no / Experimental solubilities of budesonide, hydrocortisone, and prednisolone in ethanol + water mixtures at 298.2 K are reported. The solubility of drugs was increased with the addition of ethanol and reached the maximum values of the volume fractions of 90 %, 80 %, and 80 % of ethanol. The Jouyban-Acree model was used to fit the experimental data, and the solubilities were reproduced using previously trained versions of the Jouyban-Acree model and the solubility data in monosolvents in which the overall mean relative deviations (OMRDs) of the models were 5.1 %, 6.4 %, 37.7 %, and 35.9 %, respectively, for the fitted model, the trained version for ethanol + water mixtures, and generally trained versions for various organic solvents + water mixtures. Solubilities were also predicted by a previously established log-linear model of Yalkowsky with the OMRD of 53.8 %.

Plusieurs méthodes et techniques sont utilisées dans le domaine de l'entraînement et la préparation sportive afin de quantifier la charge d'entraînement et ainsi d'optimiser la performance des athlètes. Cependant, bien que plusieurs d'entre-elles soit utilisées couramment sur le terrain, très peu ont été validées scientifiquement. A l'aide du cortisol salivaire, nous avons validé divers outils de quantification de la charge d'entraînement chez des marathoniens en lien avec le stress physiologique imposé par l'exercice. Nos résultats démontrent tout d'abord que le cortisol salivaire semble être une mesure fiable et non-invasive pour quantifier le stress physiologique induit par l'exercice. De plus, les valeurs de ce dernier furent corrélées avec différents outils prédicteurs du stress physiologique lors de l'entraînement. Il serait particulièrement pertinent, dans un projet de recherche futur, de développer l'instrumentation nécessaire permettant l'utilisation du cortisol salivaire par les entraîneurs sur le terrain. Ceci permettant à ces derniers d'évaluer précisément la charge d'entraînement subie par leurs athlètes.

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No description available.

no / Of particular importance in recent years has been the development of techniques for producing nanoparticles (NPs) of poorly-water soluble drugs with dimensions less than 1000 nm for which their high surface area can lead to improvements in bioavailability. Furthermore, the small size of these particles can also enable cellular uptake, particularly for positively charged systems. Therefore, an overall objective of this part of the project was to produce nanoparticles with different levels of positive surface charge using the bottom-up method.

The effect of feeding colostrum or milk to newborn calves on serum cortisol, thyroxine and immunoglobulin G was investigated. Twenty-four calves (12 males and 12 females) were obtained immediately postpartum and randomly assigned to one of two rations after being blocked by breed and sex. Both rations were force-fed at birth, 12, 24 and 36 h postpartum. Blood sampling was performed at 0 time, 1, 2, 3, 4, 6 and 12 h postfeeding with this regime followed for a 48 h period (4 feedings). The average serum cortisol concentration was highest at birth, 221.9 and 245.6 ng/ml for colostrum and milk-fed calves, respectively. Cortisol levels between treatments were different (P<.05) at 2, 3, 12, 14, 18, 24, 37 and 48 h postpartum. The sex of the calf did not affect the mean cortisol concentrations. No treatment difference was observed for serum thyroxine. A sex difference was observed with the female calves exhibiting higher average thyroxine concentrations over the entire trial. A reduction in thyroxine concentration occurred with time (P<.001) as mean concentrations peaked at 4 h postpartum (22.1 μg/dl) and declined to 10.6 μg/dl by 48 h postpartum. Both treatment groups were born with similar serum immunoglobulin G levels (~0.7 mg/ml). However, at approximately 4 h postpartum, the colostrum-fed calves acquired an increase (P<.001) in serum immunoglobulin G, peaking at 24 h postpartum (26.83 mg/ml) and remaining much higher throughout the entire trial. There was a treatment difference (P<.001) between the two groups following the 4 h sample. Muscle samples (20-30g) were surgically removed from the right semitendinosus at 36 h postpartum from 14 neonatal beef calves (male and female), homogenized, and centrifuged at 105,000 x g at 4 C for 60 min. The supernatant (cytosol) was harvested and receptor quantitation, binding kinetics and ligand specificity assays were performed via [1,2,4,³H] dexamethasone. There were no binding differences between the colostrum and milk-fed calves' muscle samples. The average protein content of the muscle cytosol fraction was 50.82 mg/ml. The binding component displayed a high apparent equilibrium dissociation constant for the binding of [³H] dexamethasone (K_d = 2.34x10 ⁻⁸ ). The apparent maximum number of binding sites determined from Scatchard plots was approximately 37.61 fmol/mg of protein in the case of the dexamethasone receptor. Maximum binding appeared to reached between 16 and 24 h (48.5 and 48.2 %, respectively). Competition assays indicated all of the ligands tested had an affinity for the glucocorticoid receptor. The percent of specific binding for each was: dexamethasone (66+/-14), corticosterone (52+/-10), cortisol (58+/-13), estradiol-17, beta (37+/-7), progesterone (29+/-9), testosterone (10+/-3), and triamcinolone (41+/-11). / Master of Science

L’objectif principal de cette thèse est de vérifier l’influence des facteurs prénataux sur le développement de l’enfant et d’explorer les mécanismes par lesquels cette influence survient. Dans un premier temps, une méta-analyse a été effectuée afin de vérifier l’association entre divers facteurs prénataux et la sécrétion de cortisol des enfants âgés de moins de 5 ans. Les variables prénatales considérées sont le stress maternel prénatal, ainsi que la consommation prénatale d’alcool, de tabac ou de drogues. Dix-neuf études ont été retenues et les résultats démontrent un lien significatif entre les facteurs prénataux et la sécrétion de cortisol chez l’enfant (d = .36, p &lt; .001). Les analyses de modération révèlent que cette association est plus élevée en ce qui concerne la consommation prénatale d’alcool, la sécrétion de cortisol basal et l’utilisation de devis de recherche rétrospectifs. Les effets de modération obtenus suggèrent entre autres que des mécanismes d’action différents pourraient être en cause selon le type d’exposition prénatale étudié. Dans un deuxième temps, une étude empirique a été réalisée afin d’explorer les mécanismes qui pourraient expliquer l’association entre les facteurs prénataux et le développement de l’enfant. Plusieurs études suggèrent que la sécrétion de cortisol de l’enfant et la sensibilité maternelle puissent agir comme médiateurs dans l’association entre le stress maternel prénatal et le développement cognitif de l’enfant. Cette étude empirique a donc pour objectif de tester ces modèles de médiation et de vérifier la présence d’effets directs du stress maternel prénatal, de la sécrétion de cortisol de l’enfant et de la sensibilité maternelle sur le développement cognitif de l’enfant. Les résultats obtenus documentent la présence d’effets directs et indépendants du stress maternel prénatal, de la sécrétion de cortisol de l’enfant et de la sensibilité maternelle afin de prédire le développement cognitif de l’enfant à 3 mois. De plus, aucune relation de médiation n’est documentée. Les résultats soutiennent ainsi à la fois l’influence des facteurs de l’environnement prénatal, celle de l’environnement postnatal et une contribution des facteurs propres à la physiologie de l’enfant dans la prédiction du développement cognitif en bas âge. / The purpose of the present doctoral thesis is to examine the association between prenatal environment and early human development and to investigate mechanisms by which fetal programming can occur. To clarify this association, we conducted two different studies. First, we did a meta-analysis to examine the relation between various prenatal variables and child cortisol secretion. Prenatal variables considered were maternal prenatal stress and maternal prenatal use of alcohol, tobacco and drugs. Nineteen studies were included in the analysis and results reveal and significant and moderate association between prenatal variables and child cortisol secretion (d = .36, p &lt; .001). Moderator analyses reveal that greater effect sizes can be traced to maternal alcohol use, to the use of retrospective research methodology, where mothers are questioned after child birth regarding programming variables, and to the use of baseline measures of cortisol secretion, as opposed to recovery measures. Moderation effects suggest that different mechanisms could be involved when different prenatal variables are considered. Secondly, an empirical study was conducted in order to examine mechanisms that could explain the association between prenatal environment and early human development. The purpose of this empirical study is to test the possibility that early differences in cortisol secretion and maternal interactive sensitivity may mediate the link between maternal prenatal stress and infant cognitive development. The results reveal independent effects of maternal prenatal stress, infant cortisol secretion and maternal sensitivity to predict infant cognitive development. However, the results do not reveal mediation neither for infant cortisol secretion nor for maternal interactive sensitivity in the association between maternal prenatal stress and infant cognitive development. Together, these results provide support for a contribution of prenatal environment, postnatal environment and of infant’s physiological characteristics to predict infant cognitive development.

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Wild populations of fish are faced with a multitude of stressors, which may include human interaction, toxins, and disease. Benzo(a)pyrene (BaP), a known carcinogen and immunotoxin, has been reported in the stomach contents of juvenile chinook salmon, Oncorhynchus tshawytscha, in urban waterways. We investigated the impact of chronic dietary exposure of environmentally relevant levels of BaP on the immune system and cytochrome P4501A1 (CYP1A1) expression in juvenile chinook salmon. Two experiments were carried out in which juvenile fish were fed food treated with ethanol (control diet), low or high concentrations of BaP, or cortisol. In the first experiment we measured mitogen-stimulated proliferation of splenic leukocytes using flow cytometry and a colorimetric assay using Alamar Blue[superscript TM] Susceptibility to a microsporidian parasite, Loma salmonae, was evaluated in the second experiment by quantification of xenomas in the gills. Hepatic CYP1A1 and plasma cortisol were measured in both experiments. No significant trends were found in leukocyte mitogen activation or plasma cortisol between treatments or days. However, western blot analysis of CYP1A1 concentration in liver revealed interesting patterns of induction: in cortisol fed groups CYP1A1 was <20% of control on all days, groups fed low levels of BaP were 250% of control values on days 8 and 21 then dropped below control values on day 29, and groups fed high levels of BaP had less CYP1A1 than controls on all days. Similar patterns of CYP1A1 levels were found in the second experiment, and diseased control groups showed about a 55% decrease in CYP1A1 concentration when compared with non-diseased control groups. Susceptibility to L. salmonae was significantly higher in groups receiving cortisol. Whereas there was no effect of the high BaP dose, the low BaP dose appeared to increase disease susceptibility. This study supports concerns of stress and toxin induced immune dysfunction in wild populations of fish. / Graduation date: 2004

The life of a preterm infant admitted to a neonatal intensive care unit may be stressful from the moment of birth. Ever since Hans Selye’s initial characterisation of the biological stress response, cortisol has been frequently measured as an indicator of stress responsivity. However, research of the stress response and cortisol in infants, especially those who are preterm and/or ill, has been scarce basically because of methodological issues. The first aim with this thesis was to investigate the acute stress response, as measured by salivary cortisol and behaviour, for preterm infants, healthy infants, and infants at high psychosocial risk in response to certain defined handling procedures. The second aim was to investigate the stress response, as measured by salivary cortisol and psychometric measures, for parents present during the handling procedure of their infants. The intention was to perform all investigations in an as naturally occurring situation as possible, which means that the studied procedures would have been performed irrespectively of the research. The present thesis includes six original articles. The results of the first study demonstrate that it is feasible to collect sufficient amounts of saliva and to analyse salivary cortisol in neonates using the presented method of collection and analysis. The second study shows that preterm infants, usually cared for in incubators, show no signs of discomfort and have variable cortisol responses during skin-to-skin care with their mothers. The mothers, however, experience stress and low control before their first skin-to-skin care with their preterm infant and do not relax completely until after the session. In the third study we found that preterm infants have higher baseline salivary cortisol as compared to healthy full-term infants. Moreover, preterm infants have higher and sustained pain response during a nappy change as compared to healthy full-term infants. The results of the fourth study shows that infants younger than three months, living in psychosocial high-risk families, have increased cortisol responses during a nappy change, performed by the mother. However, support with the aim of improving mother-infant interaction, dampens the stress response. The results of the fifth study show that oral sweet-tasting solution in combination with a pacifier dampen the levels of the stress hormone cortisol in three months old infants during routine immunisation. Moreover, parents experience more self-rated emotional stress before immunisation if it is their first child who is being immunised. The sixth paper shows that the material used for saliva collection (cotton buds with wooden or plastic sticks) is of importance when saliva is collected but for practical reasons not centrifuged within 24 hours prior to cortisol analyse. The present thesis shows that it is practically feasible to collect saliva and to analyse the stress hormone cortisol in infants. The interpretation of infants’ and parents’ salivary cortisol responses to different handling procedures are discussed in relation to shortand long-term consequences, neonatal intensive care, preterm birth, attachment, mood, and pain.