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  • 1.

    【2hr】Rabbit Models for Studying Human Infectious Diseases

    包量

    机译 研究人类传染病的兔子模型
    摘要：Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia–lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described.
  • 2.

    【2hr】Temporal Evolution of MRI Characteristics in Dogs with Collagenase-Induced Intracerebral Hemorrhage

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    机译 胶原酶诱导的脑出血狗的MRI特征的时间演变
    摘要：Intracerebral hemorrhage (ICH) is one of the most lethal types of stroke. Neuroimaging techniques, particularly MRI, have improved the diagnostic accuracy of ICH. The MRI characteristics of the evolving stages of ICH in humans—but not those in dogs—have been described. In this study, we document the temporal MRI characteristics in a canine model of collagenase-induced ICH. Specifically, ICH was induced in 5 healthy beagles by injecting 500 U of bacterial collagenase from Clostridium histolyticum, which was delivered into the parietal lobe over 5 min by using a microinfusion pump. T1- and T2-weighted, fluid-attenuated inversion recovery, gradient-echo (GRE), and diffusion-weighted (DWI) imaging and measurement of the apparent diffusion coefficient (ADC) were performed serially at 6 different time points (before and 12 h, 3 d, 5 d, 10 d and 24 d after hemorrhage) by using a 3-T MR system. The temporal changes of T1 signal intensity (SI) corresponded well with the reported human data. The temporal changes of T2 and GRE sequences, with the exception of T2 and GRE hyperintensities at the early subacute stage, also matched. ADC measurements were high at the early subacute stage, and DWI-SI positively correlated with T2- and GRE-SI from the early subacute stage onward. In conclusion, MRI is an ideal method for characterizing the temporal evolution of parenchymal alterations after ICH in dogs. These data might be useful for differentiating clinical stages of ICH in dogs.
  • 3.

    【2hr】Multispecies Epidemiologic Surveillance Study after an Outbreak of Yersiniosis at an African Green Monkey Research Facility

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    机译 非洲绿猴研究设施耶尔森病爆发后的多物种流行病学监测研究
    摘要：After an outbreak of Yersinia enterocolitica at a NHP research facility, we performed a multispecies investigation of the prevalence of Yersinia spp. in various mammals that resided or foraged on the grounds of the facility, to better understand the epizootiology of yersiniosis. Blood samples and fecal and rectal swabs were obtained from 105 captive African green monkeys (AGM), 12 feral cats, 2 dogs, 20 mice, 12 rats, and 3 mongooses. Total DNA extracted from swab suspensions served as template for the detection of Y. enterocolitica DNA by real-time PCR. Neither Y. enterocolitica organisms nor their DNA were detected from any of these samples. However, Western blotting revealed the presence of Yersinia antibodies in plasma. The AGM samples revealed a seroprevalence of 91% for Yersinia spp. and of 61% for Y. enterocolitica specifically. The AGM that were housed in cages where at least one fatality occurred during the outbreak (clinical group) had similar seroprevalence to that of AGM housed in unaffected cages (nonclinical group). However, the nonclinical group was older than the clinical group. In addition, 25%, 100%, 33%, 10%, and 10% of the sampled local cats, dogs, mongooses, rats, and mice, respectively, were seropositive. The high seroprevalence after this outbreak suggests that Y. enterocolitica was transmitted effectively through the captive AGM population and that age was an important risk factor for disease. Knowledge regarding local environmental sources of Y. enterocolitica and the possible role of wildlife in the maintenance of yersiniosis is necessary to prevent and manage this disease.
  • 4.

    【2hr】Mural Dissections of Brain-Supplying Arteries in a Chimpanzee (Pan troglodytes)

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    机译 黑猩猩（潘氏穴居人）的大脑供血动脉壁画解剖。
    摘要：We describe the pathologic features of mural arterial dissection involving brain-supplying arteries in a 31-y-old female chimpanzee (Pan troglodytes). Several hours after examination for a possible respiratory tract infection, the chimpanzee became unresponsive, developed seizures, and died within 18 h. At necropsy, the occipital cortex of the brain had a small area of congestion, and the cerebellar cortex contained a small necrotic area. Histologic evaluation confirmed the cortical lesions and revealed an additional necrotic area in the medulla oblongata characterized by mural dissection of the brain-supplying vertebral and basilar arteries and subsequent branches. Lesions in the cortices and medulla were within areas supplied by the vertebrobasilar system. Dissection of brain-supplying arteries has been described in humans but not previously in chimpanzees (or any other NHP), suggesting that these species might be useful in understanding this condition in humans. In addition, the lesion should be added to the NHP clinician's and pathologist's differential diagnosis list for similar presentations in this species.
  • 5.

    【2hr】Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis)

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    机译 食蟹猕猴（Macaca fascicularis）的阴道结石
    摘要：A 20-y-old female cynomolgus macaque (Macaca fascicularis) housed in an indoor primate facility presented for poor appetite and acute weakness after several years of no adverse health events. Physical examination revealed a firm, ovoid mass in the caudal abdomen. Further evaluation revealed the mass to be a vaginal calculus composed of calcium carbonate, apatite, and struvite. To our knowledge, this case is the first reported description of a vaginal stone in an NHP.
  • 6.

    【2hr】Abstracts of Scientific Papers: AISAL Symposium Naples

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    机译 科学论文摘要：AISAL研讨会那不勒斯
    • 作者：
    • 刊名：Comparative Medicine
    • 2015年第6期
    摘要：
  • 7.

    【2hr】2015 Scientific Reviewers

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    机译 2015年科学评论家
    • 作者：
    • 刊名：Comparative Medicine
    • 2015年第6期
    摘要：
  • 8.

    【2hr】Erratum

    包量

    机译 勘误表
    • 作者：
    • 刊名：Comparative Medicine
    • 2015年第6期
    摘要：
  • 9.

    【2hr】Murine Norovirus Infection Variably Alters Atherosclerosis in Mice Lacking Apolipoprotein E

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    机译 鼠诺如病毒感染可改变缺乏载脂蛋白E的小鼠的动脉粥样硬化
    摘要：Macrophages play a key role in the development of atherosclerosis. Murine noroviruses (MNV) are highly prevalent in research mouse colonies and infect macrophages and dendritic cells. Our laboratory found that MNV4 infection in mice lacking the LDL receptor alters the development of atherosclerosis, potentially confounding research outcomes. Therefore, we investigated whether MNV4 likewise altered atherosclerosis in ApoE−/− mice. In the presence of oxidized LDL, MNV4 infection of ApoE−/− bone marrow-derived macrophages increased the gene expression of the inflammatory markers inducible nitric oxide synthase, monocyte chemoattractant protein 1, and IL6. In addition, proteins involved in cholesterol transport were altered in MNV4-infected ApoE−/− bone marrow-derived macrophages and consisted of increased CD36 and decreased ATP-binding cassette transporter A1. MNV4 infection of ApoE−/− mice at 12 wk of age (during the development of atherosclerosis) had a variable effect on atherosclerotic lesion size. In one study, MNV4 significantly increased atherosclerotic plaque area whereas in a second study, no effect was observed. Compared with controls, MNV4-infected mice had higher circulating Ly6C-positive monocytes, and viral RNA was detected in the aortas of some mice, suggesting potential mechanisms by which MNV4 alters disease progression. Plaque size did not differ when ApoE−/− mice were infected at 4 wk of age (early during disease development) or in ApoE−/− mice maintained on a high-fat, high-cholesterol diet. Therefore, these data show that MNV4 has the potential to exert a variable and unpredictable effect on atherosclerosis in ApoE−/− mice. We therefore propose that performing experiments in MNV-free mouse colonies is warranted.
  • 10.

    【2hr】Evaluation of Nonalcoholic Fatty Liver Disease in C57BL/6J Mice by Using MRI and Histopathologic Analyses

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    机译 MRI和组织病理学分析评估C57BL / 6J小鼠非酒精性脂肪性肝病
    摘要：Nonalcoholic fatty liver disease (NAFLD) can lead to cirrhosis, hepatocellular carcinoma, and ultimately death. Magnetic resonance techniques are accurate, noninvasive methods for evaluating hepatic steatosis but, in animals, have not been fully validated against histologic findings. We sought to validate the MRI fat-signal fraction (MRI–FSF) used for diagnosing NAFLD in human nonclinical trials by comparing MRI data with histopathologic findings in C57BL/6J mice (n= 24) fed normal chow (controls) or a methionine- and choline-deficient (MCD) diet to induce NAFLD. Axial T2-weighted fast spin-echo images were used to examine the entire liver. For histopathologic analyses, liver slides were evaluated for hepatic steatosis according to the NAFLD activity score. Pearson correlation coefficient and receiver operating characteristics analyses were performed. According to the fat-fraction signal, the mean percentage of liver fat in mice with induced NAFLD was 57%, which correlated with the histologically determined steatosis grade. The proton-density fat fraction effectively distinguished severe from mild hepatic steatosis, with an AUC of 0.92. Evaluation accuracy decreased when lobular inflammation and hepatocellular ballooning were considered. This study showed strong concurrence between MRI–FSF and histopathologic steatosis in a murine model of NAFLD. MRI–FSF had moderate sensitivity and specificity in this context. These results confirm that the MRI is a useful biomarker of hepatic steatosis in NAFLD in murine model.
  • 11.

    【2hr】Cutaneous Epitheliotropic T-Cell Lymphoma in a Marsh Rice Rat (Oryzomys palustris)

    包量

    机译 沼泽水稻大鼠（Oryzomys palustris）的皮肤上皮性T细胞淋巴瘤
    摘要：Published reports of spontaneous neoplasia in marsh rice rats (Oryzomys palustris) are sparse. We report here a case of cutaneous epitheliotropic T-cell lymphoma in a 14-mo-old marsh rice rat that involved the ear pinnae, with dissemination to the liver and spleen. Histologically, the thickened ear pinnae showed diffuse infiltration of neoplastic lymphocytes into the epidermis, dermis, and adnexal skin structures, with Pautrier microaggregations present in the epidermis. In addition, neoplastic lymphocytes were observed infiltrating and disrupting the architecture of the liver and spleen. Neoplastic lymphocytes were strongly positive for the T-cell marker CD3 but were negative for the B-cell markers CD19 and CD20. These histologic and immunohistochemical features are consistent with an epitheliotropic T-cell lymphoma, as previously reported in other species, including humans. To our knowledge, this report represents the first published case of spontaneous cutaneous epitheliotropic T-cell lymphoma in a marsh rice rat.
  • 12.

    【2hr】Diffuse Infiltrative Gastrointestinal Lipomatosis in a Guinea Pig (Cavia porcellus)

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    机译 豚鼠（Cavia porcellus）的弥漫性浸润性胃肠道脂肪瘤病
    摘要：An intact adult male guinea pig (Cavia porcellus) went into cardiopulmonary arrest during a surgical procedure, and efforts at resuscitation were unsuccessful. Gross examination revealed a gastric rupture along the greater curvature of the stomach, which was associated with free blood and ingesta in the abdominal cavity, and a 2-cm nodular, partially circumferential, soft-to-firm mass within the pyloric region. Histologically, the pyloric mass was composed of sheets of infiltrative adipocytes expanding the muscular wall. Similar infiltrative sheets of adipocytes were present adjacent to the rupture site and within the small intestine, cecum, and colon. These findings are consistent with diffuse infiltrative lipomatosis, an exceedingly rare condition in human and veterinary species. This report is the first description of this rare disease in guinea pigs, and the concurrent involvement of both the stomach and intestines has not been reported in any veterinary species.
  • 13.

    【2hr】Delayed and Aberrant Presentation of VX2 Carcinoma in a Rabbit Model of Hepatic Neoplasia

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    机译 VX2癌的延迟和异常呈现在肝肿瘤的兔子模型中。
    摘要：A socially-housed New Zealand white rabbit presented with a large subcutaneous mass on the ventral thorax approximately 11 mo after the intrahepatic delivery of a suspension of VX2 carcinoma cells to induce hepatocellular carcinoma as part of a nanoparticle study. The mass and closely associated axillary lymph node were removed en bloc. Immunohistochemical staining identified the mass as an undifferentiated carcinoma. The rabbit demonstrated no appreciable pathology at the study end point at 16 mo after VX2 inoculation. An additional rabbit from the same VX2 injection cohort was found at necropsy to have an unanticipated intraabdominal mass, also identified as an undifferentiated carcinoma. This case report summarizes the molecular analysis of both tumors through a novel PCR assay, which identified the delayed and aberrant onset of VX2 carcinoma in an extended timeframe not previously reported.
  • 14.

    【2hr】An Effective and Reproducible Model of Ventricular Fibrillation in Crossbred Yorkshire Swine (Sus scrofa) for Use in Physiologic Research

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    机译 一种有效且可复制的杂交约克夏猪（Sus scrofa）心室颤动模型，用于生理研究
    摘要：Transcutaneous electrical induction (TCEI) has been used to induce ventricular fibrillation (VF) in laboratory swine for physiologic and resuscitation research. Many studies do not describe the method of TCEI in detail, thus making replication by future investigators difficult. Here we describe a detailed method of electrically inducing VF that was used successfully in a prospective, experimental resuscitation study. Specifically, an electrical current was passed through the heart to induce VF in crossbred Yorkshire swine (n = 30); the current was generated by using two 22-gauge spinal needles, with one placed above and one below the heart, and three 9V batteries connected in series. VF developed in 28 of the 30 pigs (93%) within 10 s of beginning the procedure. In the remaining 2 swine, VF was induced successfully after medial redirection of the superior parasternal needle. The TCEI method is simple, reproducible, and cost-effective. TCEI may be especially valuable to researchers with limited access to funding, sophisticated equipment, or colleagues experienced in interventional cardiology techniques. The TCEI method might be most appropriate for pharmacologic studies requiring VF, VF resulting from the R-on-T phenomenon (as in prolonged QT syndrome), and VF arising from other ectopic or reentrant causes. However, the TCEI method does not accurately model the most common cause of VF, acute coronary occlusive disease. Researchers must consider the limitations of TCEI that may affect internal and external validity of collected data, when designing experiments using this model of VF.
  • 15.

    【2hr】Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP

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    机译 NHP减毒麻疹疫苗的多中心安全性和免疫原性试验
    摘要：Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston–Zagreb strain virus that had been attenuated after 22 passages on human diploid cells.
  • 16.

    【2hr】Effects of the Dietary ω3:ω6 Fatty Acid Ratio on Body Fat and Inflammation in Zebrafish (Daniorerio)

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    机译 饮食中ω3：ω6脂肪酸比对斑马鱼体内脂肪和炎症的影响rerio）
    摘要：The diets of populations in industrialized nations have shifted to dramatically increased consumption of ω6 polyunsaturated fatty acids (PUFA), with a corresponding decrease in the consumption of ω3 PUFA. This dietary shift may be related to observed increases in obesity, chronic inflammation, and comorbidities in the human population. We examined the effects of ω3:ω6 fatty acid ratios in the context of constant total dietary lipid on the growth, total body fat, and responses of key inflammatory markers in adult zebrafish (Danio rerio). Zebrafish were fed diets in which the ω3:ω6 PUFA ratios were representative of those in a purported ancestral diet (1:2) and more contemporary Western diets (1:5 and 1:8). After 5 mo, weight gain (fat free mass) of zebrafish was highest for those that received the 1:8 ratio treatment, but total body fat was lowest at this ratio. Measured by quantitative real-time RT–PCR, mRNA levels from liver samples of 3 chronic inflammatory response genes (C-reactive protein, serum amyloid A, and vitellogenin) were lowest at the 1:8 ratio. These data provide evidence of the ability to alter zebrafish growth and body composition through the quality of dietary lipid and support the application of this model to investigations of human health and disease related to fat metabolism.
  • 17.

    【2hr】Electrocardiographic Characterization of Cardiac Hypertrophy in Mice that Overexpress the ErbB2 Receptor Tyrosine Kinase

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    机译 心电图表征的心肌肥大的小鼠过表达ErbB2受体酪氨酸激酶。
    摘要：Electrocardiography is an important method for evaluation and risk stratification of patients with cardiac hypertrophy. We hypothesized that the recently developed transgenic mouse model of cardiac hypertrophy (ErbB2tg) will display distinct ECG features, enabling WT (wild type) mice to be distinguished from transgenic mice without using conventional PCR genotyping. We evaluated more than 2000 mice and developed specific criteria for genotype determination by using cageside ECG, during which unanesthetized mice were manually restrained for less than 1 min. Compared with those from WT counterparts, the ECG recordings of ErbB2tg mice were characterized by higher P- and R-wave amplitudes, broader QRS complexes, inverted T waves, and ST interval depression. Pearson's correlation matrix analysis of combined WT and ErbB2tg data revealed significant correlation between heart weight and the ECG parameters of QT interval (corrected for heart rate), QRS interval, ST height, R amplitude, P amplitude, and PR interval. In addition, the left ventricular posterior wall thickness as determined by echocardiography correlated with ECG-determined ST height, R amplitude, QRS interval; echocardiographic left ventricular mass correlated with ECG-determined ST height and PR interval. In summary, we have determined phenotypic ECG criteria to differentiate ErbB2tg from WT genotypes in 98.8% of mice. This inexpensive and time-efficient ECG-based phenotypic method might be applied to differentiate between genotypes in other rodent models of cardiac hypertrophy. Furthermore, with appropriate modifications, this method might be translated for use in other species.
  • 18.

    【2hr】Effect of Chronic Uremia on the Cell Surface Expression of B7 Family Costimulatory Molecules in an HLA-A2 Transgenic Mouse Model of Chronic Kidney Disease

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    机译 慢性尿毒症对慢性肾脏病HLA-A2转基因小鼠模型中B7族共刺激分子细胞表面表达的影响
    摘要：Uremia due to chronic kidney disease (CKD) in humans is associated with immune dysfunction, increased susceptibility to infections, immune-activation–associated inflammation, and poor responses to vaccines. The pathophysiologic basis of these immune defects is hypothesized to be associated with a wide range of immunologic abnormalities, including an inability to sufficiently express the B7 family (B7-1, CD80; B7-2, CD86) of T-cell costimulatory molecules. However, testing the hypothesis that a state of chronic uremia contributes to attenuated expression of CD80 or CD86 has been difficult because few animal models faithfully recapitulate the immune defects observed in human CKD patients. We used a humanized mouse in a model of surgically induced renal failure and secondary chronic uremia to evaluate the effect of uremia on the expression of these markers. In a manner that resembles the changes observed in CKD patients, surgically induced CKD in mice resulted in decreased costimulatory CD86 expression compared with that in sham-operated controls. Immunodeficiency was functionally demonstrated in this mouse model by documenting an attenuated immune response to a cholera-toxin–based hepatitis B vaccine. This model will be useful for investigating the mechanisms involved in chronic uremia-associated immunodeficiency, poor response to vaccination, and problems associated with immunization of CKD patients.
  • 19.

    【2hr】Age- and Sex-Associated Effects on Acute-Phase Proteins in Göttingen Minipigs

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    机译 哥廷根小型猪急性期蛋白的年龄和性别相关影响
    摘要：Göttingen minipigs are a useful model for diseases having an inflammatory component, and the associated use of acute-phase proteins (APP) as biomarkers of inflammation warrants establishment of their reference ranges. The objective of this study was to establish reference values for selected APP in Göttingen minipigs and to investigate the effects of age, sex, and various stimuli on these ranges. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, pig major acute-phase protein (PMAP), albumin, and porcine α-1 acid glycoprotein (PAGP) were evaluated in 4 age groups (6, 16, 24 and 40–48 wk) of male and female Göttingen minipigs. In addition, minipigs were tested under 2 housing conditions, after acute LPS challenge, and after diet-induced obesity with and without mild diabetes. Changing the pigs to a new environment induced significant increases in CRP, PMAP, haptoglobin and PAGP and a decrease in albumin. An acute LPS stimulus increased CRP, PMAP, haptoglobin, and SAA; PAGP was unchanged and albumin decreased. Obese pigs with and without diabetes showed increases in CRP and PAGP, albumin decreased, and haptoglobin and SAA were unchanged. PMAP was increased only in obese pigs without diabetes. In conclusion, reference values for CRP, PMAP, haptoglobin, SAA, PAGP and albumin were established for male and female Göttingen minipigs of different ages. These APP were influenced by age and sex, underlining the importance of considering these factors when designing and interpreting studies including aspects of inflammation. In addition, an APP response was verified after both acute and chronic stimuli.
  • 20.

    【2hr】Diffraction-Enhanced Computed Tomographic Imaging of Growing Piglet Joints by Using a Synchrotron Light Source

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    机译 同步加速器光源对生长中的小猪关节的衍射增强计算机断层扫描成像
    摘要：The objective of this project was to develop and test a new technology for imaging growing joints by means of diffraction-enhanced imaging (DEI) combined with CT and using a synchrotron radiation source. DEI–CT images of an explanted 4-wk-old piglet stifle joint were acquired by using a 40-keV beam. The series of scanned slices was later ‘stitched’ together, forming a 3D dataset. High-resolution DEI-CT images demonstrated fine detail within all joint structures and tissues. Striking detail of vasculature traversing between bone and cartilage, a characteristic of growing but not mature joints, was demonstrated. This report documents for the first time that DEI combined with CT and a synchrotron radiation source can generate more detailed images of intact, growing joints than can currently available conventional imaging modalities.
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