Radical intermediates in chloroform reactions over triphenylphosphine-protected Au nanoparticles

Reactions of chloroform over triphenylphosphine-protected Au nanoparticles have been studied using electron paramagnetic resonance (EPR) spectroscopy and a spin trapping technique. Two competing reactions, abstraction of hydrogen and halogen atoms, were identified. The hydrogen abstraction reaction showed an inverse kinetic isotope effect. Treatment of nanoparticles with oxidizing or reducing reagents made it possible to tune the selectivity of radical formation from halogen to hydrogen (deuterium) abstraction. Treatment with PbO2 promoted the deuterium abstraction reaction followed by the loss of nanoparticle activity, whereas treatment with NaBH4 regenerated the nanoparticle activity towards Cl atom abstraction. X-ray photoelectron spectroscopy showed an increased Au:P ratio upon treatment with oxidizing reagents. This is likely due to the oxidation of some phosphine ligands to phosphine oxides which then desorb from the nanoparticle surface. © 2009 The Royal Societ of Chemistry.

Usability of prostaglandin monotherapy eye droppers

AIM: To determine the force needed to extract a drop from a range of current prostaglandin monotherapy eye droppers and how this related to the comfortable and maximum pressure subjects could exert. METHODS: The comfortable and maximum pressure subjects could apply to an eye dropper constructed around a set of cantilevered pressure sensors and mounted above their eye was assessed in 102 subjects (mean 51.2±18.7 years), repeated three times. A load cell amplifier, mounted on a stepper motor controlled linear slide, was constructed and calibrated to test the force required to extract the first three drops from 13 multidose or unidose latanoprost medication eye droppers. RESULTS: The pressure that could be exerted on a dropper comfortably (25.9±17.7 Newtons, range 1.2-87.4) could be exceeded with effort (to 64.8±27.1 Newtons, range 19.9-157.8; F=19.045, p<0.001), and did not differ between repeats (F=0.609, p=0.545). Comfortable and maximum pressures exerted were correlated (r=0.618, p<0.001), neither were influenced strongly by age (r=0.138, p=0.168; r=-0.118, p=0237, respectively), but were lower in women than in men (F=12.757, p=0.001). The force required to expel a drop differed between dropper designs (F=22.528, p<0.001), ranging from 6.4 Newtons to 23.4 Newtons. The force needed to exert successive drops increased (F=36.373, p<0.001) and storing droppers in the fridge further increased the force required (F=7.987, p=0.009). CONCLUSIONS: Prostaglandin monotherapy droppers for glaucoma treatment vary in their resistance to extract a drop and with some a drop could not be comfortably achieved by half the population, which may affect compliance and efficacy.

Expression and regulation of microsomal prostaglandin E synthase-1 in human osteoarthritic cartilage and chondrocytes

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

Expression and regulation of microsomal prostaglandin E synthase-1 in human osteoarthritic cartilage and chondrocytes

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

Hydroalumination of Thioacetylenes: A Versatile Generation and Reactions of -Aluminate Sulfides Intermediates

Hydroalumination of thioacetylenes using DIBAL-H and lithium di-(isobutyl)-n-(butyl)-aluminate hydride (Zweifel's reagent), followed by addition of water, furnished exclusively the (Z)- and (E)-vinyl sulfides, respectively. The regio- and stereochemistry of the intermediates generated, (Z)- and (E)-phenylthio vinyl alanates, were determined by capture with iodine, which afforded the corresponding (E)- and (Z)-1-iodo-1-phenylthio-2-organoyl ethenes. Reactions of the (E)-iodo(thio)ketene acetals with n-BuLi followed by addition of hexanal afforded the (Z)-phenylthio allylic alcohol, while the (Z)-iodo(thio)ketene acetals under similar reactions conditions gave the (E)-phenylthio allylic alcohol exclusively.

Hydroalumination of seleno acetylenes: a versatile generation and reactions of alpha-aluminate vinyl selenide intermediates in the highly regio and stereoselective synthesis of telluro(seleno)ketene acetals

The hydroalumination of butylseleno acetylenes with DIBAL-H followed by addition of n-butyllithium generated in situ the (Z)-butylseleno vinyl alanates intermediates which were captured with C(4)H(9)TeBr furnishing the (E)-telluro(seleno)ketene acetals exclusively. The isomers with opposite stereochemistry (Z)-telluro(seleno)ketene acetals were obtained by the reduction of phenylseleno acetylenes with lithium di-(isobutyl)-n-butyl aluminate hydride (Zweifel's reagent) followed by reaction of (E)-phenylseleno vinyl alanates intermediates with C(4)H(9)TeBr. (c) 2008 Elsevier Ltd. All rights reserved.

The administration of exogenous prostaglandin may improve ovulation in pacu (Piaractus mesopotamicus)

Based on the reports of unsuccessful ovulation in pacu (Piaractus mesopotamicus) by fish farmers and researchers undertaking artificial reproduction programs, we evaluated the use of prostaglandin F (PGF) to improve pacu ovulation. This study was conducted during two spawning seasons (2009/2010 and 2010/2011) with two samplings in the first season and one sampling in the second season. A total of 45 females was sampled in this study. The control group was injected with carp pituitary extract (crude extract, 6 mg/kg), and the treatment group received PGF (2 mL per fish in the 2009/2010 season and 5 mL per fish in the 2010/2011 season) in addition to the crude extract. In both seasons, 100% (N = 4, 2009/2010 first sampling; N = 5, 2009/2010 second sampling; and N = 3, 2010/2011) of the PGF-treated fish spawned. In contrast, 53.0% (N = 9) and 83.3% (N = 10) of the control fish spawned in the first and second samplings of the 2009/2010 season, respectively, and only 25.0% (N = 1) spawned in the 2010/2011 season. Fecundity, fertility, and hatching rates did not differ (P > 0.05) between the treated and control fish. Based on oocyte volume frequency analysis, ovaries of the control fish had more (P < 0.05) vitellogenic oocytes with germinal vesicle breakdown that remained unovulated after spawning, whereas more (P < 0.05) of previtellogenic oocytes were present in the ovaries of the PGF-treated fish. In conclusion, administration of exogenous prostaglandin may improve the outcome of hormonally induced spawning in tropical migratory fish. (C) 2012 Elsevier B.V. All rights reserved.

Étude des voies de signalisation activées par la prostaglandine F2α dans les cellules de cancer colorectal

Le cancer colorectal représente la troisième forme de cancer la plus fréquente au Canada. Malgré les récents développements, aucun traitement curatif n’est disponible pour les patients diagnostiqués à un stade avancé de la maladie. Plusieurs évidences supportent un rôle important des prostaglandines dans cette maladie. En effet, une surexpression des récepteurs de type EP et FP est remarquée. Ces derniers ainsi que les molécules de signalisations intracellulaires qu’ils activent représentent donc de nouvelles cibles pour traiter ce cancer. Nous et d’autres groupes avons démontré que les protéines G monomériques sont des petits interrupteurs moléculaires importants dans la signalisation intracellulaire engagée par les récepteurs dans des cellules saines mais qu’un dérèglement de celles-ci est associé au cancer. L’objectif principal de ce projet de recherche vise donc à identifier les voies de signalisations par lesquelles le récepteur FP contribue aux capacités invasives des cellules tumorales d’origine colorectale. Notre hypothèse est que la protéine ARF6, une des 6 isoformes des ARFs, et la protéine RhoA, agissent pour coordonner l’activation des voies de signalisations associées à la migration et l’invasion cellulaire. Nos résultats ont indiqué que la stimulation des cellules HEK293 exprimant de façon stable le récepteur FP (HA-FP) ainsi que les cellules SW480, une lignée invasive de cancer colorectal, par le PGF2α augmentait les niveaux d’activation d’ARF6 mais également de la protéine RhoA. De plus, d’autres médiateurs et intermédiaires associés à la réorganisation du cytosquelette comme la cofiline et la chaine légère de la myosine (MLC) ont été hautement phosphorylés suite à la stimulation par la prostaglandine. Ces observations sont associées avec une augmentation des fibres de stress dans les cellules. Nous avons tenté de déterminer si l’inhibition de ces protéines G affectait la capacité du PGF2α à activer ces intermédiaires de signalisation ainsi que certains effets biologiques. Ainsi, nos expériences contribueront à identifier de nouvelles cibles thérapeutiques potentielles pour le traitement du cancer colorectal.

PRODUCTION OF BIOFUEL INTERMEDIATES FROM WOODY FEEDSTOCKS VIA FAST PYROLYSIS AND TORREFACTION

The main objective of this research was to investigate pyrolysis and torrefaction of forest biomass species using a micropyrolysis instrument. It was found that 30-45% of the original sample mass remained as bio-char in the pyrolysis temperature range of 500 - 700˚C for aspen, balsam, and switchgrass. The non-char mass was converted to gaseous and vapor products, of which 10-55% was water and syngas, 2-12% to acetic acid, 2-12% to hydroxypropanone, 1-3% to furaldehyde, and 5-15% to various phenolic compounds. In addition, several general trends in the evolution of gaseous species were indentified when woody feedstocks were pyrolyzed. With increasing temperature it was observed that: (1) the volume of gas produced increased, (2) the volume of CO2 decreased and the volumes of CO and CH4 increased, and (3) the rates of gas evolution increased. In the range of torrefaction temperature (200 - 300˚C), two mechanistic models were developed to predict the rates of CO2 and acetic acid product formation. The models fit the general trend of the experimental data well, but suggestions for future improvement were also noted. Finally, it was observed that using torrefaction as a pre-curser to pyrolysis improves the quality of bio-oil over traditional pyrolysis by reducing the acidity through removal of acetic acid, reducing the O/C ratio by removal of some oxygenated species, and removing a portion of the water.

Étude des voies de signalisation activées par la prostaglandine F2α dans les cellules de cancer colorectal

Le cancer colorectal représente la troisième forme de cancer la plus fréquente au Canada. Malgré les récents développements, aucun traitement curatif n’est disponible pour les patients diagnostiqués à un stade avancé de la maladie. Plusieurs évidences supportent un rôle important des prostaglandines dans cette maladie. En effet, une surexpression des récepteurs de type EP et FP est remarquée. Ces derniers ainsi que les molécules de signalisations intracellulaires qu’ils activent représentent donc de nouvelles cibles pour traiter ce cancer. Nous et d’autres groupes avons démontré que les protéines G monomériques sont des petits interrupteurs moléculaires importants dans la signalisation intracellulaire engagée par les récepteurs dans des cellules saines mais qu’un dérèglement de celles-ci est associé au cancer. L’objectif principal de ce projet de recherche vise donc à identifier les voies de signalisations par lesquelles le récepteur FP contribue aux capacités invasives des cellules tumorales d’origine colorectale. Notre hypothèse est que la protéine ARF6, une des 6 isoformes des ARFs, et la protéine RhoA, agissent pour coordonner l’activation des voies de signalisations associées à la migration et l’invasion cellulaire. Nos résultats ont indiqué que la stimulation des cellules HEK293 exprimant de façon stable le récepteur FP (HA-FP) ainsi que les cellules SW480, une lignée invasive de cancer colorectal, par le PGF2α augmentait les niveaux d’activation d’ARF6 mais également de la protéine RhoA. De plus, d’autres médiateurs et intermédiaires associés à la réorganisation du cytosquelette comme la cofiline et la chaine légère de la myosine (MLC) ont été hautement phosphorylés suite à la stimulation par la prostaglandine. Ces observations sont associées avec une augmentation des fibres de stress dans les cellules. Nous avons tenté de déterminer si l’inhibition de ces protéines G affectait la capacité du PGF2α à activer ces intermédiaires de signalisation ainsi que certains effets biologiques. Ainsi, nos expériences contribueront à identifier de nouvelles cibles thérapeutiques potentielles pour le traitement du cancer colorectal.

Peripheral P2x7 Receptor-induced Mechanical Hyperalgesia Is Mediated By Bradykinin.

P2X7 receptors play an important role in inflammatory hyperalgesia, but the mechanisms involved in their hyperalgesic role are not completely understood. In this study, we hypothesized that P2X7 receptor activation induces mechanical hyperalgesia via the inflammatory mediators bradykinin, sympathomimetic amines, prostaglandin E2 (PGE2), and pro-inflammatory cytokines and via neutrophil migration in rats. We found that 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate triethylammonium salt (BzATP), the most potent P2X7 receptor agonist available, induced a dose-dependent mechanical hyperalgesia that was blocked by the P2X7 receptor-selective antagonist A-438079 but unaffected by the P2X1,3,2/3 receptor antagonist TNP-ATP. These findings confirm that, although BzATP also acts at both P2X1 and P2X3 receptors, BzATP-induced hyperalgesia was mediated only by P2X7 receptor activation. Co-administration of selective antagonists of bradykinin B1 (Des-Arg(8)-Leu(9)-BK (DALBK)) or B2 receptors (bradyzide), β1 (atenolol) or β2 adrenoceptors (ICI 118,551), or local pre-treatment with the cyclooxygenase inhibitor indomethacin or the nonspecific selectin inhibitor fucoidan each significantly reduced BzATP-induced mechanical hyperalgesia in the rat hind paw. BzATP also induced the release of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1), an effect that was significantly reduced by A-438079. Co-administration of DALBK or bradyzide with BzATP significantly reduced BzATP-induced IL-1β and CINC-1 release. These results indicate that peripheral P2X7 receptor activation induces mechanical hyperalgesia via inflammatory mediators, especially bradykinin, which may contribute to pro-inflammatory cytokine release. These pro-inflammatory cytokines in turn may mediate the contributions of PGE2, sympathomimetic amines and neutrophil migration to the mechanical hyperalgesia induced by local P2X7 receptor activation.

Inflammatory Sensitization Of Nociceptors Depends On Activation Of Nmda Receptors In Drg Satellite Cells.

The present study evaluated the role of N-methyl-D-aspartate receptors (NMDARs) expressed in the dorsal root ganglia (DRG) in the inflammatory sensitization of peripheral nociceptor terminals to mechanical stimulation. Injection of NMDA into the fifth lumbar (L5)-DRG induced hyperalgesia in the rat hind paw with a profile similar to that of intraplantar injection of prostaglandin E2 (PGE2), which was significantly attenuated by injection of the NMDAR antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) in the L5-DRG. Moreover, blockade of DRG AMPA receptors by the antagonist 6,7-dinitroquinoxaline-2,3-dione had no effect in the PGE2-induced hyperalgesia in the paw, showing specific involvement of NMDARs in this modulatory effect and suggesting that activation of NMDAR in the DRG plays an important role in the peripheral inflammatory hyperalgesia. In following experiments we observed attenuation of PGE2-induced hyperalgesia in the paw by the knockdown of NMDAR subunits NR1, NR2B, NR2D, and NR3A with antisense-oligodeoxynucleotide treatment in the DRG. Also, in vitro experiments showed that the NMDA-induced sensitization of cultured DRG neurons depends on satellite cell activation and on those same NMDAR subunits, suggesting their importance for the PGE2-induced hyperalgesia. In addition, fluorescent calcium imaging experiments in cultures of DRG cells showed induction of calcium transients by glutamate or NMDA only in satellite cells, but not in neurons. Together, the present results suggest that the mechanical inflammatory nociceptor sensitization is dependent on glutamate release at the DRG and subsequent NMDAR activation in satellite glial cells, supporting the idea that the peripheral hyperalgesia is an event modulated by a glutamatergic system in the DRG.