Evaluation of Selected Markers in Kidneys of Cynomolgus Monkey (Macaca fascicularis) with Induced Diabetes during Renal Ischemia-reperfusion Injury.

We previously reported that induced type 1 diabetes mellitus (DM) increases the susceptibility of acute kidney injury in- duced by ischemia-reperfusion injury (IRI) in cynomolgus monkeys. In this follow-up study, we compared the expression of selected markers in the renal tissues of monkeys subjected to bilateral renal IRI with and without diabetes. All tissues were obtained from the original study. Renal biopsies were obtained before and 24 and 48 h after ischemia and were examined for expression of KI-67 (tubular proliferation), Na+ /K+ ATPase (sodium-potassium pump), TNF-α(tumor necrosis factor-α, inflammation), CD31 (microvessels), CD3 (T-cells), 2 fibrotic markers (fibroblast specific protein-1, FSP-1;α-smooth muscle actin,α -SMA), and cleaved caspase 3 (apoptosis). Generally, the expression of these markers differed in monkeys with and without DM. As compared with non-DM monkeys, DM monkeys had more cells that expressed KI-67 during progression of acute kidney injury (AKI). Na+ /K+ ATPase expression was clearly present at baseline in the basolateral tubular areas only in the non-DM monkeys. At 48 h, its expression in the basolateral area was not visible in DM monkeys, but was still present in intercellular junctions of non-DM monkeys. The expression of TNF-αwas higher in DM before and 48 h after ischemia. Before and 24 h after ischemia, the number of CD31-positive capillaries was not different between 2 groups, although more collapsed vessels were found at in DM at 24 h. At 48 h, the number of capillaries was less in DM compared with those from non-DM animals. DM monkeys had more interstitial CD3-positive cells than did non-DM monkeys at 24 and 48 h after ischemia. Finally, FSP-1-stained cells were more abundant in DM than non-DM at 24 and 48 h. Our results show that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting tubular proliferation, capillary density, T cell infil- tration and by altering protein and mRNA expression of various genes involved in ion channel, inflammation, and fibrotic change. The results from this observational study demonstrate that DM aggravates the recovery of renal ischemia/reperfusion injury by affecting multiple events including tubular necrosis, proliferation, function, inflammation and by inducing capillary rarefaction in cynomolgus monkeys.

A Simple Way to Eradicate Methicillin-Resistant Staphylococcus aureus in Cynomolgus Macaques (Macaca fascicularis).

Our investigation of indoor-housed cynomolgus macaques (Macaca fascicularis) by using automated identification followed by antibiotic susceptibility testing revealed 1 of 7 immunocompetent animals and 2 of 9 immunosuppressed monkeys as carriers of methicillin-resistant Staphylococcus aureus (MRSA). Follow-up management involving mupirocin treatment resulted in the conversion of the 3 MRSA carriers into MRSA-negative cases. Prospective assessment of newly imported monkeys involving 24-h culture of nasal swabs on chromogenic agar revealed that 22% (18 of 82 animals) were MRSA-positive. Mupirocin treatment successfully converted all of the MRSA-positive macaques into non-carriers, suggesting the feasibility of this simple, one-step screening procedure for rapidly identifying MRSA carriers in large cohorts. In addition, 8 animals that had been diagnosed MRSA-positive and subsequently treated with mupirocin demonstrated no recolonization during follow-up, even under immunosuppressive conditions. We propose rapid screening using chromogenic agar followed by mupirocin treatment as a time- and cost-effective regimen for managing MRSA in cynomolgus monkeys.