Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the Pathophysiology of Diabetic Retinopathy

Novel therapeutics such as inhibitors of PI3K/Akt/mTOR pathway presents a unique opportunity for the management of diabetic retinopathy (DR). Second generation mTOR inhibitors have the prospect to be efficacious in managing various stages of disease progression in DR. During early stages, the mTOR inhibitors suppress HIF-1α, VEGF, leakage, and breakdown of the blood-retinal barrier. These mTOR inhibitors impart a pronounced inhibitory effect on inflammation, an early component with diverse ramifications influencing the progression of DR. These inhibitors suppress IKK and NF-κB along with downstream inflammatory cytokines, chemokines, and adhesion molecules. In proliferative DR, mTOR inhibitors suppress several growth factors that play pivotal roles in the induction of pathological angiogenesis. Lead mTOR inhibitors in clinical trials for ocular indications present an attractive treatment option for chronic use in DR with favorable safety profile and sustained ocular pharmacokinetics following single dose. Thereby, reducing dosing frequency and risk associated with chronic drug administration.

Acute Gastric Dilatation in Nonhuman Primates: Review and Case Studies

Acute gastric dilatation occurs sporadically in laboratory-housed nonhuman primates. Clinical histories often include chronic drug administration, food restriction, accidental overfeeding, and prior anesthesia. Monkeys may be found dead or may have clinical signs of colic, abdominal distention, and dyspnea. Death in untreated cases is due to impaired venous return and cardiopulmonary failure. Gastric distention with fermented gaseous ingesta and congestion of the abdominal viscera are the predominant lesions. The cause of acute gastric dilatation is unknown, but it probably is multifactorial. Two principal factors seem to be intragastric fermentation associated with Clostridium perfringens, and abnormal gastric function.