Prolidase enzyme is required for extracellular matrix integrity and impacts on postnatal cerebellar cortex development.

The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency.

Modification of abdominal fat distribution after aromatase inhibitor therapy in breast cancer patients visualized using 3-D computed tomography volumetry.

INTRODUCTION/BACKGROUND: The purpose of this study was to describe modification of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) distributions in breast cancer patients after aromatase inhibitor (AI) therapy using computed tomography (CT) volumetric measurement of abdominal body fat distribution. PATIENTS AND METHODS: Sixty-four consecutive patients who were receiving adjuvant AI therapy were included in this study. Patients were evaluated using CT before and after at least 6 months of AI therapy with imaging follow-up of 4.3 ± 2.2 years. Abdominal fat distribution was automatically calculated using a workstation that obtained total abdominal adipose tissue (TAAT) area (mm(3)). SAT was manually segmented and VAT was determined as TAAT - SAT. Percentages were calculated for change of TAAT, VAT, and SAT. VAT/SAT ratio was calculated. RESULTS: Percentage of TAAT after AI therapy was increased by a mean of 9.1% from baseline (16,280.3 ± 6953.3 mm(3)) to (17,763.6 ± 6850.8 mm(3)). Two groups of patients were observed; those with an increase in TAAT and those with a decrease. Modification of VAT/SAT ratio was observed (from 1.38 to 1.69) in all subjects, reflecting a relative increased volume of VAT (mean, 18%) and slight mean reduction of SAT (mean 1.9%). CONCLUSION: In our study, therapy with AI in breast cancer patients was accompanied with a change in fat distribution to relatively greater VAT/SAT ratio in patients, regardless of whether they gained or lost weight after therapy. Because this pattern of fat distribution is associated with metabolic disorders, attention must be paid to these clinical manifestations in patients during their follow-up management.