Drug Vaping: From the Dangers of Misuse to New Therapeutic Devices.

Users of e-cigarettes are unwitting volunteers participating in a worldwide epidemiological study. Because of the obvious benefits of e-cigarettes compared with traditional cigarette smoking, these electronic devices have been introduced all around the world to support tobacco smoking cessation. Same potential harm reduction could be considered by cannabis vaping for marijuana smokers. However, the toxicities of liquids and aerosols remain under investigation because although the use of e-cigarettes is likely to be less harmful than traditional cigarette smoking, trace levels of contaminants have been identified. Simultaneously, other electronic devices, such as e-vaporisers, e-hookahs or e-pipes, have been developed and commercialised. Consequently, misuse of electronic devices has increased, and experimentation has been documented on Internet web fora. Although legal and illegal drugs are currently consumed with these e-devices, no scientific papers are available to support the observations reported by numerous media and web fora. Moreover, building on illegal drug vaping and vaporisation with e-devices (vaping misuse), legal drug vaping (an alternative use of vaping) could present therapeutic benefits, as occurs with medical cannabis vaporisation with table vaporisers. This review seeks to synthesise the problems of e-cigarette and liquid refill toxicity in order to introduce the dangers of illegal and legal drugs consumed using vaping and vaporisation for recreational purposes, and finally, to present the potential therapeutic benefits of vaping as a new administration route for legal drugs

Automatic quantification of the microvascular density on whole slide images, applied to paediatric brain tumours

Angiogenesis is a key phenomenon for tumour progression, diagnosis and treatment in brain tumours and more generally in oncology. Presently, its precise, direct quantitative assessment can only be done on whole tissue sections immunostained to reveal vascular endothelial cells. But this is a tremendous task for the pathologist and a challenge for the computer since digitised whole tissue sections, whole slide images (WSI), contain typically around ten gigapixels. We define and implement an algorithm that determines automatically, on a WSI at objective magnification $40\times$, the regions of tissue, the regions without blur and the regions of large puddles of red blood cells, and constructs the mask of blur-free, significant tissue on the WSI. Then it calibrates automatically the optical density ratios of the immunostaining of the vessel walls and of the counterstaining, performs a colour deconvolution inside the regions of blur-free tissue, and finds the vessel walls inside these regions by selecting, on the image resulting from the colour deconvolution, zones which satisfy a double-threshold criterion. A mask of vessel wall regions on the WSI is produced. The density of microvessels is finally computed as the fraction of the area of significant tissue which is occupied by vessel walls. We apply this algorithm to a set of 186 WSI of paediatric brain tumours from World Health Organisation grades I to IV. The segmentations are of very good quality although the set of slides is very heterogeneous. The computation time is of the order of a fraction of an hour for each WSI on a modest computer. The computed microvascular density is found to be robust and strongly correlates with the tumour grade. This method requires no training and can easily be applied to other tumour types and other stainings

Confirmation of natural gas explosion from methane quantification by headspace gas chromatography-mass spectrometry (HS-GC-MS) in postmortem samples: a case report

A new analytical approach for measuring methane in tissues is presented. For the first time, the use of in situ-produced, stably labelled CDH3 provides a reliable and precise methane quantification. This method was applied to postmortem samples obtained from two victims to help determine the explosion origin. There was evidence of methane in the adipose tissue (82nmol/g) and cardiac blood (1.3nmol/g) of one victim, which corresponded to a lethal methane outburst. These results are discussed in the context of the available literature to define an analysis protocol for application in the event of a gas explosio

Carbon monoxide analysis method in human blood by Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS): Relevance for postmortem poisoning diagnosis.

Carbon monoxide is one of the most abundant toxic air pollutants. Symptoms of a CO intoxication are non-specific, leading to a high number of misdiagnosed CO poisoning cases that are missing in the disease statistics. The chemical nature of the molecule makes it difficult to detect for long periods and at low levels, thus requiring a very accurate and sensitive method. Current methods capable of accurate and sensitive analyses are available, however an inconsistency between results and symptoms are frequently reported. Therefore, an improved method for the analysis of carbon monoxide in blood and in the headspace (HS) of the sampling tube with the use of Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS) is hereby presented and validated, for CO concentrations in a range of 10-200 nmol/mL HS (2-40 μmol/mL blood). Analytical LOQ is found at 0.9 nmol/mL HS (0.18 μmol/mL blood) and LOD at 0.1 nmol/mL gas. Application to intoxicated samples from autopsies and comparison to previously published methods show that this method is more appropriate, since performed under fully controlled conditions. Results show higher CO concentrations compared to previous approaches, indicating that results might have been underestimating the true blood CO burden. Therefore, this approach has the potential to help reduce the misdiagnosed cases and the gap between measurement and diagnosis of CO poisonings

Total Blood Carbon Monoxide: Alternative to Carboxyhemoglobin as Biological Marker for Carbon Monoxide Poisoning Determination.

As one of the most abundant toxic contaminants in the atmosphere, carbon monoxide (CO) plays a significant role in toxicology and public health. Every year, around half of the accidental non-fire-related poisoning deaths are attributed to CO in the USA, UK and many other countries. However, due to the non-specificity of the symptoms and often encountered inconsistency of these with the results obtained from measurements of the biomarker for CO poisonings, carboxyhemoglobin (COHb), there is a high rate of misdiagnoses. The mechanism of toxicity of CO includes not only the reduced transport of oxygen caused by COHb but also the impairment of cellular respiration and activation of oxidative metabolism by binding to other proteins. Therefore, in this study we propose the measurement of the total amount of CO in blood (TBCO) by airtight gas syringe-gas chromatography-mass spectrometry (AGS-GC-MS) as an alternative to COHb for the determination of CO exposures. The method is validated for a clinical range with TBCO concentrations of 1.63-104 nmol/mL of headspace (HS) (0.65-41.6 μmol/mL blood). The limit of quantification was found between 2 and 5 nmol/mL HS (0.8 and 2 μmol/mL blood). The method is applied to a cohort of 13 patients, who were exposed to CO under controlled conditions, and the results are compared to those obtained by CO-oximetry. Furthermore, samples were compared before and after a "flushing" step to remove excess CO. Results showed a significant decrease in TBCO when samples were flushed (10-60%), whereas no constant trend was observed for COHb. Therefore, measurement of TBCO by AGS-GC-MS suggests the presence of more dissolved CO than previously known. This constitutes a first step into the acknowledgment of a possibly significant amount of CO present not in the form of COHb, but as free CO, which might help explain the incongruences with symptoms and decrease misdiagnoses

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