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Effects of Cyclosporin A on Peripheral Immune ToleranceVanier, Laurent E. January 1994 (has links)
Note:
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The financial obligations of non-resident fathers and the implications for social policySkinner, Christine Bridget Edgar January 1999 (has links)
No description available.
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The effect of Cyclosporin A on delayed-type hypersensitivity to a tolerogenic dose of Xenogeneic erythrocytesin the mouseWebster, L. M. January 1987 (has links)
When administered to mice, by various routes, two days before immunization with a tolerogenic dose (10<sup>9</sup>) of sheep red blood cells, the immunosuppressive drug Cyclosporin A (CsA) prevents the suppression of delayed-type hypersensitivity (DTH) reactions. This was observed over a wide range of CsA doses (5-200 mg/kg), given, in a single dose, from a week before immunization to a day after, and with circulating CsA levels ranging below 45 ng/ml at the time of sensitization or challenge. The augmentation of DTH was characterized by induration, intense mononuclear cell infiltration, increased deposition of <sup>125</sup>I-fibrin within the challenge site and was also reflected in <i>in vitro</i> assays of DTH. Cell transfer experiments showed that the CsA-enhanced DTH could be adoptively transferred to naive recipients, and suggested that CsA may be acting to inhibit a population of Ts cells normally effective during DTH, or to allow T<sub>H</sub>/T<sub>DTH</sub> cell priming. In addition, an increase in L3T4<sup>+</sup> cells (T<sub>H</sub>/T<sub>DTH</sub>) was observed in the CsA-treated mice showing the break in suppression of DTH, suggesting that CsA allowed T<sub>H</sub>/T<sub>DTH</sub> cell priming. The augmented DTH reactions in CsA-treated mice were accompanied by profound inhibition of the production of splenic IgM antibody-producing cells and circulating anti-SRBC antibody levels. CsA was also shown to increase basal and mitogen-induced splenic macrophage procoagulant activity. These observations indicate that this model could prove useful in separation and study of cell-mediated and humoural immunity. In addition, they have important cautionary implications for the continuing investigation of the clinical potential of CsA.
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Comparing health-related physical fitness and activity between old order Mennonite children in Ontario and rural children in SaskatchewanBarnes, Joel David 09 January 2004
Temporal trend research in some components of health-related physical fitness and activity among young people is lacking. However, the increasing prevalence of overweight and obesity in young people over the last couple decades has created speculation of secular deterioration in health-related physical fitness and activity. In an effort to address the speculation, this research project compared health-related physical fitness and activity between two groups of children: Old Order Mennonite children in southwestern Ontario (n = 124; aged 9.1 to 13.8 years), who live an agrarian lifestyle which does not include motorized transportation, computer use, or television viewing and rural children in central Saskatchewan (n = 165; aged 8.8 to 13.2 years), who live a contemporary Canadian lifestyle. The Canadian Physical Activity, Fitness, and Lifestyle Appraisal (CPAFLA) was used to measure health-related physical fitness. The CPAFLA is a battery of tests measuring anthropometry (standing height, body mass, skinfolds, and waist girth), cardiorespiratory endurance (step test), and musculoskeletal fitness (handgrip strength, push-ups, partial curl-ups, and trunk forward flexion). Physical activity was measured on seven consecutive days using the Model AM7164 activity monitor. The Physical Activity Questionnaire for Older Children (PAQ-C) was also employed. The PAQ-C is a guided, self-administered seven-day recall questionnaire, which assesses general levels of physical activity in schoolchildren of grades four to eight during the school year. With biological age as a covariate, univariate and multivariate analyses of covariance were used to compare health-related physical fitness and activity between groups respectively. Old Order Mennonite children evinced greater mean handgrip strength (p < 0.0001) and rural Saskatchewan children demonstrated greater mean trunk forward flexion (p < 0.001). However, there were no significant differences between groups in the other health-related physical fitness variables. Old Order Mennonite children had significantly greater mean activity counts·min-1 (p < 0.001), mean activity counts·day-1 (p < 0.0001), and mean minutes of moderate physical activity·day-1 (p < 0.0001). Collectively, these results suggest that Old Order Mennonite children have greater static strength and are more physically active than rural Saskatchewan children. Assuming that Old Order Mennonite children represent Canadian children from previous generations, these results may lend support to secular deterioration in some aspects of health-related physical fitness and activity among Canadian children.
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Comparing health-related physical fitness and activity between old order Mennonite children in Ontario and rural children in SaskatchewanBarnes, Joel David 09 January 2004 (has links)
Temporal trend research in some components of health-related physical fitness and activity among young people is lacking. However, the increasing prevalence of overweight and obesity in young people over the last couple decades has created speculation of secular deterioration in health-related physical fitness and activity. In an effort to address the speculation, this research project compared health-related physical fitness and activity between two groups of children: Old Order Mennonite children in southwestern Ontario (n = 124; aged 9.1 to 13.8 years), who live an agrarian lifestyle which does not include motorized transportation, computer use, or television viewing and rural children in central Saskatchewan (n = 165; aged 8.8 to 13.2 years), who live a contemporary Canadian lifestyle. The Canadian Physical Activity, Fitness, and Lifestyle Appraisal (CPAFLA) was used to measure health-related physical fitness. The CPAFLA is a battery of tests measuring anthropometry (standing height, body mass, skinfolds, and waist girth), cardiorespiratory endurance (step test), and musculoskeletal fitness (handgrip strength, push-ups, partial curl-ups, and trunk forward flexion). Physical activity was measured on seven consecutive days using the Model AM7164 activity monitor. The Physical Activity Questionnaire for Older Children (PAQ-C) was also employed. The PAQ-C is a guided, self-administered seven-day recall questionnaire, which assesses general levels of physical activity in schoolchildren of grades four to eight during the school year. With biological age as a covariate, univariate and multivariate analyses of covariance were used to compare health-related physical fitness and activity between groups respectively. Old Order Mennonite children evinced greater mean handgrip strength (p < 0.0001) and rural Saskatchewan children demonstrated greater mean trunk forward flexion (p < 0.001). However, there were no significant differences between groups in the other health-related physical fitness variables. Old Order Mennonite children had significantly greater mean activity counts·min-1 (p < 0.001), mean activity counts·day-1 (p < 0.0001), and mean minutes of moderate physical activity·day-1 (p < 0.0001). Collectively, these results suggest that Old Order Mennonite children have greater static strength and are more physically active than rural Saskatchewan children. Assuming that Old Order Mennonite children represent Canadian children from previous generations, these results may lend support to secular deterioration in some aspects of health-related physical fitness and activity among Canadian children.
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Examining Child Abuse Disclosure Patterns: A Retrospective Approach to Estimating Denial and Recantation RatesMcGuire, Kathy M.L. January 2012 (has links)
No description available.
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The role of TGF β in drug-induced gingival overgrowthMorgan, Clare Louise January 2000 (has links)
No description available.
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Aproximacions i estudis nous CSAs. Adamantil, Fluorenil i altres derivats tipus PirkleAlmer Surribas, Sandra 28 September 2001 (has links)
En la present tesi s'ha avançat en el coneixement de la influència de l'estructura molecular en la capacitat d'acció com a agent de solvatació quiral (CSA). S'han preparat i estudiat diversos compostos derivats de l'alcohol de Pirkle, substituint la part aromàtica per grups fluorenil o naftacenil i modificant el substituent del carboni quiral per grups adamantil o tert-butil. Aquests estudis inclouen la síntesi i la resolució d'aquestes molècules, la seva aplicació sobre mostres diastereoisomériques i el seu posterior estudi per ressonància magnètica nuclear i càlculs de mecànica molecular. Els resultats obtinguts mostren que el compost 1-adamantil-9-antrilmetanol presenta una barrera de rotació elevada de l'enllaç C9-C11 que es pot determinar per mitjà del mètode descrit en el nostre laboratori basat en la transferència de nOe entre diversos nuclis. El comportament d'aquest compost com agent de solvatació és comparable al comportament del compost 1-(9-antril)-2,2-dimetilpropanol.Per altra banda, els compostos derivats del grup fluorè, 1-(9H-9-fluorenil)-2,2-dimetilopropanol i 1-(9H-9-fluorenil)-2,2,2-trifluoroetanol, presenten una conformació preferent que situa els tres anells coplanars i el substituent de forma perpendicular entre ells. De les tres conformacions alternades de l'enllaç C9-C10, és la que te el grup hidroxil per sobre de l'anell de fluorè la més estable i la única que s'observa en l'espectre de protó de RMN.S'ha pogut disposar del 2,2,2-trifluoro-1-(5-naftacenil)etanol, però aquest compost s'ha mostrat molt inestable en condicions de laboratori ja que descomposa després de poques hores de la seva síntesi.S'han preparat els diésters derivats de l'àcid adamantandioic i antracendioic del a,a'-bis(trifluorometil)-9,10-antracendimetanol que es presenta com les primeres aproximacions en la preparació de cavitats quirals antracenderivades. Així doncs, són un bon punt de partida per la seva ciclació en la preparació de compostos cíclics de relació molar 2:2. / The present work it's a progress in the knowledge of the influence of the molecular structure in its acting capacity as a chiral solvating agent (CSA). There are a study and preparation of several compounds coming from derived of Pirkle's alcohol where the anthryl ring is substituted by fluorenyl and naphtacenyl groups.Adamanthyl and tert-butyl groups are used instead of trifluoromethyl groups. These studies include the synthesis and the resolution of compounds, its application as a CSA on diastereoisomeric samples and its posterior study by nuclear magnetic resonance and molecular mechanics calculations. The obtained results show a high rotation barrier of the binding C9-C11 for the compound 1-adamantil-9-antrilmetanol, which can be determined by a method described in our research group based on the transfer of the nOe effect among several atoms. The behaviour of this compound as a chiral solvating agent is similar to the behaviour of the compound 1-(9-antril)-2,2-dimetilpropanol.On the other hand, the compounds coming from the fluorene group, present a preferential conformation which situates the tree coplanar rings and its substitute in a perpendicular form. The conformational study of C9-C10 bonds demonstrates that the most stable structure show the hydroxyl group over the fluorenyl ring.We have been able to synthesized 2,2,2-trifluoro-1-(5-naphtacenyl)ethanol, however this compound is very unstable in the laboratory conditions, due to its decomposition after a few hours of its synthesis. The a,a'-bis(trifluoromethyl)-9,10-anthracenedimethanol, diesther derivatives of 1,3-adamantanedicarboxylic and 9,10-anthracenedicarboxylic acids were prepared. There is a good starting point to obtain high chiral cavities.
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Preparació enantioselectiva i estructura de l'[alfa], [alfa]'-bis(trifluorometil)-9,10-antracendimetanol (abte), l'[alfa], [alfa]'-bis(trifluorometil)-9,10-antracendimetanamina (ABTA) i aproximació a l'[alfa]-trifluorometil-9-[10-(2,2,2-trifluoroetanamino)]antracenmetanol (ABTEA). RMN: utilització com a CSAs i estudi dels complexos bidentatsEstivill Domènech, Carla 10 July 2006 (has links)
A la present tesi doctoral es desenvolupen nous estudis sobre agents de solvatació quiral (CSA) difuncionals. Els CSAs tenen la capacitat d'interaccionar de forma diferencial amb cada un dels enantiòmers d'una mescla d'un substrat quiral, mitjançant la formació d'enllaços no covalents, és a dir, de tipus àcid-base, ponts d'hidrògen, dipolars,... formant complexes d'associació diastereomèrics. Aquest reconeixement quiral produeix un diferent entorn químic i magnètic dels enantiòmers, el que per RMN es podrà observar en una anisocronia dels seus senyals, principalment de protó. Aquesta diferència dels desplaçaments químics ens permetrà determinar la composició de la mescla. Ja que l'observació dels senyals és una mitja d'un sistema dinàmic entre els elements lliures i complexats, la separació dels senyals dependrà tant de la termodinàmica de l'associació com de les característiques estructurals dels complexes.En el nostre grup d'investigació es va abordar la síntesi de CSAs difuncionals. En el primer cas que ens ocupa a la present tesi doctoral, l'?,?'-bis(trifluorometil)-9,10-antracendimetanol (ABTE) va aportar una gran capacitat enantiodiferenciadora. Els estudis per RMN ens permeteren atribuir aquests resultats en la capacitat que té el confórmer Cisoide de l'ABTE en generar complexes bidentats amb els substrats quirals, en els que la major proximitat del CSA a cada una dels enantiòmers del substrat, provoca una major diferenciació en l'entorn magnètic.A la present tesi doctoral s'abordà la síntesi estereoselectiva de l'ABTE. La reducció tipus CBS del 9,10-bis(trifluoroacetil)antracè ens permeté obtenir el CSA desitjat en un 65% de rendiment i amb una proporció estereomèrica de RR/RS/SS= 89:11:0. Aquesta ruta es va dur a escala més gran, per tal de fer la seva fabricació per a la seva comercialització (ACRÔS).Per RMN també s'estudien les associacions entre l'ABTE i l'1,2-benzendimetanol i l'1,3-benzendimetanol, per evidenciar l'existència dels complexes bidentats. S'observen les variacions dels senyals de protó del CSA, també es determinen les estequiometries dels complexos i les seves constants de formació. L'estudi es completa amb un estudi teòric per mecànica molecular. Amb tots els resultats es pot concloure que el CSA forma un complex bidentat amb l'1,2-benzendimetanol i també amb l'1,3-benzendimetanol, però amb aquest últim no de forma exclusiva sinó que també existeixen associacions monodentades.També s'estudien les diferències estructurals i d'estabilitat de la interacció entre l'ABTE i l'1-aminoindà i l'1-amino-2-indanol. L'existència de l'associació bidentada s'evidencià amb la major variació dels desplaçaments químics de cada un dels enantiòmers del substrat en relació a la que es va obtenir en la solvatació amb el CSA homòleg monofuncional. Amb el primer substrat es va poder atribuir en un augment de l'estabilitat de l'associació, degut, segurament a una disminució de l'entropia. En canvi, amb l'1-amino-2-indanol no es van apreciar diferències en l'estabilitat, amb el que podem atribuir una major variació dels desplaçaments químics a efectes estructurals de la complexació, principalment en una associació bidentada més íntima.A la segona part de la tesi es desenvolupa la síntesi estereoselectiva de l'?,?'-bis(trifluorometil)-9,10-antracendimetanamina (ABTA), que s'obté per la doble trifluorometilació de la sulfinimina quiral derivada de la condensació del 9,10-antracendimetanol amb la sulfinamida de Ellman, amb un rendiment global d'ABTA del 57% i de forma enantiopura. També es descriuen les síntesis de la 2,2,2-trifluoro-1-(9-antril)etilamina, la 1-(9-antril)etilamina i l'aproximació de l'?-trifluorometil-9-[10-(2,2,2-trifluoroetanamino)]antracenmetanol (ABTEA).Es fan diversos estudis de solvatació mitjançant RMN, del nou CSA difuncional ABTA. En ells es va observar la separació de les bandes dels protons dels enantiòmers en afegir un elevat nombre d'equivalents de CSA, fins a 15, i l'estudi termodinàmic, que també es va realitzar per RMN, ens va donar constants d'associació molt baixes. Probablement, aquests resultats es deuen a la poca basicitat del grup amino, que no afavoreix la formació de ponts d'hidrògen. / In the current thesis new studies about difunctional chiral solvating agents (CSA) are developed. CSAs have the ability to interact differentially with each of the enantiomers of a chiral substrate, through non covalent bonds, like acid-base interactions, hydrogen bonds, dipolar interactions.giving diastereomeric associative complexes. This chiral recognition produces distinct chemical and magnetic properties to each enantiomer, that will be observed, in RMN, as an anisocrony of its signals, mainly the proton signals. This chemical shift difference will allow us to determine the composition of the mixture. Since the observed chemical shifts are an average of a dynamic system where elements are free or complexate, the chemical shift variation will depend on the thermodynamic of the association and either on the structural properties.In our research group, the synthesis of difunctional CSAs has been developed. The first case which we're dealing with at the current thesis, is the ?,?'-bis(trifluoromethyl)-9,10-anthracenedimethanol (ABTE), that showed, in last studies, an excellent chiral recognition capacity. The NMR studies allowed us to conclude that this attribute is due to the capability of the Cisoid conformer of the ABTE to give bidentate complexes with the chiral substrates, where the greater proximity of the CSA to each one of the enantiomers of the substrate, induces a greater differentiation of their magnetic fields.In the current thesis, the stereoselective synthesis of ABTE has been developed. The CBS reduction of 9,10-bis(trifluoroacetyl)anthracene allowed us to obtain the desired CSA in a 65% yield with an stereomeric ratio of RR/RS/SS=89:11:0. This reaction has been scaled up for the manufacture and commercialization of the product (ACRÔS).With the NMR, we have been studied the association between ABTE and 1,2-benzenedimethanol and 1,3-benzenedimethanol, to demonstrate the existence of the bidentate complexes. We observed the chemical shift of the proton signals of the CSA, and we determined the stequiometry of the complexes and their binding constant. The study is completed with a theoretical estimation by molecular mechanics. With all the results, we could conclude that the CSA generates a bidentate complex with 1,2-benzenedimethanol and also with 1,3-benzenedimethanol, but not as an exclusive form with the last one, which would be in equilibrium with monodentate associations.There has been studied, also, the structural and thermodynamic differences of the interactions of the ABTE with 1-aminoindane and 1-amino-2-indanole. The greater difference of the chemical shifts between enantiomers of each substrate compared to the results obtained when using the comparable monofunctional CSA, gives us evidences of the existence of the bidentate association. With several NMR experiments, we could attribute the greater chiral recognition with the first substrate to a more stable association, due to probably lower entropy. On the other hand, the association with the second substrate didn't improve because of a more stable complex, but for the structural properties, mainly in a more close bidentate association.At the second part of the thesis, the stereoselective synthesis of ?,?'-bis(trifluoromethyl)-9,10-antracenedimethanamine (ABTA) is developed. It consists in a double stereoselective trifluoromethylation of the chiral sulfinimine derived from the condensation of 9,10-anthracendimethanol with the Ellman sulfinamide, with a 56% global yield of the ABTA in its enantiopure form. There are also described the synthesis of 2,2,2-trifluoro-1-(anthryl)ethylamine, 1-(9-anthryl)-ethylamine and the approach to the ?-trifluoromethyl-9-[10-(2,2,2-trifluoroethanamino)]anthracenemethanol (ABTEA).The chiral recognition capability of the new difunctional CSA, ABTA, is studied with several chiral substrates. The registered NMR experiments showed us a generally low capacity, observing the differentiation of the chemical shifts of the enantiomers after adding great amounts of CSA. The thermodynamic study could be done also with the NMR, and it gave us very low binding constants of the diastereomeric complexes. These results could come, probably, of the low basicity of the amino group, that wouldn't favour the formation of hydrogen bonds.
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Síntesis y estudio de nuevos agentes de solvatación quiral polifuncionalesEnrech López, Raquel 25 November 2011 (has links)
La presente Tesis doctoral se centra en la separación enantioselectiva, desarrollando nuevos agentes de solvatación quiral (CSA) y nuevas fases estacionarias quirales (CSP).
En una primera parte de la Tesis se sintetizaron compuestos antracénicos trifuncionales como el 1,8,10-tribromoantraceno y 10-bromo-α,α’-bistrifluorometil-1,8-antracenedimetanol, que permiten la síntesis de CSAs trifuncionales o el anclaje a una fase estacionaria, para una posterior aplicación en HPLC quiral.
Otro apartado de esta Tesis se ha centrado en la síntesis de nuevos CSAs tipo pinza molecular, dónde se ha realizado un estudio estructural mediante RMN. Se han ensayado sus capacidades enantiodiferenciadoras con diferentes solutos, obteniendo resultados diversos y se han estudiado los complejos CSA-soluto formados. Se ha comprobado que en algunos de los casos, la rigidez del CSA no ha permitido realizar la función “pinza”, obteniendo pobres resultados en el enantioreconocimiento, pero en otros casos, hemos comprobado que el enantioreconocimiento es espectacular cuando el soluto contiene un grupo amino, y el CSA tiene o un grupo amino o nitro, permitiendo otro punto de interacción entre el CSA y el soluto. En estos casos, la estequiometria del complejo CSA:soluto es de 1:2, en vez de 1:1 como es lo habitual.
El último apartado de esta Tesis se ha centrado en la síntesis de nuevas fases estacionarias quirales (CSP) tipo Brush. El objetivo era preparar una CSP con terminaciones en pinza molecular. La primera CSP sintetizada no se consiguió obtener la terminación deseada, por eso se planteó preparar otra CSP que contuviera el CSA isoftalato de ABTE, quedándonos a un paso de su preparación completa. / This thesis focuses on the enantioselective separation, developing new chiral solvating agents (CSA) and new chiral stationary phases (CSP).
In the first part of the thesis, there were synthesized trifunctional compounds such as 1,8,10-tribromoanthracene and 10-bromo-α,α'-bistrifluorometyl-1,8-anthracenedimethanol, allowing the synthesis of trifunctional CSAs or anchor these compounds in stationary phases for a subsequent application in chiral HPLC.
Another section of this thesis, the molecular tweezers were synthesized and characterized by NMR. Enantiodiscrimination capabilities have been tested with different solutes, obtaining different results. We also have studied the CSA-solute complexes formed. In some cases, the rigidity of the CSA has not permitted the tweezers function, obtaining poor results in chiral recognition, but in other cases, we found that this chiral recognition was spectacular when the solute contains an amino group and the CSA has a nitro or amino group, allowing another point of interaction between the CSA and solute. In these cases, the stoichiometry of the complex CSA:solute is 1:2 rather than 1:1 as usual.
The last section of this thesis was focused on the synthesis of new chiral stationary phases (CSP) type Brush. The aim was to prepare a CSP with molecular tweezers terminations. The first CSP synthesized I didn’t achieve my goal, as it didn’t have tweezers terminations, so another CSP was prepared containing the ABTE isophthalate, staying one step away from full preparation.
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