It can be useful to discover a person’s chronic drinking consumption in child custody cases and to aid in the diagnosis of diseases like fetal alcohol spectrum disorder. When one alcohol marker in hair is analysed to indicate chronic use false negatives and false positives can occur. When two (ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs)) are analysed false negatives and false positives can be recognized and provide stronger evidence as is underlined statistically in this work. For a combined method, the sample preparation and analytical procedures were optimized. The effect of the decontamination step was difficult to interpret, which shows that addressing issues with external contamination is challenging. Analytes may be extracted from the hair matrix during decontamination and analytes can diffuse into the hair shaft from external contamination. The last is illustrated by the incorporation via excretions of endogenous EtG and FAEEs. A novel and sensitive analytical procedure was developed and validated which saves time and possibly money compared to analysing of both markers separately. The best overall method had a linear calibration curve (r2 > 0:99) and an intra-day (n=3) and inter-day (n=9) accuracy for the quality control samples at three concentration levels between 84–118% with a coefficient of variation of 3–30% for both EtG and the FAEEs. The Bayesian approach was suggested as a new interpretation framework for hair tests, to account for the uncertainties in these tests in a transparent manner. In this work databases were constructed with EtG and FAEEs hair concentrations linked to the subject’s chronic alcohol use, the likelihood ratios were calculated and working examples were provided. This showed that a positive hair test for either EtG or FAEEs may very well be only ’limited’ evidence and therefore should only be used with a high prior odds. This means that a hair test result should not be used in isolation. The large confidence interval in this study also underlines the need for more control data.

As a result of alcohol consumption being highly prevalent in today’s society, research has been done to investigate the effects of alcohol on the body’s physiological systems. Research has indicated that heavy alcohol consumption is detrimental to the normal structure and function of some organs, especially the liver. However, little research has focused on the effects of chronic alcohol consumption on the female reproductive system. To investigate these effects, the uterine tissues of mice fed an ethanol diet (the NIAAA model also known as the Lieber-DeCarli diet) and mice fed a control diet were compared. The NIAAA model was chosen for this research because it simulates the drinking pattern that is known to cause liver disease in alcoholic hepatitis patients. This is achieved by incorporating both chronic and binge drinking patterns of alcohol consumption. In this study, the mucin layer that lines the endometrial surface of the uterus was analyzed in mice separated into ethanol and control fed groups. The ethanol fed mice were put on the Lieber-DeCarli 5% (v/v) ethanol diet ad libitum for 10-days followed by a single high dose of ethanol (5g/kg) on the 11th day. The control fed mice were placed on an ethanol free isocaloric diet (supplemented with maltose dextrin to match the calories of ethanol). After the 11th day, the mice were sacrificed, and uterine tissues were harvested. The tissues were then embedded in paraffin, sectioned, stained via the Hematoxylin and Eosin (H&E) technique, and examined under a microscope. The thickness of the uterine mucin layer was then measured for each animal and the average thicknesses were calculated. A one-way ANOVA test was employed to compare the mucin thickness between the two groups of animals. The test revealed no statistically significant difference between the thicknesses of the uterine mucin layer in the control and ethanol fed animals (P-value: 0.774).

L’inflammation est un processus essentiel à prendre en compte dans la pratique clinique. Nous avons montré durant cette thèse que le statut (neuro)inflammatoire précédant la survenue d’une pathologie cérébrale est à prendre en compte nécessairement puisqu’il modifie drastiquement la réponse inflammatoire suite à un deuxième stimulus comme la survenue d’un AVC. Il est d’autant plus important que 90% des AVC sont associés à des comorbidités comme l’hypertension artérielle, le diabète ou la consommation chronique d’alcool, qui ont d’ores et déjà été décrites comme des maladies avec une composante inflammatoire. Nous avons caractérisé ce statut neuroinflammatoire silencieux, aussi appelé priming, dans le cadre de la consommation chronique d’alcool et dans le traumatisme crânien léger. De plus, nous avons identifié les macrophages périvasculaires comme participants à l’effet aggravateur du priming inflammatoire sur les lésions ischémiques. Ils semblent alors être une cible thérapeutique de choix et feront l’objet de futures études. Il est donc nécessaire de trouver des techniques d’imagerie non invasives pour détecter le priming. L’autoradiographie ciblant le TSPO nous a permis de révéler le priming inflammatoire dans le cadre du traumatisme crânien léger. Nous proposons, au vu de nos résultats obtenus durant cette thèse, la tomographie par émission de positons pour la détection de la neuroinflammation invisible dans les atteintes cérébrales aigüe(s) et chronique(s). / Inflammation is an essential process to be considered in clinical practice. We have shown during this thesis that the (neuro)inflammatory status preceding the occurrence of a cerebral pathology must necessarily be taken into account since it drastically modifies the inflammatory response following a second stimulus such as stroke. This is even more important given that 90% of strokes are associated with comorbidities such as chronic hypertension, diabetes or chronic alcohol consumption, for which inflammation is an important pathophysiological feature. We have characterized this silent inflammatory status, also called priming, in the context of chronic alcohol consumption and in mild traumatic brain injury. We have identified perivascular macrophages (PVM) as mediators of the aggravating effect of inflammatory priming on ischemic stroke. PVM appear to be potential therapeutic targets and will be the subject of future investigations. It is therefore necessary to find non-invasive imaging techniques to detect inflammatory priming. We show that autoradiography targeting TSPO reveals the inflammatory priming provoked by a single mild traumatic brain injury. We propose, in light of the results obtained during this thesis, the positron emission tomography imaging to detect the invisible neuroinflammation in acute and chronic brain diseases.