Antinociceptive effect of vapocoolant medium stream spray on hotplate latency in rat pups.

Background: Heel sticks account for most blood tests performed in neonates without analgesia because topical local anesthetics are ineffective on heel glabrous skin. We investigated the antinociceptive effect of an alternative topical analgesic, a vapocoolant spray, on hind paw glabrous skin of rat pups. The spray was applied by two methods: method 1 for 4 s at a distance of 8 cm and method 2 for 10 s at a distance of 18 cm.

Improved Efficacy in a Fabry Disease Model Using a Systemic mRNA Liver Depot System as Compared to Enzyme Replacement Therapy.

Fabry disease is a lysosomal storage disorder caused by the deficiency of α-galactosidase A. Enzyme deficiency results in a progressive decline in renal and cardiac function, leading to cardiomyopathy and end-stage renal disease. Current treatments available, including enzyme replacement therapies, have provided significant benefit to patients; however, unmet medical needs remain.

Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system.

DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) has the potential to provide for transient production of therapeutic proteins, without the need for nuclear delivery and without the risk of insertional mutagenesis. Here we describe the sustained delivery of therapeutic proteins in vivo in both rodents and non-human primates via nanoparticle-formulated mRNA.

The analgesic effect of a vapocoolant stream spray in reducing heat nociception on the glabrous skin of rat pups.

Background: Blood sampling is a common screening and diagnostic test in newborn infants in the neonatal intensive care unit, and heel lancing accounts for two-thirds of these tests. Heel lancing causes acute pain and distress, and most infants rarely receive analgesics because of fear of respiratory depression from opioids and lack of effectiveness of topical local anesthetics on the glabrous skin. To circumvent this latter problem, we investigated the analgesic efficacy and safety of a topical vapocoolant spray.

Development of standardized insulin treatment protocols for spontaneous rodent models of type 1 diabetes.

Standardized protocols for maintaining near-normal glycemic levels in diabetic rodent models for testing therapeutic agents to treat disease are unavailable. We developed protocols for 2 common models of spontaneous type 1 diabetes, the BioBreeding diabetes-prone (BBDP) rat and nonobese diabetic (NOD) mouse. Insulin formulation, dose level, timing of dose administration, and delivery method were examined and adjusted so that glycemic levels remained within a normal range and fluctuation throughout feeding and resting cycles was minimized.