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1
Rouillé, Jocelyn. "Mécanismes d'alvéolation de la pâte et la mie de pain français". Nantes, 2003. http://www.theses.fr/2003NANT2119.
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L'élaboration du pain met en oeuvre des actions mécaniques, fermentaires, microbiologiques et thermiques qui permettent de transformer un solide divisé (la farine de blé) en un matériau alvéolé, via les étapes de pétrissage (formation d'un solide viscoélastique), de fermentation (transformation en mousse) et de cuisson (transformation finale en éponge solide). Les modifications structurales subies par la pâte au cours de ces deux dernières étapes sont ici étudiées sur le modèle du pain français (farine, eau, sel, levure), afin de comprendre les mécanismes de formation de la texture. Après instrumentation d'un four traditionnel pour mesurer en continu les températures, masse et périmètre du pâton, les effets des constituants mineurs de la farine (CMF = solubles du blé, ratio lipides/puroindolines) sur la mise en place de la texture sont mis en évidence notamment sur l'expansion et la finesse de la mie définie grâce à l'analyse d'images par la fraction des cellules de taille <1mm. La transition pâte/mie débute vers 65-70°C et coïncide avec la réticulation du gluten et le début de gélatinisation de l'amidon. La détermination des propriétés rhéologiques de la pâte, en grande déformation, précise le rôle des CMF sur la stabilité des bulles de gaz. Le suivi de la fermentation par imagerie par résonnance nucléaire confirme cette tendance et montre que la densité de la mie ainsi que la distribution surfacique des alvéoles sont déterminées dès la fin de la fermentation. L'importance de ces critères et leur évolution pendant la conservation du pain sont établies par des mesures de texture. Finalement, une interprétation d'ensemble des résultats est proposée sur la base d'un modèle de rétention des gaz et de croissance des bulles pour décrire l'obtention de la texture de la mie de painBreadmaking process of wheat flour involves mechanical, fermenting, microbiological and thermal stages including mixing (formation of a viscoelastic solid), proofing (foam) and baking (final transformation into solid sponge) to produce an open gas cell structure. This study focuses on structural modifications during fermentation and baking of a typical breach bread (i. E. Flour, water, salt and yeast) in order to understand mechanisms of texture creation. A pilot scale instrumented oven was designed in order to follow on line temperatures, mass loss and dough section. The effect of flour minor component (FMC, i. E. Wheat solubles, lipids and puroindolines) on texture formation was assessed by baking test and digital image analysis. Crumb fineness defined as surface proportion of gas cell <1mm. Is ~38 % for French Bread. The dough/crumb transition starts around 65-70°C and occurs with gluten reticulation and starch gelatinization. Rheological properties of dough at high strains, show the important role of FMC on gas bubble stability. Dynamic follow-up of dough fermentation by MR Imaging confirms this trend and emphasis the fact that crumb texture and surface distribution of gas cells is set since the end of fermentation. Those physical characteristics was related to crumb mechanical properties assessed by compression test. Finally, all those results together led us to propose mechanisms of formation of bread crumb, based on gas retention and bubble expansion model described elsewhere
2
Rzigue, Asma. "Phénomènes physiques à l’interface moule-pain de mie : effets sur la structure alvéolaire, le corsetage et l’adhésion". Nantes, 2016. http://www.theses.fr/2016NANT083F.
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L’objectif principal des travaux présentés dans ce mémoire est la compréhension des phénomènes physiques survenant à l’interface moule-pain au cours de la fermentation, de la cuisson et du refroidissement de pain de mie cuits en moule. La structure alvéolaire de sa mie et l’aspect de la croûte d’un pain de mie sont des caractéristiques importantes qui sont liées aux interactions entre moule et produit au cours du procédé de fabrication. Sur le plan technologique, la phase de démoulage et le risque d’adhésion du pain au moule représente un enjeu majeur qui conditionne la durée de vie du moule. La compréhension de l’origine de ce phénomène depuis son origine est essentielle et constitue une partie importante des travaux présentés iciThe main objective of the works presented in this report is the understanding of the physical phenomena arising in the interface mold-bread. These phenomena are linked to the interaction between the pan and the product during the manufacturing process. The main objective of this study is the understanding of physical phenomena occuring at the pan-bread interface during the fermentation, baking and cooling in the pan. The importance of the study of crust and crumb structure, is the fact that they are involved in depaning problems in bread industry and are linked to bread collapse, phenomena leading to concave walls, which can be a drawback for consumers. In industry, bread collapse is only detected at the stage of bread depaning, so too late to try to correct this default. This is why understanding the phenomenon from its origin is essential and is an important part of the present work
3
Lassoued, Nejla. "Structure alvéolaire des produits céréaliers de cuisson en lien avec les propriétés rhéologiques et thermiques de la pâte : Effet de la composition". Phd thesis, ENSIA (AgroParisTech), 2005. http://pastel.archives-ouvertes.fr/pastel-00003695.
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La structure alvéolaire et la fermeté de la mie des produits céréaliers de cuisson sont deux facteurs de qualité que la profession cherche à maîtriser. Dans ce contexte, des outils d'aide à la décision proposant, notamment, l'apport des paramètres de composition et du procédé intervenant dans la construction de la structure alvéolaire seraient utiles. Une série de « pains de mie enrichis », contenant les composants de base du pain (farine, eau, sel, levure) plus du saccharose et de l'huile de colza, a été fabriquée. Les gammes de concentration en eau, huile et saccharose, respectivement 50-60%, 2-20% et 0-15% (p/p base farine) ont été choisies de manière à fabriquer des produits de masse volumique réaliste par rapport aux produits du commerce (0,25-0,36 g/cm3) et de structures alvéolaires variées : mies fines ou grossières, homogènes ou hétérogènes. Les produits ont été caractérisés à toutes les étapes de leur fabrication en utilisant différentes techniques permettant l'observation de la structure et l'étude des propriétés rhéologiques et thermiques du produit. Ces techniques ont été choisies en fonction de l'échelle souhaitée et des propriétés à caractériser. Parmi elles, la microscopie, la rhéologie, l'analyse calorimétrique différentielle, l'analyse d'images, l'analyse sensorielle. En sélectionnant, à chaque étape de fabrication les paramètres pertinents et indépendants, et en analysant, ensuite, les corrélations toutes étapes confondues, il apparaît, notamment, que, pour la gamme de compositions étudiées dans ce travail, la masse volumique du produit alvéolaire dépend essentiellement de la viscosité et du caractère rhéofluidifiant de la pâte. La finesse de la mie est corrélée à la valeur de tan δ mesurée à l'issue du gonflement des grains d'amidon, et une fois que le réseau de gluten a thermocoagulé. L'hétérogénéité de la mie semble liée au niveau du caractère rhéodurcissant de la pâte en fin de fermentation. L'étude systématique de l'effet composition (farine, huile et saccharose) permet également de proposer des pistes de choix de compositions permettant l'obtention de structures alvéolaires souhaitées.
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Huault, Lucie. "Étude de l’évolution des contacts moules / pains de mie au cours de la cuisson en fonction des propriétés de surface des moules". Thesis, Paris, AgroParisTech, 2016. http://www.theses.fr/2016AGPT0038.
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Les revêtements perfluorés sont utilisés comme anti-adhésifs dans des moules de cuisson pour pains de mie. Ils font l’objet de diverses interrogations relatives à leur vieillissement. Dans ce contexte, la problématique de ce travail a porté sur l’étude des conséquences du vieillissement de revêtements perfluoroalkoxy (PFA) sur leurs performances anti-adhésives. De plus, les conséquences de la perte des propriétés anti-adhésives des revêtements ont été évaluées en termes de risque chimique. La production de néoformés dans la croûte de pain au contact des moules a donc été étudiée. Pour répondre à la problématique, des moules ont été vieillis en conditions industrielles, puis à partir d’un protocole mis au point spécifiquement dans le cadre de cette étude, des mesures de forces ont pu être réalisées pendant le démoulage des pains. Par ailleurs, plusieurs formules de pains de mie ont été testées. Il s’agissait d’étudier d’une part l’effet de l’état physique des lipides sur le démoulage. De plus, l’effet d’autres constituants tels que protéines et fibres a été étudié (utilisation de farine complète).Le vieillissement en conditions industrielles n’affecterait que les propriétés physiques (rugosité) des revêtements PFA. Ces modifications de surface n’ont cependant pas entraîné de problème de démoulage en fin de cuisson. Par ailleurs, les marqueurs choisis de la réactivité (furane, acrylamide et CML) évoluent peu avec le vieillissement, et ce quelle que soit la formule. La CML montre toutefois une tendance à augmenter avec le vieillissement, ce qui pourrait malgré tout indiquer un effet du vieillissement des revêtements sur la réactivité du produit.Par ailleurs, pour caractériser plus spécifiquement l’adhésion de pâtes de farine au cours de la cuisson, une méthodologie basée sur des tests d’adhérence en simulateur expérimental sur rhéomètre a été mise au point. Ces tests d’adhérence ont été effectués avec des surfaces modèles en verre, choisies pour être représentatives des propriétés chimiques des revêtements PFA. Il apparaît que les propriétés adhésives des pâtes évoluent de la même façon que les propriétés viscoélastiques en fonction de la température. Par ailleurs, les propriétés interfaciales contribuent pour une part à l’évolution d’adhésion des pâtes avec la température. Les pâtes tendent à adhérer plus facilement sur des surfaces hydrophiles. D’ailleurs, sur ces surfaces, les ruptures peuvent devenir cohésives au-delà d’une certaine température, indiquant une diminution de leur hydrophobicité de surfacePerfluorinated coatings used as anti-adhesive coatings in bread pans are subjected questions relating to their aging. In this context, the objective of this work was to focus on the consequences of aging of perfluoroalkoxy (PFA) coatings on their anti-adhesive performance. The consequences of loss of anti-adhesive properties were studied in terms of chemical risks and neoformed compounds in bread crust during baking in contact with a pan were investigated. To do so, pans were aged under industrial conditions, then a method was specifically developed for this study to measure forces during depanning step. Moreover, several bread formulas were tested. The aim was to determine the impact of physical state of lipids (rapeseed oil versus concrete fat) and of other components as proteins and fibers (by adding whole-wheat flour) on depanning step.Aging in industrial conditions seems to only affect physical properties (roughness) of PFA coatings. These modifications of the pan surface did not led to depanning problem at the end of the baking step. Moreover, the chosen reactivity markers evolve slightly with aging, whatever the bread formula used, even if a slightly increase of CML quantity with aged pan was highlighted.Furthermore, in order to characterize the adhesion of wheat dough depending on the temperature, a new methodology was developed. It consisted in measuring the adherence forces under experimental simulations on rheometer. We selected model glass surfaces which had chemical properties close to the properties of PFA coatings. We showed that adhesion and viscoelastic properties evolve in the same way with temperature, and interfacial properties also contribute to evolution of dough adhesion. Wheat dough tend to adhere more easily on hydrophilic surfaces. Anyway, on these surfaces, failure may become cohesive from a specific temperature, showing a decrease of the dough surface hydrophobicity
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Cauchetiez, Elisabeth. "Ce théâtre que nous faisions...el théâtre de la mie de pain, una experiència del teatre de l'actor-dramaturg en el context de la creació col·lectiva, 1979-1990". Doctoral thesis, Universitat Rovira i Virgili, 2015. http://hdl.handle.net/10803/386419.
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En primer lloc, la recerca pretèn dibuixar un retrat sociològic i cultural de l'últim període del segle XX, marcat per la fascinació per la creació col·lectiva i els principis de mutació dels gustos del públic que presagien el declivi d'aquesta pràctica teatral. Intenta donar resposta a la delicada qüestió de saber si aquest canvi d'orientació era fruit d'una voluntat política o d'una evolució del sistema econòmic o simplement el final d'una moda. Remarca que el teatre de creació col·lectiva té un fort lligam amb l'associacionisme que suggereix una via alternativa en el funcionament relacional del món laboral. Per contrarestar la jerarquització, proposa un model igualitari de presa de responsabilitat i l'autogestió dels mitjans econòmics. Cap als anys 90, la influència de l'esperit de l'associacionisme s'ha reduït i en conseqüència la forma teatral que representava els gustos d'aquest moviment social ha perdut ressó. La creació col·lectiva magnifica la figura de l'actor, perquè posar l'executant com a responsable de la creació suposa crear un espectacle partint dels coneixements de l'intèrpret. L'obra s'elabora a l'escenari durant els assaigs a base d'improvisacions i privilegia l'acció i el gest. Les troballes neixen de "l'estat de joc" que l'actor desenvolupa per la pràctica diària. Es busca l'espontaneïtat, entesa com una recerca sobre sí mateix i no com un tot s'hi val. L'impuls de la persona és filtrat pels coneixements de l'actor que domina el seu Art.En primer lugar, la investigación pretende dibujar un retrato sociológico y cultural del último período del siglo XX, marcado por la fascinación por la creación colectiva y el inicio del cambio de gustos del público que presagian el declive de esta práctica teatral. Intenta dar respuesta a la delicada pregunta de dilucidar si este cambio de orientación fue fruto de una voluntad política, de una evolución del sistema económico, o simplemente el final de una moda. Realza que el teatro de la creación colectiva mantiene un destacable lazo con el sistema asociativo que sugiere una alternativa en el funcionamiento relacional del mundo laboral. Para contrarrestar la imposición de la jerarquía, propone un modelo igualitario y la auto-gestión de los medios económicos. Hacia los años 90, la influencia del sistema asociativo se reduce y en consecuencia la forma teatral que representaba los gustos de este movimiento social pierde fuelle. La creación colectiva magnifica la figura del actor porque otorgar al ejecutante la responsabilidad de la creación presupone crear un espectáculo a partir de los conocimientos del intérprete. La obra se elabora en el escenario, en los ensayos, a base de improvisaciones. Los hallazgos nacen del "estado de juego" que el actor desarrolla con la práctica diaria. Se busca la espontaneidad, entendida como una investigación sobre sí mismo y no como "todo vale". El impulso de la persona se filtra a través de los conocimientos del actor que domina su arte.
First of all, the research tries to draw a sociological and cultural picture of the last period of the XXth Century, characterized by the fascination for collective creation and the beginning of change: the taste of public mutated and this fact foresaw the decline of that theatre practice.The author aims to understand this process and answer a sensitive question: was that change planed by political will or was it the result of an evolution of the economic system, or more simply, was it the end of a state of mood? She remarks that this practice has a link with the encrease of the spirit of association which proposes an alternative way for the relationships in the labour.To counteract the hierarchy, it presents a pattern of equality to take decisions and it suggests the self-management of the economic means. In nineties, spirit of association partly lost its weight and consequently that teatrical aesthetics which stood for the taste of that social movement faded. Collective creation puts the actor in the loop. This one becomes responsible of the creation because he creates the show taking account of his own knowledge of interpretation art. The show moves forward on stage during rehearsals thank to improvisations. Actors discover the findings of the play when they are in a particular state, a playing mood. They develop it throughout the daily practice. They look for spontaneity as a research upon themselves but not everything is accepted. Personal impulse is filtered through actor's skills.
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Maurice, Bastien. "Transformations alimentaires industrielles, artisanales ou à domicile : quels impacts sur les qualités des produits et les perceptions par les consommateurs ?" Electronic Thesis or Diss., université Paris-Saclay, 2022. http://www.theses.fr/2022UPASB071.
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La consommation de produits industriels transformés est pointée du doigt pour être pour partie reliée à la prévalence de maladies cardiovasculaires, d'obésité ou encore de cancer. Pour aider à la mise en place de recommandations auprès des consommateurs, mais également des industriels et des pouvoirs publics, il est nécessaire d'étudier l'impact des transformations alimentaires, réalisées dans différents contextes (industriel, artisanal, domestique), sur les qualités des produits et sur les perceptions des consommateurs.Pour cela, le pain de mie et la pizza ont été sélectionnés en tant que modèles. Des cartographies multicritères (nutritionnels et technologiques) ont été réalisées sur les produits industriels afin de rendre compte de la variabilité au sein de chaque catégorie de produit. Le Process-Score, développé pour caractériser le niveau de transformation des produits, s'est révélé être corrélé au Nutri-Score. 24 pains de mie industriels, artisanaux, et faits maison ont ensuite été sélectionnés pour être représentatifs de l'offre d'un point de vue composition nutritionnelle et transformation. Quel que soit le mode de transformation, ces pains présentaient des propriétés physiques et technologiques semblables. Toutefois, les produits présentaient des profils en molécules volatiles différents, en particulier pour les pains de mie industriels qui avaient moins de marqueurs de fermentation et plus de marqueurs d'oxydation.Ces données objectives ont été confrontées aux perceptions de plus de 60 participants. Les pains industriels ont été perçus comme moins bons nutritionnellement, bien qu'ayant les meilleurs Nutri-Scores.Les pizzas industrielles étaient supposées avoir davantage d'additifs alors qu'elles en contenaient le moins. La perception d'un produit sain semblait être anti-corrélée au Process-Score pour les deux produits, tandis que la perception du degré de transformation d'un pain de mie était anti-corrélée aux teneurs en lipides et sel, ce qui n'était pas le cas pour la pizza.L'impact d'informations nutritionnelle et technologique a été testé sur les perceptions des pains de mie, et a montré que les consommateurs modifiaient leurs perceptions, sans pour autant effacer complètement le poids de leurs croyances.Par ailleurs, il a été montré quelles priorités étaient déclarées par 1 000 participants lors d'un achat de produit alimentaire transformé (les attentes sur le goût et la naturalité des produits semblent plus prioritaires que la présence de labels), et comment ces priorités variaient selon le mode de transformation du produit, avec une moindre attention portée sur les produits achetés en restaurant.Ces résultats offrent donc des pistes de réflexion pour la reformulation de produits par les industriels, pour la communication des pouvoirs publics autour de ces thèmes et également pour éclairer les consommateurs dans leurs choix, ou encore apporter des données consolidées de calcul d'un Process-Score pour, par exemple, des études épidémiologiques sur l'incidence des produits transformés sur la santéThe consumption of processed industrial products is pointed out to be partly related to the prevalence of cardiovascular diseases, obesity or cancer. In order to help the implementation of recommendations to consumers, but also to manufacturers and public authorities, it is necessary to study the impact of food processing, elaborated in different contexts (industrial, artisanal, domestic), on the qualities of the products and on the perceptions of the consumers.For this purpose, soft bread and pizza were selected as models. Multi-criteria mappings (nutritional and technological) were performed on industrial products in order to highlight intra-category variability. In particular, the Process-Score was found to be correlated with the Nutri-Score. From this, 24 industrial, artisanal, and homemade soft breads were selected to be representative from a nutritional and processing point of view. They presented similar physical and technological properties, and different profiles of volatile molecules in particular for industrial soft breads showing less fermentation markers and more oxidation markers.These objective data were compared to the perceptions of more than 60 participants. Industrial breads were perceived as less good nutritionally, although they had the best Nutri-Scores.Industrial pizzas were perceived to have more additives, although they contained the least.The perception of a healthy product seemed to be anti-correlated to the Process-Score for both products, while the perception of the degree of processing of a soft bread was anti-correlated to the fat and salt contents, which was not the case for the pizza.The impact of nutritional and technological information was tested on the perceptions of soft breads, and showed that consumers modified their perceptions, without completely erasing the weight of their beliefs.In addition, it was shown what priorities were declared by 1,000 participants when purchasing a food product (expectations on the taste and naturalness of products seemed to be more important than the presence of labels), and how these priorities varied according to the way the product was processed, with less attention paid to products purchased in restaurants.These results therefore provide avenues for product reformulation by manufacturers, for communication by public authorities on these themes and also to enlighten consumers in their choices, or to provide consolidated data for calculating a Process-Score for, for example, epidemiological studies on the impact of processed products on health
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Magid, Jessica R. "Does early-life pain in mice affect adulthood pain sensitivity, stress behavior, and learning behavior?" Diss., Connect to the thesis, 2006. http://hdl.handle.net/10066/749.
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Shires, Alice. "Brief mindfulness exposure interventions in acute and chronic pain". Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/27781.
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Mindfulness-based interventions (MBIs) have been shown to be efficacious in the management of chronic pain, but some forms of MBIs are very intensive. This thesis aims to harness the benefits of mindfulness for people with pain by developing and testing a brief strategy, the mindfulness-based interoceptive exposure task (MIET), to help manage pain. The theoretical and conceptual basis of the MIET is described followed by a series of empirical studies testing the efficacy of the MIET. In the first study the MIET was administered to 15 consecutive patients with chronic pain. Results showed large within-subjects changes in outcomes, indicating that the MIET has potential as a brief strategy to improve outcomes in people with chronic pain. The second study, a randomized control trial for people with chronic pain found that the MIET resulted in reductions in pain within the session and at 2 and 12 weeks later. However, the broader benefits of the MIET found in the first study were not demonstrated in a comparison with the control group. In the final empirical study, the MIET was compared to distraction and a no-instruction control for healthy participants who then completed a cold pressor test. For acute rather than chronic pain, the MIET was not associated with differences in pain, although it was associated with large benefits for pain threshold and tolerance. To confirm the findings of the third study, a meta-analysis was conducted that confirmed that in the context of acute pain, MBIs do have an impact on pain tolerance and threshold, with little evidence for their benefit for pain severity or pain-related distress. In conclusion, the MIET does appear to be a useful strategy to reduce pain severity in people with chronic pain, but not acute pain. However, in acute pain the MIET appears to improve pain tolerance and threshold, as do other MBIs, and so MBIs likely have benefits in some acute pain settings, but large clinical trials are needed to confirm this.
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Wright-Williams, Sian Louise. "Behaviour-based assessment of post-operative pain in laboratory mice". Thesis, University of Newcastle upon Tyne, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.489318.
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There are currently no practical objective measures for assessing the duration and intensity of post-operative pain in laboratory mice. There is a lack of specific behavioural indicators making pain detection and analgesic use difficult; however behavioural measures of pain are likely to be the most practicable for widespread application. The behaviour of mice undergoing laparotomy or vasectomy surgery was analysed to investigate the overall effects of surgery and presumably, unalleviated post-operative pain. Meloxicam and buprenorphine were administered to determine the effects of analgesic administration on the behaviour of mice following surgery. In addition to behavioural measures, faecal corticosterone levels were used to quantify the stress response to surgery. Abnormal behaviours were observed in mice that underwent surgery; these behaviours were either not seen, or occurred only in very low frequencies, in normal control animals. Normal behaviours such as digging and rearing were seen to decrease following surgery compared with controls. The observed abnormal behaviours were: writhe, belly press, flinch, twitch, and rear leg lift. The occurrence of these behaviours differed between surgery type and strain, but was generally lower in mice that had received analgesic treatment prior to surgery compared with untreated mice, although dose-dependent reductions were not observed. Faecal corticosterone levels increased following vasectomy surgery· compared with un-operated controls, and this rise was prevented by either a low dose of buprenorphine or a high dose ofmeloxicam. Behavioural pain assessment in mice is not straight-forward; the behaviours thought to be pain-related are subtle, mice display high levels of activity, and strain differences in the behavioural response to surgery have been demonstrated. The behavioural responses to analgesic treatment in mice that have undergone surgery vary; and it was not possible to establish whether this was because the drugs administered were not fully effective at the doses prescribed, or whether the behaviours observed are not useful for discriminating between drug and non-drug treated mice. It has been demonstrated here that behavioural changes do occur in mice following laparotomy and vasectomy surgery, and that these behaviours most probably indicate the presence of post-operative pain. Further work is needed to develop the behavioural changes identified into a practically applicable pain scoring system, but if this can be done it will improve the welfare in the vast number of mice used in biomedical research worldwide and present a significant refinement to the management of post-operative pain in laboratory mice.
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COMI, ELEONORA. "Chronic pain evaluation in animal models of osteoarthritis: behavioural and pharmacological considerations". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/158318.
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L'osteoartrite (OA) è una patologia degenerativa cronica molto comune negli anziani. Il dolore rappresenta il sintomo di OA più invalidante e precoce per il paziente. Ad oggi non esistono terapie curative per questa patologia. Inoltre, i farmaci più comunemente usati per contrastare il dolore OA sono spesso associati ad effetti collaterali. CR4056, ligando dei recettori imidazolinici-2, è un nuovo farmaco analgesico dimostratosi efficace in diversi modelli animali di dolore.
Gli scopi di questo progetto sono stati analizzare la progressione del dolore OA e valutare l'efficacia di CR4056, comparato ad un FANS standard (naproxene), in due modelli di OA in ratto, in grado di replicare le componenti dolorose e strutturali della patologia umana.
L’OA è stata indotta mediante singola iniezione intra-articolare di 1 mg/50 μl di monosodio iodoacetato (MIA) o mediante rottura del menisco mediale (MMT) nel ginocchio destro di ratti maschi. L’iniezione di MIA causa la degenerazione della cartilagine, mediante inibizione locale della glicolisi, mentre la resezione del legamento collaterale mediale e del menisco mediale destabilizza l’articolazione, inducendo degradazione della cartilagine e alterazioni dell’osso subcondrale.
Nei modelli MIA e MMT la soglia algogena meccanica è stata valutata come allodinia e rispettivamente iperalgesia primaria o secondaria. Sono stati poi determinati l’asimmetria statica o dinamica del peso supportato delle zampe posteriori ipsilaterale e contralaterale (HPWD), la funzionalità motoria e l’attività locomotoria. L’espressione di proteine correlate al dolore (GFAP, pp38, pERKs e Iba-1) è stata valutata nel midollo spinale lombare ipsilaterale e contralaterale o nei DRG L4 e L5 ipsilaterali.
CR4056 (2, 6 e 20 mg/kg) e naproxene (10 mg/kg) sono stati somministrati come trattamenti acuti e subacuti in entrambi i modelli.
L’iniezione di MIA ha indotto uno sviluppo significativo di iperalgesia meccanica primaria, allodinia meccanica e asimmetria statica e dinamica di HPWD; nessun cambiamento si è verificato nell’attività locomotoria. CR4056 (6 e 20 mg/kg) ha ridotto significativamente l’allodinia e l’iperalgesia, dopo trattamento acuto (7 e 14 giorni post MIA) e soprattutto subacuto (da 14 a 21 giorni post MIA), mentre il naproxene è stato efficace solo dopo trattamento subacuto. Entrambi i composti sono risultati privi di effetto sull’asimmetria statica e dinamica di HPWD. L’espressione di pp38 e pERKs nel midollo spinale lombare ipsilaterale non si è dimostrata differente tra sham e MIA. L’iniezione di MIA ha invece indotto un aumento significativo delle cellule microgliali attivate (Iba1+) nella corna dorsale ipsilaterale del midollo spinale L4. Il trattamento subacuto con entrambi i composti ha ridotto significativamente tale attivazione della microglia.
L’operazione MMT ha indotto uno sviluppo significativo di una progressiva asimmetria statica di HPWD e di una stabile iperalgesia meccanica secondaria. Non sono stati invece evidenziati allodinia, asimmetria dinamica di HPWD e cambiamenti nell’attività locomotoria e funzionalità motoria. CR4056 (20 mg/kg) e naproxene hanno dimostrato un significativo effetto anti-iperalgesico solo dopo trattamento acuto (28 giorni post MMT). Invece, il trattamento subacuto (da 28 a 42 giorni post MMT) con CR4056 (6 mg/kg) ha ridotto significativamente l’asimmetria statica di HPWD, mentre il naproxene è risultato privo di effetti. Non si sono verificate variazioni nell’espressione di GFAP e Iba-1, rispettivamente nei DRG L4 e L5 ipsilaterali e nella corna dorsale ipsilaterale del midollo spinale L4, tra sham e MMT.
Entrambi i modelli MIA e MMT sono caratterizzati da una componente di dolore OA comparabile a quella umana, con tuttavia un differente contributo dei meccanismi dolorosi periferici e centrali. Inoltre, i dati ottenuti dimostrano che CR4056 potrebbe costituire un nuovo efficace trattamento per il dolore OA.Aim: Osteoarthritis (OA) is a disabling and painful condition very common in the elderly. Pain is the earliest symptom of OA. To date there are still no curative drugs for this condition. Moreover, the chronic use of first-line pharmacological treatments to handle OA pain is frequently associated with side effects. CR4056, an imidazoline-2 receptor ligand, is a promising analgesic drug that has been reported to be effective in several animal models of pain. The aims of my project were to analyze and compare the time-related progression of OA pain and to evaluate the efficacy of CR4056, in comparison with a standard NSAID (naproxen), in two well-established rat models of OA, able to mimic the painful and structural components of the human pathology. Methods: Knee OA was induced either by single intra-articular injection of 1 mg/50 μl monosodium iodoacetate (MIA) or by medial meniscal tear (MMT) in the right knee of male rats. The local injection of MIA produces cartilage degeneration, through the local inhibition of glycolisis, while the transection of both the medial collateral ligament and the medial meniscus leads to joint destabilization, resulting in cartilage degeneration and subchondral bone alterations. The withdrawal threshold to mechanical stimulation was assessed both as allodynia and either as primary or secondary hyperalgesia, in MIA and MMT model, respectively. Pain behaviour was further evaluated as static and dynamic hind paw weight bearing (HPWD) asymmetry between the ipsilateral and the contralateral limb, and as changes in motor function and/or locomotor activity. Pain-related proteins (GFAP, pp38, pERKs and Iba-1) expression was assessed in either ipsilateral and contralateral lumbar spinal cord or ipsilateral L4 and L5 dorsal root ganglions (DRGs), in either MIA or MMT model. CR4056 (2, 6 and 20 mg/kg) and 10 mg/kg naproxen were administered as acute and sub-acute treatments in both models. Results: MIA model was characterized by the significant development of primary mechanical hyperalgesia, mechanical allodynia and asymmetry in both static and dynamic HPWD. No changes were detected in locomotor activity after MIA injection. 6 and 20 mg/kg CR4056 significantly and dose-dependently reduced both allodynia and hyperalgesia, after acute (7 and 14 days after MIA) and especially after repeated treatment (from 14 to 21 days post-MIA), whereas naproxen was effective after sub-acute treatment only. Both compounds had no significant effect on static and dynamic HPWD changes. No difference was detected in pp38 and pERKs expression in ipsilateral lumbar spinal cord, between MIA and sham group. On the other hand, a significant increase in the number of Iba-1 positive, morphologically identified, activated microglia in ipsilateral L4 spinal cord dorsal horn occurred, 21 days after MIA injection. Sub-acute treatment with 6 mg/kg CR4056 and naproxen reversed MIA-induced microglia activation. MMT surgery induced the significant development of a progressive asymmetry in static HPWD and a long-lasting secondary mechanical hyperalgesia. No mechanical allodynia nor changes in dynamic HPWD, motor function and locomotor activity were detected after MMT surgery. 20 mg/kg CR4056 and naproxen promoted a mild but significant anti-hyperalgesic effect, after acute treatment (28 days post-surgery) only. Conversely, repeated treatment (from 28 to 42 days post-surgery) with 6 mg/kg CR4056 significantly reduced the progression of static HPWD asymmetry, whereas naproxen had no effects. No difference in GFAP or Iba-1 expression were detected, in either ipsilateral L4 and L5 DRGs or ipsilateral L4 spinal cord dorsal horn, between MMT and sham group. Conclusions: Both MIA and MMT OA models display a pain behaviour comparable to human OA, with however different relative contribution of peripheral and central pain mechanisms. Moreover, the data obtained showed that CR4056 may represent a new effective treatment option for OA pain.
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Bitler, Elizabeth Alspector Emily. "The relationship between drug-induced neurogenesis and pain behavior in mice /". Diss., Connect to the thesis, 2008. http://hdl.handle.net/10066/1326.
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Umaretiya, Puja Jagdish. "Cathepsin Inhibitor, VBY-825, Attenuates Bone Cancer Induced Pain in Mice". Thesis, The University of Arizona, 2011. http://hdl.handle.net/10150/145000.
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Alexander, Jessica K. "STRESS HORMONE INFLUENCES ON NEURAL AND IMMUNE MECHANISMS OF NEUROPATHIC PAIN". The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1275580267.
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Randall, J. I. "Behavioural and neurochemical mechanisms of social conflict analgesia in Mus musculus : Involvment of endogenous opioid and benzodiazepine substrates in two situation-dependent forms of social conflict analgesia in male laboratory mice". Thesis, University of Bradford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381069.
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Gomes, Angelina. "Alterations in hippocampal neurogenesis and pain behavior in mice an experimental study /". Diss., Connect to the thesis, 2009. http://hdl.handle.net/10066/3726.
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Walker, Christopher J. "The Role of Neurotensin Receptors on Visceral Pain and Activity Levels in Mice". UNF Digital Commons, 2015. http://digitalcommons.unf.edu/etd/588.
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This study examines the effects of neurotensin (NT) receptor sites on the sensation of visceral pain. Previous work by researchers has found, through the use of NT analogs, that visceral pain is closely associated with NT receptor 2 (NTSR2). This study tested 70 genetically modified mice. The mice were either missing NTSR1, NTSR2, or were wild-type (WT) mice that were not missing any NT receptors. The mice were injected intraperitoneally with either saline or acetic acid then observed for a 60 minute period and writhing behavior was recorded. Twenty four hours later activity levels were recorded in the open field assay. We found that contrary to previous research, NTSR2 is not solely responsible in the sensation of visceral pain. We also found that NTSR1 plays a more significant role than NTSR2, contrary to previous research. Additionally, we found that the NT receptors may be affected by age related factors. The findings of this study suggest that NTSR2 does in fact play a role in the sensation of visceral pain but that NTSR1 may modulate the degree of activation of NTSR2. It can also be concluded that age may have a role in the effectiveness of NTSR sites in visceral pain. This information allows for further research to analyze possible age-dependent effects of NT receptor sites that could alter the possible usefulness of NT analogues in the future.
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Vaccarino, Anthony Leonard. "Naloxone analgesia in BALBc mice : a dose-dependent relationship". Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66239.
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Neelakantan, Harshini. "REWARD-RELATED BEHAVIORAL EFFECTS OF PRESCRIPTION OPIOIDS AS A FUNCTION OF PUTATIVE ACUTE AND CHRONIC PAIN-LIKE STATES IN MALE AND FEMALE C57BL/6 MICE". Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/270439.
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Pharmaceutical SciencesPh.D.
Pain is a leading cause of disability and the most common reason for clinical care. The field of pain research has focused on sex differences in the recent years with an expansive body of literature demonstrating sex-related differences in pain behavior and responsiveness to pharmacological interventions. Prescription opioids are potent analgesics and the mainstay for the clinical management of moderate-to-severe acute and chronic pain conditions. However, the long-term clinical use of prescription opioids for chronic pain remains controversial due to concerns about severe adverse effects, including tolerance, dependence, and addiction associated with opioid use. The non-medical use and abuse of prescription opioids has become a public health crisis, the problem even arising in a subset of chronic pain patients receiving opioid therapy. The vulnerability factors, specifically the role of pain in the propensity to prescription opioid abuse, are poorly understood. The present research project sought to investigate the propensity to opioid reward as a function of pain in male and female mice by incorporating acute (acetic acid-induced) visceral nociceptive and chronic chemotherapy (paclitaxel)-induced peripheral neuropathic pain models. Sexually dimorphic variations in the sensitivities of mice to nociceptive and allodynic behaviors were initially assessed using the two putative pain models. Following that, the two prescription opioids, morphine and oxycodone were examined under both pain contexts and the capacity of the two prescription opioids to produce reward-related behavioral effects were measured using drug discrimination, conditioned place preference, and intravenous drug self-administration procedures. The presence of acute noxious state but not chronic pain selectively attenuated the discriminative stimulus effects of the prescription opioid, morphine in male mice. The magnitude of modulation of the stimulus effects of opioids by the acute noxious state were further observed to be inversely related to the relative intrinsic antinociceptive effectiveness of the two opioids in reversing the acute noxious state and sex-specific sensitivities of mice to opioid-induced antinociception. In contrast, while no change was observed in opioid-reward as a function of the acute noxious state in both sexes, the presence of paclitaxel-induced chronic pain opioid-selectively and dose-selectively enhanced the conditioned rewarding effect of morphine (0.3 mg/kg dose), and the effect was more pronounced in male relative to female mice. These data were further supported by the self-administration results, in that the reinforcing efficacy (breakpoints under progressive ratio (PR) responding) and the incentive-motivational salience of morphine significantly increased in the presence of chronic pain in male mice, while non-selectively increasing regardless of the presence/absence of pain in female mice. Overall, the converging empirical evidence presented here suggest that these models provide preclinical tools to further understand the overlapping neurobiology of pain and opioid abuse, the behavioral effects of prescription opioids, and advance the development of novel sex-specific pain therapeutics with low addiction liability.
Temple University--Theses
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Teotonio, Maria Aline Alves. "Transection of the medial meniscus in mice promotes more pain and injury that your recession". Universidade Federal do CearÃ, 2013. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=12943.
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Abstract Osteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint of function and disability, reduced with the quality of life. In humans, the lack of reliable and objective methods to evaluate the progression of OA limits their clinical study. Thus, animals are commonly used as model in an attempt to understand the pathophysiology of the disease and investigate new therapies. Considered one of the most experimental models of OA used, the mechanical instability of surgically induced experimentally reproduce the chronic trauma observed in human OA. Using models of surgical meniscectomy (meniscus removal) and destabilization of the medial meniscus (DMM) aimed to evaluate the difference in the development of OA in these experimental models and their response to different anti-inflammatory drugs. Swiss mice underwent surgery and the animals were sacrificed after 7 weeks, with daily assessment of joint pain (hypernociception). After sacrifice, the intra-articular lavage was colleted. The supernatant stored for evaluate cytokine-induced nitric oxide (NO). Histopathologic evaluation of the joints was performed according to the OARSI scores. Groups false-operated (Sham) were used for comparison. Meniscotomizados groups of animals receiving morphine (2 mg/kg, ip), naloxone (1 mg/kg, ip), indomethacin (2 mg/kg, sc), 1400W (0.5 mg/kg, sc), HOE-140 (1 mg/kg, sc) or anti-TNF (25-50 l) intraarticular. The hypernociception was recorded first and third hours after drug administration. Untreated group received vehicle only. Data were expressed as mean  SEM, and ANOVA followed by Tukey test. The histopathological scores were expressed as median followed by Kruskal-Wallis. Statistical significance was set at P <0.05. In destabilization of the medial meniscus and meniscectomy, articular hyperalgesia increased significantly in the 16 days after surgery, compared to the sham group (false-operated animals). This hyperalgesia persisted in group destabilization of the medial meniscus until the 49th day of observation (P <0.05). The cellular influx was higher and articular lesions were more severe, particularly in tibial portion, destabilization of the medial meniscus group (P <0.05). Indomethacin, 1400W, HOE and morphine significantly reduced hypernociception, with reversal of the effect of morphine by naloxone. The analgesic effect of anti-TNF persisted for 7 days after administration. The levels of IL-1, TNF-α, IFN-γ and NO were undetectable. The destabilization of the medial meniscus is a more severe OA, involving the participation of cyclooxygenase, inducible nitric oxide synthase, bradykinin, opioids and TNF.A Osteoartrite (OA) à uma doenÃa articular crÃnica degenerativa, caracterizada pela perda da funÃÃo e incapacitaÃÃo, interferindo na qualidade de vida. Em humanos, a inexistÃncia de mÃtodos objetivos e confiÃveis para avaliar a evoluÃÃo da OA limita o seu estudo clÃnico. Assim, modelos animais sÃo amplamente utilizados na tentativa de se compreender os aspectos fisiopatolÃgicos da doenÃa e investigar novas terapias. Considerado como um dos modelos experimentais de OA mais utilizado, o de instabilidade mecÃnica induzida por cirurgia reproduz experimentalmente o trauma crÃnico observado na OA humana. Utilizando os modelos cirÃrgicos de meniscectomia (retirada do menisco) e desestabilizaÃÃo do menisco (corte do menisco) objetivou-se avaliar a diferenÃa do desenvolvimento da OA nesses modelos experimentais e sua resposta a diferentes drogas anti-inflamatÃrias. Camundongos Swiss foram submetidos à cirurgia e sacrificados apÃs 7 semanas, com avaliaÃÃo diÃria da dor articular (hipernocicepÃÃo). ApÃs o sacrifÃcio, o lavado articular foi coletado e o sobrenadante armazenado para a dosagem de citocinas e Ãxido nÃtrico (NO). AvaliaÃÃo histopatolÃgica das articulaÃÃes foi feita segundo os escores Osteoartrite Research Society International (OARSI).Grupos falso-operados (Sham) foram utilizados para comparaÃÃo. Grupo de animais meniscotomizados receberam morfina (2 mg/kg; i.p.), naloxona (1 mg/kg; i.p.), indometacina (2 mg/kg; s.c.), 1400W (0,5 mg/kg; s.c.), HOE-140 (1 mg/kg; s.c.) ou anti-TNF (25-50 μL) intra-articular . A hipernocicepÃÃo foi registrada 1 e 3 horas apÃs a administraÃÃo das drogas. Grupo nÃo tratado recebeu apenas veÃculo. Os dados foram expressos como mÃdia  e.p.m, seguidos por ANOVA e teste de Tukey. Os escores histopatolÃgicos foram expressos como mediana, seguidos por teste de Kruskal-Wallis. O nÃvel de significÃncia foi de P<0,05. Na meniscectomia e meniscotomia, a hiperalgesia articular aumentou significativamente nos 16 dias apÃs o procedimento cirÃrgico, comparada ao grupo sham (animais falso-operados). Essa hiperalgesia persistiu no grupo meniscotomia atà o 49 dia de observaÃÃo (P<0,05). O influxo celular foi maior e as lesÃes articulares foram mais graves, particularmente na porÃÃo tibial, no grupo meniscotomia (P<0,05). Indometacina, 1400W, HOE e morfina reduziram significativamente a hipernocicepÃÃo, com reversÃo do efeito da morfina pelo naloxona. O efeito analgÃsico de anti-TNF persistiu por 7 dias apÃs a administraÃÃo. Os nÃveis de IL-1, TNF-α, IFN-γ e NO foram indetectÃveis. A meniscotomia à um modelo mais grave de OA, envolvendo a participaÃÃo de cicloxigenase, Ãxido nÃtrico sintase indutÃvel, bradicinina, opioides e TNF.
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Danco, Alexander. "Beneficial effects of running exercise on intervertebral disc degeneration and low back pain in mice". Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119506.
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Chronic low back pain (LBP) affects over 10% of Canadians and seriously decreases quality of life. The aging intervertebral disc (IVD) is prone to degeneration, frequently contributing to low back pain. Physical activity influences IVD physiology, and animal studies show that cyclic loading increases proteoglycan synthesis in the disc, suggesting a role for running exercise in disc repair. Our laboratory has validated a rodent model of LBP, the aging SPARC-null mouse, which displays axial and radiating pain that parallels LBP in humans and is pharmacologically reversible. We therefore aimed to demonstrate that habitual running exercise will delay disc degeneration and decrease pain behavior in the aging SPARC-null mouse. After two months with free access to running wheels, SPARC-null mice show significantly reduced cold sensitivity in the hindpaw compared to baseline (p<.05) and control group (p<.05), indicating reduced radiating LBP. Axial LBP was unaffected, suggesting the effect was specific to radiating pain. In older animals, cold sensitivity was significantly reduced compared to control group after four months (p<.05), suggesting exercise is still beneficial in animals with more advanced disc degeneration. If running wheels are withdrawn from the home cage, SPARC-null mice continue to show reduced cold sensitivity for two months (p<.01). Only after three months without wheel access do they return to baseline behaviour. X-ray analysis showed that both young and older SPARC-null animals display significant improvement in lumbar disc height after habitual exercise (p<.01). However, exercise had no effect on the severity of disc degeneration in SPARC-null mice by histological analysis using the FAST staining method. Immunohistochemical staining of sensory nerve fibers in the IVD revealed that running exercise reduces the number and total length of CGRP-positive nerve fibers in the outer IVD in older SPARC-null mice (p<.05). The number of CGRP-positive nerve fibers in the outer IVD correlated both with disc height and with cold hypersensitivity in the hindpaw in SPARC-null mice, suggesting that IVD nerve ingrowth may mediate the relationship between disc degeneration and radiating low back pain behaviour in mice. Overall, we see that voluntary running exercise specifically reduces radiating LBP and improves disc height, but does not improve axial LBP or histological signs of disc degeneration. Running exercise may reduce IVD sensory nerve ingrowth, which could help explain the relationship between disc health and low back pain behaviour. Improving our understanding of this relationship will hopefully lead to improved therapies and preventions for the LBP patient.La douleur chronique du bas du dos (lombalgie) affecte plus de 10% des Canadiens et diminue gravement la qualité de vie. Le disque intervertébral (DIV) peut dégénérer avec l'âge, ce qui peut contribuer à la lombalgie. L'activité physique peut influencer la physiologie du DIV, et des études chez l'animal montrent que le chargement cyclique augmente la synthèse des protéoglycans dans le disque, ce qui suggère un rôle pour l'exercice dans la réparation du DIV. Notre laboratoire a validé un modèle expérimental de la lombalgie, la souris SPARC-nulle âgée, qui démontre de la douleur axiale et sciatique qui ressemble la lombalgie chez l'humain et est pharmacologiquement réversible. Nous avons donc cherché à démontrer que l'exercice habituel de la course retardera la dégénérescence du DIV et diminuera le comportement indiquant la lombalgie chez la souris SPARC-nulle âgée. Après deux mois en accès libre à des roues tournantes dans leurs cages domestiques, les souris SPARC-nulles montrent une réduction de leur hypersensibilité au froid sur la patte arrière par rapport à leur seuil de départ (p <.05) et au groupe de contrôle sans roues tournantes (p <.05), indiquant une réduction de douleur sciatique. La douleur axiale n'a pas été affectée, ce qui suggère que l'effet était spécifique à la douleur sciatique. Chez les animaux âgés, la sensibilité au froid a été réduite par rapport au groupe de contrôle après quatre mois (p <.05). Si les roues sont retirées des cages, les souris SPARC-nulles continuent à montrer une sensibilité au froid réduite pendant deux mois (p <.01). C'est seulement après trois mois sans accès aux roues qu'ils reviennent au comportement de base. L'analyse radiographique a montré que les souris SPARC-nulles (jeunes et vieux) avec des roues tournantes démontrent une amélioration significative de la hauteur discale lombaire (p <.01). Toutefois, l'exercice n'a eu aucun effet sur la gravité de la dégénérescence discale par l'analyse histologique. La détection immunohistochimique des fibres nerveuses sensorielles dans le DIV a montré que l'exercice habituel réduit le nombre et la longueur totale des fibres nerveuses marquées au CGRP dans le DIV chez les souris SPARC-nulles âgés (p <.05). Le nombre de nerfs dans la DIV corrèle avec la hauteur du disque et aussi avec l'hypersensibilité au froid dans la patte arrière chez la souris SPARC-nulle, ce qui suggère que la croissance des nerfs dans la DIV peut influer la relation entre la dégénérescence discale et la lombalgie chez la souris. En conclusion, nous voyons que l'exercice de course volontaire améliore la douleur sciatique et la hauteur de la DIV, mais n'améliore pas la douleur axiale ou les signes histologiques de dégénérescence de la DIV. L'exercice de course volontaire réduit possiblement la croissance des nerfs dans le DIV, ce qui pourrait aider à expliquer la relation entre la santé du disque et le comportement douloureux chez la souris. Une meilleure compréhension de cette relation devrait mener à l'amélioration des traitements et de la prévention pour le patient lombalgique.
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Bura, S. Andreea. "New animals models to evaluate therapeutic targets for pain, cognitive and eating disorders". Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/31821.
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Animal models are crucial to improve the knowledge of the mechanisms underlying the different pathological processes. These models are also excellent tools to facilitate the research of new targets for the treatment of different diseases and to evaluate the benefit/risk ratio of the potential new treatments. We have focussed this research work in the study of a new potential targets for pain, cognitive and eating disorders using new animal models developed in our laboratory. We first investigated the effects of the interaction between cannabinoids and nicotine on cognitive processes and metabolism using different behavioural models and new experimental devices. In a second part of this work, we investigated new therapeutic targets for neuropathic pain and for this purpose we developed a new behavioural model to improve the study of the therapeutic potential and possible side-effects of novel compounds.Los modelos animales son cruciales para mejorar el conocimiento sobre los mecanismos que constituyen la base de los diversos procesos patológicos. Estos modelos representan también excelentes herramientas para facilitar la investigación de nuevas dianas para el tratamiento de estas enfermedades y para evaluar el cociente beneficio/riesgo de los nuevos tratamientos potenciales. Este trabajo de investigación se encuentra centrado en el estudio de nuevos dianas terapéuticas para el dolor, los procesos cognitivos y los desórdenes alimentarios utilizando nuevos modelos animales desarrollados en nuestro laboratorio. En primer lugar, hemos investigado los efectos de la interacción entre los cannabinoinoides y la nicotina a nivel los procesos cognitivos y del metabolismo usando diversos modelos comportamentales y nuevos dispositivos experimentales. En una segunda parte de este trabajo, hemos estudiado nuevas dianas terapéuticas para el dolor neuropático y hemos desarrollado para este propósito un nuevo modelo comportamental que permite evaluar el potencial terapéutico y los posibles efectos secundarios de nuevos compuestos.
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Inan, Saadet. "Pharmacological and Neuroanatomical Analysis of GNTI-Induced Repetitive Behavior in Mice". Diss., Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/75332.
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PharmacologyPh.D.
This thesis is comprised of two parts. In the first part, we investigated a) the pharmacology of GNTI, a selective kappa opioid receptor antagonist, as a scratch-inducing compound in mice and b) possible mediators and receptors that may be involved in GNTI-induced scratching (itch). We studied if GNTI induces scratching through opioid, histamine, gastrin-releasing peptide (GRP) and/or muscarinic M1 receptors. In the second part, we established similarities and differences between pain and itch using GNTI-induced scratching and formalin-induced nociception models in mice. We found that GNTI (0.03-3 mg/kg, s.c., behind the neck) induces compulsive and vigorous scratching behavior in a dose-dependent manner. A standard submaximal dose (0.3 mg/kg) of GNTI caused animals to scratch 500-600 times in a 30 min observation period. Intrathecal (i.t.) or intraperitoneal (i.p.) administration of GNTI did not elicit scratching behavior. Duration of action of GNTI was 60-70 min and tolerance to the repetitive behavior did not develop. C-fos expressing neurons, in response to GNTI injection, were localized on the lateral side of the superficial layers of the dorsal horn of the cervical spinal cord. Compound 48/80, a chemically different pruritogen, evoked c-fos expression in neurons which are located on the lateral side of the superficial layer of the dorsal horn. These data suggest that both GNTI and compound 48/80 activate a group of sensory neurons located on the lateral side of lamina I and II. Pretreating (at -20 min) and posttreating (at +5 min) mice with the kappa opioid receptor agonist, nalfurafine (0.001-0.03 mg/kg, s.c.), significantly attenuated scratching induced by GNTI (0.3 mg/kg). These effects were not a consequence of behavioral depression. Tolerance did not develop to the anti-scratch activity of nalfurafine. Pretreating mice with nalfurafine (0.02 mg/kg) prevented both GNTI- and compound 48/80-provoked c-fos expression. Our c-fos results suggest that the preclinical antipruritic activity of nalfurafine occurs at the spinal level. Moreover, our results reinforce the need to evaluate nalfurafine as a potentially useful antipruritic in human conditions involving itch. GNTI still elicited excessive scratching in mice lacking mu, delta or kappa opioid receptors, respectively, as well as in mice pretreated with either naloxone or norbinaltorphimine. The H1 receptor antagonist, fexofenadine, or the H4 receptor antagonist, JNJ 10191584, did not attenuate GNTI-induced scratching. Also, pretreating mice with the peptide GRPR antagonist, [D-Phe6]bombesin(6-13) methyl ester, or the non-peptide GRPR antagonist, RC-3095, did not antagonize scratching induced by GNTI. Furthermore, GRPR mRNA levels did not change in response to GNTI injection. Telenzepine, a standard M1 receptor antagonist, had no marked effect against GNTI-elicited scratching, however (unexpectedly) McN-A-343, an M1 receptor agonist, attenuated this behavior in a dose-dependent manner. In the second part of our studies, we found that pretreating mice with lidocaine (i.d., behind the neck) inhibits GNTI-induced scratching and prevents GNTI-provoked c-fos expression in the dorsal horn of the spinal cord. Similarly, lidocaine (i.d., hind leg) inhibits formalin-induced nociception as well as formalin-provoked c-fos expression. While injection (s.c.) of formalin to the face of mice induced only wiping (indicating pain) by forepaws of the injection side, injection (s.c.) of GNTI to the face elicited grooming and scratching (indicating itch). In contrast to formalin, GNTI did not induce c-fos expression in the trigeminal nucleus suggesting that pain and itch sensations are projected differently along the sensory trigeminal pathway. In short, our main results indicate that a) the scratch-inducing activity of GNTI is not mediated by opioid, histamine or GRP receptors; b) kappa opioid receptors are involved, at least in part, in the inhibition of itch sensation and thus, on the basis of our results, nalfurafine holds promise as a potentially useful antipruritic in human conditions involving itch; and c) agonism at M1 receptors inhibits GNTI-induced scratching therefore the M1 receptor may be a key target for antipruritic drug development.
Temple University--Theses
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Folkesson, Hellstadius Lisa. "Psychobiological functioning in mid-adolescent girls and boys : Linkages to self reported stress, self-esteem and recurrent pain". Doctoral thesis, Stockholms universitet, Psykologiska institutionen, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-107167.
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Among adolescents, the day-to-day functioning of the hypothalamo-pituitary-adrenal-axis (HPA-axis) and of the autonomic nervous system (ANS) and their relationships with stress, subjective health complaints and psychological factors such as self-esteem, studied in naturalistic settings, have been largely unexplored. This thesis aimed to investigate the diurnal activity of the HPA-axis (Studies I & II) in terms of salivary cortisol and the ANS/SNS system (Study III) in terms of salivary alpha-amylase (sAA) in mid-adolescent girls and boys. Additionally, linkages between self-reported stress, self-esteem, recurrent pain and biomarkers were investigated. A further aim was to describe potential differences between girls and boys respectively. Study I showed that both girls and boys exhibited the typical diurnal cortisol profile with high levels in the morning that decreased throughout the day. Girls had higher total cortisol levels, while no differences emerged for measures of the cortisol increase. Study II showed no significant linkages between self-ratings of stress and cortisol. However, stress was associated with recurrent pain in girls. Study III showed that, for girls, both self-esteem and self-reported stress were related to morning levels of both cortisol and sAA, to the diurnal sAA output and to a conjoint measure of amylase over cortisol, AOC. To conclude, the findings suggest that both stress and self-esteem may be linked to different measures of ANS and HPA-axis activity, but also to measures of ANS and HPA-axis dysregulation, particularly among mid-adolescent girls.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript.
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Santos, Daniella Soares dos. "Avaliação do efeito anti-inflamatório do toque terapêutico no modelo experimental de edema de pata induzido por adjuvante completo de Freund em camundongos". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/83/83131/tde-18072011-132224/.
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A dor é um dos sintomas que mais comprometem a produtividade, o bem estar e a qualidade de vida das pessoas, sobretudo dos idosos. Com o crescimento da utilização de Terapias Complementares para o seu tratamento surge a necessidade da realização de pesquisas que forneçam evidências sobre sua indicação e efetividade. Considerando a ampla utilização do Toque Terapêutico (TT) no tratamento complementar da dor decorrente de diversas condições clínicas e as críticas metodológicas aos resultados encontrados pelos autores, esta pesquisa buscou responder ao seguinte questionamento: Quais os efeitos do Toque Terapêutico sobre a dor inflamatória? Para tanto foi realizado um experimento utilizando o modelo de edema de pata induzido por Adjuvante Completo de Freund (CFA) em camundongos machos. A ação anti-inflamatória do TT foi verificada por meio de variação na dor, edema e migração de neutrófilos, antes e após a intervenção, aplicada durante 15 minutos, uma vez ao dia, por quatro dias. Os resultados apontaram aumento significativo no limiar nociceptivo mecânico e aumento na área do edema nas patas dos animais tratados com TT, no segundo dia de aplicação (p ? 0,05). A redução observada na migração de neutrófilos não foi estatisticamente significativa. Concluímos que a redução na dor corrobora os dados obtidos em estudos com seres humanos, com controle do efeito placebo. O modelo de edema de pata induzido por CFA é adequado à investigação experimental dos efeitos do TT sobre a dor inflamatória. Sugerimos a realização de novos experimentos para a elucidação dos mecanismos fisiológicos de ação envolvidos nos achados, sobretudo em decorrência do aumento do edema no grupo tratado com TT.Pain is one of the symptoms that most endanger productivity, welfare and life quality of people, especially the elderly. With the increasing use of Complementary Therapies for its treatment there is the need to conduct studies that provide evidence about its indication and effectiveness. Considering the wide use of Therapeutic Touch (TT) in the adjunctive treatment of pain as a result of various clinical conditions and the methodological criticisms of the authors\' results, this research seeks to answer the following question: What are the effects of the Therapeutic Touch on inflammatory pain? For such, it was conducted an experiment using the model of paw edema induced by Freund\'s Complete Adjuvant (FCA) in male mice. The anti-inflammatory action of TT was verified by means of variation in pain, edema and neutrophilic migration, before and after the intervention, it was applied for 15 minutes once a day for four days. The results showed a significant increase in mechanical nociceptive threshold and an increase in the edema area in the paws of animals treated with TT, in the second day of treatment (p < 0.05). The observed reduction of neutrophilic migration was not statistically significant. It was concluded that the reduction in pain corroborates the data obtained in human studies, with control of the placebo effect. The model of paw edema induced by FCA is suitable for experimental investigation of the effects of TT on inflammatory pain. It is suggested further experiments to elucidate the physiological mechanisms of action underlying the findings, mainly due to the increase of edema in the group treated with TT.
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Hoschouer, Emily Laurel. "Evaluating Sensory Abnormalities in Mice after Spinal Cord Injury and the Anatomical Evidence for Likely Mechanisms". The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261082175.
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Magnusson, Amanda y Sandra Myrberg. "Hör mig, se mig och tro på min smärta : En litteraturstudie om hur patienter med långvarig smärta upplever bemötandet inom vården, samt hur de önskar bli bemötta?" Thesis, Högskolan i Gävle, Avdelningen för hälso- och vårdvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-14228.
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Syfte - Syftet med studien var att utifrån litteraturen beskriva hur patienter med långvarig smärta upplever och vill bli bemötta inom sjukvården samt vilken kvalitet de till studien valda artiklarna hade rörande urval. Metod – 13 artiklar rörande patienter med långvarig smärta sammanställdes i en litteraturstudie. Artiklarna söktes i Pubmed samt Cinahl. Huvudresultat – I resultatet framkom det att patienter upplever både positiva och negativa upplevelser gällande bemötande i vården. Negativa upplevelser som beskrevs var exempelvis att personalen inte lyssnade på patienterna samt att de kände sig misstrodda. Patienterna beskrev positiva upplevelser när personalen tog sig tid till att lyssna och skapa en förståelse. Patienterna upplevde och önskade att det kunde möjliggöra ett ökat samarbete mellan personal och patient så att en ökad förståelse för patienternas smärta kunde skapas. Slutsats – Det förekom både positiva och negativa upplevelser hos patienter med långvarig smärta av bemötande inom vården. För att sträva mot positiva upplevelser krävs ett samarbete samt att alla parter blir accepterade som en del av vården. Personalen behöver mer utbildning och riktlinjer för att kunna hantera smärta hos patienter. Studien visar på viktiga aspekter gällande bemötande som kan öka förståelsen för patienter med långvarig smärta.
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Bernal, Laura [Verfasser], Katharina [Akademischer Betreuer] Zimmermann y Katharina [Gutachter] Zimmermann. "Characterization of peripheral nociceptors during chronic secondary pain: experimental studies in mice / Laura Bernal ; Gutachter: Katharina Zimmermann ; Betreuer: Katharina Zimmermann". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/1228214697/34.
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Dandoush, Abdulhalim. "L'Analyse et l'Optimisation des Systèmes de Stockage de Données dans les Réseaux Pair-à-Pair". Phd thesis, Université de Nice Sophia-Antipolis, 2010. http://tel.archives-ouvertes.fr/tel-00470493.
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Cette thèse évalue les performances de systèmes de stockage de données sur des réseaux de pairs. Ces systèmes reposent sur trois piliers: la fragmentation des données et leur dissémination chez les pairs, la redondance des données afin de faire face aux éventuelles indisponibilités des pairs et l'existence d'un mécanisme de recouvrement des données perdues ou temporairement indisponibles. Nous modélisons deux mécanismes de recouvrement des données par des chaînes de Markov absorbantes. Plus précisément, nous évaluons la qualité du service rendu aux utilisateurs en terme de longévité et de disponibilité des données de chaque mécanisme. Le premier mécanisme est centralisé et repose sur l'utilisation d'un serveur pour la reconstruction des donnée perdus. Le second est distribué : la reconstruction des fragments perdus met en oeuvre, séquentiellement, plusieurs pairs et s'arrête dès que le niveau de redondance requis est atteint. Les principales hypothèses faites dans nos modèles sont validées soit par des simulations soit par des traces réelles recueillies dans différents environnements distribués. Pour les processus de téléchargement et de recouvrement des données nous proposons un modèle de simulation réaliste qui est capable de prédire avec précision le comportement de ces processus mais le temps de simulation est long pour de grands réseaux. Pour surmonter cette restriction nous proposons et analysons un algorithme efficace au niveau flux. L'algorithme est simple et utilise le concept de (min-max). Il permet de caractériser le temps de réponse des téléchargements en parallèle dans un système de stockage distribué.
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Jun, Yong In. "Designing and implementing the paid staff development program through mentoring". Theological Research Exchange Network (TREN), 2005. http://www.tren.com/search.cfm?p049-0452.
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Cholez, Thibault. "Supervision des réseaux pair à pair structurés appliquée à la sécurité des contenus". Phd thesis, Université Henri Poincaré - Nancy I, 2011. http://tel.archives-ouvertes.fr/tel-00608907.
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L'objectif de cette thèse est de concevoir et d'appliquer de nouvelles méthodes de supervision capables d'appréhender les problèmes de sécurité affectant les données au sein des réseaux P2P structurés (DHT). Ceux-ci sont de deux types. D'une part les réseaux P2P sont utilisés pour diffuser des contenus illégaux dont l'activité est difficile à superviser. D'autre part, l'indexation des contenus légitimes peut être corrompue (attaque Sybil). Nous proposons tout d'abord une méthode de supervision des contenus basée sur l'insertion de sondes et le contrôle du mécanisme d'indexation du réseau. Celle-ci permet d'attirer l'ensemble des requêtes des pairs pour un contenu donné, puis de vérifier leur intention en générant des appâts très attractifs. Nous décrivons ainsi les faiblesses du réseau permettant la mise en œuvre de notre méthode en dépit des protections existantes. Nous présentons les fonctionnalités de notre architecture et en évaluons l'efficacité sur le réseau P2P KAD avant de présenter un déploiement réel ayant pour but l'étude des contenus pédophiles. Nous considérons ensuite la sécurité des données indexées dans une DHT. Nous supervisons le réseau KAD et montrons que celui-ci est victime d'une pollution particulièrement néfaste affectant 2/3 des fichiers mais aussi de nombreuses attaques ciblées affectant la sécurité des contenus stockés. Nous proposons un moyen de détecter efficacement cette dernière attaque en analysant la distribution des identifiants des pairs autour d'une référence ainsi qu'une contre-mesure permettant de protéger les pairs à un coût négligeable. Nous terminons par l'évaluation de la protection au sein de réseaux P2P réels.
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Gonzalez-Liencres, Cristina [Verfasser], Martin [Gutachter] Brüne y Albert [Gutachter] Newen. "Factors modulating empathy for pain in mice and humans / Cristina Gonzalez-Liencres ; Gutachter: Martin Brüne, Albert Newen ; International Graduate School of Neuroscience". Bochum : Ruhr-Universität Bochum, 2015. http://d-nb.info/1212661958/34.
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JÃnior, Roberto CÃsar Pereira Lima. "Antinociceptive effect of the mixture of pentacyclic triterpenes alpha- and beta- amyrin in models of visceral nociception in mice". Universidade Federal do CearÃ, 2005. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorProtium heptaphyllum March (Burseraceae), a medicinal plant commonly found in the Amazon and in the Northeast regions of Brazil, releases an oil-resin rich in pentacyclic triterpenes, such as the binary mixture of alpha- and beta- amyrin, that manifests antiinflamatory, antinociceptive and gastroprotective properties. This work was aimed to evaluate the antinociceptive effect of the alpha- and beta- amyrin mixture in the cyclophosphamide (400 mg/kg), acetic acid (0,6%, 10mL/kg, i.p.) and mustard oil-induced visceral nociception models in mice and to establish the likely mechanism(s) of action. In the cyclophosphamide-induced visceral pain model, pretreatment of mice with triterpene mixture at the oral doses of 10, 30 and 100 mg/kg significantly reduced (p<0.001) the pain-related behavioral expression time (59,7; 75,5 e 92,3%, respectively, versus the cyclophosphamide-treated group 12,25 +/- 2,98 min) in a dose-dependent manner. Suppression of visceral painârelated behaviors was also evidenced to the triterpenoid mixture (10 mg/kg) in the intraperitoneal acetic acid- and intracolonically injected mustard oil-induced test models of visceral nociception 50,4% e 61,1%, respectively compared to the acetic acid-treated group (42,33 +/- 3,78 abdominal constrictions/20 min) in the writhing test and to the control in the mustard oil (0,75%, 50 mcL/animal) experiment (39,28 +/- 3,26). In these tests, the maximal suppression of visceral pain was observed at 10 mg/kg. The possible mechanisms involved in the antinociceptive action of alpha- and beta- amyrin (10 mg/kg) were analyzed in the mustard oil-induced visceral pain model. In the evaluation of the opioid receptor involvement, both the triterpene mixture and morphine (5 mg/kg, s.c.) effectively inhibited (p<0.001) the number of pain-related behaviors, which could be significantly reversed by pretreatment of animals with an opioid antagonist naloxona (2mg/kg, i.p.), suggesting the opioid participation in the alpha- and beta- amyrin mechanism of action. In the study of the alpha2-adrenoreceptor involvement, the triterpene mixture as well as clonidine (0.1 mg/kg, i.p.), a known alpha2 agonist, inhibited (p<0.001) the nociceptive behavioral expression. However, when the animals were pretreated with yohimbine, an alpha2-adrenoreceptor antagonist, only the inhibitory action of clonidine was reversed, suggesting the non-participation of alpha2- adrenoreceptor in the antinociceptive action of alpha- and beta- amyrin. In the evaluation of TRPV1 receptor involvement, mice pretreated with either the alpha- and beta- amyrin, ruthenium red, a TRPV1 non-competitive antagonist, (3 mg/kg, s.c.) or their combination induced a significant and similar inhibition (p<0.001) of the number of nociceptive behaviors. The degree of inhibition with no potentiation or antagonism suggests that alpha- and beta- amyrin may act as a TRPV1 non-competitive antagonist, like ruthenium red. In order to evaluate a possible sedative, motor impairment and motor incoordination effects related to alpha- and beta- amyrin, the penthobarbitone-induced sleeping time, open-field and rota-rod tests were performanced, respectively. The data indicated that the treatment of animals with the alpha- and beta- amyrin mixture (10 mg/kg) was unable to cause sedation, motor impairment or motor incoordination effects (p>0.05), being even able to reverse (p<0.05) a mustard oil-induced motor impairment in the open field test. The results taken together strongly suggest the therapeutic potential of alpha- and beta- amyrin in oblitering visceral nociception through the mechanisms that involve the opioids and TRPV1 receptors.
O Protium heptaphyllum March. (Burseraceae), uma planta medicinal encontrada na regiÃo AmazÃnica e Nordeste do Brasil, produz uma resina rica em triterpenos pentacÃclicos, como a mistura binÃria alpha- e beta- amirina, que apresentam atividade antiinflamatÃria, gastroprotetora e antinociceptiva. Este trabalho objetivou investigar a atividade antinociceptiva de alpha- e beta- amirina em modelos de dor visceral induzida por ciclofosfamida, Ãcido acÃtico e Ãleo de mostrada em camundongos, alÃm dos possÃveis mecanismos de aÃÃo envolvidos. No modelo de nocicepÃÃo visceral induzida por ciclofosfamida (400 mg/kg, i.p.), a mistura de triterpenos nas doses de 10, 30 e 100 mg/kg, v.o., reduziu (p<0,001) de forma dose-dependente o tempo de expressÃo dos comportamentos relacionados à dor visceral (59,7; 75,5 e 92,3%, respectivamente, versus o controle ciclofosfamida 12,25 +/- 2,98 min). Realizou-se o estudo nos modelos de contorÃÃes abdominais induzidas por Ãcido acÃtico (0,6%, 10mL/kg, i.p.) e dor visceral induzida por Ãleo de mostarda (0,75%, 50 mcL/animal) intracolÃnico. Os resultados indicaram uma inibiÃÃo do nÃmero de comportamentos de dor expressos pelos animais, sendo o maior nÃvel de inibiÃÃo (p<0,001) encontrado na dose de 10 mg/kg da alpha- e beta- amirina 50,4% e 61,1% comparados respectivamente ao controle Ãcido acÃtico (42,33 +/- 3,78 contorÃÃes/20min) no teste de contorÃÃes abdominais e ao controle Ãleo de mostarda (39,28 +/- 3,26) no modelo de dor visceral por Ãleo de mostarda. Para o estudo do possÃvel mecanismo de aÃÃo de alpha- e beta- amirina foi utilizada a dose de 10 mg/kg da mistura de triterpenos no modelo de nocicepÃÃo por Ãleo de mostarda. Na avaliaÃÃo da participaÃÃo do sistema opiÃide, a mistura dos triterpenos e a morfina (5 mg/kg, s.c.) inibiram significativamente (p<0,001) o nÃmero de comportamentos de dor expressos, havendo uma reversÃo da antinocicepÃÃo (p<0,05) quando prÃ-tratados com naloxona (2 mg/kg, i.p.), sugerindo a participaÃÃo opiÃide no mecanismo da alpha- e beta- amirina. No estudo do envolvimento do sistema adrenÃrgico, a mistura de triterpenos e a clonidina (0,1 mg/kg, i.p.), um agonista alpha2-adrenÃrgico, inibiram (p<0,001) a expressÃo dos comportamentos nociceptivos. PorÃm, com o prÃ-tratamento com ioimbina, um antagonista alpha2, houve reversÃo (p<0,05) da antinocicepÃÃo induzida pela clonidina, mas nÃo da alpha- e beta- amirina, sugerindo o nÃo envolvimento deste receptor na antinocicepÃÃo da mistura de triterpenos. No estudo do envolvimento do receptor TRPV1, o prÃ-tratamento dos animais com alpha- e beta- amirina, vermelho de rutÃnio (3 mg/kg, s.c.), um antagonista nÃo competitivo deste receptor, ou com a combinaÃÃo da mistura de triterpenos com vermelho de rutÃnio, houve uma inibiÃÃo (p<0,001) semelhante, para todos os tratamentos, dos comportamentos de dor. A nÃo potencializaÃÃo, ou antagonismo, do efeito antinociceptivo de alpha- e beta- amirina pelo vermelho de rutÃnio sugere que a mistura atue como um antagonista nÃo-competitivo TRPV1. Para avaliar a existÃncia de um efeito sedativo, de um impedimento locomotor ou de uma incoordenaÃÃo motora, foram utilizados os testes do tempo de sono induzido por pentobarbital, teste do campo aberto e o teste do rota rod, respectivamente. Os dados indicaram que o tratamento com a mistura de triterpenos (10 mg/kg) nÃo induziu (p>0,05) sedaÃÃo, impedimento locomotor ou incoordenaÃÃo motora nos animais, sendo ainda capaz de reverter (p<0,05) o impedimento locomotor induzido pelo Ãleo de mostarda no teste do campo aberto. Em conjunto os dados revelaram a efetividade da mistura de alpha- e beta- amirina em modelos de nocicepÃÃo visceral possivelmente envolvendo receptores opiÃides e TRPV1.
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Mellor, Fiona E. "An evaluation of passive recumbent quantitative fluoroscopy to measure mid-lumbar intervertebral motion in patients with chronic non-specific low back pain and healthy volunteers". Thesis, Bournemouth University, 2014. http://eprints.bournemouth.ac.uk/22421/.
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Introduction: The biomechanical model of back pain has failed to find distinct relationships between intervertebral movement and pain due to limitations and variation in methods, and errors in measurement. Quantitative fluoroscopy (QF) reduces variation and error and measures dynamic intervertebral motion in vivo. This thesis used recumbent QF to examine continuous mid-lumbar intervertebral motion (L2 to L5) in patients with assumed mechanical chronic non-specific low back pain (CNSLBP) that had been clinically diagnosed. It aimed to develop kinematic parameters from the continuous data and determine whether these could detect subtle mechanical differences by comparing this to data obtained from healthy volunteers. Methods: This was a prospective cross sectional study. Forty patients with CNSLBP (age 21 to 51 years), and 40 healthy volunteers matched for gender, age and body mass index underwent passive recumbent QF in the coronal and sagittal planes. The patient group completed questionnaires for pain and disability. Four kinematic parameters were developed and compared for differences and diagnostic accuracy. Reference intervals were developed for three of the parameters and reproducibility of two were assessed. The radiation dose was compared to lumbar spine radiographs and diagnostic reference levels were established. Finally, relationships between patient’s pain and disability and one of the kinematic parameters (continuous proportional motion CPM) were explored. Results: Reproducibility was high. There were some differences in the coronal plane and flexion for each kinematic parameter, but no consistency across segments and none had high diagnostic accuracy. Radiation dose for QF is of the same magnitude as radiographs, and there were no associations between patient characteristics of pain and disability and CPM. Conclusion: Although the kinematic differences were weak, they indicate that biomechanics may be partly responsible for clinically diagnosed mechanical CNSLBP, but this is not detectable by any one kinematic parameter. It is likely that other factors such as loading, central sensitisation and motor control may also be responsible for back pain that is considered mechanical. QF is easily adapted to clinical practice and is recommended to replace functional radiography, but further work is needed to determine which kinematic parameters are clinically useful.
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Al-Shehri, M. A. S. "Analysis of the behavioural effects of barley and sertraline in two in-vivo models of stress.Anti-depressant and anti-nociceptive effects of barley in mice and sertraline effects on anxiety in the offspring of prenatally-stressed rats". Thesis, University of Bradford, 2015. http://hdl.handle.net/10454/14131.
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To prove the post-natal depression model, the antidepressant sertraline, was assessed in rat mothers (n=14) divided into Prenatally Stressed (PS) and Non-Stressed (NS) groups. The data failed to support the hypothesis that ‘the progeny of 10mg of sertraline-treated PS mothers displayed less anxiety than the progeny of vehicle-treated PS mothers’.
The forced swim test (FST) was used to examine depressive-like behaviour in mice. Barley successfully increased mobility in mice exposed to the FST. Barley was antidepressant at low doses (0.8g/kg and upwards) if used subchronic; and at high doses(6.4g/kg and 12.8g/kg) if used acutely;(n=113,56acute,57 subchronic- treated).
Barley (6.4g/kg) was also able to alleviate the depressive-behaviour in mice induced by the Reserpine Test (n=114, 58 reserpinised, 56 non-reserpinised) and Social ‘Defeat’ Test (n=24, 8 vehicle undefeated, 8 barley defeated, 8 vehicle defeated mice).
To confirm that the anti-depressant effects of barley(6.4g/kg) were not simply due to increased locomotor activity in the FST, an Open Field Test(OFT) was undertaken (n=14,7 vehicle, 7 barley). Barley had no effect on locomotor activity and also caused no significant changes in weight (n=16, 8vehicle, 8 barley).
In mice,Barley(6.4g/kg) significantly delayed the tremorogenic effects of Physostigmine (n=18, 6 control,6 Physostigmine, 6 Physostigmine with barley); reduced bradykinesia induced by reserpine (n=18,6 control, 6 vehicle, 6 barley treated);and was analgesic in nociception tests (n =20, 5 control, 5 barley, 5 pain, 5 pain with barley).
Overall, barley was seen to have many useful properties, though its effect in PND remains to be assessed.Saudi Cultural Bureau in London; Medical Services Department of the Ministry of Interior in Riyadh, Saudi Arabia.
The full text of this thesis is embargoed indefinitely.
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Karl, Franziska [Verfasser], Claudia Gutachter] Sommer y Thomas [Gutachter] [Dandekar. "The role of miR-21 in the pathophysiology of neuropathic pain using the model of B7-H1 knockout mice / Franziska Karl ; Gutachter: Claudia Sommer, Thomas Dandekar". Würzburg : Universität Würzburg, 2017. http://d-nb.info/114951034X/34.
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Al-Shehri, M. A. S. "Analysis of the behavioural effects of barley and sertraline in two in-vivo models of stress : anti-depressant and anti-nociceptive effects of barley in mice and sertraline effects on anxiety in the offspring of prenatally-stressed rats". Thesis, University of Bradford, 2015. http://hdl.handle.net/10454/14131.
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To prove the post-natal depression model, the antidepressant sertraline, was assessed in rat mothers (n=14) divided into Prenatally Stressed (PS) and Non-Stressed (NS) groups. The data failed to support the hypothesis that ‘the progeny of 10mg of sertraline-treated PS mothers displayed less anxiety than the progeny of vehicle-treated PS mothers’. The forced swim test (FST) was used to examine depressive-like behaviour in mice. Barley successfully increased mobility in mice exposed to the FST. Barley was antidepressant at low doses (0.8g/kg and upwards) if used subchronic; and at high doses(6.4g/kg and 12.8g/kg) if used acutely;(n=113,56acute,57 subchronic- treated). Barley (6.4g/kg) was also able to alleviate the depressive-behaviour in mice induced by the Reserpine Test (n=114, 58 reserpinised, 56 non-reserpinised) and Social ‘Defeat’ Test (n=24, 8 vehicle undefeated, 8 barley defeated, 8 vehicle defeated mice). To confirm that the anti-depressant effects of barley(6.4g/kg) were not simply due to increased locomotor activity in the FST, an Open Field Test(OFT) was undertaken (n=14,7 vehicle, 7 barley). Barley had no effect on locomotor activity and also caused no significant changes in weight (n=16, 8vehicle, 8 barley). In mice,Barley(6.4g/kg) significantly delayed the tremorogenic effects of Physostigmine (n=18, 6 control,6 Physostigmine, 6 Physostigmine with barley); reduced bradykinesia induced by reserpine (n=18,6 control, 6 vehicle, 6 barley treated);and was analgesic in nociception tests (n =20, 5 control, 5 barley, 5 pain, 5 pain with barley). Overall, barley was seen to have many useful properties, though its effect in PND remains to be assessed.
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Gai, Bibiana Mozzaquatro. "3-(4-Fluorofenilselenil)-2,5 difenilselenofeno produz ação do tipo-antidepressiva em diferentes modelos de depressão em camundongos". Universidade Federal de Santa Maria, 2014. http://repositorio.ufsm.br/handle/1/4478.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoSelenophenes are a promising class of heterocyclic selenium-containing compounds presenting important pharmacological properties. Based on selenium well-described role on mood regulation and since depression is a serious and prevalent disease affecting a wide part of the world s population, the main aim of this work was to investigate de antidepressant-like action of 3-(organosseleno)-2,5-diphenyl-selenophenes in mice. The pharmacological effect of these compounds was analyzed by using different experimental models of depression and results were shown by three scientific articles. Firstly, results of Article 1 demonstrated the antidepressant-like action of five selenophene compounds. H-DPS, CH3-DPS, Cl-DPS, FDPS and CF3-DPS reduced the total immobility time of mice evaluated in the forced swimming test (FST), which seems to be related to their chemical structure. The antidepressant-like action of F-DPS was observed at lower doses than other selenophenes e involves the phosphorylation of extracellular-signal-regulated kinases (ERK), whose signaling pathway is commonly modulated by antidepressant drugs. Articles 2 and 3 investigated the pharmacological effect of F-DPS in mouse models of depression induced by both neuropathic pain and chronic corticosterone administration, respectively. Both the acute and subchronic treatments with F-DPS significantly reversed the depression-related behavior produced by partial sciatic nerve ligation (PSNL), whereas pain sensibility was only reduced after repeated treatment with this selenophene. Besides, repeated administration of the glucocorticoid hormone corticosterone induced behavior, endocrinal and neurochemical changes similar to those clinically observed in depression, which were also reversed by treatment of animals with F-DPS. Based on these data, the mechanisms of pharmacological action of this organoselenium compound seem to involve, at least in part, a modulation of glutamatergic and serotonergic systems, the hypothalamic-pituitary-adrenal (HPA) axis regulation and changes on neuronal pathways related to the synaptic plasticity. Together, the results shown in this thesis suggest the pharmacological properties of selenophene compounds, particularly F-DPS, as an interesting tool in the study and development of future therapies for depressive disorders.
Os selenofenos são uma classe de compostos heterocíclicos aromáticos com promissoras propriedades farmacológicas. Tendo em vista o importante papel do selênio na regulação do humor e a grande prevalência populacional das doenças depressivas, o principal objetivo deste estudo foi investigar a ação do tipo antidepressiva de 3-(organosseleno)-2,5-difenilselenofenos em camundongos. A fim de atender a este objetivo, o efeito farmacológico destes compostos foi analisado pelo uso de diferentes modelos experimentais de depressão e os resultados foram apresentados em três artigos científicos. Primeiramente, os resultados do Artigo 1 demonstraram a ação do tipo antidepressiva de cinco representantes da classe dos selenofenos. Os compostos H-DPS, CH3-DPS, Cl-DPS, F-DPS e CF3-DPS reduziram significantemente o tempo total de imobilidade de camundongos avaliados no teste do nado forçado (TNF), efeito este que parece estar relacionado às suas estruturas químicas. A ação do tipo antidepressiva do F-DPS foi observada em menores doses em comparação aos outros selenofenos e envolve a fosforilação da proteína quinase regulada por sinal extracelular (ERK), cuja via de sinalização é comumente modulada por drogas antidepressivas. Os Artigos 2 e 3 investigaram o efeito farmacológico do F-DPS em modelos crônicos de depressão induzida pela dor neuropática e pela administração crônica de corticosterona em camundongos, respectivamente. Tanto o tratamento agudo como o subcrônico com F-DPS reverteram significantemente o comportamento do tipo depressivo produzido pela ligação parcial do nervo ciático (LPNC), enquanto que a sensibilidade à dor foi reduzida somente após a terapia prolongada com este composto. Por sua vez, a administração repetida do hormônio glicocorticoide corticosterona induziu alterações comportamentais, endócrinas e neuroquímicas similares às observadas clinicamente na depressão e que também foram revertidas pelo tratamento dos animais com F-DPS. Com base nestes resultados, acredita-se que os mecanismos de ação farmacológica deste composto orgânico de selênio envolvam, pelo menos em parte, a modulação dos sistemas glutamatérgico e serotonérgico, a regulação da atividade do eixo hipotálamo-pituitária-adrenal (HPA) e modificações em vias neuronais relacionadas à plasticidade sináptica. Juntos os resultados apresentados nesta tese de doutorado sugerem que o estudo das propriedades farmacológicas de compostos selenofenos, particularmente do F-DPS, parece ser interessante no desenvolvimento de futuras terapias para o tratamento dos distúrbios neurológicos relacionados às doenças depressivas.
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Ceredig, Rhian Alice. "Delta opioid receptor expression in various models of chronic clinical conditions". Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ100/document.
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Les travaux présentés ici visent à déterminer l’implication du récepteur aux opioïdes delta dans des modèles de pathologies chroniques telles que la douleur chronique et l’administration d’opiacés. Nous avons mis en oeuvre des approches génétiques, d’imagerie et comportementales afin de décrire précisément les changements de distribution neuronale du récepteur aux opioïdes delta dans un modèle de douleur neuropathique et dans l’administration chronique de morphine, dans les tissus du système nerveux central et périphérique. Nous avons étudié l’implication des récepteurs aux opioïdes delta périphériques dans l’effet thérapeutique de traitements antiallodyniques dans un modèle de douleur neuropathique, et examiné le rôle des récepteurs aux opioïdes delta dans la sensibilité viscérale et dans les effets thérapeutiques de la Prégabaline. Nos travaux ont permis de décrire précisément les changements et l’implication du récepteur aux opioïdes delta dans plusieurs modèles de pathologies chroniques, dans le but de dégager des pistes thérapeutiques futuresIn this work, we used genetic, imaging and behavioral approaches to describe the changes which the distribution of the delta opioid receptor underwent in models of clinical conditions such as neuropathic pain and chronic opioid exposure, at the peripheral and supraspinal levels. We investigated the role of peripheral delta opioid receptor populations in the antiallodynic effect of chronic treatment by antidepressant and β2 agonist molecules in a model of neuropathic pain. We also described the implication of delta opioid receptors in visceral sensitivity, and their involvement in the pain-relieving effects of Pregabalin in a model of neuropathic pain. Thus, we have brought insight as to the role of delta opioid receptors in these various clinical conditions, and thoroughly described the distribution changes; which may lead the way to therapeutic strategies to treat chronic pain or drug addiction
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Costa, Vinícius Pelarin do Nascimento. "Empatia em camundongos: avaliação do papel da amídala, insula e córtex cingulado anterior na nocicepção em camundongos expostos ao teste de contorções abdominais". Universidade Federal de São Carlos, 2014. https://repositorio.ufscar.br/handle/ufscar/1376.
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Previous issue date: 2014-05-09Universidade Federal de Minas Gerais
Empathy can be defined as the capacity for perceive emotional signals from others. Among these signals, the ability to perceive pain has clear adaptive and evolutionary value. Pain can be defined as a subjective experience that includes sensorial, emotional and cognitive components. Evidence has emphasized the role of amygdala, anterior cingulate cortex (ACC) and insula in modulation of pain and empathy. Research indicates the capacity of rodents to express empathy to a conspecific in pain or suffering. Works from literature and finds from our laboratory demonstrated that living together with a cagemate is able to alter the nociceptive behavior in mice. However, there are no works evidencing if occur alterations in nociception by living together with a cagemate with chronic pain and which encephalic structures would be involved in this modulation. To overcome this, male Swiss-albino mice were housed in groups or in pairs. The role of amygdala, ACC and insula are accessed by non-selective inactivation with cobalt chloride (CoCl2). Mice housed in groups (Experiment 1), aging 6-8 weeks, underwent a stereotaxic surgery. 4 to 5 days after surgery, these animals received saline or CoCl2 microinjection, and, after 10 minutes, they were submitted to the writhing test during 5 minutes (acetic acid 0.6%, i.p., nociceptive stimulus). On the dyads (Experiment 2), animals lived together for 28 days since weaning. On the 14th day, one animal of each pair were submitted to a sciatic nerve constriction (SNC animal) or not (sham animal). On the 24th day, the cagemate underwent a stereotaxic surgery, and, on the 28th day, they were submitted to the writhing test after microinjection of saline or CoCl2, like the procedure described to Experiment 1. To Experiment 1 were utilized Student s t test to independent samples; to Experiment 2 were utilized two-way analysis of variance (ANOVA; living together x treatment). Duncan s multiple range tests were utilized as post hoc. A p value of 0.05 or less was required for significance in both experiments. In Experiment 1, inactivation of the amygdala increased the number of writhing, while inactivation of ACC and insula did not alter this measure, suggesting a distinct modulatory role of these structures on the sensorial compound of pain. Our results demonstrated that for the mice that lived in groups, while inactivation of the ACC and insula did not change writhing, inactivation of amygdala increased it, suggesting a distinct modulatory role of these structures on sensory component of pain in the writhing test. In Experiment 2, living together with a SNC-cagemate increased writhing on the pair, suggesting that this experience activates the circuitry of neural representation of pain on the observer mouse (state of priming ). Thus, when this animal experienced nociception, its response was exacerbated. In this condition, inactivation of insula and amygdala produces opposite results, i.e., decreased and increased in contortions in those animals that lived together with a SNC animal, respectively. ACC inactivation did not alter writhing behavior. In this sense, our results suggest a different modulatory role of these structures on cognitive, affective-emotional and sensorial components of pain, and on empathy for pain.
Sob uma perspectiva evolucionista, a empatia é expressa pela capacidade de captar sinais emocionais nos outros. Neste sentido, a habilidade em perceber a dor também possui valor claramente adaptativo e evolutivo. A dor pode ser definida como uma experiência subjetiva que inclui componentes sensoriais, afetivo-emocionais e cognitivos. Evidencias apontam para o papel da amídala, córtex cingulado anterior (CCA) e insula na modulação da dor e da empatia. Estudos indicam para a capacidade de roedores em apresentarem empatia frente à dor ou ao sofrimento de seus coespecíficos. Trabalhos da literatura e do nosso grupo demonstram que a convivência em pares é capaz de alterar bidirecionalmente a resposta nociceptiva em camundongos. Entretanto, nenhum estudo havia ainda evidenciado se ocorrem alterações nociceptivas devido à convivência com um coespecífico em quadro de dor crônica, e quais estruturas encefálicas estariam envolvidas nessa modulação. Neste sentido, camundongos machos Suiço-albinos foram alojados em grupos ou em duplas para avaliação do papel da amídala, insula e córtex cingulado anterior por meio de inativação com cloreto de cobalto (CoCl2). Os animais alojados em grupo (Experimento 1), ao atingirem idade entre 6-8 semanas, passaram por cirurgia estereotáxica. De 4 à 5 dias após a cirurgia, esses animais receberam microinjeção de salina ou CoCl2 e, após 10 minutos, foram submetidos ao teste de contorções abdominais (ácido acético 0,6%, i.p., estímulo nociceptivo) durante 5 minutos. Nas duplas (Experimento 2), os animais conviveram por um período de 28 dias após o desmame. No 14º dia, um animal de cada par foi submetido à cirurgia de constrição do nervo ciático (animal CNC) ou não (animal sham). No 24º dia, o camundongo que conviveu com o animal CNC ou animal sham passou por uma cirurgia estereotáxica, e, no 28º dia, foi submetido ao teste de contorções abdominais, após microinjeção de salina ou CoCl2, conforme Experimento 1. Para o Experimento 1 foi utilizado o teste t de Student para amostras independentes; no Experimento 2 foi utilizada a análise de variância (ANOVA) de dois fatores (convívio x tratamento). O post hoc utilizado foi o teste de comparações múltiplas de Duncan. Os valores de p menores ou iguais a 0,05 foram considerados como significativos nos dois experimentos. No Experimento 1, a inativação da amídala aumentou o número de contorções, enquanto a inativação do CCA e da insula não alterou esse parâmetro, sugerindo um papel modulatório distinto dessas estruturas no componente sensorial da dor para o teste de contorções. No experimento 2, o convívio com um animal CNC aumentou o número de contorções no parceiro, sugerindo que essa convivência causou ativação dos circuitos de representatividade neural da dor no camundongo observador (state of priming ). Dessa forma, quando esse animal experiencia nocicepção, sua resposta é exacerbada. Nessa condição, a inativação da insula e amídala produziu resultados opostos, ou seja, diminuição e aumento das contorções naqueles animais que conviveram com o animal CNC, respectivamente. A inativação do CCA não alterou o número de contorções. Nesse sentido, nossos resultados sugerem um papel modulatório distinto dessas estruturas nos componentes cognitivo, afetivo-emocional e sensorial da dor, e na empatia para a dor.
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Albertazzi, Davide. "Utilizzo degli esercizi di stabilizzazione del core per il miglioramento della sintomatologia dolorosa nei soggetti con chronic non-specific low back pain: revisione basata sulle evidenze". Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2019.
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Obiettivo: Confrontare gli esercizi di stabilizzazione del core con esercizi generici e globali per la gestione della sintomatologia dolorosa e della disabilità a breve, medio e lungo termine, nei soggetti con chronic non-specific LBP.
Contesto: Il Low Back Pain (LBP) è un disordine multifattoriale ad alta prevalenza. L’intervento più comune in questi casi è quello conservativo fisioterapico. Dopo le ricerche sull’instabilità lombare condotte da Panjabi e colleghi si è sviluppato il concetto di core stability. Negli anni, molti clinici hanno adottato questa pratica rendendola famosa ma in letteratura non si è ancora giunti alla conclusione di quale sia l’approccio più adatto al trattamento del LBP.
Materiali e metodi: La ricerca è stata condotta su PubMed, Cochrane Library e PEDro tra febbraio 2019 e agosto 2019. Sono state incluse solo revisioni sistematiche con meta-analisi, pubblicate negli ultimi 10 anni e che confrontassero esercizi di stabilizzazione del core ed esercizi generici nel miglioramento di dolore e disabilità a breve, medio e lungo termine, in soggetti con LBP cronico e aspecifico.
Risultati: Nel follow-up a breve termine tutte e 4 le meta-analisi hanno trovato differenze statisticamente significative a favore degli esercizi di stabilizzazione del core rispetto ad esercizi generici nel miglioramento del dolore e della disabilità. Nel follow-up a medio termine solamente 2 dei 4 studi trovano differenze significative a favore del primo gruppo. Nel follow-up a lungo termine non sono state registrate differenze statisticamente significative tra i due approcci per il miglioramento del dolore mentre solo uno studio trova differenze statisticamente significative circa la disabilità.
Conclusioni: Una differenza statisticamente significativa ha favorito gli esercizi di stabilizzazione del core rispetto ad esercizi generici nel diminuire dolore e disabilità a breve termine. Tuttavia, nessuna differenza significativa è stata osservata a lungo termine.
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Langaro, Fabíola. "(Des)construções do masculino e do feminino na relação de mulheres-mães com seus filhos e filhas". reponame:Repositório Institucional da UFSC, 2012. http://repositorio.ufsc.br/xmlui/handle/123456789/95686.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Programa de Pós-graduação em Psicologia, Florianópolis, 2011Made available in DSpace on 2012-10-26T04:58:15Z (GMT). No. of bitstreams: 1 290727.pdf: 1077773 bytes, checksum: 96970cb96cee8b2d0036321c0a43f2ed (MD5)
As experiências da maternidade e da paternidade sofrem alterações vinculadas a questões econômicas, culturais e sociais. Entretanto, as experiências de homens/pais e mulheres/mães não acontecem sem conflitos, pois, a tradição marcada pela hierarquia e por modelos pré-determinados sobre o homem e a mulher atravessam os modos de subjetivação. Neste trabalho buscamos problematizar a experiência de mulheres-mães na relação construída com seus filhos e filhas a partir da elaboração subjetiva dos lugares sociais/sexuais frente às normas calcadas na heteronormatividade e no binarismo que dispõe em pares opostos e hierárquicos o masculino e o feminino, o heterossexual e o homossexual, entre outros. Foram realizadas cinco entrevistas com mulheres-mães e suas falas foram consideradas como texto, na perspectiva derridiana. A partir da estratégia da desconstrução foi realizada a leitura destas falas-textos buscando as inconstâncias e aberturas e apontando seus elementos silenciosos, seu jogo de oposições e dicotomias, essências e hierarquias. Consideramos nos textos o jogo de forças atuante entre o desvelamento da desconstrução e o esforço de barreira operado pela metafísica da presença, explicitando o embate entre uma operação feminina e uma operação masculina que nos constitui, a todos e todas. Este embate, continuamente operante, abre os espaços e as brechas para a construção de práticas que embaralhem os limites que demarcam o que é estar na norma ou fora dela, ampliando as possibilidades de experiências subjetivas.
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Garcia, Ana Carolina Falcone. "Da relação pai-filha à profissional mulher Um estudo qualitativo com mulheres adultas jovens, numa abordagem junguiana". Pontifícia Universidade Católica de São Paulo, 2006. https://tede2.pucsp.br/handle/handle/15535.
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Previous issue date: 2006-10-06This paper aimed at showing the relationship father-daughter in attempt to understand the way this relationship affects the development of a woman in her career. In this sense, we looked forward both to some characteristics of this relationship and the attitude of a young adult woman in her professional work. The analysis also permitted the discussion about these characteristics whether they were attached to the image of the father or to the parental complex, thus, affecting or not the behavior of a woman in her professional environment. In addition, we also examined a partial integration of the animus in this crucial moment of the life of a woman. The qualitatative method was employed in this search and semi-structured interviews were conducted with six young adult women. The participants´ mean age was between 28 and 35 years of age. The results indicate that the relationship father-daughter is significant for the women both in terms of development of affection as well as in terms of guidance to her career. Anyway, we realized that the majority of women are still attached to one or other parental complex, so, while the influence of the father is important at the moment of choosing a career, conversely, the representation of the mother works as an anti-model . We also realized that the dimension of the animus of action influences most of our interviewees. In this way, the animus has been partially integrated in the life of a woman, playing an important role in this particularly period of her life
Esta pesquisa procurou compreender o relacionamento pai-filha, e suas conseqüências no desenvolvimento da mulher no trabalho profissional. Buscou-se desenvolver de que forma determinadas características dessa relação refletem-se no posicionamento profissional das mulheres adultas jovens, bem como, se elas estão presas à imagem do pai ou do complexo paterno no desenvolvimento de seu papel profissional. Também procuramos investigar se ocorre a emergência de aspectos do animus nesse momento da vida da mulher. Para o desenvolvimento desse estudo, partimos do princípio de que o pai exerce uma função importante na vida da filha e contribui, assim, para a discriminação dos aspectos Masculinos da mulher em relação à figura paterna. Sendo assim, o objetivo foi verificar como determinadas características da relação pai-filha se refletiram no posicionamento profissional de mulheres adultas jovens, utilizando para isso o referencial da Psicologia Analítica. O método escolhido foi qualititativo, tendo como população de estudo seis mulheres jovens adultas, entre 28 e 35 anos de idade. O procedimento adotado foi o da entrevista semidirigida, com roteiro previamente construído. Os resultados encontrados apontam para o vínculo muito forte com o pai e também com a mãe, destacando que a maioria das mulheres entrevistadas encontra-se ainda vinculada a algum complexo parental. Nesta pesquisa, a mãe parece ter servido como antimodelo , para a maioria dessas mulheres, na construção de seus papéis profissionais. Percebemos, também, que a dimensão do animus da ação já se encontra parcialmente integrada na maioria das mulheres estudadas, na primeira metade da vida
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Eriksson, Ingela. "”Hur ska jag kunna lära mig det här när jag inte förstår?” : Hur elever erfar lust och olust i skolmatematiken". Thesis, Högskolan i Skövde, Institutionen för kommunikation och information, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-4637.
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The aim of the study is to examine factors influencing students’ feelings of pleasure or pain associated with school mathematics. Own experience of students’ frustration about mathematics and concern about students not reaching desired goals is the driving force in this study. It contributes with knowledge from the students' perspective. Hopefully the result can help others, teachers and parents, to strengthen pupils’ desire and ability to learn. Students’ emotions about mathematics are important for learning and mathematics can cause joy as well as anxiety. The students who are positive often need stimulation and challenge, but are usually not a problem for the adults. The negative emotions, especially fear, is something that adults should take into account and try to develop for the better. Anxiety can be described as "a lack of well-being". It can cause panic, paralysis and mental disorganization when students are required to solve math tasks. Math anxiety can also be defined as a combination of stress before the test, low self-esteem, fear of failure and negative attitudes towards learning mathematics. Symptoms can include avoidance of formal mathematics instruction, poor test results and that instructions will not have the expected effect. There is a phenomenological approach of the study. Phenomenology studies how the consciousness creates meaning. The focal point is trying to learn about the students’ experience of their 'Being-in-the-World'. How do students view school mathematics, and why? What can create desire for learning mathematics? What can create uneasiness in learning mathematics? In order to get a better view of this complex area four different data sources are used. Eight pupils are interviewed individually. 19 students participated in focus group interviews. 134 students, ages 11-13, answered questions in a web survey. One class observation was also made. The result was formed into three important factors, Student’s own view of capacity and attitude to mathematics, Importance of relations to others (teachers, class mates, parents) and Content and working forms. Three different themes came into focus – Understanding, Working atmosphere and Safety. The four main areas of importance, as seen in this study, are Interaction student-teacher, Understanding and feeling of success, Good atmosphere in the classroom and Awareness about the use of mathematics. The results show areas of importance for pupils who are feeling math anxiety. They are less aware of how mathematics can be of use for them also outside school and the importance of mathematics in their future lives. They need a much stronger support from adults, teachers and parents, in their math studies, than pupils without anxiety. The classroom environment can also cause problems, if students do not feel safe or feel stressed or disturbed by other pupils or teachers. There are also a few differences between the girls’ and the boys’ experiences, where girls seem to reflect more about their uneasiness when it comes to mathematics, sometimes caused by the boys. What can teachers learn from this study? In short: motivate, teach and let the pupils talk.
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El, Hawari Khaled. "Occurrence des résidus et contaminants chimiques dans les miels produits et consommés au Liban : développement et standardisation de méthodes de dépistage adaptées : application aux résidus d'antibiotiques". Thesis, Rennes 1, 2016. http://www.theses.fr/2016REN1B054/document.
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Une nouvelle méthode, simple et rapide, a été développée pour isoler dans le miel différents antimicrobiens usuellement recherchés en contrôle sanitaire et appartenant à quatre classes différentes: les sulfamides, les tétracyclines, les macrolides et lincosamides associés et les aminoglycosides. Ces molécules antimicrobiennes sont analysées par chromatographie liquide couplée à la spectrométrie de masse en tandem (CL-SM/SM) après avoir été extraites de l’échantillon de miel par une méthode d’extraction unique. Afin de définir les conditions optimales de séparation et de détection, l’influence de la nature et de la concentration d’un agent d’appariement d’ions tel que le HFBA ou le PFPA, introduit dans la phase mobile, a pu être évaluée sur une colonne analytique en chromatographie de phase inversée de type C18. Plusieurs paramètres ont été pris en compte et étudiés lors de l’élaboration de la méthode d’extraction tels que la nature du solvant d’extraction, le pH, l’étape d’hydrolyse acide, l’efficacité de l’extraction par ultrasons et enfin la purification de l’extrait avant injection. La méthode développée a ensuite été validée suivant les recommandations de la Décision de la Commission Européenne (CE) No 2002/657 puis a subi une étape de validation supplémentaire en participant à une comparaison inter-laboratoire organisée sur des matériaux de miel contaminés et gérée par un organisme extérieur accrédité suivant la norme ISO17043. Par la suite, une démarche de transfert de la méthode analytique validée en CL-SM/SM a été mise en place pour son utilisation en chromatographie liquide couplée à la spectrométrie de masse à haute résolution (CL-SMHR). Une validation de cette démarche a été menée par l’application d’une étude statistique descriptive basée sur la notion de profil d’exactitude. Finalement, un programme expérimental de surveillance a été entrepris sur une série d’échantillons de divers miels collectés sur des marchés locaux pour tester la qualité des produits commercialisés au Liban. Contrôlés au regard de leur contamination en résidus d’antimicrobiens en CL-SM/SM parmi la trentaine de molécules prédéfinies dans l’étude, la positivité et/ou la non-conformité de certains échantillons ont pu être confirmées par l’utilisation de la CL-SMHRA new, simple and rapid method has been developed for the determination of multiclass antimicrobial residues in honey (sulfonamides, tetracyclines, macrolides, lincosamides and aminoglycosides). All the compounds were extracted from honey within single extraction method and analyzed by liquid chromatography - tandem mass spectrometry (LC-MS/MS) operating in positive electrospray ionization mode. In our study, we examined the behavior of volatile perfluorinated carboxylic acids (HFBA and PFPA) used as ion-pairing reagents for the separation of multiclass of antibiotic residues by reversed phase Zorbax SB C18 column. Furthermore, the extraction and clean-up steps were investigated and optimized by using ultrasonic-assisted extraction and dispersive solid phase extraction (d-SPE). Different parameters affecting the extraction efficiency including type of solvent, pH, breaking efficiencies of N-glycosidic linkage by hydrochloric acid, ultrasonic extraction and its duration compared to shaking technique, along with dispersive SPE clean-up were examined prior sample injection. The method was then validated according to European Commission Decision (EC) No 2002/657. Furthermore, the method was tested for its validity through participation in proficiency testing scheme organized by FAPAS for the analysis of tetracycline in honey. Afterwards, a transfer of the validated LC-MS/MS analytical method has been applied for the determination of antimicrobial residues in honey from low resolution to High Resolution Mass Spectrometry (HRMS). For that purpose, descriptive statistical approach was performed to assess the performance of the method based on simultaneous evaluation of the trueness and the intermediate precision. Finally, the method was applied for the determination of antimicrobial residues in honey collected from local markets at different regions in Lebanon. Positive samples were then analyzed by the LC-HRMS to confirm the presence of analytes detected by LC-MSMS
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Svärling, Sofie. "Den andra världen i barn- och ungdomslitteraturen : Funktion och gestaltning". Thesis, Uppsala universitet, Litteraturvetenskapliga institutionen, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-155314.
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Maduna, Tando Lerato. "Vasoactive intestinal peptide (VIP) controls the development of the nervous system and its functions through VPAC1 receptor signalling : lessons from microcephaly and hyperalgesia in VIP-deficient mice". Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ009/document.
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Mes études doctorales ont permis de démontrer que les souris déficientes en VIP présentent une microcéphalie ayant principalement une origine maternelle qui affecte secondairement le développement de la substance blanche. Cette production placentaire par les lymphocytes T pourrait être affectée dans des pathologies du système immunitaire. De plus, nos données indiquent qu’une déficience en VIP prédispose à l'apparition de troubles sensoriels, en particulier de la nociception. Il est donc possible que les déficits précoces de développement du cerveau murin et l'apparition de l'hypersensibilité cutanée mécanique et thermique froide soient deux facettes d'une même pathologie. Des mesures d'activité de décharge spontanée des neurones dans le thalamus sensoriel chez des mâles adultes anesthésiés ont montré que les neurones des animaux KO sont hyper-excités, ce qui suggère un traitement aberrant des informations, notamment nociceptives, ou que l'activité inhibitrice des interneurones des réseaux locaux est réduiteThe studies carried out during my PhD demonstrate that VIP-deficient mice suffer from microcephaly and as well as white matter deficits mainly due to the absence of maternal VIP during embryogenesis, Placental secretion of VIP is dependent on T lymphocytes and could be altered in pathologies of the immune system. Moreover, our data links VIP deficiency to sensory alterations, specifically, the nociceptive system. Thus, it is possible that early developmental defects and hypersensitivity to mechanical and cold stimuli are two manifestations of the same pathology. This hypothesis was reinforced following analysis of spontaneous firing patterns of neurons in the sensory thalamus of anesthetized adult males. Neurons from VIP-KO mice are hyperactive, which suggests aberrant local processing of nociceptive input or that the inhibitory inputs from local interneuron networks is reduced
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Adolfsson, Karin y Stina Albinsson. "Friår - av vilken anledning? : Kopplingar mellan anledningar till friår och livsformerna". Thesis, Karlstad University, Faculty of Economic Sciences, Communication and IT, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-610.
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Undersökningens syfte är att se vilka anledningar individen har till att välja friår och hur det kopplas samman med livsformerna de lever. Syftet har också varit att se individens upplevelse av friåret och vad de använt friåret till. Undersökningen bygger på kvalitativa intervjuer med sex friårslediga. Intervjuerna har handlat om individens upplevelse av friåret och tiden före det.
Friår är en arbetsmarknadspolitisk åtgärd med målsättning att ge arbetstagare en längre ledighet från sitt arbete. Arbetslösa får samtidigt en chans att komma in på arbetsmarknaden. Friåret innebär att vara ledig från sitt arbete i tre till tolv månader för att kunna göra något annat utanför arbetsplatsen. För att kunna undersöka av vilka anledningar individen har friår och hur det kopplas med de olika sociala strukturer som villkorar människors vardag. Vi har studerat om livsformsanalysen kan användas till att beskriva, förklara och förstå skillnaderna i människors vardag. Livsformerna är sociala strukturer som villkorar människors vardag. De olika livsformsbegreppen som vi har använt oss av är arbetarlivsformen – husmorslivsformen, karriärenslivsform – representationshustrunslivsform och självständighetens livsform – medhjälperskans livsform. Det är dock vanligt att leva en blandning mellan två eller flera livsformer, det kallas en blandform.
Vi har kommit fram till att livsformerna till viss del kan kopplas samman med hur intervjupersonerna lever under sitt friår och av vilken anledning de har friår. Det visar sig i att de som använder friåret till att starta ett företag lever till stor del självständighetens livsform. Att använda friåret till utbildning kan kopplas samman med karriärens livsformer. Vidare kan vi se att karriärenslivsform kan kopplas samman med att pressen på arbetet är stor och då är rekreation under friåret vanligt. Många kvinnor lever blandformer och det gör att de har svårt att kombinera de olika arbets- och kärleksformerna. De använder friåret till att ta hand om sin familj och sig själva.
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Nagy, Danielle Giacometti. "Intervenção fonoaudiológica junto a mães de crianças com múltiplas deficiencias". Pontifícia Universidade Católica de São Paulo, 2005. https://tede2.pucsp.br/handle/handle/11993.
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Previous issue date: 2005-12-13This essay has, as its core objective, the analysis of clinical situations that reveal a mother s difficulties in the reception, acknowledgement and care of her offspring, when the child displays multiple deficiencies. As an integral part of this, the analysis also discusses how the Speech Therapy may, in the course of therapeutic intervention, contribute for a mother s development of a greater disposition for facing the hindrances that may be presented by her child. To that end, the main theoretical basis that served as reference were Winnicott s psychoanalytic theories on the relationship between a mother and her impaired child (Winnicott, D.W. (1957). Mother and Child. A Primer of First Relationships., New York: Basic Books, Inc.), which is important in understanding the phono-audiologic work dedicated to the relationship between mother and disabled child. The methodology employed was a qualitative-clinic one with four distinct relationship dynamics being applied under frequent observation of Speech Therapy Clinic. These, once understood by the healthcare professional, may aid in the success of a particular treatment by propitiating a singular analysis of factors contributing to the dysfunctional relationship between mother and child, such as: body stigmas that prevent attachment, excessive or insufficient care, denial and hindrances to the feeding process. Seven distinct cases had their summarised profiles presented and, through categories, it was ultimately possible to understand and analyse their clinic indications. For every one among the cases, phono-audiological procedures were reviewed to demonstrate that clinical intervention may cause the psychological profile of these challenged women to be altered positively, in a manner such as to enable them to internally transform that which has brought them suffering, and assimilate it. Hence, the essay deals with a Speech Therapy intervention such, that is not restricted to the technical questions of the sort of the suitability of phono-articulatory organs, feeding or the development of communication, but open to fundamental aspects of a child s psychological development. Additionally, in so doing, this proposition will be possibly contributing to the Speech Therapyst s referential in considering developing an effort with the mothers of impaired children that surpasses the orientation and teaching of procedures to offer a basis in interventions that promote the embracing of these mothers and consequential better development of children with multiple deficiencies
Este trabalho teve como objetivo analisar situações clínicas que revelam algumas dificuldades das mães na recepção, no reconhecimento e no cuidado de seus filhos que apresentam múltiplas deficiências; e discutir como o fonoaudiólogo, em sua intervenção terapêutica, pode contribuir para que elas desenvolvam uma disponibilidade maior para o enfrentamento dos entraves e das complicações que uma criança com deficiência pode apresentar. Para tanto, o principal referencial teórico foi a teoria psicanalítica de Winnicott, importante para a compreensão do trabalho fonoaudiológico voltado à relação da mãe com seu filho deficiente. A metodologia utilizada foi a clínico-qualitativa, sendo apresentadas quatro dinâmicas relacionais entre mãe e filho, as quais foram observadas com certa freqüência na clinica fonoaudiológica, e que, uma vez compreendidas pelo terapeuta, podem auxiliar no sucesso do tratamento, já que permitem que cada díade seja acolhida de maneira singular. São elas: evidências no corpo dificultando o vínculo; cuidados excessivos ou insuficientes; negação do diagnóstico; problemas para alimentar o filho. Sete casos tiveram seus perfis apresentados resumidamente, e através das categorias, foi possível compreender e analisar vinhetas clínicas destes casos, sendo que em cada uma delas foram abordados procedimentos fonoaudiológicos, mostrando como a intervenção clínica pôde provocar deslizamentos no perfil destas mulheres, ajudando a transformar aquilo que as faz sofrer. Trata-se de uma intervenção fonoaudiológica que não se restringe às questões técnicas, como a adequação dos órgãos fonoarticulatórios, da alimentação ou do desenvolvimento de linguagem, mas abre campo para aspectos fundamentais do desenvolvimento psíquico da criança, podendo contribuir na constituição de referenciais para o fonoaudiólogo pensar em um trabalho com mães de deficientes que não seja, apenas, voltado para as orientações e o ensino de procedimentos, mas que possa se basear em intervenções que promovam o acolhimento dessas mães e que facilitem o amadurecimento da criança com múltipla deficiência.
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Salga, Marjorie. "Inflammation et paraostéoarthropathies neurogènes Blocking neuromuscular junctions with botulinum toxin A injection enhances neurological heterotopic ossification development after spinal cord injury in mice Traumatism brain injury: if neurological damage was not the key to the development of neurogenic heterotopic ossification? Corticosteroid injection is an alternative therapeutic strategy to treat pain in Neurogenic Heterotopic Ossification: a Case Series". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLV072.
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Les ossifications hétérotopiques (OH) sont des formations osseuses bénignes anormalement situées dans les tissus mous du corps humain. Les OH peuvent être d’origine génétique, acquise et idiopathique. Elles sont appelées paraostéoarthropathies neurogènes (POAN) lorsqu’elles se développent après une lésion du système nerveux central. Cette thèse a pour objectif de préciser les facteurs inflammatoires locaux et systémiques, impliqués dans la survenue de POAN. Nous avons tout d’abord étudié l’effet de l’injection de composants de paroi membranaire bactérienne dans un modèle de souris développant des ossifications hétérotopiques neurogènes (OHN) après section médullaire et injection intramusculaire d’un myotoxique chimique. L’injection locale intramusculaire comme systémique d’un composant de paroi d’Escherichia Coli ou de Staphylococcus Aureus a permis d’augmenter de façon significative le volume des OHN. A l’issu de ces expériences, il semble que le niveau d’inflammation intramusculaire influence de façon importante le volume des OHN, selon un effet-dose. La provenance des agents de paroi bactérienne fait supposer que l’inflammation pourrait être spécifiquement induite par des pathogènes infectieux. Il semblerait qu’il existe un niveau inflammatoire seuil à partir duquel, la section médullaire ne soit plus obligatoire à la survenue d’OH. Toujours dans le même modèle murin, nous avons montré que le blocage de la jonction neuro-musculaire par une injection de toxine botulique augmente le volume des OHN. La jonction neuro-musculaire semble réguler le développement de OHN dans un muscle pathologique chez la sourie avec section médullaire. Il est possible que cette régulation s’effectue via un mécanisme de neuro-inflammation locale. Suite à ces découvertes en recherche fondamentale, nous avons mené une étude cas-témoins recherchant des facteurs pourvoyeurs d’inflammation à la phase très précoce suivant l’accident neurologique, qui pourraient être corrélés à l’apparition de POAN. Cette étude a été la première à montrer que les patients avec POAN présentent de façon plus importante des infections à Pseudomonas Aeruginosa. La présence de traumatismes associés et de chirurgies était corrélée à la survenue de POAN, tout comme la longueur de la ventilation mécanique, du coma, du séjour en réanimation et la présence d’une trachéotomie. En revanche, aucun critère neurologique n’était associé à une augmentation du risque de POAN. A gravité neurologique égale, il semble donc que les patients développant des POAN présentent un niveau d’inflammation plus élevé (infections, polytraumatisme, chirurgies multiples, réanimation) que les patients sans POAN. Comme pour d’autres pathologies articulaires avec une composante inflammatoire, nous avons infiltrer des dérivés cortisonés localement, dans le but de traiter les douleurs induites par certaines POAN. Un mois après l’injection, 80% des patients présentaient un soulagement des douleurs. Ce traitement local parait être une alternative intéressante à la prise en charge antalgique des POAN douloureux.Les POAN sont toujours, à l’heure actuelle, diagnostiqués et prises en charge tardivement lors de l’apparition de complications. L’enjeu actuel est d’identifier les patients à risque de développer des POAN, le plus tôt possible après leur accident neurologique de façon à leur assurer un suivi et une prise en charge adaptée et précoce. En se basant sur les études cliniques et les données issues du modèle murin développant des POAN, nous allons relever des critères cliniques et biologiques reconnus comme étant corrélés à l’apparition de POAN dans une base de données clinico-biologique. Ce tout premier travail prospectif sur les POAN permettra de repérer les patients à risque de développer des POAN et peut être à terme d’identifier des cibles thérapeutiques qui permettrons de prévenir ou de guérir les POANHeterotopic ossifications (H0) are abnormal ectopic bone formations that develop in soft tissues. HO can be related to genetic factors or acquired pathologies. HO occurring after central nervous system lesion are called neurogenic HO (NHO). The objective of this project is to identify local and systemic inflammatory factors that may be associated with occurrence of NHO. We study first, the effect of bacterial membrane components on the development of NHO in a mouse model of spinal cord injury triggered by injection of a myotoxic compound into muscle. Local and systemic administration of membrane components from Escherichia coli or Staphylococcus aureus significantly increased the volume of NHO. Changes in the level of inflammation, which was dose responsive, correlated with changes in NHO volume suggesting that inflammation influences NHO formation. As bacterial membrane components were also linked to increased volumes of NHO, it is possible that inflammation triggered by infectious pathogens could also be involved in NHO development. Furthermore, we identified that after reaching a certain threshold of inflammation, triggered by administration of bacterial membrane components, spinal cord injury was not required for NHO formation. Further experiments with this model involved determining the effect of blocking neuromuscular signaling on NHO formation. Botulinum toxin injection increased the size of NHO. Therefore, neuromuscular signaling also modulates NHO development in damaged muscles of spinal cord-injured mice. By extension, local neuroinflammation was implicated in regulating neuromuscular signals received by affected muscles. Based on these preclinical results, we carried out a case-control study to look for factors inducing inflammation that could be linked with NHO occurrence, and which occur at early stages after neurological trauma. This study identifies for the first time that patients with Pseudomonas Aeruginosa-positive infections were more likely to develop NHO. NHO patients more frequently experience surgery and polytrauma, compared to patients without NHO. Furthermore, extended stays in intensive care, long periods of mechanical ventilation, enduring coma, or patients with a tracheotomy were more frequent in patient with NHO. In contrast, no neurological factors were associated with a higher risk of developing NHO. Patients with comparable neurological trauma severity were more susceptible to develop NHO when they were experiencing a high level of inflammation (infection, polytrauma, surgeries, intensive care). Like for other inflammatory joint pathologies, we performed a further study which involved the infiltration of NHO with corticosteroid locally, in order to treat pain induced by NHO formation. One month after treatment, 80% of patients reported an improvement of pain. Therefore, we demonstrate that corticosteroid infiltration at the site of NHO is an effective treatment for pain associated with NHO. Detecting patients that are at risk to develop NHO as early as possible after an accident is imperative, to adapt rehabilitative strategies or treatment needs specific for patients that develop NHO. However, NHO diagnosis occurs during late phase of disease, when complications are occurring. To address this shortfall in the detection of NHO formation, we are undertaking the first prospective study of NHO, where clinical and biological information will be recorded to make a database. The specific data to be collected has been defined by our previous research in the mouse model and earlier clinical studies, and will identify specific biological and clinical factors that can be monitored to identify patients at risk to develop NHO. The outcomes of this project have specific implications in the understanding the drivers of NHO formation and its detection. Global outcomes of this project include improving patient management and possibly the prevention of NHO formation in patients
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Vivier, Delphine. "Vers de nouveaux antalgiques : optimisation de molécules activatrices des canaux potassiques TREK-1". Thesis, Clermont-Ferrand 2, 2014. http://www.theses.fr/2014CLF22518/document.
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La morphine demeure l'antalgique de référence pour le traitement de la douleur (nociception), mais elle est également responsable d‘effets secondaires importants. Des études ont montré que les animaux privés de canaux potassiques TREK-1 (TWIK-related K+channels) étaient plus sensibles à la douleur. Plus récemment, il a été démontré que le canal potassique TREK-1 joue un rôle crucial dans l'analgésie induite par la morphine chez les souris, alors qu'il n'est pas impliqué dans les effets secondaires (constipation, dépression respiratoire et dépendance). Ces résultats suggèrent que les canaux TREK-1 constituent des cibles d‘intérêt pour la conception de nouveaux antalgiques sans effets indésirables liés aux opioïdes. Des études antérieures au sein de notre laboratoire ont permis l'identification de quatre structures chefs de file, activatrices des canaux TREK-1, présentant une activité antalgique in vivo. La structure 3D du canal TREK-1 n‘étant pas élucidée au moment de nos travaux, nous avons décidé d'effectuer une optimisation basée sur une étude de relation structure-activité (RSA). Trente-six analogues ont été synthétisés par condensation de Knoevenagel et évalués pour leur effet antalgique (test de l‘acide acétique, test de la plaque chaude) et leur capacité à activer le canal TREK-1 (électrophysiologie). La capacité des substituants du noyau aromatique à établir des interactions de type liaison hydrogène ainsi que le volume de ces substituants ont une influence déterminante sur l'activité. Des résultats prometteurs ont émergé de cette étude RSA: 5 molécules présentent une très bonne activité antalgique (> 50% d'inhibition de la douleur, test de la plaque chaude) ainsi que d'une bonne activation de TREK-1 canaux (R ≥ 2 à 10 μM ou R ≥ 4 au-dessus de 20 μM)Morphine remains the analgesic of reference for the treatment of pain (nociception), but it is also responsible for serious adverse effects. Research studies have shown that animals deprived of potassium channels TREK-1 (TWIK-related K+ channels) were over-sensitive to pain. More recently, it has been demonstrated that the TREK-1 potassium channel is a crucial contributor of morphine-induced analgesia in mice, while it is not involved in morphine-induced constipation, respiratory depression and dependence. These results suggest that the TREK-1 channels constitute targets of interest for the design of novel analgesics without opioid-like adverse effects. Previous studies within our consortium led to the identification of four lead structures as TREK-1 activators exhibiting analgesic activity in vivo.Since the 3D structure of TREK-1 was not available at the time, we decided to perform hit optimization by conventional structure-activity relationship (SAR) studies. Thirty six analogs were synthesized via Knoevenagel condensation and evaluated for their analgesic effect (writhing test, hot plate assay) and their ability to activate TREK-1 channel (electrophysiology). It turned out that the possibility to form hydrogen bonding interaction (aryl moiety) and the volume of substituents of the amide or ester has a crucial influence on activity. Promising results emerged from this SAR study: 5 molecules display a very good analgesic activity (> 50% inhibition of pain, hot plate assay) as well as a good activation of TREK-1 channels (R ≥ 2 at 10μM or R ≥ 4 above 20μM)