Many physiological and molecular processes are strongly rhythmic and profoundly influenced by sleep. The continuing effort of biological, medical, and veterinary science to understand the temporal organization of cellular, physiological, be- havioral and cognitive function holds great promise for the improvement of the welfare of animals and human beings. As a result, attending veterinarians and IACUC are often charged with the responsibility of evaluating experiments on such rhythms or the effects of sleep (or its deprivation) in vertebrate animals. To produce interpretable data, animals used in such research must often be maintained in carefully controlled (often constant) conditions with minimal disruption. The lighting environment must be strictly controlled, frequent changes of cages and bedding are undesirable, and daily visual checks are often not possible. Thus deviations from the standard housing procedures specified in the Guide for the Care and Use of Laboratory Animals are often necessary. This report reviews requirements for experiments on biological rhythms and sleep and discusses how scientific considerations can be reconciled with the recommendations of the Guide.

The purpose of this study was to determine the 12-h fasting preprandial and 2-h postprandial serum bile acid concentration (SBAC) reference intervals for healthy, adult rhesus macaques (Macaca mulatta). We hypothesized that the mean 2-h postprandial SBAC would be significantly higher than the mean preprandial SBAC. We included 40 (24 male, 16 female) macaques after confirming that their health records, physical examinations, CBC, serum chemistry panels, and urinalyses were all within normal limits. In addition, hepatitis A titers were determined, an ultrasound examination of the liver was performed, and two 16-gauge ultrasound guided percutaneous liver biopsies were collected and submitted for histopathology. Macaques were confirmed healthy according to hepatitis A screens and sonographic and histologic evaluation of hepatic tissue. Within 2 wk of the screening procedures, preprandial and postprandial SBACs were measured. Preprandial SBAC (mean ± 1 SD) was 11.1 ± 1.9 μmol/L and postprandial SBAC was 19.7 ± 8.0 μmol/L, which was significantly higher than the preprandial value. Sex and hepatitis titers did not significantly influence preprandial and postprandial SBAC. The current study indicates that the SBAC reference values for rhesus macaques are higher than those reported for humans and companion animals.

Our goal was to assess a nonhuman primate diet that mimicked the Western-type diet of humans with regard to palatability and the diet's effects on plasma lipid concentrations and other cardiometabolic risk factors. We evaluated male (n = 8) and female (n = 11) African green monkeys (vervets; Chlorocebus aethiops sabaeus) that initially were fed a standard diet. Each cohort then was divided into 2 groups, which received either standard chow or the Western diet. Food consumption and fecal quality were measured weekly. Body weight, waist circumference, and body–mass index were measured every 2 wk. CBC and clinical chemistry analyses were performed at baseline and 4 wk after the diet change. Plasma lipid concentrations, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, insulin, and fructosamine were measured at baseline and at 4, 8, and 12 wk after the diet change. Isoflavones were measured in the male monkeys at 6 wk after diet change, and lipid particle size was measured in the female monkeys at the 12-wk point. Green monkeys readily ate the Western diet and maintained baseline body weight and morphometric measures, with no adverse effects on fecal quality or clinical measures. Total plasma cholesterol was higher in monkeys fed the Western diet compared with standard chow. Isoflavones were higher in male monkeys fed standard chow compared with the Western diet, but lipid particle size did not differ by diet in female monkeys. Our data indicate that the Western diet led to changes in various biomedical risk factors of green monkeys to become similar to those of humans in the United States.

Alopecia is a common problem in rhesus macaque colonies. A possible cause of this condition is hair-pulling; however the true relationship between hair-pulling and alopecia is unknown. The purpose of this study was to examine the relationship between hair loss and hair-pulling in 1258 rhesus macaques housed in 4 primate colonies across the United States. Alopecia levels ranged from 34.3% to 86.5% (mean, 49.3%) at the primate facilities. At facilities reporting a sex-associated difference, more female macaques were reported to exhibit alopecia than were males. In contrast, more males were reported to hair-pull. Animals reported to hair-pull were significantly more likely to have some amount of alopecia, but rates of hair-pulling were substantially lower than rates of alopecia, ranging from 0.6% to 20.5% (mean, 7.7%) of the populations. These results further demonstrate that hair-pulling plays only a small role in alopecia in rhesus macaques.

Corynebacterium bovis has been associated with hyperkeratotic dermatitis and acanthosis in mice. We studied 3 different strains of C. bovis: one previously described to cause hyperkeratotic dermatitis (HAC), one that infected athymic nude mice without leading to the classic clinical signs, and one of bovine origin (ATCC 7715). The 3 strains showed a few biochemical and genetic differences. Immunodeficient nude mice were housed in 3 independent isolators and inoculated with pure cultures of the 3 strains. We studied the transmission of these C. bovis studies to isolator-bedding and contact sentinels housed for 5 to 12 wk in filter-top or wire-top cages in the respective isolators. Using a 16S rRNA-based qPCR assay, we did not find consistent differences in growth and transmission among the 3 C. bovis strains, and neither the incidence nor severity of hyperkeratosis or acanthosis differed between strains. Housing in filter-top compared with wire-top cages did not alter the morbidity associated with any of the strains. Our findings confirmed the variability in the gross and histologic changes associated with C. bovis infection of mice. Although bacteriology was a sensitive method for the detection of Corynebacterium spp., standard algorithms occasionally misidentified C. bovis and several related species. Our study demonstrates that PCR of skin swabs or feces is a sensitive and specific method for the detection of C. bovis infection in mice. An rpoB-based screen of samples from North American vivaria revealed that HAC is the predominant C. bovis strain in laboratory mice.

C57BL/6 (B6) mice briefly shed low levels of MPV, and transmission is inefficient. To determine whether deficits in B or T cells or in interferon γ on a B6 background increased the duration of MPV shedding or transmission, B-cell–deficient (Igh), interferon-γ–deficient (Ifnγ), B- and T-cell–deficient (Rag), and B6 mice were inoculated with MPV. At 1 and 2 wk postin- oculation (wpi), 11% to 94% of mice shed MPV. From 4 to 18 wpi, 80% to 100% of Rag mice and 0% of B6 and Ifnγ mice shed MPV; Igh mice sporadically shed MPV through 20 wpi. MPV was transmitted from B6 mice and Ifnγ mice at 2 to 4 wpi. Rag and Igh mice transmitted MPV to sentinels at all or most time points, respectively, between 2 to 16 wpi. Once transmission ceased from B6, Ifnγ, and Igh mice, breeding trios were setup and showed that MPV was transmitted to offspring in only one cage of Igh mice. In another experiment, MPV shedding ceased from B6, CD8-deficient (CD8), CD4-deficient (CD4), and T-cell–receptor-deficient (TCR) mice by 2, 6, 8, and 8 wpi, respectively. MPV was transmitted to sentinels only at 1 to 4 wpi. Mesenteric lymph nodes collected from 61% to 100% of B6, Ifnγ, TCR, CD4, CD8, and Rag mice were MPV DNA-positive. In conclusion, MPV transmission did not differ between mice deficient in T cell functions or Ifnγ and B6 mice. In contrast, B-cell deficiency posed an increased risk for MPV transmission in mice.

Acupuncture is an ancient practice that is currently used to treat disorders ranging from osteoarthritis to cardiomyopathy. Acupuncture involves the insertion of thin, sterile needles into defined acupuncture points that stimulate physiologic processes through neural signaling. Numerous scientific studies have proven the benefits of acupuncture, and given this scientific support, we hypothesized that acupuncture could benefit the nonhuman primates at our facility. As our chimpanzee colony ages, we are observing an increase in osteoarthritis and have focused our initial acupuncture treatments on this condition. We successfully trained 3 chimpanzees, by using positive-reinforcement training techniques, to voluntarily participate in acupuncture treatments for stifle osteoarthritis. We used 3 acupuncture points that correlate with alleviation of stifle pain and inflammation in humans. A mobility scoring system was used to assess improvements in mobility as a function of the acupuncture treatments. The 2 chimpanzees with the most severe osteoarthritis showed significant improvement in mobility after acupuncture treatments. Acupuncture therapy not only resulted in improved mobility, but the training sessions also served as enrichment for the animals, as demonstrated by their voluntary participation in the training and treatment sessions. Acupuncture is an innovative treatment technique that our data show to be safe, inexpensive, and, most importantly, effective for chimpanzees.

We compared ketamine–xylazine (K, 100 mg/kg; X, 10 mg/kg) and ketamine–dexmedetomidine (K, 75 mg/kg; D, 1.0 mg/kg) for their ability to produce anesthesia, their tissue tolerance, and the reversibility of their effects by atipamezole (1.0 mg/kg) after intraperitoneal administration to Wistar Han rats. Both anesthetic combinations led to a comparable level of anesthesia over a 30-min period. However, the administration of KD led to a 20% decrease in heart rate, 33% decrease in respiratory rate, and a 20% decrease in peripheral oxygen saturation from baseline levels. Intraperitoneal administration of saline and both anesthetic combinations was associated with mild transient increases in serum ALT and AST concentrations in the absence of histomorphologic findings in liver. Muscle and tissue necrosis at the intraperitoneal injection sites correlated with increases in serum creatine kinase concentrations in rats given KD or KX; these increases were more severe in the KX group than the KD group. Compared with KX, intraperitoneal administration of KD offered better local tolerance and anesthesia of similar quality and depth.

To determine the effects of intravenous and intramuscular xylazine–ketamine on intraocular pressure (IOP) in laboratory rabbits, 10 New Zealand white rabbits received xylazine (0.46 mg/kg) and ketamine (1.5 mg/kg) intravenously whereas another 10 rabbits received intramuscular xylazine (10 mg/kg) and ketamine (50 mg/kg). IOP was measured at baseline and 5, 10, 20, and 25 min after administration in rabbits that were injected intravenously and at baseline and 10, 20, 30, and 45 min in rabbits injected intramuscularly. Baseline IOP (mean ±1 SD; intravenous group, 20.15 ± 2.24 mm Hg; intramuscular group, 19.03 ± 1.77 mm Hg) did not differ between groups. Compared with baseline values, IOP decreased significantly after intravenous administration at 10, 20, and 25 min (decreases of 2.73, 4.10, and 4.55 mm Hg, respectively) but not at 5 min (decrease of 1.40 mm Hg). IOP in intramuscularly dosed rabbits showed significant differences from baseline at 10, 20, 30, and 45 min (decreases of 2.88, 3.30, 3.95, and 4.60 mm Hg, respectively). In the intravenous group, IOP differed at 10 min compared with 25 min (1.83 mm Hg, P = 0.0143) but not at 20 min compared with 25 min (0.450 mm Hg). In the intramuscular group, differences in IOP at 10 min compared with 20 min, 20 min compared with 30 min, and 30 min compared with 45 min were nonsignificant. Intravenous and intramuscular xylazine–ketamine decreased IOP in laboratory rabbits and may be used safely during ocular procedures for which increased IOP is a concern.

The electrocardiogram of nonhuman primates is similar to that of humans because of similar intrathoracic heart position and structure. Despite the frequent use of nonhuman primates in biologic studies, few electrocardiographic studies of Japanese monkeys (Macaca fusucata) have been reported, and no reference data are available for this species. We obtained limb-lead electrocardiograms from indoor-bred and housed ketamine-sedated Japanese macaques (48 male; 56 female; mean age, 44.3 mo; mean body weight, 4.84 kg) in the dorsal recumbency. The following quantitative data was obtained: heart rate, P wave amplitude and width, R wave amplitude, QRS duration, PR interval, QT interval, T wave height, and mean electrical axis. Corrected QT intervals were calculated by using the Bazett and Fridericia formulae. Measurements were evaluated according to sex and age. The duration of the QRS complex showed moderate correlation with age in male monkeys. All parameters, except heart rate, were similar to previous reports from Japanese, cynomolgus, and other macaques. P waves, R waves and mean electrical axis did not differ significantly between humans and Japanese macaques, but the wave amplitude in macaques was half that in humans. Our electrocardiographic measurements can serve as normal reference data for sedated, young Japanese monkeys.

After rederivation of a mouse parvovirus (MPV)-contaminated transgenic mouse strain, serology and PCR testing of the surrogate dam showed it to be infected with mouse parvovirus strain 1 (MPV-1). The rederived pups (n = 3) also were MPVpositive, according to serology. Despite MPV seropositivity, fecal PCR tests of the pups were negative, as were serologic results from direct-contact sentinels. Only one rederived pup survived, and this male was bred successfully. None of its mates or progeny seroconverted to MPV. At 14.5 mo of age, the rederived male mouse was euthanized; tissues were collected and submitted for MPV testing; both serologic tests and PCR analysis of mesenteric lymph nodes were MPV-negative. One explanation for the rederived pups' MPV seropostivity is passive transfer of maternal antibodies or a nonproductive MPV infection. This case illustrates that although routine serological testing of surrogate mothers and pups is appropriate, any positive results should be further investigated by using transmissibility testing (fecal PCR or contact sentinels or both) prior to repeat rederivation.