Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice
are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic
assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of
E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed
decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the
experimental use of mice until at least 6 wk after treatment should be considered.
Spontaneous tumors are reported to occur in 45% to 71% of Sprague-Dawley rats, yet few studies have considered the effect of the sedentary condition of standard laboratory cages on tumorigenesis. Tumor profiles and tumor promoting hormone prolactin were compared in female Sprague-Dawley
rats (108) that were allocated into 3 groups: those housed without outside activity (SED group), with twice-weekly 1-h sessions of physical activity in large box (PA group), and with regular voluntary running-wheel exercise (EX). Compared with the EX group, SED rats had more and larger tumors
throughout most of their lifespan; tumor profiles of PA rats were similar to those of the SED group. A larger percentage of animals in the SED group had tumors (54%), compared with EX rats (38%). At 64 wk, tumors in SED animals included thyroid carcinoma, malignancy, mammary fibroadenoma,
cystadenoma, and granuloma, whereas benign mammary gland cysts were most common in EX. Prolactin levels were highest in SED animals at 24 and 52 wk. In conclusion, increased tumor number, increased tumor size, type of spontaneous tumor, and increased prolactin in rats were associated with
standard laboratory housing, which limited physical activity, and were not primarily due to aging.
Mouse parvovirus (MPV) infection is difficult to address because it is asymptomatic, persists for as long as 9 wk, and occurs in small subpopulations of mice. The efficacy of a PCR-based cage swabbing strategy for MPV detection was tested. On postinoculation days (PID) 3 through 63,
feces were collected from MPV-infected SW mice or the wire bars and cage wall above and below the bedding were swabbed. MPV DNA was detected in all cages in all locations on PID 7 and 14 but only below the bedding on PID 21. Swabbing below the bedding detected MPV in most cages through PID
42. Sentinels exposed to soiled cages on PID 7 and 14 but not on PID 21 seroconverted. MPV was detected in feces from all cages until PID 33 and in at least 1 cage until PID 56. In BALB/c mice, MPV was detected in feces and on cage swabs on PID 5 to 14, and 80% of sentinels exposed to soiled
cages on PID 7 and 14 seroconverted. In comparison, MPV infection of C57BL/6 mice was detected in feces on PID 5 to 14 and on swabs on PID 5 and 7, and 30% of sentinels exposed to soiled cages on PID 7 and 14 seroconverted. Swabbing of multiple cages in rows in which only 1 cage contained
MPV-infected mice was ineffective. In conclusion, swabbing of individual cages can be used in a genotype-dependent manner as an adjunct to soiled bedding sentinels during the first 2 wk of infection.
Although considered the 'gold standard' for measuring blood pressure in laboratory animals, telemetry would benefit from refinement. In the present study, we tested the hypothesis that the small telemetric device used for blood pressure recording in mice would work for rats as well
and would serve as an alternative for those studies where abdominal cavity space is quite limited (such as in young animals and pregnant females). Here we report that the use of a smaller and lighter telemetric device implanted in the abdominal aorta of rats led to acquisition of stable and
high-quality blood pressure and heart rate data, similar to those obtained by using a larger telemetric device developed for rats. The use of smaller transmitters represents an alternative telemetry technique, especially for those cases in which space in the abdominal cavity is particularly
limited such as during pregnancy.
The present study examined changes in maternal blood parameters, particularly those related to blood coagulation, as well as alterations in blood coagulation-related gene expression in the liver during gestation in rats. Fibrinogen concentration and platelet count increased as pregnancy
progressed whereas prothrombin time and overall activity of vitamin-K–dependent coagulation factors decreased before delivery, suggesting a physiologic response to prevent prolonged bleeding at parturition. Conversely, compared with values for nonpregnant rats, activated partial thromboplastin
time was prolonged before delivery and antithrombin time was significantly higher during fetal organogenesis and thereafter, indicating a mechanism to prevent the development of deep tissue thrombosis in dams. DNA microarray analysis revealed no differences in coagulation-related gene expression
in the liver on gestation day 13 between pregnant and nonpregnant rats, whereas the gene expression of various fibrinogen-related factors, coagulation factors II and X, and the anticoagulation factor-related factor leuserpin 2 were increased on gestational day 19. In addition, changes similar
to those reported previously in pregnant rats were confirmed. The data obtained from the present study can be used as background data for effective evaluation of reproductive toxicology in rats, and they suggest that the rat is a useful animal model for investigating the mechanisms of disorders
in the blood coagulation system that can occur during late pregnancy in women.
One of the challenges facing veterinarians and investigators who use rabbits (Oryctolagus cuniculus) as a surgical model in biomedical research is choosing an appropriate and efficacious postoperative analgesic without systemic complications and side effects. The objective of
this study was to evaluate the gastrointestinal side effects associated with the postoperative use of buprenorphine in Dutch Belted rabbits. We also evaluated the analgesic meloxicam as an alternative to opioid administration during the postoperative period. Rabbits were assigned to 1 of 3
treatment groups during the postoperative period after routine ovariohysterectomy: buprenorphine (n = 10), meloxicam (n = 10), and incisional infiltration with bupivicaine (no treatment control; n = 10). Feed intake, fecal production, weight loss, urine output, and other physiologic parameters
were monitored and behavior and pain assessments were performed for 7 d after surgery and compared with baseline values collected before surgery. All rabbits showed decreased pellet consumption, fecal production, and weight on day 1 after surgery. This effect was severe in some rabbits that
received bupivicaine; therefore treatment of this entire group with metoclopramide, fluids, and hay was instituted to reverse gut stasis. No significant difference in feed consumption and fecal production was present between the buprenorphine- and meloxicam-treated groups. On the basis of
these results, meloxicam appears to be a suitable alternative or adjunct to buprenorphine for alleviating postoperative pain with minimal risk of anorexia and gastrointestinal ileus.
Previous studies have suggested that images of conspecifics are useful for environmental enrichment for nonhuman primates, but whether the age and sex of the animals alter the effectiveness of such images is unclear. We investigated preferences to movies in Japanese macaques (Macaca
fuscata; male and female; age, 2 to 19 y). Each monkey was housed individually in a cage outfitted with a touch-sensitive computer display. A subject monkey that touched the display was shown 1 of 30 movies that were recorded at an open enclosure containing their conspecifics. During the
experimental sessions, 25 of 38 subjects touched the display at least once. The response duration was longer when monkeys appeared in the movies. The response duration decreased with age in male monkeys but not female monkeys. The results suggested the movies of conspecifics are useful for
environmental enrichment, but further consideration seems appropriate for various subpopulations, particularly aged monkeys.
Many laboratory studies require oral administration of drugs. Dietary administration in food or water is useful, but is not always the best method. Orogastric gavage can be stressful. Here, we describe in detail a relatively stress-free technique that can be applied to multiple daily
administrations using a palatable food item. This method was successfully used to administer water or methylphenidate 3 times daily to young pair-housed adolescent rats.
Male and female mice were anesthetized by intraperitoneal injection with a mixture delivering 0.5 mg/kg medetomidine and 50 mg/kg ketamine to achieve immobilization for whole-body radiographs and bone densitometry, as part of a phenotypic screen for bone and mineral disorders in mice
carrying genetic modifications induced through mutagenesis with N′-ethyl-N′-nitrosourea. Morbidity and mortality occurred in 19 of 628 (3%) of male mice 24 to 72 h after a seemingly uneventful recovery from anesthesia. No morbidity or mortality occurred in 1564 female
mice that were similar in age to the affected male mice and that underwent the same procedure. Of the 7 male mice that underwent postmortem examinations, 5 had urinary bladders grossly distended with urine and 1 had ascites. In addition, the pelvic or penile urethra in 5 of the examined male
mice was obstructed with seminal coagulum associated with varying degrees of erosion of the urothelial lining and inflammation of the urethra. In 2 of these animals, from which plasma samples were recovered, azotemia, hyperphosphatemia, and hyperkalemia were present. The predilection for delayed
morbidity and mortality in males after anesthesia suggests that anesthesia with 0.5 mg/kg medetomidine and 50 mg/kg ketamine is a potential risk factor for obstructive uropathy due to release of seminal coagulum. This adverse effect did not recur when we altered our anesthesia protocol to
10 mg/kg xylazine and 100 mg/kg ketamine.
The 'water-wheel' or 'mill-wheel' murmur is classically associated with large intracardiac air emboli and described as a "characteristic splashing auscultatory sound due to the presence of gas in the cardiac chambers." We used 64-slice computed tomography (slice thickness, 0.5 mm; revolution
time, 400 msec) and 3D fly-through software imagery to capture previously unreported intracardiac air–blood interface dynamics associated with this murmur and ineffective right ventricular contraction in a porcine model.
In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia
in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naïve, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ
infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney,
adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous
triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate.
An adult, male, rhesus macaque presented with pruritus and a focal, exudative, inflamed, erythematous skin lesion of approximately 2 cm in diameter on the ventral aspect of the mandible. The lesion resolved after 10 d of treatment with 1% chlorhexidine solution and triple-antibiotic
ointment. However, the skin lesion subsequently recurred several times over a 2-mo period. A punch biopsy was performed, and histological changes were most consistent with a diagnosis of atopic dermatitis. Treatment with topical tacrolimus ointment, an immunosuppressive drug, proved successful
in the resolution of all clinical signs after 4 mo. According to a literature review, this article is the first report of the use of tacrolimus ointment as a topical treatment of atopic dermatitis in a rhesus macaque.