Journal of the American Association for Laboratory Animal Science : JAALAS最新文献

The former [Pasteurella] pneumotropica complex has rendered until now 12 Rodentibacter species, which has implications in the monitoring of these highly prevalent laboratory rodent microorganisms. Rodentibacter spp. are known as classic opportunistic pathogens of laboratory rodents and represent noteworthy members of the oral and genital microbiome, with potential pathophysiological interferences in colonized animals. Laboratory mice and rats are predominantly colonized by host-specific Rodentibacter spp., with R. pneumotropicus and R. heylii as mouse-specific species and R. ratti, R. heidelbergensis, R. rarus, and R. trehalosifermentans as rat-specific species; however, host specificity of R. haemolyticus, currently prevalent in both species, remains to be elucidated. Nevertheless, cross contaminations with the taxa from the opposite host occurs between mice and rats. The monitoring occurs by classic culture and/or by molecular techniques, although the latter are currently available only for a few Rodentibacter taxa. Unfortunately, many current health monitoring strategies do not take into consideration the host specificities of these taxa and are often focused nearly exclusively on the molecular diagnostics of R. pneumotropicus and R. heylii, thus neglecting the remaining taxa. Until future research addresses the lack of molecular tests available for all relevant Rodentibacter spp. and a host-specific monitoring is implemented, we consider that monitoring exclusively by current molecular methods risks missing opportunistic members of this genus. Importing laboratory rodents based on health reports relying solely on molecular assays is currently associated with an increased risk of accepting Rodentibacter-positive animals.

Pain management is an expansive and ever-evolving component of managing nonhuman primates in the research setting. Opioids are a commonly used analgesic medication and are available in a variety of formulations. A novel, long-acting transdermal buprenorphine topical solution was recently approved for use in cats to provide up to 4 days of postoperative analgesia. The purpose of this study was to evaluate the pharmacokinetic profile of this transdermal formulation in cynomolgus macaques. Five male cynomolgus macaques were used in a 2-formulation crossover study to compare the pharmacokinetics of a single transdermal dose (20 mg) to a single intravenous dose of buprenorphine HCl (0.01 mg/kg). Plasma buprenorphine levels were measured for animals receiving transdermal buprenorphine topical solution at time points 0 (baseline), 1, 3, 6, 12, 24, 36, 48, 72, 96, and 120 hours postdosing. Plasma buprenorphine levels were measured for animals receiving intravenous buprenorphine at time points 0 (baseline), 2, 5, 10, 25, 45, and 60 minutes and at 3, 6, 12, and 24 hours postdosing. Animals weighing 3.55-6.2 kg reached therapeutic plasma levels, as hypothesized in the literature (0.1 ng/mL), within 1 hour of administration and maintained therapeutic levels for at least 72 hours. This study demonstrates that this novel transdermal buprenorphine topical solution can offer a refinement in pain management of nonhuman primates through a less invasive route of administration with an extended duration of action.

The study described here evaluated the efficacy of supplemental oxygen in preventing hypoxemia (pO2 < 80 mm Hg) in pigs chemically restrained with ketamine, dexmedetomidine, and diazepam. Twenty gilts (154.5 ± 4.8 kg, 250 ± 2 days old) received a combination of ketamine (2 mg/kg), dexmedetomidine (10 µg/kg), and diazepam (0.1 mg/kg) via the auricular vein. Following induction, animals were positioned in right lateral recumbency and assigned to receive either ambient air (ambient air group, n = 10) or 100% oxygen at 5 L/min via a nasal cannula inserted 16 cm into one nostril (oxygen group, n = 10). Heart rate, peripheral oxygen saturation, and rectal temperature were monitored every 5 minutes. Arterial blood samples were collected at 5, 15, and 30 minutes to assess blood gas and electrolyte parameters. Induction time, time to sternal recumbency, time to standing, and recovery quality were also recorded. All gilts in the ambient air group developed hypoxemia, whereas those in the oxygen group maintained pO2 > 80 mm Hg. Peripheral oxygen saturation values were consistently higher in the oxygen group, whereas HR, respiratory rate, and temperature did not differ significantly between groups. Induction and recovery times, as well as recovery quality scores, were also similar between groups. Intranasal oxygen supplementation at 5 L/min effectively maintained arterial oxygenation and prevented hypoxemia in gilts anesthetized with the ketamine-dexmedetomidine-diazepam combination.

Mice are a valuable tool for preclinical research, enabling the investigation of fundamental questions about disease mechanisms, drug delivery, and pharmacokinetics. Intestinal pH influences drug delivery and pharmacokinetics of orally administered compounds. However, little is known about variations in pH along different sections of the mouse gastrointestinal tract. We therefore compared pH in 7 gastrointestinal tract sections of 48 male and female BALB/c, C57BL/6, and NMRI mice from 2 different vendors, as well as 8 streptomycin-treated and 8 germ-free BALB/c male and female mice from one vendor. The pH in the duodenum and cecum varied between strains and vendors. Relative to untreated barrier-bred mice, streptomycin-treated mice had significantly higher pH in the jejunum, and germ-free mice had significantly higher pH in the jejunum, cecum, and proximal colon, underlining the role of gut microbes in regulating pH levels throughout the gastrointestinal tract. In conclusion, we show that mouse strain, vendor, and microbial presence, but not sex, influence gastrointestinal pH in mice. Given the importance of gastrointestinal pH for pharmacokinetics, drug delivery systems, and gastrointestinal microbial behavior, these data will provide an important foundation for the choice of mouse models for research involving the gastrointestinal tract.

In preclinical models, indwelling intravenous catheters and vascular access ports are often essential components of biomedical research aimed at modeling human disease. For instance, animal models of drug self-administration are used for many reasons, including to assess abuse liability, to study physiologic and neurologic consequences of drug exposure, and to examine the efficacy of behavioral and/or pharmacological interventions. The most frequent route of drug self-administration in preclinical animal models is the intravenous route via indwelling intravenous catheters. The present study examined 23 years of drug self-administration studies in Old World macaques used in drug self-administration studies at Wake Forest University School of Medicine. The medical records for individually or pair-housed adult rhesus monkeys (n = 10 females and 172 males) and socially housed cynomolgus monkeys (n = 64 females and 92 males), all implanted with indwelling intravenous catheters and associated vascular access ports, were examined. The most frequent vein catheterized was the femoral vein, followed by the internal and external jugular vein; the least frequent was the brachial vein. The infection rates over 23 years and >500 catheters in cynomolgus and rhesus monkeys were 13.7% and 10.3%, respectively. The average catheter remained patent and implanted in the vein for 22.5 months in cynomolgus monkeys and 15.5 months in rhesus monkeys. These findings highlight significant strengths in using Old World macaques, both rhesus and cynomolgus, in long-term, longitudinal studies involving indwelling intravenous catheters.

Segmented filamentous bacteria (SFB), or Candidatus savagella, are gram-positive, spore-forming, filamentous commensal bacteria that colonize the ilea of mice and rats. SFB can impact certain research studies due to their effect on the innate and adaptive immune system. Therefore, there is a need to eliminate SFB from some rodent colonies. Antibiotics are an effective treatment method that have been shown to be successful at eradicating this bacterium. Commonly, antibiotics are supplied to rodents via water. However, antibiotics in water have several limitations, depending on the type of water and the length of time in water, and administration is labor intensive. Therefore, this study sought to create a rodent diet containing the antibiotic ampicillin. The feed was constructed to counter an expected ampicillin concentration decrease from the pelleting process and irradiation. Mice were placed on the ampicillin feed for 4 weeks, and SFB was measured via PCR fecal analysis. After one week of feeding the ampicillin diet, all mice in the treatment group were negative for SFB. These mice remained negative for 2 additional weeks after treatment cessation. This study shows ampicillin diet is an effective method to eliminate SFB from mouse colonies.

A female, research-naive, strain 13 guinea pig with no previous significant health history was noted to have a persistent vaginal discharge. On physical examination a soft mass was noted in the lower abdomen accompanied by a serosanguineous vaginal discharge. Due to a poor prognosis, the animal was euthanized. At necropsy, the left uterine horn was markedly enlarged and contained a large amorphous mass. Light microscopy examination showed that the mass had dense areas containing stromal cells surrounded by connective tissue, congested blood vessels, areas of necrosis, hemorrhage, and occasional cyst formation. In some areas numerous bacteria, both rods and cocci, were noted and the uterine wall showed increased thickness caused by a polymorphonuclear cell inflammatory infiltrate. Bacteriological culture and isolation from the vaginal discharge revealed a mixed infection with Escherichia coli, Bacteroides fragilis, Proteus mirabilis, Enterococcus spp., and α-hemolytic Streptococcus spp. while culture and isolation from the uterus revealed a mixed infection with E. coli, Pseudomonas aeruginosa, B. fragilis, and Globicatella sanguinis. The pathology findings were consistent with decidual cell reaction and endometritis. Vaginal bleeding is not a common clinical sign in decidual cell reaction and usually does not require treatment since the lesion in many cases resolves on its own by apoptosis and resorption. However, in this case, systemic antibiotics may have been beneficial to treat the endometrial infection. These findings suggest that decidual cell reactions may occur accompanied by, or as a result of, intrauterine infections in guinea pigs. The potential role of bacteria in decidual cell reaction should be further explored in guinea pigs.

Guinea pigs have been a standard model in cardiovascular pharmacology and physiology research, but the advent of transgenic models has largely replaced them with mouse and rat models. However, guinea pigs remain important models in cardiac electrophysiology, drug-induced arrhythmias, or atherosclerosis research, and they have recently gained importance for studying one specific research question, that is, transplantation of pluripotent stem cell derived cardiomyocytes to repair the cryo-injured heart. Their human-like cardiac electrophysiology, together with their small size that facilitates handling and housing, make guinea pigs a valuable experimental model for these studies. However, repeated open heart surgeries in guinea pigs are technically demanding and accompanied by high mortality. In this study, we retrospectively examined sequential protocol modifications and describe how protocol refinements led to improved survival rates. Cryo-injury was performed in female Dunkin-Hartley guinea pigs under general anesthesia with a liquid nitrogen-cooled probe via a lateral thoracotomy. Cells were transplanted during a second surgery 7 days later. We analyzed data from up to 558 animals to determine mortality rates and morphologic and functional parameters. Initial studies revealed a mortality rate of ∼50%. Sequential modifications led to a significant reduction, with the refined protocol achieving a perioperative mortality rate of ∼30%. The procedures were completed in <35 minutes, and survival rates for the observation period (up to 8 weeks) were 70%. Scar size was evaluated in 144 (4 weeks, n = 92; 8 weeks, n = 52) animals and showed a significant, but shallow correlation with echocardiographically determined heart function. Taken together, refined surgery protocols allow safe and reproducible cryo-injury with subsequent cell injections in guinea pigs with an improved mortality rate.

Fischer 344 rats are a well-characterized laboratory animal. Of note, their popularity as a research model declined due to the high incidence of spontaneous tumor development in the strain. Among these tumors, testicular interstitial cell tumors (ICTs) are frequently observed. We describe here three aged male Fischer 344 rats that were submitted for diagnostic pathology due to an increase in morbidity (increased respiratory effort, general malaise, and weight loss) in the research cohort. In all animals, there was bilateral enlargement of the testes. On the cut surface, multiple well-demarcated masses were compressing and replacing the original testicular tissue. Histologically, these masses were identified as ICTs. The tumors were composed of 3 distinct cell types that correlate with varying degrees of interstitial cell maturation. In one rat, intravascular pulmonary metastases were observed, which resembled the ICT cells morphologically. Malignant ICTs are an unusual finding despite the very high incidence of ICTs in Fischer 344 rats. Our assessment suggests that there are no morphologic criteria that reliably predict malignant and metastatic behavior of ICTs in F344 rats, highlighting the need for clinical monitoring of animals for which castration is chosen as a treatment.

Rabbits are widely used in biomedical research as models for atherosclerosis with disease induction achieved through a high-cholesterol diet, transgenic approaches, or spontaneous development with aging. At our institution, New Zealand White rabbits were induced to develop atherosclerosis via a high-cholesterol diet followed by arterial balloon injury. This model was established to support intravascular molecular imaging studies aimed at tracking atheromatous plaque progression in vivo. To accelerate plaque development, a subcutaneous osmotic pump delivering angiotensin II at 50 ng/kg/min was implanted. While this method enhanced disease progression, unexpected clinical complications were observed. In this retrospective case report, we reviewed clinical records from 54 rabbits over a 2-year period. Clinically, most study animals showed different levels of inappetence. Three presented respiratory symptoms including cyanosis, dyspnea, or tachypnea, while another 3 exhibited neurologic signs such as altered mentation and paralysis. Eight rabbits (14.8%) were euthanized due to severe clinical signs. Necropsy findings in the affected animals commonly revealed pleural and/or peritoneal effusion; one case included chyloabdomen, a condition not previously reported in rabbits. Of these, 7 had myocardial degeneration and fibrosis. These findings suggest that angiotensin II infusion in this rabbit model of atherosclerosis may induce myocardial fibrosis as a significant adverse effect. This report highlights potential complications associated with the model and provides guidance for clinical monitoring, diagnosis, and management in future studies.