Cardiovascular risk-associated allele frequencies for 15 genes in healthy elderly French and Chinese.

In order to investigate possible ethnic differences in genetic and environmental determinants, we investigated several cardiovascular disease-associated genetic variations in successful ageing populations of France (Nancy) and China (Hong Kong). Allelic frequencies of these genetic variations were compared between healthy elderly Chinese (n=103) and French populations (n=100). A multi-locus assay was used to genotype 15 genes for 29 biallelic sites, genes implicated in lipid and homocysteine metabolism, thrombosis, leukocyte adhesion, and blood pressure regulation. For most of the candidate markers within lipid metabolism genes, the less frequent alleles were more common in the Chinese population compared with the French population, while the less frequent alleles of the majority of the other markers were detected only or more commonly in the French population. In conclusion, polymorphisms in 13 genes exhibited statistically significant differences in allelic frequencies between the two populations. Since the two populations were selected as examples of successful ageing, we could hypothesise that genetic factors that could play a role in a successful ageing process may be different between the two populations.     

Pharmacologic inhibition of CDC25 phosphatases impairs interphase microtubule dynamics and mitotic spindle assembly

The CDC25 cell cycle regulators are promising targets for new pharmacologic approaches in cancer therapy. Inhibitory compounds such as BN82685 have proven to be effective in specifically targeting CDC25 in cultured cells and in inhibiting tumor cell growth. Here, we report that BN82685 impairs microtubule dynamic instability and alters microtubule organization and assembly at the centrosome in interphase cells. Treatment of mitotic cells with BN82685 delays mitotic spindle assembly, chromosome capture, and metaphase plate formation. Furthermore, we show that combining low concentrations of both BN82685 and paclitaxel inhibits the proliferation of HT29 human colon cancer cells. Our results show a role for CDC25 phosphatases in regulating microtubule dynamics throughout the cell cycle and suggest that combinations of CDC25 inhibitors with microtubule-targeting agents may be of therapeutic value.     

Acceptability for French people of physician-assisted suicide

Our aim was to understand better how people judge the acceptability of physician-assisted suicide (PAS). We found that, for people in France of all ages and for elderly people with life-threatening illnesses, acceptability is an additive combination of the number of requests for PAS, the patient's age, the amount of physical suffering, and the degree of curability of the illness, not only when judging for hypothetical patients, but also for their spouses and for themselves. PAS can be highly acceptable to people even when the patient does not satisfy all the criteria of legislation about PAS.     

Family studies: their role in the evaluation of genetic cardiovascular risk factors.

Early epidemiological studies showed that genetic factors contribute to the risk of cardiovascular disease. Genetic epidemiological studies based upon families can be used to investigate familial trait aggregation, to localize genes implicated in cardiovascular diseases in the human genome, and to establish the role of environmental factors. Family studies can be also used to identify the physiological role of candidate genes for cardiovascular diseases, and to characterize shared environmental risk factors and their impact on the expression of genetic predisposition. The present paper reviews the existing family studies with special emphasis on those which have studied healthy populations in relation to cardiovascular disease such as the Framingham Heart Study, the National Heart, Lung, and Blood Institute Family Heart Study, and the STANISLAS cohort.     

Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non‐invasive murine model of post‐traumatic osteoarthritis

Joint injury is the predominant risk factor for post‐traumatic osteoarthritis development (PTOA). Several non‐invasive mouse models mimicking human PTOA investigate molecular mechanisms of disease development; none have characterized the inflammatory response to this acute traumatic injury. Our aim was to characterize the early inflammatory phase and later degenerative component in our in vivo non‐invasive murine model of PTOA induced by anterior cruciate ligament (ACL) rupture. Right knees of 12‐week‐old C57Bl6 mice were placed in flexion at a 30° offset position and subjected to a single compressive load (12N, 1.4 mm/s) to induce ACL rupture with no obvious damage to surrounding tissues. Tissue was harvested 4 h post‐injury and on days 3, 14, and 21; contralateral left knees served as controls. Histological, immunohistochemical, and gene analyzes were performed to evaluate inflammatory and degenerative changes. Immunohistochemistry revealed time‐dependent expression of mature (F4/80 positive) and inflammatory (CD11b positive) macrophage populations within the sub‐synovial infiltrate, developing osteophytes, and inflammation surrounding the ACL in response to injury. Up‐regulation of genes encoding acute pro‐inflammatory markers, inducible nitric oxide synthase, interleukin‐6 and interleukin‐17, and the matrix degrading enzymes, ADAMTS‐4 and MMP3 was detected in femoral cartilage, concomitant with extensive cartilage damage and bone remodelling over 21‐days post‐injury. Our non‐invasive model describes pathologically distinct phases of the disease, increasing our understanding of inflammatory episodes, the tissues/cells producing inflammatory mediators and the early molecular changes in the joint, thereby defining the early phenotype of PTOA. This knowledge will guide appropriate interventions to delay or arrest disease progression following joint injury. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2118–2127, 2018.