Poxvirus Infection in a Colony of Laboratory Pigeons (Columba livia).

Pigeons (Columba livia) are used in biomedical research for studies of vision, cognition, neuronal pathways, and spatial orientation. Because there are few commercial laboratory sources, research pigeons are typically acquired from local fancier breeders or bred onsite. For acquired pigeons, the health and vaccine status is often unknown. A juvenile pigeon, born onsite and living in an enclosed outdoor loft, presented with small, bleeding, wart-like lesions on the medial aspects of digits 1 and 4. Topical treatment was initiated. Within a week, 4 fledglings were reported for small, dark papular lesions on the face, head, neck, and beak, and shortly thereafter, 2 additional juvenile pigeons developed similar lesions. The fledglings were euthanized, and histologic examination revealed numerous intralesional eosinophilic cytoplasmic viral inclusions (Bollinger bodies) confirming a diagnosis of poxvirus infection, likely pigeon pox. Although usually self-limiting, pigeon pox can cause moderate to severe lesions in fledgling and juvenile birds. Vaccination with a modified live poxvirus labeled for chickens was used to create herd immunity to pigeon poxvirus. Since vaccination of our entire flock and implementation of more stringent health protocols, all lesions have resolved, and no new lesions have been noted.

Recombinant human arginase toxicity in mice is reduced by citrulline supplementation.

Human recombinant arginase I cobalt coupled to polyethylene glycol 5000 (HuArg I [Co]-PEG5000) achieved potent in vitro depletion of arginine from tissue culture medium and cytotoxicity to many cancer cell lines. The recombinant enzyme also produced tumor growth inhibition of hepatocellular carcinoma and pancreatic carcinoma xenografts. Although these results were promising, the therapeutic index was narrow. Toxicities were seen in normal cells in tissue culture. In vivo normal tissue injury occurred at doses twice the effective dose. The current study was conducted to define, in greater detail, the maximum tolerated dose (MTD), pharmacodynamics, and dose-limiting toxicities (DLTs) of twice-weekly intraperitoneal HuArg I [Co]-PEG5000 in Balb/c mice. Animal weight and survival were monitored, serum arginine levels measured, and complete blood cell counts, chemistries, necropsies, and histologies were performed. In addition, methods to ameliorate the HuArg I [Co]-PEG5000 adverse effects were tested. Supplemental l-citrulline was given concurrently with the arginase drug. The HuArg I [Co]-PEG5000 MTD in mice was 5 mg/kg twice weekly, and DLTs included weight loss and marrow necrosis. No other organ damage or changes in blood cell counts or chemistries were observed. Arginase reduced serum arginine levels from 60 µM to 4 to 6 µM. Supplemental l-citrulline given per os or daily subcutaneously reduced and delayed toxicities, and l-citrulline given twice daily subcutaneously completely prevented animal toxicities. On the basis of these results, we hypothesize that HuArg I [Co]-PEG5000, particularly with supplemental l-citrulline, may be an attractive therapeutic agent for argininosuccinate synthetase-deficient tumors.

Effects of the macrolide drug tylosin on chronic diarrhea in rhesus macaques (Macaca mulatta).

Diarrhea is the gastrointestinal disease most frequently encountered in captive rhesus macaques. The precise pathogenic mechanisms underlying chronic diarrhea in nonhuman primates are not well understood, but a persistent inflammatory component has been implicated strongly. This study evaluated the inflammatory changes in the colon of macaques with diarrhea and assessed the efficacy of a 10-d course of tylosin in a cohort of 21 animals with chronic diarrhea. Stool quality was evaluated daily, and fecal consistency was scored. Colonoscopies were performed; biopsy samples were characterized histologically and assayed for expression of TNFalpha mRNA. Blood samples collected pre-, mid-, and post-treatment were assayed for C-reactive protein (CRP). The results indicated that 63% of the animals receiving tylosin showed improvement in stool quality, compared with 10% in the sham-treated group. Histologically, 82% of animals in the tylosin-treated group had a reduction in the severity of colonic lesions post-treatment, compared with 40% of animals in the sham group. The amount of TNFalpha mRNA before treatment did not differ from that afterward in either tylosin- or sham-treated animals. CRP levels serially decreased in tylosin-treated monkeys; the average post-treatment CRP value for tylosin-treated animals was 11.96 +/- 3.86 microg/ml compared with 26.48 +/- 4.86 microg/ml for sham-treated controls. In conclusion, tylosin significantly improved the fecal consistency score, significantly decreased colonic inflammation, and significantly decreased serum CRP levels post-treatment in rhesus macaques with chronic diarrhea.