SCH 412499: biodistribution and safety of an adenovirus containing P21(WAF-1/CIP-1) following subconjunctival injection in Cynomolgus monkeys.

Monkey studies were conducted for the preclinical safety assessment of SCH 412499, an adenovirus encoding p21, administered by subconjunctival injection prior to trabeculectomy for postoperative maintenance of the surgical opening. Biodistribution of SCH 412499 was minimal and there was no systemic toxicity. Findings included swollen, partially closed or shut eye(s) and transient congestion in the conjunctiva.

Quantitative gene expression analysis in a nonhuman primate model of antibiotic-induced nephrotoxicity.

Gene expression patterns using microarrays have been described for rodent models of nephrotoxicity. To determine if significant gene expression changes previously identified have application across multiple species, we studied quantitative gene expression changes in the kidneys of female cynomolgus monkeys after exposure to two nephrotoxicants. Animals were dosed with the aminoglycoside gentamicin (10 mg/kg), the experimental oligosaccharide antibiotic everninomicin (30 or 60 mg/kg), or a combination of gentamicin (10 mg/kg) and everninomicin (30 mg/kg) for 7 days.

Characterization of glomerular cell phenotypes following repeated cycles of benzo[a]pyrene injury in vitro.

Exposure of cultured glomeruli to benzo[a]pyrene (BaP), a carcinogenic hydrocarbon, modulates mesangial and visceral epithelial cell proliferation in vivo and in vitro. The present studies were conducted to characterize mitogenic signaling profiles of cultured glomeruli following repeated cycles of BaP challenge. Enhanced rates of DNA synthesis were observed by the third passage in randomly cycling cultures after single or repeated carcinogen exposure.

Collagen suppresses the proliferative phenotype of allylamine-injured vascular smooth muscle cells.

Repeated cycles of oxidative injury by allylamine induce proliferative rat vascular smooth muscle cell (vSMC) phenotypes characterized by enhanced secretion of osteopontin (OPN). The present study was designed to evaluate the role of extracellular matrix (ECM) interactions in the induction of proliferative phenotypes in this model of oxidant injury. Because OPN is involved in ECM/integrin signaling, and may participate in proliferative control, the proliferation profiles of control and allylamine vSMCs seeded on different matrices were compared.