STUDY QUESTIONAre protein oxidative stress markers [thiols, advanced oxidation protein products (AOPP), protein carbonyls and nitrates/nitrites] in perioperative peritoneal fluid higher in women with histologically proven endometriosis when compared with endometriosis-free controls?
Abstract The human placenta is a transitory organ essential for fetal development, whose functions can be disrupted by xenobiotics in maternal blood. Benzo-[a]-pyrene (B[a]P) is a carcinogenic, mutagenic and reprotoxic pollutant as well as an endocrine disruptor that can be internalized in the human body by respiratory exposure. Cerium dioxide nanoparticles (CeO2 NP) have been introduced into our environment, mainly for their catalytic properties and share the same emission sources as B[a]P (cigarette smoke and diesel engine exhaust). The aim of our study is to determine the impact of these two atmospheric pollutants on the human placenta in concomitant exposure, in order to get closer to the environmental reality. Chorionic villi and villous cytotrophoblasts (VCT) from human placentas at term of pregnancy were exposed in vitro to the pollutants. The internalization of the pollutants was observed by confocal and Raman microscopy. Cytotoxicity was assessed using WST-1 test and extracellular LDH assay. Placental endocrine activity was assessed by ELISA. The signaling pathways impacted have been studied by Western Blot, RT-qPCR and IHC. CeO2 NP and B[a]P can be internalized within the chorionic villi. B[a]P alone or in co-exposure with CeO2 NP activate the metabolic pathway of the aryl hydrocarbon receptor (AhR), causing DNA damage. B[a]P also stabilizes the stress transcription factor p53 and its transcriptional target p21. Although these two pollutants do not cause major toxicity on term human trophoblasts after in vitro exposures, cellular stress markers are induced.
Objective Netrin-1 expression in articular cartilage is correlated with osteoarthritic changes. We aimed to investigate the contribution of Netrin-1 secreted by human osteoarthritic articular chondrocytes to angiogenesis process in vitro. Design Human articular chondrocytes were extracted from non-osteoarthritic ( n = 10) and osteoarthritic ( n = 22) joints obtained from surgical specimens and incubated for 24 hours. Medium conditioned by non-osteoarthritic and osteoarthritic articular chondrocytes were collected. Human umbilical vein endothelial cells (HUVEC) were treated with control and conditioned medium and assessed using assays for cell adherence, migration, and tube formation. Netrin-1 expression and secretion was compared between non-osteoarthritic and osteoarthritic chondrocytes by qPCR, Western blot, and ELISA. The role of chondrocyte-secreted Netrin-1 on HUVEC functions was assessed by immunological neutralization using an anti-Netrin-1 monoclonal antibody. Results As compared with medium conditioned by non-osteoarthritic chondrocytes, medium conditioned by osteoarthritic chondrocytes permitted tube formation by HUVEC. Both non-osteoarthritic and osteoarthritic chondrocytes expressed Netrin-1 at the RNA and protein levels. At the RNA level, Netrin-1 expression did not differ between non-osteoarthritic and osteoarthritic chondrocytes. At the protein level, Netrin-1 appeared as a full protein of 64 kDa in non-osteoarthritic chondrocytes and as two cleaved proteins of 55 kDa and 64 kDa in osteoarthritic chondrocytes. Immunological neutralization of endogenous Netrin-1 reduced the pro-angiogenic and pro-inflammatory transcriptional profile of HUVEC treated with the medium conditioned by osteoarthritic chondrocytes, as well as their capacities to form tubes. Conclusions Medium conditioned by osteoarthritic chondrocytes permits tube formation by HUVEC in vitro. This permissive effect is mediated by Netrin-1.
Presepsin could help for early diagnosis of systemic infection. Little is known regarding its kinetics. We studied presepsin concentration after challenge with bacterial agonist lipopolysaccharide (LPS) stimulation in peripheral mononuclear cells (PMNC) collected from 5 healthy volunteers and in a human cell line of monocytic cells (THP1). In PMNC, an exposure to LPS (100 ng/mL) induced an increase of median presepsin levels as early as hour 1 (+31%, p=0.007), concomitantly to IL-6 synthesis. In THP1 cells, presepsin was detected at 1 hour after LPS exposure, and peaked at 3 hours, in THP1 cells. In conclusion, we report here that presepsin, a surrogate marker of the host response to bacteria, increases early in PMNC and in a monocytic cell lineage. Our findings might confirm the potential usefulness of presepsin bedside as an early marker of infectious diseases.
Despite experimental evidence, clinical demonstration of acute state of oxidative stress and inflammation during post-cardiac arrest syndrome is lacking. Plasma level of thioredoxin (TRX), a redox-active protein induced under conditions of oxidative stress and inflammation, is increased in various critical care conditions. We determined plasma TRX concentrations after cardiac arrest and assessed relationships with severity and outcome.Retrospective study of consecutive patients admitted to a single academic intensive care unit (ICU) for out-of-hospital cardiac arrest (between July 2006 and March 2008). Plasma levels of TRX were measured at admission, day (D) 1, 2 and 3.Of 176 patients included, median TRX values measured in ICU survivors and non-survivors were, respectively: 22 ng/mL (7.8 to 77) vs. 72.4 (21.9 to 117.9) at admission (P < 0.001); 5.9 (3.5 to 25.5) vs. 23.2 (5.8 to 81.4) at D1 (P = 0.003); 10.8 (3.6 to 50.8) vs. 11.7 (4.5 to 66.4) at D2 (P = 0.22); and 16.7 (5.3 to 68.3) vs. 17 (4.3 to 62.9) at D3 (P = 0.96). Patients dying within 24 hours had significantly (P < 0.001) higher TRX levels (118.6 ng/mL (94.8 to 280)) than those who died after 24 hours or survived (50.8 (13.9 to 95.7) and 22 (7.8 to 77)). The area under the ROC curve to predict early death was 0.84 (0.76 to 0.91).Our data show for the first time that TRX levels were elevated early following cardiac arrest, suggestive of oxidative stress and inflammation occurring with this condition. Highest values were found in the most severe patients. TRX could be a useful tool for further exploration and comprehension of post-cardiac arrest syndrome.
Osteoarthritis (OA) is the most prevalent rheumatic disease in the world. Although its etiology is still unknown, one of the key processes in OA progression and development is oxidative stress. In this context, resveratrol, a well-known anti-oxidant from the stilbene family, could be of particular interest in future OA therapeutic strategies. However, currently, because of its low bioavailability, use of resveratrol in human health is very limited. In this study, we tested two resveratrol self-emulsifying systems previously developed in our laboratory in order to determine if they could improve cellular uptake of resveratrol in a human immortalized chondrocytic cell line (T/C28a2) and enhance protection against oxidative stress. Our results showed that resveratrol self-emulsifying systems were able first to increase cellular tolerance towards resveratrol, thus to decrease resveratrol intrinsic cellular toxicity allowing the use of higher concentrations; second, to increase resveratrol uptake in membrane and intracellular fractions; and finally to improve protection against oxidative stress-mediated death in human immortalized chondrocytic cell line T/C28a2. These data suggest that new formulations of resveratrol could be considered as potential beneficial effectors in future OA treatments.
L'osteoporose est caracterisee par une diminution de la masse osseuse et des modifications de la microarchitecture conduisant a une fragilite osseuse et a un risque fracturaire accru [1]. Selon l'OMS, l'osteoporose est definie par une densite osseuse inferieure a une limite situee a 2,5 ecarts-types au-dessous de la densite osseuse moyenne de l'adulte jeune. La perte de l'architecture normale de l'os represente un facteur additionnel de fragilite, la structure osseuse possedant des qualites biomecaniques moindres. La frequence de l'osteoporose chez les femmes serait de 10 % a 65 ans, et atteindrait 40 % a 75 ans [2]. Les fractures de l'extremite superieure du femur, dont l'incidence a augmente considerablement en raison de l'accroissement regulier de l'esperance de vie, representent la complication majeure de l'osteoporose apres 70 ans en terme de morbidite et de cout socio-economique. Leur nombre annuel est de pres de 50 000 pour la France et les projections demographiques permettent d'evaluer a plus de 120 000 fractures de l'extremite superieure du femur en 2050 [3]. L'etude de l'evolution de la masse osseuse au-dela de 70 ans revet en pratique un interet considerable tant au plan de la physiopathogenie de la fracture que de sa prevention. Elle peut se faire par la mesure de la masse osseuse par osteodensitometrie et la determination des marqueurs biochimiques du remodelage osseux. Apres avoir rappele les mecanismes de la perte osseuse du sujet âge, nous presenterons les resultats des marqueurs biochimiques et leurs implications pratiques dans l'evaluation du remodelage osseux du sujet âge.
