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Comparative Medicine

Gregory L King, David J Sandgren, Jennifer M Mitchell, David L Bolduc, William F Blakely
We developed a clinical assessment tool for use in an NHP radiation model to 1) quantify severity responses for subsyndromes of the acute radiation syndrome (ARS; that is, hematopoietic and others) and 2) identify animals that required enhanced monitoring. Our assessment tool was based primarily on the MEdical TREatment ProtocOLs for Radiation AccidentVictims (METREPOL) scoring system but was adapted for NHP to include additional indices (for example, behaviors) for usein NHP studies involving limited medical intervention...
October 10, 2018: Comparative Medicine
Janice M Rusnak, Lesley C Dupuy, Nancy A Niemuth, Andrew M Glenn, Lucy A Ward
Licensure of medical countermeasure vaccines to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires the use of the Animal Rule to assess vaccine efficacy, because human studies are not feasible or ethical. We therefore performed a retrospective study of VEE cases that occurred in at-risk laboratory workers and support personnel during the United States Biowarfare Program (1943-1969) to better define percutaneous- and aerosol-acquired VEE in humans and to compare these results with those described for the NHP model (in which high-dose aerosol VEEV challenge led to more severe encephalitis than parenteral challenge)...
October 1, 2018: Comparative Medicine
Geoffroy Napon, Alicia J Dafferner, Ashima Saxena, Oksana Lockridge
Drugs to protect against nerve agent toxicity are tested in animals. The current preferred small animal model is guinea pigs because their plasma bioscavenging capacity resembles that of NHP. We stained nondenaturing polyacrylamide slab gels with a variety of substrates, inhibitors, and antibodies to identify the esterases in heparinized guinea pig plasma. An intense band of carboxylesterase activity migrated behind albumin. Minor carboxylesterase bands were revealed after background activity from paraoxonase was inhibited by using EDTA...
October 1, 2018: Comparative Medicine
Kathleen M Donovan, Mariah R Leidinger, Logan P McQuillen, J Adam Goeken, Christine M Hogan, Sailesh C Harwani, Heather A Flaherty, David K Meyerholz
Allograft inflammatory factor 1 (AIF1) is a commonly used marker for microglia in the brains of humans and some animal models but has had limited applications elsewhere. We sought to determine whether AIF1 can be used as a macrophage marker across common laboratory animal species and tissues. We studied tissues (that is, spleen, liver, and lung) with defined macrophage populations by using an AIF1 immunostaining technique previously validated in human tissue. Tissues were collected from various mouse strains ( n = 20), rat strains ( n = 15), pigs ( n = 4), ferrets ( n = 4), and humans ( n = 4, lung only)...
October 1, 2018: Comparative Medicine
Cynthia J Doane, Karuna Patil, Emely A Hoffman, Jessica Stokes, Emmanuel Katsanis, David G Besselsen
Multiple adult female CB6F1 mice presented with supernumerary incisors after preconditioning with chemotherapy and total body irradiation for bone marrow transplantation (BMT). Mice received nonmyeloablative total body irradiation (3 Gy) and either cyclophosphamide or bendamustine, followed by BMT and posttransplantation cyclophosphamide or bendamustine. Here we describe the clinical presentation, μCT findings, and histopathologic evaluation of the affected mice. These analyses confirmed the gross diagnosis and revealed details of the abnormal tooth morphology...
October 1, 2018: Comparative Medicine
Leah M Zadrozny, Lauren R Brinster, Barry A Rosenzweig, Kristina E Howard
Unexpected mortality occurred in a group of 12 NOD.Cg-NOD.Cg- Prkdcscid Il2rgtm1Wjl /SzJ (NSG) and 12 NOD.Cg- Rag1tm1Mom Il2rgtm1Wjl /SzJ (NRG) immunodeficient mice. At 10 d after routine bone marrow-liver-thymus humanization surgery, 9 mice were found dead without observation of initiating clinical signs; 1 d later (day 11), 3 additional mice showed signs of morbidity, including severe hunching, lateral recumbency, slow movement, shallow respiration, and decreased response to external stimulus. All remaining mice rapidly decompensated and were found dead or were euthanized within 4 d after the first death...
October 1, 2018: Comparative Medicine
Patrick C Ng, Tara B Hendry-Hofer, Alyssa E Witeof, Matthew Brenner, Sari B Mahon, Gerry R Boss, Vikhyat S Bebarta
Cyanide is a readily available and potentially lethal substance. Oral exposure can result in larger doses, compared with other routes. Currently, there are no antidotes specific for use in the treatment of oral cyanide poisoning, and studies cannot be done in humans. We report on a new large animal model of oral cyanide toxicity to evaluate potential antidotes. Six female swine ( Sus scrofa ; weight, 45 to 55 kg) were anesthetized, intubated, and instrumented. Animals received a KCN bolus of either 5 or 8 mg/kg delivered via orogastric tube...
October 1, 2018: Comparative Medicine
Hayato Iwase, Edwin C Klein, David Kc Cooper
Xenotransplantation can provide a solution to the current shortage of human organs for patients with terminal renal failure. The increasing availability of genetically engineered pigs, effective immunosuppressive therapy, and antiinflammatory therapy help to protect pig tissues from the primate immune response and can correct molecular incompatibilities. Life-supporting pig kidney xenografts have survived in NHP for more than 6 mo in the absence of markers of consumptive coagulopathy. However, few reports have focused on the physiologic aspects of life-supporting pig kidney xenografts...
October 1, 2018: Comparative Medicine
Catherine J Leader, Barbara J Clark, Amber R Hannah, Ivan A Sammut, Gerard T Wilkins, Robert J Walker
Hypertension is a leading risk factor for cardiovascular and chronic kidney disease. A new rodent model (transgenic male Cyp1a1-Ren2 rats) provides reversible induction of hypertension through the addition of indole-3-carbinol (I3C) to the diet, without the need for surgical intervention, thus giving researchers control over both the onset of hypertension and its magnitude (I3C dose-dependency). We here report the breeding performance and productivity of Cyp1a1-Ren2 rats. Despite being transgenic, these animals proved to be efficient breeders...
October 1, 2018: Comparative Medicine
Jennifer L Asher, Grace J Barnett, Caroline J Zeiss
This report describes the clinical, radiographic, and pathologic findings in a female rhesus macaque that presented with acute abdominal distension and tympany. The macaque was euthanized after evidence of severe colonic distension on radiography and observation of widespread peritoneal adhesions on exploratory laparotomy. Gross and histopathologic evaluation revealed extensive entrapment of gastrointestinal and reproductive tracts by serosal fibrovascular proliferative tissue containing foci of endometriosis...
October 1, 2018: Comparative Medicine
Mila C Kundu, Liz R Gore, Sean Maguire, Aidan G Gilmartin
Hydroxyurea induces production of fetal hemoglobin (HbF), a tetramer of α and γ globin proteins and corresponding heme molecules, normally found in less than 1% of adult RBC. Increases in circulating HbF are correlated with clinical improvement of patients with hemoglobinopathies, and hydroxyurea, as a daily medication, is the standard treatment for sickle cell anemia. Although olive baboons ( Papio anubis ) are considered a key model species for HbF induction, cynomolgus macaques ( Macaca fasicularis ) are another species that conserves the ability to produce HbF into maturity...
October 1, 2018: Comparative Medicine
Marie-Josee Mf Lemoy, Gregory W Salyards, Rebekah I Keesler, J R Reader
We here report a spontaneous case of primary myxoid liposarcoma of the greater omentum with subsequent transperitoneal recurrence. The primary mass was incidentally found during an exploratory laparotomy for a presumed diagnosis of trichobezoar or phytobezoar and was removed surgically. Histopathologic examination of the mass revealed the presence of a myxoid liposarcoma. Eleven months later, recurrence with severe transperitoneal sarcomatosis of the myxoid liposarcoma was noted and confirmed by necropsy and histopathology...
August 1, 2018: Comparative Medicine
Marinus Fw Te Pas, Sietse-Jan Koopmans, Leo Kruijt, Sjef Boeren, Mari A Smits
Recognition of the preclinical stages of metabolic diseases such as diabetes helps to prevent full development of the disease. In our research, we alter the diet composition of pigs to create a model of human metabolic disease. The objective of the current study was to identify plasma proteins and biologic mechanisms that differed in expression between pigs fed a 'cafeteria diet' (considered unhealthy; high in saturated fats) and those fed a 'Mediterranean diet' (considered healthy; high in unsaturated fats)...
August 1, 2018: Comparative Medicine
Gabrielle C Musk, Murray J Adams, Haruo Usuda, Matthew W Kemp, Claire R Sharp
We investigated the incidence of ex vivo incompatibility between ovine maternal RBC and fetal plasma. Time-mated singleton pregnant ewes (n = 8) underwent cesarean delivery of the fetus; at the time of delivery, paired maternal and fetal blood samples were collected and subsequently separated for storage as packed RBC and fresh frozen plasma. Gel column crossmatching was performed 3 to 4 wk later. All fetus-dam crossmatches were considered major crossmatches, combining fetal (recipient) plasma with dam (donor) RBC...
August 1, 2018: Comparative Medicine
A Marissa Wolfe, Masmudur Rahman, D Grant McFadden, Eric C Bartee
Myxoma virus is a member of Leporipoxviridae whose tropism is tightly restricted to lagomorphs. In susceptible Oryctolagus rabbits, the virus causes a highly lethal disease known as myxomatosis, which begins as a localized infection but rapidly disseminates throughout the animal, leading to immune compromise, mucosal infections, multiorgan failure, and death. In a research setting, myxoma infection of susceptible Oryctolagus cuniculus rabbits is used as a model of poxviral disease progression and represents one of only a few means to study the pathogenesis of this viral family in a native host species...
August 1, 2018: Comparative Medicine
Kenneth J Salleng, Carissa P Jones, Kelli L Boyd, Donna J Hicks, Michelle M Williams, Rebecca S Cook
Female nude mice (J:NU-Foxn1nu; age, 6 wk) were injected with 1 million MCF7 human breast cancer cells in the fourth mammary fat pads and received a 21-d sustained-release estrogen pellet (0.25 mg) subcutaneously in the dorsum of the neck. All mice were maintained in sterile housing and provided sterile water and irradiated rodent chow. Approximately 6 wk after implantation, 4 of the 30 mice showed clinical signs of depression and dehydration. The 2 animals most severely affected were euthanized and presented for necropsy...
August 1, 2018: Comparative Medicine
Caroline Bodi Winn, Stephen C Artim, Morgan S Jamiel, Monika A Burns, Jennifer L Haupt, James G Fox, Sureshkumar Muthupalani
A 6-y-old, intact, pair-housed male common marmoset (Callithrix jacchus) presented with acute onset dyspnea and tachypnea immediately after sedation with alfaxalone; a history of gradual weight loss initiated the examination under sedation. Thoracic radiographs revealed significant right-lung consolidation, with a vesicular gas pattern in the right caudodorsal lung field, pleural effusion, and dorsal displacement of the heart. The marmoset was euthanized due to his unstable condition and poor prognosis. At necropsy, the cranial and middle lobes of the right lung were homogenously dark red-brown, enlarged, edematous, and twisted around the longitudinal axis at the hilus...
August 1, 2018: Comparative Medicine
Kendra L Bauer, James C Steeil, Elizabeth A Adkins, April L Childress, James F X Wellehan, Kenton L Kerns, Steven J Sarro, Kali A Holder
A 20-y-old male intact white-faced saki monkey (Pithecia pithecia) presented with an acute ocular disease of the right eye. Clinical signs included periocular swelling, conjunctivitis, and anisocoria with a miotic right pupil. Conjunctival swabs were positive for Human herpesvirus 1 (HHV1) according to PCR amplification with sequencing. Initial clinical signs resolved with supportive treatment, and the animal was managed chronically by using acyclovir (5 mg/kg PO twice daily) during flare-ups. After more than 2 y, the progression of clinical disease led to enucleation of the right eye...
August 1, 2018: Comparative Medicine
Ana M Misic, Emily L Miedel, Angela K Brice, Stephen Cole, Grace F Zhang, Cecilia D Dyer, Anthony Secreto, Abigail L Smith, Gwenn Danet-Desnoyers, Daniel P Beiting
Immunocompromised mice are used frequently in biomedical research, in part because they accommodate the engraftment and study of primary human cells within a mouse model; however, these animals are susceptible to opportunistic infections and require special husbandry considerations. In 2015, an outbreak marked by high morbidity but low mortality swept through a colony of immunocompromised mice; this outbreak rapidly affected 75% of the colony and ultimately required complete depopulation of the barrier suite...
August 1, 2018: Comparative Medicine
Robert T Dauchy, Melissa A Wren-Dail, Lynell M Dupepe, Steven M Hill, Shulin Xiang, Muralidharan Anbalagan, Victoria P Belancio, Erin M Dauchy, David E Blask
Liver cancer is the second leading cause of cancer death worldwide. Metabolic pathways within the liver and liver cancers are highly regulated by the central circadian clock in the suprachiasmatic nuclei (SCN). Daily light and dark cycles regulate the SCN-driven pineal production of the circadian anticancer hormone melatonin and temporally coordinate circadian rhythms of metabolism and physiology in mammals. In previous studies, we demonstrated that melatonin suppresses linoleic acid metabolism and the Warburg effect (aerobic glycolysis)in human breast cancer xenografts and that blue-enriched light (465-485 nm) from light-emitting diode lighting at daytime (bLAD) amplifies nighttime circadian melatonin levels in rats by 7-fold over cool white fluorescent (CWF) lighting...
August 1, 2018: Comparative Medicine
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