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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Adaptation of LASCA method for diagnostics of malignant tumours in laboratory animals

The LASCA method is adapted for diagnostics of malignant neoplasms in laboratory animals. Tumours are studied in mice of Balb/c inbred line after inoculation of cells of syngeneic myeloma cell line Sp.2/0 Ag.8. The appropriateness of using the tLASCA method in tumour investigations is substantiated; its advantages in comparison with the sLASCA method are demonstrated. It is found that the most informative characteristic, indicating the presence of a tumour, is the fractal dimension of LASCA images.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

High-resolution short-exposure small-animal laboratory x-ray phase-contrast tomography

X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten μm spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-power small-spot liquid-metal-jet electron-impact source. Lastly, the tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

STEM Infrastructure Improvement: Wilson-Booker Science Building (WBSB)

The Division of Natural Sciences and Mathematics is housed in the Wilson-Booker Science Building (WBSB) which previously consisted of six classrooms, a lecture room, three biology laboratories, one physics laboratory, one chemistry laboratory, one research laboratory, and three computer laboratories. However, due to rapid expansion in STEM majors, there was a dire need for more classroom and laboratory space to accommodate this expansion. Further, since the College started integrating research into the curriculum in 2004 in order to keep pace with the national trend in science education, it has become apparent that one small research laboratory that accommodates 10 students will not keep pace with the growing needs of the new students interested in research. Therefore, it became imperative to add another research laboratory to augment the existing one. Thus, the new instrumentation/Research Laboratory will provide space for the new equipment and research space for an additional 8 - 10 students. In addition, the new WBSB wing also houses a Biochemisty/Molecular Biology Laboratory, an Organic Chemistry laboratory, an Animal Laboratory, a Seminar Room, two spacious classrooms, and 3 Faculty Offices. The impact of the new facility will be far-reaching.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2014

Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL shares morphologic/mechanistic similarities with Niemann–Pick type C disease. • Di-22:6-BMP is an effective DIPL biomarker in humans via NPC patient validation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Estimation of reactogenicity of preparations produced on the basis of photoinactivated live vaccines against brucellosis and tularaemia on the organismic level. 2. Using the method of speckle-microscopy with high spatial resolution

The method of speckle microscopy was adapted to estimate the reactogenicity of the prototypes of vaccine preparations against extremely dangerous infections. The theory is proposed to describe the mechanism of formation of the output signal from the super-high spatial resolution speckle microscope. The experimental studies show that bacterial suspensions, irradiated in different regimes of inactivation, do not exert negative influence on the blood microcirculations in laboratory animals. (optical technologies in biophysics and medicine)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Estimation of reactogenicity of preparations produced on the basis of photoinactivated live vaccines against brucellosis and tularaemia on the organismic level. 1. Using the LASCA method

A new method of photoinactivation of bacteria aimed at producing prototypes of vaccine preparations against extremely dangerous infections is described. The reactogenicity of the new prophylactic preparations was studied using the laser speckle contrast analysis (LASCA). The performed experimental studies show that bacterial suspensions, irradiated using different regimes of photoinactivation, do not cause detrimental effect on the blood microcirculation in laboratory animals. (optical technologies in biophysics and medicine)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Recent advances in the risk assessment of melamine and cyanuric acid in animal feed

Melamine can be present at low levels in food and feed mostly from its legal use as a food contact material in laminates and plastics, as a trace contaminant in nitrogen supplements used in animal feeds, and as a metabolite of the pesticide cyromazine. The mechanism of toxicity of melamine involves dose-dependent formation of crystals with either endogenous uric acid or a structural analogue of melamine, cyanuric acid, in renal tubules resulting in potential acute kidney failure. Co-exposure to melamine and cyanuric acid in livestock, fish, pets and laboratory animals shows higher toxicity compared with melamine or cyanuric acid alone. Evidence for crystal formation between melamine and other structural analogs i.e. ammelide and ammeline is limited. Illegal pet food adulterations with melamine and cyanuric acid and adulteration of milk with melamine resulted in melamine–cyanuric acid crystals, kidney damage and deaths of cats and dogs and melamine–uric acid stones, hospitalisation and deaths of children in China respectively. Following these incidents, the tolerable daily intake for melamine was re-evaluated by the U.S. Food and Drug Administration, the World Health Organisation, and the Scientific Panel on Contaminants in the Food Chain of the European Food Safety Authority (EFSA). This review provides an overview of toxicology, the adulteration incidents and risk assessments for melamine and its structural analogues. Particular focus is given to the recent EFSA risk assessment addressing impacts on animal and human health of background levels of melamine and structural analogues in animal feed. Recent research and future directions are discussed. - Highlights: ► Melamine in food and feed. ► Forms crystals in kidney with uric acid or cyanuric acid. ► Toxicity higher with cyanuric acid. ► Recent EFSA risk assessment. ► Animal and human health.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Development of computational small animal models and their applications in preclinical imaging and therapy research

The development of multimodality preclinical imaging techniques and the rapid growth of realistic computer simulation tools have promoted the construction and application of computational laboratory animal models in preclinical research. Since the early 1990s, over 120 realistic computational animal models have been reported in the literature and used as surrogates to characterize the anatomy of actual animals for the simulation of preclinical studies involving the use of bioluminescence tomography, fluorescence molecular tomography, positron emission tomography, single-photon emission computed tomography, microcomputed tomography, magnetic resonance imaging, and optical imaging. Other applications include electromagnetic field simulation, ionizing and nonionizing radiation dosimetry, and the development and evaluation of new methodologies for multimodality image coregistration, segmentation, and reconstruction of small animal images. This paper provides a comprehensive review of the history and fundamental technologies used for the development of computational small animal models with a particular focus on their application in preclinical imaging as well as nonionizing and ionizing radiation dosimetry calculations. An overview of the overall process involved in the design of these models, including the fundamental elements used for the construction of different types of computational models, the identification of original anatomical data, the simulation tools used for solving various computational problems, and the applications of computational animal models in preclinical research. The authors also analyze the characteristics of categories of computational models (stylized, voxel-based, and boundary representation) and discuss the technical challenges faced at the present time as well as research needs in the future.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

Purpose: to study the potential utility of 1-thio-D-glucose labeled with {sup 99m}Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of {sup 99m}Tc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with {sup 99m}Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of {sup 99m}Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with {sup 99m}Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of {sup 99m}Tc-1-thio-D-glucose at the tumor site. The accumulation of {sup 99m}Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that {sup 99m}Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of {sup 99m}Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Isolation of rat adrenocortical mitochondria

Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Study of blood plasma optical properties in mice grafted with Ehrlich carcinoma in the frequency range 0.1–1.0 THz

In the course of in vitro studies of blood of laboratory animals with progressing Ehrlich carcinoma, we have revealed the change of the blood plasma optical properties in the THz range, which can be used for developing the express diagnostics of the presence of oncological diseases. An applied software package is elaborated that allows the phantoms of biological samples having a complex structure to be numerically simulated and the parameters of the electromagnetic wave reflected from these samples in the THz frequency range to be calculated. (paper)

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Flexible radioluminescence imaging for FDG-guided surgery

Purpose: Flexible radioluminescence imaging (Flex-RLI) is an optical method for imaging {sup 18}F-fluorodeoxyglucose (FDG)-avid tumors. The authors hypothesize that a gadolinium oxysulfide: terbium (GOS:Tb) flexible scintillator, which loosely conforms to the body contour, can enhance tumor signal-to-background ratio (SBR) compared with RLI, which utilizes a flat scintillator. The purpose of this paper is to characterize flex-RLI with respect to alternative modalities including RLI, beta-RLI (RLI with gamma rejection), and Cerenkov luminescence imaging (CLI). Methods: The photon sensitivity, spatial resolution, and signal linearity of flex-RLI were characterized with in vitro phantoms. In vivo experiments utilizing 13 nude mice inoculated with the head and neck (UMSCC1-Luc) cell line were then conducted in accordance with the institutional Administrative Panel on Laboratory Animal Care. After intravenous injection of {sup 18}F-FDG, the tumor SBR values for flex-RLI were compared to those for RLI, beta-RLI, and CLI using the Wilcoxon signed rank test. Results: With respect to photon sensitivity, RLI, beta-RLI, and flex-RLI produced 1216.2, 407.0, and 98.6 times more radiance per second than CLI. Respective full-width half maximum values across a 0.5 mm capillary tube were 6.9, 6.4, 2.2, and 1.5 mm, respectively. Flex-RLI demonstrated a near perfect correlation with {sup 18}F activity (r = 0.99). Signal uniformity for flex-RLI improved after more aggressive homogenization of the GOS powder with the silicone elastomer during formulation. In vivo, the SBR value for flex-RLI (median 1.29; interquartile range 1.18–1.36) was statistically greater than that for RLI (1.08; 1.02–1.14; p < 0.01) by 26%. However, there was no statistically significant difference in SBR values between flex-RLI and beta-RLI (p = 0.92). Furthermore, there was no statistically significant difference in SBR values between flex-RLI and CLI (p = 0.11) in a more limited dataset. Conclusions: Flex-RLI provides high quality images with SBRs comparable to those from CLI and beta-RLI in a single 10 s acquisition.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Study of the epidermis ablation effect on the efficiency of optical clearing of skin in vivo {sup *}

We present the results of a comparative analysis of optical immersion clearing of skin in laboratory animals in vivo with and without preliminary ablation of epidermis. Laser ablation is implemented using a setup based on a pulsed erbium laser ( λ = 2940 nm). The size of the damaged region amounted to 6 × 6 mm, the depth being smaller than 50 μm. As an optical clearing agent (OCA), use is made of polyethylene glycol (PEG-300). Based on optical coherence tomography, we use the single scattering model to estimate the scattering coefficient in the process of optical clearing in 2 regions at depths of 50−170 μm and 150−400 μm. The results show that skin surface ablation leads to the local oedema of the affected region that increases the scattering coefficient. However, the intense evaporation of water from the ablation zone facilitates the optical clearing at the expense of tissue dehydration, particularly in the upper layers. The assessment of the optical clearing efficiency shows that the efficiency exceeding 30% can be achieved at a depth from 50 to 170 μm in 120 min after ablation, as well as after the same ablation with subsequent application of PEG-300, which increases the efficiency of the immersion method by almost 1.8 times. At a depth from 150 to 400 μm, dehydration of upper layers cannot completely compensate for an increase in light scattering by dermis after epidermis ablation. The additional effect of OCA enhances the optical clearing of skin at the expense of improving the refractive index matching between dermis components, but the maximal efficiency of optical clearing in 120 min does not exceed 6%. (biophotonics)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Transcriptional profiling of rat white adipose tissue response to 2,3,7,8-tetrachlorodibenzo-ρ-dioxin

Polychlorinated dibenzodioxins are environmental contaminants commonly produced as a by-product of industrial processes. The most potent of these, 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), is highly lipophilic, leading to bioaccumulation. White adipose tissue (WAT) is a major site for energy storage, and is one of the organs in which TCDD accumulates. In laboratory animals, exposure to TCDD causes numerous metabolic abnormalities, including a wasting syndrome. We therefore investigated the molecular effects of TCDD exposure on WAT by profiling the transcriptomic response of WAT to 100 μg/kg of TCDD at 1 or 4 days in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. A comparative analysis was conducted simultaneously in identically treated TCDD-resistant Han/Wistar (Kuopio; H/W) rats one day after exposure to the same dose. We sought to identify transcriptomic changes coinciding with the onset of toxicity, while gaining additional insight into later responses. More transcriptional responses to TCDD were observed at 4 days than at 1 day post-exposure, suggesting WAT shows mostly secondary responses. Two classic AHR-regulated genes, Cyp1a1 and Nqo1, were significantly induced by TCDD in both strains, while several genes involved in the immune response, including Ms4a7 and F13a1 were altered in L-E rats alone. We compared genes affected by TCDD in rat WAT and human adipose cells, and observed little overlap. Interestingly, very few genes involved in lipid metabolism exhibited altered expression levels despite the pronounced lipid mobilization from peripheral fat pads by TCDD in L-E rats. Of these genes, the lipolysis-associated Lpin1 was induced slightly over 2-fold in L-E rat WAT on day 4. - Highlights: • Exposure to TCDD causes wasting syndrome in L-E rats but not in H/W rats. • We examined the transcriptome of TCDD-treated L-E and H/W rat white adipose tissue. • L-E WAT demonstrated altered abundance of several genes involved in immune response. • Few genes had altered abundance in both L-E rat WAT and human adipocytes (hMADS). • Pmepa1 was induced in both L-E WAT and differentiated hMADS cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2013

Equine cytochrome P450 2B6 — Genomic identification, expression and functional characterization with ketamine

Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug–drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V{sub max} for S-/and R-norketamine formation was 0.49 and 0.45 nmol/h/mg cellular protein and K{sub m} was 3.41 and 2.66 μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC{sub 50} of 5.63 and 6.26 μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP enzyme involved in ketamine and norketamine metabolism, thus confirming results from inhibition studies with horse liver microsomes. Clopidogrel seems to be a feasible inhibitor for equine CYP2B6. The specificity still needs to be established with other single equine CYPs. Heterologous expression of single equine CYP enzymes opens new possibilities to substantially improve the understanding of drug metabolism and drug interactions in horses. -- Highlights: ► We annotate, express and functionally characterize equine CYP2B6. ► 3 genetic variants within this gene are described. ► Equine CYP2B6 N-demethylates ketamine and metabolizes norketamine. ► Equine CYP2B6 can be inhibited by clopidogrel.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Efficacy of Naloxone as a Treatment for an Acute Exposure to Aerosolized Carfentanil

Carfentanil (CRF) is a powerful synthetic opioid that is approximately 100 times more potent than fentanyl and 10,000 times more potent than morphine. CRF originally was intended to be used as a sedative for big game animals in a veterinary setting, but is becoming increasingly common in the illicit drug trade. The increased use of CRF by people has put strain on first responders, who need to administer increased doses of naloxone (Naracan®, Evzio®), an FDA‐approved opioid antagonist, to counteract the effects. First responders may also worry about the potential of self‐exposure through inhalation or dermal contact with CRF. We set out to study the effectiveness of naloxone against a potentially lethal dose of inhaled CRF in male ferrets. Ferrets were implanted with telemetry devices to study cardiac parameters and exposed to aerosolized CRF in a whole‐body plethysmography chamber to record respiratory parameters. We observed profound depression of respiration which resulted in the animals becoming apneic 23% ± 9% of the time during exposure. We also observed cardiac abnormalities, in the form of premature junctional contractions (PJCs), in the ferrets during the apneic periods. At our acute exposure dose, which was lethal in 9% of our animals, ferrets were unresponsive and incapacitated for 105.6 ± 20.0 minutes following the end of exposure. Naloxone, when administered intramuscularly at human equivalent doses ranging from 4 to 40 mg, significantly reduced the time that ferrets were incapacitated following exposure. Although we saw no significant difference in the reduction of time that the animals were incapacitated between the treatment groups (average times between treatment and revival ranged from 6.5 to 9.7 minutes), higher doses of naloxone did revive a portion of the ferrets quicker than the lower doses (some as soon as 1.5–3.5 minutes post‐treatment). We also observed that naloxone was able to significantly reduce the amount of apneic episodes in CRF‐exposed ferrets and resolved the observed cardiac PJCs. Our results suggest that naloxone is a viable treatment against the effects of a potentially lethal dose of inhaled CRF in ferrets. These data have the potential to inform and aid treatment strategies for an acute inhalation exposure to synthetic opioids. Support or Funding Information Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the US Army. This research complied with the Animal Welfare Act and implementing Animal Welfare Regulations and adhered to the principles noted in The Guide for the Care and Use of Laboratory Animals. This research was supported by DTRA RD‐CB. M.R. and N.A.A. were supported in part by an appointment to the Postgraduate Research Participation Program at the US Army Medical Research Institute of Chemical Defense administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and USAMRMC. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

McCranor, Bryan J.↗