Charles W. Leathers

Does caloric restriction extend life in wild mice

To investigate whether mice genetically unaltered by many generations of laboratory selection exhibit similar hormonal and demographic responses to caloric restriction (CR) as laboratory rodents, we performed CR on cohorts of genetically heterogeneous male mice which were grandoffspring of wild‐caught ancestors. Although hormonal changes, specifically an increase in corticosterone and decrease in testosterone, mimicked those seen in laboratory‐adapted rodents, we found no difference in mean longevity between ad libitum (AL) and CR dietary groups, although a maximum likelihood fitted Gompertz mortality model indicated a significantly shallower slope and higher intercept for the CR group. This result was due to higher mortality in CR animals early in life, but lower mortality late in life. A subset of animals may have exhibited the standard demographic response to CR in that the longest‐lived 8.1% of our animals were all from the CR group. Despite the lack of a robust mean longevity difference between groups, we did note a strong anticancer effect of CR as seen in laboratory rodents. Three plausible interpretations of our results are the following: (1) animals not selected under laboratory conditions do not show the typical CR effect; (2) because wild‐derived animals eat less when fed AL, our restriction regime was too severe to see the CR effect; or (3) there is genetic variation for the CR effect in wild populations; variants that respond to CR with extended life are inadvertently selected for under conditions of laboratory domestication.

Diffuse cerebral and leptomeningeal astrocytoma in dogs: MR features.

Magnetic resonance (MR) imaging has increased sensitivity in detection of nonenhancing brain tumors and may show the extent of CNS neoplasia with greater detail than CT. Magnetic resonance images of the canine brain were acquired in two dogs with diffuse leptomeningeal and cerebral low grade astrocytoma. Abnormalities were identified with MR imaging when CT and CSF analysis were noncontributory. Changes seen with MR included decreased signal on T1-weighted images and increased signal on T2-weighted images consistent with vasogenic edema. Neither MR nor CT showed post-contrast enhancement. Magnetic resonance did not show the full extent of cellular infiltration, however. This was attributed to the diffuse submacro-scopic distribution and absence of corresponding edema and contrast enhancement in certain regions of brain.

The Biodistribution of Boron in Canine Spontaneous Intracranial Tumors Following Borocaptate Sodium Infusion

Dogs with naturally-occurring, intracranial tumors were chosen as a model for evaluating the pharmacokinetics and biodistribution of boron using a single dose, intravenous administration of borocaptate sodium (Na2B12H11SH or BSH). Biologic variability was high with this model because of differences in tumor type, stage, location, and size. However, the natural behavior of these tumors provides results with a spectrum similar to that of actual treatment conditions. The relatively large size of the subject permitted extensive sampling of tumor, peritumor, and normal tissues for boron analysis. The results from these biodistribution studies have been applied toward related studies on boron neutron capture therapy (BNCT), including canine dose tolerance studies and BNCT of canine intracranial tumors.