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  • 机译 C57BL / 6小鼠溃疡性皮炎危险因素和治疗方法的系统文献综述
    • 作者:
    • 刊名:Comparative Medicine
    • 2016年第2期
    摘要:
  • 机译 使用光学成像的近红外荧光标记双特异性单克隆抗体的生物分布分析。
    摘要:In recent years, biodistribution analyses of pharmaceutical compounds in preclinical animal models have become an integral part of drug development. Here we report on the use of optical imaging biodistribution analyses in a mouse xenograft model to identify tissues that nonspecifically retained a bispecific antibody under development. Although our bispecific antibody bound both the epidermal growth factor receptor and insulin growth factor 1 receptor are expressed on H358, nonsmall-cell lung carcinoma cells, the fluorescence from labeled bispecific antibody was less intense than expected in xenografted tumors. Imaging analyses of live mice and major organs revealed that the majority of the Alexa Fluor 750 labeled bispecific antibody was sequestered in the liver within 2 h of injection. However, results varied depending on which near-infrared fluorophore was used, and fluorescence from the livers of mice injected with bispecific antibody labeled with Alexa Fluor 680 was less pronounced than those labeled with Alexa Fluor 750. The tissue distribution of control antibodies remained unaffected by label and suggests that the retention of fluorophores in the liver may differ. Given these precautions, these results support the incorporation of optical imaging biodistribution analyses in biotherapeutic development strategies.
  • 机译 C57BL / 6背景对小鼠溃疡性皮炎的三种局部治疗方法的比较
    摘要:Ulcerative dermatitis (UD) is a common condition in C57BL/6 mice and strains with this background. The etiology of UD is unclear but appears to have a genetic component associated with the C57BL/6 strain and has been reported as secondary to a variety of conditions. Treatment is unrewarding, resulting in euthanasia in many cases. In the present study we compared 3 topical treatments against spontaneous UD in mice with a C57BL/6 background. In total, 301 mice of both sexes were included in this study, and the tested treatments comprised bacitracin–neomycin sulfate–polymixin B sulfate ointment twice daily, 10% povidone–iodine ointment plus 1% silver sulfadiazine cream once daily, and 0.005% sodium hypochlorite once daily. Lesion healing was defined as complete skin reepithelialization with or without hair regrowth. Sex, age, lesion location, and type and length of treatment were analyzed by using univariate and multivariate logistic regression. Of the 79 mice treated with triple-antibiotic ointment, 27 (34%) healed, compared with 43 of the 125 (34%) treated with povidone–iodine and sulfadiazine and 69 of the 97 (71%) treated with hypochlorite. Lesion size and treatment with 0.005% sodium hypochlorite were the only significant predictors of healing; all other variables were not statistically significant in multivariate analysis. We conclude that 0.005% sodium hypochlorite is an effective topical treatment alternative for UD in C57BL/6 mice and strains on this background, and a favorable prognosis depends on the early identification and treatment of those lesions.
  • 机译 缺乏支持FVB / N小鼠亚致死性自发性发作的慢性组织学病变
    摘要: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.
  • 机译 几种治疗剂在干眼症小鼠模型中的功效
    摘要:In the current study, we used 56 female BALB/c mice with induced dry eye syndrome to evaluate the therapeutic effects of formal saline (FS), sodium hyaluronate (SH), diclofenac sodium (DS), olopatadine (OP), retinoic acid (RA), fluoromethanole (FML), cyclosporine A (CsA), and doxycycline hyclate (DH). All subjects were kept in an evaporative ‘dry eye cabinet’ for the assessment of blink rate, tear production, tear break-up time, and impression cytology prior to (baseline) and during weeks 2, 4, and 6 of the study. The right eyes of all subjects were treated topically with 5 µL of the test agent twice daily during weeks 2 through 6. Impression cytology and tear break-up time differed between time points in all groups and differed between groups at weeks 4 and 6. Blink rate differed by time point only in the FS, FML, and DH groups. Tear production according to the phenol red cotton thread test differed by time point for all groups except RA, CsA, and DH and differed between groups only at week 6. Among the compounds tested in the present study, DS and CsA were the most effective therapeutic agents in our mouse model of dry eye syndrome; these agents likely exert their therapeutic effect through their antiinflammatory activity.
  • 机译 Vaxar:基于Web的实验室动物对疫苗接种反应的数据库及其在不同动物对结核疫苗接种反应的荟萃分析中的应用
    摘要:Animal models are indispensable for vaccine research and development. However, choosing which species to use and designing a vaccine study that is optimized for that species is often challenging. Vaxar () is a web-based database and analysis system that stores manually curated data regarding vaccine-induced responses in animals. To date, Vaxar encompasses models from 35 animal species including rodents, rabbits, ferrets, primates, and birds. These 35 species have been used to study more than 1300 experimentally tested vaccines for 164 pathogens and diseases significant to humans and domestic animals. The responses to vaccines by animals in more than 1500 experimental studies are recorded in Vaxar; these data can be used for systematic meta-analysis of various animal responses to a particular vaccine. For example, several variables, including animal strain, animal age, and the dose or route of either vaccination or challenge, might affect host response outcomes. Vaxar can also be used to identify variables that affect responses to different vaccines in a specific animal model. All data stored in Vaxar are publically available for web-based queries and analyses. Overall Vaxar provides a unique systematic approach for understanding vaccine-induced host immunity.
  • 机译 同伴饲养对群居恒河猴(Macaca mulatta)异常和物种适当活动的持久影响而对社会行为没有影响。
    摘要: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.
  • 机译 狒狒(Papio spp。)在怀孕和肥胖期间的血清维生素D浓度
    摘要:Obesity is associated with vitamin D deficiency, which can lead to serious problems during pregnancy. However, the mechanisms of the deficiency and guidelines for vitamin D supplementation during pregnancy are not established yet, and variations in environmental exposures combined with the difficulties of performing research in pregnant women are obstacles in the evaluation of vitamin D metabolism. Baboons (Papio spp.) are an excellent, well-established model for reproductive research and represent a unique opportunity to study vitamin D metabolism in a controlled environment. This study used secondary data and specimen analysis as well as a novel experimental design to evaluate pregnant and nonpregnant baboons that were or were not exposed to sunlight while they were obese and after weight reduction. Daily D3 intake was 71% higher in nonpregnant obese baboons than in their nonobese counterparts, but serum vitamin D concentrations did not differ between these populations. In addition, serum 25-hydroxyvitamin D concentrations correlated negatively with the obesity index. This report is the first to show the effect of obesity and pregnancy on vitamin D concentrations in a NHP population. These data underline the importance of adequate vitamin D supplementation in obese animals.
  • 机译 NHP 3个大菌落中残留胎盘发生率的回顾性分析
    摘要:During 1999 through 2014, retained placenta was the most common cause of clinical admission for reproductive complications in breeding colonies of baboons (approximate colony size, 2000 animals), cynomolgus macaques (approximately 1000), and rhesus macaques (approximately 500) at the Southwest National Primate Research Center. Retained placentas occurred in 2.7% of baboons, 3.3% of cynomolgus macaques, and 1.0% of rhesus macaques. Apparent risk factors for retained placenta included stillbirth or abortion and at least one prior cesarean section. There was a significant association between stillbirth and retained placenta in all species. Cesarean sections were performed routinely for baboons to meet research objectives but occurred only as needed for cynomolgus and rhesus macaques. Having had at least one prior cesarean section was an incidence factor for retained placenta in 37.0% of baboons and 4.7% of cynomolgus macaques; none of the rhesus macaques with retained placentas had undergone cesarean section previously. More than 90% of dams with retained placenta returned to a successful reproductive life or assignment to a nonbreeding research protocol. Advances in reproductive management will benefit from prospective studies that capture additional data from all members of a breeding group prior to reproductive complications.
  • 机译 恒河猴(猕猴)的全身照射后Cercopithecine疱疹病毒9(猿猴水痘病毒)感染。
    摘要:This case report describes a rhesus macaque (Macaca mulatta; male; age, 5 y; weight, 6.7 kg) with anorexia, dehydration, lethargy, ataxia, and generalized skin rashes that occurred 30 d after total-body irradiation at 6.5 Gy (60Co γ-rays). Physical examination revealed pale mucus membranes, a capillary refill time of 4 s, heart rate of 180 bpm. and respirations at 50 breaths per minute. Diffuse multifocal maculopapulovesicular rashes were present on the body, including mucocutaneous junctions. The CBC analysis revealed a Hct of 48%, RBC count of 6.2 × 106/µL, platelet count of 44 × 103/µL, and WBC count of 25 × 103/µL of WBC. The macaque was euthanized in light of a grave prognosis. Gross examination revealed white foci on the liver, multifocal generalized petechiation on serosal and mucosal surfaces of the gastrointestinal tract, hemorrhagic lymph nodes, and hemorrhagic fluid in the thoracic cavity. Microscopic examination revealed cutaneous vesicular lesions with intranuclear eosinophilic viral inclusions within the epithelial cells, consistent with herpesvirus. Immunohistochemistry was positive for herpesvirus. The serum sample was negative for antibodies against Macacine herpesvirus 1 and Cercopithecine herpesvirus 9 (simian varicella virus, SVV). Samples submitted for PCR-based identification of the etiologic agent confirmed the presence of SVV DNA. PCR analysis, immunohistochemistry, and histology confirmed that lesions were attributed to an active SVV infection in this macaque. This case illustrates the importance of screening for SVV in rhesus macaques, especially those used in studies that involve immunosuppressive procedures.
  • 机译 加利福尼亚国家灵长类动物研究中心恒河猴(猕猴)的左心室肥大(1992-2014年)
    摘要:Necropsy records and associated clinical histories from the rhesus macaque colony at the California National Primate Research Center were reviewed to identify mortality related to cardiac abnormalities involving left ventricular hypertrophy (LVH). Over a 21-y period, 162 cases (female, 90; male, 72) of idiopathic LVH were identified. Macaques presented to necropsy with prominent concentric hypertrophy of the left ventricle associated with striking reduction of the ventricular lumen. Among all LVH cases, 74 macaques (female, 39; male, 35), mostly young adults, presented for spontaneous (sudden) death; more than 50% of these 74 cases were associated with a recent history of sedation or intraspecific aggression. The risk of sudden death in the 6- to 9-y-old age group was significantly higher in male macaques. Subtle histologic cardiac lesions included karyomegaly and increased cardiac myocyte diameter. Pedigree analyses based on rhesus macaque LVH probands suggested a strong genetic predisposition for the condition. In humans, hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, associated with diverse clinical outcomes ranging from asymptomatic disease to sudden death. Although the overall risk of disease complications such as sudden death, end-stage heart failure, and stroke is low (1% to 2%) in patients with HCM, the absolute risk can vary dramatically. Prima facie comparison of HCM and LVH suggest that further study may allow the development of spontaneously occurring LVH in rhesus macaques as a useful model of HCM, to better understand the pathogenesis of this remarkably heterogeneous disease.
  • 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
    • 2016年第2期
    摘要:
  • 机译 断奶后社会隔离的F344大鼠海马谷氨酸能和GABA能基因的亚区域表达
    摘要:Many studies have shown that postweaning social isolation (pwSI) alters various behavioral phenotypes, including hippocampus-dependent tasks. Here, we report the comprehensive analysis of the expression of glutamatergic and GABAergic neurotransmission-related genes in the distinct hippocampal subregions of pwSI rats. Male F344 rats (age, 4 wk) experienced either pwSI or group housing (controls). At 7 wk of age, the hippocampus of each rat was removed and laser-microdissected into the CA1 and CA3 layers of pyramidal cells and the granule cell layer of the dentate gyrus. Subsequently, the expression of glutamatergic- and GABAergic-related genes was analyzed by quantitative RT-PCR. In the CA1 and CA3 pyramidal cell layers, 18 of 24 glutamate receptor subunit genes were at least 1.5-fold increased in expression after pwSI. In particular, the expression of several N-methyl-D-aspartate and kainate receptors (for example, Grin2a in CA1, Grik4 in CA3) was significantly increased after pwSI. In contrast, pwSI tended to decrease the expression of GABAA receptor subunit genes, and Gabra1, Gabra2, Gabra4, Gabra5, Gabrb2, Gabrg1, and Gabrg2 were all significantly decreased in expression compared with the levels in the group-housed rats. These results indicate a subregion-specific increase of glutamate receptors and reduction of GABAA receptors, suggesting that the hippocampal circuits of pwSI rats may be in more excitable states than those of group-housed rats.
  • 机译 性腺切除术对幼年仓鼠神经节中类似神经节细胞的雄激素依赖性行为的影响
    摘要:Ganglion cell-like (GL) cells reside in the dermis of the ventral skin of mature male Djungarian hamsters (Phodopus sugorus) and express androgen receptor (AR). To assess whether GL cells have androgen-dependent behavior, we evaluated the histologic changes of GL cells after gonadectomy. Five male and 5 female hamsters were gonadectomized at the age of 4 wk and necropsied 14 wk later. The number, distribution, and proliferative activity of GL cells in the thoracoabdominal and dorsal skins were evaluated histologically and compared with those of corresponding intact animals. GL cells were more numerous, were distributed throughout the skin more widely, and had higher proliferative activity in the intact male hamsters than in their gonadectomized counterparts. Similar trends regarding these 3 parameters were seen in ovariectomized compared with intact female hamsters and between intact male and intact female hamsters. These results suggest that the GL cells of Djungarian hamsters demonstrate sex-associated differences in their distribution and proliferative activity and that androgen may be involved in the development of these cells.
  • 机译 幼猪和成年猪窒息半月板的基因表达和超微结构分析
    摘要:The origin of the age-associated degenerative processes in meniscal tissue is poorly understood and may be related to an imbalance of anabolic and catabolic metabolism. The aim of the current study was to compare medial menisci isolated from juvenile pigs and degenerated medial menisci from adult pigs in terms of gene expression profile and ultrastructure. Medial menisci were isolated from the knee joints of juvenile and adult pigs (n = 8 for each group). Degeneration was determined histologically according to a scoring system. In addition, the gene expression profiles of 14 genes encoding extracellular matrix proteins, catabolic matrix metalloproteinases and mediators of inflammation were analyzed. Changes in the ultrastructure of the collagen network of the meniscal tissue were analyzed by using transmission electron microscopy. The histologic analysis of menisci showed significantly higher grade of degeneration in tissue isolated from adult porcine knee joints compared with menisci isolated from juvenile knee joints. In particular, destruction of the collagen network was greater in adult menisci than in juvenile menisci. Degenerated menisci showed significantly decreased gene expression of COL1A1 and increased expression of MMP2, MMP13, and IL8. The menisci from adult porcine knee joints can serve as a model for meniscal degeneration. Degenerative changes were manifested as differences in histopathology, gene expression and ultrastructure of collagen network.
  • 机译 在黑猩猩(盘状穴居人)中使用可植入式循环记录仪来监测心脏心律不齐并评估针灸和激光疗法的效果
    摘要:Cardiovascular disease is a leading cause of death in captive chimpanzees and is often associated with myocardial fibrosis, which increases the risk of cardiac arrhythmias. In this case report, we present a 36-y-old male chimpanzee (Pan troglodytes) diagnosed with frequent ventricular premature complexes (VPC). We placed a subcutaneous implantable loop recorder for continual ECG monitoring to assess his arrhythmias without the confounding effects of anesthetics. During his initial treatment with the antiarrhythmia medication amiodarone, he developed thrombocytopenia, and the drug was discontinued. After reviewing other potential therapies for the treatment of cardiac arrhythmias, we elected to try acupuncture and laser therapy in view of the positive results and the lack of adverse side effects reported in humans. We used 2 well-known cardiac acupuncture sites on the wrist, PC6 (pericardium 6) and HT7 (heart 7), and evaluated the results of the therapy by using the ECG recordings from the implantable loop recorder. Although periodic increases in the animal's excitement level introduced confounding variables that caused some variation in the data, acupuncture and laser therapy appeared to decrease the mean number of VPC/min in this chimpanzee.
  • 机译 老化恒河猴(Macaca mulatta)中氧化再生纤维素引起的肉芽肿
    摘要:Bioabsorbable hemostatic agents such as oxidized regenerated cellulose are widely used to control intraoperative diffuse capillary bleeding. Compared with electrocautery or ligation, oxidized regenerated cellulose has the advantage of controlling bleeding without occluding the vessel lumen or causing thermal injuries to adjacent tissue. Although the manufacturer recommends removal of the material once hemostasis is achieved, oxidized regenerated cellulose is a bioabsorbable hemostatic agent and is often left in the surgical bed to prevent subsequent bleeding after surgical closure. However, noninvasive imaging techniques have revealed granulomatous foreign-body reactions that mimic infection or tumor recurrence. We present a case report of sterile peritonitis and granuloma formation secondary to the presence of oxidized regenerated cellulose after intestinal resection to excise a colonic adenocarcinoma in an aged rhesus macaque.
  • 机译 松鼠猴(Saimiri sciureus)的自发性胆石症
    摘要:A mature female squirrel monkey was noted during routine semiannual examinations to have moderate progressive weight loss. Serum chemistry panels revealed marked increases in hepatic enzyme, bilirubin, and bile salt concentrations and hypoalbuminemia. Abdominal ultrasonography revealed echogenic, shadowing debris in the gallbladder, consistent with cholelithiasis. At necropsy, marked thickening and distension of the gallbladder, cystic duct, and common bile duct was noted, and more than 50 irregularly shaped, black gallstones were removed from the biliary tract. Gallbladder tissue, bile, and gallstones cultured positive for Escherichia coli and Proteus spp., suggesting a brown-pigment gallstone type secondary to a bacterial nidus. Histopathology revealed severe chronic–active diffuse cholecystitis and severe chronic-active hepatic degeneration and necrosis with severe cholestasis. To our knowledge, this report is the first description of spontaneous choleilthiasis in a squirrel monkey.
  • 机译 成年雌性黑长尾猴(Chlorocebus sabaeus)的哮喘
    摘要:A 9-y-old, colony-bred, female vervet monkey (Chlorocebus sabaeus) presented with a 6-y history of open-mouth breathing, tachypnea, and sibilant wheezing. These symptoms did not significantly affect her activity or quality of life. Thoracic radiographs and results of bronchoalveolar lavage supported the diagnosis of asthma. Treatment comprising intramuscular prednisolone (tapered over 2 mo from twice daily to every other day), inhaled salmeterol–fluticasone (25 µg–250 µg per actuation twice daily) by mask, and a metered dose inhaler was successful in restoring a normal respiratory pattern. Despite the availability of several primate models of human asthma, this case represents the first report of spontaneous asthma in a NHP.
  • 机译 科学论文摘要:AISAL研讨会那不勒斯
    • 作者:
    • 刊名:Comparative Medicine
    • 2016年第1期
    摘要:

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