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Multi-Compartment SCFA Quantification in Human

American Journal of Analytical Chemistry 2024年第6期15卷 177-200页

作者： Jérémy Monteiro Antoine Lefèvre Diane Dufour-Rainfray Adeline Oury Gabrielle Chicheri Laurent Galineau Hélène Blasco Lydie Nadal-desbarats Patrick Emond Imaging Brain & Neuropsychiatry iBraiN U1253 Universit de Tours INSERM MetaboHub Tours Tours France chru de tours Service de Mdecine Nuclaire in Vitro Tours France Service de Biochimie et Biologie Molculaire CHRU Tours France

Short-chain fatty acids (SCFA) play an important role in human biochemistry. They originate primarily from the digestive system through carbohydrates microbial fermentation. Most SCFA produced in the colon are absorbed by the intestinal wall and enter the bloodstream to be distributed throughout the body for multiple purposes. At the intestinal level, SCFA play a role in controlling fat storage and fatty acid metabolism. The effects of these beneficial compounds therefore concern overall health. They facilitate energy expenditure and are valuable allies in the fight against obesity and diabetes. SCFA are also involved in the regulation of the levels of several neurotransmitters such as GABA (γ-aminobutyric acid), glutamate, serotonin, dopamine, and norepinephrine. Their role is also highlighted in many inflammatory and neurodegenerative diseases such as Alzheimer’s disease (AD) or Parkinson’s disease (PD). To have a realistic picture of the distribution of SCFA in different biological compartments of the human body, we propose to study SCFA simultaneously in five human biological samples: feces, saliva, serum, cerebrospinal fluid (CSF), and urine, as well as in Dried Blood Spot (DBS). To evaluate their concentration and repeatability, we used 10 aliquots from pooled samples, analyzed by 3-nitrophenylhydrazine (3-NPH) derivation and liquid chromatography coupled with high sensitivity mass spectrometry (LC-QqQ-MS). We also evaluated the SCFA assay on Dried Blood Spot (DBS). In this work, we adapted the pre-analytical parts for each sample to be able to use a common calibration curve, thus facilitating multi-assay quantification studies and so being less time-consuming. Moreover, we proposed new daughter ions from the same neutral loss (43 Da) to quantify SCFAs, thus improving the sensitivity. In conclusion, our methodology, based on a unique calibration curve for all samples for each SCFA, is well-suited to quantified them in a clinical context.

关键词： LC-MS 3-Nitrophenylhydrazine Short-Chain Fatty Acids Human Biological Samples Quantification

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Is it possible to use the HCR-20 V2 to assess the risk of violent recidivism of French offenders?

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Forensic Sciences Research 2022年第3期7卷 402-411页

作者： Ingrid Bertsch Robert Courtois Elodie Gallard Christian Réveillère Thierry H.Pham department of Psychology EE 1901 Qualipsy(Qualitéde vie et santépsychologique)University of ToursToursFrance Centre Ressource pour les Intervenants auprès des Auteurs de Violences Sexuelles Centre Val-de-Loire CHRU de ToursToursFrance Centre de Recherche en Défense Sociale CRDSTournaiBelgium detention Center of Mauzac Mauzac-et-Grand-CastangFrance department of Forensic Psychology University of Mons-HainautMonsBelgium

The Historical-Clinical-Risk Management Scale 20(HCR-20)is a structured tool to assess the risk of violence and assist in its management.French professionals are reluctant to use it because only a few studies have shown its psychometric qualities with French samples.The objective of this study is to test the psychometric qualities of the HCR-20 with samples of violent detainees in France.The HCR-20 and Level of Service/Case Management Inventory(LS/CMI)were administered to 128 violent offenders with an average age of(44.16±12.30)years.We evaluated the reliability,internal consistency and validity of the HCR-20 and conducted an exploratory factor analysis.The results show that the HCR-20 has good psychometric qualities with a sample of French prisoners.Only the Risk domain presents weak results due to the data collection locations and the participants’age.Correlations were observed between certain factors.The exploratory factor analysis shows four factors explaining 44%of the variance.The continuation of this work will enable French professionals to use sound tools to assess the risk of recidivism.

关键词： HCR-20 assessment recidivism risk violence

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Alpha-7 nicotinic acetylcholine receptor agonist treatment in a rat model of Huntington's disease and involvement of heme oxygenase-1

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Neural Regeneration Research 2018年第4期13卷 737-741页

作者： Laura Foucault-Fruchard Claire Tronel Sylvie Bodard Zuhal Gulhan Julie Busson Sylvie Chalon Daniel Antier UMR 1253 iBrainUniversité de Tours chru de tours H?pital Bretonneau

Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases.We recently reported that repeated alpha-7 nicotinic acetylcholine receptor（α7 n ACh R） activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons.To further investigate the underlying mechanism,we established rat models of early-stage Huntington＇s disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water,twice a day during 4 days.Western blot assay results showed that the expression of heme oxygenase-1（HO-1）,the key component of the cholinergic anti-inflammatory pathway,in the right striatum of rat models of Huntington＇s disease subjected to intraperitoneal injection of PHA 543613 for 4 days was significantly increased compared to the control rats receiving intraperitoneal injection of sterile water,and that the increase in HO-1 expression was independent of change in α7 n ACh R expression.These findings suggest that HO-1 expression is unrelated to α7 n ACh R density and the increase in HO-1 expression likely contributes to α7 n ACh R activation-related neuroprotective effect in early-stage Huntington＇s disease.

关键词： alpha 7 nicotinic receptor PHA 543613 quinolinic acid cholinergic anti-inflammatory pathway neuroinflammation neurodegenerative disease

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Pazopanib-induced posterior reversible encephalopathy syndrome with possible syndrome of inappropriate secretion of antidiuretic hormone: an incidental or pathophysiological association?

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Neural Regeneration Research 2020年第6期15卷 1166-1168页

作者： Jonathan Wong So Bérenger Largeau Frédérique Beau-Salinas Stephan Ehrmann Christophe Magni Jérome Meunier CHR d’Orléans Service d’Oncologie MédicaleOrléansFrance chru de tours Centre d’Investigation Clinique-CIC INSERM 1415ToursFrance chru de tours Service de PharmacosurveillanceCentre Régional de Pharmacovigilance Centre-Val de LoireToursFrance Universitéde tours INSERMCentre d’étude des pathologies respiratoires(CEPR)-UMR 1100CHRU de ToursService de Médecine Intensive RéanimationCIC INSERM 1415réseau CRICS-TRIGGERSEPToursFrance CHR d’Orléans Service de NeuroradiologieOrléansFrance

Introduction:Pazopanib is an oral protein kinase inhibitor(PKI)that targets vascular endothelial growth factor(VEGF)receptors,fibroblastic growth factor receptors,platelet-derived growth factor receptors,and stem cell factor that inhibits VEGF-induced cellular proliferation.Pazopanib is approved for use in advanced renal cell carcinoma and subtypes of advanced soft-tissue sarcoma(deguchi et al.,2018).Major adverse drug reactions of pazopanib include hypertension,high-grade hyponatremia and posterior reversible encephalopathy syndrome(PRES)(Berardi et al.,2016;deguchi et al.,2018).In clinical trials,few investigations have been conducted to determine the aetiology of PKI-associated hyponatremia,the mechanism remains therefore unknown.Only rare cases of PKI-induced syndrome of inappropriate secretion of antidiuretic hormone(SIADH)(Largeau et al.,2019),and none with pazopanib,have been reported.PRES is a clinical and radiological entity where a bilateral white matter oedema,occurring predominantly in the posterior occipital and parietal lobes,is associated with several neurologic symptoms.Interestingly,a recent review suggests that SIADH could be a symptom of PRES(Largeau et al.,2019).To our knowledge,this is the first case published where pazopanib-induced PRES occurs contemporaneously with possible SIADH.

关键词： al. SIADH antidiuretic

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Evaluation of Doppler-ultrasonography in the diagnosis of transjugular intrahepatic portosystemic shunt dysfunction: A prospective study

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World Journal of Hepatology 2017年第27期9卷 1125-1132页

作者： Charlotte Nicolas Amelie Le Gouge Louis d’Alteroche Jean Ayoub Monica Georgescu Vincent Vidal denis Castaing Jean-Pierre Cercueil Patrick Chevallier Jerome Roumy Herve Trillaud Louis Boyer Vincent Le Pennec Christophe Perret Bruno Giraudeau Jean-Marc Perarnau STIC-TIPS group Service d’Hepato-Gastroenterologie Hopital TrousseauCHRU Tours CIC CHRU de Tours INSERM United’echographie-doppler Hopital TrousseauCHRU Tours Service de Radiologie Hopital de la Timone Centre Hepato-Biliaire Hopital Paul Brousse Service de Radiologie CHRU Dijon Service d’Imagerie Medicale Diagnostique et interventionnelle Hopital de l’ArchetⅡNice Service de Radiologie et Echographie CHRU Poitiers Service d’Imagerie Medicale Hopital Saint Andre CHRU Bordeaux Service d’Imagerie viscerale et vasculaire CHRU Clermont Ferrand Service de Radiologie CHRU Caen Service de Radiologie CHRU Nantes 不详

AIM To prospectively evaluate the performance of Dopplerultrasonography(US) for the detection of transjugular intrahepatic portosystemic shunt(TIPS) dysfunction within a multicenter cohort of cirrhotic patients.METHODS This study was conducted in 10 french teaching hospitals. After TIPS insertion, angiography and liver Doppler-US were carried out every six months to detect dysfunction(defined by a portosystemic gradient ≥ 12 mm Hg and/or a stent stenosis ≥ 50%). The association between ultrasonographic signs and dysfunction was studied by logistic random-effects models, and the diagnostic performance of each Doppler criterion was estimated by the bootstrap method. This study was approved by the ethics committee of tours.RESULTS Two hundred and eighteen pairs of examinations performed on 87 cirrhotic patients were analyzed. Variables significantly associated with dysfunction were: The speed of flow in the portal vein(P = 0.008), the reversal of flow in the right(P = 0.038) and left(P = 0.049) portal branch, the loss of modulation of portal flow by the right atrium(P = 0.0005), ascites(P = 0.001) and the overall impression of the operator(P = 0.0001). The diagnostic performances of these variables were low; sensitivity was detection of TIPS dysfunction is poor compared to angiography. New tools are needed to improve diagnosis of TIPS dysfunction.

关键词： Transjugular intrahepatic portosystemic shunt Dysfunction Doppler-ultrasonography

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Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

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Neural Regeneration Research 2017年第9期12卷 1418-1421页

作者： Laura Foucault-Fruchard Daniel Antier UMR INSERM U930 Université Fran?ois Rabelais chru de tours H?pital Bretonneau

Neurodegenerative diseases, such as Alzheimer＇s, Parkinson＇s and Huntington＇s diseases, are all character- ized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

关键词： α7 nicotinic receptors cholinergic anti-inflammatory pathway Alzheimer＇s disease Huntington＇s disease Parkinson＇s disease neuroinflammation neurodegeneration positive allosteric modulators

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Awake prone positioning for patients with COVID-19-induced acute hypoxemic respiratory failure

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Journal of Intensive Medicine 2022年第4期2卷 233-240页

作者： Yonatan Perez Jian Luo Miguel Ibarra-Estrada Jie Li Stephan Ehrmann Médecine Intensive Réanimation Hôpital de HautepierreHôpitaux universitaires de StrasbourgStrasbourg 67000France Respiratory Medicine Unit and Oxford NIHR Biomedical Research Centre NDM Experimental MedicineUniversity of OxfordOxford OX39DUUK Unidad de Terapia Intensiva Hospital Civil Fray Antonio Alcalde.Universidad de Guadalajara.GuadalajaraJalisco 44280Mexico department of Cardiopulmonary Sciences Division of Respiratory CareRush UniversityChicagoIL 60612USA Médecine Intensive Réanimation CIC 1415 INSERMCRICS-TriggerSep F-CRIN research networkCHRU de ToursTours France and Centre d’étude des pathologies respiratoires(CEPR)INSERM U1100Universitéde ToursTours 37000France

Whereas prone positioning of intubated patients suffering from acute respiratory distress syndrome represents the standard of care,proning non-intubated patients,so-called“awake prone positioning(APP),”has only recently gained popularity and undergone scientific evaluation.In this review,we summarize current evidence on physiological and clinical effects of APP on patients’centered outcomes,such as intubation and mortality,the safety of the technique,factors and predictors of success,practical issues for optimal implementation,and future areas of research.Current evidence supports using APP among patients suffering from acute hypoxemic respiratory failure due to COVID-19 and undergoing advanced respiratory support,such as high-flow nasal cannula,in an intensive care unit setting.Healthcare teams should aim to prone patients at least 8 h daily.Future research should focus on optimizing the tolerance of the technique and comprehensively evaluating benefits in other patient populations.

关键词： Respiratory distress syndrome Intensive care units Prone position Intubation

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A multiplatform metabolomic approach to characterize fecal signatures of negative postnatal events in chicks: a pilot study

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Journal of Animal Science and Biotechnology 2019年第2期10卷 424-434页

作者： Stéphane Beauclercq Antoine Lefèvre Frédéric Montigny Anne Collin Sophie Tesseraud Christine Leterrier Patrick Emond Laurence A.Guilloteau BOA INRAUniversitéde Tours37380 NouzillyFrance Universitéde tours PST Analyse des systèmes biologiquesToursFrance PRC INRACNRSUniversitéde ToursIFCE37380 NouzillyFrance UMR 1253 iBrainUniversitéde ToursInsermToursFrance chru de tours Service de Médecine Nucléaire In VitroToursFrance.

Background: Negative experiences in early life can induce long-lasting effects on the welfare, health, and performance of farm animals. A delayed placement of chicks in rearing houses has negative effects on their performance, and results in fecal-specific odors detectable by rats. Based on this observation, the volatile organic compounds(VOCs) and metabolites from the feces of 12-day-old chickens were screened for early markers of response to negative events using gas-chromatography and liquid-chromatography coupled with mass spectrometry(GC-MS, LC-HRMS).Results: The low reproducibility of solid-phase micro-extraction of the VOCs followed by GC-MS was not suitable for marker discovery, in contrast to liquid extraction of metabolites from freeze-dried feces followed by GC-MS or LC-HRMS analysis. Therefore, the fecal metabolome from 12-day-old chicks having experienced a normal or delayed placement were recorded by GC-MS and LC-HRMS in two genotypes from two experiments. From both experiments, 25 and 35 metabolites, respectively explaining 81% and 45% of the difference between delayed and control chickens, were identified by orthogonal partial least-squares discriminant analysis from LC-HRMS and GC-MS profiling.Conclusion: The sets of molecules identified will be useful to better understand the chicks’ response to negative events over time and will contribute to define stress or welfare biomarkers.

关键词： Biomarker Chick Feces GC-MS LC-HRMS Negative postnatal event

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development of a Fast and Facile Analytical Approach to Quantify Radiometabolites in Human Plasma Samples Using Ultra High Performance Liquid Chromatography

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American Journal of Analytical Chemistry 2019年第5期10卷 185-201页

作者： Cé cile Malherbe Rudy Bidault Claude Netter denis Guilloteau Johnny Vercouillie Nicolas Arlicot UMR 1253 iBrain Universit&#233 de tours Inserm Tours France chru de tours Unit&#233 de Radiopharmacie Tours France Thermo Fisher Scientific Waltham MA USA chru de tours Service de M&#233 decine Nuclé aire in Vitro Tours France INSERM CIC 1415 University Hospital Tours France

Introduction: Conventional metabolite analyses often require manual sample preparation, generating variability of measurements. This study describes a new method to quantify radiometabolites in blood, combining ultra high performance liquid chromatography (UHPLC) and turbulent flow chromatography, an alternative fully automated process allowing analyte’s extraction. Methods: A new radiotracer for dopamine transporter imaging, namely LBT-999, was used to demonstrate the method’s robustness. Matrix effect, Turboflow column loading, linearity, specificity and precision were evaluated with in vitro samples of LBT-999 in human plasma. Radiodetector sensitivity and preliminary evaluation were respectively determined by analysis of calibrated samples of [18F]LBT-999 and blood samples from 4 healthy subjects injected with [18F]LBT-999, withdrawn at 5, 15, 30 and 45 min pi. Results: With three sequential loadings (3 × 100 μL) of the Turboflow column, mean coefficients of variation were 1%, below 2%, 2% and 30.9% for matrix effect, specificity, repeatability and intermediate precision, respectively. Correlation coefficients for linearity were superior to 0.97. Limits of detection and quantification of the radiodetector were fixed at 3 and 9 c/s. Retention times for [18F]LBT-999 and the two radiometabolites detected by radio-UHPLC were 6.5, 4.8 and 9.6 min. Forty-five min after the injection, parent fraction was still predominant with 57.8% ± 25% of the total radioactivity. Conclusions: An innovative approach, allying UHPLC and Turboflow column, was developed and its sensitivity, linearity, specificity and repeatability validated. Preliminary results of the clinical trial are in accordance with literature data, demonstrating its efficiency in radiometabolites quantification.

关键词： Radiometabolite Ultra High Performance Liquid Chromatography Turboflow Method Validation [18F]LBT-999

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Transit time ultrasound perivascular flow probe technology is superior to MR imaging on hepatic blood flow measurement in a porcine model

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 538-545页

作者： Mohamed Bekheit Chloe Audebert Petru Bucur Hans Adriaensen Emilie Bled Mylène Wartenberg Irene Vignon-Clementel Eric Vibert Inserm Unité 1193 112 Boulevard Paul Valliant CuturierVillejuifFrance Institute of medical sciences University of AberdeenAberdeenUK Centre de recherche Inria de Paris ParisFrance Sorbonne Universités UPMC University of Paris 6Laboratoire Jacques-LouisLionsParisFrance chru hopitaux de ToursChirurgie Héato-biliaire et pancréatiqueTransplantation HéatiqueToursFrance Plateforme Chirurgie et Imagerie pour le Recherche et l’Enseignement(CIRE) ImagerieUMR-PRC37380 NouzillyCentre INRA Val de LoireFrance AP-HP Hoital Paul BrousseCentre Héato-BiliaireVillejuifFrance

Background: The hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound(TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI(PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events. Methods: Eighteen large white pigs were anaesthetized for PC-MRI and approximately 75% hepatic resection was performed under a unified protocol. The blood flow was measured in the hepatic artery(Qha), the portal vein(Qpv), and the aorta above the celiac trunk(Qca) using PC-MRI, and was compared to the TTUS probe. The Bland-Altman method was conducted and a partial least squares regression(PLS) model was implemented. Results: The mean Qpv measured in PC-MRI was 0.55 ± 0.12 L/min, and in the TTUS probe was 0.74 ± 0.17 L/min. Qca was 1.40 ± 0.47 L/min in the PC-MRI and 2.00 ± 0.60 L/min in the TTUS probe. Qha was 0.17 ± 0.10 L/min in the PC-MRI, and 0.13 ± 0.06 L/min in the TTUS probe. The Bland-Altman method revealed that the estimated bias of Qca in the PC-MRI was 32%(95% CI:-49% to 15%); Qha 17%(95% CI:-15% to 51%); and Qpv 40%(95% CI:-62% to 18%). The TTUS probe had a higher weight in predicting adverse outcomes after 75% resection compared to the PC-MRI( β= 0.35 and 0.43 vs β = 0.22 and 0.07, for tissue changes and premature death, respectively). Conclusions: There is a tendency of the PC-MRI to underestimate the flow measured by the TTUS probes. The TTUS probe measures are more predictive of relevant post-hepatectomy outcomes.

关键词： Hepatic blood flow Phase contrast MRI Transit time ultrasound probe Porcine model Liver surgery

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