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

Mice are commonly infected with Nippostrongylus brasiliensis (Nb) to study their immune responses. However, biosecurity measures have not been established for housing Nb-infected mice and rats. Transmission reportedly does not occur when infected mice are cohoused with naive mice. To test this, we inoculated female NOD. Cg-Prkdc^scid Il2rg^tm1Wjl /Sz(NSG;n = 12) and C57BL/6J (B6;n = 12) mice with 750 Nb L₃ larvae. These mice were then cohoused with naïve NSG ( n = 24) and B6 ( n = 24) mice (1 infected and 2 naïve mice per cage (24 cages) for 28 d in static microisolation cages that were changed every 14 d. We also did several studies to determine the conditions that favor horizontal transmission. First, we assessed in vitro development to the L₃ stage of Nb egg-containing fecal pellets maintained under 4 environmental conditions (dry, moist, soiled bedding, and control). Second, we assessed infection of naïve NSG mice ( n = 9) housed in microisolation cages that contained soiled bedding spiked with infective L₃ larvae (10,000/cage). Third, we gavaged NSG mice ( n = 3) with Nb eggs to model the potential for infection after coprophagy. We found that naïve NSG (9 of 24) and B6 (10 of 24) mice cohoused with an infected cagemate passed Nb eggs in feces as early as 1 d after cohousing and intermittently thereafter for varying periods. This shedding was presumably the result of coprophagy because adult worms were not detected in the shedding mice at euthanasia. Although eggs developed in vitro into L₃ larvae under moist and control environmental conditions, none of the NSG mice housed in cages with L₃ -spiked bedding or gavaged with eggs became infected with Nb. These findings indicate that infectious horizontal transmission does not occur when mice are housed with Nb-shedding cage mates in static microisolation cages with a 14-d cage-changing interval. Results from this study can be used to inform biosecurity practices when working with Nb-infected mice.

Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits (n = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E₂ (PGE₂ ) and thromboxane (TxB₂) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB₂ and PGE₂ plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE₂ concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.

Since 2015, the National Institutes of Health has called for its funded preclinical research to include both male and female subjects. However, much of the basic animal research that has studied heart rate and blood pressure in the past has used male rats. Male rats have been preferred for these studies to avoid the possible complicating effects of the female estrous cycle. The aim of the current study was to determine whether blood pressure and heart rates vary as a function of the estrous cycle phase of young normotensive Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) female rats. Blood pressure and heart rate were measured at the same time of day throughout the estrous cycle by using a noninvasive tail cuff sphygmomano- metric technique. As expected, 16-wk-old female SHR rats had higher blood pressure and heart rates than did age-matched female WKY rats. However, no significant differences in mean, systolic, or diastolic arterial blood pressure or heart rate were detected across the different stages of the estrous cycle in either strain of female rats. Consistent with previous reports, heart rates were higher and showed less variation in the hypertensive SHR female rats as compared with the normotensive WKY female rats. These results indicate that studies measuring blood pressure and heart rate can include young female SHR and WKY rats with no effect of estrous cycle stage.

Minimization of potential pain and distress of rodents undergoing euthanasia is a touchstone of veterinary clinical medicine. Evaluation of this issue in postweanling rodents has supported revisions to the AVMA (American Veterinary Medical Association) Guidelines on Euthanasia in 2020. However, relatively little information is available on humane aspects of anesthesia and euthanasia in neonatal mice and rats. These neonates are not reliably euthanized by exposure to commonly used inhalant anesthetic agents due to their physiologic adaptations to hypercapnic environments. Therefore, options such as prolonged inhalant anesthetic gas exposure, decapitation, or use of injectable anesthetics are recommended for neonates. All of these recommended methods have operational implications, ranging from reported job dissatisfaction by animal care staff to rigorous reporting requirements associated with the use of controlled substances. This lack of a euthanasia method that does not entail operational issues hampers the ability of veterinary professionals to provide appropriate guidance to scientists working with neonates. This study was designed to assess the effectiveness of carbon monoxide (CO) as an alternative euthanasia agent for mouse and rat pups on postnatal days (PND) 0 to 12. The study demonstrates that CO may be a potential alternative for preweanling mice and rats at PND6 or older but is not appropriate for neonates at PND5 or younger.

Nasal drug delivery in rodents is a challenging procedure, especially for brain targeting, as the position of the material in the nasal cavity determines the success of the administration method. The objective of this study was to assess a novel intranasal administration technique for nose-to-brain delivery of biodegradable nasal films. The method was performed in C57BL/6 (n = 10; age, 8 wk) under inhaled sevoflurane. Twenty-four gauge catheters were used for the procedure. Hydroxypropyl methyl-cellulosebased film was formed in the lumen of the catheter and then delivered into the mouse nostril by pushing it out of the lumen using a trimmed and polished needle. Methylene blue was incorporated in the film-forming gel to indicate the delivery area in which the films were deposited. After administration, all mice recovered from anesthesia without incident. None of the mice showed any signs of injury, discomfort, or nose bleeding, thus allowing us to characterize the administration method as noninvasive. Furthermore, postmortem evaluation revealed olfactory-centered placement of the polymeric films, confirming the accuracy and repeatability of the method. In conclusion, this study documented the use of, a novel, noninvasive, intranasal administration technique for nose-to-brain drug delivery in biodegradable films for use in mice.

The goals of this study were to determine whether mice would adapt to a low-calorie flavored water gel as their sole source of hydration and whether the addition of acetaminophen, tramadol, meloxicam, or buprenorphine to the gel would affect their intake. Water and gel intakes were measured during a 4-phase study, each of which lasted 1 wk: phase 1, standard water bottle only; phase 2, standard water bottle and a separate tube containing water gel; phase 3, water gel only; and phase 4, water gel containing an analgesic drug. Water consumption, corrected for body mass, was not different between male and female mice when water was available (phases 1 and 2). However, the total consumption of water and water gel was higher for females than males during phase 2, and female mice consumed more gel than males during phase 3. When male and female data were combined, total corrected water intake was not different among the first 3 phases of the study. Gel intake did not change significantly after the addition of acetaminophen, meloxicam, buprenorphine or tramadol as compared with untreated water gel. These data suggest that drugs presented in the low-calorie flavored water gel may be a viable alternative to injection or gavage for the administration of analgesic drugs.