Trimethoprim–sulfamethoxazole (TMP–SMX) medication in the feed or water is commonly administered to immunocompromised mice to prevent the occurrence of Pneumocystis murina (formerly P. carinii) pneumonia. Therapeutic doses of SMX can cause decreased total and free thyroxine (T₄) levels in dogs and thyroid hypertrophy and hyperplasia in mice, rats, and dogs. Our primary objective was to determine whether SMX at doses present in commercially available rodent TMP–SMX feed would produce hypothyroidism in mice. Plasma T₄ levels were determined prior to and after placement of Brand A TMP–SMX feed (daily SMX dose, 240 mg/kg), Brand B TMP–SMX feed (daily SMX dose, 2400 mg/kg), and their respective controls (doses calculated for a 25-g mouse according to vendor's information). T₄ levels in the mice fed Brand B TMP–SMX feed were significantly decreased by 2 wk after feed placement. Levels of thyroid stimulating hormone in male and female mice given Brand B TMP–SMX feed were significantly elevated compared with those of control groups at 6 wk after feed placement, when only these mice showed evidence of thyroid hypertrophy and hyperplasia. No significant change in T₄ levels occurred over the course of 11 wk in mice given the Brand A TMP–SMX chow or either control feed. In light of the significant clinical hypothyroidism that occurred in our mice while receiving Brand B TMP–SMX diet, we recommend SMX levels more similar to that of Brand A to avoid such unwanted effects which could confound research data.

Sleep–wake disturbances are common in epilepsy, yet the potential adverse effect of seizures on sleep is not well characterized. Genetically epilepsy-prone rats (GEPRs) are a well-studied model of genetic susceptibility to audiogenic seizures. To assess their suitability for investigating relationships between seizures and disordered sleep, we characterized the sleep, activity, and temperature patterns of 2 GEPR strains (designated 3 and 9) and Sprague–Dawley (SD) rats in the basal state, after forced wakefulness, and after exposure to sound-induced seizures at light onset and dark onset. Because of observed differences in rapid-eye-movement sleep (REMS), we also assessed serum levels of prolactin, which is implicated in REMS regulation. The data reveal that under basal conditions, the GEPR3 strain shows less SWS and REMS, higher core temperatures, and higher serum prolactin concentrations than do GEPR9 and SD strains. All 3 strains respond similarly to enforced sleep loss. Seizures induced at light onset delay the onset of SWS in both GEPR strains. Seizures induced at dark onset do not significantly alter sleep. Genotype assessment indicates that although both GEPR strains are inbred (that is, homozygous at 107 genetic markers), they differ from each other at 74 of 107 loci. Differences in basal sleep, temperature, and prolactin between GEPR3 and GEPR9 strains suggest different homeostatic regulation of these functions. Our detection of concurrent alterations in sleep, temperature, and prolactin in these 2 GEPR strains implicates the hypothalamus as a likely site for anatomic or physiologic variation in the control of these homeostatic processes.

Pigs are increasingly used as in vivo models in neuroscience, including studies using positron emission tomography. During anesthesia, cerebral blood flow (CBF) and cerebral blood volume (CBV) are mainly regulated by the partial pressure of CO₂ (pCO₂) in arterial blood. We sought to determine the effects of increased arterial pCO₂ (hypercapnia) on CBF and CBV in anesthetized domestic pigs. We anesthetized 4 pigs and manipulated the tidal volume of the ventilator to different pCO₂ levels. Baseline pCO₂ was on average 6.5 kPa (n = 9 periods) and hypercapnia pCO₂ ranged from 11 to 20 kPa, mean 18.5 kPa (n = 9 periods). Series of dynamic PET scans with H₂¹⁵O (CBF measurements) and C¹⁵O (CBV measurements) were performed. CBF increased on average 54%, from mean 0.48 ml blood/min/ml brain tissue during normoxia to 0.74 ml blood/min/ml brain tissue during hypercapnia. CBV increased 41% from mean 0.061 ml blood/ml brain tissue (n = 6) during normoxia to 0.086 ml blood/ml brain tissue (n = 6) during hypercapnia. Our observations indicate that pCO₂ levels have a major influence on porcine CBF and CBV and should be controlled in studies where a constant level is crucial.

Primate lab diets typically contain high vitamin A concentrations when compared with human recommended intakes. In this study, we analyzed the vitamin A contents of liver and serum from 13 adult female African green vervet monkeys (Chlorocebus aethiops). These monkeys were wild-caught and held in captivity for 2 y, during which time they consumed a standard primate diet. Liver vitamin A concentration (mean ± 1 standard deviation) was 14.6 ± 2.3 μmol retinol/g liver; subtoxicity in humans is defined as at least 1 μmol/g liver. The serum retinol concentration (0.93 ± 0.21 μM) was not elevated. Hypertrophy and hyperplasia of hepatic stellate cells were present which, in conjunction with elevated hepatic vitamin A concentrations, are evidence of toxicity. Although the ramifications of chronically toxic vitamin A status in experimental monkeys have not been defined, this state may influence nonhuman primate research outcomes and confound data interpretation. The validity of bone mineral research using nonhuman primates is of greatest concern, in light of the association between vitamin A toxicity and compromised bone health.

Surgical implantation of devices into the abdomen of PL/J mice was associated with fatal hemorrhage at 9 to 11 d after surgery. Coagulation profiles were evaluated to determine the underlying cause of this effect. The mean activated partial thromboplastin time (aPTT) of untreated PL/J mice was significantly higher than that of BALB/cByJ and C57BL/6J strains. The addition of human plasmas deficient in factors VIII, XI, or XII, prekallikrein, or high molecular-weight kininogen corrected the elevated aPTT of PL/J mice, but correction did not occur when factor IX-deficient human plasma was added. When compared to an assigned factor IX activity of 100% for pooled plasma from BALB/cByJ mice, C57BL/6J and PL/J mice revealed percent activities of 67% and 16%, respectively. PL/J mice could represent a new model for the study of pathogenesis and therapy of mild factor IX deficiency that is expressed and becomes clinically apparent secondary to major surgery.

Among 585 sentinel ICR mice (Mus musculus), 8 (7 female, 1 male) had unusual microscopic lesions in the kidney. Light microscopy revealed occasional tubular epithelial cells with large, karyomegalic nuclei that contained intranuclear inclusions and marginated chromatin. These cells were randomly present in the cortex and medulla but were more prominent near the corticomedullary junction. Rare pyknotic cells and mild interstitial infiltrates of lymphocytes and plasma cells were associated with occasional foci of abnormal cells. Electron microscopy performed on 2 (1 female, 1 male) of the mice demonstrated intranuclear inclusions composed of abundant flocculent, electron-lucent material. No viral particles or other pathogens were identified. General health monitoring that included serology, microbiology, parasitology, necropsy, and histopathology was negative for pathogens. Polymerase chain reaction-based testing for polyomavirus and immunohistochemistry for adenovirus were performed on 5 of the 7 female mice; all were negative for both viruses. In light of microscopy findings and the lack of evidence for an infectious agent, the tubular lesions were considered degenerative changes, possibly due to a toxic insult. The cause and significance of the findings in these mice cannot be explained fully.