Collaborating for the Successful Retirement and End-of-Life Care of Non-Human Primates in Biomedical Research.

Research facilities have established animal adoption programs for laboratory animals. However, adoption to private owners is not an option for non-human primates (NHPs), so their post-research life presents a unique challenge. Here, we describe a collaborative effort between laboratory animal veterinarians and behavioral management staff in retiring NHPs in place to ensure their quality of life after the completion of research projects.

Determination of an Acclimation Period for Swine in Biomedical Research.

Swine are widely used models in biomedical research due to their physiologic and anatomic similarities to humans. During transport from vendors to research facilities, pigs are subject to a number of stressors, including environmental, social, and stress as a result of deprivation from food and water. As stress can have a number of adverse psychologic and physiologic effects, an acclimation period, defined as the period of time that an animal has to adjust and stabilize in a new environment, is recommended.

The Use of Guanfacine to Mediate Anxiety-related Reactivity and Reduce Associated Agonistic Behavior in Two Pigtail Macaques ().

Guanfacine, an α ₂adrenoceptor agonist, has been used to successfully treat self-injurious behavior in nonhuman primates, including macaques () and baboons (). It does so by facilitating a correction to the dopaminergic system that mediates a reduction in impulsivity and reactivity. Given this, we assessed the potential efficacy of guanfacine to treat socially directed agonistic behavior in primates with an apparent reactive behavioral phenotype.

Comparing different strategies to reduce hepatocellular damage in obese common marmosets (Callithrix jacchus).

Background: Obesity in common marmosets (Callithrix jacchus) can lead to various liver pathologies. In other species, reduced caloric intake and weight loss improve prognosis, and, often, hepatoprotectants are used to halt or reverse hepatocellular damage from fat deposition in the liver. There are no published therapies for reducing hepatocellular damage in obese marmosets.

Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to .

Extracellular vesicles (EVs) have potential in disease treatment since they can be loaded with therapeutic molecules and engineered for retention by specific tissues. However, questions remain on optimal dosing, administration, and pharmacokinetics. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available for larger animals.

A comparison of different antibiotic regimens for the treatment of naturally acquired shigellosis in rhesus and pigtailed macaques (Macaca mulatta and nemestrina).

Background: Shigella spp. are common enteric pathogens in captive non-human primates. Treatment of symptomatic infections involves supportive care and antibiotic therapy, typically with an empirical choice of antibiotic.

Improving transparency-A call to include social housing information in biomedical research articles involving nonhuman primates.

The social setting of animal subjects in the research environment has known effects on a variety of dependent measures used in biomedical research. Proper evaluation of the robustness of published research is dependent upon transparent, detailed, and accurate reporting of research methods, including the animals' social housing conditions. However, to date, most research articles utilizing nonhuman primates (NHPs) provide only partial data on this topic, hampering transparency, and reproducibility.

Elucidation of the Central Serotonin Metabolism Pathway in Rhesus Macaques () with Self-injurious Behavior.

Macaques with self-injurious behavior (SIB) have been used as a model of human SIB and have previously been shown to respond to treatments targeting enhancement of central serotonin signaling, whether by supplementation with tryptophan, or by inhibiting synaptic reuptake. Decreased serotonin signaling in the brain has also been implicated in many human psychopathologies including major depression disorder. A disturbance in tryptophan metabolism that moves away from the production of serotonin and toward the production of kynurenine has been proposed as a major etiological factor of depression.

Pluripotent stem cell-derived corneal endothelial cells as an alternative to donor corneal endothelium in keratoplasty.

Here, we evaluate the efficacy of cryopreserved human embryonic stem cell (hESC)-derived corneal endothelial cells (CECs) to form a functional monolayer of corneal endothelium (CE) in rabbits and monkeys. We injected cryopreserved hESC-derived CECs into the anterior chamber of rabbits and monkeys either immediately after mechanical scraping of the central CE or a few days later when corneal edema developed. All preclinical models developed deturgesced and clear corneas following the injection of cryopreserved hESC-derived CECs and remained comparable to the corneas of the untreated eye.

The use of midazolam as an appetite stimulant and anxiolytic in the common marmoset (Callithrix jacchus).

Background: Food avoidance secondary to disease or stress can lead to weight loss and rapid deterioration of clinical condition in the common marmoset (Callithrix jacchus). Currently, there are no data supporting the use of any pharmaceuticals as an appetite stimulant in this species; however, benzodiazepines are frequently used for this purpose in other species.

Methods: Six marmosets were used in a crossover study design to evaluate the benzodiazepine midazolam as an appetite stimulant and anxiolytic.

Biokinetics of Radiolabeled Monoclonal Antibody BC8: Differences in Biodistribution and Dosimetry Among Hematologic Malignancies.

We reviewed In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain the biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Serial whole-body scintigraphic images (4 time points) were obtained after infusion of the In-DOTA-BC8 (176-406 MBq) into 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in men), and 2 marrow sites (acetabulum and sacrum), and correction for attenuation and background was made.

Evaluation of the guaiac fecal occult blood test for detection of gastrointestinal bleeding in the rhesus macaque (Macaca mulatta).

Background: Gastrointestinal (GI) hemorrhage accompanies several common diseases of rhesus macaques (Macaca mulatta). Guaiac fecal occult blood testing (gFOBT) is a non-invasive means to detect such bleeding in several species; however, there are currently no data indicating reliability of this test to detect GI hemorrhage in macaques.

Methods: We evaluated sensitivity and specificity of gFOBT to detect simulated and biopsy-associated bleeding in the stomach, duodenum, and colon of 15 rhesus macaques.

Serum Cobalamin (Vitamin B12) Concentrations in Rhesus Macaques (Macaca mulatta) and Pigtailed Macaques (Macaca nemestrina) with Chronic Idiopathic Diarrhea.

Chronic diarrhea poses a significant threat to the health of NHP research colonies, and its primary etiology remains unclear. In macaques, the clinical presentation of intractable diarrhea and weight loss that are accompanied by inflammatory infiltrates within the gastrointestinal tract closely resembles inflammatory bowel disease of humans, dogs, and cats, in which low serum and tissue cobalamin (vitamin B12) levels are due to intestinal malabsorption. We therefore hypothesized that macaques with chronic idiopathic diarrhea (CID) have lower serum cobalamin concentrations than do healthy macaques.

Severity and Distribution of Wounds in Rhesus Macaques (Macaca mulatta) Correlate with Observed Self-Injurious Behavior.

Self-injurious behavior (SIB) occurs within laboratory-housed NHP at low frequency but can have a devastating effect on animal research and wellbeing. One barrier to the study and clinical management of these cases is the cost of equipment and personnel time to quantify the behavior according to the current standard of observation and to score remotely obtained video recordings. In studies of human SIB, in which direct observation is difficult or prohibited, researchers have demonstrated that quantifying the tissue damage resulting from SIB can be a useful proxy to represent the underlying behavior.

The use of glucocorticoids in marmoset wasting syndrome.

Background: Marmoset wasting syndrome (MWS) is one of the leading causes of morbidity and mortality in captive marmosets, and thus far no reliable treatment has been found. Glucocorticoids are used widely to treat inflammatory conditions of the GI tract such as human and feline inflammatory bowel disease, which, such as MWS, are histologically characterized by chronic lymphoplasmacytic inflammation in the intestines. Budesonide is a glucocorticoid with few reported side effects due to the majority of it being metabolized into inactive compounds by the liver before entering the systemic circulation.

Limits to using HPA axis activity as an indication of animal welfare.

HPA axis activity is often measured by corticosteroid release as a means to evaluate stress and well-being in animals. While the analysis of corticosteroid levels can provide useful information in some circumstances, a variety of methodological and technical problems make them difficult to accurately interpret. Furthermore, there is considerable evidence that is inconsistent with the widespread notion that high levels of stress result in a large amount of corticosteroid release, and in some cases the converse is true.

Use of an aquarium as a novel enrichment item for singly housed rhesus macaques (Macaca mulatta).

Locomotor stereotypies are behaviors often seen in singly housed rhesus macaques (Macaca mulatta) and are considered to represent a maladaptive response to captive environments. Active and passive enrichment items are commonly used to mitigate these and other abnormal behaviors. Active enrichment items allow physical manipulation and may be temporarily successful in reducing stereotypies, but their beneficial effects usually are confined to relatively short periods of active use.

Refinement.

The ultimate goal of the Three Rs is the full replacement of animals used in biomedical research and testing. However, replacement is unlikely to occur in the near future; therefore the scientific community as a whole must continue to devote considerable effort to ensure optimal animal welfare for the benefit of the science and the animals, i.e.

Serum albumin and body weight as biomarkers for the antemortem identification of bone and gastrointestinal disease in the common marmoset.

The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease.

Diagnosis of amyloidosis and differentiation from chronic, idiopathic enterocolitis in rhesus (Macaca mulatta) and pig-tailed (M. nemestrina) macaques.

Amyloidosis is a progressive and ultimately fatal disease in which amyloid, an insoluble fibrillar protein, is deposited inappropriately in multiple organs, eventually leading to organ dysfunction. Although this condition commonly affects macaques, there is currently no reliable method of early diagnosis. Changes in clinical pathology parameters have been associated with amyloidosis but occur in late stages of disease, are nonspecific, and resemble those seen in chronic, idiopathic enterocolitis.

Environmental enrichment during rearing alters corticosterone levels, thymocyte numbers, and aggression in female BALB/c mice.

The goal of environmental enrichment for laboratory animals is to improve welfare, but some enrichment practices may affect research in unintended ways or even be harmful to the animals themselves. We previously found that mice raised at a commercial vendor then given multiple enrichment devices upon arrival at our facilities experienced thymic atrophy and greater variation in measured parameters than did their unenriched counterparts, suggesting that enrichment conditions affected corticosteroid expression in mice. The current study verified and expanded these results, examining 120 female BALB/c mice raised with or without nesting material at a commercial vendor (n = 60 per group) and allocated (n = 20 per group) to receive no enrichment, nesting material, or 'superenrichment' on arrival at our facilities.

Effect of fenbendazole on three behavioral tests in male C57BL/6N mice.

Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice.

Environmental enrichment for laboratory rodents.

Modernization of housing and husbandry techniques for rodents has minimized confounding variables. The result has been vastly improved health maintenance and reproducibility of research findings, advances that have decreased the numbers of animals needed to attain statistically significant results. Even though not all aspects of rodent manipulation have been strictly defined, as housing and handling procedures have become increasingly standardized, many animal care personnel have recognized the lack of complexity of the rodents' environment.

A canine socialization and training program at the National Institutes of Health.

Well-socialized and obedient dogs are easier to handle and may make better research models. The authors describe the program they have implemented at the NIH, which has benefited both the animals and their caretakers.