Publications by authors named "Vincent Sapin"

152 Publications

Predictive performance of blood S100B in the management of patients over 65 years old with mild traumatic brain injury.

J Gerontol A Biol Sci Med Sci 2021 Feb 27. Epub 2021 Feb 27.

University Hospital, Biochemistry and Molecular Genetic Department, Clermont-Ferrand, France.

Background: We previously assessed the inclusion of S100B blood determination into clinical decision rules for mild traumatic brain injury (mTBI) management in the Emergency Department (ED) of Clermont-Ferrand Hospital. At the 0.10 µg/L threshold, S100B reduced the use of cranial computed tomography (CCT) scan in adults by at least 30% with a ~100% sensitivity. Older patients had higher serum S100B values, resulting in lower specificity (18.7%) and decreased CCT reduction. We conducted this study to confirm the age effect on S100B concentrations, and to propose new decisional thresholds for older patients.

Methods: A total of 1172 mTBI patients aged 65 and over were included. They were divided into three age-groups: 65-79, 80-89, and ≥ 90 years old. S100B's performance to identify intracranial lesions (sensitivity (SE) and specificity (SP)) was assessed using the routine 0.10 µg/L threshold and also other more efficient thresholds established for each age group.

Results: S100B concentration medians were 0.18 µg/L, 0.26 µg/L, and 0.32 µg/L for the 65-79, 80-89, and ≥ 90 years old age-groups, respectively (p < 0.001). The most efficient thresholds were 0.11 µg/L for the 65-79 age-group and 0.15 µg/L for the other groups. At these new thresholds, SP was respectively 28.4%, 34.3%, and 20.5% for each age-group vs. 24.9%, 18.2%, and 10.5% at the 0.10 µg/L threshold.

Conclusions: Adjustment of the S100B threshold is necessary in older patients' management. An increased threshold of 0.15 µg/L is particularly interesting for patients ≥ 80 years old, allowing a significant increase of CCT scan reduction (29.3%).
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http://dx.doi.org/10.1093/gerona/glab055DOI Listing
February 2021

[SARS-CoV-2 and neurological disorders: the revelance of biomarkers?]

Ann Biol Clin (Paris) 2021 02;79(1):7-16

DMU BioGeM, Service de biochimie métabolique, APHP, Sorbonne Université, Hôpitaux universitaires Pitié-Salpêtrière, Paris, France.

Soon after the pandemic, numerous publications described cases of neurological disorders associated with the SARS-CoV-2 infection. The range of neurological symptoms is becoming increasingly more extensive as the pandemic progresses. However, it is not yet well established whether the manifestations are due to direct viral damage to the nervous system or indirect consequences of the infection. This review presents an inventory of the biochemical markers studied in the context of neurological disorders related to SARS-CoV-2. By reflecting various physiopathological mechanisms, these biomarkers allow both a better understanding of the pathophysiology of Covid-19 and a contribution to the diagnosis of neurologic troubles; they could participate in the prognostic evaluation of patients.
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http://dx.doi.org/10.1684/abc.2021.1622DOI Listing
February 2021

A proposed Common Training Framework for Specialists in Laboratory Medicine under EU Directive 2013/55/EC (The Recognition of Professional Qualifications).

Clin Chem Lab Med 2021 Feb 30;59(3):505-512. Epub 2020 Nov 30.

European Federation of Clinical Chemistry and Laboratory Medicine, Brussels/Milan, Belgium/Italy.

European Union (EU) Directive 2013/55/EC (The Recognition of Professional Qualifications) allows Member States to decide on a common set of minimum knowledge, skills and competences that are needed to pursue a given profession through a Common Training Framework. To be adopted the framework must combine the knowledge, skills and competences of at least one third of the Member States. Professionals who have gained their qualifications under a Common Training Framework will be able to have these recognised automatically within the Union. The backbone of the European Federation of Clinical Chemistry and Laboratory Medicine's (EFLM) proposed Common Training Framework for non-medical is outlined here. It is based on an Equivalence of Standards in education, training, qualifications, knowledge, skills, competences and the professional conduct associated with specialist practice. In proposing the recognition of specialist practice EFLM has identified 15 EU Member States able to meet Equivalence and in whom the profession and/or its training is regulated (an additional EU Commission requirement). The framework supports and contributes to the Directive's enabling goals for increasing professional mobility, safeguarding consumers and ensuring a more equitable distribution of skills and expertise across the Member States. It represents EFLM's position statement and provides a template for professional societies and/or competent authorities to engage with the EU Commission.
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http://dx.doi.org/10.1515/cclm-2020-1504DOI Listing
February 2021

Oxidative and antioxidative stress markers in keratoconus: a systematic review and meta-analysis.

Acta Ophthalmol 2020 Dec 23. Epub 2020 Dec 23.

Preventive and Occupational Medicine, CNRS, LaPSCo, Physiological and Psychosocial Stress, CHU Clermont-Ferrand, Université Clermont Auvergne, University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.

Purpose: To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject.

Method: The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium).

Results: We included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD) = 0.94, 95% confidence interval (95% CI) 0.55-1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41-1.78) and malondialdehyde (1.78, 0.83-2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (-0.63, -0.89 to -0.36), with a significant decrease in total antioxidant capacity/status (-1.65, -2.88 to -0.43), aldehyde/NADPH dehydrogenase (-0.77, -1.38 to -0.17), lactoferrin/transferrin/albumin (-1.92, -2.96 to -0.89) and selenium/zinc (-1.42, -2.23 to -0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium.

Conclusion: Oxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.
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http://dx.doi.org/10.1111/aos.14714DOI Listing
December 2020

Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia.

PLoS Biol 2020 12 7;18(12):e3000948. Epub 2020 Dec 7.

Université Clermont Auvergne, GReD, CNRS UMR 6293, INSERM U1103, Clermont-Ferrand, France.

Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.
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http://dx.doi.org/10.1371/journal.pbio.3000948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752095PMC
December 2020

[Remethylation disorders: about two cases].

Ann Biol Clin (Paris) 2020 Dec;78(6):647-654

Service de biochimie et génétique moléculaire, CHU Clermont-Ferrand, Clermont-Ferrand, France, Service de biochimie, Faculté de médecine et des professions paramédicales, Université Clermont Auvergne, CNRS UMR 6293, Inserm U1103, Clermont-Ferrand, France.

In order to propose a course of action to be taken in the face of any hyperhomocysteinemia, we have reported for the first time in a French journal the recommendations made within the framework of the European E-HOD project for the diagnosis and treatment of remethylation disorders. The remethylation route ensures homocysteine-methionine conversion. It is linked to the folate cycle and the intracellular metabolism of cobalamins. Remethylation disorders can be classified into three groups: 1) isolated disorders (cblD-HC, cblE, cblG) corresponding to an isolated deficit in the production of methylcobalamin, cofactor of methionine synthase; 2) combined disorders (cblC, cblD-MMA/HC, cblF, cblJ) corresponding to an alteration of the transport and intracellular metabolism of cobalamins, which causes a defect in the synthesis of the two functional forms of cobalamin: methylcobalamin and adenosylcobalamin, a cofactor for methyl malonylCoA mutase; 3) MTHFR deficit, an abnormality of the folate cycle. The biological anomalies observed are hyperhomocysteinemia and hypomethioninaemia associated in the case of disorders combined with increased urinary excretion of methylmalonic acid. The clinical presentation is however heterogeneous according to the remethylation disorder but also for the same pathology according to the age. Given the large number of pathologies grouped together in remethylation disorders, this point is illustrated by only two clinical cases concerning the same deficit (deficit in MTHFR) but with different discovery circumstances: a neonatal form and a late form.
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http://dx.doi.org/10.1684/abc.2020.1606DOI Listing
December 2020

Impact of disease activity and treatments on ovarian reserve in patients with rheumatoid arthritis in the ESPOIR cohort.

Rheumatology (Oxford) 2021 Apr;60(4):1863-1870

Assistance Medicale à la Procréation, CECOS, CHU Estaing, Clermont-Ferrand University, France.

Objectives: Patients with RA have a higher prevalence of infertility than the general population. This study sought to examine the impact of RA disease activity and treatments on ovarian reserve measured by serum anti-Müllerian hormone (AMH) levels in the ESPOIR cohort. We sought to better define the indications for fertility preservation.

Methods: Patients and serum analysis data were derived from the French national cohort ESPOIR. Enrolled patients (n = 102; 18-37-year-olds) fulfilled ACR/EULAR 2010 criteria for RA. Serum AMH levels were measured at T0, T6, T12, T24 and T36 months post-diagnosis. The impacts of RA activity (DAS28 and CRP level) and treatments (MTX only or with other medications) were evaluated at each study visit.

Results: A gradual decrease in patients' serum AMH levels was observed over time, in line with the descending curve described for healthy women. Serum AMH levels of RA patients in comparison with the values considered normal for age did not reveal any significant differences (P > 0.05). We did not observe any impact of RA treatments. We demonstrated an inverse correlation between AMH variation and disease activity (DAS28: r = -0.27, P = 0.003; CRP: r = -0.16, P = 0.06).

Conclusion: This is the first study to determine serum AMH levels of a large cohort of RA patients over 36 months. Rapid disease activity control appears to be required to limit changes in the ovarian reserve. Fertility preservation is not likely to be necessary if inflammation is promptly controlled.

Clinicaltrials.gov Identifier: NCT03666091.
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http://dx.doi.org/10.1093/rheumatology/keaa535DOI Listing
April 2021

Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device.

J Vis Exp 2020 09 24(163). Epub 2020 Sep 24.

Department of Perioperative Medicine, CHU Clermont-Ferrand; GReD, CNRS, INSERM, Université Clermont Auvergne; Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center.

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent need to find effective therapies. Preclinical studies have shown that inhaled halogenated agents may have beneficial effects in animal models of ARDS. The development of new devices to administer halogenated agents using modern intensive care unit (ICU) ventilators has significantly simplified the dispensing of halogenated agents to ICU patients. Because previous experimental and clinical research suggested potential benefits of halogenated volatiles, such as sevoflurane or isoflurane, for lung alveolar epithelial injury and inflammation, two pathophysiologic landmarks of diffuse alveolar damage during ARDS, we designed an animal model to understand the mechanisms of the effects of halogenated agents on lung injury and repair. After general anesthesia, tracheal intubation, and the initiation of mechanical ventilation, ARDS was induced in piglets via the intratracheal instillation of hydrochloric acid. Then, the piglets were sedated with inhaled sevoflurane or isoflurane using an ICU-type device, and the animals were ventilated with lung-protective mechanical ventilation during a 4 h period. During the study period, blood and alveolar samples were collected to evaluate arterial oxygenation, the permeability of the alveolar-capillary membrane, alveolar fluid clearance, and lung inflammation. Mechanical ventilation parameters were also collected throughout the experiment. Although this model induced a marked decrease in arterial oxygenation with altered alveolar-capillary permeability, it is reproducible and is characterized by a rapid onset, good stability over time, and no fatal complications. We have developed a piglet model of acid aspiration that reproduces most of the physiological, biological, and pathological features of clinical ARDS, and it will be helpful to further our understanding of the potential lung-protective effects of halogenated agents delivered through devices used for inhaled ICU sedation.
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http://dx.doi.org/10.3791/61644DOI Listing
September 2020

[Management of a global health crisis: first COVID-19 disease feedback from Overseas and French-speaking countries medical biologists].

Ann Biol Clin (Paris) 2020 10;78(5):499-518

Service de biochimie, CHU de Bordeaux ; RMSB, UMR5536 CNRS Université Bordeaux, France.

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).
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http://dx.doi.org/10.1684/abc.2020.1586DOI Listing
October 2020

S100B Blood Level Determination for Early Management of Ski-Related Mild Traumatic Brain Injury: A Pilot Study.

Front Neurol 2020 14;11:856. Epub 2020 Aug 14.

Biochemistry and Molecular Genetic Department, CHU Clermont-Ferrand, Clermont-Ferrand, France.

Mild traumatic brain injury (mTBI) management in emergency departments is a complex process involving clinical evaluation, laboratory testing, and computerized tomography (CT) scanning. Protein S100B has proven to be a useful blood biomarker for early evaluation of mTBI, as it reduces the required CT scans by one-third. However, to date, the ability of S100B to identify positive abnormal findings in the CT scans of patients suffering from mTBI caused by ski practice has not been investigated. Thus, the primary aim of this study was to investigate the diagnostic performance of S100B as an mTBI management biomarker in patients with ski-related mTBI. One hundred and thirty adult mTBI patients presenting to the emergency department of Hôpital du Valais in Sion, Switzerland, with a Glasgow Coma Scale (GCS) score of 13-15 and clinical indication for a CT scan were included in the study. Blood samples for S100B measurement were collected from each patient and frozen in 3-hour post-injury intervals. CT scans were performed for all patients. Later, serum S100B levels were compared to CT scan findings in order to evaluate the biomarker's performance. Of the 130 included cases of mTBI, 87 (70%) were related to ski practice. At the internationally established threshold of 0.1 μg/L, the receiver operating characteristic curve of S100B serum levels for prediction of abnormal CT scans showed 97% sensitivity, 11% specificity, and a 92% negative predictive value. Median S100B concentrations did not differ according to sex, age, or GCS score. Additionally, there was no significant difference between skiers and non-skiers. However, a statistically significant difference was found when comparing the median S100B concentrations of patients who suffered fractures or had polytrauma and those who did not suffer fractures. The performance of S100B in post-mTBI brain lesion screenings seems to be affected by peripheral lesions and/or ski practice. The lack of neurospecificity of the biomarker in this context does not allow unnecessary CT scans to be reduced by one-third as expected.
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http://dx.doi.org/10.3389/fneur.2020.00856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456809PMC
August 2020

Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome.

Front Immunol 2020 7;11:1645. Epub 2020 Aug 7.

Genetics, Reproduction and Development (GReD) Laboratory, Clermont Auvergne University, CNRS UMR 6293, INSERM U1103, Translational Approach to Epithelial Injury and Repair Team, Clermont-Ferrand, France.

Inflammation is the leading mechanism involved in both physiological and pathological rupture of fetal membranes. Our aim was to obtain a better characterization of the inflammasome-dependent inflammation processes in these tissues, with a particular focus on the nucleotide-binding oligomerization domain (NOD)-like receptor, pyrin domain containing protein 7 (NLRP7) inflammasome. The presence of NLRP7 inflammasome actors [NLRP7, apoptosis-associated speck-like protein containing a CARD domain (ASC), and caspase-1] was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in human amnion and choriodecidua at the three trimesters and at term. The protein concentrations were then determined by enzyme-linked immunosorbent assay in term tissues, with or without labor. The presence of and in human fetal membranes was investigated using a PCR approach. Human amnion epithelial cells (AECs) were treated for 4 or 20 h with fibroblast-stimulating lipopeptide-1 (FSL-1), a -derived ligand. Transcripts and proteins quantity was then measured by RT-quantitative PCR and Western blotting, respectively. NLRP7 and ASC colocalization was confirmed by immunofluorescence. Western blots allowed analysis of pro-caspase-1 and gasdermin D cleavage. NLRP7, ASC, and caspase-1 transcripts were expressed in both sheets of human fetal membranes during all pregnancy stages, but only ASC protein expression was increased with labor. In addition, and were detected for the first time in human fetal membranes. NLRP7 and caspase-1 transcripts, as well as NLRP7, ASC, and pro-caspase-1 protein levels, were increased in FSL-1-treated AECs. The NLRP7 inflammasome assembled around the nucleus, and pro-caspase-1 and gasdermin D were cleaved into their mature forms after FSL-1 stimulation. Two new mycoplasmas, and , were identified in human fetal membranes, and a lipopeptide derived from was found to induce NLRP7 inflammasome formation in AECs.
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http://dx.doi.org/10.3389/fimmu.2020.01645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426397PMC
April 2021

Interest of blood biomarkers to predict lesions in medical imaging in the context of mild traumatic brain injury.

Clin Biochem 2020 Nov 8;85:5-11. Epub 2020 Aug 8.

Biochemistry and Molecular Genetic Department, CHU Clermont-Ferrand, Clermont Auvergne University, CNRS, INSERM, GReD, Clermont-Ferrand, France. Electronic address:

Mild traumatic brain injury (mTBI) is one of the common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnostic tool for adults with mTBI. Alternatively, children can be admitted for inpatient observation with CCT scans performed only on those with clinical deterioration. The use of blood biomarkers is a supplementary tool for identifying patients at risk of intracerebral lesions who may need imaging. This review provides a contemporary clinical and laboratory framework for blood biomarker testing in mTBI management. The S100B protein is used routinely in the management of mTBI in Europe together with clinical guidelines. Due to its excellent negative predictive value, S100B protein is an alternative choice to CCT scanning for mTBI management under considered, consensual and pragmatic use. In this review, we propose points to help clinicians and clinical pathologists use serum S100B protein in the clinical routine. A review of the literature on the different biomarkers (GFAP, UCH-L1, NF [H or L], tau, H-FABP, SNTF, NSE, miRNAs, MBP, β trace protein) is also conducted. Some of these other blood biomarkers, used alone (GFAP, UCH-L1) or in combination (GFAP + H-FABP ± S100B ± IL10) can improve the specificity of S100B.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.08.001DOI Listing
November 2020

Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes.

Front Physiol 2020 25;11:581. Epub 2020 Jun 25.

CNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, France.

Context: Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the receptor for advanced glycation end products (RAGE), an axis implied in physiological sterile inflammation, in conjunction with two major ligands: AGEs and High-Mobility Group Box 1 (HMGB1). Our first objective was to determine the spatiotemporal expression profiles of the different actors of the RAGE-signaling axis in human FMs, including its intracellular adaptors Diaphanous-1 and Myd88. Our second goal was to evaluate the functionality of RAGE signaling in terms of FMs inflammation.

Methods: The presence of the actors (RAGE, HMGB1, Myd88, and Diaphanous-1) at the mRNA level was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the human amnion and choriodecidua at the three trimesters and at term. Measurements were conducted at two distinct zones: the zone of intact morphology (ZIM) and the zone of altered morphology (ZAM). Then, proteins were quantified using Western blot analysis, and their localization was evaluated by immunofluorescence in term tissues. In addition, pro-inflammatory cytokine secretion was quantified using a Multiplex assay after the treatment of amnion and choriodecidua explants with two RAGE ligands (AGEs and HMGB1) in the absence or presence of a RAGE inhibitor (SAGEs).

Results: The FMs expressed the RAGE-signaling actors throughout pregnancy. At term, RNA and protein overexpression of the RAGE, HMGB1, and Diaphanous-1 were found in the amnion when compared to the choriodecidua, and the RAGE was overexpressed in the ZAM when compared to the ZIM. The two RAGE ligands (AGEs and HMGB1) induced differential cytokine production (IL1β and TNFα) in the amnion and choriodecidua.

Conclusion: Considered together, these results indicate that RAGE signaling is present and functional in human FMs. Our work opens the way to a better understanding of FMs weakening dependent on a RAGE-based sterile inflammation.
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http://dx.doi.org/10.3389/fphys.2020.00581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330021PMC
June 2020

Study of sRAGE, HMGB1, AGE, and S100A8/A9 Concentrations in Plasma and in Serum-Extracted Extracellular Vesicles of Pregnant Women With Preterm Premature Rupture of Membranes.

Front Physiol 2020 23;11:609. Epub 2020 Jun 23.

Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec City, QC, Canada.

Preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 37 weeks of gestation, complicates approximately 2-4% of pregnancies and is responsible for 40% of all spontaneous preterm births. PPROM arises from complex pathophysiological pathways with a key actor: inflammation. Sterile inflammation is a feature of senescence-associated fetal membrane maturity. During specific steps of sterile inflammation, cells also release highly inflammatory damage-associated molecular pattern markers (DAMPs), such as high-mobility group box 1 (HMGB1) or S100A8/A9, known to link and activate the receptor for advanced glycation end products (RAGE). The objective of this study was to measure longitudinally during pregnancy concentrations of the soluble form of RAGE (sRAGE) and its main ligands (AGE, HMGB1, S100A8/A9) in blood specimens. We studied 246 pregnant women (82 with PPROM and 164 matched control pregnant women without complications) from a cohort of 7,866 pregnant women recruited in the first trimester and followed during pregnancy until delivery. sRAGE, AGE, HMGB1, and S100A8/A9 concentrations were measured in plasma and in serum-extracted extracellular vesicles from first trimester (T1), second trimester (T2), and delivery (D). In plasma, we observed, in both PPROM and control groups, (i) a significant increase of HMGB1 concentrations between T1 vs. T2, T1 vs. D, but not between T2 vs. D; (ii) a significant decrease of sRAGE concentrations between T1 and T2 and a significant increase between T2 and D; (iii) a significant decrease of AGE from T1 to D; (iv) no significant variation of S100A8/A9 between trimesters. In intergroup comparisons (PPROM vs. control group), there were no significant differences in time variation taking into account the matching effects. There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.
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http://dx.doi.org/10.3389/fphys.2020.00609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324632PMC
June 2020

[Transient hyperprolactinemia secondary to benzodiazepines: a case report].

Ann Biol Clin (Paris) 2020 08;78(4):438-440

Service de biochimie et génétique moléculaire, CHU Hôpital G Montpied, Clermont-Ferrand, France.

Hyperprolactinemia is common and accounts for 20 to 25% of secondary amenorrhea causes. Here, we report a case of moderate hyperprolactinemia observed in a 40-year-old patient consulting for spaniomenorrhea and inguinal pain during a bartholinitis episode. After eliminating all known causes of hyperprolactinemia, alprazolam intake is finally assumed. This hyperprolactinemia is found in a few bibliographic studies and is also noted in the summary of product characteristics. However, benzodiazepines are not known as hyperprolactinemia-inducing drugs by the endocrinologists and do not appear in the list of drugs established by a consensus of experts from the French Society of Endocrinology. This article aims to increase awareness of prescribing physicians and biologists of the possible occurrence of hyperprolactinemia in patients treated by benzodiazepines, especially since the intake of this molecule is particularly common in France, whether it is a medical prescription or self-medication.
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http://dx.doi.org/10.1684/abc.2020.1565DOI Listing
August 2020

[SFBC working group "Biochemical markers of COVID-19"].

Ann Biol Clin (Paris) 2020 06;78(3):269-277

Biochimie et génétique moléculaire, CHU Clermont-Ferrand ; UMR CNRS 6293, Inserm 1103, Université Clermont Auvergne, France.

The SARS-CoV-2 virus is responsible for an epidemic disease called COVID-19, which was initially evidenced in Wuhan, China, and spread very rapidly in China and around the world. In France, the first isolated case seems now to be reported in December 2019, stage 3 of the COVID-19 epidemic was triggered on March 14, the start of the planned containment exit from May 11. Healthcare services have faced a large influx of patients who may be beyond their capacity to receive and care, particularly in the Large-East and Ile-de-France regions. Some patients show an evolution of the disease never observed before with other coronaviruses and develop in a few days a very important inflammatory reaction, which can lead to death of patients. A working group of the French Society of Clinical Biology (SFBC) was set up with the objective of providing updated information on the current status of the biological prescriptions (focusing on biochemistry ones) and their evolution during the epidemic, and of analyzing the biological parameters associated with comorbidities and patient evolution in order to link biological results with medical events. The expanded working group covers all sectors of medical biology in France and extends to the French-speaking world: hospital sectors (CHU and CH, Army Training Hospitals) and the private sector opening a field of view on the biological situation in establishments for dependent elderly, social establishments and clinical medical institutions. The purpose of this article is the presentation of this working group and its immediate and future actions.
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http://dx.doi.org/10.1684/abc.2020.1563DOI Listing
June 2020

EPA is Cardioprotective in Male Rats Subjected to Sepsis, but ALA Is Not Beneficial.

Antioxidants (Basel) 2020 Apr 29;9(5). Epub 2020 Apr 29.

UNH, Unité de Nutrition Humaine, UMR 1019, Université Clermont Auvergne, INRAE, CRNH Auvergne, 63000 Clermont-Ferrand, France.

It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats; (ii) evaluating the influence of dietary α-linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology; and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.
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http://dx.doi.org/10.3390/antiox9050371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278601PMC
April 2020

A procedure to extract functional isolated mitochondria from small-sized human atrial samples. Application to obesity with a partial characterisation of the organelles.

Free Radic Biol Med 2020 06 21;153:71-79. Epub 2020 Apr 21.

Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000, Clermont-Ferrand, France; Heart Surgery Department, Gabriel Montpied Hospital, Clermont-Ferrand University Hospital, France; New Address: Service de Chirurgie Cardiaque, Hôpital Nord, CHU de Saint-Etienne, Avenue Albert Raimond, 42270, Saint-Priest-en-Jarez, France.

Evaluating the activity of cardiac mitochondria is probably the best way to estimate early cellular damage in chronic pathology. Early diagnosis allows rapid therapeutic intervention thus increasing patient survival rate in a number of diseases. However, data on human cardiac mitochondria are scarce in the international literature. Here, we describe a method to extract and study functional mitochondria from the small-sized right atrial aliquots (minimum of 400 mg) obtained during extracorporeal circulation and usually considered as surgical waste products. The mitochondria were purified through several mechanical processes (fine myocardial cutting, tissue grinding and potter Elvehjem homogenising), an enzymatic proteolytic action (subtilisin) and differential centrifugations. In chronic pathologies, including obesity, early disturbances of mitochondrial function can occur. The effects of obesity on the rate of mitochondrial oxygen consumption and HO release were thus determined with three different substrates (glutamate/malate, succinate/rotenone and palmitoylcarnitine/malate). The human atrial mitochondria were of high quality from a functional viewpoint, compared to rat ventricle organelles, but the extraction yield of the human mitochondria was twice lower than that of rat mitochondria. Tests showed that glutamate/malate-related ADP-stimulated respiration was strongly increased in obese subjects, although the oxidation of the other two substrates was unaffected. Reactive oxygen species (ROS) production by the isolated mitochondria was low in comparison with that of the lean subjects. These results confirm those found in one of our previous studies in the ventricles of rats fed a high-fat diet. In conclusion, the described method is simple, reliable and sensitive. It allows for the description of the impact of obesity on the function of atrial mitochondria while using only a small patient sampling (n = 5 in both the lean and the obese groups).
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.04.006DOI Listing
June 2020

The receptor for advanced glycation end-products enhances lung epithelial wound repair: An in vitro study.

Exp Cell Res 2020 06 21;391(2):112030. Epub 2020 Apr 21.

Université Clermont Auvergne, CNRS, INSERM, GReD, Clermont-Ferrand, France; Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address:

Re-epithelialization of the alveolar surface is a key process of lung alveolar epithelial barrier repair after acute lung injury. The receptor for advanced glycation end-products (RAGE) pathway plays key roles in lung homeostasis, and its involvement in wound repair has been already reported in human bronchial epithelial cells. However, its effects on lung alveolar epithelial repair after injury remain unknown. We investigated whether RAGE stimulation with its ligands high-mobility group box 1 protein (HMGB1) or advanced glycation end-products (AGEs), alone or associated with RAGE inhibition using RAGE antagonist peptide, affects in vitro wound healing in human alveolar epithelial A549 cells. We further asked whether these effects could be associated with changes in cell proliferation and migration. We found that treatment of A549 cells with HMGB1 or AGEs promotes RAGE-dependent wound healing after a scratch assay. In addition, both RAGE ligands increased cell proliferation in a RAGE-dependent manner. Treatment with HMGB1 increased migration of alveolar epithelial cells at 12 h, independently of RAGE, whereas AGEs stimulated migration as measured 48 h after injury in a RAGE-dependent manner. Taken together, these results suggest that RAGE pathway is involved in lung alveolar epithelial wound repair, possibly through enhanced cell migration and proliferation.
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http://dx.doi.org/10.1016/j.yexcr.2020.112030DOI Listing
June 2020

Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis.

Respir Res 2020 Apr 7;21(1):81. Epub 2020 Apr 7.

Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France.

Background: Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits.

Methods: We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects.

Discussion: This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation.

Systematic Review Registration: PROSPERO (ID: CRD42019157236).
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http://dx.doi.org/10.1186/s12931-020-01337-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137453PMC
April 2020

Advanced Glycation End Products and Receptor (RAGE) Promote Wound Healing of Human Corneal Epithelial Cells.

Invest Ophthalmol Vis Sci 2020 03;61(3):14

,.

Purpose: We used a human corneal epithelial cell (HCE) line to determine the involvement of the advanced glycation end products (AGEs) / receptor for AGEs (RAGE) couple in corneal epithelium wound healing.

Methods: After wounding, HCE cells were exposed to two major RAGE ligands (HMGB1 and AGEs), and wound healing was evaluated using the in vitro scratch assay. Following wound healing, the HCE cells were used to study the influence of the RAGE ligands on HCE proliferation, invasion, and migration. Activation of the nuclear factor (NF)-κB signaling pathway by the AGEs/RAGE couple was tested using a luciferase reporter assay. Functional transcriptional regulation by this pathway was confirmed by quantification of expression of the connexin 43 target gene. For each experiment, specific RAGE involvement was confirmed by small interfering RNA treatments.

Results: AGEs treatment at a dose of 100 µg/mL significantly improved the wound healing process in a RAGE-dependent manner by promoting cell migration, whereas HMGB1 had no effect. No significant influence of the AGEs/RAGE couple was observed on cell proliferation and invasion. However, this treatment induced an early activation of the NF-κB pathway and positively regulated the expression of the target gene, connexin 43, at both the mRNA and protein levels.

Conclusions: Our results demonstrate that the RAGE pathway is activated by AGEs treatment and is involved in the promotion of corneal epithelial wound healing. This positive action is observed only during the early stages of wound healing, as illustrated by the quick activation of the NF-κB pathway and induction of connexin 43 expression.
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http://dx.doi.org/10.1167/iovs.61.3.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401750PMC
March 2020

Inherited Metabolic Diseases and Cardiac Pathology in Adults: Diagnosis and Prevalence in a CardioMetabo Study.

J Clin Med 2020 Mar 4;9(3). Epub 2020 Mar 4.

Biochemistry and Molecular Genetic Department, CHU Clermont-Ferrand, Faculty of Medicine, Université Clermont-Auvergne, CNRS 6293, INSERM 1103, GReD, 63000 Clermont-Ferrand, France.

Many inherited metabolic diseases (IMD) have cardiac manifestations. The aim of this study was to estimate the prevalence of IMD in adult patients with hypertrophic cardiomyopathy (HCM) and cardiac rhythm abnormalities that require cardiac implantable electronic devices (CIEDs). The study included a review of the medical files of patients aged 18 to 65 years who were followed in our cardiology department during the period 2010-2017. Metabolic explorations for Fabry disease (FD), mitochondrial cytopathies, and fatty-acid metabolism disorders were carried out in patients with unexplained etiology. The prevalence of IMD in patients with HCM was 5.6% (confidence interval (CI): 2.6-11.6). Six cases of IMD were identified: 1 mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, 1 Hurler syndrome, 2 Friedreich's ataxia, 1 FD, and 1 short-chain acyl-CoA dehydrogenase deficiency. Three cases of IMD were identified in patients requiring CIEDs: 1 patient with Leber hereditary optic neuropathy, 1 FD, and 1 short chain acyl-CoA dehydrogenase (SCAD) deficiency. IMD prevalence in patients with CIEDs was 3.1% (CI: 1.1-8.8). IMD evaluation should be performed in unexplained HCM and cardiac rhythm abnormalities adult patients, since the prevalence of IMD is relatively important and they could benefit from specific treatment and family diagnosis.
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http://dx.doi.org/10.3390/jcm9030694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141305PMC
March 2020

[Analytical validation of 13 biochemistry parameters (CEA, CA 19-9, amylase, lipase, sodium, potassium, chloride, creatinine, glucose, protein, albumin, LDH, triglycerides) in body fluids].

Ann Biol Clin (Paris) 2020 02;78(1):93-107

Service de biochimie et génétique moléculaire, CHU Clermont-Ferrand, Clermont-Ferrand, France.

The measurement performance of 13 biochemistry parameters (CEA, CA 19-9, amylase, lipase, sodium, potassium, chloride, creatinine, glucose, protein, albumin, LDH, triglycerides) was tested in a panel of biological fluids other than blood and urine (peritoneal, pleural, pancreatic fluids ...). Our protocol, based on a risk analysis, allowed us to justify our choices and compare the performance obtained with those of the serum or plasma matrix already validated. Thus, the coefficients of variation obtained in body fluids are comparable. The assessment of accuracy (spiking and dilution tests) shows the absence of bias, which is consistent with the absence of matrix effect. The linearity studied by dilution tests shows that the upper limits of the measurement interval communicated by the supplier are applicable to body fluids. The absence of contamination and stability have been also confirmed. All analytes are stable for 3 days at room temperature, 7 days between 2 and 8̊C, and 6 months at -20̊C; except LDH and lipase. For most analytes, at least one interference (hemolysis, icterus, lipemia) was found. Finally, a bibliographical study, confronted with the experience of prescribers, led us to define optimal thresholds to help interpret patients' results. In conclusion, this work has allowed us to validate analytical methods for body fluids testing after relying on their comparability to the blood matrix. We have also been able to adapt our practices and finally be accredited according to the standard NF IN ISO 15189.
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http://dx.doi.org/10.1684/abc.2020.1524DOI Listing
February 2020

[The wishes of the SFBC President].

Authors:
Vincent Sapin

Ann Biol Clin (Paris) 2020 02;78(1)

Président de la SFBC.

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http://dx.doi.org/10.1684/abc.2020.1526DOI Listing
February 2020

Risk Factors and Outcomes of Preterm Premature Rupture of Membranes in a Cohort of 6968 Pregnant Women Prospectively Recruited.

J Clin Med 2019 Nov 15;8(11). Epub 2019 Nov 15.

Department of Molecular Biology, Medical biochemistry and Pathology, Faculty of Medicine, Centre de recherche du CHU de Québec-Université Laval, Québec City, QC G1V 0A6, Canada.

We revisited risk factors and outcomes related to the preterm premature rupture of membranes (PPROM). A total of 7866 pregnant women were recruited during 5 years at their first prenatal visit to the perinatal clinic of the institution. We compared three groups (women without prematurity, women with spontaneous preterm labor with intact membranes (sPL with IM), women with PPROM) regarding 60 criteria about characteristics, lifestyle, medical, gynecological, obstetrical history of mothers, medication during pregnancy, events at delivery, and complications in neonates. Logistic regression analyses adjusting for potential confounding factors were used. Of the 6968 women selected, 189 (2.8%) presented a PPROM, and 225 (3.2%) an sPL with IM. The specific risk factors for PPROM were body mass index (BMI) <18.5 kg/m (adjusted odds ratio, aOR: 2.00 (1.09-3.67)), history of PPROM (aOR: 2.75 (1.19-6.36)), nulliparity (aOR: 2.52 (1.77-3.60)), gestational diabetes (aOR: 1.87 (1.16-2.99)), and low level of education (aOR: 2.39 (1.20-4.78)). The complications associated with PPROM were abruption placentae, cesarean, APGAR 5' <4, birth weight <2500 g, stillbirth, neonatal jaundice, and hospitalization of mother and neonates. All these complications were also associated with sPL with IM. Our study confirms some of the risk factors of PPROM and highlights a new one: gestational diabetes. Outcomes of PPROM are related to prematurity.
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http://dx.doi.org/10.3390/jcm8111987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912547PMC
November 2019

Dietary EPA Increases Rat Mortality in Diabetes Mellitus, A Phenomenon Which Is Compensated by Green Tea Extract.

Antioxidants (Basel) 2019 Nov 4;8(11). Epub 2019 Nov 4.

Unité de Nutrition Humaine (UNH), INRA/Université Clermont Auvergne, 63000 Clermont-Ferrand, France.

Diabetes is characterized by a high mortality rate which is often associated with heart failure. Green tea and eicosapentaenoic acid (EPA) are known to lessen some of the harmful impacts of diabetes and to exert cardio-protection. The aim of the study was to determine the effects of EPA, green tea extract (GTE), and a combination of both on the cardiac consequences of diabetes mellitus, induced in Wistar rats by injection of a low dose of streptozotocin (33 mg/kg) combined with a high fat diet. Cardiac mechanical function, coronary reactivity, and parameters of oxidative stress, inflammation, and energy metabolism were evaluated. In the context of diabetes, GTE alone limited several diabetes-related symptoms such as inflammation. It also slightly improved coronary reactivity and considerably enhanced lipid metabolism. EPA alone caused the rapid death of the animals, but this effect was negated by the addition of GTE in the diet. EPA and GTE combined enhanced coronary reactivity considerably more than GTE alone. In a context of significant oxidative stress such as during diabetes mellitus, EPA enrichment constitutes a risk factor for animal survival. It is essential to associate it with the antioxidants contained in GTE in order to decrease mortality rate and preserve cardiac function.
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http://dx.doi.org/10.3390/antiox8110526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912216PMC
November 2019

Cord blood S100B: reference ranges and interest for early identification of newborns with brain injury.

Clin Chem Lab Med 2020 01;58(2):285-293

Centre de recherche du CHU de Québec-Université Laval, Québec City, Canada.

Background Neurological complications are common in the premature and full-term neonates admitted to the intensive care unit, but the diagnosis of these complications is often difficult to make. S100B protein, measured in cord blood, may represent a valuable tool to better identify patients at risk of brain injury. Methods As a first step, we established S100B cord blood serum reference intervals from 183 preterm and 200 full-term neonates. We then measured cord blood serum S100B to identify neurological complications in 272 neonates hospitalized at the neonatal intensive care unit (NICU). Diagnosis of brain injury relied on imaging examination. Results The 95th percentiles of S100B concentration in cord blood were established as 1.21 μg/L for the 383 neonates, 0.96 μg/L for full-term neonates and 1.36 μg/L for premature neonates. Among the 272 neonates hospitalized at the NICU, 11 presented neurological complications. Using 1.27 μg/L as the optimal sensitivity/specificity threshold, S100B differentiate neonates with and without neurological complications with a sensitivity of 45.5% (95% confidence intervals [CI]: 16.7-76.6) and a specificity of 88.9% (95% CI: 84.4-92.4) (p = 0.006). In combination with arterial pH (<7.25), sensitivity increased to 90.9% (95% CI: 58.7-99.8), while specificity was 51.2% (95% CI: 44.8-57.7). The sensitivity is significantly (p = 0.03) increased in comparison to S100B alone. The specificity is significantly higher with S100B only than with pH + S100B (p < 0.001). Conclusions Cord blood S100B protein, in combination with arterial cord blood pH, has the potential to help clinicians to detect at birth neurological complications in neonates hospitalized in an NCIU.
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http://dx.doi.org/10.1515/cclm-2019-0737DOI Listing
January 2020

Antioxidant and Cardioprotective Effects of EPA on Early Low-Severity Sepsis through UCP3 and SIRT3 Upholding of the Mitochondrial Redox Potential.

Oxid Med Cell Longev 2019 26;2019:9710352. Epub 2019 Aug 26.

Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, 63000 Clermont-Ferrand, France.

Sepsis still causes death, often through cardiac failure and mitochondrial dysfunction. Dietary 3 polyunsaturated fatty acids are known to protect against cardiac dysfunction and sepsis lethality. This study set out to determine whether early low-severity sepsis alters the cardiac mitochondrial function in animals fed a Western-type diet and whether dietary eicosapentaenoic acid (EPA) administration protects the myocardium against the deleterious effects of sepsis and if so to seek possible mechanisms for its effects. Rats were divided into two groups fed either an 3 PUFA-deficient diet ("Western diet," DEF group) or an EPA-enriched diet (EPA group) for 5 weeks. Each group was subdivided into two subgroups: sham-operated rats and rats subjected to cecal ligation and puncture (CLP). cardiac mechanical function was examined, and mitochondria were harvested to determine their functional activity. Oxidative stress was evaluated together with several factors involved in the regulation of reactive oxygen species metabolism. Sepsis had little effect on cardiac mechanical function but strongly depressed mitochondrial function in the DEF group. Conversely, dietary EPA greatly protected the mitochondria through a decreased oxidative stress of the mitochondrial matrix. The latter was probably due to an increased uncoupling protein-3 expression, already seen in the sham-operated animals. CLP rats in the EPA group also displayed increased mitochondrial sirtuin-3 protein expression that could reinforce the upholding of oxidative phosphorylation. Dietary EPA preconditioned the heart against septic damage through several modifications that protect mitochondrial integrity. This preconditioning can explain the cardioprotective effect of dietary EPA during sepsis.
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http://dx.doi.org/10.1155/2019/9710352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732625PMC
March 2020

[Reports from EuroMedLab 2019].

Ann Biol Clin (Paris) 2019 08;77(4):365

Président de la SFBC.

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http://dx.doi.org/10.1684/abc.2019.1463DOI Listing
August 2019

Inhibition of the Receptor for Advanced Glycation End-Products in Acute Respiratory Distress Syndrome: A Randomised Laboratory Trial in Piglets.

Sci Rep 2019 06 25;9(1):9227. Epub 2019 Jun 25.

Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont, Ferrand, France.

The receptor for advanced glycation end-products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will require assessment of this strategy in larger animals. Forty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid (i) alone; (ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), or (iii) recombinant soluble (s)RAGE. The primary outcome was net AFC at 4 h. Arterial oxygenation was assessed hourly and alveolar-capillary permeability, alveolar inflammation and lung histology were assessed at 4 h. Treatment with either RAP or sRAGE improved net AFC (median [interquartile range], 21.2 [18.8-21.7] and 19.5 [17.1-21.5] %/h, respectively, versus 12.6 [3.2-18.8] %/h in injured, untreated controls), oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after ARDS. These findings suggest that RAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.
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http://dx.doi.org/10.1038/s41598-019-45798-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592897PMC
June 2019