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  • 机译 恒河猴(Macaca mulatta)中包含子宫和双侧附件的不可复位腹股沟疝
    摘要:Inguinal herniation of abdominal viscera is a relatively common condition in both humans and domestic animal species. In captive rhesus macaques (Macaca mulatta), the highest incidence occurs in overweight, aged males. However, inguinal herniation of the uterus with bilateral adnexa is extremely rare in both human and veterinary medicine. Here we report a previously undescribed uterine inguinal herniation with bilateral adnexa in a 3-y-old female rhesus macaque. Although uterine herniation remains a rare condition in rhesus macaques, it should be considered as a differential diagnosis in animals with unilateral subcutaneous enlargements in the inguinal region.
  • 机译 2017年审稿人审稿人
    • 作者:
    • 刊名:Comparative Medicine
    • 2017年第6期
    摘要:
  • 机译 AALAS关于人道关怀和使用实验动物的立场声明
    • 作者:
    • 刊名:Comparative Medicine
    • 2017年第6期
    摘要:
  • 机译 早期肠道粘膜损害对NOD小鼠疾病进展的影响
    摘要:Disease expression in spontaneous nonobese diabetic (NOD) mice depends on environmental stimuli such as stress, diet, and gut microbiota composition. We evaluated a brief, early-life gut intervention in which pups were weaned to low-dose dextran sulfate sodium (DSS). We hypothesized that the mucus-reducing effect of this compound and subsequent increased host–bacterial contact would delay disease onset and decrease insulitis due to enhanced oral tolerance. However, disease incidence did not differ between groups, although median survival (time point when 50% of the mice are still alive) of the control group was 184 d compared with 205 d for DSS-treated mice. Mean age at disease onset (that is, blood glucose of at least 12 mmol/L) was 164 d for control mice and 159 d for DSS-treated mice. In addition, 62.5% of control mice reached a blood glucose of 12 mmol/L before 30 wk of age compared with 59% in DSS-treated mice, which had a significant transient increase in serum insulin in week 4. No changes were found in immune cells collected from spleen, pancreatic lymph nodes, and mesenteric lymph nodes. Although mice received a low dose of DSS, the subsequent reduction in the diversity of the microbiota during weeks 4 through 6 led to increased cecal length and weight and, in week 13, a tendency toward decreased colon length, with increased leakage of LPS to the blood. We conclude that mucus reduction and subsequent increased host–bacterial contact did not affect overall disease progression in NOD mice.
  • 机译 鼠星状病毒感染对NLRP3缺陷小鼠硫酸葡聚糖诱导的结肠炎的影响不足
    摘要:Murine astrovirus (MuAstV) is a recently identified, widespread infection among laboratory mice. MuAstV is found predominantly in the gastrointestinal tract of mice. Human and turkey astroviruses have been shown to disrupt tight junctions in the intestinal epithelium. The potential of MuAstV to alter research results was tested in a well-established dextran sodium sulfate (DSS)-induced colitis model in Nod-like receptor 3 (NLRP3)-deficient mice. This model offers a direct approach to determine whether MuAstV, as a component of the mouse microbiome, contributes to the issue of poor reproducibility in murine inflammatory bowel disease research. In this model, defective inflammasome activation causes loss of epithelial integrity, resulting in leakage of intestinal bacteria and colitis. Our goal was to determine whether MuAstV, which also may affect intestinal permeability, altered the onset or severity of colitis. Male and female mice (age, 8 to 12 wk) homozygous or heterozygous for an NLRP3 mutation were inoculated orally with MuAstV or mock-inoculated with media 3 or 20 d prior to being exposed to 2% DSS in their drinking water for 9 d. MuAstV infection alone did not cause clinical signs or histopathologic changes in NLRP3−/− or NLRP3+/– mice. No significant difference was seen in weight loss, clinical disease, intestinal inflammation, edema, hyperplasia, or mucosal ulceration between MuAstV- infected and mock-infected mice that received 2% DSS for 9 d. Therefore, MuAstV does not appear to be a confounding variable in the DSS colitis model in NLRP3 mice.
  • 机译 κB激酶2抑制剂的细胞特异性删除与小鼠皮肤鳞状细胞癌的自发发展。
    摘要:The deletion of NFκB in epithelial tissues by using skin-specific promoters can cause both tumor formation and severe inflammatory dermatitis, indicating that this signaling pathway is important for the maintenance of immune homeostasis in epithelial tissues. In the present study, we crossed mice transgenic for loxP-Ikbk2 and human Gfap-cre to selectively delete IKK2 in CNS astrocytes. Unexpectedly, a subset of mice developed severe and progressive skin lesions marked by hyperplasia, hyperkeratosis, dysplasia, inflammation, and neoplasia with a subset of lesions diagnosed as squamous cell carcinoma (SCC). The development of lesions was monitored over a 3.5-y period and over 4 filial generations. Average age of onset of was 4 mo of age with 19.5% of mice affected with frequency increasing in progressive generations. Lesion development appeared to correlate not only with unintended IKK2 deletion in GFAP expressing cells of the epidermis, but also with increased expression of TNF in lesioned skin. The skins changes described in these animals are similar to those in transgenic mice with an epidermis-specific deletion of NFκB and thus represents another genetic mouse model that can be used to study the role of NFκB signaling in regulating the development of SCC.
  • 机译 无乳链球菌在KK-Ay小鼠中引起的自发感染
    摘要:During 2006 through 2012, spontaneous group B Streptococcus infections were reported in 22 female KK-Ay mice, an animal model of type 2 diabetes. The affected mice were 5 to 27 wk old, and the cases involved various body sites, including cases of submandibular, caudal, and lumbar abscesses (n =18) or led to torticollis (n = 2), hydrocephalus (n = 1), or moribund clinical signs (n = 1). At necropsy, the mouse with hydrocephalus also demonstrated retained exudate in the uterus, and the moribund mouse showed renal inflammation. Streptococcus agalactiae was isolated in pure culture from all except 2 cases: the facial abscess also yielded Klebsiella pneumoniae, and the uterine exudate was coinfected with Staphylococcus aureus. In addition, S. agalactiae was isolated from the oral cavity and feces of normal KK-Ay mice. S. agalactiae potentially can cause a clinically significant spontaneous infection in a mouse model of diabetes.
  • 机译 野外捕获的非洲袋鼠(Cricetomys ansorgei)的实验室菌落中的肠道寄生虫和驱虫治疗。
    摘要:African giant pouched rats (Cricetomys spp.) are large rodents native to subSaharan Africa. Wild-caught pouched rats identified as Cricetomys ansorgei (n = 49) were imported from Tanzania. A survey of gastrointestinal parasitism by fecal flotation revealed the presence of multiple parasites, including Nippostrongylus spp., Heterakis spp., Trichuris spp., Hymenolepis spp., Raillietina spp., and Eimeria spp. Oral self-administered fenbendazole (150 ppm), topical moxidectin (2 mg/kg), pyrantel pamoate (15 mg/kg), piperazine (100 mg/kg daily), and injectable ivermectin (0.25 mg/kg) were used to determine effective treatment options for the gastrointestinal parasites present in the colony. Pyrantel pamoate in a treat vehicle and piperazine in water bottles were easily administered and significantly reduced the numbers of animals shedding Nippostrongylus spp. and Heterakis spp. during the study. Moxidectin and ivermectin were clinically ineffective at reducing fecal egg shedding. Fenbendazole was most effective at clearing infection with Trichuris spp. Although 10 mg/kg praziquantel was ineffective, a single dose of 30 mg/kg praziquantel significantly reduced the number of African pouched rats that shed cestode embryos. A combination treatment may be necessary to successfully treat all parasites present in any given animal.
  • 机译 隐匿性侵害的后遗症使未成年在社会上居住的雌性新西兰白兔(Oryctolagus cuniculus)失去参与皮肤毒理学研究的资格
    摘要:International animal welfare organizations and federal, regional, and institutional oversight bodies encourage social housing of gregarious species, such as New Zealand white rabbits (Oryctolagus cuniculus), to promote animal wellbeing in research, teaching, testing and farming settings. At our institution, 2 groups of female New Zealand white rabbits (approximate age, 11 wk; mean weight, 2.35 kg), compatibly paired at the vendor for 5 wk, were paired in caging or group-housed in a floor pen. The rabbits appeared compatible, demonstrating primarily affiliative behaviors throughout 6 wk of daily observations. However, occult aggression that occurred between daily observations or nocturnally resulted in skin wounding. The skin injuries, first identified during prestudy clipping of fur from the back of each rabbit 6 wk after arrival, disqualified every animal from participation in skin toxicology and muscle implantation studies. Success meeting scientific research requirements while promoting animal welfare and health when socially housing New Zealand white rabbits requires examining the behavioral repertoire of their wild counterparts, European rabbits. Factors including age, sex, and housing density influence territoriality, dominance hierarchy, social ranking, and natural, agonistic, injurious, behavioral tendencies. IACUC and other relevant oversight bodies, researchers, and animal care staff should consider this case study and the species-specific natural history of New Zealand white rabbits when assessing the harm and benefit of social housing in regard to research utility and animal welfare.
  • 机译 新型H分流静脉旁路用于食蟹猕猴的肝移植
    摘要:Cynomolgus monkeys are often used in preclinical transplantation research. Performing liver transplantation in cynomolgus monkeys is challenging because they poorly tolerate portal vein clamping during the anhepatic phase. Finding an alternative to portal vein clamping is necessary before preclinical liver transplant models can be performed with reliable outcomes. We used 3 different techniques to perform 5 liver transplants in male cynomolgus macaques (weight, 7.4–10.8 kg; mismatched for MHC I and II; matched for ABO). In procedure A, we clamped the portal vein briefly, as in human transplants, as well as the superior mesentery artery to minimize congestion at the expense of temporary ischemia (n = 2). In procedure B, we performed a temporary portocaval shunt with extracorporeal venovenous bypass (n = 1). For procedure C, we developed an H-shunt system (modified portocaval shunt) with extracorporeal bypass (n = 2). Postoperative immunosuppression comprised cyclosporine A, mycophenolate mofetil, and steroids. Recipients in procedure A developed hemodynamic instability and were euthanized within 2 d. The recipient that underwent procedure B was euthanized within 11 d due to inferior vena caval thrombosis. The H-shunt in procedure C led to minimal PV congestion during the anhepatic phase, and both recipients reached the 21-d survival endpoint with good graft function. Our novel H-shunt bypass system resulted in successful liver transplantation in cynomolgus macaques, with long-term posttransplant survival possible. This technical innovation makes possible the use of cynomolgus monkeys for preclinical liver transplant tolerance models.
  • 机译 对非人类灵长类动物进行约束的方法的国际调查
    摘要:Specifically designed restraint chairs are the preferred method of restraint for research studies that require NHP to sit in place for sustained periods of time. In light of increasing emphasis on refinement of restraint to improve animal wellbeing, it is important to have a better understanding of this potentially stressful procedure. Although chair restraint is used internationally, very little published information is available on this subject. We developed a survey to obtain an overview of equipment, procedures, and plans for improvement regarding chair restraint. We received 101 responses from people working in academic, government, contract research, and pharmaceutical laboratories within the Americas, Europe and Asia. Findings indicate that the majority of laboratories using restraint chairs work with macaque species. Restraint chairs are used for a wide range of procedures, including cognitive testing, recording neuronal activity, functional MRI, intravenous infusion, and blood sampling. Approximately 2/3 of laboratories use an enclosed ‘box chair,’ which the animal is trained to enter and then to extend its head through an opening on the top of the chair; the remaining one third of laboratories use an ‘open chair’ design, in which manual handling or the pole-and-collar system is used to transfer and secure the animal into the chair. Respondents reported that when selecting the type of chair to use, they considered comfort for the animal, ease of use, and the ability to adjust fit between animals of different sizes. Various training methods and timeframes are used to prepare macaques for restraint chair procedures. Several laboratories are incorporating greater use of positive reinforcement training. The community that uses these restraint procedures needs to work together to define best practice; our survey results can help in that effort.
  • 机译 室内恒河猴(Macaca mulatta)中的球孢子菌病
    摘要:Coccidioides spp. are saprophytic, dimorphic fungi that are endemic to arid climates, are capable of infecting many species, and result in diverse clinical presentations. An indoor-housed laboratory rhesus macaque presented with weight loss and decreased activity and appetite. During the diagnostic evaluation, a bronchiolar–alveolar pattern in the cranial lung lobes, consistent with bronchopneumonia, was noted on radiographs. Given the poor prognosis, the macaque was euthanized. Confirming the radiographic assessment, gross necropsy findings included multifocal to coalescing areas of consolidation in the right and left cranial lung lobes. Microscopically, the consolidated regions were consistent with a pyogranulomatous bronchopneumonia and contained round, nonbudding, fungal yeast structures considered to be morphologically consistent with Coccidioides immitis. Culture and colony morphology results were confirmed through additional diagnostic testing. Sequencing of the D1–D2 domain of the 28S large ribosomal subunit positively matched with a known sequence specific to C. immitis. Serology for Coccidioides spp. by both latex agglutination (IgM) and immunodiffusion (IgG) was positive. In this rhesus macaque, the concordant results from histology, culture, DNA sequencing, and serology were collectively used to confirm the diagnosis of coccidioidomycosis. This animal likely acquired a latent pulmonary infection with Coccidioides months prior to arrival, when housed outdoors in a Coccidioides-endemic area. The nonspecific clinical presentation in this macaque, coupled with the recent history of indoor housing and lag between clinical presentation and outdoor housing, can make similar diagnostic cases challenging and highlights the need for awareness regarding animal source when making an accurate diagnosis in an institutional laboratory setting.
  • 机译 圈养的小胡子Ta猴的腹部主动脉急性闭塞伴突然截瘫(Saguinus mystax)
    摘要:A wild-caught, research-naïve, adult male mustached tamarin (Saguinus mystax) experienced sudden onset of bilateral hindlimb paresis. Physical examination established the presence of paralysis and the lack of femoral pulses and deep pain in both legs. There were no signs of external trauma and, due to a poor prognosis, euthanasia was elected. Necropsy findings included pleural effusion, partial pulmonary atelectasis and congestion, dilatatory cardiomyopathy, a renal hemorrhagic infarct, and a thromboembolus located at the trifurcation of the distal abdominal aorta. The clinical and histologic findings were indicative of an aortic–iliac thrombosis.
  • 机译 AALAS关于人道关怀和使用实验动物的立场声明
    • 作者:
    • 刊名:Comparative Medicine
    • 2017年第5期
    摘要:
  • 机译 胶质母细胞瘤小鼠原位异种移植模型的优化用于转化研究
    摘要:Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panel of patient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex. Glioblastoma CSC from 4 patients and a glioblastoma nonstem-cell line were then implanted by using the same coordinates for evaluation of tumor location, growth rate, and morphologic and histologic features. Dye injections into one of the defined locations resulted in dye dissemination throughout the ventricles, whereas tumor cell implantation at the same location resulted in a much higher percentage of small multifocal ventricular tumors than did the other 3 locations tested. Ventricular tumors were associated with a lower tumor growth rate, as measured by in vivo bioluminescence imaging, and decreased survival in 4 of 5 cell lines. In addition, tissue oxygenation, vasculature, and the expression of astrocytic markers were altered in ventricular tumors compared with nonventricular tumors. Based on this information, we identified an optimal implantation location that avoided the ventricles and favored cortical tumor growth. To assess the effects of stress from oral drug administration, mice that underwent daily gavage were compared with stress-positive and ‑negative control groups. Oral gavage procedures did not significantly affect the survival of the implanted mice or physiologic measurements of stress. Our findings document the importance of optimization of the implantation site for preclinical mouse models of glioblastoma.
  • 机译 使用微计算机断层扫描技术来测量松弛素诱导的小鼠耻骨内韧带的扩展
    摘要:Relaxin is a 6-kDa peptide in the insulin superfamily of hormones. In addition to its effects on reproductive and musculoskeletal ligaments, relaxin has demonstrated beneficial effects on cardiac, renal, and vascular systems in preclinical models. The mouse intrapubic ligament ex vivo bioassay is the current standard for measuring in vivo relaxin bioactivity. However, this bioassay necessitates euthanasia and dissection of large cohorts to measure the intrapubic ligament at specified time points. We hypothesized that µCT imaging could be used to reduce the number of animals necessary for the intrapubic ligament bioassay by enabling a single animal to be followed longitudinally throughout the study rather than euthanizing different cohorts at established time points. Female CD1 mice were used to compare µCT imaging with the current standard. Both protocols revealed significant differences in intrapubic ligament length, with the µCT data having greater power when corrected for baseline imaging. From these data, we concluded that using µCT to measure the intrapubic ligament in mice primed with estrogen and dosed with relaxin is a viable refinement and will allow the use of fewer animals in longitudinal studies and provide more robust data, because animals can serve as their own controls.
  • 机译 NOD小鼠的肠道菌群的抗生素相关操作和表型恢复。
    摘要:Segmented filamentous bacterium (SFB) a gram-positive, anaerobic, and intestinal commensal organism directly influences the development of Th17 helper cells in the small intestine of mice. In NOD mice, SFB colonization interferes with the development of type 1 diabetes (T1D), a T-cell–mediated autoimmune disease, suggesting that SFB may influence Th17 cells to inhibit Th1 populations associated with the anti-β-cell immune response. This effect is a serious concern for investigators who use NOD mice for diabetes research because the expected incidence of disease decreases markedly when they are colonized by SFB. A room housing mice for T1D studies at The Jackson Laboratory was determined by fecal PCR testing to have widespread SFB colonization of multiple NOD strains after a steady decline in the incidence of T1D was noted. Rederivation of all NOD-related mouse strains was not feasible; therefore an alternative treatment using antibiotics to eliminate SFB from colonized mice was undertaken. After antibiotic treatment, soiled bedding from NOD mouse strains housed in SFB-free high-health–status production barrier rooms was used to reintroduce the gastrointestinal microbiota. Over the past 16 mo since treating the mice and disinfecting the mouse room, regular PCR testing has shown that no additional SFB colonization of mice has occurred, and the expected incidence of T1D has been reestablished in the offspring of treated mice.
  • 机译 Rag – / – Tpl2-/ –小鼠自发性葡萄球菌感染引起的严重皮炎
    摘要:Staphylococcus xylosus is a commensal bacterium found on the skin and mucosal surfaces of SPF mice. S. xylosus is rarely pathogenic, most often causing skin lesions and dermatitis in immunocompromised mice, particularly those with impaired NADPH oxidase function. Here we report spontaneous infection with S. xylosus in Rag1−/−Tpl2−/− mice. Infection was characterized by the presence of alopecia, crusts, and scaly skin. S. xylosus was detected in the feces, skin, lymph nodes, and lungs of Rag1−/−Tpl2−/− mice and led to mortality or euthanasia due to humane endpoints. C57BL/6 mice were culture-positive for S. xylosus on the skin, and Rag1−/− and Tpl2−/− mice were culture-positive on the skin and occasionally in the feces. However, S. xylosus did not cause clinical symptoms in C57BL/6, Rag1−/−, or Tpl2−/− mice. Compared with those in Rag1−/− mice, relative concentrations of circulating monocytes, but not neutrophils or lymphocytes, were increased in Rag1−/−Tpl2−/− mice, consistent with their increased incidence of clinical symptoms. Overall, this case study suggests a novel role for Tpl2 in T-cell–independent host resistance to the otherwise commensal organism S. xylosus.
  • 机译 非动脉粥样硬化性猪冠状动脉球囊过度伸展和支架过度扩张之间的血管反应差异
    摘要:Which preclinical models are best suited for restenosis research remains uncertain. Here we compared the restenotic responses after balloon or stent overstretch injury in a porcine coronary artery. A total of 30 coronary lesions in 5 pigs were treated by balloon overdilatation or oversized stent implantation at various balloon-to-artery (B:A) ratios. Four weeks later, the lesions were examined in vivo by using coronary angiography, intravascular ultrasound, and optical coherence tomography (OCT). At follow-up, the lumen area stenosis and plaque burden at the minimal lumen area site were greater in stented sites than in balloon injury site (lumen area stenosis, 21.7 ± 8.9% compared with 32.8 ± 12.1%; plaque burden, 30.1% ± 10.1% compared with 44.7% ± 10.1%, respectively). The remodeling index was significantly smaller for the balloon-injury group than the stent group (0.86 ± 0.11 compared with 1.00 ± 0.04). Only the stent group that was dilated at a high B:A ratio resulted in increased plaque burden. In the balloon-injury sites, high B:A ratios were significantly associated with greater negative remodeling. Tissue morphology assessment by OCT revealed that the predominant pattern in balloon injury sites was homogeneous, whereas that in stented sites was a layered to heterogeneous pattern. Neointimal proliferation was significantly greater after oversized stenting than after balloon overstretch injury. Together these findings suggest that stent overexpansion of porcine coronary arteries might be appropriate for researching restenosis than is the balloon overstretch injury model.
  • 机译 消除食蟹猕猴(Macaca fascicularis)中耐甲氧西林金黄色葡萄球菌的简单方法
    摘要:Our investigation of indoor-housed cynomolgus macaques (Macaca fascicularis) by using automated identification followed by antibiotic susceptibility testing revealed 1 of 7 immunocompetent animals and 2 of 9 immunosuppressed monkeys as carriers of methicillin–resistant Staphylococcus aureus (MRSA). Follow-up management involving mupirocin treatment resulted in the conversion of the 3 MRSA carriers into MRSA-negative cases. Prospective assessment of newly imported monkeys involving 24-h culture of nasal swabs on chromogenic agar revealed that 22% (18 of 82 animals) were MRSA-positive. Mupirocin treatment successfully converted all of the MRSA-positive macaques into non-carriers, suggesting the feasibility of this simple, one-step screening procedure for rapidly identifying MRSA carriers in large cohorts. In addition, 8 animals that had been diagnosed MRSA-positive and subsequently treated with mupirocin demonstrated no recolonization during follow-up, even under immunosuppressive conditions. We propose rapid screening using chromogenic agar followed by mupirocin treatment as a time- and cost-effective regimen for managing MRSA in cynomolgus monkeys.

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