Rectal temperature is a prognostic indicator in client-owned guinea pigs.

OBJECTIVES: To determine whether rectal temperature was associated with patient mortality in client-owned guinea pigs upon presentation to a veterinary hospital. MATERIALS AND METHODS: The medical record database at a veterinary teaching hospital was searched for records of guinea pigs from January 2016 through June 2019. Guinea pigs were included in the study if a rectal temperature was measured at presentation and there was data on survival status 7 days post-presentation. If survivor status was not documented in the medical record, follow-up information was obtained from the client via telephone or email. The data was ultimately collected from 201 client-owned guinea pigs who presented for 388 independent examinations. Univariable, multivariable and sensitivity analyses were performed. RESULTS: Guinea pigs with hypothermia (<37.9°C) at presentation had a relative risk of mortality within 7 days of presentation almost 3 times greater than guinea pigs without hypothermia (relative risk: 2.88; 95% confidence interval: 1.86 to 4.48). For each 0.55°C decrease in rectal temperature, the odds of death increased 1.6 times (odds ratio: 1.64; 95% confidence interval: 1.42 to 2.89). Sensitivity analyses confirmed the robustness of the finding. CLINICAL SIGNIFICANCE: Rectal temperature was a predictor of death for guinea pigs presenting for care at a veterinary hospital. Obtaining a rectal temperature recording should be considered for patient guinea pigs.

Age-dependent influence of dietary zinc restriction on short-term memory in male rats.

Zinc is an essential micro-nutrient involved in numerous physiological functions. The high content of zinc in the hippocampus, coupled with the integral involvement of the hippocampus in memory, strongly implicates zinc in memory processing. The hypothesis of the current study was that dietary zinc restriction influenced short-term memory in postweaned rats, and this influence was age-dependent. Male rats (43 days to 18 months old) were divided into five experimental groups based on age, and fed zinc-adequate (zinc at 20 mg/kg as zinc chloride) or zinc-deficient (zinc less than 1-2 mg/kg) diets for a minimum of 3 weeks. Short-term memory was assessed using the distal-cue version of the Morris water maze (MWM). All rats fed the zinc-restricted diet exhibited cyclic anorexia, decreased weight gain, and significantly lower liver and femur zinc concentrations compared to age-matched controls. Further, whole brain, hippocampal, and cerebral wet weights were significantly reduced in the zinc-restricted treatment groups of all the age groups. Only zinc-restricted rats that were less than 62 days of age at the start of zinc restriction demonstrated significantly prolonged escape latencies in the water maze, indicating deficits in short-term memory. Regression analyses confirmed that the short-term memory deficits were correlated with significantly lower hippocampal and cerebral zinc concentrations compared to age-matched control and pair-fed rats. These results emphasize the significance of a critical age of influence for dietary zinc in memory processing, and the importance of considering age when studying zinc nutriture and CNS function.

Supplementation with L-histidine during dietary zinc repletion improves short-term memory in zinc-restricted young adult male rats.

Zinc, an essential dietary element, modulates neurotransmission in brain regions associated with cognition. Cognitive dysfunction has been reported in offspring of female rats fed zinc-restricted diets during gestation and/or lactation. Studies on the cognitive effects of zinc restriction during young adulthood are limited. After a 3-wk period of dietary zinc restriction, male rats (71-75 d old) were repleted with zinc chloride alone, or zinc chloride supplemented with L-histidine, and short-term memory was measured using the Morris water maze. During restriction, zinc-restricted rats demonstrated significantly longer (86.0%) retrieval latencies than nonrestricted controls, and significantly lower liver (25.5%), bone (32.5%) and hippocampal (3.2%) zinc concentrations. During subsequent repletion, rats repleted with zinc chloride supplemented with L-histidine improved their retrieval latencies to the extent that they were no longer significantly different from controls by repletion d 3. This was associated with a return of hippocampal zinc concentrations to control values by repletion d 3. The mean retrieval escape latencies of the zinc chloride-repleted rats remained significantly prolonged (75.0%). Collectively, these data indicate the following: 1) feeding a zinc-restricted diet for 3 wk impairs short-term memory in young adult male rats, and 2) repletion with dietary zinc supplemented with L-histidine improves short-term memory function more efficiently than dietary zinc chloride alone. The latter point suggests that dietary zinc supplemented with L-histidine is more bioavailable to the brain than zinc provided as zinc chloride alone. These findings are important in that they highlight the importance of both dietary zinc formulation and the use of functional assessments in determining zinc nutriture.

The rationale for culling of rodent litters.

Based on a review of the pertinent literature and our own unpublished data, it is recommended that culling of rodent litters in the early postnatal period should be a standard practice in delivery-type reproduction studies. This, in turn, will reduce the litter size-induced variability in the growth and development of pups during the postnatal period and thus increase the sensitivity of statistical analyses to detect treatment-related effects. This will also ensure that any adverse effects on pup growth (body weight gain) and development (reflex and behavior development) are not masked by a treatment-induced reduction in litter size. The culling should be carried out randomly and no attempt should be made to selectively cull sick or underweight pups. Since male pups weigh significantly more than females and studies have shown differences in maternal behavior toward one sex over the other, whenever possible each culled litter should consist of an equal number of males and females.

Inhalation toxicity study of a haloalkene degradant of sevoflurane, Compound A (PIFE), in Sprague-Dawley rats.

BACKGROUND: Under certain circumstances in the clinical setting, contact of the anesthetic sevoflurane with a CO2 absorbent (e.g., soda lime, Baralyme) leads to the formation of a degradant designated as pentafluoroisopropenyl fluoromethyl ether (PIFE; Compound A). Previous studies have shown that the kidney is the primary target organ for toxicity in the rat. This study was designed to determine the impact of PIFE on rat renal histology correlated with functional changes. The findings are discussed in terms of probable mechanism of action and relevance to humans. METHODS: Male and female Sprague-Dawley rats were exposed to 0, 30, 61, 114, or 202 ppm PIFE for a single 3-h period via nose-only inhalation. Rats were observed daily for behavioral changes or external physical signs of toxicity (i.e., lacrimation, dyspnea, piloerection, etc.) and body weights were recorded at 6, 4, and 1 day preexposure and 1, 3, 7, and 13 days postexposure. Animals were evaluated for hematologic, clinical chemistry and/or urinalysis changes immediately postexposure and/or at 1, 4, and 14 days postexposure. Rats were killed, subjected to a macroscopic postmortem examination, and evaluated for histopathologic changes in all major tissues and organs at 1, 4, and 14 days postexposure. RESULTS: Labored breathing was observed in 3 of the 20 and 2 of the 20 rats in the 114 ppm and 202 ppm groups, respectively, during the 3-h exposure period. No significant reductions in body weight gain were noted during the 2-week study period. Clinical chemistry evaluations revealed increases in blood urea nitrogen and creatinine 1 day postexposure in males and females exposed to 202 ppm PIFE. Changes in urinary glucose, protein and N-acetyl-beta-glucoaminidase/creatinine were evident one day postexposure in males and females exposed to 202 ppm and in males exposed to 114 ppm PIFE. Most values were within normal ranges by 4 or 14 days postexposure. No drug-related alterations in hematologic parameters were noted. Evidence of olfactory epithelial degeneration and desquamation in the nasal turbinates was noted at 4 days postexposure in male and female rats exposed to 202 ppm PIFE. Concentration-dependent renal tubular necrosis and tubular cell hyperplasia, in the corticomedullary border, were observed in males and females exposed to 114 and 202 ppm PIFE. The severity of tubular necrosis in both males and females was considered minimal to slight at the 114 ppm exposure concentration and slight to moderate at the 202 ppm exposure. Both the numbers of affected animals and severity were reduced over time. The most marked changes in serum and urine chemistry were associated with the animals described as having moderate renal necrosis. Male rats appeared more susceptible to nephropathy than female rats. There were no other PIFE-related histopathologic findings. CONCLUSIONS: The renal histopathologic findings in this study are consistent with those reported in previous acute studies in rats after PIFE administration. Functional changes in the kidney, as evidenced by serum chemistry and urinalyses, were observed at exposure concentrations that induced morphologic alterations.

Potential human developmental toxicants and the role of animal testing in their identification and characterization.

Some 50 chemicals have been identified from environmental, occupational, or therapeutic exposure data as being potential developmental toxicants in humans. The toxicity pattern of these chemicals in humans has been characterized and correlated with developmental toxicity end points in laboratory animal models in order to determine the relevance and predictiveness of the results of testing in animals in extrapolation to human data. In general, animal developmental toxicity data closely paralleled human outcomes, and while humans in most cases were more sensitive than animals, the data support the concept that, imperfections aside, studies in animals serve a vital role in the hazard identification process.

Reproductive and developmental toxicological evaluation of sanguinaria extract.

Reproductive and developmental toxicology studies were conducted with orally administered sanguinaria extract in rats and rabbits. Groups of animals which received no test article served as controls in all studies reported. No adverse effects on estrous cycling, male or female copulatory and fertility indices or gestation/lactation parameters were observed in rats given 10-100 mg/kg/day. Reduced body weights in the offspring during lactation were observed at the 100 mg/kg/day treatment level concomitant with maternal toxicity. No developmental toxicity, including teratogenicity, was observed on the fetuses of rats following maternal administration of 5-60 mg/kg/day. An increase in post-implantation loss was observed at maternally toxic dosage levels of 50 and 75 mg/kg/day in rabbits. Oral administration of sanguinaria extract in a perinatal and postnatal study in rats caused no adverse effects on litter size, parturition, or lactation of female rats nor on survival and growth of their offspring at dosage levels of 5-60 mg/kg/day. Maternal oral toxicity thresholds were 60 mg/kg/day in rats and 25 mg/kg/day in rabbits. It was concluded that the oral intake of sanguinaria extract has no selective effect on fertility, reproduction or fetal and neonatal development in rats or rabbits.

Beam profile generator for asymmetric fields.

A boundary factor technique for predicting beam profiles has been described by Chui and Mohan [Med. Phys. 13, 409 (1986)]. Boundary factors are calculated as the ratio of the intensity measured in the central plane of a collimated field to the intensity measured in the same location in a 40 X 40 cm field. However, significant discrepancies arise if these factors are applied to the 40 X 40 cm intensity function at off-axis points to predict the beam profile for independently collimated fields. These discrepancies are primarily due to the assumption that the 40 X 40 cm profile approximates an unperturbed intensity function that would exist in the absence of the collimators or scattering media. Two techniques to reduce the residual perturbation are presented. The resulting refined boundary factors allow further factoring so as to permit the calculation of beam profiles for any field size and offset from three discrete functions.

Mice exposed in utero to 20 ppm benzene exhibit altered numbers of recognizable hematopoietic cells up to seven weeks after exposure.

Pregnant Swiss Webster mice were exposed from Day 6 through Day 15 of gestation to either air, 5 ppm, 10 ppm, or 20 ppm benzene. On Day 16 of gestation, 2 days after birth, and 6 weeks after birth, progeny of the exposed dams were assayed for the amount and type of hemoglobin produced and for recognizable hematopoietic cells in the peripheral blood and hematopoietic organs. None of the benzene exposures induced significant changes in the indices assayed from the 16-day fetuses. In contrast, 2-day neonates exposed in utero to all concentrations of benzene exhibited reduced numbers of circulating erythroid percursor cells. In addition, those 2-day neonates exposed in utero to 20 ppm benzene exhibited increased numbers of hepatic hematopoietic blast cells and granulopoietic precursor cells accompanied by decreased numbers of erythropoietic precursor cells. Six-week adult mice exposed in utero to 20 ppm benzene exhibited a similar pattern of enhanced granulopoiesis. These animals exhibited elevated numbers of splenic hematopoietic blast cells and granulopoietic precursor cells accompanied by decreased numbers of marrow erythropoietic precursor cells. These results suggest that in utero exposures to low concentrations of benzene can induce persistent enhanced production of recognizable granulopoietic elements in the hematopoietic systems of mice.

Mice exposed in utero to low concentrations of benzene exhibit enduring changes in their colony forming hematopoietic cells.

Pregnant Swiss-Webster mice were exposed to either 0, 5, 10, or 20 ppm benzene from days 6 through 15 of gestation. Hematopoietic progenitor cell assays were performed on fetal, neonatal and adult progeny of the exposed dams. All concentrations of benzene employed induced marked changes in the numbers of the more differentiated erythroid colony forming cells, the CFU-E. Granulocytic colony forming cells (GM-CFU-C) were affected by the 2 higher exposure concentrations. When mice previously exposed in utero to 10 ppm benzene were re-exposed as adults, marked depressions in the numbers of CFU-E and GM-CFU-C were observed. Thus, in utero exposures to concentrations of benzene at the current occupational exposure limit induce alterations of the murine hematopoietic system which persist into adulthood.

Embryotoxicity of cisplatin in rats and mice.

Cisplatin [cis-dichlorodiammineplatinum (II)], a broad spectrum antitumor agent, was tested for possible teratogenic and embryolethal effects on Wistar rats and Swiss Webster mice. Rats were given a single ip injection of 0.3, 1.0, 2.5, or 3.0 mg/kg cisplatin on Day 6, 8, 11, or 14 of gestation, whereas mice were given a single ip injection of 0.3, 3.0, 6.0, 8,0, or 13.0 mg/kg on Day 8 only. The embryonic LD50's in the rat were 2.88, 1.28, and 1.0 mg/kg for day 6, 8, and 11, respectively. There was no significant increase in embryolethality at any of the doses given on Day 14. The embryonic LD50 for mice was 5.24 mg/kg. An increase in the incidence of growth retardation or gross malformations was not discernable in the surviving fetuses with the number of dams used in this study. Cisplatin is highly embryolethal in rats and mice at dosages well below the adult therapeutic dosage in humans. This embryolethality is gestational stage-specific with the highest mortality corresponding to the period of rapid DNA replication in early organogenesis.