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1.
Radiat Res ; 176(1): 89-101, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21520996

ABSTRACT

Additional large animal models for the acute radiation syndrome (ARS) would facilitate countermeasure development. We demonstrate here that Gottingen minipigs develop hematopoietic ARS symptoms similar to those observed in canines, non-human primates (NHPs) and humans. Dosimetry for whole-body γ irradiation (0.6 Gy/min) was performed using electronic paramagnetic resonance (EPR) with alanine; National Institute of Standards and Technology (NIST)-calibrated alanine pellets and water-filled Plexiglas phantoms were used. After irradiations of 1.6-2.0 Gy, blood pancytopenia was observed for several weeks, accompanied by the characteristic ARS stages: prodromal symptoms, latent period, illness and recovery or morbidity. Morbidity occurred between days 14 and 27, with a preliminary LD(50/30) estimate between 1.7 and 1.9 Gy. The criterion of whether platelet counts were <200 × 10(3)/µl 7 days postirradiation predicted whether animals would survive in 18 out of 20 cases. The degree of granulocytosis 3 h postirradiation was inversely correlated with survival. Animals euthanized based on preset morbidity criteria displayed signs of multi-organ dysfunction, including widespread internal hemorrhage and alterations in organ function reflected in blood chemistry. Circulating C-reactive protein (CRP), a marker for inflammation, became elevated within hours after irradiation, subsided after several days, and increased again after 14 days. The results support further development of the Gottingen minipig as a model for ARS.


Subject(s)
Acute Radiation Syndrome , Disease Models, Animal , Hematopoiesis/radiation effects , Acute Radiation Syndrome/blood , Acute Radiation Syndrome/pathology , Acute Radiation Syndrome/physiopathology , Animals , C-Reactive Protein/metabolism , Clinical Chemistry Tests , Hematology , Humans , Male , Survival Analysis , Swine
2.
J Am Assoc Lab Anim Sci ; 50(1): 65-72, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21333166

ABSTRACT

Threats of nuclear and other radiologic exposures have been increasing, but no countermeasure for acute radiation syndrome has been approved by regulatory authorities. Because of their similarity to humans in regard to physiology and anatomy, we are characterizing Gottingen minipigs as a model to aid the development of radiation countermeasures. Irradiated minipigs exhibit immunosuppression, severe thrombocytopenia, vascular leakage, and acute inflammation. These complications render serial acquisition of blood samples problematic. Vascular access ports (VAP) facilitate serial sampling, but their use often is complicated by infections and fibrin deposition. We demonstrate here the successful use of VAP for multiple blood samplings in irradiated minipigs. Device design and limited postoperative prophylactic antimicrobial therapy before irradiation were key to obtaining serial sampling, reducing swelling, and eliminating infection and skin necrosis at the implantation site. Modifications of previous protocols included the use of polydioxanone sutures instead of silk; eliminating chronic port access; single-use, sterile, antireflux prefilled syringes for flushing; strict aseptic weekly maintenance of the device, and acclimating animals to reduce stress. VAP remained functional in 19 of 20 irradiated animals for as long as 3 mo. The remaining VAP failed due to a small leak in the catheter, leading to clot formation. VAP-related sepsis occurred in 2 minipigs. Blood sampling did not cause detectable stress in nonanesthetized sham-irradiated animals, according to leukograms and clinical signs.


Subject(s)
Catheters, Indwelling/veterinary , Radiation Injuries, Experimental/surgery , Swine, Miniature/surgery , Animal Welfare , Animals , Antibiotic Prophylaxis/veterinary , Catheters, Indwelling/adverse effects , Equipment Design/veterinary , Male , Postoperative Care/veterinary , Radiation Injuries, Experimental/blood , Stress, Physiological , Swine , Swine, Miniature/blood , Swine, Miniature/microbiology
3.
Lab Anim (NY) ; 37(2): 81-6, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18216799

ABSTRACT

Though carbon dioxide asphyxiation is a common method of euthanasia for laboratory animals, species-specific guidelines have not been established for this procedure in the domestic ferret (Mustela putorius furo). The authors investigated the efficacy and stress effects of carbon dioxide euthanasia in 24 ferrets that had participated in previous experimental protocols. They euthanized ferrets by placing them in cages that were either prefilled with carbon dioxide or gradually filled at a displacement rate of 10%, 20% or 50% of the cage volume per min. Blinded observers subjectively evaluated ferret distress. Prefilling the cage or filling it at a rate of 50% volume per min resulted in less time to recumbency and to last breath than did filling the cage at a slower displacement rate. Slower carbon dioxide displacement rates also caused an increase in ferret blood glucose concentrations, which may indicate distress. Overall, observers found that prefilling the euthanasia cage caused the least stress to ferrets.


Subject(s)
Carbon Dioxide/toxicity , Euthanasia, Animal/methods , Stress, Psychological/chemically induced , Administration, Inhalation , Animals , Behavior, Animal , Blood Glucose/analysis , Female , Ferrets , Stress, Psychological/blood , Stress, Psychological/physiopathology , Time Factors
4.
Mil Med ; 169(6): 421-8, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15281669

ABSTRACT

The Department of Defense (DoD) has engaged in West Nile virus (WNV) surveillance and response since 1999. In 2002, the three Services continued their cooperative, multidisciplinary approach to the WNV outbreak. Activities included a doubling of mosquito surveillance and vector control responses, extension of and doubling of bird and nonhuman mammal surveillance to all four continental United States regions, expanded diagnostic testing by DoD laboratories, and installation environmental clean up and personnel protection campaigns. Medical treatment facilities conducted passive surveillance and reported possible cases in DoD health care beneficiaries. Efforts were coordinated through active communication within installations, with commands, and with surrounding communities. Undertaken activities complemented each other to maximize surveillance coverage. The surveillance detected WNV on 44 DoD installations. It led directly to vector control and prevention activities, and there were no confirmed cases of WNV reported in the DoD force. This multi-Service effort is a surveillance template for future outbreaks that threaten DoD force health.


Subject(s)
Military Medicine , Population Surveillance/methods , West Nile Fever/prevention & control , West Nile virus/isolation & purification , Animals , Humans , United States/epidemiology , West Nile Fever/epidemiology
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