New imaging tools for mouse models of osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disease characterized by a disruption of articular joint cartilage homeostasis. Mice are the most commonly used models to study OA. Despite recent reviews, there is still a lack of knowledge about the new development in imaging techniques. Two types of modalities are complementary: those that assess structural changes in joint tissues and those that assess metabolism and disease activity. Micro MRI is the most important imaging tool for OA research. Automated methodologies for assessing periarticular bone morphology with micro-CT have been developed allowing quantitative assessment of tibial surface that may be representative of the whole OA joint changes. Phase-contrast X-ray imaging provides in a single examination a high image precision with good differentiation between all anatomical elements of the knee joint (soft tissue and bone). Positron emission tomography, photoacoustic imaging, and fluorescence reflectance imaging provide molecular and functional data. To conclude, innovative imaging technologies could be an alternative to conventional histology with greater resolution and more efficiency in both morphological analysis and metabolism follow-up. There is a logic of permanent adjustment between innovations, 3R rule, and scientific perspectives. New imaging associated with artificial intelligence may add to human clinical practice allowing not only diagnosis but also prediction of disease progression to personalized medicine.

[Undernutrition of the elderly]. / Dénutrition du sujet âgé.

Malnutrition remains a particularly important issue in elderly. Physiological ageing induces many changes but ageing cannot entirely explain a Protein-Energy Malnutrition (PEM). Nutritionnal screening is indicated once a year in community medicine or in the first 48hours in case of an acute disease or of hospitalization. The Mini Nutritional Assessment is recommended for screening and for the diagnostic of malnutrition. Possible aetiologies are large and must be investigated in order to be careful not to dismiss curable disease and to be able to take corrective actions. PEM is associated to functional decline, length of stay in hospital and to morbi-mortality. Recommendations for dietary intakes in healthy old subjects are about 30 kcal/kg/day and 1 g/kg/day of protein and are strongly enhanced in case of acute or chronic diseases. The nutritional strategy depends on spontaneous food intake, medical situation, patient profile and opinion. Appropriate nutritional care could reduce morbidity-mortality and prevent functional decline in various disease contexts.

Reactive oxygen species and NADPH oxidase 4 involvement in osteoarthritis.

Osteoarthritis (OA) is a degenerative chronic disease affecting >300,000 million people around the world as of 2016. Symptomatic measures exist, but there are hardly any curative treatments available. Disruption of the cartilage homeostasis in favor of catabolism leads to cartilage destruction. ROS-macromolecular-induced damage is significantly greater in OA cartilage and OA is described as low-grade chronic systemic inflammation. This review aimed to assess the critical role of cartilage ageing and oxidative stress in the OA process, focusing in particular on NADPH oxidase and especially Nox4 involvement. With age, hypertrophic senescent cells with an altered redox cell profile accumulated. Chondrocytes are more sensitive to oxidant-mediators and the serum level of pro-inflammatory mediators increases. Age-related advanced glycation end products impact on extra cellular matrix (ECM) properties leading to the apoptosis of chondrocytes. A focus on NADPH oxidase-mediated-ROS signaling highlighted the very specific Nox4 isoform, which plays a role on the final common pathway targeting chondrocyte cells. IL-1ß-mediated Nox4 stimulation induced an increase in the levels released by the chondrocyte of MMP-1 and MMP-13 proteins, which are involved in ECM degradation. In comparison with the other Nox isoforms, Nox4 remains unusual, since it is constitutively active, does not depend on cytosolic activator proteins and seems to generate H2O2 thanks to the specific conformation of the Nox4 E-loop. Nox4-induced ROS production appears an essential actor in the OA process and it could be relevant to focus on this target in the aim of discovering and developing new therapeutic strategies.

Prevalence of protein-energy malnutrition in hospital patients over 75 years of age admitted for hip fracture.

INTRODUCTION: One percent of falls in over-75 years old cause hip fracture (HF). Protein-energy malnutrition (PEM) is associated with falls and fracture. PEM screening and perioperative nutritional management are recommended by the European Society of Parenteral and Enteral Nutrition, yet data on nutritional status in elderly HF patients are sparse. The Mini Nutritional Assessment (MNA) score is presently the most effective screening tool for PEM in over-75 years old. OBJECTIVE: The principal objective of the present study was to determine the prevalence on MNA of PEM in patients aged over 75 years admitted for HF. Secondary objectives were to identify factors associated with PEM and its role as a factor of evolution. MATERIALS AND METHODS: A prospective observational epidemiological study included 50 patients aged over 75 years admitted for HF in an 8-bed orthopedic surgery department with a geriatric follow-up unit. PEM was defined by MNA<17/30. Assessment systematically comprised associated comorbidity (Cumulative Illness Rating Scale-Geriatric [CIRS-G]), cognitive status on the Mini Mental State Examination (MMSE), functional status on activities of daily life (ADL), and mean hospital stay (MHS). Scores were compared on quantitative tests (Student t) with the significance threshold set at P<0.05. RESULTS: Mean age for the 50 patients was 86.1 years (range, 77-94 years). Prevalence of PEM was 28%; a further 58% of patients were at risk for PEM. PEM was associated with elevated CIRS-G (P<0.006), greater numbers of severe comorbidities (P=0.006), more severe cognitive disorder (P=0.005) and functional dependence (P=0.002), and 8 days' longer MHS (P=0.012). DISCUSSION: The present study confirmed the high prevalence of PEM in HF patients aged over 75 years, supporting longer hospital stay. MNA is a diagnostic gold standard, not to be replaced by albuminemia or body-mass index in this perioperative clinical situation. Given the present economic stakes relating to geriatric trauma patients' hospital stay, it is essential to prevent, diagnose and treat PEM in elderly subjects. LEVEL OF EVIDENCE: Level IV; prospective cohort study.

Involvement of calcium-independent phospholipase A2 in uterine stromal cell phospholipid remodelling.

The role of Ca2+-independent phospholipase A2 (iPLA2) in arachidonic (AA) and docosahexaenoic (DHA) acid incorporation and phospholipid remodelling in rat uterine stromal cells (UIII cells) was studied. Incorporation of AA and DHA into UIII cell phospholipids was Ca2+-independent. Bromoenollactone (BEL), a potent inhibitor of iPLA2, reduced lysophosphatidylcholine level and AA incorporation into phospholipids by approximately 20%. DHA incorporation was not affected by BEL, indicating that the pathways for AA and DHA incorporation are partially different. In control cells, the transfer of AA occurred mainly from diacyl-glycerophosphocholine (GroPCho) to alkenylacyl-glycerophosphoethanolamine (GroPEtn) and to a lesser extent from diacyl-GroPCho to diacyl-GroPEtn. [3H]DHA was redistributed from diacyl-GroPCho and alkylacyl-GroPEtn to alkenylacyl-GroPEtn. BEL treatment inhibited completely the redistributrion of AA within diacyl-GroPCho and diacyl -GroPEtn and reduced the [3H]DHA content of diacyl-GroPEtn, indicating that a BEL-sensitive iPLA2 controls the redistribution of polyunsaturated fatty acids to diacyl-GroPEtn. In contrast the redistribution of radioactive AA and DHA to alkenylacyl-GroPEtn was almost insensitive to BEL. The analysis of substrate specificity and BEL sensitivity of iPLA2 activity indicates that UIII cells exhibit at least two isoforms of iPLA2, one of which is BEL-sensitive and quite selective of diacyl species, and another one that is insensitive to BEL and selective for alkenylacyl-GroPEtn. Taken together, these results suggest that several iPLA2 participate independently in the remodelling of UIII cell phospholipids.