👤 Antonio Pozzi

To report the surgical outcomes of treating patellar luxation (PL) in dogs with surgical planning based on three-dimensional (3D) automated measurement of femoral angles. Multicenter retrospective study. Forty-one dogs with PL underwent preoperative computed tomography (CT). Three-dimensional femur models were exported as stereolithographic files, and imported into computer-aided design (CAD) software where 3D measurements were performed. The anatomical laterodistal femoral (aLDFA), femoral neck (FNA), and femoral torsion (FTA) angles were recorded. Surgical records, complications, radiographic femoral postoperative alignment, preoperative and postoperative lameness evaluation, and patellar position were reviewed. The success of the surgical outcome was based on the presence of normal patellar tracking at the last clinical recheck. Forty-seven limbs were included; 46% of the cases (22/47) were affected by grade 3 PL. Mean (±SD) 3D aLDFA, FNA, and FTA measurements were 101.4° (±3.6), 132.5° (±2.6), and 17.6° (±4.3) in dogs with medial patellar luxation (MPL) and 89.3° (±7.6), 134.8° (±2.9), 36.9° (±5.3) with lateral patellar luxation (LPL), respectively. Based on the 3D preoperative planning, corrective osteotomies were performed in 34 of 47 cases. The mean radiographic follow-up was 4.7 months. At the final follow-up, PL was successfully treated in 45 of 47 cases. Patella reluxated in five cases. In three of five cases, the 3D automated plan was not followed by the surgeon. Surgical treatment of PL based on 3D femoral measurements successfully corrected PL in 45 of 47 cases (96%). This is the first study reporting the use of 3D automated femoral angle measurement in clinical cases affected by PL. Show less

The main laminin-binding integrins α3β1, α6β1 and α6β4 are co-expressed in the developing kidney collecting duct system. We previously showed that deleting the integrin α3 or α6 subunit in the ureteric bud, which gives rise to the kidney collecting system, caused either a mild or no branching morphogenesis phenotype, respectively. To determine whether these two integrin subunits cooperate in kidney collecting duct development, we deleted α3 and α6 in the developing ureteric bud. The collecting system of the double knockout phenocopied the α3 integrin conditional knockout. However, with age, the mice developed severe inflammation and fibrosis around the collecting ducts, resulting in kidney failure. Integrin α3α6-null collecting duct epithelial cells showed increased secretion of pro-inflammatory cytokines and displayed mesenchymal characteristics, causing loss of barrier function. These features resulted from increased nuclear factor kappa-B (NF-κB) activity, which regulated the Snail and Slug (also known as Snai1 and Snai2, respectively) transcription factors and their downstream targets. These data suggest that laminin-binding integrins play a key role in the maintenance of kidney tubule epithelial cell polarity and decrease pro-inflammatory cytokine secretion by regulating NF-κB-dependent signaling. Show less

Human apolipoprotein A-IV (apoA-IV) is involved in chylomicron assembly and secretion, and in reverse cholesterol transport. Several apoA-IV isoforms exist, the most common in Caucasian populations being apoA-IV-1a (T347S) and apoA-IV-2 (Q360H). The objective of the present study was to investigate the impact of these common aminoacid substitutions on the ability of apoA-IV to bind lipids, to promote cell cholesterol efflux via ABCA1, and to maintain endothelial homeostasis. Recombinant forms of wild-type apoA-IV, apoA-IV Q360H, and apoA-IV T347S were produced in Escherichia coli. ApoA-IV Q360H and apoA-IV T347S showed a slightly higher alpha-helical content compared to wild-type apoA-IV, and associated with phospholipids faster than wild-type apoA-IV. The capacity to promote ABCA1-mediated cholesterol efflux was significantly greater for the apoA-IV T347S than the other apoA-IV isoforms. No differences were observed in the ability of apoA-IV isoforms to inhibit the production of VCAM-1 and IL-6 in TNFalpha-stimulated endothelial cells. In conclusion, the apoA-IV T347S common variant has increased lipid binding properties and cholesterol efflux capacity, while the apoA-IV Q360H variant has only slightly increased lipid binding properties. The two common aminoacid substitutions have no effect on the ability of apoA-IV to maintain endothelial homeostasis. Show less