Considerations for Applying Route-to-Route Extrapolation to Assess the Safety of Oral Exposure to Substances.

The safety evaluation of oral exposure to substances, such as food ingredients, additives, and their constituents, relies primarily on a careful evaluation and analysis of data from oral toxicity studies. When relevant oral toxicity studies are unavailable or may have significant data gaps that make them inadequate for use in safety evaluations, data from non-oral toxicity studies in animals, such as studies on inhalation, dermal exposure, etc., might be used in support of or in place of oral toxicity studies through route-to-route (R-t-R) extrapolation.

High glucose-induced effects on Na-K-2Cl cotransport and Na/H exchange of blood-brain barrier endothelial cells: involvement of SGK1, PKCβII, and SPAK/OSR1.

Hyperglycemia exacerbates edema formation and worsens neurological outcome in ischemic stroke. Edema formation in the early hours of stroke involves transport of ions and water across an intact blood-brain barrier (BBB), and swelling of astrocytes. We showed previously that high glucose (HG) exposures of 24 hours to 7 days increase abundance and activity of BBB Na-K-2Cl cotransport (NKCC) and Na/H exchange 1 (NHE1).

Acute and chronic neuroinflammation is triggered by diabetic ketoacidosis in a rat model.

Introduction: Cognitive decline is common in patients with type 1 diabetes and has been attributed to the effects of chronic hyperglycemia and severe hypoglycemia. Diabetic ketoacidosis (DKA) has only recently been suspected to be involved in causing cognitive decline. We hypothesized that DKA triggers both acute and chronic neuroinflammation, contributing to brain injury.

Ipsilateral femoral vein compression: a contraindication to thrombin injection of femoral pseudoaneurysms.

Development of a femoral artery pseudoaneurysm occurs in 0.6% to 3.2% of interventional procedures.