Investigator Engagement: Somewhat Radical Considerations on Practices to Improve Animal Care Program Compliance.

The authors discuss approaches to bolster investigator engagement, inviting investigators to be partners within the Animal Care Program. Regulatory burden in animal research endeavors continues to be reviewed and critiqued; therefore, this article intends to encourage Animal Care Programs to promote transparency and incorporation of unique educational training initiatives to tailor and focus compliance efforts across research programs. Borrowing from concepts of patient engagement, adherence, and enrollment efforts within the medical profession, it is likely that gains in trust, understanding, and communication between stakeholders within animal programs can be achieved without excessive efforts to alter existing approaches. Institutions will continue to be challenged to balance animal welfare expectations with promotion of research missions. This article provides a framework for somewhat radical ideas, including the use of collaborative orientations, assistance with self-evaluations, timely self-reporting, and meaningful and directed trainings, that are all aimed to resonate in contemporary animal care programs and foster investigator engagement in ongoing compliance efforts.

Differential recovery from exercise and hypoxia exposure measured using 31P- and 1H-NMR in white muscle of the common carp Cyprinus carpio.

Phosphocreatine (PCr) was reduced to equivalent levels in carp white muscle by high-intensity exhaustive exercise and exposure to hypoxia at 15 degrees C and 25 degrees C in order to assess the influence of intracellular pH (pH(i)), temperature and lactate levels on PCr recovery in vivo. High-intensity exercise resulted in a significantly lower pH(i) compared with hypoxia exposure and the rate of PCr depletion and tissue acidification during hypoxia exposure was significantly higher in carp held at 25 degrees C compared with those at 15 degrees C. During recovery, PCr and pH(i) returned towards normoxia/resting levels at a faster rate following hypoxia exposure than after exercise. The lower pH(i) in exercised carp caused a greater perturbation to cellular energy status (assessed as the free energy of ATP hydrolysis; DeltafG') and resulted in a higher [ATP]/[ADP(free)] ratio, which may limit mitochondrial ATP production and contribute to the slower recovery from exercise compared with recovery from hypoxia exposure. Rates of recovery from exercise and hypoxia exposure were not affected by acclimation temperature (15 and 25 degrees C), suggesting that the processes involved in acclimation compensate for the Q(10) effects of temperature on metabolic processes. Finally, using a dual 31P-NMR and 1H-NMR analysis technique, we demonstrated that the greater tissue acidification observed after high-intensity exercise compared with hypoxia exposure occurred at similar white muscle lactate concentrations.

Site-specific atherogenic gene expression correlates with subsequent variable lesion development in coronary and peripheral vasculature.

OBJECTIVE: The relationship between specific gene regulation and subsequent development and progression of atherosclerosis is incompletely understood. We hypothesized that genes in the vasculature related to cholesterol metabolism, inflammation, and insulin signaling pathways are differentially regulated in a site-specific and time-dependent manner. METHODS AND RESULTS: Expression of 59 genes obtained from coronary, carotid, and thoracic aortic arteries were characterized from diabetic (DM)/hypercholesterolemic (HC) swine (n=52) 1, 3, and 6 months after induction. Lesion development in the 3 arterial beds was quantified and characterized at 1, 3, 6, and 9 months. Progressive lesion development was observed in the coronary>thoracic aorta>>carotid arteries. Genes involved in cholesterol metabolism and insulin pathways were upregulated in coronaries>thoracic aortae>carotids. Inflammatory genes were more markedly upregulated in coronary arteries than the other 2 arteries. Genes implicated in plaque instability (eg, matrix metalloproteinase-9, CCL2 and Lp-PLA(2) mRNAs) were only upregulated at 6 months in coronary arteries. CONCLUSIONS: Variable gene expression, both in regard to the arterial bed and duration of disease, was associated with variable plaque development and progression. These findings may provide further insight into the atherosclerotic process and development of potential therapeutic targets.

The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions.

Interstitial nephritis occurs spontaneously in kd/kd mice, but the mechanisms leading to this disease have not been fully elucidated. The earliest manifestation of a phenotype is the appearance of ultrastructural defects in the mitochondria of mice as young as 42 days of age. To examine the influence of the environment on the phenotype, homozygous B6.kd/kd mice were transferred from specific pathogen-free (SPF) conditions to a germfree (GF) environment, and the development of the disease was observed. The GF state resulted in a highly significant reduction in the frequency of tubulointerstitial nephritis. In addition, GF conditions markedly reduced the appearance of the mitochondrial phenotype, with no sign of mitochondrial abnormalities in GF mice of up to 155 days of age. These results suggest that environmental factors are involved in the progression of all known manifestations of this disease phenotype.