Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a leading cause of death worldwide, despite the development of various therapeutic strategies. Cardiac dysfunction, also referred to as septic cardiomyopathy, is a frequent and well-described complication of sepsis and associated with worse clinical outcomes. Recent research has increased our understanding of the role of mitochondrial dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions

Carnosinase-1 overexpression, but not aerobic exercise training, affects the development of diabetic nephropathy in BTBR ob/ob mice

Manipulation of circulating histidine-containing dipeptides (HCD) has been shown to affect the development of diabetes and early-stage diabetic nephropathy (DN). The aim of the present study was to investigate whether such interventions, which potentially alter levels of circulating HCD, also affect the development of advanced-stage DN. Two interventions, aerobic exercise training and overexpression of the human carnosinase-1 (hCN1) enzyme, were tested. BTBR ob/ob mice were either subjected to aerobic exercise training (20 wk) or genetically manipulated to overexpress hCN1, and different diabetes- and DN-related markers were compared with control ob/ob and healthy (wild-type) mice. An acute exercise study was performed to elucidate the effect of obesity, acute running, and hCN1 overexpression on plasma HCD levels. Chronic aerobic exercise training did not affect the development of diabetes or DN, but hCN1 overexpression accelerated hyperlipidemia and aggravated the development of albuminuria, mesangial matrix expansion, and glomerular hypertrophy of ob/ob mice. In line, plasma, kidney, and muscle HCD were markedly lower in ob/ob versus wild-type mice, and plasma and kidney HCD in particular were lower in ob/ob hCN1 versus ob/ob mice but were unaffected by aerobic exercise. In conclusion, advanced glomerular damage is accelerated in mice overexpressing the hCN1 enzyme but not protected by chronic exercise training. Interestingly, we showed, for the first time, that the development of DN is closely linked to renal HCD availability. Further research will have to elucidate whether the stimulation of renal HCD levels can be a therapeutic strategy to reduce the risk for developing DN

Estimating actual foot size from a static bare foot print in a White British Population

In forensic intelligence-gathering it would be useful to be able to estimate the size of a perpetrator's foot from a standing bare footprint found at the scene of crime. Currently, the advice is to add a fixed amount to the length of the footprint (typically 1.5 or 2.0 cm), but there is little evidence for this approach. This study used measured footprint and actual foot lengths from 146 participants from the white British student population of a University in the UK. Data were analysed using multiple regression with foot length as the dependent (outcome) variable and footprint length and sex as the independent variable/factor respectively. Sex was not a significant predictor. The regression equation for the best estimate of the foot length is 19.89 + 0.95 × print length ± 8 mm

Recent developments in preparative-scale supercritical fluid- and liquid chromatography for chiral separations

International audienceThis review covers preparative-scale chromatography for enantioseparations in both supercritical fluid and liquid chromatography published between 2016 and 2020. When pertinent, some fundamental publications from outside this time window are cited. The recent developments in instrumentation, novelties in method development and chiral stationary- and mobile phases are placed in context, while throughput, scale-up and sample issues are presented for supercritical fluid chromatography, and large-batch techniques together with computer-assisted method development, are described for liquid chromatography. Preparative-scale applications are reported for natural products, pharmaceutical compounds and pesticides, as well some other small molecules. Finally, a section is devoted to reports comparing supercritical fluid- and liquid chromatography and the strategies of various commercial users are briefly described. The goal of this review is to present current practices in the field of medium to large-scale chiral separations and offer indications as to how the best approach may be chosen for a given application

Maltodextrin-Nanoparticles as a Delivery System for Nasal Vaccines: A Review Article

Nanoparticles are increasingly being studied as antigen delivery systems for immunization with nasal vaccines. The addition of adjuvants is still generally required in many nanoparticle formulations, which can induce potential side effects owing to mucosal reactogenicity. In contrast, maltodextrin nanoparticles do not require additional immunomodulators, and have been shown to be efficient vaccine delivery systems. In this review, the development of maltodextrin nanoparticles is presented, specifically their physico-chemical properties, their ability to load antigens and deliver them into airway mucosal cells, and the extent to which they trigger protective immune responses against bacterial, viral, and parasitic infections. We demonstrate that the addition of lipids to maltodextrin nanoparticles increases their potency as a vaccine delivery system for nasal administration

The LepR db/db mice model for studying glycation in the context of diabetes

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Effect of Advanced Glycation End-Products and Excessive Calorie Intake on Diet-Induced Chronic Low-Grade Inflammation Biomarkers in Murine Models

International audienceChronic Low-Grade Inflammation (CLGI) is a non-overt inflammatory state characterized by a continuous activation of inflammation mediators associated with metabolic diseases. It has been linked to the overconsumption of Advanced Glycation End-Products (AGEs), and/or macronutrients which lead to an increase in local and systemic pro-inflammatory biomarkers in humans and animal models. This review provides a summary of research into biomarkers of diet-induced CLGI in murine models, with a focus on AGEs and obesogenic diets, and presents the physiological effects described in the literature. Diet-induced CLGI is associated with metabolic endotoxemia, and/or gut microbiota remodeling in rodents. The mechanisms identified so far are centered on pro-inflammatory axes such as the interaction between AGEs and their main receptor AGEs (RAGE) or increased levels of lipopolysaccharide. The use of murine models has helped to elucidate the local and systemic expression of CLGI mediators. These models have enabled significant advances in identification of diet-induced CLGI biomarkers and resultant physiological effects. Some limitations on the translational (murine → humans) use of biomarkers may arise, but murine models have greatly facilitated the testing of specific dietary components. However, there remains a lack of information at the whole-organism level of organization, as well as a lack of consensus on the best biomarker for use in CLGI studies and recommendations as to future research conclude this revie

Comparison of POCIS passive samplers vs. composite water sampling: A case study

International audienceThe relevance of Polar Organic Chemical Integrative Samplers (POCIS) was evaluated for the assessment of concentrations of 46 pesticides and 19 pharmaceuticals in a small, peri-urban river with multi-origin inputs. Throughout the period of POCIS deployment, 24 h-average water samples were collected automatically, and showed the rapid temporal evolution of concentrations of several micropollutants, as well as permitting the calculation of average concentrations in the water phase for comparison with those estimated from POCIS passive samplers. In the daily water samples, cyproconazol, epoxyconazol and imidacloprid showed high temporal variations with concentrations ranging from under the limit of detection up to several hundreds of ng L−1. Erythromycin, cyprofloxacin and iopromide also increased rapidly up to tens of ng L−1 within a few days. Conversely, atrazine, caffeine, diclofenac, and to a lesser extent carbamazepine and sucralose, were systematically present in the water samples and showed limited variation in concentrations. For most of the substances studied here, the passive samplers gave reliable average concentrations between the minimal and maximal daily concentrations during the time of deployment. For pesticides, a relatively good correlation was clearly established (R2 = 0.89) between the concentrations obtained by POCIS and those gained from average water samples. A slight underestimation of the concentration by POCIS can be attributed to inappropriate sampling rates extracted from the literature and for our system, and new values are proposed. Considering the all data set, 75% of the results indicate a relatively good agreement between the POCIS and the average water samples concentration (values of the ratio ranging between 0,33 and 3). Note further that this agreement between these concentrations remains valid considering different sampling rates extracted from the literature.</p

Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a leading cause of death worldwide, despite the development of various therapeutic strategies. Cardiac dysfunction, also referred to as septic cardiomyopathy, is a frequent and well-described complication of sepsis and associated with worse clinical outcomes. Recent research has increased our understanding of the role of mitochondrial dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions