Lang Cm

Hazards of urethane (ethyl carbamate): a review of the literature

Urethane (ethyl carbamate) is used alone or in combination with other drugs to produce anaesthesia in laboratory animals. Although originally studied as a potential phytocide, urethane demonstrated antineoplastic properties when administered to rats with the Walker rat carcinoma 256. Subsequent trials in humans led to its use as a chemotherapeutic agent for various leukaemias. Mice develop pulmonary adenomas earlier in life and at a higher incidence following urethane administration. Urethanes carcinogenic influence is greater in neonatal mice; it also has a transplacental influence in mice. In rats, urethane increases the incidence of pulmonary adenomas, Zymbal Gland tumours, and a variety of other neoplasms. Urethane is absorbed sufficiently from the skin of laboratory animals to produce a transient narcosis. The carcinogenic effect appears to be due to an undefined oncogenic intermediate formed in the blood. Considering the properties urethane demonstrates in animals, the safety of its use by laboratory personnel is in question. However, if appropriate guidelines are followed, urethane should continue to be a useful anaesthetic agent for laboratory animals.

Paracoccidioidomycosis (South American blastomycosis) in a squirrel monkey (Saimiri sciureus).

A female squirrel monkey (Saimiri sciureus) had granulomatous lesions in the liver and colon. There were many fungal organisms in sections of liver and many of these organisms had multiple buds on their surface. Although we did not prepare fungal cultures, the appearance of the organisms was sufficient to identify them as Paracoccidioides brasiliensis, the cause of paracoccidioidomycosis (South American blastomycosis).

Spontaneous reproductive tract leiomyomas in aged guinea-pigs

Seven of 83 female guinea-pigs were found to have reproductive tract leiomyomas at necropsy. Sixty-three of these guinea-pigs also had cystic rete ovarii. Eleven separate leiomyomas were identified, the most common site of formation being the uterine body or horn. The tumours contained histological evidence of smooth muscle, abundant fibrous connective tissue and occasional foci of fibrocartilage and bone. Mitotic figures were identified in only one tumour. The mean age of guinea-pigs with leiomyomas was 47.6 months, and the mean age of the study population was 33.1 months. Two other reproductive tract tumours identified in the 83 guinea-pigs were an ovarian teratoma and a cavernous haemangioma. These data indicate that leiomyomas are the most common reproductive tract tumour in this colony of aged female guinea-pigs and that they are frequently seen in conjunction with cystic rete ovarii.

Reproductive Failure Associated with Cystic Rete Ovarii in Guinea Pigs

Cystic ovaries were found at necropsy in 54 of 71 (76%) female guinea pigs between 18 and 60 months of age. Histologic appearance and location of the cysts within the ovary were consistent with cystic rete ovarii. Microscopic appearance of the large ovarian cysts suggested reproductive performance in these guinea pigs should be compromised. Breeding records indicated that fertility was markedly reduced in affected females over fifteen months of age. Cystic endometrial hyperplasia, mucometra, endometritis in appropriate placental tissue, or fibroleiomyomas were seen in 21 of 54 (39%) guinea pigs with cystic ovaries, but in only one of 17 (6%) guinea pigs without cystic ovaries.

Cilia-associated Respiratory (CAR) Bacillus Infection of Obese Mice:

Cilia-associated respiratory (CAR) bacillus was identified in respiratory tract lesions of obese mice dying of chronic respiratory disease. Neither Mycoplasma pulmonis nor pathogenic bacteria were isolated from cultures of the lesions at necropsy, but there was serologic and histologic evidence of respiratory virus infection. Cranial-ventral areas of lung were firm and demarcated from unaffected lung at gross examination, and representative tissue sank in water. Microscopically, there was suppurative bronchopneumonia with extensive peribronchiole lymphocyte and plasma cell proliferation. The affected bronchiole epithelium was covered with a sheet of slightly basophilic, filamentous, gram negative bacteria. Bronchioles with lesser amounts of lymphocyte accumulations contained lesser amounts of filamentous bacteria. Bronchioles without filamentous bacteria lining the respiratory epithelium lacked peribronchiole lymphocyte accumulations. There was a high correlation between CAR bacillus-positive serology and the identification of diagnostic histologic lesions. CAR bacillus was readily stained using immunohistochemical methods, and the ultrastructural features were similar to that described in rat infections.

Cystitis, urolithiasis and cystic calculi in ageing guineapigs

Nineteen cases of cystitis were diagnosed at necropsy and/or by histology in a group of 170 (96 females, 74 males) guineapigs (11·2%). Seventeen of the 19 cases (89·4%) were females. The mean age of guineapigs with cystitis was 34·7 months, which was higher than the mean age of 24 months of the 170 members of the study group. In addition, 6 cases of urolithiasis and cystic calculi in 5 females and one male were also found in the 170 guineapigs (3·5%). The mean age of the 6 cases was 30 months, which was also higher than the mean age of the 170 animals. The study suggests that aged female guineapigs were much more predisposed to cystitis and urolithiasis or cystic calculi than male and young guineapigs. The cause may be related to infection with Escherichia coli and Staphylococcus sp, cystic calculi, diabetes mellitus and female guinea pig urogenital anatomy and function.

Use of cage space by guineapigs

Cage space requirements for laboratory animals have been established by Government Regulation and Recommendations. In order to test the adequacy of these space allocations, the use of cage floor area by breeding groups of guineapigs was studied. A computer-coupled video tracking system capable of imaging in low light intensity as well as total darkness was used to determine the average per cent occupancy by guineapigs in all portions of a cage over 12-h light and dark cycles. Simultaneous time synchronized slow motion video recordings permitted an analysis of activity to be coordinated with cage use data. Results of the study revealed that breeding groups of guinea pigs utilize the periphery of the cage almost to the total exclusion of the centre of the cage. Approximately 75-85% of all occupancy in both the day and evening hours occurred in 47% of the cage floor area located along the periphery. Analysis of video recordings revealed that the animals remained active throughout the day and night with no prolonged period of quiescence that could be associated with sleep. Results of this study suggest that while guidelines for housing guineapigs based on area allocation per animal can be formulated and are easy to administer, they cannot be supported by the behavioural characteristics of these animals or careful quantitation of their pattern of cage space utilization.

The opioid growth factor, [Met5]‐enkephalin, inhibits DNA synthesis during recornification of mouse tail skin

Opioid peptides serve as tonically active negative growth regulators in renewing and regenerating epithelia. To examine the involvement of opioids in renewal of the stratum corneum after tape stripping of tail skin, C57BL/6 J mice were given systemic injections of the potent opioid antagonist, naltrexone (NTX, 20 mg/kg i.p.) following injury. Blockade of opioidreceptor interaction by NTX for 4 h resulted in an elevation of 36–;66% in basal cell DNA synthesis measured 24 h after injury. Injection of the endogenous opioid peptide, [Met5]‐enkephalin (OGF, 10 mg/kg i.p.) 4 h before termination, suppressed radiolabelled thymidine incorporation in the basal cell layer by 37–46%at 24 h after wounding. The magnitude of the effects on DNA synthesis of OGF, but not NTX, depended on the timing of administration with respect to injury. OGF maximally depressed basal cell labelling (72%) when given 16 h after tape stripping. Concomitant administration of naloxone (10 mg/kg) with OGF blocked the inhibition of DNA synthesis; naloxone alone at the dosage utilized had no effect on cell labelling. Both OGF and its receptor, OGFr, were detected by immunocytochemistry in the basal and suprabasal cell layers, but not the cornified layer of tape stripped and uninjured tail skin. These results indicate: (a) a native opioid peptide and its receptor are expressed in epidermal cells of injured and uninjured mouse tail skin; (b) removal of the stratum corneum by tape stripping does not disrupt the function of the endogenous opioid growth system; (c) the proliferative response to wounding of the tail is tonically inhibited by the receptor‐mediated action of an endogenous opioid peptide; and (d) DNA synthesis by basal cells can be elevated by disrupting opioid peptidereceptor interactions.

Optic neuropathy following simulation of orbital hemorrhage in the nonhuman primate

The goal of the study was to determine, using a nonhuman primate (NHP) model, the minimum duration of elevated intraocular pressure (IOP) (induced by an inflated catheter) necessary to produce significant visual system deficits. In Old World monkeys (Macaca mulatta), a catheter was placed retrobulbarly in one orbit and inflated with saline for either 180 min (10 monkeys) or 240 min (six monkeys subjects). Baseline color fundus photographs, monochromatic photography, fluorescein angiography, and IOP measurements were performed preoperatively and at either 2, 4, or 6 weeks postoperatively on both eyes of each monkey prior to killing and histological analysis. Optic neuropathy was demonstrated in eight of these NHPs. In the two most severe cases (240 min inflation condition), complete nerve fiber atrophy with central retinal artery occlusion was observed. Sector nerve fiber atrophy, extending from the temporal disc to beyond the macula, was noted in the other six monkeys, five of which were in the 180 min inflation condition. Thus, optic neuropathy, sufficient to produce visual loss, was noted following increased IOP (> or = 50 mm Hg) for 180 min or 240 min. These data emphasize the need for timely intervention to mitigate the potential detrimental effects of retrobulbar hemorrhage when it occurs in humans.

Osseous choristoma of the ciliary body in guinea pigs.

ronts have many organisms. The multinucleate meronts of References the organisms in the calf are distinct from Toxoplasma and Besnoitia, because the latter divided by endodyogeny (division into two). No species of Isospora has been known to develop in tissues of ruminants (cattle, sheep, goat^).^ Thus, by exclusion, the organism may be Eimeria, although sexual stages were not seen. Lesions in the present study were considered to be due to the coccidium because the infection was localized in the small bile ducts and protozoa were seen in lesions. Moreover, the hepatobiliary lesions were similar to those caused by Eimeria hiepei in mink3 and Eimeria stiedae in rabbits.’ Intestinal coccidiosis due to Eimeria is among the most common of parasitic infections of cattle, sheep, and goats.5 Although species of Eimeria occasionally invade the gallbladder of goats’ and mesenteric lymph nodes of sheep and goats,6 none have been reported to do so in cattle. The parasite of cattle in the present case was similar to that in the gallbladder of a goat, but sexual stages were not observed.