85 research outputs found
Accuracy Profile Validation of a New Analytical Method for Propane Measurement Using Headspace-Gas Chromatography-Mass Spectrometry
Propane can be responsible for several types of lethal intoxication and explosions. Quantifying it would be very helpful to determine in some cases the cause of death. Some gas chromatography-mass spectrometry (GC-MS) methods of propane measurements do already exist. The main drawback of these GC-MS methods described in the literature is the absence of a specific propane internal standard necessary for accurate quantitative analysis. The main outcome of the following study was to provide an innovative Headspace-GC-MS method (HS-GC-MS) applicable to the routine determination of propane concentration in forensic toxicology laboratories. To date, no stable isotope of propane is commercially available. The development of an in situ generation of standards is thus presented. An internal-labeled standard gas (C3DH7) is generated in situ by the stoichiometric formation of propane by the reaction of deuterated water (D2O) with Grignard reagent propylmagnesium chloride (C3H7MgCl). The method aims to use this internal standard to quantify propane concentrations and, therefore, to obtain precise measurements. Consequently, a complete validation with an accuracy profile according to two different guidelines, the French Society of Pharmaceutical Sciences and Techniques (SFSTP) and the Gesellschaft für toxikologische und Forensische Chemie (GTFCh), is presente
Hydrogen Sulfide Measurement by Headspace-gas Chromatography-mass Spectrometry (HS-GC-MS): Application to Gaseous Samples and Gas Dissolved in Muscle
The aim of our study was to present a new headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable to the routine determination of hydrogen sulfide (H2S) concentrations in biological and gaseous samples. The primary analytical drawback of the GC/MS methods for H2S measurement discussed in the literature was the absence of a specific H2S internal standard required to perform quantification. Although a deuterated hydrogen sulfide (D2S) standard is currently available, this standard is not often used because this standard is expensive and is only available in the gas phase. As an alternative approach, D2S can be generated in situ by reacting deuterated chloride with sodium sulfide; however, this technique can lead to low recovery yield and potential isotopic fractionation. Therefore, N2O was chosen for use as an internal standard. This method allows precise measurements of H2S concentrations in biological and gaseous samples. Therefore, a full validation using accuracy profile based on the β-expectation tolerance interval is presented. Finally, this method was applied to quantify H2S in an actual case of H2S fatal intoxicatio
Postmortem Internal Gas Reservoir Monitoring Using GC×GC-HRTOF-MS
Forensic investigations often require postmortem examination of a body. However, the collection of evidence during autopsy is often destructive, meaning that the body can no longer be examined in its original state. In order to obtain an internal image of the body, whole body postmortem computed tomography (PMCT) has proven to be a valuable non-destructive tool and is currently used in medicolegal centers. PMCT can also be used to visually locate gas reservoirs inside a cadaver, which upon analysis can provide useful information regarding very volatile compounds that are produced after death. However, the non-targeted profiling of all potential volatile organic compounds (VOCs) present in these reservoirs has never been attempted. The aim of this study was to investigate the VOC profile of these reservoirs and to evaluate potential uses of such information to document circumstances surrounding death, cause of death and body taphonomy. Comprehensive two-dimensional gas chromatography coupled to time-of-flight high-resolution mass spectrometry (GCxGC-HRTOF-MS) was used for VOC measurements. This study demonstrated that the chemical composition of VOCs within the gas reservoirs differed between locations within a single body but also between individuals. In the future, this work could be expanded to investigate a novel, non-destructive cadaver screening approach prior to full autopsy procedures
Astrocytes reverted to a neural progenitor-like state with transforming growth factor alpha are sensitized to cancerous transformation.
International audienceGliomas, the most frequent primitive central nervous system tumors, have been suggested to originate from astrocytes or from neural progenitors/stem cells. However, the precise identity of the cells at the origin of gliomas remains a matter of debate because no pre-neoplastic state has been yet identified. Transforming growth factor (TGF)-alpha, an epidermal growth factor family member, is frequently overexpressed in the early stages of glioma progression. We previously demonstrated that prolonged exposure of astrocytes to TGF-alpha is sufficient to trigger their reversion to a neural progenitor-like state. To determine whether TGF-alpha dedifferentiating effects are associated with cancerous transforming effects, we grafted intracerebrally dedifferentiated astrocytes. We show that these cells had the same cytogenomic profile as astrocytes, survived in vivo, and did not give birth to tumors. When astrocytes dedifferentiated with TGF-alpha were submitted to oncogenic stress using gamma irradiation, they acquired cancerous properties: they were immortalized, showed cytogenomic abnormalities, and formed high-grade glioma-like tumors after brain grafting. In contrast, irradiation did not modify the lifespan of astrocytes cultivated in serum-free medium. Addition of TGF-alpha after irradiation did not promote their transformation but decreased their lifespan. These results demonstrate that reversion of mature astrocytes to an embryonic state without genomic manipulation is sufficient to sensitize them to oncogenic stress
The Boston criteria version 2.0 for cerebral amyloid angiopathy:a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study
BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. FUNDING: US National Institutes of Health (R01 AG26484)
Caractérisation des composés volatils responsables des qualités odorantes du saumon fumé (Salmo salar) et évaluation des contaminants du fumage (Hydrocarbures aromatiques polycycliques)
Les travaux décrits dans ce manuscrit ont pour objectif la caractérisation des composés volatils responsables des qualités odorantes du saumon fumé ainsi que l évaluation des contaminants chimiques apportés par le fumage. L évaluation organoleptique a nécessité un développement méthodologique de caractérisation simultanée de l odeur globale et des composés volatils odorants du saumon fumé. L odeur globale a ainsi été évaluée par analyse sensorielle et la caractérisation des composés volatils odorants a nécessité la mise au point d une méthode d extraction quantitative et représentative de l arôme de saumon fumé et d une méthode d analyse par chromatographie en phase gazeuse couplée à l olfactométrie et la spectrométrie de masse. Cette double caractérisation a permis d identifier les principaux composés volatils odorants de l arôme du saumon fumé et d en étudier l influence sur la perception odorante globale du saumon fumé. L évaluation sanitaire a nécessité un développement méthodologique pour la détermination des Hydrocarbures Aromatiques Polycycliques, contaminants du fumage, analysés par chromatographie en phase gazeuse couplée à la spectrométrie de masse en tandem. Les méthodes développées ont été validées par leurs capacités à discriminer des saumons fumés par quatre techniques de fumage industriel aboutissant à l obtention de produits aux qualités sensorielles, à des profils aromatiques et sanitaires différents.The works described in this manuscript aim to characterise the volatile compounds responsible for the odorant qualities of smoked salmon and to evaluate the chemical smoking contaminants occurence. The organoleptic evaluation required a methodological development of simultaneous characterisation of the overall odour and odorant volatile compounds of smoked salmon. Therefore overall odour was assessed by sensory analysis and the characterisation of odorant volatile compounds required the optimisation of a representative and quantitative extraction method of the smoked salmon aroma and an analysis method by gas chromatography coupled to olfactometry and mass spectrometry. This double characterisation allowed to identify the main odorant volatile compounds and to study their influence on the overall odorant perception of smoked salmon. The sanitary evaluation required a methodological development for the determination of Polycyclic Aromatic Hydrocarbons, contaminants of smoking process, by means of gas chromatography coupled to tandem mass spectrometry. The methods used were validated by their ability to discriminate smoked salmons processed by four industrial smoking techniques leading to products with differences for sensory qualities, aroma and PAH profiles.NANTES-BU Sciences (441092104) / SudocSudocFranceF
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