Business models for transnational organizations include linking different geographies through common codes of conduct, policies, and virtual teams. Global companies with laboratory animal science activities (whether outsourced or performed inhouse) often see the need for these business activities in relation to animal-based research and benefit from them. Global biomedical research organizations can learn how to better foster worldwide cooperation and teamwork by understanding and working with sociocultural differences in ethics and by knowing how to facilitate appropriate virtual team actions. Associated practices include implementing codes and policies transcend cultural, ethnic, or other boundaries and equipping virtual teams with the needed technology, support, and rewards to ensure timely and productive work that ultimately promotes good science and patient safety in drug development.

The black-tailed prairie dog (Cynomys ludovicianus) is a member of the order Rodentia and the family Sciuridae. Ecologically, prairie dogs are a keystone species in prairie ecology. This species is used as an animal model for human gallbladder disease and diseases caused by infection with Clostridium difficile, Yersinia pestis, Francisella tularensis, and most recently, Orthopoxvirus. Despite increasing numbers of prairie dogs used in research and kept as pets, few data are available on their baseline physiology in animal facility housing conditions. To establish baseline physiologic reference ranges, we designed a study using 18 wild-caught black-tailed prairie dogs. Telemetry data were analyzed to establish circadian rhythms for activity and temperature. In addition, hematologic and serum chemistry analyses were performed. Baseline measurements were used to establish the mean for each animal, which then were compiled and analyzed to determine the reference ranges. Here we present physiologic data on serum chemistry and hematology profiles, as well as weight, core body temperature, and daily activity patterns for black-tailed prairie dogs. These results reflect the use of multiple measurements from species- and age-matched prairie dogs and likely will be useful to ecologists, scientists interested in using this animal model in research, and veterinarians caring for pet prairie dogs.

The goal of this study was to identify objective criteria that would reliably predict imminent death in aged mice. Male and female ICR mice (age, 8 mo) were subcutaneously implanted with an identification chip for remote measurement of body temperature. Mice then were weighed and monitored regularly until spontaneous death occurred or until euthanasia was administered for humane reasons. Clinical signs that signaled implementation of euthanasia included inability to walk, lack of response to manipulation, large or ulcerated tumors, seizures, and palpable hypothermia. In mice that died spontaneously, gradual weight loss was the most frequent and earliest sign of imminent death. Hypothermia developed during the 2 wk prior to death. Slow or labored breathing were observed in about half of the mice before death. A composite score of temperature × weight can be used to provide an objective benchmark to signal increased observation or euthanasia of individual mice. Such assessment may allow the collection of terminal tissue samples without markedly altering longevity data, although application of this criterion may not be appropriate for all studies of longevity. Timely euthanasia of mice based on validated markers of imminent death can allow implementation of endpoints that alleviate terminal distress in aged mice, may not significantly affect longevity data, and can permit timely collection of biologic samples.

Seasonal changes in menstrual cycle patterns and internal reproductive organs were studied in female rhesus macaques (n = 16) in indoor–outdoor housing in Chongqing, China. Uterine size and shape and endometrial thickening were evaluated during the early-secretory phase by using ultrasonography and MRI. From October to February, the macaques' menstrual cycles were short and regular, and the endometrial lining were easily visible by ultrasonography and MRI. However, from March through to September, menstrual cycles became irregular, endometrial lining were unclear, and the endometrium did not change markedly during the early-secretory phase. We conclude that the reproductive season for a female rhesus macaque in Chongqing, China is from October through February, whereas the nonreproductive season is from March through September. The menstrual cycle patterns and reproductive organs of the macaques showed marked seasonal variation throughout the 12-mo observation period. In addition, uterine size, volume, and imaging characteristics varied dramatically between reproductive and nonreproductive seasons.

A commercial 4-drug diet has shown promise in eradicating Helicobacter spp. from rodents; however, its effectiveness in immunocompromised mice is unknown. This study evaluated the efficacy of this treatment in eradicating Helicobacter spp. from mice deficient in functional natural killer cells (Cd1^−/−) or complement factor D (Df^−/−). Cd1^−/− mice naturally infected with H. hepaticus with or without H. rodentium were fed either control or medicated diet for 8 wk followed by 4 wk on control diet. Fecal samples were PCR-evaluated for Helicobacter spp. before mice began treatment and then every 2 wk thereafter for 12 wk. The same experimental design was repeated for eighteen 9- to 21-wk-old Df^–/– mice naturally infected with H. bilis with or without H. rodentium. All Df^–/– mice and 8- to 21-wk-old Cd1^−/− mice ceased shedding Helicobacter spp. after 2 wk of treatment and remained negative throughout the study. In contrast, the Cd1^−/− mice that were 24 wk or older shed Helicobacter spp. for the first 8 wk but tested negative at 10 and 12 wk. All treated animals had enlarged ceca and gained less weight than control untreated mice, and 6 of 7 treated Cd1^−/− male mice developed mild portal fibrosis. These findings show that within 2 wk of treatment, the 4-drug diet eradicated H. hepaticus and H. rodentium from young Cd1^−/− mice and H. bilis and H. rodentium from Df^−/− mice, but eradication of established infections in Cd1^−/− mice required 8 wk of treatment.

Audiogenic stress is a well-documented phenomenon in laboratory rodents. Despite the recommendation in the Guide for the Care and Use of Laboratory Animals to consider noise a concern in the animal facility, only a small body of literature empirically addresses the effects of facility noise on laboratory rodents, particularly mice. The objective of this study was to determine whether facility noise generated by a vacuum cleaner induces an acute stress response in a commonly used strain of laboratory mouse under common housing conditions. In each of 2 experiments, 10 young adult, female C57BL/6Cr mice were exposed for 1 h to noise produced by a vacuum cleaner, and 10 control mice were not. In the first experiment, fecal samples were collected to measure concentrations of fecal corticosterone metabolites just before and 2, 4, 6, 8, 10, 14, 24, and 32 h after noise exposure. In the second experiment, stress-sensitive behavioral tests were performed 2 d before, immediately after, and 24 h after noise exposure. Physiologic and behavioral measurements indicated that vacuum cleaner noise did not cause an acute stress response in the noise-exposed mice but may have affected the diurnal variation of their corticosterone levels. These findings could contribute to the development of best practices in noise-control protocols for animal facilities.

The development of new rodent models of human disease and advances in surgical equipment and technologies have increased the demand for expertise in rodent surgery. Because of the limited availability of rodent surgical training courses, electronic (e-) learning is presented as an alternative to in-person education and as a means to hone the expertise of current surgeons in biomedical research, similar to e-learning applications for human surgery training. Translating this model to the biomedical research field provides participants with an opportunity to train themselves on rodent surgical techniques prior to operating on live models. An e-learning rodent surgery course was incorporated into a training class of undergraduate (n = 39) and graduate (n = 12) laboratory animal students, and a portion of the course was presented to laboratory animal professionals (n = 15). The effectiveness of the method was evaluated using written examination and postcourse surveys. The exam data demonstrated that the e-learning course transferred knowledge comparable to a lecture course on surgery that was presented in-person. Students responded favorably to videos, step-by-step photographs of surgical procedures, and the ready accessibility of the course. Critiques included the need to improve video resolution and quality of the voice-overs. These results support the continued development and implementation of electronic rodent surgical technique courses for use in laboratory animal and biomedical research communities.

Mice used in biomedical research typically are tested for the presence of Helicobacter spp., including Helicobacter hepaticus. Here we evaluated the ability of a commercially available colorimetric Helicobacter dipstick assay to detect H. hepaticus in experimentally and naturally infected mice, with use of a Helicobacter PCR assay as the 'gold standard' test. None of the fecal samples from experimentally infected A/JCr mice (n = 12) tested positive for Helicobacter by the colorimetric dipstick test. In naturally infected A/JCr and C57BL/6 mice, 11% (1 of 9) and 30% (3 of 10) of fecal samples, respectively, tested positive for Helicobacter by the colorimetric dipstick assay. In these 3 groups of H. hepaticus-infected mice, statistically fewer mice tested positive by the colorimetric dipstick test than by PCR. The colorimetric Helicobacter dipstick assay had an overall diagnostic sensitivity of 13%, diagnostic specificity of 94%, and analytical sensitivity of 10⁸ H. hepaticus cfu/mL. As currently formulated, the colorimetric dipstick assay had high specificity but lacked sensitivity for detecting H. hepaticus infections in 2 strains of mice commonly used in research, thereby limiting its utility as a diagnostic screening test for H. hepaticus infections in research mice.

We and others frequently have noted serum potassium levels of 8.0 ± 0.85 mEq/L or greater in laboratory mice; this concentration has even been published as the upper limit of a 'normal' reference range. However, if bone fide, this potassium concentration would be incompatible with life in all species. We investigated conditions frequently encountered in the research setting to distinguish artifactual from true hyperkalemia. Variables evaluated included site of collection, time allowed for clot formation before serum separation, time elapsed between collection and analysis of samples collected in a serum separator tube, precollection method of anesthesia, and euthanasia technique. Serum potassium was measured from 75 C57BL/6NTac 10-wk-old female mice and divided into at least 5 mice per variable. Animals were euthanized by exsanguination immediately after terminal CO₂ or ketamine–xylazine (KX) administration. Mice euthanized with CO₂ had higher mean serum potassium (7.0 ± 0.5 mEq/L) and range serum potassium (6.0 to 8.1 mEq/L) than did KX-treated mice. CO₂ inhalation resulted in significantly lower blood pH (6.9 ± 0.1), higher pCO₂ (153.3 ± 38.8 mm Hg), and higher lactate levels (3.9 ± 0.9 mmol/L) than did KX anesthesia followed by exsanguination. These results suggest that antemortem respiratory acidosis from CO₂ administration causes artifactual hyperkalemia in mice. Therefore, blood collection under KX anesthesia is preferable over CO₂ inhalation to obtain accurate potassium values from mice.

Concern regarding the potential for radiation exposure from accidents or nuclear and radiologic terrorism is increasing. The purpose of this study was to determine whether the addition of minimal supportive care consisting of hydration or nutritional gels could be used to reduce mortality in mice exposed to ⁶⁰Co γ-radiation. Male CD2F1 mice received 0, 8.50, or 9.25 Gy ⁶⁰Co at a dose rate of 0.6 Gy/min. These groups were further divided into 3 treatment groups that—in addition to pelleted food and water—received no supportive care, hydration gel, or nutritional gel. Overall survival, mean survival time, consumption of pelleted food and gel, and body weight were recorded for 30 d. Radiation caused dose-dependent decreases in overall survival, consumption of pelleted food and supplemental gel, and body weight. However, at each radiation dose (0, 8.50, 9.25 Gy), the type of supportive care did not modify overall survival, mean survival time, or changes in body weight. These results demonstrate that hydration and nutritional gels were not effective methods of supportive care after high-dose total body irradiation in mice.

Oral gavage is a common route of precise oral dosing for studies in rodents. Complications including tracheal administration, esophageal trauma, and aspiration are common and usually related to animal resistance to the procedure, and the stress induced by oral gavage can be a confounding variable in many studies. The taste of sucrose conveys a pacifying and analgesic effect in newborns, whereas sour solutions can induce the swallow reflex in humans that are dysphagic. We hypothesized that precoating a gavage needle with sucrose or citrate (or both) would pacify mice and induce them to swallow, reducing the stress and complications associated with the technique. To validate this hypothesis, we quantitated time to passage, stress-related behavioral reactions to the procedure, and plasma corticosterone levels in mice after precoating gavage needles with water, sucrose, citrate, sucrose and citrate, or sodium chloride prior to oral gavage. Precoating needles with sucrose reduced the time to passage, decreased observable stress-related reactions to the procedure, and maintained plasma corticosterone levels similar to those in ungavaged control mice. Coating needles with water, sucrose and citrate, or citrate had no beneficial effects on these parameters. Our findings describe a novel, validated technique that measurably decreases signs of stress and thereby improves animal welfare during oral gavage. Furthermore, the use of sucrose may be a valuable tool to refine other minor or nonsurgical procedures in the field of laboratory animal research.

Oral administration of drugs to laboratory rodents typically is achieved by using the gavage technique. Although highly effective, this method occasionally can cause esophageal injury as well as restraint-associated distress, particularly with repeated use. The aim of this study was to assess an alternative oral dosing method that could reduce the distress and morbidity associated with standard gavage techniques. The palatability and pharmacokinetic profile of 2 medicines approved for the treatment of Alzheimer disease, donepezil and galantamine, were investigated in male Lister hooded rats by using a syringe-feeding method and compared with results from traditional gavage administration. In addition, the stimulant nicotine was tested by using the syringe-feeding method in a separate series of experiments. Animals reliably learned to drink voluntarily from the syringe, and latency to drink decreased rapidly. The addition of donepezil, galantamine, or nicotine to sucrose had no apparent effect on the palatability of the solution, although nicotine produced aversive effects that inhibited subsequent voluntary intake. Oral bioavailability was improved by using syringe feeding with donepezil but not galantamine. Both drugs improved cognitive performance in the novel object recognition test, with similar behavioral profiles between the 2 methods of administration. Our results suggest that the syringe-feeding technique is an effective alternative oral dosing method in rats.

The goal of this study was to identify an injectable anesthetic protocol that provides sedation sufficient for peripheral vascular catheterization, intubation, and transport while minimizing cardiovascular changes in Yorkshire and Yucatan pigs with and without cardiovascular injury and intervention (CI). Phase 1 examined the safety and efficacy of acepromazine–ketamine, diazepam–ketamine, midazolam–ketamine, and medetomidine–ketamine in 5 healthy Yorkshire pigs. For each drug combination, we obtained multiple measurements of heart rate, blood pressure, respiratory rate, temperature, sedation score, ability to catheterize and intubate, and recovery score. Phase 2 evaluated and refined the dose of the most effective Phase 1 anesthetic combination (midazolam–ketamine) in healthy and CI Yorkshire pigs (n = 53 trials). Phase 3 mirrored Phase 2 but tested midazolam–ketamine in healthy and CI Yucatan pigs (n = 34 trials). Midazolam (0.5 mg/kg)–ketamine (25 to 27 mg/kg) was the most effective anesthetic combination in healthy Yorkshire pigs, but this dose was less effective in healthy Yucatan pigs and CI Yorkshire and Yucatan pigs. Midazolam–ketamine resulted in tachycardia and apnea more frequently in CI pigs than healthy pigs. This combination also caused vomiting in one CI Yucatan pig. Overall, midazolam–ketamine provided safe and effective sedation for catheterization and intubation of both healthy and CI pigs. This study suggests Yucatan pigs may require a higher dose midazolam–ketamine to achieve the same level of sedation as that in Yorkshire pigs. Although anesthetic complication rates were higher in CI pigs, our results indicate that midazolam–ketamine can be safely used for sedation of both pig breeds with and without CI.

Electrocardiograms (ECGs) often are collected from sedated cynomolgus macaques (Macaca fascicularis) in drug safety studies to support investigational new drug applications. ECGs are evaluated either manually or electronically, and the quality of the ECG tracing can affect the quality of that evaluation. The body position of the subject sometimes is manipulated to eliminate noise or clarify ECG complex morphology, and typically multiple technicians collect ECG data over time. Both factors—body position and multiple technicians—could affect ECG quality. This study was designed to determine whether body position or multiple technicians affects heart rate, mean electrical axis, or ECG parameters (RR interval, P wave duration, PR interval, QRS duration, QT interval (uncorrected and rate-corrected by using the Bazett [QTcb] and Fridericia [QTcf] formulas), P wave amplitude, R wave amplitude, T wave height, T wave height negative, and ST segment elevation). The results reveal minimal (coefficient of variation [CV] less than 10%) within-animal variation between body positions (ventral, dorsal, right or left lateral), with the exception of P wave amplitude (17.5%), R wave amplitude (23.7%), and ST segment elevation (43%). Minimal variation in ECG parameters (no more than 7%) was detected between technicians, across animals, and across body positions. These findings suggest that neither a change in body position to increase the quality of an ECG tracing nor the use of multiple technicians significantly affect the evaluation of quantitative ECG parameters, especially QTcb (0.1% CV) and QTcf (1.3% CV).

Cleft lip (with or without cleft palate) has been documented in several species of nonhuman primates, which in general are susceptible at similar doses and stages of gestation to the same teratogens as humans. Cleft lip can be unilateral or bilateral, isolated, syndromic, familial, or genetic. Here we report the first case of syndromic cleft lip and palate in a male bare-eared squirrel monkey (Saimiri ustus). Associated with the orofacial clefts, the monkey manifested absence of bones, malformation of vertebrae L3, only 4 fingers in each hand, and shortening of tendons leading to inflection of the hands and fingers. Previous reports describing cleft lip and palate in other squirrel monkeys (Saimiri sciureus) in other breeding units have suggested consanguineous mating as a possible cause. Although the etiology in the case we present is unknown, we discuss factors associated with orofacial clefts in humans and various nonhuman primates.