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Since the anthrax attacks of 2001, the emphasis on developing animal models of aerosolized select agent pathogens has increased. Many scientists believe that nonhuman primate models are the most appropriate to evaluate pulmonary response to, vaccines for, and treatments for select agents such as Yersinia pestis (Y. pestis), the causative agent of plague. A recent symposium concluded that the cynomolgus macaque (Macaca fascicularis) plague model should be characterized more fully. To date, a well-characterized cynomolgus macaque model of pneumonic plague using reproducible bioaerosols of viable Y. pestis has not been published. In the current study, methods for creating reproducible bioaerosols of viable Y. pestis strain CO92 (YpCO92) and pneumonic plague models were evaluated in 22 Indonesian-origin cynomolgus macaques. Five macaques exposed to doses lower than 250 CFU remained free of any indication of plague infection. Fifteen macaques developed fever, lethargy, and anorexia indicative of clinical plague. The 2 remaining macaques died without overt clinical signs but were plague-positive on culture and demonstrated pathology consistent with plague. The lethal dose of plague in humans is reputedly less than 100 organisms; in this study, 66 CFU was the dose at which half of the macaques developed fever and clinical signs (ED(50)), The Indonesian cynomolgus macaque reproduces many aspects of human pneumonic plague and likely will provide an excellent model for studies that require a macaque model.

Purpose: The goals of the study were to find a safe intraperitoneal injection anesthesia protocol for medium-duration surgery in mice (e.g., embryo transfer/vasectomy) coupled with a simple method to assess anesthesia depth under routine laboratory conditions., Methods: Eight anesthetic protocols consisting of combinations of dissociative anesthetics (ketamine, tiletamine), alpha2-agonists (xylazine, medetomidine), and/or sedatives (acepromazine, azaperone, zolazepam) were compared for their safety and efficacy (death rate, surgical tolerance), using observations and reflex tests. The four best protocols were further evaluated during vasectomy: physiologic measurements (respiratory rate, electrocardiogram, arterial blood pressure, body temperature, blood gas tensions, and acid-base balance) were used to characterize the quality of anesthesia. The reactions of physiologic parameters to surgical stimuli were used to determine anesthesia depth, and were correlated with reflex test results., Results: The protocol with the highest safety margin and the longest time of surgical tolerance (54 min) was ketamine/ xylazine/acepromazine. Three further anesthetic combinations were associated with surgical tolerance: ketamine/ xylazine, ketamine/xylazinelazaperone, and tiletamine/xylazine/zolazepam (Telazol/xylazine). The protocols consisting of ketamine/medetomidine and ketamine/azaperone were not associated with clearly detectable surgical tolerance. The most reliable parameter of surgical tolerance under routine laboratory conditions was the pedal withdrawal reflex., Conclusions: The best intraperitoneal injection anesthesia regimen consisted of ketamine/xylazine/acepromazine. The dose must be adapted to the particulars of each experimental design (mouse strain, sex, age, mutation). This is best done by measuring surgical tolerance, using the pedal withdrawal reflex.

A 45-year-old male veterinarian was found dead in bed. Police investigation showed no evidence of trauma or other suspicious circumstances. Autopsy was unremarkable except for cardiomegaly and hepatosplenomegaly. Toxicological analysis revealed the presence of Telazol and ketamine. Telazol is a veterinary anesthetic agent that is composed of equal parts of tiletamine and zolazepam. Tiletamine is a disassociative anesthetic similar to ketamine and phencyclidine, and zolazepam is a diazepine derivative tranquilizer used to minimize the muscle hypertonicity and seizures associated with tiletamine. Quantitation of tiletamine and zolazepam was performed using gas chromatography-mass spectrometry in the selected ion monitoring mode following a solid-phase extraction. Postmortem blood, urine, and liver concentrations of tiletamine were 295 ng/mL, 682 ng/mL, and 196 ng/g, respectively, whereas postmortem concentrations of zolazepam for the same tissues were 1.71 microg/mL, 1.33 microg/mL, and 15.5 microg/g, respectively. Blood and urine ketamine levels were 37 ng/mL and 381 ng/mL, respectively. The cause of death was ruled an acute mixed drug intoxication of tiletamine, zolazepam, and ketamine with the manner of death ruled as unclassified.