This review summarizes findings from toxicologic, carcinogenic, immunologic, and metabolic studies on fenbendazole (FBZ). Currently, FBZ is used to treat or prevent pinworm outbreaks in laboratory rodents. Because antiparasitic treatments usually are not part of experimental designs, interactions from the medication on the outcomes of ongoing experiments are a concern. At therapeutic levels, FBZ does not alter the total content of cytochromes P450 but does induce certain hepatic cytochrome P450 isoforms, namely 1A1, 1A2, and 2B1. Although expressed constitutively at low or undetectable levels, these isoforms particularly are known for bioactivating a number of procarcinogens. Lifetime studies in rats have shown that FBZ is not a carcinogen but that it may behave as a tumor promoter when given after certain initiators. Unlike in other animal species, FBZ treatment-associated myelosuppression has not been reported to occur in rodents. The few currently available immunologic studies in mice, including an autoimmune model, have not shown effects on selected immune responses. However, data from other animal species suggest that the ability of B and T lymphocytes to proliferate in the secondary immune response may be suppressed during treatment with FBZ.

Forty male Dutch belted rabbits (Oryctolagus cuniculus) enrolled in a minimally invasive pharmacokinetics study were used to compare the efficacy of an anesthetic combination delivered through 2 injection routes. Rabbits were randomly assigned to 4 groups (n = 10/group) to determine the sedative and physiologic effects of ketamine (25 mg/kg)–medetomidine (0.5 mg/kg) given either intramuscularly (IM) or subcutaneously (SC). Palpebral, pedal, ear pinch, and righting reflexes, as well as cardiopulmonary parameters (heart rate, respiratory rate, and arterial blood oxyhemoglobin saturation), were recorded every 5 min. In addition, the reversal effects of an intravenous dose of atipamezole (1 mg/kg), an α2 adrenoreceptor antagonist, were assessed by comparing the return of the righting reflex in rabbits given the reversal agent with those that recovered spontaneously. Compared with the IM route, SC ketamine–medetomidine effectively induced chemical restraint with less than a 2-min difference in onset of anesthesia and markedly less resistance (for example, flinching, kicking, and so forth) during the injection. In all groups, the anesthetic regimen, regardless of the route of administration, provided an adequate level of anesthesia. Reversal with atipamezole improved arterial hemoglobin oxygen saturation for both the SC and IM groups; however, an enhanced rate of recovery from anesthesia was clinically apparent only for animals given the combination by the IM route.

Physiologic measurements in nonhuman primates usually are collected from animals that are chemically or physically restrained. Both types of restraint may affect the parameters measured, and those effects can vary with age. Heart rate, respiratory rate, oxygen saturation, expired CO₂, blood pressure, temperature, blood glucose, hematocrit, and venous blood gasses were measured in rhesus monkeys that were either infused intravenously with ketamine for 24 h or were cage-housed and physically restrained for sample collection. The subjects were pregnant monkeys at gestational day 120 to 123, infants 5 to 6 d old, and infants 35 to 37 d old. Heart rate and blood pressure were lower in ketamine-treated monkeys than physically restrained monkeys. Heart rate was higher in infants than adults, whereas blood pressure was lower in infants. Respiratory rate was higher in infants than adults and higher in physically restrained infants than ketamine-sedated infants but was not affected by ketamine in pregnant adults. Hematocrit was decreased in older infants. In summary, both physical restraint and ketamine sedation altered several physiologic parameters in pregnant and infant rhesus macaques. Investigators should consider these effects when designing experiments and evaluating experimental outcomes in monkeys.

As part of a study addressing chronic alcohol consumption and simian immunodeficiency virus, 31 rhesus macaques (Macaca mulatta) were implanted with gastric catheters used to deliver alcohol or isocaloric sucrose (control). Once implanted, the animals wore jackets and were housed in specialized cages modified with swivels and tethers. During the course of the study, 3 animals developed clinical signs indicating possible instability of the implanted gastric catheter. All 3 animals were found to have a string foreign body wrapped around the distal end of the catheter, with 2 of the catheters perforating the intestinal wall. Gastroscopy was used to screen remaining animals to determine catheter position and the presence of a foreign body attached to the end of the catheter. Results of the screening revealed that of the 28 remaining animals, 9 had malpositioned catheters; string foreign bodies were associated with 3 of the 9 malpositioned catheters. We initially hypothesized that the peristaltic motion of the stomach, combined with the attachment of string, which was probably ingested by subjects after manipulating their jackets, led to eventual catheter displacement. We later concluded that the string may have played a secondary role but was not the primary cause of catheter instability, because several malpositioned catheters had no string attached at the time of diagnosis. Subsequent modifications were instituted, including modifying the surgical technique, altering the type of gastric catheter used, and increasing environmental enrichment for animals with known tendency to manipulate their jackets.

Providing captive or laboratory animals with the best possible living conditions has led to many ideas about how caging environments can be enhanced and the animals' lives can be enriched. This study focused primarily on 2 issues: more efficient use of existing caging and providing animals with a measure of control over their environments. We designed a new spring-loaded folding perching apparatus that, when modified for size, could be added to almost any caging system. Experiment 1 measured usage by animals in standard laboratory caging for rhesus macaque monkeys (Macaca mulatta). Experiment 2 measured usage by this same species in social groups in a 5-acre outdoor–indoor field setting, where several other forms of enrichment were available to the animals. Results indicated that the folding perches were used in both environments. Animals quickly learned to fold down the devices to use as a place to perch, even in the presence of permanent fixed perches. The folding perches did not significantly affect existing behavioral repertoires, but they altered how the animal used the cage. Increased animal presence near folding perches during experiment 2 suggests that these devices actually were preferred. The preference results can only partially be explained by novelty. The folding perches afforded animals a measure of control over their immediate environment without interfering in research or animal care efforts. Including at least 1 folding perch per cage satisfies both the letter and the spirit of regulations on environmental enhancement for captive primates.

Phenotype-driven N-ethyl-N-nitrosourea (ENU) mutagenesis screens in the mouse are being used to elucidate gene function and develop disease models. Many of the earlier screens focused on identifying dominant mutations, whereas many newer mutagenesis programs have arisen that focus on identifying recessive mutations. Recessive screens require more complex breeding and phenotyping procedures, yet little information is available on the optimal breeding and phenotyping strategies for identifying recessive mutations. Optimization involves minimizing the numbers of mice that must be bred and subjected to phenotypic screens while maximizing the number of mutant phenotypes that can be identified. Analysis of expected frequencies of mutants has been used to determine which of the typically used mating and screening strategies will produce the best returns in terms of identifying recessive phenotypes. As a general guideline, to minimize the number of mice to be screened, the optimal strategy is to mate a single generation 2 (G₂) female and G₁ male and screen either 11 or 17 G₃ offspring to obtain at least 1 or 2 homozygous mutants, respectively. When the expense of producing and housing the mice is the greatest cost factor and the phenotype is so robust that a single outlier will suffice, then the optimal strategy is to mate 2 G₂ sisters with the G₁ male parent and screen a single litter from each. Intercrossing of G₂ brothers and sisters is not an efficient method for maximizing returns from ENU screens.

The ability to perform murine neonatal intravascular injections likely will prove useful in studying many newborn-specific disease states that are modeled in mice. Unfortunately, effective intravascular injection in the neonatal mouse has been limited by developmental immaturity and small size. To establish a mouse model of neonatal intravascular injection, C57Bl/6 pups between birth and 6 d of age were injected with a buffered solution containing cells or vehicle alone. For both external jugular and superficial temporal vein injections, a 2-member team was used to position the pup, insert the needle, and perfuse the injectate. For superficial temporal vein injections, the vascular anatomy was visualized by using transillumination. After injection into the jugular or superficial temporal vein, the survival rate to adulthood was 100% (n = 30 pups per group), with no long-term complications. Occasional extravasation of injectate was well tolerated, allowing for serial injections (n = 40 pups). Intravascular access was confirmed by using fluorescent dye perfusion studies and cellular engraftment analysis. The 2 techniques are safe and reproducible methods of obtaining intravascular access via the external jugular and superficial temporal veins in newborn mice. These methods provide a mechanism for delivering a wide variety of substances, ranging from aqueous solutions to suspensions.

An adult female golden hamster (Mesocricetus auratus) developed a firm subcutaneous mass on the lateral distal right forelimb that progressed to diffuse limb enlargement accompanied by extensive cutaneous ulceration and drainage and axillary lymph node metastasis. Touch imprint cytology revealed pleomorphic neoplastic mesenchymal cells. On histology, the invasive neoplasm merged with a large subcutaneous nerve and was composed of spindle cells with a high mitotic index, and lymph node metastasis was confirmed. Histologic morphology and positive immunohistochemical staining of neoplastic cells for vimentin, S100, and neuron-specific enolase were consistent with a malignant peripheral nerve sheath tumor. Although relatively common in dogs, peripheral nerve sheath tumors had not been reported previously in hamsters.

During a 3-mo period, 9 of the 15 New Zealand White rabbits used in a heart failure study developed a hemolytic anemia. The heart failure model involved the creation of an aortic insufficiency (AI) followed 2 to 6 wk later by the creation of an aortic stenosis (AS). None of the 9 animals that developed hemolytic anemia responded to medical management, and 6 of the 9 were euthanized for humane concerns. Necropsies and blood cultures were performed on all anemic animals; 7 of these cultures yielded growth of Achromobacter xylosoxidans. In addition, cultures from the heart valves of 2 rabbits yielded growth of Achromobacter xylosoxidans. We presume that the endocarditis caused by Achromobacter xylosoxidans led to the mechanical damage of red blood cells (RBCs) and subsequent intravascular hemolysis or splenic destruction of damaged RBCs, resulting in a severe, regenerative hemolytic anemia. Achromobacter xylosoxidans is an aerobic, catalase-positive, oxidase-positive, gram-negative bacillus. This organism is an environmentally resistant and opportunistic bacterium that typically inhabits aqueous environments. Microbial samples from the investigator's laboratory and equipment were collected to identify the source of the bacteria. A pressure transducer and bag of intravenous fluid were identified as sources of contamination.

Intramuscular injection of tiletamine–zolazepam and xylazine is commonly used as a preanesthetic for veterinary surgical procedures and for short-term restraint. However, this combination can have marked cardiodepressive and hypothermic effects that persist for hours to days. Here we present a case report of these effects in a swine heart failure model.

We describe severe necrohemorrhagic cystitis in a female rhesus macaque and a female cynomolgus macaque due to colonization of the urinary bladder by Corynebacterium sp. Clinically, both macaques presented with perineal bleeding and depression and, despite extensive and prolonged treatment, succumbed to the disease. At necropsy, the contents of the urinary bladders in both cases were hemorrhagic to greenish black, and the bladder mucosa was necrotic. The major microscopic finding in each case was transmural necrohemorrhagic cystitis, with vasculitis, fibrin thrombi, and myriad gram-positive coryneform bacilli. Corynebacterium renale, Streptococcus acidominimus, and S. oralis were cultured from the urinary bladder of the rhesus macaque, and a nondiphtheritic Corynebacterium was cultured from the urinary bladder of the cynomolgus macaque. Neither animal had any other noteworthy pathologic lesions unrelated to bacterial cystitis. Corynebacterial necrohemorrhagic cystitis therefore was determined to be the cause of death in both animals. To our knowledge, this is the first report of corynebacterial cystitis in nonhuman primates.