mRNA as a Novel Treatment Strategy for Hereditary Spastic Paraplegia Type 5.

Hereditary spastic paraplegia type 5 is a neurodegenerative disease caused by loss-of-function mutations in the gene encoding the oxysterol 7-α-hydroxylase involved in bile acid synthesis in the liver. Lack of CYP7B1 leads to an accumulation of its oxysterol substrates, in particular 25-hydroxycholesterol and 27-hydroxycholesterol that are able to cross the blood-brain barrier and have neurotoxic properties. A potential therapeutic strategy for SPG5 is the replacement of CYP7B1 by administration of mRNA.

Tonicity inversely modulates lipocalin-2 (Lcn2/24p3/NGAL) receptor (SLC22A17) and Lcn2 expression via Wnt/β-catenin signaling in renal inner medullary collecting duct cells: implications for cell fate and bacterial infection.

Background: We have previously evidenced apical expression of the 24p3/NGAL/lipocalin-2 receptor (Lcn2-R; SLC22A17) in inner medullary collecting duct (IMCD) cells, which are present in vivo in a hyperosmotic/-tonic environment that activates canonical Wnt/β-catenin signaling. The localization of Lcn2-R in the inner medulla is intriguing considering local bacterial infections trigger toll-like receptor-4 (TLR-4)-mediated secretion of the bacteriostatic Fe-free (apo-)Lcn2.

Aim: To determine the effects of osmolarity/tonicity changes, Wnt/β-catenin and TLR-4 activation on Lcn2-R and Lcn2 expression and cell viability in rat primary IMCD and mouse (m)IMCD3 cells.

Experimental evaluation of Harrington rod fixation supplemented with sublaminar wires in stabilizing thoracolumbar fracture-dislocations.

Segments of the spinal column of calves were instrumented with Harrington rods with and without sublaminar wires. Grossly unstable lesions were created by resecting a 2-cm segment from the central spinal segment. Testing on an Instron tester documented the improvement in stability provided by the sublaminar wires in this grossly unstable experimental fracture.