Objective—To determine the prognostic importance
of the DNA content and nuclear morphometric variables
in melanocytic tumors of cats and dogs.
Sample Population—27 melanocytic tumors of dogs
Procedures—Biopsy specimens were investigated
by quantitative image analysis after the Feulgen staining
method. The DNA content (index), nuclear diameter,
ploidy balance, proliferation index, hyperploidy,
and growth fraction (Ki67) were measured. Using 1-
way ANOVA and a Pearson correlation test, the relationships
between the different variables were tested.
Their role in the prognosis in affected dogs and
cats was estimated using the Cox regression test
with respect to 6 months postoperative survival rate.
Results—Significant correlations were found between
DNA index and ploidy balance and proliferation index. A
significant correlation was also found between hyperploidy
and DNA index, and between ploidy balance and
proliferation index. Significant differences were found
between histologically malignant and benign
melanocytic tumors but not between primary malignant
tumors and metastatic malignant tumors for DNA
index and ploidy balance. No correlation was found
between DNA variables and survival time.
Conclusion and Clinical Relevance—In melanocytic
tumors of cats and dogs, DNA index and ploidy balance
can be used to differentiate histologically benign
from malignant tumors. However, DNA content and
nuclear morphometric variables have little value in
predicting survival time. The DNA index and ploidy
balance provide an additional tool to evaluate
melanocytic tumors of cats and dogs. Survival in dogs
and cats with melanocytic tumors, however, is not
determined by modifications of DNA content or
changes in nuclear morphometry of tumor cells. (Am
J Vet Res 2000;61:1074–1079)
Objective—To evaluate the impact of modulation of the membrane-bound efflux pump P-glycoprotein (P-gp) on plasma concentrations of orally administered prednisolone in dogs.
Animals—7 healthy adult Beagles.
Procedures—Each dog received 3 treatments (control [no treatment], rifampicin [100 mg/d, PO, for 21 days, as an inducer of P-gp], and ketoconazole [100 mg/d, PO, for 21 days, as an inhibitor of P-gp]). A single dose of prednisolone (1 mg/kg, PO) was administered on day 8 of each treatment period. There was a 7-day washout period between subsequent treatments. Plasma concentrations of prednisolone were determined by use of a validated liquid chromatography–tandem mass spectrometry method. Duodenum and colon biopsy specimens were obtained endoscopically from anesthetized dogs and assessed for P-gp protein labeling via immunohistochemical analysis and mRNA quantification via real-time PCR assay. Total fecal collection was performed for evaluation of effects of P-gp modulation on digestion of nutrients.
Results—Rifampicin treatment upregulated duodenal P-gp in dogs and significantly reduced the area under the plasma concentration-time curve of prednisolone. Ketoconazole typically downregulated expression of duodenal P-gp, with a subsequent increase in the area under the plasma concentration-time curve of prednisolone. There was a noticeable interindividual difference in response. Digestion of nutrients was not affected.
Conclusions and Clinical Relevance—Modulation of P-gp expression influenced plasma concentrations of prednisolone after oral administration in dogs. Thus, treatment response to prednisolone may be influenced by coadministration of P-gp–modulating medications or feed ingredients.