Nicotinamide Phosphoribosyltransferase Attenuates Methotrexate Response in Juvenile Idiopathic Arthritis and In Vitro.

Variability in response to methotrexate (MTX) in the treatment of juvenile idiopathic arthritis (JIA) remains unpredictable and poorly understood. Based on previous studies implicating an interaction between nicotinamide phosphoribosyltransferase (NAMPT) expression and MTX therapy in inflammatory arthritis, we hypothesized that increased NAMPT expression would be associated with reduced therapeutic response to MTX in patients with JIA. A significant association was found between increased plasma concentrations of NAMPT and reduced therapeutic response in patients with JIA treated with MTX. Inhibition of NAMPT in cell culture by either siRNA-based gene silencing or pharmacological inhibition with FK-866 was found to result in a fourfold increase in the pharmacological activity of MTX. Collectively, these findings provide evidence that NAMPT inhibits the pharmacological activity of MTX and may represent a predictive biomarker of response, as well as a therapeutic target, in the treatment of JIA with MTX.

Serologic response of the opossum Didelphis virginiana to a temperature-sensitive mutant (ts-4) of Toxoplasma gondii.

A study was designed to measure the Toxoplasma gondii-specific IgM and IgG antibody responses of opossums inoculated with tachyzoites of the temperature-sensitive mutant of T. gondii, ts-4, and to examine its persistence in the tissues. Four young opossums seronegative for anti-Toxoplasma gondii IgM and IgG antibodies immediately after capture and 4 wk later were injected subcutaneously with 1.8 x 10(6) ts-4 tachyzoites; a fifth opossum (also seronegative) received an injection of saline only. Serum was collected weekly and titered by modified direct agglutination for anti-Toxoplasma gondii IgM and IgG. IgM titers were detectable from week 1 to week 6 postinoculation (PI). IgG was measurable by week 3 and remained high for 30 wk PI when the opossums were killed and examined. The control opossum did not develop a specific antibody response. At necropsy major lesions were not found. No anti-Toxoplasma gondii IgG was detected in serum collected from mice injected with tissues prepared from the opossums at necropsy, and no T. gondii was found on impression smears made at necropsy from these mice. Modified direct agglutination performed with or without 0.2 M 2-mercaptoethanol worked well for measuring specific IgM and IgG antibodies in experimentally infected opossums.

Evaluation of the Schirmer tear test in clinically normal rabbits.

Mean (+/- SD) value for results of the Schirmer tear test without use of topical anesthesia on 142 rabbit eyes was 5.30 (+/- 2.96) mm/min; range was 15 mm/min, with low value of 0 and high value of 15 mm/min. Two SD from the mean provided a normal clinical range of 0 to 11.2 mm/min for inclusion of 95% of the population. Significant differences were not evident between eye (right vs left) or gender or among breeds; interaction among eye, gender, and breed also was not observed. Although mean values for 2 breeds were significantly different from values in the other 10 breeds and from each other, they were still within the proposed normal range of 2 SD. The Schirmer tear test without topical anesthesia may be useful in rabbits for evaluation of increased values correlated with ocular irritation, rather than for determination of decreased values associated with keratoconjunctivitis sicca.

Fatal lungworm infection in an opossum.

A 3-mo-old male, feral opossum (Didelphis virginiana) was presented to the University of Tennessee College of Veterinary Medicine (USA) for evaluation of prolonged dyspnea. The animal died shortly after examination and a necropsy was performed. The cause of death was attributed to a verminous pneumonia, associated with numerous intrabronchial and intrabronchiolar nematodes, subsequently identified as Didelphostrongylus hayesi.

A formulary for lizards, snakes, and crocodilians.

A formulary of drug dosages for use in lizards, snakes, and crocodilians based primarily on a survey of the existing literature is provided. The formulary is presented as a series of four tables: antimicrobial drugs; parasiticide drugs; anesthetic and analgesic drugs; and miscellaneous drugs. An extensive bibliography is included.

Coinfection of a bearded dragon, Pogona vitticeps, with adenovirus- and dependovirus-like viruses.

Four neonate bearded dragons, Pogona vitticeps, from two collections became ill and died. Multiple tissues were collected and processed for light microscopy. In hematoxylin and eosin-stained sections of liver of one lizard, numerous basophilic intranuclear inclusions were observed. In three lizards, intranuclear inclusions were primarily seen within enterocytes in the small intestine. A portion of paraffin-embedded liver of one lizard and small intestine of a second lizard were removed, deparaffinized, and examined by electron microscopy. For the most part, inclusions in the liver consisted of nonenveloped viral particles 60-66 nm in diameter. Smaller nonenveloped virions 15-17 nm in diameter were occasionally seen in association with these particles. In the intestine, inclusions consisted only of 60-70 nm particles. Based on morphology and location, the larger particles were consistent with an adenovirus. Based on size and presence within nuclei of host cells coinfected with the adenovirus-like virus, the smaller viral agent was consistent with members of the genus Dependovirus.