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  • 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
    • 2018年第2期
    摘要:
  • 机译 比较医学推出新的封面概念
    • 作者:Linda Toth
    • 刊名:Comparative Medicine
    • 2018年第1期
    摘要:
  • 机译 野生型和重组人T细胞白血病病毒在人源化NSG小鼠淋巴增生性疾病中的作用
    摘要:Chronic infection with human T-cell leukemia virus type 1 (HTLV1) can lead to adult T-cell leukemia (ATL). In contrast, infection with HTLV2 does not lead to leukemia, potentially because of distinct virus–host interactions and an active immune response that controls virus replication and, therefore, leukemia development. We created a humanized mouse model by injecting human umbilical-cord stem cells into the livers of immunodeficient neonatal NSG mice, resulting in the development of human lymphocytes that cannot mount an adaptive immune response. We used these mice to compare the ability of molecular clones of HTLV1, HTLV2, and select recombinant viruses to induce leukemia–lymphoma in vivo. Infection with HTLV1 strongly stimulated the proliferation of CD4+ T cells, whereas HTLV2 preferentially stimulated the proliferation of CD8+ T cells; both HTLV1 and HTLV2 induced lymphoproliferative disease. Uninfected and HTLV-infected humanized mice both showed granulomatous inflammation as a background lesion. Similarly, recombinant viruses that expressed the HTLV1 envelope protein (Env) on an HTLV2 background (HTLV2–Env1) or Env2 on an HTLV1 background (HTLV1–Env2) induced lymphoproliferative disease. HTLV2–Env1 stimulated the proliferation of CD4+ T cells, whereas HTLV1–Env2 stimulated both CD4+ and CD8+ T-cell subsets. Our results show that T-cell transformation in vivo is guided by the Env protein of the virus. Furthermore, our humanized mouse model is useful for exploring the preferred T-cell tropisms of HTLV1 and HTLV2.
  • 机译 淋巴细胞对小鼠胰岛素抵抗和肥胖发展影响的菌株特异性差异
    摘要:Obesity is characterized as a chronic, low-grade inflammatory disease owing to the infiltration of the adipose tissue by macrophages. Although the role of macrophages in this process is well established, the role of lymphocytes in the development of obesity and metabolism remains less well defined. In the current study, we fed WT and Rag1−/− male mice, of C57BL/6J and BALB/c backgrounds, high-fat diet (HFD) or normal diet for 15 wk. Compared with WT mice, Rag1−/− mice of either of the examined strains were found less prone to insulin resistance after HFD, had higher metabolic rates, and used lipids more efficiently, as shown by the increased expression of genes related to fatty acid oxidation in epidydimal white adipose tissue. Furthermore, Rag1−/− mice had increased Ucp1 protein expression and associated phenotypic characteristics indicative of beige adipose tissue in subcutaneous white adipose tissue and increased Ucp1 expression in brown adipose tissue. As with inflammatory and other physiologic responses previously reported, the responses of mice to HFD show strain-specific differences, with increased susceptibility of C57BL/6J as compared with BALB/c strain. Our findings unmask a crucial role for lymphocytes in the development of obesity and insulin resistance, in that lymphocytes inhibit efficient dissipation of energy by adipose tissue. These strain-associated differences highlight important metabolic factors that should be accommodated in disease modeling and drug testing.
  • 机译 草甸跳鼠(Zapus hudsonius)皮肤性皮肤病
    摘要:A laboratory-housed, wild-caught, subadult, male meadow jumping mouse (Zapus hudsonius) presented with extensive scaling of the face, limbs, and tail and severe edema of the paws. Postmortem examination revealed marked distal limb edema with focal digital hematomas and white scales, scabs, and crusts affecting the majority of nonhaired skin. Histopathologic analysis revealed severe, multifocal, chronic-active exudative and proliferative dermatitis characterized by multilaminated crusts covering the epidermis. The epidermis was expanded by hyperkeratosis, acanthosis, and hyperplasia. The superficial dermis contained moderate edema, hemorrhage, and pigmentary incontinence, and was infiltrated by granulocytes and mononuclear cells. The laminated crusts contained numerous branching filaments of gram-positive coccoid bodies arranged in parallel rows, consistent with cutaneous Dermatophilus congolensis infection. This diagnosis was confirmed through bacterial culture and 16S rRNA PCR analysis. In the presented case, factors that might have contributed to disease progression include climatic conditions at the capture site and stress associated with trapping and laboratory housing.
  • 机译 棉花大鼠(Sigmodon hispidus)嗜酸性粒细胞的特征,包括其对呼吸道合胞病毒感染的反应
    摘要:Eosinophils have been postulated to play a protective role against infection with respiratory syncytial virus (RSV), increase the severity of allergic asthma during respiratory viral infection, and drive vaccine-enhanced disease. To address these questions in the cotton rat model of RSV infection, we characterized cotton rat eosinophils by electron microscopy as well as by bronchoalveolar lavage and histology of lung sections. Using these methods, we demonstrated that eosinophils comprise approximately half of all cells in the bronchoalveolar lavage fluids from cotton rats. The function of these cells was comparable to that of eosinophils of other species. Ex vivo, eosinophils stimulated with calcium ionophores secreted eosinophil peroxidase. In vivo, treatment with house dust mite antigen increased eosinophil numbers in lung. Infection with Staphylococcus aureus lead to a marked increase in neutrophils without an increase in eosinophils, and eosinophil numbers were not influenced by infection with influenza virus or measles virus. Similarly, infection with RSV did not result in an increase in eosinophils. Lastly, RSV infection did not increase eosinophil recruitment into the lung after challenge with house dust mite antigen, but it did increase eosinophil recruitment into the lungs of cotton rats previously immunized with formalin-inactivated RSV vaccine, thus contributing to vaccine-enhanced disease.
  • 机译 用于结核分枝杆菌疫苗研究的豚鼠的人道终点
    摘要:Guinea pigs are a commonly used model for tuberculosis vaccine research. Loss of body weight is the most frequently described humane endpoint for animals used in these studies. During a chronic study, we noted labored breathing in some tuberculosis-infected guinea pigs. To develop consistent humane endpoints for these guinea pigs, we performed an observational study using multiple clinical signs. A combination of body weight loss, labored breathing, and activity level during handling estimated the time to euthanasia within approximately 7 d. Histologic severity scores of lesions in the cranial or caudal lung lobe (or both) supported clinical endpoints. This study presents humane endpoints for the refinement of studies using guinea pigs in tuberculosis research.
  • 机译 食蟹猕猴的创伤性脊髓损伤评价药物治疗的模型
    摘要:Here we present the results of experiments involving cynomolgus macaques, in which a model of traumatic spinal cord injury (TSCI) was created by using a balloon catheter inserted into the epidural space. Prior to the creation of the lesion, we inserted an EMG recording device to facilitate measurement of tail movement and muscle activity before and after TSCI. This model is unique in that the impairment is limited to the tail: the subjects do not experience limb weakness, bladder impairment, or bowel dysfunction. In addition, 4 of the 6 subjects received a combination treatment comprising thyrotropin releasing hormone, selenium, and vitamin E after induction of experimental TSCI. The subjects tolerated the implantation of the recording device and did not experience adverse effects due the medications administered. The EMG data were transformed into a metric of volitional tail moment, which appeared to be valid measure of initial impairment and subsequent natural or treatment-related recovery. The histopathologic assessment demonstrated widespread axon loss at the site of injury and areas cephalad and caudad. Histopathology revealed evidence of continuing inflammation, with macrophage activation. The EMG data did not demonstrate evidence of a statistically significant treatment effect.
  • 机译 猕猴(猕猴)的假性动脉瘤和动静脉瘘
    摘要:An 8-y-old female rhesus macaque (Macaca mulatta) presented for swelling of the left lower limb distal to the inguinal region and associated with the femoral artery. Physical and ultrasound examinations suggested an arteriovenous fistula combined with a pseudoaneurysm. After review of possible treatment options, we determined that open surgical repair was the best course of action. The pseudoaneurysm and arteriovenous fistula were surgically resected, and the macaque recovered without complication.
  • 机译 Colopexy对成年女性黑冠cre(Lophocebus aterrimus)复发性直肠脱垂的手术治疗
    摘要:A 13-y-old, multiparous female black-crested mangabey (Lophocebus aterrimus) underwent surgical treatment for chronically recurring rectal prolapse by laparotomy and subsequent colopexy. Initially, a laparoscopic approach was attempted but was converted to an open approach after intraabdominal adhesions were noted. The colopexy was performed through a ventral midline incision, with no complications intraoperatively or postoperatively. The predisposing factors responsible for the development of this condition likely were related to pelvic floor weakness due to multiple past pregnancies. Transport-associated stressors likely contributed to the acute worsening of this patient's condition. Rectal prolapse is a common condition in laboratory-housed NHP. This case report describes an effective surgical treatment for recurring or otherwise nonreducible rectal prolapse in these species.
  • 机译 动物模型与转化医学:实验设计的质量和可重复性米兰国际学术交流会
    • 作者:
    • 刊名:Comparative Medicine
    • 2018年第1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
    • 2018年第1期
    摘要:
  • 机译 AALAS出版物:适合所有读者
    摘要:
  • 机译 治疗或不治疗:疼痛对实验参数的影响
    摘要:A common dilemma faced by all animal bioethics committees arises when exceptions are proposed to the use of analgesics in painful procedures. The committee and researcher must weigh the possible confounding effects of including additional drugs (analgesics) in their treatment regimen against the moral obligation to perform humane research. Often neglected in these considerations are the potential confounding effects of unrelieved pain and consistency with pain-relieving practices in human medicine. In this review, we summarize what is currently known regarding the molecular and physiologic effects of pain and analgesics in common animal models used across several therapeutic areas. This work is intended to help provide guidance and assurance that a comprehensive approach has been taken when contemplating how pain relief will be applied in animal research protocols.
  • 机译 生殖年龄雌性C57BL / 6小鼠维生素D消耗和补充的时程
    摘要:The use of animal models in vitamin D deficiency (VDD) research, particularly in regard to maternal deficits, has increased dramatically, yet these studies may be confounded due to ill-conceived experimental timelines. We conducted 2 experiments to (1) characterize the time course of VDD induction and repletion and (2) explore the long-term consequences of VDD on calcium homeostasis and body composition in reproductive-age female mice. Eight-week-old female C57BL/6 mice were randomized to receive either a vitamin D sufficient (VDS) or VDD diet; serum was collected weekly. At week 4, VDD mice were switched to VDS diet, and serum was collected weekly until week 8. Another group of same-age female mice was maintained on VDD diet for 40 wk. Body weights and serum were collected every 2 wk until week 40, when body composition was measured by using echoMRI. Mice did not become VDD until week 3 of the VDD diet and, after decreasing slightly at 4 wk, serum 25-hydroxyvitamin D remained unchanged through 40 wk. Vitamin D repletion to 25-hydroxyvitamin D concentrations considered adequate by the Institute of Medicine took 2 to 3 wk. Prolonged VDD in mice was marked by hypocalcemia and hyperparathyroidism and led to proportional decreases in both lean and fat mass. These data provide guidance in the design of studies using mice as a maternal VDD model, especially those exploring its effects on the developmental origins of health and disease and highlight the importance of monitoring and controlling the calciotropic effects of diet-induced VDD. This study also shows that prolonged VDD in reproductive-age female C57BL/6 mice induces metabolically meaningful changes in absolute, but not relative, body composition.
  • 机译 饲养在较高饲养温度下的小鼠显示出增强的T细胞反应和对弗朗西斯菌的存活土拉ensis
    • 作者:Robert L Rubin
    • 刊名:Comparative Medicine
    • 2017年第6期
    摘要:The inability to translate findings from studies performed in mouse models to the corresponding human condition is well known, especially those involving infectious, atherosclerotic, and other inflammatory diseases. We hypothesize that mice fail to a mount robust or adequate immune response to infectious agents because of physiologic effects of cold stress due to housing temperatures below the mouse thermoneutral zone (TNZ). This hypothesis was tested by comparing the immune response to the Francisella tularensis live vaccine strain in mice housed at a typical vivarium temperature, which is below the TNZ, with that of mice housed at a temperature near their TNZ. Mice maintained at 28 °C displayed elevated antigen-specific T-cell responses compared with mice housed at 22 °C and survived intranasal challenge that was fatal to immunized mice at 22 °C. These results demonstrate that cold stress due to housing below the mouse TNZ results in a blunted immune response and may compromise their translational value a models for infectious diseases and vaccine development.
  • 机译 阳离子脂质体-寡核苷酸复合物可作为新西兰白兔多克隆抗体生产的替代佐剂(盲肠)刺柏)
    摘要:Because of their ideal size and temperament, rabbits are commonly used in polyclonal antibody production. Immunostimulatory adjuvants—such as Freund complete and incomplete adjuvants as well as various proprietary products—trigger a robust immune response, which increases antibody concentrations. However, these adjuvants can cause excessive soft tissue reactions, prompting concerns regarding animal wellbeing. This study assessed the safety and efficacy of cationic liposome–oligonucleotide complexes (CLDC) as an alternative adjuvant to conventional adjuvants. On days 0 and 14, 15 female New Zealand white rabbits were vaccinated subcutaneously with 15 μg ovalbumin mixed with either CLDC, Freund adjuvant (day 0, complete; day 14, incomplete), or a proprietary adjuvant (n = 5 per group). Antibody titers were measured by direct ELISA on days 0, 14, and 28. Rabbits were palpated daily for lesion development, and all lesions were measured. Rabbits in all groups developed a significant antibody response to ovalbumin over 28 d. However, the differences between groups were not statistically significant. No rabbits in the CLDC group developed skin lesions, whereas 80% of rabbits that received Freund adjuvant and 100% of those that received the proprietary product developed skin lesions. This study demonstrates that CLDC may be a valuable and effective alternative adjuvant for polyclonal antibody production in rabbits—one that avoids the palpable injection-site lesions often seen with other adjuvants.
  • 机译 新西兰白兔端对端肠吻合术中腔内琼脂糖支架的好处
    摘要:In the present study, we evaluated the utility of an intraluminal agarose stent (IAS) for end-to-end intestinal anastomoses in rabbits. Female New Zealand white rabbits (n = 14) underwent conventional sutured anastomosis (CSA) with or without an IAS. IAS were used to maintain the luminal diameter for more rapid and accurate suturing, and then was squeezed transluminally to crush it into fragments, which passed through the intestines and were eliminated. The rabbits were euthanized on postoperative day 21. At necropsy, the anastomoses were assessed for adhesion formation, stenosis, and bursting pressure and were examined histologically for collagen content and blood vessel formation. Anastamosis surgery took less time in the IAS group (15.0 ± 2.6 min) than in the CSA-only group (30.1 ± 7.9 min). Only 1 postoperative death occurred (in the CSA group), and postmortem examination revealed evidence of anastomotic leakage. Adhesion formation and stenosis did not differ between groups, but bursting pressure, collagen content, and blood vessel formation were all significantly increased in the IAS group. IAS may decrease the operative time by maintaining a clear surgical field at the anastomotic site. In addition, the use of IAS promotes rapid healing and maintains the luminal diameter during end-to-end intestinal anastomosis.
  • 机译 热量限制对幼小拉帕奇家族性高胆固醇血症猪(Sus scrofa)代谢功能障碍的影响
    摘要:The Rapacz familial hypercholesterolemic (FH) swine model is well-characterized and used for studies of both spontaneous and inducible atherosclerosis but has not been used for studies of metabolic dysfunction to date. We examined whether parameters of metabolic syndrome including weight and adiposity, serum cholesterol, and glucoregulatory function could be modulated by restriction of caloric intake in the FH swine. Three groups of FH swine (n = 6 per group) were fed without restriction (AL), 80% of AL caloric intake, or 60% of AL caloric intake for 8.8 ± 0.5 mo beginning 2 wk after weaning. Caloric intake influenced the rate and magnitude of body weight gain and change in adiposity, as determined by dual-emission X-ray absorptiometry. At the conclusion of the study, pigs in the AL group reached a total least-square mean body weight of 94.2 kg and fat mass of 31.1%, whereas those fed 80% AL were 71.6 kg and 24.3% fat, and swine fed 60% AL were 46.1 kg and 14.1% fat. Serum cholesterol was greater in AL than 60% AL pigs at the end of the study. At 10 mo of age, intravenous glucose tolerance testing, performed to assess glucoregulatory function, indicated significant differences in serum glucose clearance profiles and insulin sensitivity between the AL- and 60% AL-fed swine. The AL-fed animals showed almost 5-fold lower insulin sensitivity when compared with animals fed 60% AL caloric intake. These results highlight the value of the FH swine model to study metabolic dysfunction due to changes in caloric intake.
  • 机译 血管移植颈动脉和颈静脉后2头猪(Sus scrofa)的Horner综合征
    摘要:The term Horner syndrome refers to the clinical presentation of oculosympathoparesis, comprising miosis, ptosis, and facial anhydrosis. To date, there are 2 reports of postoperative Horner syndrome in pigs. In this species the cervical sympathetic chain and cranial cervical sympathetic ganglion are consistently within the carotid artery sheath. This case study describes the sudden onset of Horner syndrome in 2 pigs, from a study cohort of 8, after the placement of a vascular graft between the carotid artery and external jugular vein. Anesthesia and surgery was uneventful in all the pigs in the study, but 2 pigs demonstrated clinical signs including ptosis, enophthalmos and prolapse of the nictitating membrane immediately after recovery from anesthesia. Horner syndrome was diagnosed in light of the clinical signs. These clinical signs persisted throughout the 2-mo study period and did not appear to improve or deteriorate in that time. Gross examination of the surgery site at the end of the study did not reveal an obvious lesion in the carotid artery sheath. The risk of Horner syndrome after surgery involving the carotid artery in pigs had not been reported prior to this study. Without specific measures to protect the cervical sympathetic ganglion during surgery, the incidence of postoperative Horner syndrome was 25% in our population of pigs. Although the welfare implications of this syndrome are minimal, concerted effort to avoid intraoperative damage to the cervical ganglion is essential for future work.

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