Performance and Consistency of Circulating Warm Water Blankets for Rodents.

General anesthesia as used for rodent research can have adverse effects on physiologic mechanisms. Thermoregulation is often greatly inhibited, with resultant deleterious effects on cardiac and respiratory function. These potential effects can be mitigated by providing external heat support. The circulating warm water blanket and associated heat pump are often used in rodent procedures. The current study demonstrated that the heating pump and water blanket require quality control assessment to ensure adequate function. Our data showed that of the 6 pumps tested, 5 were able to achieve a temperature that met or exceeded the documented thermoneutral zone for mice. Pumps required 20 min of warming to reach their maximal attainable temperatures for the designated user setting. Although the pumps reached a temperature that was sufficient to provide external thermal support, only 1 of the 6 pumps reached the temperature that was set by the user during the trial. Surface temperatures across the water blanket were recorded to analyze whether a difference in heat support was influenced by animal placement along the water blanket; however, the location points did not yield statistically different results. Two pumps were eliminated from the study due to failure to pass the preparation phase of the trial. The results of this study support the need for facilities to establish quality control measures to ensure that heat support systems are functioning at a level required to maintain normothermia during anesthetic procedures.

Nonexperimental Xenobiotics: Unintended Consequences of Intentionally Administered Substances in Terrestrial Animal Models.

Review of the use of nonexperimental xenobiotics in terrestrial animal models and the potential unintended consequences of these compounds, including drug-related side effects and adverse reactions.

Use of Air-activated Thermal Devices during Recovery after Surgery in Mice.

Laboratory mice (Mus musculus) are susceptible to hypothermia, especially during anesthetic events, disease states, and exposure to environmental stressors. Thermal support devices for small mammals are numerous, but often require a power source and may be impractical to use for cages on a rack. Air-activated thermal devices (AATD) are mixtures of chemicals that cause an exothermic reaction. In this study, we examined the environmental effects of AATD on internal cage temperatures without the use of additional equipment as well as the physiologic effects of AATD as postoperative thermal support in mice. For environmental experiments, temperatures measured inside the cage and above the AATD peaked at 35.6 ± 2.5 °C (13.4 °C higher than control cages). We also demonstrated that the amount of heat produced by AATD and its temporal distribution are dependent on cage and rack types. For physiologic experiments, mice were surgically implanted with an intraperitoneal temperature telemetry device in a static cage setting. Recovery times and final body temperature at 5 h postoperatively did not differ significantly between mice with and without AATD. During the first 0 to 3 h after mice returned to their home cages, body temperature dropped markedly in mice without AATD but not in mice with AATD. Based on this result the physiologic results of our study support that AATD can be useful in providing extended thermal support for mice housed in static microisolation cages to help maintain body temperature postsurgically. Environmental results of our studies demonstrated that AATD provide local clinically relevant thermal support for 2.5 to 6 h, depending on cage set-up.

Duodenal Cannulation in Pigs (Sus scrofa) as a Drug Delivery Method.

Currently available animal models for delivery of drug capsules and pharmacokinetic testing are limited by either intersubject variability in gastric emptying time or the need to sedate animals when using targeted delivery methods of drug capsules. With the increasing development of large-molecule biologics, better in vivo models for testing the pharmacokinetics of capsule-delivered drugs are urgently needed. To this end, we made engineering modifications to an existing bovine surgical cannula device, successfully implanted this modified cannula into pigs, and delivered drug capsules directly to the proximal duodenum. In our porcine model, capsule insertion and serial blood samples were all acquired without the use of sedatives. Furthermore, we were able to maintain cannulated pigs for weekly pharmacokinetic testing for more than 18 mo, with minimal postoperative complications. This study demonstrates a novel and effective porcine model of sedation-free drug delivery and blood collection that eliminates inconsistencies associated with models that require either gastric emptying or animal sedation.

Isolation and molecular characterization of group B Streptococcus from laboratory Long-Evans rats (Rattus norvegicus) with and without invasive group B streptococcal disease.

Purpose. Group B Streptococcus (S. agalactiae, GBS) is a Gram-positive opportunistic pathogen that inhabits the respiratory, urogenital and gastrointestinal tracts of humans and animals. Maternal colonization of GBS is a risk factor for a spectrum of clinical diseases in humans and a principle cause of neonatal meningitis and septicaemia.Methodology. We describe polymicrobial sepsis including GBS in two gravid adult female Long-Evans rats experiencing acute mortality from a colony of long-term breeding pairs. Fluorescent in situ hybridization confirmed GBS association with pathological changes in affected tissues, including the heart and uterus.Results. Characterization of seven GBS strains obtained from clinically affected and non-affected animals indicated similar antibiotic resistance and susceptibility patterns to that of human strains of GBS. The rat strains have virulence factors known to contribute to pathogenicity, and shared serotypes with human invasive isolates. Phylogenetic analyses revealed that one rat-derived GBS strain was more closely related to human-derived strains than other rat-derived strains, strengthening the notion that interspecies transmission is possible.Conclusions. To our knowledge, this is the first investigation of genotypic and phenotypic features of rat-derived GBS strains and their comparison to human- and other animal-derived GBS strains. Since GBS commonly colonizes commercially available rats, its exclusion as a potential pathogen for immunocompromised or stressed animals is recommended.

Opposing roles for NF-kappa B/Rel factors p65 and c-Rel in the modulation of neuron survival elicited by glutamate and interleukin-1beta.

The nuclear transcription factors NF-kappaB/Rel have been shown to function as key regulators of either cell death or survival in neuronal cells. Here, we investigated whether selective activation of diverse NF-kappaB/Rel family members might lead to distinct effects on neuron viability. In both cultured rat cerebellar granule cells and mouse hippocampal slices, we examined NF-kappaB/Rel activation induced by two opposing modulators of cell viability: 1) interleukin-1beta (IL-1beta), which promotes neuron survival and 2) glutamate, which can elicit toxicity. IL-1beta produced a prolonged stimulation of NF-kappaB/Rel factors by inducing both IkappaBalpha and IkappaBbeta degradation. Glutamate produced a delayed and transient activation of NF-kappaB/Rel, which was associated with a brief loss of IkappaBalpha. Moreover, IL-1beta activated the p50, p65, and c-Rel subunits of NF-kappaB/Rel, whereas glutamate activated only the p50 and p65 proteins. The inhibition of NF-kappaB/Rel protein expression by antisense oligonucleotides in cerebellar granule cells showed that p65 was involved in glutamate-mediated cell death, whereas c-Rel was essential for IL-1beta-preserved cell survival. Furthermore, the depletion of c-Rel in cultured neurons as well as in the hippocampus from the c-Rel(-/-) mouse converted the IL-1beta effect into toxicity. These findings suggest that, within a single neuron, the balance between cell death and survival in response to external stimuli may rely on the activation of distinct NF-kappaB/Rel proteins.