Buprenorphine (Bup) is the most commonly used analgesic in mice, yet few objective assessments address its superiority for postsurgical recovery. In mice, IP implantation of a radiotelemetry device induces decreases in body weight (BW), food and water intake (FI, WI), core temperature (T_c), and activity levels that persist approximately 14 d in the absence of analgesia. To compare the efficacy of Bup with that of the nonsteroidal antiinflammatory drug indomethacin (Indo) for postsurgical recovery, male C57BL/6J mice were treated on the day of radiotelemetry implantation with Bup (0.3 mg/kg SC) or Indo (1 mg/kg SC) followed by treatment with Indo (1 mg/kg PO) on the next day (Bup–Indo versus Indo–Indo). Responses were compared between treatments in mice implanted with a radiotelemetry device and those that did not undergo surgery. Changes in BW, FI, WI, T_c, and activity were examined throughout 14 d of recovery. Indo–Indo was more efficacious in inhibiting postsurgical BW, FI, and WI reductions, compared with Bup–Indo. Bup also reduced BW and FI in the absence of surgery, indicating a nonspecific effect of this drug on these variables. Indo–Indo treatment was associated with higher activity levels during lights-on–to–lights-off transition periods compared with that observed with Bup–Indo. According to 5 objective measures of surgical recovery, our data suggest that Indo–Indo treatment is more efficacious than is Bup–Indo for postsurgical recovery of radiotelemetry-implanted mice.

The use of analgesics to prevent or treat postprocedural pain in rodents is increasingly encouraged by the laboratory animal community and federal funding agencies. However, the effects of analgesics on experimental outcomes are not well-documented. In this study, we incorporated ketoprofen into a well-established experimental protocol. Of the 44 Sprague–Dawley (SD) rats obtained from vendor A that were given either ketoprofen (10 mg/kg SC) or saline and underwent ovariectomy, 19 that received ketoprofen died or were euthanized due to clinical illness within 3 to 7 d after surgery. Necropsy revealed gastrointestinal ulceration consistent with toxicity from nonsteroidal antiinflammatory drug. In an attempt to identify factors responsible for this unanticipated outcome, SD rats from vendors A and B were subjected to the same protocol, but no clinical signs or pathologic lesions were observed in any of these rats, regardless of source. A third experiment with rats obtained from vendor A and housed in barriers 1 and 2 was done to clarify the conflicting results and to determine whether response to ketoprofen differed at the barrier level. Three of the 6 rats from barrier 2 that received ketoprofen in the third study had gastrointestinal lesions similar to those observed in the first study, whereas none of the rats from barrier 1 had any lesions. These results suggest that the adverse effects seen after administration of ketoprofen were due to differences between barriers.

Housing laboratory animals under lighting conditions that more closely mimic the natural environment may improve their wellbeing. This study examined the effects of dim light or a long-night photocycle on resting heart rate (HR) of rats and their HR responses to acute procedures. Male and female Sprague–Dawley (SD) and spontaneously hypertensive (SHR) rats, instrumented with radiotelemetry transmitters and housed individually under a 12:12-h light:dark photocycle with 10 lx illumination (dim light) or under an 8:16-h light:dark photocycle with 200 lx illumination (long nights), were compared with control rats individually housed under a 12:12-h light:dark photocycle with 200 lx illumination. Dim light and long nights significantly reduced the HR of undisturbed SD and SHR male and SHR female rats during the day and at night; however, the HR of undisturbed SD females was not affected. When rats were subjected acutely to husbandry, experimental, or stressful procedures, dim light or long nights (or both) reduced HR responses to some procedures, did not alter responses to others, and increased responses to yet other procedures. The pattern of effects varied between strains and between male and female rats. Because basal HR was reduced when rats were housed under 10 lx illumination or an 8:16-h light:dark photocycle, we concluded that housing rats under 12:12-h light:dark, 200 lx ambient light conditions was potentially stressful, We also concluded that dim light or long nights did not uniformly reduce the increased HR responses induced by acute procedures.

Plasma biochemical and hematologic values are important parameters for assessing animal health and experimental results. Although normal reference values for many rodent species have been published, there is a dearth of similar information for the genus Microtus. In addition, most studies use a mean and standard deviation to establish reference intervals, but doing so is not the recommendation of the Clinical and Laboratory Standards Institute (formerly the National Committee on Clinical Laboratory Standards) or the International Federation of Clinical Chemistry and Laboratory Medicine. The purpose of this study was to establish normal reference parameters for plasma biochemistry and hematology in mature pine voles (Microtus pinetorum) by using the nonparametric rank percentile method as recommended by the 2 laboratory medicine organizations mentioned. Samples of cardiac blood from a closed colony of pine voles were collected at euthanasia and evaluated under rodent settings on 2 automated hematology analyzers from 2 different manufacturers and on the same type of automated biochemistry analyzer. There were no sex-associated clinically significant differences between the sexes; younger animals had a lower hematocrit, higher mean corpuscular volume, and lower mean corpuscular hemoglobin concentration than did older animals. Only platelet counts differed when comparing hematologic values from different analyzers. Relative to rats and mice, pine voles have a lower mean corpuscular volume and higher red blood cell count, higher blood urea nitrogen, much higher alanine aminotransferase, and lower glucose and phosphorous concentrations. Hematology and plasma biochemical results obtained in this study are considered representative for healthy adult laboratory pine voles under similar environmental conditions.

The macrolide antibiotic clarithromycin (CLARI) has a wide spectrum of activity and efficacy for Mycoplasma species. In addition, CLARI accumulates during re-dosing of Mojave desert tortoises (Gopherus agassizii). Here, we characterized plasma concentrations after a single dose, after 3.5 months of dosing, and after per rectum administration; all doses were 15 mg/kg. After a single dose, the median maximal plasma concentration (Cmax) was 1.69 mg/ml and occurred at a median of 6 h after administration, the estimated elimination half-life was 6.9 h, and the median accumulation index was 10%. Plasma concentrations after long-term dosing showed consistent intraturtle concentrations of at least 2 μg/ml, with 1 turtle showing increasing accumulation of CLARI at all 3 time points and the remaining 5 turtles showing increases by 3.5 mo. Compared with expected Cmax values, the median long-term values were approximately 3 times higher than expected in 4 of 6 turtles and approximately 2/3 of that expected in the remaining 2 turtles. Per rectum dosing caused antibiotic retention below target values. Together, these results support accumulation of CLARI after repeated oral dosing and indicate that stable concentrations are reached long-term. Either cystoenteric recycling of CLARI or large intestinal absorption of bypass CLARI may explain the observed cumulative increases. In addition, twice-weekly CLARI maintains target concentrations over time, and per rectum dosing will require higher doses or increased dose frequency to be successful. Based on this work, pharmacokinetic studies in exotic species should include multidose studies to verify initial kinetic estimates from single-dose trends.

This study investigated the use of regulated cyclic breath-holds to improve microcomputed tomography (μCT) imaging of small (diameter, less than 1 mm) mouse lung tumors in vivo. Two novel techniques that use a modified small-animal ventilator were examined and compared with a previously used respiratory gating μCT technique and a free-breathing μCT technique. Two mice were scanned with each of these 4 μCT techniques (voxel size, 92 μm). The appearance of small lung tumors (maximal diameter, 0.5 to 1.0 mm) and the characteristics of line profiles of the lung–diaphragm boundary were used to compare the images obtained from the 4 acquisition techniques. The use of cyclic breath-holds, synchronized with the CT exposures, led to marked improvement in the visualization of the mouse lung structure and lesion conspicuity. A secondary experiment was performed to assess the stress placed on mice by the acquisition techniques.

The sudden onset of unilateral blepharospasm and hyphema, without evidence of corneal damage, initiated a thorough diagnostic work-up of an 11-wk-old purpose-bred intact male domestic shorthair kitten. Secondary acute anterior uveitis and hyphema were most likely due to trauma within the primary enclosure.

A 73-d-old white-tailed deer (Odocoileus virginianus) fawn was diagnosed at necropsy with a ventral abdominal cellulitis secondary to urine after preputial swelling, urethral obstruction and hemorrhage, and focal urethral rupture. During the acute antemortem disease phase, the urinary obstruction tentatively was attributed to potential urethral uroliths, but after euthanasia, extensive gross and microscopic examinations of the urogenital tract revealed no uroliths. This fawn had been copenned with another male fawn, both of which exhibited nonnutritive suckling of the penmate's genitalia before and after periodic milk replacer feedings. We attribute this uncommon presentation of urine-induced cellulitis to urethritis and urethral rupture secondary to repeated, nursing-induced, physical trauma to the prepuce. We examine the husbandry implications of this disease with regard to management of deer fawns in a laboratory setting.

Large ascarid larvae within granulomas were noted histologically in the mesenteric and pancreatic lymph nodes of 13 of 21 rhesus macaques (Macaca mulatta) euthanized as part of an experimental viral pathogenesis study. In addition, 7 of the 13 monkeys had cerebral granulomas, which in 4 animals contained nematode larvae similar to those within the lymph nodes. Despite the lesions, the animals did not show clinical signs associated with the parasitic infections. Characteristics of the larvae included, on cross-section, a midbody diameter of approximately 60 to 80 μm, a centrally located and slightly compressed intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. The morphology of the larvae was compatible with Baylisascaris spp. Baylisascariasis is a well-described infection of animals and humans that is caused by migrating larvae of the raccoon roundworm, Baylisascaris procyonis. A similar species, B. columnaris, is found in skunks and can cause cerebrospinal nematodiasis, but most reported cases of baylisascariasis have been due to B. procyonis. Our macaques were born free-ranging on an island in the southeastern United States where raccoons, but not skunks, were found to be common inhabitants, indicating that B. procyonis was the most likely parasite involved. These cases are similar to the low-level or covert cases of Baylisascaris infection described to occur in humans and provide further evidence of the existence of this parasite in the southeastern United States.

Dyscoria was noted in a female owl monkey and 2 of her offspring. The third offspring was found dead with necrohemorrhagic encephalitis. Two male monkeys paired with the female died, 1 of which showed oral ulcers at necropsy. Histologic examination of the oral ulcers revealed syncytia and eosinophilic intranuclear inclusion bodies in epithelial cells. Ocular examination revealed posterior synechia associated with the dyscoria in all 3 animals. Serum samples from the female and her offspring were positive for Herpesvirus simplex antibodies by ELISA. The clinical history, gross and microscopic lesions, and serology results suggests a herpesviral etiology, possibly H. simplex or H. saimiri 1. This report underscores the risks associated with introducing into breeding or research colonies animals that previously were kept as pets or those from unknown origin that could carry asymptomatic pathogenic Herpesvirus infections. In addition, herpesviral infection should be considered among the differential diagnoses if dyscoria is noted in nonhuman primates.