Comparative medicine最新文献

MISTRG is an immunodeficient mouse strain that expresses multiple human cytokines that support hematopoietic stem cell maintenance and myelopoiesis. While establishing a breeding colony of MISTRG mice in a dedicated barrier room, 6 cases of death or disease occurred in pregnant or postpartum mice. Clinically, this manifested as hunched posture, dyspnea, and 1 case of emaciation with ataxia. Pathologic analysis of 7 mice revealed multisystemic necrosuppurative inflammation variably affecting the uterus and placenta, joints, meninges, inner and middle ears, kidneys, and small intestine. Bacteria cultured from the blood of septic mice were identified with 89% probability by the Vitek 2 identification system as Streptococcus sanguinuswith atypical biochemical parameters; the API 20E/NE system fully differentiated the isolates as a novel Streptococcusspecies. MALDI Biotyper-based mass spectrometry also indicated that the phenotype represented a novel Streptococcusspp. Sequencing revealed that the full-length 16S rRNA gene identity was below 97% with known Streptococcus species, including the 2 closest species Streptococcus acidominimus and Streptococcus azizii. We propose the name Streptococcus murisepticum spp. nov to our novel isolates. All male mice in this colony remained healthy despite their association with diseased female mice. Overall, 19% of the colony carried the novel Streptococcus in their oral cavity, but it could not be detected in feces. The organism was sensitive to amoxicillin, which was administered via drinking water throughout pregnancy and weaning to establish a colony of pathogen-negative future breeders. The colony remained disease-free and culture-negative for Streptococcus murisepticum spp. nov after treatment with amoxicillin. We suspect that oral colonization of MISTRG mice with the novel Streptococcus species and its associated unique pathology in periparturient mice is potentially the principal cause of loss of this strain at several institutions. Therefore, screening the oral cavity for α-hemolytic streptococci followed by targeted antibiotic treatment may be necessary when establishing MISTRG and allied immunodeficient mouse strains.

Four zebra finches in a closed research colony presented with variable clinical signs, including masses, skin lesions,shivering, and/or ruffled feathers. These birds were not responsive to treatment efforts; 3 died and one was euthanized. All4 were submitted for necropsy to determine the cause of the clinical signs. Gross necropsy and histopathologic findings fromall birds resulted in a diagnosis of round cell neoplasia in multiple organs, including the skin, liver, kidney, and reproductivetract, with intranuclear inclusion bodies in the neoplastic cells. In all 4 cases, immunohistochemical staining showed strongimmunoreactivity for CD3 in 70% to 80% of the neoplastic round cells, with a relatively small subset that were immunopositivefor Pax5. These findings supported a diagnosis of T-cell lymphoma. Frozen liver tissue from one case was submittedfor next-generation sequencing (NGS), which revealed viral RNA with 100% sequence homology to canary polyomavirusstrain 34639 that had originally been identified in a European goldfinch. Formalin-fixed paraffin-embedded scrolls fromanother case were also submitted for NGS, which revealed viral RNA with 97.2% sequence homology to canary polyomavirusstrain 37273 that had originally been identified in a canary. To localize the virus in situ, RNAscope hybridizationwas performed using a probe designed to target the VP1 gene of the sequenced virus in frozen liver tissue. In all 4 cases,disseminated and robust hybridization signals were detected in neoplastic cells. These findings indicate that polyomaviruseshave the potential to be oncogenic in zebra finches.

Laboratory rodents are generally maintained under standardized conditions in order to control the effects of extrinsic factors on research. However, despite attempts to standardize conditions, variability can nonetheless confound efforts directed toward research reproducibility. Here we explore some of the existing literature on the potential impact of seasonal variability as an extrinsic factor that can potentially impact research results. We discuss the influence of seasonal changes in association with an internal clock mechanism that might account for such variation, noting that the mechanisms and interactions of seasonal and internal time-keeping remain largely undetermined. Finally, we speculate that seasonal changes experienced by personnel who handle animals may influence the animals in ways that result in physiologic and behavioral changes.

Risperidone is an antipsychotic medication used in the treatment of conditions like autism and schizophrenia. The goal of the current study was to examine the effects of risperidone in zebrafish embryos ( Danio rerio ) with regard to survival, development, and cardiac and neural systems. The results showed that concentrations above 100 μM were associated with deaths, teratogenic effects, and cardiotoxic and neurotoxic effects. The findings support the utility of zebrafish for toxicological screening studies.

Fibrosis that occurs after nonfatal myocardial infarction (MI) is an irreversible reparative cardiac tissue remodeling process characterized by progressive deposition of highly cross-linked type I collagen. No currently available therapeutic strategy prevents or reverses MI-associated fibrotic scarring of myocardium. In this study, we used an epicardial graft prepared of porcine cholecystic extracellular matrix to treat experimental nonfatal MI in rats. Graft-assisted healing was characterized by reduced fibrosis, with scanty deposition of type I collagen. Histologically, the tissue response was associated with a favorable regenerative reaction predominated by CD4-positive helper T lymphocytes, enhanced angiogenesis, and infiltration of proliferating cells. These observations indicate that porcine cholecystic extracellular matrix delayed the fibrotic reaction and support its use as a potential biomaterial for mitigating fibrosis after MI. Delaying the progression of cardiac tissue remodeling may widen the therapeutic window for management of scarring after MI.

Tree shrews display obvious reproductive cycles, and sexually mature male tree shrews produce little or no sperm with extremely low motility during the nonreproductive season; the mechanism underlying this phenomenon remains unknown. Because testis-specific serine/threonine kinases (TSSK) are specifically expressed in the testis and male germ cells of mammals, we hypothesized that they may have an important role in spermatogenesis or sperm function regulation in tree shrews. In addition, the expression, distribution, subcellular localization, and dynamic changes of TSSK in tree shrew sperm are unclear. Here we show that during the reproductive season, the seminiferous tubules were significantly larger as compared with the nonreproductive season and contained mature sperm and other germ cells. The mRNA expression of Tssk genes in testis was significantly higher than that in other tissues, and the mRNA level in the testis during the reproductive season was significantly higher than that in nonreproductive season. In addition, the mRNA level of Tssk3 in the testis and sperm was significantly higher than that of other members. Specifically, Tssk1 mRNA was distributed in the acrosome and throughout the flagellum of tree shrew sperm, Tssk2 was present in the acrosome, Tssk3 was localized to postacrosomal region and relocated to the main part of the flagellum after capacitation, and Tssk6 was distributed in the acrosome and postacrosomal region. These results indicate that the TSSK are important regulating reproductive function in tree shrews.

Chronic asymptomatic and acute symptomatic anterior uveitis are forms of ocular inflammation associated with juvenile idiopathic arthritis (JIA) Chronic JIA-associated uveitis is characterized by young age of onset, female predilection, oligoarthritis, and antinuclear antibody (ANA) positivity. Acute JIA-associated uveitis predominantly affects older male juveniles who also develop enthesitis. A type I collagen-derived peptide (melanin-associated antigen [MAA]) induces anterior uveitis in rodents. In this study, we evaluated MAA-induced uveitis in rats as a potential model for JIA-uveitis. We characterized MAA-induced uveitis by assessing its relationship to age and sex; tracking the occurrence of arthritis, enthesitis, and ANA positivity; and measuring vitreous fluid inflammatory biomarkers. Juvenile and adult and male and female Lewis rats (Rattus norvegicus) were inoculated with MAA. Slit-lamp biomicroscopy, indirect ophthalmoscopy, and joint examinations were performed 3 times weekly. Rats were euthanized at 4 wk after MAA inoculation, and plasma ANA testing, vitreous inflammatory biomarker assays, and globe histopathology assessments were conducted. Uveitis, arthritis, ANA status, levels of inflammatory biomarkers, histopathology, and joint tomographic images were assessed in relation to age and sex and compared with nonuveitic controls. All MAA-immunized rats developed uveitis characterized by anterior chamber fibrin, iridal vessel dilation, and miosis, and uveal and choroidal lymphocytic infiltration. Levels of the vitreous fluid biomarker CCL5 were higher in uveitic rats compared with control rats. Time to uveitis onset, clinical uveitis scores, and biomarker levels did not differ based on age or sex. None of the MAA-exposed rats had arthritis, enthesitis, or ANA. None of the rats inoculated with MAA that had been treated with matrix metallopeptidase 1 had clinical, histologic, or immunohistochemical evidence of ocular inflammation. In contrast to JIA-associated uveitis in humans, MAA-induced uveitis in rats is not associated with age or sex predilections and MAA is not arthritogenic.

Rodents are currently the most common animals used for hepatic surgical resection studies that investigate liver regeneration, chronic liver disease, acute liver failure, hepatic metastasis, hepatic function, and hepatic cancer. Our previous work has shown that dietary consumption of linoleic acid (LA) stimulates the growth of rodent and human tumors in vivo. Here we compared 3 diets - a 5% corn oil diet (control), a diet deficient in essential fatty acids (EFAD), and an EFAD supplemented with LA in amounts equal to those in the control diet (EFAD+LA). We hypothesized that consumption of the LA provided in the EFAD+LA diet would elevate plasma levels of LA and stimulate regeneration in rats after a 70% hepatectomy (HPX), and that regeneration would not occur in the EFAD rats. Each diet group was comprised of 30 male and 30 female Buffalo rats (BUFF/CrCrl). Rats were fed one of the 3 diets and water ad libitum. After 8 wk on the assigned diet, rats were underwent a 70% HPX. On days 4 and 21 after HPX, 30 male and 30 female rats from each diet group were anesthetized for in vivo study and then were euthanized for tissue collection. For the in vivo study, arterial and venous blood samples were collected from the liver. LA-, glucose-, and O₂ -uptake, and lactate- and CO₂ -output were significantly higher in LA-replete rats as compared with LA-deficient rats. After a 70% HPX, the remaining liver mass in control and EFAD+LA groups had doubled at day 4, reaching 60% of the original total weight, and had regenerated completely at day 21. However, no regeneration occurred in the EFAD group. At day 4 the portions of livers removed from the control and EFAD+LA groups had significantly higher content of LA, protein, cAMP, and DNA as compared with their livers on day 21. [³ H]thymidine incorporation into liver DNA was significantly higher in the 2 LA-replete groups, with male values greater than female values, as compared with LA-deficient group. These data indicate that liver regeneration after HPX is dependent on dietary LA. Understanding the mechanisms of LA-dependent liver regeneration in rats supports our current efforts to enhance successful surgical resection therapies in humans.

The vector-borne protozoal parasite Trypanosoma cruzi causes Chagas disease in humans and animals. This parasite is endemic to the southern United States where outdoor-housed NHP at biomedical facilities are at risk of infection. In addi- tion to the direct morbidity caused by T. cruzi, infected animals are of limited biomedical research use because infections can produce confounding pathophysiologic changes even in animals with no clinical disease. In part due to concerns for direct T. cruzi transmission between animals, infected NHP at some institutions have been culled, removed, or otherwise isolated from uninfected animal populations. However, data that document horizontal or vertical transmission in captive NHP in the United States are not available. To evaluate the potential for inter-animal transmission and to identify environmental factors that affect the distribution of new infections in NHPs, we conducted a retrospective epidemiologic study of a rhesus macaque ( Macaca mulatta ) breeding colony in south Texas. We used archived biologic samples and husbandry records to identify the time and location of macaque seroconversion. These data were used to perform a spatial analysis of how geographic location and animal associations affected the spread of disease and to infer the importance of horizontal or vertical routes of transmission. The majority of T. cruzi infections were spatially clustered, suggesting that environmental factors promoted vector exposure in various areas of the facility. Although we cannot not rule out horizontal transmission, our data suggest that horizontal transmission was not a critical route for spread for the disease. Vertical transmission was not a contributing factor in this colony. In conclusion, our findings suggest that local triatome vectors were the major source of T. cruzi infections in captive macaques in our colony. Therefore, limiting contact with vectors, rather than segregation of infected macaques, is a key strategy for disease prevention at institutions that house macaques outdoors in the southern United States.

Our goal in this manuscript is to advance the assessment and treatment of monkey species in neuroscience research. We hope to begin a discussion and establish baseline data on how complications are identified and treated. We surveyed the neuroscience research community working with monkeys and compiled responses to questions about investigator demographics, assessment of animal wellbeing, treatment choices, and approaches to mitigate risks associated with CNS procedures and promote monkey health and wellbeing. The majority of the respondents had worked with nonhuman primates (NHP) for over 15 y. Identification of procedure-related complications and efficacy of treatment generally rely on common behavioral indices. Treatments for localized inflammatory responses are generally successful, whereas the treatment success for meningitis or meningoencephalitis, abscesses, and hemorrhagic stroke are less successful. Behavioral signs of pain are treated successfully with NSAIDs and opioids. Our future plans are to collate treatment protocols and develop best practices that can be shared across the neuroscience community to improve treatment success rates and animal welfare and therefore science. Human protocols can be used to develop best practices, assess outcomes, and promote further refinements in treatment practices for monkeys to enhance research outcomes.