Idiopathic ulcerative dermatitis is a well-recognized disease in C57BL mice and related strains. This disease manifests as a pruritic dermatitis with resulting self-mutilation, dermal ulceration, necrosis, and fibrosis. Ulcerative dermatitis has the ability to confound ongoing research
by causing systemic pathologic changes, such as lymphadenopathy and splenomegaly. Although various treatments have been described, none has been curative consistently; therefore, minimizing negative effects on research through prevention of disease is ideal. To identify etiologic factors,
we conducted a 2-y retrospective study of 1352 mice with a C57BL/6 genetic background; these mice demonstrated an overall prevalence of 4.1% and a seasonal effect with a peak incidence during midsummer. Corroborating previous studies, our study revealed a disease predilection for female mice.
In contrast to prior reports, the disease prevalence was greatest in 10- to 16-mo-old mice. In addition, mice with a C57BL/6 background that were deficient in the gene for inducible nitric oxide synthase had a 50% disease incidence, suggesting a potential animal model for further characterizing
the pathogenesis, prevention, and treatment of ulcerative dermatitis.
Previous work in our laboratory showed that the recommended oral dose of buprenorphine (0.5 mg/kg) was not as effective as the standard therapeutic subcutaneous dose for postoperative analgesia in male Long-Evans (hooded) and Sprague-Dawley (albino) rats. The aim of the current study
was to extend this analysis to female rats. We measured the pain threshold in adult female rats in diestrus or proestrus before and 30 and 60 min after oral buprenorphine (0.5 mg/kg), the standard subcutaneous dose of buprenorphine (0.05 mg/kg), or vehicle only (1 ml/kg each orally and subcutaneously).
Female rats showed an increased pain threshold (analgesia) after subcutaneous buprenorphine but no change in pain threshold after either oral buprenorphine or vehicle only. Estrous cycle stage (proestrus versus diestrus) did not affect the analgesic effects of buprenorphine, but rats in proestrus
showed significantly lower pain thresholds (less tolerance to pain) than did those in diestrus. These results show that the oral dose of buprenorphine recommended for postoperative analgesic care does not induce significant analgesia in female rats and therefore is not as effective as the
standard subcutaneous dose.
We applied novel noninvasive fecal steroid measures to characterize aged rats' responses to a series of common animal room disturbances, including a direct comparison of male and female immunoreactive corticosterone metabolites in feces. The fecal measure provides a unique method to
measure the physiologic responses of laboratory animals to altered husbandry procedures. This assay is noninvasive and, because rodents produce fecal pellets throughout the day, long-term monitoring can be conducted to capture abnormal levels associated with alterations in husbandry procedures.
Over a 3-h period, 10 male and 10 female Fischer 344 rats (age, 82 wk) were exposed to a series of events that can occur in a colony housing room (keys jingling, cage lids opening, alteration of the light cycle). Fecal samples were collected at timed intervals on the day before and several
days after the exposure, extracted, and analyzed for fecal corticoid metabolites by use of a commercial enzyme immunoassay. Fecal metabolites in these aged rats were elevated 3- to 5-fold above baseline levels approximately 20 h after exposure to the experimental events. Overall, we detected
more immunoreactive fecal corticoid metabolites in feces from male rats than female rats, even though female rats normally secrete greater amounts of glucocorticoids into circulation. Our results indicate that this assay can be used to identify marked elevations in corticoid metabolite levels
after alterations in laboratory husbandry procedures. We discuss the implications of these findings for animal researchers and those involved in animal husbandry.
Surgical harvest of Xenopus laevis oocytes for developmental research is a common procedure that requires closure of a 0.5- to 2.0-cm incision with suture material. Although such harvests are a frequent practice, little published information exists to provide guidance regarding
the most appropriate suture material for wound closure in laboratory amphibians. To determine which suture material elicits the least response in amphibian skin, we used Xenopus laevis as a model to investigate the gross and histologic tissue reactions to 5 commonly used suture materials—3-0
silk, monofilament nylon, polydioxanone, polyglactin 910, and chromic gut. The skin reacted in 3 ways to suture material, showing edema, epidermal changes, and inflammation. Although the gross reactions to monofilament nylon, polydioxanone, and polyglactin 910 were clinically indistinguishable
and were associated with lowest gross reaction scores, monofilament nylon elicited the least histologic reaction and therefore seems to be the most appropriate choice for use in amphibian skin.
Vascular access ports (VAPs) for studies requiring intermittent or continuous infusion and frequent sampling are well accepted and widely used in large animal species. However, the use of medical devices such as VAPs to facilitate sample collection can lead to complications. Noninfectious
complications of VAP implantation can result from thrombotic or mechanical obstructions, other mechanical problems, and animal-associated complications. To facilitate our research, we surgically implanted VAPs in the right external jugular vein of 6 adult male and 3 female Yucatan miniswine
(age, 12 mo) to enable collection of blood samples every 30 min for 8 h and then every 8 h for as long as 60 d. The VAPs were operational an average of 35.6 d (range, 29 to 56 d) and had an overall success rate of 77.8% with 7 of 9 VAPs functional. In these 7 animals, 53.1 samples on average
(range, 28 to 95 samples) were collected from each VAP. Rates of noninfectious complications were 60% for thrombotic events and 40% for nonthrombotic events over the course of this study.
Fenbendazole is commonly used in laboratory animal medicine as an anthelmintic for elimination of pinworms. It is generally regarded as a safe drug with minimal side effects. In our facility, 2 breeding colonies of rats were treated with fenbendazole to eliminate pinworms. Analysis
of the breeding records revealed that feeding Sprague-Dawley rats a diet containing fenbendazole on a continuous basis for 7 consecutive weeks was associated with a significant reduction in litter size. Although the mechanism underlying this effect is unknown, the finding prompts caution when
using fenbendazole to treat valuable breeding colonies or strains that are poor breeders.
The Guide for the Care and Use of Laboratory Animals states that sanitization of caging accessories (for example, filter tops and wire-bar lids) should be done every 2 wk. In this study we tested the hypothesis that organic contamination measured by the presence of ATP associated
with organic material (measured with luciferase test swabs) and the number of bacterial colony-forming units (as determined by use of replicate organism detection and counting plates) on caging accessories did not differ significantly at 2 wk versus several months of use. The study evaluated
4 groups: mouse and rat ventilated and static wire-bar cages with or without filter tops (n = 10 per group). The cages were evaluated at several time points from 2 wk to 6 mo. For every cage type, ATP levels did not differ significantly between 14 and 90 d and, in most cases, between 14 and
180 d. In addition the number of bacterial colonies did not differ significantly between 14 and 120 d (and, in some cases, between 14 and 180 d). This study provides data relevant to establishing a validated frequency for sanitization of rodent caging accessories while controlling, and potentially
decreasing, costs associated with sanitization.
Reactions to allergens created by laboratory animals are among the most frequently encountered occupational illnesses associated with research animals. Personnel are exposed to these allergens through airborne particulate matter. Although the use of microisolation caging systems can
reduce particulate matter concentrations in rooms housing mice, the operating parameters of ventilated caging systems vary extensively. We compared room air in mouse rooms containing 5 different types of caging: 1) individually ventilated caging under positive pressure with filtered intake
air and exhaust air returned to the room (VCR+), 2) individually ventilated caging under negative pressure with exhaust air returned to the room (VCR–), 3) individually ventilated caging under positive pressure with exhaust air returned to the heating, ventilation, and air-conditioning
(HVAC) system, 4) individually ventilated caging under negative pressure with exhaust air returned to the HVAC system, and 5) static microisolation cages. We found that rooms under VCR conditions had fewer large particles than did those under other conditions, but the numbers of 0.3 μm
particles did not differ significantly among systems. Static, positive or negative pressure applied to caging units as well as route of air exhaust were found to have little influence on the total number of particles in the atmosphere. Therefore, considering the heat load, odor, and overall
particulate concentration in the room, placing individually ventilated caging under negative pressure with exhaust air returned to the HVAC system appears to be the optimal overall choice when using microisolation housing for rodents.
Automated plasmapheresis is an optimal method of plasma collection because the donor is a part of a closed loop where whole blood is withdrawn and separated and packed cells are returned in a serial fashion until the desired amount of plasma is obtained. The typical approach to collection
of antibody-rich plasma involves withdrawal of whole blood from vaccinated animals, yielding approximately 1000 ml plasma from each animal, which is euthanized after this process. In the present study, 32 goats (Capra hircus) were vaccinated and conditioned for restraint in a modified
Panepinto sling. Each animal was monitored clinically, including complete and differential blood counts and serum chemistries 24 h before and 24 to 48 h after each procedure. A jugular vein was surgically prepped, a 16-gauge needle catheter was placed, and the animal was attached to an automated
plasmapheresis machine. After plasma removal, return of the resuspended packed blood cells, and infusion of 500 ml 0.9% NaCl, the animal was disconnected from the machine, the catheter removed, and the animal returned to the barn. There were no clinically significant changes in either the
complete blood counts or the clinical chemistries during the course of this study. These 32 animals produced 240,000 ml of immunoglobulin-rich plasma over the course of this project and more than 949,000 ml of plasma to date. This study identifies a refinement in current antibody-recovery
techniques and potentially reduces the number of animals necessary to produce bioreagents on a long-term and continual basis.
Experimental induction of ventricular fibrillation in animals yields valuable information about this deadly arrhythmia. Human adult or pediatric defibrillators and their paddles can be used easily in larger animals such as dogs and pigs, but these animals are more difficult to house
and handle, and available biochemical assays may be limited. In contrast, rats are easy and relatively inexpensive to house and handle, and numerous biochemical tests are available. However, in most cases, even pediatric electrodes are impractical for use in rats. Proper placement of defibrillation
electrodes on the thorax requires that the electrical axis of the heart be situated between the defibrillator paddles. The most common approach to defibrillation in rats uses 2 electrodes: one is built into a board that underlies and touches the rat's back, and another is positioned manually
on the anterior thorax. The aim of this study was to produce electrodes that are 1) easy to handle, 2) specifically designed for rats, 3) efficiently deliver defibrillation shocks along the electric axis of the heart, and 4) can be used for both in vivo defibrillation and on isolated heart
preparations.
Investigators of our research facility generally accept the concept of asepsis as an important component of adequate surgical care for animals. However, they experience difficulties putting it into practice, especially in the case of rodents. The reasons for this are inconvenience,
cost, and lack of training. To better assist investigators in the implementation of aseptic surgical techniques in their laboratories, we have created an Operating Room (OR) Committee modeled after OR committees found in human hospitals. A reconstructive surgeon, a veterinarian, a research
scientist, a nurse involved in the training of OR personnel, interns, graduate students, and an animal health technician were chosen as committee members in light of their OR and animal care expertise. The first task of the OR Committee was to establish institutional guidelines for aseptic
surgery, taking into account the costs imposed on research budgets by these procedures. The OR Committee also supports a complete training program in aseptic surgery techniques, which consists of lectures, a training manual, videos, and a practical course. Furthermore, when experimental procedures
require specialized equipment, the OR Committee collaborates with researchers to develop strategies to achieve asepsis. This OR Committee and the training program proved to be important tools to promote and improve the quality of animal care during surgery.
A group of 12 domestic pigeons (Columba livia domestica) was treated for capillariasis by use of fenbendazole at 30 mg/kg orally once daily for 5 d. After treatment, 8 of the 12 pigeons exhibited signs of anorexia, lethargy, and dehydration; these birds died within 2 d after
the onset of clinical signs. A total of 6 birds were necropsied, and all had unremarkable gross findings. Microscopic examination of tissues revealed acute hemorrhagic enteritis, diffuse lymphoplasmacytic enteritis, small intestinal crypt necrosis, periportal lymphoplasmacytic hepatitis, bile
duct hyperplasia, and renal tubular necrosis. Erythrocytes in blood samples collected from surviving birds demonstrated polychromasia compatible with a regenerative anemia. The clinical and histopathologic findings in these pigeons were consistent with recent reports of fenbendazole toxicity
in domestic pigeons and other columbiform birds.
This case report describes sublaryngeal tracheal injury and ulceration in 15 rabbits from 3 institutions as sequelae to routine intubation and general anesthesia with isoflurane in oxygen. The rabbits were intubated for general anesthesia and mechanically ventilated for experimentally
diverse procedures, with periods of anesthesia lasting 1.5 to 5 h. Of the 15 animals, 6 developed minimal to moderate postanesthesia clinical signs of moist rales or cyanosis or both; 2 of these 6 rabbits later died unexpectedly, their deaths attributed to respiratory obstruction by necrotic
tracheal debris. The pathogenesis of this lesion is reviewed. Our findings suggest that rabbits may be predisposed to developing serious tracheal injury and clinically significant sequelae in association with routine intubation.
The purpose of this study was to evaluate 3 anesthetic protocols for intraduodenal drug administration by endoscopy in rhesus monkeys (Macaca mulatta). Anesthesia was induced using intramuscular ketamine and midazolam, isoflurane (inhalant gas), or intravenous propofol in male
and female rhesus monkeys. A noninvasive dosing line was placed in the duodenum by use of endoscopy, and 50% dextrose (3 ml/kg) was administered. Blood pressure, heart rate, body temperature, and reflexes (corneal, palpebral, pharyngeal) and myorelaxation (mandibular reflex and reaction to
limb manipulation) were evaluated every 5 min. To estimate intestinal absorption, glycemia was evaluated prior to dextrose administration and at 2, 5, 10, 15, 20, 30, 45, and 60 min after dosing. All 3 protocols resulted in successful induction of anesthesia. Recovery from isoflurane and propofol
was significantly faster than from ketamine–midazolam. Duration of the recovery period after isoflurane was less variable than with propofol, but isoflurane produced greater hypothermia. Isoflurane and propofol resulted in predictable glucose absorption after intraduodenal dextrose administration,
whereas ketamine–midazolam led to an inconsistent increase in glycemia.
Reports of severe enteric disease of unknown etiology affecting lactating mice have appeared in the literature. Clostridial disease similar to that seen in cattle and sheep on high-carbohydrate rations and caused by Clostridium perfringens has been suspected in these mouse outbreaks
but has not been isolated from affected mice. The present report describes a severe, necrotizing enterocolitis associated with overgrowth of C. perfringens type A in lactating Swiss-derived (ND4) mice. Mice nursing large litters of pups in the second week of life were the most severely
affected. The organism isolated from dead or moribund mice was positive by polymerase chain reaction assay for the gene for the C. perfringens α toxin, but actual toxin production was not determined. The disease in this mouse colony was ameliorated by increasing the fat and calorie
content of the diet of lactating dams, which each received 1 g peanut butter every 48 h.