Barking up the right tree: advancing our understanding and treatment of lymphoma with a spontaneous canine model.

PURPOSE OF REVIEW: Spontaneous lymphoma in pet dogs is increasingly recognized as an ideal model for studying the disease in humans and for developing new targeted therapeutics for patients. Increasing interest by funding agencies, the private sector, and multidisciplinary academic collaborations between different disciplines and sectors now enables large knowledge gaps to be addressed and provides additional proof-of-concept examples to showcase the significance of the canine model. RECENT FINDINGS: The current review addresses the rationale for a canine lymphoma model including the valuable role it can play in drug development, serving as a link between mouse xenograft models and human clinical trials and the infrastructure that is now in place to facilitate these studies. Research in this field has focused on filling in the gaps to make the canine lymphoma model more robust. These advances have included work on biomarkers, detection of minimal residual disease, expansion of genomic and proteomic data, and immunotherapy. SUMMARY: Incorporating pet dogs into the drug development pipeline can improve the efficiency and predictability of preclinical models and decrease the time and cost required for a therapeutic target to be translated into clinical benefit.

Preliminary evaluation of a gel tube agglutination major cross-match method in dogs.

BACKGROUND: A major cross-match gel tube test is available for use in dogs yet has not been clinically evaluated. OBJECTIVES: This study compared cross-match results obtained using the gel tube and the standard tube methods for canine samples. METHODS: Study 1 included 107 canine sample donor-recipient pairings cross-match tested with the RapidVet-H method gel tube test and compared results with the standard tube method. Additionally, 120 pairings using pooled sera containing anti-canine erythrocyte antibody at various concentrations were tested with leftover blood from a hospital population to assess sensitivity and specificity of the gel tube method in comparison with the standard method. RESULTS: The gel tube method had a good relative specificity of 96.1% in detecting lack of agglutination (compatibility) compared to the standard tube method. Agreement between the 2 methods was moderate. Nine of 107 pairings showed agglutination/incompatibility on either test, too few to allow reliable calculation of relative sensitivity. Fifty percent of the gel tube method results were difficult to interpret due to sample spreading in the reaction and/or negative control tubes. CONCLUSIONS: The RapidVet-H method agreed with the standard cross-match method on compatible samples, but detected incompatibility in some sample pairs that were compatible with the standard method. Evaluation using larger numbers of incompatible pairings is needed to assess diagnostic utility. The gel tube method results were difficult to categorize due to sample spreading. Weak agglutination reactions or other factors such as centrifuge model may be responsible.

Comparative shell buffering properties correlate with anoxia tolerance in freshwater turtles.

Freshwater turtles as a group are more resistant to anoxia than other vertebrates, but some species, such as painted turtles, for reasons not fully understood, can remain anoxic at winter temperatures far longer than others. Because buffering of lactic acid by the shell of the painted turtle is crucial to its long-term anoxic survival, we have tested the hypothesis that previously described differences in anoxia tolerance of five species of North American freshwater turtles may be explained at least in part by differences in their shell composition and buffering capacity. All species tested have large mineralized shells. Shell comparisons included 1) total shell CO2 concentration, 2) volume of titrated acid required to hold incubating shell powder at pH 7.0 for 3 h (an indication of buffer release from shell), and 3) lactate concentration of shell samples incubated to equilibrium in a standard lactate solution. For each measurement, the more anoxia-tolerant species (painted turtle, Chrysemys picta; snapping turtle, Chelydra serpentina) had higher values than the less anoxia-tolerant species (musk turtle, Sternotherus odoratus; map turtle, Graptemys geographica; red-eared slider, Trachemys scripta). We suggest that greater concentrations of accessible CO2 (as carbonate or bicarbonate) in the more tolerant species enable these species, when acidotic, to release more buffer into the extracellular fluid and to take up more lactic acid into their shells. We conclude that the interspecific differences in shell composition and buffering can contribute to, but cannot explain fully, the variations observed in anoxia tolerance among freshwater turtles.