Drug metabolism and pharmacokinetic (DMPK) studies are an important phase in drug discovery research. Compounds are administered via the intravascular or extravascular routes to animals to calculate various pharmacokinetic parameters. An important step in this process is dissolving the novel compound in a safe vehicle. This procedure is particularly challenging for compounds that must be administered intravenously, as the solution must be clear before injection. There are no published guidelines on which vehicles, or combination of vehicles, are acceptable in a particular species, nor are there published data on the effects these vehicles have on clinical chemistry or hematology parameters, particularly in dogs. In this study, 9 vehicles commonly used at sanofi-aventis USA (propylene glycol, polyethylene glycol 400, glycofurol, hydroxypropyl β-cyclodextrin, dimethyl sulfoxide, N-methyl-2-pyrrolidone, dimethylacetamide, ethyl alcohol, and saline) were tested for adverse clinical reactions (such as vomiting or diarrhea) and for their effect on hematology and clinical chemistry parameters. Each vehicle was administered to a group of 8 Beagles by slow intravenous infusion, and blood was collected prior to infusion and at 24 h and 7 d postinfusion. Of 8 dogs given propylene glycol, 2 developed mild gastrointestinal signs (vomitus, diarrhea) after their infusions. None of the vehicles tested induced significant hematology or serum clinical chemistry abnormalities, nor were significant clinical signs noted after administration. We conclude that at the dose, route, and manner described, all of the vehicles tested in this study are clinically safe to use and have no acute effects on hematology or serum chemistry parameters.

Rats are used routinely for the discovery of new pharmaceuticals and for toxicology testing to fulfill regulatory requirements. In 1999, a survey showed that 80% of all rodents housed in toxicology studies were housed in wire-bottom cages. However, both the National Research Council and Association for the Assessment and Accreditation of Laboratory Animal Care, International, recommend housing rats in solid-bottom cages with bedding. In this study 2 groups of male Sprague Dawley rats were housed in the same room for 4 wk and provided the same food and water by the same husbandry staff person. The only variable in the study was the type of housing. One group was housed in solid-bottom polycarbonate cages with bedding and the other group in standard wire-bottom caging. Clinical pathology laboratory evaluations of complete blood count, serum chemistries, urinalysis, urine creatinine, urine corticosterone, blood coagulation, and hepatic cytochrome P450 isoenzyme mRNA levels were performed. No clinically relevant differences were found between the 2 groups for any of the laboratory data.

One of the most prevalent pathogens found in zebrafish (Danio rerio) research facilities is the microsporidian parasite Pseudoloma neurophilia. Infections occur primarily in the spinal cord and are associated with emaciation and scoliotic changes. It is unclear why P. neurophilia is so widespread among research colonies, although transfer of infected animals and eggs between laboratories is a likely contributor. In addition to preventing the spread of this pathogen among facilities, it is desirable to have parasite-free fish for use in experiments. Therefore we have developed a polymerase chain reaction (PCR)-based diagnostic test for P. neurophilia. Compared with conventional diagnostic methods, PCR diagnosis is rapid, allows for screening of large numbers of fish, and can be applied to eggs, water filtrates, biofilms, and other samples. Using PCR primers specific to the small subunit ribosomal DNA of P. neurophilia, the test was consistently capable of detecting 10 spores per reaction and often as few as 0.1 spore per reaction, and it did not cross-react with other selected microsporidian species from fish. We recommend this PCR diagnostic assay for use by the research community to determine the presence (or absence) of P. neurophilia in colonies and for screening fish shipped between facilities, especially when parasite-free fish are required for experiments. Furthermore, we currently are using this PCR method to investigate the potential role of vertical transmission in the spread of P. neurophilia.

Although the California sea hare, Aplysia californica, is well known from neurobiological studies and is raised in the laboratory for this purpose, various aspects of its life history in the laboratory, such as aging dynamics, are unknown. Therefore we collected life history data on 4 cohorts of eggs from hatchery-reared animals and performed an actuarial analysis of mortality data. Temperature was controlled at 13 to 15 °C, the photoperiod was a 14:10-h light:dark cycle, and the seawater O₂ concentration, pH, and salinity were held at optimized levels. The feeding protocol for 3 cohorts was unrestricted access to the red macroalga Gracilaria ferox, whereas the remaining cohort was fed standard hatchery rations of G. ferox 4 times per week. Growth was sigmoidal in each cohort and resulted in linear growth rates of 1.25 to 3.62 g/d during the exponential phase; these rates were not influenced by feeding level. Sexual maturity occurred at approximately 160 g, at ages ranging from 144 to 241 d. Egg production was highly variable in the different cohorts. Mean lifespan of cohorts fed ad libitum was approximately 228 d. In contrast, the cohort fed standard rations lived an average of 375 d and showed a lower initial mortality rate, suggesting that calorie restriction on a single-species diet prolongs lifespan in California sea hares.

Incisional hernias due to trauma, infection, or tumor are a common abdominal wall defect. Repair of these defects when autogenous tissue is insufficient or inadequate often results in abdominal tissue adhesion. These adhesions often lead to complications such as intestinal obstruction and enterocutaneous fistula. Previous reports have shown that application of prosthetic materials, such as polypropylene mesh and anionic polysaccharides, has been effective in reducing the amount of tissue adhesion. However, some tissue adhesion still occurs with application of these materials when previously described methodologies are used. We evaluated the efficacy of a novel surgical approach that combines the application of Sepramesh, a coated polypropylene mesh, and Seprafilm, composed of anionic polysaccharides (both products from Genzyme, Cambridge, MA), in the repair of abdominal wall hernias. We report that combined application of these 2 materials in a "sandwich technique," by placing the peritoneum between the Seprafilm and Sepramesh, further reduces (and in some instances prevents) tissue adhesion after abdominal wall defects in mice. Moreover, our combined treatment markedly decreased tissue inflammation after hernia repair.

Measurements of standardized ileal digestibility yield more useful results than do those of fecal digestibility. To that end, cecal cannulation of the pig has been performed extensively in an attempt to model the digestive processes of humans. Here we introduce a technique for the placement of a permanent cecal cannula with a silicon port that is larger in diameter than those previously described in the literature. A large lumen offers several advantages, most notably ease in collection of larger samples and introduction of materials into the cecum. To date, this technique has been used successfully to cannulate 39 Yucatan minipigs at our institution. Long-term, there have been no major complications with the procedure or cannulas.

This study compared rabbit rectal thermometry with 4 other thermometry techniques: an implantable microchip temperature transponder, an environmental noncontact infrared thermometer, a tympanic infrared thermometer designed for use on humans, and a tympanic infrared thermometer designed for use on animals. The microchip transponder was implanted between the shoulder blades; the environmental noncontact infrared thermometer recorded results from the base of the right pinna and the left inner thigh, and the tympanic infrared thermometer temperatures were taken from the right ear. Results from each technique were compared to determine agreement between the test modality and the rectal temperature. The practicality and reliability of the modalities were reviewed also. According to this study, the implantable microchip transponder measurements agreed most closely with the rectal temperature.

Here we describe the unusual finding of herpesvirus pneumonia in a 7-d-old infant baboon (Papio hamadryas anubis). This animal had been separated from its dam the morning of its birth and was being hand-reared for inclusion in a specificpathogen-free colony. The baboon was presented for anorexia and depression of 2 d duration. Physical examination revealed a slightly decreased body temperature, lethargy, and dyspnea. The baboon was placed on a warm-water blanket and was given amoxicillin–clavulanate orally and fluids subcutaneously. The animal's clinical condition continued to deteriorate despite tube feeding, subcutaneous fluid administration, and antibiotic therapy, and it died 2 d later. Gross necropsy revealed a thin carcass and severe bilateral diffuse pulmonary consolidation. Histopathology of the lung revealed severe diffuse necrotizing pneumonia. Numerous epithelial and endothelial cells contained prominent intranuclear herpetic inclusion bodies. Virus isolated from lung tissue in cell culture was suspected to be Herpesvirus papio 2 (HVP2) in light of the viral cytopathic effect. Real-time polymerase chain reaction (PCR) analysis and DNA sequencing of PCR products both confirmed that the virus was HVP2. This case is interesting because the age at onset suggests perinatal transmission at or immediately after birth, and the disease course suggests inoculation of the virus into the respiratory tract.

Although environmental enhancement plans for nonhuman primates vary between facilities, feeding enrichment represents a component of most programs. As part of a facility's feeding enrichment program, offering hand-fed food items by trained staff provides an opportunity for positive human interaction. We hypothesized that increased implementation of such enrichment would be associated with increased likelihood of a monkey accepting a hand-fed treat from a stranger. Several species of monkeys were tested at the Tulane National Primate Research Center. In 2002 and 2005, we recorded the number of caged monkeys that accepted a treat tablet from an unfamiliar person within 10 s. We compared the frequency of caretaker-implemented feeding enrichment documented for each animal room during the month proceeding data collection with the proportion of animals within the room that accepted the treat from the stranger. In 2002, 29.8% of the 500 subjects accepted the treat from the unfamiliar person. The proportion of animals that accepted the treat was significantly correlated with the number of days during which feeding enrichment had been implemented. In 2005, feeding enrichment frequency had increased by 76%, and 53.4% of the 676 subjects accepted the treat. These findings suggest that this simple form of enrichment may improve monkeys' responses to unfamiliar people, and that it holds promise as a method for mediating the stress imposed by human activity in animal rooms. In addition, a stranger's treat-feeding attempts may be a useful indicator of an institution's implementation of their environmental enrichment program.

To determine whether noise-induced stress disrupts the intestinal mucosa of laboratory rats, one group of 8 rats ('noise' rats) was subjected to 15 min of white noise (90 dB) daily for 3 wk. Another group ('quiet' rats) was housed for 3 wk in an acoustically similar room but with no additional noise. A 3rd group ('recovery' rats) was housed in the noise room for 3 wk and then in the quiet room for a further 3 wk. The ilea were fixed for microscopy. Villi adjacent to Peyer patches showed significantly more degranulated mast cells (mean ± standard error of the mean, 3.95 ± 0.80 versus 0.35 ± 0.29, respectively) and eosinophils (mean ± standard error of the mean, 9.46 ± 0.44 versus 4.58 ± 0.38) per villus section in noise rats than in quiet rats. Similar results were obtained with rooms reversed, to account for any differences in room characteristics. The mean width of villus laminar propria was significantly greater in noise rats than quiet rats, suggesting edema. In addition, mucosal epithelial cells of noise rats were often separated, sometimes detaching from the basement membrane, whereas those of quiet rats were intact. Behaviorally, noise rats exhibited significantly more grooming and rearing than quiet rats. Compared with noise rats, recovery rats showed no reduction in mast cell degranulation or mean width of villus lamina propria, but there were increased numbers of secreting goblet cells in villi adjacent to Peyer patches and some recovery of epithelial integrity.

Ringtail is a condition characterized by dry skin and annular constrictions that sometimes result in loss of portions of the tail. This condition most commonly affects preweanling rats, and low relative humidity is thought to be a principal cause. The use of transgenic rats in our facility has been increasing since 2002, and we recently diagnosed several litters from transgenic Fischer 344 rats (Rattus norvegicus) with ringtail. Treatment was necessary to maintain the health and integrity of the tails to allow genotyping. Lanolin ointment was chosen because it is a nontoxic, inexpensive, effective moisturizer used for treating human skin conditions. We examined 5 litters comprising 37 pups total, ranging in age from 7 to 17 days at the time of presentation. Animals in 3 litters were randomly assigned to a treatment or nontreatment group, and all animals in the remaining 2 litters were treated. Lanolin was applied to the tails of treatment groups once daily for 6 d. Treatment was tolerated well by pups and no animals were rejected by the dams. After treatment, tail condition was scored from 0 to 3, with 0 representing a tail normal in appearance, and 3 representing severe disease. Chi square testing showed marginal statistical significance, with a trend for a higher percentage of treated rats having healthier tails on day 7 compared to untreated pups. The Pearson correlation between treatment and tail condition scores was significant. Results indicate that lanolin was an efficacious treatment option for ringtail.

The research paradigm of using large laboratory animals, in which oroendotracheal intubations are relatively easy, is shifting toward the use of small animals, such as rodents, in which oropharyngeal access is limited, the arytenoid cartilage cycles are faster, and the glottis is much smaller. The considerable growth recently seen in preclinical imaging studies is accompanied by an increased number of rats and mice requiring in vivo intubation for airway management. Tracheal access is important for ventilation, administration of inhaled anesthetics, instillation of drugs or imaging agents, and maintenance of airway patency to reduce mortality during and after operations. I fashioned a light-carrying laryngoscopic blade (laryngoscope) from readily available acrylic–polymethyl methacrylate tubing and used it to perform rapid, effective tracheal intubation in rats. The laryngoscope design and intubation techniques are presented.