Reproductive Outcomes in Rhesus Macaques (Macaca mulatta) with Naturally-acquired Trypanosoma cruzi Infection.

Chagas disease is a zoonotic vector-borne disease caused by infection with the protozoan parasite Trypanosoma cruzi. T. cruzi is found in Latin America and the Southern United States, where it infects many species, including humans and nonhuman primates (NHPs). NHPs are susceptible to natural infection and can develop clinical symptoms consistent with human disease, including Chagasic cardiomyopathy, gastrointestinal disease and transplacental transmission, leading to congenital infection. Due to evidence of Chagas transmission in Texas, this study hypothesized T. cruzi infection was present in a closed, outdoor-housed breeding colony of rhesus macaques (Macaca mulatta) located at a biomedical research facility in Central Texas. In addition, we questioned whether seropositive female rhesus macaques might experience reproductive complications consistent with maternal-fetal Chagas disease. The seroprevalence of T. cruzi infection in the colony was assessed using an Enzyme Linked Immunosorbant Assay (ELISA) to detect antibodies against Tc24 antigen as a screening assay, and a commercially available immunochromatographic test (Chagas Stat Pak) as a confirmatory assay. Retrospective serologic analysis was performed to confirm the status of all T. cruzi-infected animals between the years 2012 to 2016. The medical history of all seropositive and seronegative breeding females within the colony from 2012 to 2016 was reviewed to determine each animals' level of reproductive fitness. The percentage of T. cruzi-seropositive animals ranged from 6.7% to 9.7% in adult animals and 0% to 0.44% in juveniles or weanling animals, depending on the year. An overall 3.9% seroprevalence of T. cruzi infection was found in the total population. No significant differences in any measure of reproductive outcomes were identified between seropositive and seronegative females from 2012 to 2016. The lack of significant adverse reproductive outcomes reported here may help inform future management decisions regarding seropositive female rhesus macaques within breeding colonies.

Effects of Extruded Compared with Pelleted Diets on Laboratory Mice Housed in Individually Ventilated Cages and the Cage Environment.

The physical form of the diet fed to laboratory animals should be evaluated to reduce experimental variations and confoundingfactors. This 14-d study evaluated the effects of diet form (pelleted or extruded) on intracage ammonia concentrations,feed disappearance, body weight, cage weight, and the degree of cage soilage and whether these effects were influenced bystrain or stock or sex. Mice (C57BL/6, ICR, and nude; age, 4 wk) were randomly assigned to 4 treatment groups representingpelleted and extruded diets from each of 2 vendors (pelleted diet groups, P1 and P2; extruded diet groups, E1 and E2).Intracage ammonia concentrations depended on strain or stock, diet, and day and were higher in cages housing nude micethat consumed P1. Diet type did not affect the weight of mice at the end of the study. Feed disappearance was dependent ondiet type and mouse strain or stock and was greatest in the cages of mice that consumed P1. In addition, the greatest feeddisappearance was seen with ICR mice, whereas the least was seen with C57BL/6 mice. Cages housing male nude mice hadgreater cage soilage than those housing female nude mice. The degree of cage soilage was influenced by diet type and dayalso. These results show that diet form and mouse strain or stock significantly affect intracage ammonia concentrations, feeddisappearance, cage weight, and the degree of cage soilage.

Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor.

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.

Effect of Enrichment Devices on Aggression in Manipulated Nude Mice.

Agonistic behavior in group-housed male mice is a recurring problem in many animal research facilities. Common management procedures, such as the removal of aggressors, are moderately successful but often fail, owing to recurrence of aggressive behavior among cagemates. Studies have incorporated enrichment devices to attenuate aggression, but such devices have had mixed results. However, these studies did not include research manipulations when assessing the benefits of various enrichment devices. We obtained 100 male athymic nude mice and studied the efficacy of various enrichment devices, including cotton squares, paper rolls, shredded paper, nylon bones, and a mouse house and wheel combination in the reduction of fighting during an ongoing study that involved randomization followed by prostate and intratibial injections. Groups were evaluated according to a numerical grading system for wound assessment. Examination of the data revealed that the enrichment devices had no effect on the presence of wounds, thus none of the devices tested affected fighting in nude mice. However, when mice began experimental use, fight wounds increased significantly at cage change and after randomization, reflecting a disruption of existing social hierarchies. Therefore, in the context of an actual research study that involves common manipulations, the specific enrichment device had less effect on aggression in male nude mice than did the destruction and reconstruction of social structures within each group.

Training veterinary care technicians and husbandry staff improves animal care.

Our animal care facility has always relied on an animal health team consisting of veterinarians, veterinary care technicians, and husbandry staff to provide a high level of animal care. As our rodent population increased, it became necessary to modify the roles and responsibilities of these staff members to accommodate the program's expansion. To accomplish that modification, we developed a training program that focused primarily on technicians by using a case-management algorithm. To support our technicians, we provided additional training to animal husbandry staff as they assumed the primary role in the initial assessment of the animals' health. After completing the training, technicians made the transition from simply identifying health issues to actually making decisions for treating and euthanizing rodents. This training program empowered all team members and resulted in a staff that could provide consistent, high-quality veterinary care more efficiently.

Effective drug delivery, in vitro and in vivo, by carbon-based nanovectors noncovalently loaded with unmodified Paclitaxel.

Many new drugs have low aqueous solubility and high therapeutic efficacy. Paclitaxel (PTX) is a classic example of this type of compound. Here we show that extremely small (<40 nm) hydrophilic carbon clusters (HCCs) that are PEGylated (PEG-HCCs) are effective drug delivery vehicles when simply mixed with paclitaxel. This formulation of PTX sequestered in PEG-HCCs (PTX/PEG-HCCs) is stable for at least 20 weeks. The PTX/PEG-HCCs formulation was as effective as PTX in a clinical formulation in reducing tumor volumes in an orthotopic murine model of oral squamous cell carcinoma. Preliminary toxicity and biodistribution studies suggest that the PEG-HCCs are not acutely toxic and, like many other nanomaterials, are primarily accumulated in the liver and spleen. This work demonstrates that carbon nanomaterials are effective drug delivery vehicles in vivo when noncovalently loaded with an unmodified drug.

Noise produced by vacuuming exceeds the hearing thresholds of C57Bl/6 and CD1 mice.

Daily vacuuming of floors and flat-shelf racks is a standard procedure in our rodent housing rooms. To determine whether the noise produced by this activity is a potential stressor to animals used for transgenic and knockout mouse production, we measured the sound levels in our genetically engineered mouse facility under ambient conditions and at the in-cage and room levels during vacuuming. Spectral analysis showed that vacuuming produces a multitonal, low-frequency noise that is not attenuated by microisolation caging with bedding material. Comparison of cage-level spectral analysis results with age-specific audiograms of C57Bl/6 and CD1 mice showed that vacuuming produces frequencies audible to C57Bl/6 mice at 3 and 6 mo of age and to CD1 mice at 1 mo of age. These findings suggest that vacuuming in animal rooms could be a source of stress to animals with these genetic backgrounds.