Biologic samples from 18 (12 female, 6 male) Siberian hamsters (Phodopus sungorus) representing an aged colony (17 to 27 mo) were examined. Values for CBC and serum biochemical parameters were determined, and macroscopic and microscopic pathologic evaluations were performed. Blood urea nitrogen levels were significantly higher in male (54.2 ± 14 mg/dL) compared with female (35.3 ± 22 mg/dL) hamsters and correlated histologically with a higher incidence of chronic glomerulonephropathy in males (5 of 6 males; 0 of 12 females). All 18 hamsters had histologic evidence of follicular mite infestation. Half (6 of 12) of the female hamsters showed cystic rete ovarii. Other histologic findings included thymic or thyroid branchial cysts (3 of 18), focal enteritis (2 of 18), and single cases of hepatic hemangiosarcoma, renal adenoma, subcutaneous mast cell tumor, cutaneous sebaceous adenoma, cutaneous trichofolliculoma, squamous papilloma of the nonglandular stomach, epididymal cholesteatoma, pyometra, and pituitary craniopharyngeal cyst. This study is the first published report of hematologic and serum chemical values for any population of Siberian hamsters and the first published report showing a potential male predisposition for chronic progressive glomerulonephropathy and a potential female predisposition for cystic rete ovarii.
New Zealand white rabbits are commonly used in cardiovascular research. Complete echocardiographic examination of the heart includes the evaluation of tissue Doppler (TDI) parameters, yet normal data are unavailable for rabbits. In addition, tissue velocity imaging (TV) is a potentially
useful measure of myocardial function that has not yet been applied to rabbits. Anesthetized New Zealand white rabbits (n = 31) underwent echocardiography to establish the feasibility of performing TDI and TV and establishing corresponding reference values. Standard 2D, M-mode, and
Doppler measurements were obtained in all rabbits and showed values comparable to previously published data. Interpretable TDI images were obtained in all 31 rabbits and TV in 24 of 31 rabbits. The values obtained were similar to those seen in healthy cats and are comparable to the values
found in adult humans. TDI and TV can easily be added to standard echocardiographic evaluation in rabbits. The values from the current study, obtained in normal rabbits, can be used as reference values to improve characterization of cardiac disease in this species.
In nature, free-ranging raccoons typically do not live longer than 2 y; most raccoons in the wild die young due to accidents and diseases. Therefore, few data are available regarding lesions associated with advancing age in raccoons. This communication documents the lesions present
in raccoons (7 male; 3 female) that were older than 7 y and had been used as breeders at a commercial facility in central Iowa. The most frequent microscopic lesions in these raccoons included accumulation of iron pigment in livers and spleens (10 of 10 animals evaluated), neuroaxonal degeneration
in caudal medulla (10 of 10), vascular mineralization (psammoma body) in choroid plexus (9 of 10), myocardial inclusions (7 of 8), and cystic endometrial hyperplasia (2 of 3). Other conditions were seen with less prevalence. Except for the detection of gastritis with bacteria in the gastric
mucosa of 1 raccoon, the presence of inflammatory cells in 3 choroid plexuses, and the presence of Lafora bodies in the brain of 1 animal, all conditions observed had previously been reported in raccoons. Surprisingly, islet-cell amyloidosis, previously observed as common incidental finding
in older captive raccoons, was not seen in any of the raccoons we examined. Because free-ranging raccoons are distributed over wide geographic areas, their local environment may have considerable influence on the range of spontaneous lesions that would occur in raccoons obtained from a specific
location. Therefore, the lesions found in these raccoons from central Iowa may differ from those of other raccoon populations.
Appropriate laboratory animal facility lighting and lighting protocols are essential for maintaining the health and wellbeing of laboratory animals and ensuring the credible outcome of scientific investigations. Our recent experience in relocating to a new laboratory facility illustrates the importance of these considerations. Previous studies in our laboratory demonstrated that animal room contamination with light-at-night (LAN) of as little as 0.2 lx at rodent eye level during an otherwise normal dark-phase disrupted host circadian rhythms and stimulated the metabolism and proliferation of human cancer xenografts in rats. Here we examined how simple improvements in facility design at our new location completely eliminated dark-phase LAN contamination and restored normal circadian rhythms in nontumor-bearing rats and normal tumor metabolism and growth in host rats bearing tissue-isolated MCF7(SR−) human breast tumor xenografts or 7288CTC rodent hepatomas. Reducing LAN contamination in the animal quarters from 24.5 ± 2.5 lx to nondetectable levels (complete darkness) restored normal circadian regulation of rodent arterial blood melatonin, glucose, total fatty and linoleic acid concentrations, tumor uptake of O2, glucose, total fatty acid and CO2 production and tumor levels of cAMP, triglycerides, free fatty acids, phospholipids, and cholesterol esters, as well as extracellular-signal-regulated kinase, mitogen-activated protein kinase, serine–threonine protein kinase, glycogen synthase kinase 3β, γ-histone 2AX, and proliferating cell nuclear antigen.
Fur mites are one of the most common ectoparasites of laboratory mice and traditionally are diagnosed through surveillance of individual colony animals. Although multiple diagnostic modalities exist, few recommendations suggest optimal testing methods, target colony populations, or
sampling sites. We compared the fur pluck and sticky paper techniques for the diagnosis of Myocoptes musculinus in naturally infested immunocompetent mice and evaluated the effect of mouse age and sampling site on the efficacy of fur plucks. We found that the sticky paper technique
was more likely to detect fur mites than were fur plucks. Housing mice individually increased the incidence of false-negative fur pluck tests, whereas sensitivity was equivalent for preweanling and adult mice. The ventral abdomen was the most likely single sampling location to detect evidence
of any stage of Myocoptes musculinus, but fur mite eggs were overrepresented on the neck. We found that the surface temperature of the murine neck surface was warmer than was the rump and therefore may represent a unique microenvironment for fur mite egg development. Given our findings,
we recommend that group-housed adult or preweanling mice should be selected for Myocoptes musculinus evaluation and that the ventral abdomen should be sampled. When possible, the postmortem sticky paper technique should be used rather than the antemortem fur pluck method.
Although ketamine–xylazine (KX) anesthesia is commonly used in rats, it is often reported to have an inconsistent anesthetic effect, with a prolonged induction time, an inadequate anesthetic plane, or a very short sleep time. Blood flow to the liver is known to shift after a meal
in rats, perhaps explaining anesthetic variability among rats with variable prandial status. The current study tested the hypothesis that a short period of fasting (3 h) prior to induction with intraperitoneal KX anesthesia would provide a shorter time to recumbency, a longer total sleep time,
and a more consistent loss of toe pinch response than would fed rats. Two groups of male Sprague–Dawley rats were used in blinded, crossover experiments. KX anesthesia was administered at 2 different doses (50 mg/kg–5 mg/kg and 70 mg/kg–7 mg/kg) after ad libitum feeding or
a 3-h fast. There were no significant differences between groups in induction time, total sleep time, or loss of toe pinch response. We conclude that fasting rats for 3 h prior to KX intraperitoneal anesthesia does not affect induction time, total sleep time, loss of toe pinch response or
reduce KX anesthetic variability in male Sprague–Dawley rats.
High Doses of Ketamine–Xylazine Anesthesia Reduce Cardiac Ischemia–Reperfusion Injury in Guinea Pigs
Choosing an appropriate anesthetic protocol that will have minimal effect on experimental design can be difficult. Guinea pigs have highly variable responses to a variety of injectable anesthetics, including ketamine–xylazine (KX). Because of this variability, supplemental doses often are required to obtain an adequate plane of anesthesia. Our group studies the isolated guinea pig heart, and we must anesthetize guinea pigs prior to harvesting this organ. In this study, we sought to determine whether a higher dose of KX protected isolated guinea pig hearts against myocardial ischemia–reperfusion injury. Male Hartley guinea pigs (Crl:HA; 275 to 300 g; n = 14) were anesthetized with either of 2 doses of KX (K: 85 mg/kg, X: 15 mg/kg; or K: 200 mg/kg, X: 60 mg/kg). After thoracotomy, hearts underwent 20 min of ischemia followed by 2 h of reperfusion. The high dose of KX significantly reduced myocardial infarct size as compared with the low dose (36% ± 3% and 51% ± 6%, respectively). Furthermore, the high dose of KX improved hemodynamic function over that associated with the low dose as measured by increases in both left ventricular developed pressure (49 ± 4 and 30 ± 8 mm Hg, respectively) and maximal rate of left ventricular relaxation (−876 ± 70 and −576 ± 120 mm Hg/s, respectively). However, the high dose of KX did not alter the maximal rate of left ventricular contraction or coronary flow. These results suggest that supplementation of KX to ensure an adequate anesthetic plane may introduce unwanted variability in ischemia–reperfusion studies.
We evaluated analgesic use and analgesiometry in aquatic African-clawed frogs (Xenopus laevis). We used the acetic acid test (AAT) to assess the analgesic potential of systemic xylazine hydrochloride, meloxicam, flunixin meglumine, and morphine sulfate after injection into the
dorsal lymph sac. Flunixin meglumine provided better analgesia than did the other drugs, most evident at 5 and 9 h after administration. Because the AAT was associated with the development of dermal lesions, we discontinued use of this assay and chose the Hargreaves test as an alternative
method of measuring nociception in Xenopus. This assay is commonly performed in rodents, but its efficacy in an aquatic species such as Xenopus was unknown prior to this study. We found that the Hargreaves test was an effective measure of nociception in Xenopus, and we
used it to evaluate the effectiveness of the nonopiod agents xylazine hydrochloride, meloxicam, and flunixin meglumine both in the absence of surgery and after surgical oocyte harvest. Similar to findings from the AAT, flunixin meglumine provided better analgesia in the Hargreaves test than
did the other agents when analyzed in the absence of surgical intervention. Results were equivocal after oocyte harvest. Although surgical oocyte harvest is a common procedure in Xenopus, and currently there are no published recommendations for analgesia after this invasive surgery.
Future studies are needed to clarify the efficacy of nonsteroidal antiinflammatory drugs for that purpose.
We describe a surgical method for ileal resection and anastomosis in newborn germfree piglets that was undertaken to establish a model that can be used for immunologic research and other applications. A preliminary experiment indicated that neonatal piglets with resection of approximately 60 cm of their ileum (removal of approximately 90% of the continuous ileal Peyer patches; group A) and those in which the ileum was transected (group B) could be maintained germfree for 35 d, colonized with defined gut flora, and maintained in a clean room until 70 d of age. In the final study, 12 piglets (4 each for groups A and B and 4 untreated controls), were monitored for postoperative feeding behavior, malaise, evidence for contamination with pathogenic bacteria, and weight gain. All surgical animals were free from incidental contamination from pathogens and environmental organisms with atypical colony types for 35 d. Two piglets in group B died postoperatively (1 during the preliminary experiment and 1 during the final study). Control (group C) piglets gained significantly more weight than did those in group A. These studies demonstrated that surgical resection of the ileal Peyer patches under germfree conditions can be accomplished successfully without compromising piglet health or introducing pathogens and with only a modest reduction in weight gain.
We performed 2 studies to assess the function and longevity of a novel intraosseous catheter device. For study 1, 9 goats were assigned to 3 groups (intraosseous catheter in the proximal humerus, intraosseous catheter in the proximal tibia, or standard jugular catheter). Devices in
the tibia remained in place for less time than did those in the humerus, and no goats exhibited radiographic evidence of resulting damage or structural change in surrounding bone. Positive bacterial cultures were found in all 9 goats at various time points. In study 2, 18 goats were assigned
to 2 groups (intraosseous catheter in the wing of the ilium or proximal humerus). Samples for serial aerobic and anaerobic blood cultures and CBC were collected while devices remained in use. Clinical monitoring and removal criteria were identical those for study 1. Catheters in the ilium
remained in place for less than 24 h on average, and those in the humerus remained in place for an average of 2.5 d. Several goats with proximal humeral catheters demonstrated moderate lameness after removal, and radiographic evidence of periosteal bone growth was noted in another goat. Bloodwork
indicated mild elevations of WBC counts from baseline in some cases. Bacterial growth was found in samples from 4 of 18 goats at various time points. Our study indicated that intraosseous catheters may remain safely in place for more than 24 h, but animals should be monitored closely for negative
side effects for several days after removal.
The initial goal of this study was to evaluate proteinuria by using the protein to creatinine (UPC) ratio of urine obtained by cystocentesis of healthy adult captive chimpanzees. Urine samples were collected by using ultrasound-guided cystocentesis from 125 (80 male, 45 female) captive
chimpanzees. All samples were collected over a 17-mo time period (August 2008 to January 2010) during the animal's annual physical examination. Samples were assayed at a veterinary diagnostic laboratory. Results indicated that both age and blood contamination affect the UPC ratio and therefore
alter the diagnostic utility of the UPC ratio in chimpanzees. In addition, this research establishes reference ranges by age for the UPC ratio in healthy adult chimpanzees. Chimps younger than the median age of 24.6 y have a median UPC ratio of 0.098 (range, 0 to 1.76), whereas older animals
have a median UPC of 0.288 (range, 0 to 2.44). Our results likely will enable veterinarians working with chimpanzees to better evaluate their renal function.
Athymic nude mice infected with Corynebacterium bovis typically exhibit transient hyperkeratotic dermatitis. Our vivarium experienced an increased incidence of disease characterized by persistent skin lesions and increased mortality, leading to this study. For detection of infection, skin and buccal swab methods showed comparable sensitivities in nude mice. Various prevention, treatment, and eradication strategies were evaluated through clinical assessment, microbiology, and histopathology. In experimentally naïve athymic nude mice, a 2-wk course of prophylactic amoxicillin-containing
diet (1200 ppm amoxicillin; effective dose, 200 mg/kg) was ineffective at preventing infection or disease. There was also no significant difference in disease duration or severity in athymic nude mice that received amoxicillin diet or penicillin–streptomycin topical spray (penicillin, 2500 U/mL; streptomycin, 2500 μg/mL). Prolonged treatment with 4 or 8 wk of amoxicillin diet cleared only a small number of athymic nude mice that had subclinical C. bovis infections. Antibiotic sensitivity of C. bovis isolates demonstrated a small colony isolate with less susceptibility to all antibiotics compared with a large colony isolate. Resistance did not appear to develop after prolonged treatment with amoxicillin. Provocation testing by administration of cyclophosphamide (50 mg/kg IP every 48 to 72 h for 90 d) to subclinically infected athymic nude mice resulted in prolonged clinical disease that waxed and waned without progression to severe disease. Our findings suggest that antibiotic prophylaxis and treatment of clinical disease in experimentally naïve mice is unrewarding, eradication of bacterial infection is difficult, and severe disease associated with C. bovis is likely multifactorial.
Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis),
and rhesus macaques (Macaca mulatta) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic
parameters. The half-life of cefovecin was 4.95 ± 1.47 h in cynomolgus macaques, 9.17 ± 1.84 h in olive baboons, and 8.40 ± 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended
half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that
active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study
highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.
This case study details the unusual clinical findings in a unique paw-pad disorder that recently emerged among 2 male and 1 female naïve purpose-bred beagle dogs (Canis familiaris) newly received into our facility. During acclimation period physical examinations, the affected
dogs demonstrated constantly moist, soft paw pads on all 4 feet. No information was available regarding the epidemiology and pathogenesis of this pad condition in beagle dogs. Here, we report the results of physical examination, clinical chemistry analysis, hematology, histopathology, detailed
observations, and novel testing techniques performed during the acclimation period. Histopathology of several sections of affected footpads was compared with that of an age-matched dog with clinically normal paw pads. We describe the morphologic features of a distinctive cutaneous canine footpad
condition and discuss the possible differential diagnoses. The histologic and clinical features were most consistent with those of hyperhidrosis; to our knowledge, this report is the first description of hyperhidrosis as a distinct condition in purpose-bred beagle dogs.
In subclavian steal phenomenon (SSP), the subclavian artery develops a stenoocclusive disease proximal to the origin of the vertebral artery, leading to pronounced hemodynamic changes such as arterial flow reversal. Although SSP is a common echographic finding in humans, the phenomenon
occurs only rarely in animals; consequently its physiologic features have not been reported previously. Here we describe the clinical and morphologic features of a spontaneous left SSP that was an incidental finding in an 18-y-old female rhesus macaque (Macaca mulatta). Our findings
were documented through high-quality imaging studies obtained by using a computerized 3D tomography apparatus and clinical assessment of systolic and diastolic blood pressures.
A 3-y-old male rhesus macaque (Macaca mulatta) was noticed to be lethargic in the compound. Physical exam revealed cyanotic mucous membranes, dyspnea, bilateral harsh lung sounds, wheezing on expiration, and a firm mass possibly associated with the liver. Radiographs revealed
bilateral soft tissue opacities in the thorax. Due to poor prognosis, the rhesus was euthanized, and a necropsy was performed. Both right and left lung lobes were consolidated and had multifocal white–tan masses. On cut section, the masses were firm, had areas of necrosis, hemorrhage,
and often contained a tenacious exudate. Masses were identified in the liver and both kidneys. Given the morphologic features of the neoplasm, a diagnosis of squamous cell carcinoma was made. Immunohistochemistry staining for thyroid transcription factor, a nuclear transcription factor normally
found in lung, thyroid, and tumors arising from either of those tissues, confirmed that the masses originated from the lung. Malignant primary lung tumors are divided into 8 main histologic subtypes: squamous cell carcinoma, small-cell carcinoma, large-cell carcinoma, adenocarcinoma, adenosquamous
carcinoma, sarcomatoid carcinoma, carcinoid tumor, and salivary gland tumors. Clinical signs associated with lung tumors include, but are not limited to, dyspnea, coughing, hemoptysis, lethargy, anorexia, and weight loss. Although squamous cell carcinoma will be low on the differential list
for these clinical signs, we encourage clinicians and researchers to not rule it out solely based on incidence and age of the animal.