Decreased Cell Wall Galactosaminogalactan in Aspergillus nidulans Mediates Dysregulated Inflammation in the Chronic Granulomatous Disease Host

Author Disclosure Statement No competing financial interests exist.

Inflammation dans les bronches du modèle d'asthme chez le rat Brown Norway = Inflammation in the airways of the Brown Norway rat model of asthma

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Influence de l'inflammation sur le métabolisme catalysé par les cytochromes P450 chez le rat : approches in vitro et implications sur la pharmacocinétique d'agonistes delta

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Regulation of lipocalin 2 (Lcn2) gene expression by iron stores, anemia and inflammation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Hypoxémie et inflammation systémique après ischémie cérébrale aiguë chez le rat Wistar

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Diminution du cytochrome P450 par l'inflammation : voies de signalisation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Study of Rgmc regulation by iron levels, anemia, inflammation and hypoxia

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain.

TRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV4 are available. Here we developed TRPV4-inhibitory molecules based on modifications of a known TRPV4-selective tool-compound, GSK205. We not only increased TRPV4-inhibitory potency, but surprisingly also generated two compounds that potently co-inhibit TRPA1, known to function as chemical sensor of noxious and irritant signaling. We demonstrate TRPV4 inhibition by these compounds in primary cells with known TRPV4 expression - articular chondrocytes and astrocytes. Importantly, our novel compounds attenuate pain behavior in a trigeminal irritant pain model that is known to rely on TRPV4 and TRPA1. Furthermore, our novel dual-channel blocker inhibited inflammation and pain-associated behavior in a model of acute pancreatitis - known to also rely on TRPV4 and TRPA1. Our results illustrate proof of a novel concept inherent in our prototype compounds of a drug that targets two functionally-related TRP channels, and thus can be used to combat isoforms of pain and inflammation in-vivo that involve more than one TRP channel. This approach could provide a novel paradigm for treating other relevant health conditions.

The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.

Inflammation dans les bronches du modèle d'asthme chez le rat Brown Norway = Inflammation in the airways of the Brown Norway rat model of asthma

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Influence de l'inflammation sur le métabolisme catalysé par les cytochromes P450 chez le rat : approches in vitro et implications sur la pharmacocinétique d'agonistes delta

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Regulation of lipocalin 2 (Lcn2) gene expression by iron stores, anemia and inflammation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Hypoxémie et inflammation systémique après ischémie cérébrale aiguë chez le rat Wistar

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Diminution du cytochrome P450 par l'inflammation : voies de signalisation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Study of Rgmc regulation by iron levels, anemia, inflammation and hypoxia

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.