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You searched for subject:(Medical Countermeasures). Showing records 1 – 2 of 2 total matches.

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University of Minnesota

1. Moeller, Bryant. Characterization Of The Preclinical Cyanide Antidote Sulfanegen.

Degree: PhD, Pharmacology, 2017, University of Minnesota

Cyanide is a metabolic poison that inhibits utilization of oxygen to form ATP. The consequences of acute cyanide exposure are severe: toxic doses result in loss of consciousness, cardio and respiratory failure, hypoxic brain injury, and dose-dependent death from within minutes to hours. In a mass casualty scenario such as an industrial accident or terrorist attack, currently available cyanide antidotes would leave many victims untreated in the short time available for successful medical countermeasure administration. Therefore, there is a need for rapidly acting antidotes that can be quickly administered to large numbers of people who may be unconscious. Sulfanegen, a novel preclinical cyanide antidote, is being developed to meet this need. Sulfanegen is administered by intramuscular injection (IM), which has the advantages of requiring minimal training for first responders, as well as the potential for rapid antidotal administration to many affected people. Due to ethical issues involved with testing cyanide antidotes in human subjects, sulfanegen cannot go through the normal clinical trial path to drug approval. However, the FDA has published guidelines for evidence needed to gain approval under the “Animal Rule”, which this thesis attempts to address. The “Animal Rule” allows for new drug approval if the following conditions are met: 1) Effective in more than one animal model with a response predictive for humans, 2) Pharmacokinetics understood well enough to determine effective dose, and 3) A well-understood mechanism of action and pathology of the disease. v We first elucidated the animal models predictive for human efficacy testing by MST species comparison of the blood of many common laboratory animals. Based on this preliminary screen, species closest to that of humans were chosen to characterize the MST activities in metabolically active tissues. Using those findings, we determined swine were not an appropriate model for predicting efficacy in humans, while murine and rabbit models were appropriate. Next, we developed an isocratic UV-VIS HPLC method for characterizing the pharmacokinetics of sulfanegen in humans. Pre-column derivitization with NEM prevented the reformation of the 3-mercaptopyruvate (3MP) dimer and allowed for chromatographic detection. Moreover, this method is easily modified for applications to quality control, being able to separate sulfanegen from its precursor molecules and predicted decomposition products. Finally, we examined the potential secondary mechanisms of sulfanegen administration. MST catalyzed detoxification of cyanide to thiocyanate is the primary mechanism of action, but secondary mechanisms involving 3MP alone or in conjunction with MST contribute to the overall efficacy of sulfanegen. 3MP was found to be a potent antioxidant, capable of quenching cyanide induced ROS. Additionally, H2S generation by MST was confirmed after sulfanegen administration. Although it was confirmed that cyanohydrin formation was occurring, this probably does not contribute to reversing…

Subjects/Keywords: Antidote; Cyanide; Medical Countermeasures; Mercaptopyruvate sulfurtransferase; Sulfanegen

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Moeller, B. (2017). Characterization Of The Preclinical Cyanide Antidote Sulfanegen. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/206644

Chicago Manual of Style (16th Edition):

Moeller, Bryant. “Characterization Of The Preclinical Cyanide Antidote Sulfanegen.” 2017. Doctoral Dissertation, University of Minnesota. Accessed December 09, 2019. http://hdl.handle.net/11299/206644.

MLA Handbook (7th Edition):

Moeller, Bryant. “Characterization Of The Preclinical Cyanide Antidote Sulfanegen.” 2017. Web. 09 Dec 2019.

Vancouver:

Moeller B. Characterization Of The Preclinical Cyanide Antidote Sulfanegen. [Internet] [Doctoral dissertation]. University of Minnesota; 2017. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/11299/206644.

Council of Science Editors:

Moeller B. Characterization Of The Preclinical Cyanide Antidote Sulfanegen. [Doctoral Dissertation]. University of Minnesota; 2017. Available from: http://hdl.handle.net/11299/206644

2. Johnson, Mark Lawrence. Contre-mesures médicales contre les risques NRBC : quelles solutions pour un développement facilité dans une économie de marché ? : International Availability of Medical Countermeasures against Chemical, Biological, Radiological, and Nuclear Agents.

Degree: Docteur es, Sciences économiques, 2018, Paris 2; France. Institut de recherche biomédicale des armées

Pour certaines maladies causées par des agents chimiques, biologiques, radiologiques et nucléaires (CBRN), il n’existe pas de contre-mesures médicales (MedCM) et bon nombre de celles qui existent pourraient ne pas être disponibles en cas de besoin. En cas d’accident CBRN, des efforts inadéquats de financement de la R&D et de mise à disposition par les gouvernements peuvent avoir de graves conséquences économiques nettement supérieures aux coûts d’initiatives préventives. Compte-tenu des contraintes budgétaires auxquelles de nombreux gouvernements sont confrontés, il est nécessaire de définir des priorités. Parallèlement à la mise en place d’indicateurs de décision de santé efficaces qui identifient et mesurent les effets de causalité de l’impact négatif sur la santé, le processus de décision doit également prendre en considération le rapport coût-efficacité pour rendre le financement durable.Cette thèse a pour objectif de définir une voie vers une politique économique de santé publique visant à renforcer la disponibilité des MedCM pour les agents CBRN. Dans la première partie, les causes des défaillances du marché sont identifiées (lorsque les opportunités de profit ne compensent pas l’effort de R&D nécessaire). Dans la deuxième partie, des études de cas illustrent les caractéristiques et les conséquences économiques d’exemples d’accidents CBRN et des scénarios sont analysés afin de mettre en évidence comment la disponibilité de MedCM pourrait potentiellement devenir rentable. Enfin, la troisième partie propose des approches plus complètes pour mesurer et compenser les facteurs contribuant à la défaillance du marché en appliquant des modèles économiques spécifiques.

For some diseases caused by chemical, biological, radiological, and nuclear (CBRN) agents, innovative medical countermeasures (MedCMs) do not exist while many of those that do might not be readily available. In case of a CBRN event, inappropriate medical research and development (R&D) funding and government procurement efforts can result in adverse economic consequences (e.g. lost income) far exceeding the costs of strong and comprehensive preparedness initiatives. Given the budgetary constraints many governments face, priorities must be defined. Parallel to determining effective health decision metrics that identify and weigh the causal effects of negative health impact, decision making must also consider cost-effectiveness to make funding sustainable. Moreover, international cooperation is necessary since the risks increasingly transcend borders due to global travel and the global threat of terrorism. This dissertation ultimately seeks to define a path to public health economic policy to enhance the international availability of CBRN MedCMs. In Part I, the root causes of market failure are identified and depicted (i.e., where rewards for supply do not adequately compensate for the R&D effort). In Part II, case study examples illustrate the characteristics and economic consequences of CBRN incidents. Scenarios for each case are outlined to show where…

Advisors/Committee Members: Guille, Marianne (thesis director), Dorandeu, Frédéric (thesis director).

Subjects/Keywords: Economie comportementale; Agents chimiques, biologiques, radiologiques et nucléaires; Faisabilité économique; Défaillances du marché; Contre-mesures médicales; Economie politique; Politique économique de santé publique; Offre et demande; Behavioural economics; Chemical, biological, radiological and nuclear agents; Economics feasability; Market failure; Medical countermeasures; Political economics; Public health economic policy; Supply and demand

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Johnson, M. L. (2018). Contre-mesures médicales contre les risques NRBC : quelles solutions pour un développement facilité dans une économie de marché ? : International Availability of Medical Countermeasures against Chemical, Biological, Radiological, and Nuclear Agents. (Doctoral Dissertation). Paris 2; France. Institut de recherche biomédicale des armées. Retrieved from http://www.theses.fr/2018PA020014

Chicago Manual of Style (16th Edition):

Johnson, Mark Lawrence. “Contre-mesures médicales contre les risques NRBC : quelles solutions pour un développement facilité dans une économie de marché ? : International Availability of Medical Countermeasures against Chemical, Biological, Radiological, and Nuclear Agents.” 2018. Doctoral Dissertation, Paris 2; France. Institut de recherche biomédicale des armées. Accessed December 09, 2019. http://www.theses.fr/2018PA020014.

MLA Handbook (7th Edition):

Johnson, Mark Lawrence. “Contre-mesures médicales contre les risques NRBC : quelles solutions pour un développement facilité dans une économie de marché ? : International Availability of Medical Countermeasures against Chemical, Biological, Radiological, and Nuclear Agents.” 2018. Web. 09 Dec 2019.

Vancouver:

Johnson ML. Contre-mesures médicales contre les risques NRBC : quelles solutions pour un développement facilité dans une économie de marché ? : International Availability of Medical Countermeasures against Chemical, Biological, Radiological, and Nuclear Agents. [Internet] [Doctoral dissertation]. Paris 2; France. Institut de recherche biomédicale des armées; 2018. [cited 2019 Dec 09]. Available from: http://www.theses.fr/2018PA020014.

Council of Science Editors:

Johnson ML. Contre-mesures médicales contre les risques NRBC : quelles solutions pour un développement facilité dans une économie de marché ? : International Availability of Medical Countermeasures against Chemical, Biological, Radiological, and Nuclear Agents. [Doctoral Dissertation]. Paris 2; France. Institut de recherche biomédicale des armées; 2018. Available from: http://www.theses.fr/2018PA020014

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