Fish Hydrolysate Supplementation Containing n-3 Long Chain Polyunsaturated Fatty Acids and Peptides Prevents LPS-Induced Neuroinflammation

Neuroinflammation constitutes a normal part of the brain immune response orchestrated by microglial cells. However, a sustained and uncontrolled production of proinflammatory factors together with microglial activation contribute to the onset of a chronic low-grade inflammation, leading to neuronal damage and cognitive as well as behavioral impairments. Hence, limiting brain inflammatory response and improving the resolution of inflammation could be particularly of interest to prevent these alterations. Dietary n-3 long chain polyunsaturated fatty acids (LC-PUFAs) and low molecular weight peptides are good candidates because of their immunomodulatory and proresolutive properties. These compounds are present in a fish hydrolysate derived from marine-derived byproducts. In this study, we compared the effect of an 18-day supplementation with this fish hydrolysate to a supplementation with docosahexaenoic acid (DHA) on lipopolysaccharide (LPS)-induced inflammation in mice. In response to peripherally injected LPS, the fish hydrolysate supplementation decreased the hippocampal mRNA expression of the proinflammatory cytokines IL-6 (p < 0.001), IL-1β (p = 0.0008) and TNF-α (p < 0.0001), whereas the DHA supplementation reduced only the expression of IL-6 (p = 0.004). This decline in proinflammatory cytokine expressions was associated with an increase in the protein expression of IκB (p = 0.014 and p = 0.0054 as compared to the DHA supplementation and control groups, respectively) and to a modulation of microglial activation markers in the hippocampus. The beneficial effects of the fish hydrolysate could be due in part to the switch of the hippocampal oxylipin profile towards a more anti-inflammatory profile as compared to the DHA supplementation. Thus, the valorization of fish byproducts seems very attractive to prevent and counteract neuroinflammation.     

MRI dosimetry: a fast quantitative MRI method to determine 3D absorbed dose distributions

RATIONALE AND OBJECTIVES: Magnetic resonance imaging (MRI) techniques seem to be very promising for 3D dosimetry studies, but long imaging acquisition time limits their use. A new fast T1 mapping protocol, easy to implement on a conventional MR imager, has been used to determine dose distributions on Fricke gels. METHODS: The method has been tested on manganese chloride (MnCl2) doped ferrous gelatin gels. The T1 measuring times range from 1 minute 40 seconds to 3 minutes 30 seconds for a 256x256 matrix image. RESULTS: The two- and three-dimensional profiles agree with those obtained with conventional dosimetry techniques (ion chambers). The precision and the spatial resolution principally depend on the signal-to-noise ratio of the used imaging RF coil. For example, for a surface coil, the accuracy is about 2.5% with a 1.56 mm spatial resolution. CONCLUSION: These preliminary results support the feasibility of the proposed technique for accurate MRI dosimetry studies and also have potential for various clinical quantitative MRI applications.     

Expanding the mutational spectrum of LZTR1 in schwannomatosis

Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.     

Late perforation of a thoracic aortic dacron graft by a metallic stent-graft component.

PURPOSE: To describe a case involving perforation of a previously placed aortic Dacron graft by the uncovered proximal stent of a thoracic stent-graft. CASE REPORT: A 76-year-old man with a surgically treated type A dissection presented with residual type B dissection. Thoracic stent-grafting of the entry site was performed successfully. After 2 years, the patient was admitted for evaluation of a non-pulsating parasternal mass. Computed tomography showed a large, hypodense liquid-like mass affecting the mediastinum up to the subcutaneous tissue. A false aneurysm at the proximal end of the stent-graft was observed arising from an aortic perforation by the uncovered stent. One week later, the mass had almost completely resolved, and the patient has been scheduled for close surveillance. CONCLUSION: This case illustrated the importance of thoroughly examining the long-term durability and compatibility of prosthetic materials.