Comparative medicine最新文献

Corynebacterium bovis is an opportunistic pathogen of the skin of immunodeficient mice and is sensitive to oral antibiotics that reach therapeutic blood concentrations. However, prophylactic antibiotics are considered to be ineffective at preventing C. bovis infection. In addition, the effect of C. bovis on the skin microbiome (SM) of common immunodeficient mouse strains has yet to be characterized. Consequently, we evaluated whether oral prophylactic antibiotics prevent C. bovis infection after inoculation. An infectious dose of C. bovis was applied to the skin of Hsd:Athymic Nude (nude) and NOD. Cg-Prkdc^{scid Il2rgtm1Wjl}/SzJ (NSG) mice. Mice were then housed individually and assigned randomly to receive either untreated drinking water (Cb+Abx-group) or prophylactic amoxicillin-clavulanic acid in the drinking water (0.375 mg/mL) for 14 d (Cb+Abx+group). A third treatment group of each mouse strain was uninoculated and untreated (Cb-Abx-group). Mice from all groups were serially sampled by using dermal swabs to monitor C. bovis infection via quantitative real-time PCR and the SM via 16S rRNA sequence analysis. Fourteen days of prophylactic antibiotics prevented the perpetuation of C. bovis skin infection in both strains. Only the combination of C. bovis inoculation and oral antibiotics (Cb+Abx+) significantly affected the SM of NSG mice at day 14; this effect resolved by the end of the study (day 70). In mice that did not receive antibiotics, C. bovis significantly altered the SM of nude mice but not NSG mice at days 14 and 70. These findings demonstrate the potential benefit of prophylactic antibiotics for prevention of C. bovis infection. However, indirect effect of antibiotics on commensal bacteria and potential effects on xenograft models must be considered.

Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.

Establishing the appropriate yet minimal number of control mice for experiments is a critical step in experimental design. This decision is particularly important regarding the study of the hematopoietic system over time, given various age-associated changes in murine hematopoietic cell populations. Here we used flow cytometry to serially monitor the frequencies of hematopoietic stem cells, common lymphoid progenitor cells, and common myeloid progenitor cells and RT-PCR assays to study the levels of Ly6a (Sca1), Slamf1, Ikzf1, and Cebpa—4 genes that control the hematopoietic process—in wildtype male and female mice with a B6SJL genetic background. These analyses revealed many differences, both at the cellular and mRNA levels, between immature and mature mice at various developmental stages. In conclusion, although it is necessary to minimize the number of mice possible insofar as possible to reduce animal use and meet animal welfare requirements, the numerous differences shown by our findings highlight the need to establish controls for every time point selected for the study of the hematopoietic system cells. This need is especially crucial when comparing immature and mature stages of mouse development.

Although neck and low-back pain are common sources of neuropathic pain with high societal costs, the pathophysiology of neuropathic pain is not well-defined. Traditionally, most rodent pain studies rely on evoked reflex-based testing to measure pain. However, these testing methods do not reveal spontaneous pain, particularly early after injury. The rat grimace scale (RGS) for quantifying spontaneous pain has been validated after visceral, incisional, orthopedic, and inflammatory insults but not neuropathic pain. The current study used a rat model of radiculopathy to investigate the time course of RGS, the effect of the NSAID meloxicam on RGS, and the reliability and consistency of RGS across testers. RGS values at baseline and at 3, 6, 24, and 48 h after cervical nerve root compression (NRC) that induced robust evoked pain responses were compared with those obtained after sham surgery. The RGS was also evaluated at 6 h after NRC in another set of rats that had received meloxicam treatment prior to surgery. At 6 h, NRC induced higher RGS scores (1.27 ± 0.18) than did sham surgery (0.93 ± 0.20), and scores remained above baseline for as long as 48 h. Treatment with meloxicam before NRC reduced RGS at 6 h to sham levels, which were lower than those of injury without treatment. The RGS was associated with very good interobserver reliability (intraclass correlation coefficient, 0.91) and excellent internal consistency (Cronbach α, 0.87). These findings suggest that RGS is a useful approach to identifying and monitoring acute neuropathic pain in rats.

FVB/N mice with 'space cadet' syndrome are prone to audiogenic seizures and are considered excitotoxic 'sensitive' mice due to the neuronal damage that accompanies seizures. FVB/N mice found dead demonstrate acute neuronal cell death--attributed to a massive seizure episode--within the hippocampus and cerebrocortical laminae. However, the behavioral features of FVB/N mice and numerous studies using excitotoxins to induce seizure activity indicate that this strain experiences multiple sublethal seizures. To assess whether FVB/N mice develop histologically detectable lesions, we evaluated the brains of 86 aged (154-847 d) FVB/N mice without a history of seizures. The hippocampus and cerebrocortical laminae were evaluated histologically for neuronal atrophy and gliosis. Neuronal atrophy was quantified by counting neurons in the hippocampus (CA3 and dentate gyrus) and cerebral cortex. Gliosis was quantified by using immunohistochemistry for glial fibrillary acidic protein and glial counting in the cerebral cortex. In addition, ventricular area was calculated. Our study revealed no changes in brain weight with age, no neuronal loss or gliosis, no correlation between neuronal or glial cell profile densities and brain weight or age, and no differences in ventricular size between FVB/N and control mice. Neuronal densities in the cerebral cortex and granule cells of the dentate gyrus were lower in FVB/N mice than in control Swiss Webster mice. We conclude that although acute lesions of seizure activity are a previous feature of the FVB/N strain, chronic seizure activity in these mice either is negligible or does not cause morphologic or phenotypic changes.

Nursery rearing of rhesus macaques (Macaca mulatta) alters behaviors but may be necessitated by maternal rejection or death, for research protocols, or for derivation of SPF colonies. The Tulane National Primate Research Center maintains a nursery-reared colony that is free from 9 pathogens as well as a mother-reared colony free from 4 pathogens, thus affording an opportunity to assess the outcomes of differential rearing. Nursery-reared macaques had continuous contact with 2 peers and an artificial surrogate (peer rearing). Focal sampling (432 h) was collected on the behavior of 32 peer-reared and 40 mother-reared subjects (age, 1 to 10 y; immature group, younger than 4 y; adult group 4 y or older). All animals were housed outdoors in like-reared social groups of 3 to 8 macaques. Contrary to expectation, no rearing effects on affiliative or agonistic social behaviors were detected. Compared with mother-reared subjects, peer-reared macaques in both age classes had elevated levels of abnormal appetitive, abnormal self-directed, and eating behaviors and lower levels of locomoting and vigilance (highly alert to activities in surrounding environment); a trend toward reduced foraging was detected. Immature but not adult peer-reared monkeys demonstrated more enrichment-directed behavior and drinking and a trend toward more anxiety-related behavior and inactivity. No new rearing effects were detected in adults that had not been detected in immature subjects. Results suggest that modern peer-rearing practices may not result in inevitable perturbations in aggressive, rank-related, sexual, and emotional behavior. However, abnormal behaviors may be lifelong issues once they appear.