs. A fall in heart rate (bradycardia) preceded incapacitation following the highest VX dose, and occurred in the absence of incapacitation at the lower doses. Following the highest dose of VX (0.592 mg kg,1) three out of four animals died within 24 h. The lower two doses of VX (0.296 and 0.148 mg kg,1), produced extended periods of bradycardia in the absence of observable signs of poisoning. Bradycardia preceded, or occurred in the absence of, a temperature decrease; seizure-like EEG changes were not observed at any of the VX doses tested. Acetylcholinesterase activity was significantly inhibited in the blood and most brain areas at 48 h. There were significant dose-related decreases in body weight at 24 and 48 h following VX. This preliminary study suggests that decreased heart rate may be an early sign of the toxic effects of VX, whereas temperature and observable clinical signs are not good early indicators of percutaneous VX poisoning in this animal model. Future studies will use this model to assess the benefit of administering medical countermeasures in response to a defined decrease in heart rate. © Crown Copyright 2007. Reproduced with the permission of the Controller of HMSO. Published by John Wiley & Sons, Ltd. This article was published online on 5 December 2007. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected [30 May 2008]. [source] Putative role of proteolysis and in,ammatory response in the toxicity of nerve and blister chemical warfare agents: implications for multi-threat medical countermeasures,JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2003F. M. Cowan Abstract Despite the contrasts in chemistry and toxicity, for blister and nerve chemical warfare agents there may be some analogous proteolytic and in,ammatory mediators and pathological pathways that can be pharmacological targets for a single-drug multi-threat medical countermeasure. The dermal,epidermal separation caused by proteases and bullous diseases compared with that observed following exposure to the blister agent sulfur mustard (2,2,-dichlorodiethyl sul,de) has fostered the hypothesis that sulfur mustard vesication involves proteolysis and in,ammation. In conjunction with the paramount toxicological event of cholinergic crisis that causes acute toxicity and precipitates neuronal degeneration, both anaphylactoid reactions and pathological proteolytic activity have been reported in nerve-agent-intoxicated animals. Two classes of drugs already have demonstrated multi-threat activity for both nerve and blister agents. Serine protease inhibitors can prolong the survival of animals intoxicated with the nerve agent soman and can also protect against vesication caused by the blister agent sulfur mustard. Poly (ADP-ribose) polymerase (PARP) inhibitors can reduce both soman-induced neuronal degeneration and sulfur-mustard-induced epidermal necrosis. Protease and PARP inhibitors, like many of the other countermeasures for blister and nerve agents, have potent primary or secondary anti-in,ammatory pharmacology. Accordingly, we hypothesize that drugs with anti-in,ammatory actions against either nerve or blister agent might also display multi-threat ef,cacy for the in,ammatory pathogenesis of both classes of chemical warfare agent. Published in 2003 by John Wiley & Sons, Ltd. [source] Site-specific percutaneous absorption of methyl salicylate and VX in domestic swineJOURNAL OF APPLIED TOXICOLOGY, Issue 3 2002E. J. Scott Duncan Abstract The site specificity of the percutaneous absorption of methyl salicylate (MeS) and the organophosphate nerve agent VX (O -ethyl S -(2-diisopropylaminoethyl) methylphosphonothioate) was examined in anaesthetized domestic swine that were fully instrumented for physiological endpoints. Four different anatomical sites (ear, perineum, inguinal crease and epigastrium) were exposed to the MeS and the serum levels were measured over a 6-h time period. The dose absorbed at the ear region was 11 ,g cm,2 with an initial flux of 0.063 ,g cm,2min,1, whereas at the epigastrium region the dose absorbed was 3 ,g cm,2 with an initial flux of 0.025 ,g cm,2min,1. For this reason further studies were carried out with VX on the ear and the epigastrium only. In animals treated with agent on the epigastrium, blood cholinesterase (ChE) activity began to drop 90 min after application and continued to decline at a constant rate for the remainder of the experiment to ca. 25% of awake control activity. At this time there were negligible signs of poisoning and the medical prognosis was judged to be good. In contrast, the ChE activity in animals receiving VX on the ear decreased to 25% of awake control values within 45 min and levelled out at 5,6% by 120 min. Clinical signs of VX poisoning paralleled the ChE inhibition, progressing in severity over the duration of the exposure. It was judged that these animals would not survive. The dramatic site dependence of agent absorption leading to vastly different toxicological endpoints demonstrated in this model system has important ramifications for chemical protective suit development, threat assessment, medical countermeasures and contamination control protocols. Copyright © 2002 Crown in the right of Canada. Published by John Wiley & Sons, Ltd. [source] Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agentsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010S Ramasamy The use of biological agents has generally been confined to military-led conflicts. However, there has been an increase in non-state-based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre- and post-exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti-virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro-encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti-toxin therapy and anti-virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post-exposure treatment for cholera, viral encephalitis and ricin , a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post-exposure treatment options. The aim of this review is to present an update on prophylaxis and post-exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009. [source] | ||||||||||