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Schistosoma mansoni Infection in Three Green Monkeys (Chlorocebus sabaeus) Originating from Saint Kitts. 圣基茨三只绿猴的曼氏血吸虫感染。
Pub Date : 2025-10-01 DOI: 10.30802/AALAS-JAALAS-25-079
Michael A Eckhaus, Jeremy J Bearss, Rachel M Fleischmann, Jennifer Ketzis, Tiffany Lavinder, Amy Beierschmitt, Jessica Plunkard, Gregory W Salyards

Schistosomiasis, a parasitic disease caused by trematodes of the genus Schistosoma, was eliminated on the island of Saint Kitts in the 1950s after an intense program that targeted the snail intermediate host and improved sanitation. However, recently, 3 cases of schistosomiasis were identified in green monkeys (Chlorocebus sabaeus) imported from Saint Kitts over a period of 5 months from December 2023 to April 2024. The 3 cases each had hepatic manifestations of the disease. In addition, one animal had disseminated disease affecting the cerebrum, cerebellum, brainstem, and lung and is the first described case of neuroschistosomiasis in a non-human primate (NHP) due to infection with Schistosoma mansoni.

血吸虫病是一种由血吸虫属吸虫引起的寄生虫病。20世纪50年代,圣基茨岛实施了一项针对蜗牛中间宿主和改善卫生条件的密集计划,消灭了血吸虫病。然而,最近在2023年12月至2024年4月5个月期间从圣基茨进口的绿猴(绿猴)中发现了3例血吸虫病病例。3例均有肝脏表现。此外,一只动物出现了影响大脑、小脑、脑干和肺部的播散性疾病,这是第一例因感染曼氏血吸虫而在非人灵长类动物(NHP)中发现的神经血吸虫病病例。
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引用次数: 0
Extended Sanitization Frequency for Bottles: Using Volume as an Alternative to Time-Scheduled Replacements for Mice in Disposable Individually Ventilated Caging Systems. 延长瓶子的消毒频率:使用体积作为一次性单独通风笼系统中小鼠定时更换的替代方案。
Pub Date : 2025-10-01 DOI: 10.30802/AALAS-JAALAS-25-116
Alyssa L Valentyn, Jackie Olley-Williams, Venus Estrada, Naina M F Silva, Misty Williams-Fritze, Ying Wu, Courtney Easley-Neal, Laurette Burgess

The Guide for the Care and Use of Laboratory Animals specifies that sipper tubes require weekly sanitization, although reduced frequency for sterile, disposable caging components may be justified with performance-based assessments; therefore, extending bottle duration beyond 1 week, and replacing instead at a lower volume limit, may be acceptable if it does not compromise mouse health or water quality. Weekly bottle change for sterile, disposable bottles results in excessive waste of both water and plastic-bottles are typically more than half full at 7 days. A volume-based replacement schedule is a visual alternative to weekly changes for systems using sterile, disposable bottles, reducing the number of bottles processed and facilitating operations by allowing spot changes without the need to date or track bottles. Furthermore, the gravity-drip design of Innovive's Aquavive bottle minimizes contamination, suggesting that water quality and cleanliness may be maintained for longer durations. To assess the impact of a volume-based replacement schedule on mouse health and water quality, C57BL/6NCrl mice at varying housing densities were monitored for changes in animal weight and mean water consumption. At bottle replacement, packed cell volume was collected from individual mice as a marker of hydration status, and water quality was assessed by visual inspection, culture for Escherichia coli and coliform bacteria, and total microbial count. Baseline measurements were collected over 7 days, followed by a volume-based replacement period, where bottles remained on the cage until they reached 100 mL (13-47 days). No significant differences were observed in animal body weight, body condition, water consumption, or packed cell volume, regardless of cage density or the amount of time the bottle was deployed. Microbial analysis showed no bacterial growth in any bottle, and visual inspection showed no turbidity or cloudiness. Based on this information, our institution allowed prefilled disposable, acidified water bottles to be maintained well beyond 7 days, using a volume-based replacement at 100 mL.

《实验动物的护理和使用指南》规定,吸管需要每周消毒一次,尽管通过基于性能的评估可以证明减少无菌一次性笼子组件的频率是合理的;因此,在不影响小鼠健康或水质的前提下,延长瓶子的使用时间超过一周,并以更低的体积更换瓶子是可以接受的。每周更换一次性无菌瓶会导致水和塑料瓶的过度浪费——通常在7天内,塑料瓶会超过半瓶。基于容量的更换计划是使用无菌一次性瓶的系统每周更换的视觉替代方案,减少了处理的瓶数,并通过允许现场更换而无需确定日期或跟踪瓶来促进操作。此外,innovvive Aquavive瓶的重力滴注设计最大限度地减少了污染,这表明水质和清洁度可以保持更长的时间。为了评估基于体积的更换计划对小鼠健康和水质的影响,研究人员监测了不同居住密度下C57BL/6NCrl小鼠的体重和平均耗水量的变化。在换瓶时,收集单个小鼠的细胞体积作为水化状态的标志,并通过目视检查、大肠杆菌和大肠菌群培养以及总微生物计数来评估水质。基线测量是在7天内收集的,随后是基于体积的更换期,瓶子留在笼子里直到它们达到100毫升(13-47天)。无论笼子密度或瓶子放置时间如何,在动物体重、身体状况、水消耗或填充细胞体积方面均未观察到显著差异。微生物分析显示没有细菌生长在任何瓶子,目测显示没有浑浊或浑浊。根据这些信息,我们的机构允许预充的一次性酸化水瓶保持7天以上,使用100毫升的容量替换。
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引用次数: 0
De Novo Serum Biochemistry and Electrophoretic Reference Intervals for Jamaican Fruit Bats (Artibeus jamaicensis). 牙买加果蝠(Artibeus jamaicensis)从头血清生化和电泳参考区间。
Pub Date : 2025-10-01 DOI: 10.30802/AALAS-JAALAS-25-102
Samantha M Thomas, A Russell Moore, Marissa B Pollak, Katherine Bukovec, Aryn J Cummings, Jordyn Scumaci, Charla Lovelace, Tony Schountz, Vincent J Munster, Jessica D Ayers, Lon V Kendall, Jassia Pang

The Jamaican fruit bat (Artibeus jamaicensis; JFB) is a natural host and current experimental model for many viruses, including Middle East respiratory syndrome virus, dengue virus, Zika virus, rabies virus, influenza virus, tacaribe virus, and most recently SARS-CoV-2, due to their unique immune systems, which allow the harboring and transmission of disease without developing significant clinical disease themselves. In these studies, disease impact can be measured using changes in serum biochemical and protein electrophoretic blood values. However, no currently established reference intervals for JFB exist. In this study, we aimed to define these baseline parameters from our closed bat colony and determine sex differences, if any. We hypothesized that many chemistry values would be similar to other species of frugivorous bats with elevated creatine kinase and glucose due to hand capture and that sex differences would be minimal. One hundred thirty-four adult bats (62 males and 72 females) were randomly selected from an apparently healthy captive population of JFB for isoflurane euthanasia and blood collection by cardiocentesis. Serum samples were routinely processed using commercially available methods. Reference intervals for the total population and both sexes were established using the Reference Value Advisor 2.1 macro for Excel and the nonparametric method in accordance with current guidelines. When compared against reference values for other frugivorous bat species, JFB most notably had increased ALT, AST, GGT, and potassium values. Higher phosphorus and ALP levels may be attributed to sampling of juveniles, while elevated creatine kinase and glucose are secondary to capture. Males had considerably higher cholesterol, while females had higher glucose and γ-globulin. This information on serum biochemical values adds to our knowledge of the normal physiologic parameters of this species and will serve as a useful guide for future studies performed on Jamaican fruit bats.

牙买加果蝠(Artibeus jamaicensis; JFB)是许多病毒的天然宿主和目前的实验模型,包括中东呼吸综合征病毒、登革热病毒、寨卡病毒、狂犬病毒、流感病毒、塔卡里布病毒和最近的SARS-CoV-2,因为它们独特的免疫系统允许疾病的庇护和传播,而不会产生重大的临床疾病。在这些研究中,疾病的影响可以通过血清生化和蛋白质电泳血液值的变化来测量。但是,目前还没有建立JFB的参考区间。在这项研究中,我们旨在从我们封闭的蝙蝠群体中定义这些基线参数,并确定性别差异,如果有的话。我们假设许多化学值与其他种类的果食蝙蝠相似,由于手捕获而导致肌酸激酶和葡萄糖升高,性别差异将是最小的。从表面上健康的JFB圈养种群中随机选择134只成年蝙蝠(雄62只,雌72只)进行异氟醚安乐死和心脏穿刺采血。血清样本使用市售方法进行常规处理。根据现行指南,使用Excel的Reference Value Advisor 2.1宏和非参数方法建立总人口和两性的参考区间。与其他食果蝙蝠种类的参考值相比,JFB最显著地增加了ALT、AST、GGT和钾值。较高的磷和ALP水平可能归因于对幼鱼的采样,而肌酸激酶和葡萄糖的升高是继发于捕获。男性有相当高的胆固醇,而女性有更高的葡萄糖和γ-球蛋白。这些关于血清生化值的信息增加了我们对该物种正常生理参数的了解,并将为今后对牙买加果蝠进行的研究提供有用的指导。
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引用次数: 0
Determining A1C Normal Values in Rhesus Macaques (Macaca mulatta). 恒河猴(Macaca mulatta) A1C正常值的测定。
Pub Date : 2025-10-01 DOI: 10.30802/AALAS-JAALAS-25-129
Jason P Dufour, Lara Doyle-Meyers, Kathrine Falkenstein, Axelle Kamanzi Shimwa

Diabetes is a global health concern, with increasing prevalence attributed to factors such as obesity and sedentary lifestyles. Nonhuman primates (NHPs), particularly rhesus macaques (Macaca mulatta), serve as valuable models for studying type 2 diabetes mellitus due to their physiologic similarities to humans. However, there are currently no established normal ranges for glycated hemoglobin (A1C) in this species. This study aimed to determine normal A1C values in healthy, nonobese adult rhesus macaques to establish a reference for future diabetes research. A total of 210 Indian origin rhesus macaques (128 males, 82 females) 5-10 years of age were sampled. A1C was measured using the A1CNow+ kit, and blood glucose levels were assessed via a point-of-care glucometer and clinical laboratory analysis. Statistical analyses were performed using R, including a Shapiro-Wilks test for normality, regression analyses, and correlation coefficients. The mean A1C value was 5.92% (range, 4.4%-9.9%), with males exhibiting a mean of 6.07% and females 5.69%. No significant correlations were found between A1C and blood glucose levels, weight, body condition score, or age. However, males had significantly higher A1C levels than females (P = 0.004). Excluding outliers revealed a significant interaction between sex and weight (P = 0.03). The established mean A1C value for healthy adult rhesus macaques is higher than previously reported values for NHPs and human standards. This study provides a critical reference for A1C levels in rhesus macaques, facilitating future diabetes research and improving understanding of type 2 diabetes mellitus in both humans and NHPs.

糖尿病是一个全球性的健康问题,由于肥胖和久坐不动的生活方式等因素,患病率不断上升。非人灵长类动物(NHPs),特别是恒河猴(Macaca mulatta),由于其生理上与人类相似,可以作为研究2型糖尿病的有价值的模型。然而,目前该物种的糖化血红蛋白(A1C)没有确定的正常范围。本研究旨在确定健康、非肥胖的成年恒河猴正常的A1C值,为今后的糖尿病研究提供参考。本研究共采集了210只5-10岁的印度恒河猴(雄性128只,雌性82只)。使用A1CNow+试剂盒测量A1C,通过即时血糖仪和临床实验室分析评估血糖水平。使用R进行统计分析,包括夏皮罗-威尔克斯正态性检验、回归分析和相关系数。平均A1C值为5.92%(范围4.4% ~ 9.9%),其中男性平均为6.07%,女性平均为5.69%。糖化血红蛋白与血糖水平、体重、身体状况评分或年龄之间没有显著相关性。然而,男性的A1C水平明显高于女性(P = 0.004)。排除异常值显示性别和体重之间存在显著的相互作用(P = 0.03)。健康成年恒河猴确定的平均糖化血红蛋白值高于先前报道的NHPs和人类标准值。本研究为恒河猴的糖化血红蛋白水平提供了重要参考,促进了未来的糖尿病研究,提高了对人类和NHPs 2型糖尿病的认识。
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引用次数: 0
Spontaneous Hemangiosarcoma of Bone with Hepatic and Pulmonary Metastasis in a Rhesus Macaque (Macaca mulatta): A Case Report. 恒河猴(Macaca mulatta)自发性骨血管肉瘤伴肝和肺转移一例报告。
Pub Date : 2025-10-01 DOI: 10.30802/AALAS-JAALAS-25-128
Ahmad A Saied, Christopher R Brown, Avelina Y Rodgers, Victoria Shephard, Cecily C Midkiff, Monica E Embers, Rebekah L Bullard, Leslie D Wilson

Hemangiosarcoma is a malignant neoplasm of vascular endothelial cell origin that is rare in nonhuman primates (NHPs) and humans. This report describes the clinical, gross, and histopathologic findings of metastatic hemangiosarcoma in a rhesus macaque. A 4.8-year-old female Indian-origin rhesus macaque presented to the Tulane National Biomedical Research Center clinic with right hindlimb lameness and poor body condition. On physical examination, there was significant muscle atrophy of the right leg and pelvis. Radiographs revealed severe bone degeneration and lysis of the right tibia with pulmonary nodules. On necropsy, the right tibia was markedly thickened at least two times the normal size. Multifocal, 1- to 7-mm-diameter dark red nodules were present in the periosteum, compact cortical bone, and medullary cavity. Multifocal dark red nodules measuring 1-10 mm were present in the liver and lung. Histologically, the nodules were composed of neoplastic endothelial cells forming irregular vascular clefts and anastomosing vascular channels. Neoplastic cells often wrapped collagenous stroma. Neoplastic cells stained positive with CD31, as well as with von Willebrand factor immunohistochemical stains. Hemangiosarcoma in NHPs is exceptionally rare. To our knowledge, this represents the first case of metastatic hemangiosarcoma originating in bone in an NHP.

血管肉瘤是一种起源于血管内皮细胞的恶性肿瘤,在非人灵长类动物和人类中很少见。本报告描述了一例恒河猴转移性血管肉瘤的临床、大体和组织病理学结果。一例4.8岁印度裔雌性恒河猴以右后肢跛行和身体状况不佳来到杜兰国家生物医学研究中心诊所。体格检查显示右腿和骨盆有明显的肌肉萎缩。x线片显示严重的骨退化和右胫骨溶解伴肺结节。尸检发现,右胫骨明显增厚,至少是正常大小的两倍。骨膜、致密皮质骨和髓腔内可见多灶性、直径1- 7mm的暗红色结节。肝、肺多灶暗红色结节,直径1 ~ 10mm。组织学上,结节由肿瘤内皮细胞组成,形成不规则的血管裂缝和吻合的血管通道。肿瘤细胞常包裹着胶原基质。肿瘤细胞CD31和血管性血友病因子免疫组化染色呈阳性。血管性肉瘤在NHPs中极为罕见。据我们所知,这是NHP中第一例起源于骨的转移性血管肉瘤。
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引用次数: 0
Tiletamine-Zolazepam for Total Intravenous Anesthesia in Sheep. 替乐胺-唑拉西泮用于绵羊全静脉麻醉。
Pub Date : 2025-10-01 DOI: 10.30802/AALAS-JAALAS-25-108
Emily Mocarski, Kathleen Heng, Monika Huss, Yamil Saenz, Benjamin Franco, Kim Butts Pauly, Katechan Jampachaisri, Patrick Sharp, Cholawat Pacharinsak

Total intravenous anesthesia (TIVA) is an alternative to inhalant anesthesia when inhalant anesthesia is unavailable or contraindicated. This study investigated the anesthetic efficacy of tiletamine-zolazepam (TZ) through continuous rate infusion in sheep undergoing a 120-minute noninvasive imaging procedure. We hypothesized that the TZ continuous rate infusion would provide effective general anesthesia for imaging. Six male Dorset sheep were sedated with 4-6 mg/kg TZ intramuscularly, intubated, and maintained on 5-15 mg/kg/h TZ intravenous continuous rate infusion. Measured anesthetic parameters included heart rate, oxygen saturation (%SpO2), end-tidal carbon dioxide (ETCO2), body temperature, and direct arterial blood pressure (systolic, diastolic, and mean); blood gas analysis was performed during anesthesia. Time to extubation and standing (recovery) were measured. Other clinical observations (thrashing, activity, vocalization, and general appearance) were also assessed throughout recovery. Heart rate, %SpO2, ETCO2, body temperature, and direct arterial blood pressure were stable throughout imaging anesthesia. Time to extubation and standing (recovery) were 25 ± 6.5 and 34 ± 8.0 minutes, respectively. No abnormal clinical observations were noted. These data suggest that TZ TIVA provides effective general anesthesia for up to 120 minutes of noninvasive imaging.

全静脉麻醉(TIVA)是一种替代吸入麻醉时,吸入麻醉不可用或禁忌。本研究通过对绵羊进行120分钟的无创成像检查,研究了替乐胺-唑拉西泮(TZ)的连续输注麻醉效果。我们假设TZ连续输注将为成像提供有效的全身麻醉。对6只雄性多塞特羊进行4-6 mg/kg TZ肌注、气管插管麻醉,并维持5-15 mg/kg/h TZ静脉连续输注。测量的麻醉参数包括心率、血氧饱和度(%SpO2)、潮末二氧化碳(ETCO2)、体温和直接动脉血压(收缩压、舒张压和平均值);麻醉期间进行血气分析。测量拔管时间和站立时间(恢复)。其他临床观察(抽打、活动、发声和一般外观)也在整个恢复过程中进行评估。在整个成像麻醉过程中,心率、%SpO2、ETCO2、体温和直接动脉血压稳定。拔管时间25±6.5分钟,站立(恢复)时间34±8.0分钟。无异常临床观察。这些数据表明,TZ TIVA提供了有效的全身麻醉长达120分钟的无创成像。
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引用次数: 0
A Systemic Approach to Chest Radiographic Assessment in Mycobacterium tuberculosis-Infected Cynomolgus Macaques (Macaca fascicularis). 对感染结核分枝杆菌的食蟹猕猴胸部x线片的系统评价。
Pub Date : 2025-10-01 DOI: 10.30802/AALAS-JAALAS-25-056
Taratorn Kemthong, Mutchamon Kaewparuehaschai, Kirana Noradechanon, Keerati Kongrod, Suthirote Meesawat, Saradee Warit, Prapaporn Srilohasin, Angkana Chaiprasert, Suchinda Malaivijitnond

This study aimed to establish a comprehensive and accurate numerical chest X-ray radiograph (CXR) scoring system in cynomolgus macaques by using image intensity values from healthy, tuberculosis (TB)-free animals as references. The CXRs were obtained in both dorsoventral and lateral postures from 90 macaques and viewed by the RadiAnt DICOM Viewer software version 2023.1. The mean and maximum intensity values were analyzed and showed significant differences between sex (male and female) and age class (juvenile and subadult/adult), varying based on body sizes. The cutoff values were, therefore, set separately and were tested for accuracy in detecting TB status in 18 naturally Mycobacterium tuberculosis-infected macaques, which were assessed for active tuberculosis infection (ATBI) using Xpert MTB/RIF Ultra at least once during a 12-month follow-up. Only the cutoff values of maximum lateral image intensity (MLIs) correctly identified TB infection in 100% of cases. Thus, the MLIs were selected to follow up on the development of TB lesions in those 18 Mycobacterium tuberculosis-infected macaques. The lateral digital radiograph was divided further into 9 areas, and the MLIs can predict the progression of TB lesions, which were most likely located in the dorsal part of the cranial lung lobe between thoracic vertebrae 1 (T1) to T4. Finally, the CXR results of another group of 8 Mycobacterium tuberculosis-exposed macaques, whose TB status was either uninfected, latent, or ATBI, were compared between a blind test by an expert radiologist and our established CXR scoring system. The blind test results showed 62.5% (5/8) agreement with our scoring system. This suggests that the CXR-MLI scoring system can be used as a supplementary tool for TB diagnosis in cynomolgus macaques.

本研究旨在以健康、无结核(TB)动物的图像强度值为参考,建立一套全面、准确的食蟹猴胸部x线片(CXR)数值评分系统。研究人员从90只猕猴身上获得了背、腹和侧位的cxr,并通过RadiAnt DICOM Viewer软件版本2023.1进行了观察。结果表明,不同性别(雄性和雌性)和不同年龄(幼年和亚成虫/成虫)之间的平均强度和最大强度存在显著差异,且因体型而异。因此,在18只自然感染结核分枝杆菌的猕猴中单独设置了截止值,并测试了检测结核病状态的准确性,这些猕猴在12个月的随访期间使用Xpert MTB/RIF Ultra评估活动性结核病感染(ATBI)至少一次。在100%的病例中,只有最大侧位图像强度(MLIs)的截止值才能正确识别结核感染。因此,选择mli来跟踪这18只感染结核分枝杆菌的猕猴的结核病变发展。侧位数字片进一步划分为9个区域,MLIs可以预测TB病变的进展,最可能位于胸椎1 (T1)至T4之间的颅肺叶背侧。最后,将另一组8只暴露于结核分枝杆菌的猕猴(结核状态为未感染、潜伏或ATBI)的CXR结果在放射科专家的盲测和我们建立的CXR评分系统之间进行比较。盲测结果显示62.5%(5/8)与我们的评分系统一致。这表明CXR-MLI评分系统可作为食蟹猴结核诊断的辅助工具。
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引用次数: 0
Association of Primate Veterinarians Guidelines for Weight Management in Research Nonhuman Primates. 灵长类动物兽医协会非人类灵长类动物体重管理研究指南。
Pub Date : 2025-09-01 DOI: 10.30802/AALAS-JAALAS-25-123
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引用次数: 0
Pharmacokinetic Evaluation of Topical Long-Acting Buprenorphine in New Zealand White Rabbits (Oryctolagus cuniculus). 外用长效丁丙诺啡在新西兰大白兔体内的药动学评价。
Pub Date : 2025-09-01 DOI: 10.30802/AALAS-JAALAS-25-077
Stephanie Thi, Gerry Hish, Tara L Martin, Xiangbo Kong, Patrick A Lester

Rabbits are commonly used as surgical models, thus requiring analgesics for painful procedures and optimal animal welfare. Buprenorphine, a partial µ opioid, is commercially available in various concentrations and sustained-release formulations and has historically been used as an analgesic in rabbits. A topical long-acting buprenorphine formulation (Zorbium, Bup-TP) has been approved for analgesic use in cats but has not yet been evaluated in rabbits. The present study evaluated the plasma concentrations and pharmacokinetic parameters of Bup-TP in New Zealand white rabbits (Oryctolagus cuniculus). Healthy adult male (n = 4) and female (n = 4) New Zealand white rabbits were used in a randomized crossover design and received a single high (7 mg/kg) and low (3 mg/kg) dose of Bup-TP. In this study, Bup-TP achieved a plasma blood concentration >0.25 ng/mL starting at 0.5 hours after dosing that was maintained up to 72 hours after dosing in adult New Zealand white rabbits. Compared with baseline, fecal and urinary output were reduced for an average of 3.5 days after dosing; food consumption was reduced for an average of 10 days after dosing. All resolved with time and supportive care. No lesions were grossly visible on any rabbit at site of application. Bup-TP may be an effective, long-lasting, and noninvasive method of providing analgesia in rabbits. Future study is recommended to optimize dosing and procedural analgesic efficacy.

兔子通常被用作手术模型,因此需要止痛剂来缓解疼痛和优化动物福利。丁丙诺啡是一种部分微阿片类药物,市面上有各种浓度和缓释制剂,历史上一直被用作家兔镇痛药。一种外用长效丁丙诺啡制剂(Zorbium, Bup-TP)已被批准用于猫的镇痛,但尚未在家兔中进行评估。本研究对新西兰白兔(Oryctolagus cuuniculus) Bup-TP的血药浓度和药动学参数进行了评价。采用随机交叉设计,选取健康成年雄性新西兰白兔(n = 4)和雌性新西兰白兔(n = 4),分别给予高剂量(7 mg/kg)和低剂量(3 mg/kg) Bup-TP。在本研究中,Bup-TP在给药后0.5小时开始在成年新西兰大白兔中达到血浆血药浓度>0.25 ng/mL,并在给药后72小时保持不变。与基线相比,给药后粪便和尿量平均减少3.5天;在给药后平均10天,食物消耗减少。经过时间和支持性护理,一切都解决了。应用部位的任何家兔均未见明显病变。Bup-TP可能是一种有效、持久、无创的家兔镇痛方法。建议进一步研究以优化剂量和程序止痛效果。
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引用次数: 0
A Novel Strategy to Mitigate Corynebacterium bovis-Associated Hyperkeratosis in Athymic Nude Mice. 一种减轻无胸性裸鼠牛棒状杆菌相关角化过度的新策略。
Pub Date : 2025-09-01 DOI: 10.30802/AALAS-JAALAS-25-082
Abigail Michelson, Christopher Cheleuitte-Nieves, Kourtney Nickerson, Irina Dobtsis, Ileana C Miranda, Rodolfo J Ricart Arbona, Juliette Wipf, Neil S Lipman

Nude mice were inoculated with a nonpathogenic Corynebacterium bovis isolate (NPI) or Corynebacterium amycolatum to assess whether either could prevent skin lesions following inoculation with a pathogenic C. bovis isolate (PI). Crl:NU(NCr)-Foxn1nu mice (n = 6/group) were randomized into 6 groups: NPI (108 colony-forming units [CFU]); C. amycolatum (108 CFU); NPI or C. amycolatum followed 2 weeks later by PI (104 CFU); and negative and positive controls receiving sterile media or the PI (104 CFU), respectively. Colonization was assessed biweekly using isolate-specific PCR assays. Skin lesions were scored 0 to 5 daily for 4 or 6 weeks, at which point skin biopsies were collected, evaluated, and scored. No mice inoculated with the NPI and subsequently infected with the PI developed clinical signs, nor was a significant amount of the PI detected by PCR. Mice inoculated with C. amycolatum before the PI developed milder, delayed skin lesions reaching a significantly lower mean peak clinical score (MPCS; 1.2 ± 0.4) as compared with the positive control (MPCS 2.5 ± 0.5). The C. amycolatum-inoculated mice with and without PI had similar total histopathology scores, both of which were significantly higher than those for the mice inoculated with the NPI followed by the PI. These results led to evaluation of a practical exposure strategy in which nude mice (n = 6/group) were housed on NPI seeded bedding (SB) for 3 or 7 days prior to PI administration; mice housed on C. bovis-free bedding served as controls. Only 1 of 12 mice housed on SB receiving the PI developed Corynebacterium-associated hyperkeratosis (peak score of 4), whereas all unvaccinated mice receiving the PI developed Corynebacterium-associated hyperkeratosis (MPCS 2.83 ± 0.69). The PI was not detected in the SB + PI groups until 21 days postinfection with the PI. There was no significant difference in total histopathology scores across groups, but the histopathology scores were lower in mice receiving the SB.

用非致病性牛棒状杆菌(NPI)或棒状杆菌(amycolatum)接种裸鼠,以评估两者在接种致病性牛棒状杆菌(PI)后是否能预防皮肤病变。克隆:NU(NCr)-Foxn1nu小鼠(n = 6/组)随机分为6组:NPI(108个菌落形成单位[CFU]);赤柱体(108 CFU);NPI或扁桃菌2周后再进行PI治疗(104 CFU);阴性对照和阳性对照分别接受无菌培养基或PI (104 CFU)。采用分离特异性PCR检测每两周评估定植。每天对皮肤病变进行0至5分评分,持续4或6周,此时收集皮肤活检,评估并评分。接种NPI后感染PI的小鼠没有出现临床症状,PCR也没有检测到大量PI。与阳性对照(MPCS 2.5±0.5)相比,PI前接种的小鼠出现了较轻的、延迟的皮肤病变,平均峰值临床评分(MPCS; 1.2±0.4)显著降低。接种和未接种PI的amycolatum小鼠的总组织病理学评分相似,均显著高于接种NPI后再接种PI的小鼠。这些结果导致了对一种实用暴露策略的评估,在给药前,将裸鼠(n = 6/组)饲养在NPI种子床上(SB) 3天或7天;饲养在不含牛瘟杆菌的床上的小鼠作为对照。在接受PI的SB饲养的12只小鼠中,只有1只发生棒状杆菌相关性角化过度(峰值评分为4),而所有未接种PI的小鼠均发生棒状杆菌相关性角化过度(MPCS为2.83±0.69)。直到感染PI后21天,SB + PI组才检测到PI。各组间组织病理学总评分无显著差异,但注射SB的小鼠组织病理学评分较低。
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Journal of the American Association for Laboratory Animal Science : JAALAS
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