Submitted by Luanna Matias (lua_matias@yahoo.com.br) on 2015-03-16T15:01:49Z No. of bitstreams: 2 Dissertação - Pablinny Moreira Galdino - 2011.pdf: 949654 bytes, checksum: acc529e8a96b2eb2f27de38af9b11d96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-03-17T10:31:01Z (GMT) No. of bitstreams: 2 Dissertação - Pablinny Moreira Galdino - 2011.pdf: 949654 bytes, checksum: acc529e8a96b2eb2f27de38af9b11d96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-03-17T10:31:01Z (GMT). No. of bitstreams: 2 Dissertação - Pablinny Moreira Galdino - 2011.pdf: 949654 bytes, checksum: acc529e8a96b2eb2f27de38af9b11d96 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2011-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / A ansiedade está entre as patologias crônicas mais comuns em todo o mundo. Em Brasília (capital federal do Brasil) os transtornos de ansiedade afetam 12,1 % da população, sendo o diagnóstico psiquiátrico mais prevalente. Desde a introdução dos benzodiazepínicos na década de 60, eles têm sido os fármacos mais prescritos no tratamento da ansiedade, porém seus efeitos colaterais são proeminentes, tais como sedação, miorelaxamento, ataxia, amnésia e dependência farmacológica. Sendo assim, novas terapias são necessárias no tratamento dos transtornos de ansiedade e o estudo com plantas medicinais pode prover novas opções terapêuticas. A Spiranthera odoratissima A. St. Hillaire (Rutaceae), popularmente conhecida como manacá, é um arbusto encontrado em região de Cerrado utilizado na medicina popular para tratar doenças renais, hepáticas, dores de estômago e cabeça, e reumatismo. O objetivo deste trabalho foi avaliar as atividades farmacológicas do óleo essencial extraído das folhas de S. odoratissima (OEM) no sistema nervoso central, em camundongos, direcionando para o estudo do efeito tipo ansiolítico e possíveis mecanismos envolvidos. O OEM aumentou o número de cruzamentos e o tempo de permanência no centro do campo aberto sem alterar o número total de áreas cruzadas neste teste e o desempenho no teste da barra giratória. No teste do sono induzido por pentobarbital, o OEM reduziu a latência e aumentou o tempo de sono. Nos modelos experimentais de ansiedade, o OEM aumentou o número de comportamentos de mergulhos no teste da placa perfurada, as entradas e o tempo de permanência nos braços abertos no labirinto em cruz elevado (LCE). Além de aumentar também o número de transições e o tempo de permanência no compartimento claro no teste da caixa claro/escuro (CCE). Foi investigado o mecanismo de ação deste efeito tipo ansiolítico através do pré-tratamento com um antagonista benzodiazepínico (flumazenil) ou um antagonista de receptor 5- HT1A (NAN-190) nos testes de LCE e CCE. O efeito tipo ansiolítico do OEM foi antagonizado apenas pelo pré-tratamento com o NAN-190. Em conclusão, estes resultados sugerem que o óleo essencial de S. odoratissima possui efeito tipo ansiolítico sem alterar os parâmetros locomotores, sendo esse efeito mediado via receptor 5HT1A, mas não via sítio benzodiazepínico do receptor GABAA. / A ansiedade está entre as patologias crônicas mais comuns em todo o mundo. Em Brasília (capital federal do Brasil) os transtornos de ansiedade afetam 12,1 % da população, sendo o diagnóstico psiquiátrico mais prevalente. Desde a introdução dos benzodiazepínicos na década de 60, eles têm sido os fármacos mais prescritos no tratamento da ansiedade, porém seus efeitos colaterais são proeminentes, tais como sedação, miorelaxamento, ataxia, amnésia e dependência farmacológica. Sendo assim, novas terapias são necessárias no tratamento dos transtornos de ansiedade e o estudo com plantas medicinais pode prover novas opções terapêuticas. A Spiranthera odoratissima A. St. Hillaire (Rutaceae), popularmente conhecida como manacá, é um arbusto encontrado em região de Cerrado utilizado na medicina popular para tratar doenças renais, hepáticas, dores de estômago e cabeça, e reumatismo. O objetivo deste trabalho foi avaliar as atividades farmacológicas do óleo essencial extraído das folhas de S. odoratissima (OEM) no sistema nervoso central, em camundongos, direcionando para o estudo do efeito tipo ansiolítico e possíveis mecanismos envolvidos. O OEM aumentou o número de cruzamentos e o tempo de permanência no centro do campo aberto sem alterar o número total de áreas cruzadas neste teste e o desempenho no teste da barra giratória. No teste do sono induzido por pentobarbital, o OEM reduziu a latência e aumentou o tempo de sono. Nos modelos experimentais de ansiedade, o OEM aumentou o número de comportamentos de mergulhos no teste da placa perfurada, as entradas e o tempo de permanência nos braços abertos no labirinto em cruz elevado (LCE). Além de aumentar também o número de transições e o tempo de permanência no compartimento claro no teste da caixa claro/escuro (CCE). Foi investigado o mecanismo de ação deste efeito tipo ansiolítico através do pré-tratamento com um antagonista benzodiazepínico (flumazenil) ou um antagonista de receptor 5- HT1A (NAN-190) nos testes de LCE e CCE. O efeito tipo ansiolítico do OEM foi antagonizado apenas pelo pré-tratamento com o NAN-190. Em conclusão, estes resultados sugerem que o óleo essencial de S. odoratissima possui efeito tipo ansiolítico sem alterar os parâmetros locomotores, sendo esse efeito mediado via receptor 5HT1A, mas não via sítio benzodiazepínico do receptor GABAA.

Bakgrund: Forskning tyder på att preoperativ ångest utgör ett vanligt förekommande problem hos patienter som skall genomgå kirurgi. Flera studier visade att den kan leda till olika postoperativa komplikationer. Det är sjuksköterskans ansvar att både identifiera och åtgärda ångest inför ett kirurgiskt ingrepp. Syfte: Att beskriva vilka icke-farmakologiska interventioner finns för att minska preoperativ ångest hos vuxna patienter. Metod: Studiens design var en litteraturöversikt som genomfördes enligt Fribergs metodbeskrivning. Litteraturöversikten bygger på tolv kvantitativa studier publicerade mellan 01/2007 och 09/2017. Sökningar utfördes i databaserna CINAHL Complete och PubMed. Resultat: Denna litteraturöversikt tyder på att det finns flera, olika interventioner som kan användas som komplement till farmakologisk behandling för att effektivt minska preoperativ ångest hos vuxna patienter. Ångest i den preoperativa fasen kan lindras om patienten får en utökad, individuell anpassad information. Ångest kan också minskas om patienten får ett känslomässigt stöd eller hjälp med att finna tröst i andlighet/religion. Litteraturöversiktens resultat tyder dessutom på att ångestnivå kan sänkas med hjälp av en lugn musik, naturljud eller vägledd dagdröm. Det framkom även att den preoperativa ångesten kan minskas genom avslappningsövningar, aromaterapi, akupunktur och zonterapi. Endast en fotografisk utställning har inte visats vara effektiv för att minska ångest i det preoperativa skedet. Diskussion: Resultatet av litteraturöversikten har diskuterats i relation till sjuksköterskans ansvarsområde. Resultatdiskussionen koncentreras kring praktiska frågor gällande implementering av de icke-farmakologiska metoderna i vården. Jean Watsons teori om mänsklig omsorg utgjorde översiktens teoretiska referensram som hjälpte författaren i resultatdiskussionen. / Background: Research indicates that preoperative anxiety is a widespread problem among patients undergoing surgery. It has been shown in several studies that preoperative anxiety may lead to different postoperative complications. It is the nurse's responsibility to identify and to reduce patients' anxiety. Aim: To describe which non-pharmacological interventions are available to reduce preoperative anxiety in adult patients. Method: The study was designed as a literature review performed according to the Fribergs method. This literature review is based on twelve quantitative articles published between 01/2007 and 09/2017. The search for the articles was conducted in CINAHL Complete database and PubMed database. Results: The result of this review indicates that there are several, different interventions that may be used in addition to pharmacological treatment in order to effectively reduce preoperative anxiety in adult patients. Anxiety in the preoperative phase can be alleviated by providing the patient with information tailored to the individual's needs. Anxiety can also be reduced by providing emotional support or by helping the patient to find comfort in spirituality/religion. The result of this review indicates moreover that the level of anxious can be minimized by listening to soothing music, nature sounds or guided imagery. Relaxation exercises, aromatherapy, acupuncture and reflexology were also found to reduce preoperative anxiety. Only the photographic display was not found to be effective in reducing anxiety in the preoperative phase. Discussion: The result of this review was discussed in relation to the nurse's responsibilities. The discussion of the results was focused on the practical issues about implementation of the non-pharmacological methods in the clinical practice. Jean Watson's Theory of Human Caring was used as a theoretical framework that helped the author in results analysis.

Bakgrund: Cancer leder till mycket lidande för barnen och de behöver hjälp med att lindra lidandet med hjälp av icke-farmakologiska metoder. Av alla dessa drabbade barn och ungdomar har många besvär av smärta och ångest och det blir psykiskt påfrestande under sjukdomstiden. Syfte: Syftet med studien var att beskriva hur icke-farmakologiska metoder används, för att avleda smärta och ångest hos barn och ungdomar som genomgår cancerrelaterade undersökningar och behandlingar. Metod: Litteraturstudie. Artikelsökning gjordes i databasen PubMed, Cinahl och manuellt. Totalt valdes tio vetenskapliga artiklar. Resultat: Resultatet visade att icke-farmakologiska metoder såsom beröring, hypnos och distraktion i form av lek eller såpbubblor samt musik, minskar smärta och ångest hos barn och ungdomar med cancerdiagnos, som genomgår smärtsamma undersökningar, till exempel benmärgsaspiration, blodprover och andra behandlingar. Slutsats: De icke-farmakologiska metoderna är ett komplement till de farmakologiska medicinerna för att minska smärta och ångest. Det är viktigt att åldersanpassa de icke-farmakologiska metoderna. Omvårdnadspersonalen kan bli mer lyhörd för att använda icke-farmakologiska metoder, gällande smärt- och ångestlindring hos barn med cancerdiagnos. De bör få möjlighet att utveckla sin kunskap och kompetens inom detta område. I sin tur kan det leda till mer trygga barn och ungdomar, och även trygga föräldrar. / Background: Cancer leads to a lot of suffering for the children and they need help to alleviate suffering by means of non-pharmacological methods. Of all these affected children and adolescents, there are many complaints of pain and anxiety and it becomes psychologically stressful during the illness. Purpose: The purpose of the study was to describe how non-pharmacological methods are used to derive pain and anxiety in children and adolescents undergoing cancer-related studies and treatments Method: Literature study. Article search was made in the PubMed, Cinahl database and manually. A total of ten scientific articles were selected. Results: The results showed that non-pharmacological methods such as massage, hypnosis, play or soap bubbles and music distraction reduce pain and anxiety in children with cancer diagnosis undergoing painful investigations, such as bone marrow aspiration, blood samples and other treatments.Conclusion: The non-pharmacological methods complementary to the pharmacological drugs to reduce pain and anxiety. It is important to age-match the non-pharmacological methods. Nursing staff can be more responsive to using non-pharmacological methods, regarding pain and anxiety relief in children with cancer diagnosis. They should be given the opportunity to develop their knowledge and skills in this field. In turn, it can lead to more safe children and young people, and also to safeguard parents.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / The association between depression and chronic pain is frequent and bidirectional. The high number of patients with depression and chronic pain who are refractory to currently available drugs makes it important search for new drugs to treat these disease. The bis selenide is an organic selenium compound with activities such as antioxidant, antinociceptive and anti-inflammatory in mice. Thus, this study investigated the effect of bis selenide in models of depression and pain in mice, besides the pharmacological mechanisms involved. Oral administration of bis selenide (5mg/kg, p.o.) reduced the immobility time in tail suspension test (TST) with a maximal effect at 1 hour and it remained up to 6 hours in relation to control group. The effect caused by bis selenide in reducing the immobility time was observed at doses of 0.5, 1 and 5 mg/kg in the TST and the forced swimming test (FST) (article 1). The antidepressant-like activity of bis selenide was reversed by pretreatment with p-chlorophenylalanine ethyl ester (PCPA, an inhibitor of synthesis of serotonin), ketanserin (5-HT2A/2C receptor antagonist), ondansetron (5 -HT3 receptor antagonist) (article 1), L-arginine (an amino acid precursor of nitric oxide (NO)), sildenafil (phosphodiesterase inhibitor type 5, PDE-V), S-nitroso-N-acetyl-penicillamine (SNAP, an NO donor) (article 2), cromakalim (potassium channels - K+- opener), minoxidil (K+ channels opener) and GW 9662 (antagonist of peroxisome proliferator activated receptors gamma (PPARγ) (article 3). However, the antidepressant-like effect of SVBS (1 mg / kg, po) was not prevented by pretreatment with prazosin (α1-receptor antagonist), yohimbine (α2-receptor antagonist), propranolol (β-receptor antagonist), SCH 23390 (D1 receptor antagonist), sulpiride (D2 receptor antagonist) and WAY 100635 (selective antagonist of 5-HT1A) (article 1). Furthermore, when administered in a sub-active dose, the bis selenide (0.1 mg / kg, p.o.) showed a synergistic action with fluoxetine (an selective serotonin inhibitor reuptake), NG-nitro-L-arginine (an inhibitor of the NO synthase (NOS)), 7-nitroindazole (7-NI, a specific inhibitor of NOS neurornal), methylene blue (inhibitor of NOS and guanylate cyclase (GC)), 1H-1,2,4] oxadiazole [4, 3-a] quinoxaline-1-one (ODQ, a specific inhibitor of GC) (article 2), tetraethylammonium (TEA, a non-specific inhibitor of K(+) channels), glibenclamide (an ATP-sensitive K(+) channel inhibitor) charibdotoxin (a large and intermediate conductance calcium-activated K(+) channel inhibitor) and apamin (a small-conductance calcium-activated K(+) channel inhibitor) (article 3). The administration of bis selenide (0.1 5 mg/kg, p.o.) also did not modify the activity of monoamine oxidase A and B (MAO-A and MAO-B) and Na+K+ATPase in mice. The levels of nitrite/nitrate in the brain of mice were reduced by treatment of bis selenide (1 mg/kg). Treatment with bis selenide (1 and 5 mg/kg) decreased the depressive-like behavior and mechanical hypernociception in mice subjected to chronic constriction injury (CCI) (article 4). Moreover, the administration of bis selenide (5 and 10 mg/kg, po) showed a reduction in mechanical hyperalgesia and edema in inflammatory models induced by intraplantar (i.pl.) injection of Complete Freund Adjuvant (CFA), carrageenan (Cg) and prostaglandin E2 (PGE2) (article 5). The mechanical hyperalgesia induced by i.pl. injection of CFA or the brachial plexus avulsion (BPA) was attenuated by chronic administration of bis selenide without causing tolerance during treatment. Concomitant administration of bis selenide (5 and 10 mg/kg) with vincristine for 7 days attenuated the mechanical hyperalgesia from 3 to 28 days. According to this study, it may suggest that the mechanisms responsible for the antidepressant-like effect of bis selenide involve the modulation of serotonin (5-HT2A/C and 5-HT3) and PPARγ receptors and the NO/GMPc/K+ pathway. Furthermore, treatment with bis selenide reduced the depressive-like behavior induced by CCI and the mechanical hyperalgesia in inflammatory (CFA, Cg and PGE2) and neuropathic (BPA and vincristine) models. Thus, this study demonstrated that treatment with bis selenide showed antidepressant-like and anti- hyperalgesic effects in different models in mice. / A associação entre a depressão e a dor crônica é freqüente e bidirecional. O elevado número de pacientes com depressão e dores crônicas que são refratários aos medicamentos disponíveis atualmente torna importante a busca por novas drogas para o tratamento destas doenças. O seleneto vinílico bis substituído (SVBS) é um composto orgânico de selênio com atividades antioxidante, antinociceptiva e antiinflamatória em camundongos. Este estudo teve como objetivo investigar o efeito do SVBS em modelos de depressão e dor em camundongos, além dos mecanismos farmacológicos envolvidos. A administração oral do SVBS (5 mg/kg, per oral, p.o.) reduziu o tempo de imobilidade no teste da suspensão da cauda (TSC) com um efeito máximo em 1 hora e permaneceu significativo em relação ao controle até 6 horas. O efeito causado pelo SVBS em reduzir o tempo de imobilidade foi observado nas doses de 0,5, 1 e 5 mg/kg no TSC e no teste do nado forçado (TNF) (artigo 1). A atividade do tipo antidepressiva do SVBS foi revertida pelo tratamento prévio com p-clorofenilalanina etil éster (PCPA, inibidor da síntese de serotonina (5-HT)), cetanserina (antagonista dos receptores 5-HT2A/2C), ondansetrona (antagonista dos receptores 5-HT3) (artigo 1), L-arginina (aminoácido precursor de óxido nítrico (NO)), sildenafil (inibidor da fosfodiesterase tipo 5, PDE-V), S-nitroso-N-acetil-penicilamina (SNAP, um doador de NO) (artigo 2), cromacalina (abrem os canais de potássio - K+), minoxidil (abrem os canais de K+) e GW 9662 (antagonista dos receptores ativados da proliferação de peroxissomos-gama (PPARγ) (artigo 3). Entretanto, o efeito do tipo antidepressivo do SVBS (1 mg/kg, p.o.) não foi prevenido pelo tratamento prévio com prazosin (antagonista de receptores α1), ioimbina (antagonista de receptores α2), propranolol (antagonista de receptores β), SCH 23390 (antagonista de receptores D1), sulpirida (antagonista de receptores D2) e WAY 100635 (antagonista seletivo de receptores 5-HT1A) (artigo 1). Além disso, quando administrado em uma dose sub-ativa, o SVBS (0,1 mg/kg) apresentou uma ação sinérgica com a fluoxetina (antidepressivo inibidor seletivo da recaptação da serotonina), NG-nitro-L-arginina (inibidor da óxido nítrico sintase (NOS)), 7-nitroindazol (7-NI, inibidor seletivo da NOS neuronal), azul de metileno (inibidor da NOS e da guanilato ciclase (GC)), 1H- 1,2,4]oxadiazolo [4,3-a]quinoxalin-1-ona (ODQ, inibidor seletivo da GC) (artigo 2), tetraetilamônio (TEA, bloqueador dos diferentes tipos de canais de K+, inclusive os dependentes de voltagem), glibenclamida (bloqueador de canais de K+ dependente de ATP), caribdotoxina (bloqueador de canais de K+ de alta condutância ativados por cálcio) e apamina (bloqueador de canais de K+ de baixa condutância ativados por cálcio) (artigo 3). A administração do SVBS (0,1-5 mg/kg, p.o.) também não modificou a atividade das enzimas monoamina oxidase-A e B (MAO-A e MAO-B) e Na+K+ATPase no cérebro dos camundongos. Os níveis de nitrito/nitrato no cérebro foram reduzidos com o tratamento com SVBS (1 mg/kg, p.o.). O tratamento com SVBS (1 e 5 mg/kg) diminui o comportamento do tipo depressivo e a dor nos camundongos submetidos à injúria por constrição crônica (ICC) (artigo 4). Além disso, a administração do composto SVBS (5 e 10 mg/kg, p.o.) demonstrou uma redução na hiperalgesia e no edema induzidos pela administração intraplantar (i.pl.) de Adjuvante Completo de Freund (ACF), carragenina (Cg) e prostaglandina E2 (PGE2) (artigo 5). A hiperalgesia mecânica induzida pela administração i.pl. de ACF ou pela avulsão do plexo braquial (ABP) foi atenuada com a administração crônica do SVBS, sem causar tolerância durante o tratamento. A administração concomitante de SVBS (5 e 10 mg/kg, p.o.) com vincristina durante 7 dias atenuou a hiperalgesia mecânica do 3º ao 28º dia de teste. De acordo com o presente estudo pode-se sugerir que os mecanismos responsáveis pela ação do tipo antidepressiva do SVBS envolvem a modulação dos receptores serotonérgicos (5-HT2A/C e 5-HT3), PPARγ e via do NO/GMPc/K+. Além disso, o tratamento com SVBS reduziu o comportamento depressivo induzido pela ICC e a hiperalgesia mecânica em modelos inflamatórios (ACF, Cg e PGE2) e neuropáticos (ABP e vincristina). Desta forma, o presente estudo demonstrou que o tratamento com SVBS apresentou efeitos do tipo antidepressivo e anti-hiperalgésico em diferentes modelos em camundongos.

L’ischémie critique chronique définit un stade avancé d’insuffisance artérielle chronique. Le diagnostic d’ischémie critique chronique nécessite trois éléments : des signes cliniques, des mesures de perfusion artérielle témoignant de l’ischémie, ainsi qu’une durée des symptômes supérieure à 15 jours. Nous avons mis au point un modèle d’ischémie critique chronique valide chez la souris, et reproduisant au plus proche les lésions observées chez l’homme, en réalisant une ligature fémorale droite associée à une ligature iliaque droite 4 jours plus tard. Nous avons ensuite étudié à partir de ce modèle l’atteinte mitochondriale liée à l’ischémie critique chronique, notamment l’altération de la fonction respiratoire mitochondriale, la diminution de la capacité de rétention calcique, et la production de radicaux libres. Nous avons testé différents protocoles de conditionnement pharmacologique et avons mis en évidence un effet protecteur de la N acétyl cystéine, des statines et de la L arginine. Les voies de protection RISK et SAFE seraient potentiellement impliquées dans cet effet protecteur. / Critical limb ischemia defines an advances stage of peripheral arterial disease and peripheral arterial insufficiency. The diagnosis of critical limb ischemia requires three elements: clinical signs, arterial perfusion measures demonstrating the level of ischemia, as well as a duration of symptoms for more than 15 days. We developed a critical limb ischemia model in mice, nearly mimicking human pathology, by right femoral artery ligatuon followed by right artery ligation 4 days later. We then studied from this model the mitochondrial impairment associted with critical limb ischemia, including impaired mitochondrial respiratory function, reduced calcium retention capacity, and increased production of free radicals. Once these changes highlighted, we wanted to test different pharmacological conditioning, in order to identify protective molecules in critical limb ischemia. We thus demonstrated a protective effetct of N acetyl cysteine, statins and L-arginine. The protection pathways RISK and SAFE may be involved in this protective effect.

L'huile d'argane est traditionnellement utilisée au Maroc en usage externe pour le traitement des affections cutanées et en usage interne pour prévenir les troubles cardiovasculaires. Particulièrement riche en acides gras insaturés, l'huile d'argane est caractérisée également par ses composés mineurs : polyphénols, tocophérols, stérols, du squalène, et alcools triterpéniques.L'objectif de ce travail est de contribuer à la valorisation de l'huile d'argane et de ses co-produits. C'est un travail pluridisciplinaire car il est composé de deux parties : phytochimie et activité pharmacologique.Pour la partie phytochimique, onze polyphénols des co-produits d'argane ont été identifiés et quantifiés par LC-ESI-MS. Leur activité antioxydante a été évaluée par plusieurs techniques. La composition chimique des composés volatiles de l'huile d'argane a été étudiée en fonction du temps de torréfaction des amandons. Ces arômes, obtenus par microextraction en phase solide (SPME), ont été élucidés et quantifiés par CPG-MS. La deuxième partie de ce travail, a mis en exergue pour la première fois des propriétés photoprotoctrices et antioxydantes de l'huile d'argane. En effet, l'effet antioxydant de l'huile d'argane a été confirmé, lors d'une étude clinique, par la mesure sérique de la vitamine E chez des femmes ménopausées après 8 semaines de consommation de 25 ml d'huile d'argane vs huile d'olive. Les résultats sont significatifs chez le groupe consommant de l'huile d'argane. Le dosage de la vitamine E dans le sérum, a été réalisé par HPLC. Les propriétés photoprotectrices de l'huile d'argane ont été mises en évidence in-vitro par l'action des UVC sur un model moléculaire de l'ADN : la thymidylyl-(3',5')-thymidine. Les résultats préliminaires sont encourageants. L'huile d'argane, même diluée 9 fois par la paraffine, reste toujours active. / Argan oil is traditionally used in Morocco as an ointment to cure some skin pathlogies or is ingested to prevent cardiovascular diseases. Its content in unsaturated fatty acids is high as is its content in polyphenols, tocopherols, sterols, squalene and triterpenic alcohols.The aim of this thesis was to increase the value of argan oil and derivatives. Our work focuses on phytochemistry and pharmacology.Concerning the phytochemical aspect, 11 polyphenols were identified and quantified by LC-ESI-SM. Their anti-oxidant activity has been evaluated as a function of kernel roasting time. Volatils obtained by microextraction were also quantified using CPG-SM.In a second section, photoprotective and anti-oxidant properties of argan oil were studied. Blood vitamine E level was determined in post menopausal women after 8 weeks of daily consumption of 25 ml of argan. Olive oil was given as a blank. Photoproptective properties of argan oil were evidenced in vitro using UV-C and Thymidylyl-(3',5') thymidine as DNA model. Preliminary results indicate a good photoproective activity even when argan oil is diluted (1/10) in parafin oil.

Alla kirurgiska ingrepp, oavsett omfattning, orsakar vävnadsskada med efterföljande smärta. Obehandlad eller otillräckligt behandlad smärta kan leda till postoperativa komplikationer såväl fysiologiska som psykologiska. Farmakologisk behandling och framförallt behandling med opioider är ofta förknippat med biverkningar. Ett komplement till farmakologisk smärtbehandling kan vara icke-farmakologisk behandling såsom exempelvis musik. Musik är en gammal social företeelse som har visat sig ha positiv effekt på oro, stress och smärta. Studiens syfte var att undersöka musikens effekter på postoperativ smärta. Studien genomfördes som en litteraturstudie och resultatet baseras på femton vetenskapliga och peer-reviewed artiklar. Resultatet visade på att majoriteten av de patienter som genomgick ett kirurgiskt ingrepp och fick musikintervention skattade sin smärta lägre än de patienter som inte fick det. Musikintervention är en enkel, riskfri och kostnadseffektiv metod som kan ses som ett komplement till farmakologisk behandling av postoperativ smärta. / All surgical procedures, whatever the extent, cause tissue damage with subsequent pain. Untreated or inadequately treated pain can lead to both physiological and psychological postoperative complications. Pharmacological treatment and especially opioid treatment is often associated with side effects. A complement to pharmacological may be non-pharmacological pain management such as music. Music is an old social phenomenon which has shown to have a positive effect on anxiety, stress and pain. The purpose of the study was to investigate the effects of music on postoperative pain. The study was conducted as a literature study and the result is based on fifteen scientific peer-reviewed articles. The result showed that the majority of patients undergoing surgery and who received music interventions assessed their pain lower than those who did not. Music intervention is a simple, riskfree and cost-effective method which may be a complement to pharmacological treatment of post-operative pain.

La richesse moléculaire des végétaux constitue une source importante de molécules tinctoriales et bioactives d'origine naturelle, utilisées depuis toujours par les artisans et tradipraticiens dans le domaine artisanal et thérapeutique. Ces travaux contribuent principalement à l’étude chimique de cinq plantes tinctoriales : T. grandis, L. inermis, K. senegalensis, I. tinctoria et P. cyanescens, lesquelles représentent les plus employées par les artisans à l'issue d'une enquête ethnobotanique réalisée au Sud-Est du Bénin. Un essai d'optimisation des conditions d’extraction des colorants de T. grandis assistée par ultrasons a été effectué et comparée à trois autres techniques utilisées conventionnellement. Ce procédé a été établi comme le plus simple, rapide, efficace et donnant le rendement le plus important en colorants jaunes et rouges extraits des plantes étudiées, en comparaison aux extractions classiques. De la même manière, il a été mis au point un procédé d'extraction de l’indigotine par usage du dithionite de sodium. Il a pu être démontré que ce procédé permet d'extraire rapidement et efficacement cette molécule à partir de P. cyanescens comparativement à l'emploi de solvants organiques usuels. Une étude fondamentale sur l’identification des colorants extraits à partir des plantes étudiées a été effectuée. Une approche chromatographique utilisant la CLHP/UV-Vis a permis d’identifier la catéchine et l'épicatéchine ainsi que des acides phénoliques, constitutifs des tanins quantitativement caractéristiques des espèces K. senegalensis et L. inermis. En outre, la lawsone et des flavones ont été identifiées dans L. inermis. Il a été caractérisé en plus de la tectoquinone, trois autres anthraquinones Ta, Tb et Tc dont les structures n'ont pas été élucidées, à ce jour, ainsi que des flavonoïdes dont cinq n'ont jamais été décrits dans littérature de T. grandis. Quant aux plantes à indigo, elles se différencient non seulement par la teneur en indigoïdes issue de leurs divers extraits mais aussi par trois flavonoïdes identifiés spécifiquement dans P. cyanescens. L’ensemble de ces résultats expérimentaux a pu être appliqué avec succès à l’étude de colorants extraits à partir d'échantillons prélevés sur des objets du patrimoine notamment des masques, statuettes et textiles provenant de collections muséales, ce qui a contribué à la détermination de leur origine minérale et botanique. Par ailleurs, des tests chimiques sur des fractions plus ou moins enrichies en molécules colorantes issues des plantes étudiées ont permis l'évaluation des propriétés pharmacologiques réalisés in-vitro révélant une activité antioxydante et cytotoxique sur les cellules cancéreuses MCF-7 et IGROV / Molecular plant wealth is an important source of dyes and naturally occurring bioactive molecules, have always been used by artisans and crafts and traditional healers in the therapeutic field. This work contributes mainly to the chemical study of five dye plants: T. grandis, L. inermis, K. senegalensis, I. tinctoria and P. cyanescens, which represent the most used by the artisans at from a ethnobotanical study conducted in southeastern Benin. An optimization of the extraction conditions dyes from T. grandis assisted ultrasonic tests was carried out and compared with three other techniques conventionally used. This process has been established as the simplest, quick, efficient and providing the most important yield in yellow and red dyes extracted from plants studied, in comparison to conventional extractions. Similarly, a method of indigotine extraction using sodium dithionite has been developed. It could be shown that this method can extract quickly and efficiently indigotine from P. cyanescens compared to the use of conventional organic solvents. A fundamental study of the identification of dyes extracted from plants studied was performed. Chromatographic approach using HPLC / UV-Vis permits to identify catechin and epicatechin and phenolic acids, tannins constituent species characteristics quantitatively and K. senegalensis and L. inermis. Furthermore, lawsone and flavones have been identified in L. inermis. It was further characterized by the tectoquinone, three other anthraquinones Ta, Tb and Tc whose structures have not been elucidated and flavonoids which five were never been described in literature of T. grandis. As for indigo plants, they differ not only by the content of their various end indigoid extracts but also specifically identified by three flavonoids in P. cyanescens. All these experimental results have been successfully applied to the study of dyes extracted from samples of objects including heritage masks, statuettes and textiles from museum collections, which contributed to the determination of their mineral and botanical origin. Furthermore, evaluation of the pharmacological properties, by chemical tests in vitro and antioxidant showed cytotoxic activity on cancer cells MCF-7, IGROV and very important fraction of more or less enriched in the dye molecules from plants tested

Vandetanib, lenvatinib and cabozantinib are inhibitors of receptor tyrosine kinases approved to treat locally advanced or metastatic thyroid gland, kidney and liver cancers. These multi- kinase inhibitors, inhibit phosphorylation of tyrosine moieties of protein, thus modulate cell signalization in cancer cells. Metabolites of vandetanib, lenvatinib and cabozantinib were detected in vitro as well as in vivo in blood and urine. Cytochromes P450 and flavin monooxygenases were identified as primary enzymes participating in metabolism of these drugs. Literature lacks information regarding pharmacological efficacy of vandetanib, lenvatinib and cabozantinib metabolites. The aim of this diploma thesis was the investigation of pharmacological efficacy of N-oxides of vandetanib, lenvatinib and cabozantinib. The viability measurement under normoxic and hypoxic conditions was employed to determined their efficacy. The expression of enzymes of the first phase of xenobiotics metabolism (CYP 450 1A1, 1B1, 3A4 a CYP 450 oxidoreductase) and receptor tyrosine kinases RET and VEGFR2, as well as mechanism of changes in their expression were investigated using western blotting and flow cytometry. High performance liquid chromatography was utilised to investigate possible metabolism of tyrosine kinase inhibitors and...

La physiopathologie de l’anévrysme de l’aorte abdominale (AAA) est multifactorielle. De la plaque athéro-thrombotique jusqu’à l’anévrisme menaçant, les phénomènes hémodynamiques, protéolytiques, oxydatifs et inflammatoires jouent un rôle aussi complexe qu’interdépendant. Aucun traitement pharmacologique n’a fait la preuve de son efficacité. Dans ce travail, nous étudions 2 voies pharmacologiques potentielles, et développons un modèle murin d’exclusion endovasculaire. La rapamycine est utilisée en oncologie. Ses propriétés anti-inflammatoires, antiprolifératives et anti-angiogéniques stabilisaient la progression anévrismale dans un modèle établi d’AAA. L’AZD9668 est un inhibiteur sélectif de l’élastase. Sécrétée par les neutrophiles, cette protéase joue un rôle clé dans la physiopathologie anévrismale. Les propriétés thérapeutiques ont été étudiées sur un modèle murin potentialisé par l’injection systémique de Porphyromonas Gingivalis, entretenant la réaction inflammatoire et protéolytique pariétale. Dans un second temps, nous avons développé un modèle murin d’exclusion endovasculaire. La spécificité de ce traitement a soulevé de nouvelles problématiques, soulignant le rôle crucial de l’activité biologique du thrombus. L’exclusion endovasculaire d’un AAA sur les modèles de grands animaux est complexe et coûteuse. Nous avons ainsi décrit la technique sur un modèle reconnu d’AAA chez le rat. Le traitement pharmacologique des AAAs a démontré son efficacité sur modèles murins, mais est difficilement transposable à l’homme en raison des effets secondaires. Un traitement endoluminal véhiculant un principe actif délivré in-situ permettrait de stabiliser durablement les AAA. / Abdominal aortic aneurysm (AAA) pathophysiology is multifactorial. From the athero-thrombotic plaque to a threatening aneurysm, hemodynamic, proteolysis, oxidation and inflammation play a complex but interdependent role. No pharmacological treatment has yet proved to be efficient. In this work, we study 2 potential pharmacological targets, and develop a murine model of endovascular abdominal aneurysm repair (EVAR). Rapamycine is used in oncology. Its anti-inflammatory, anti-proliferative and antiangiogenic properties stabilized aneurysm progression on an established AAA. AZD9668 is an elastase selective inhibitor. Secreted by neutrophils, this protease plays a key role in aneurysmal pathophysiology. Its therapeutic benefits have been study on a murine AAA model potentiated by Porphyromonas Gingivalis systemic injection, maintaining inflammatory reaction and wall proteolysis. Then, we developed a murine endovascular aneurysm exclusion model. EVAR raised new concern, underlining the crucial role of the thrombus biological activity. Endovascular AAA exclusion on big animals is complex and expensive. We hence described the technic on a rat AAA well known model. Pharmacological AAAs treatment has proved to be efficient on murine models, but is hard to transpose to humans because of systemic side effects. An endoluminal treatment carrying active drugs, and delivered in-situ, could durably stabilize AAAs.