Memoria para optar el título de Bioquímico / Las plantas poseen una gran cantidad de compuestos antioxidantes, tales como polifenoles, los cuales han sido aprovechados ampliamente en la medicina popular a través del consumo de estas plantas medicinales para tratar diversas dolencias y enfermedades. Hoy en día, muchas enfermedades se han asociado a estrés oxidativo, frente a lo cual la búsqueda y el desarrollo de nuevas terapias antioxidantes han aumentado considerablemente. Enfermedades neurodegenerativas, tales como Parkinson y Alzheimer, se han asociado a estrés oxidativo, probablemente por altas concentraciones neuronales de cobre y hierro. Así también desordenes psiquiátricos, como depresión y ansiedad, se han asociado a niveles elevados de productos de peroxidación lipídica. De aquí surge nuestro interés en la evaluación de la capacidad antioxidante de Melissa officinalis y Rosmarinus officinalis, así como el efecto ansiolítico de la administración de preparados herbales de estas plantas en modelo murino. Se indujo lipoperoxidación de microsomas hepáticos de rata a través del sistema oxidante Cu2+/ascorbato. Ambos extractos previnieron lipoperoxidación, así como fueron capaces de prevenir la disminución de los tioles proteicos inducida por Cu2+, tanto en presencia como en ausencia de ascorbato. Esto indica que los principios activos presentes en estos extractos podrían ejercer su acción antioxidante de, al menos, dos mecanismos: atrapamiento de radicales libres del oxígeno, y quelación de iones metálicos que generan ROS a través de las reacciones de Haber-Weiss y/o Fenton. Más aún, ambos extractos fueron capaces de inhibir la actividad N-desmetilante de aminopirina del sistema citocromo P450, el cual metaboliza sustratos lipofílicos. Experimentos conductuales en ratas mostraron que extractos secos estandarizados de ambas plantas produjeron un efecto significativo sobre la actividad motora y exploratoria, lo que indica actividad ansiolítica. Estos resultados preliminares permiten dar paso al desarrollo de nuevos fitofármacos seguros y eficaces para el tratamiento de enfermedades psiquiátricas / Plants have a great amount of antioxidant compounds, such as polyphenols, which have been widely utilized in folk medicine. These medicinal plants have been used to treat various ailments and diseases. Nowadays, many diseases have been associated with oxidative stress, consequently the search and development of new antioxidant therapies have increased considerably. Neurodegenerative diseases such as Parkinson and Alzheimer’s diseases have been associated with oxidative stress, probably for high neuronal concentrations of copper and iron. Likewise, psychiatric disorders, including depression and anxiety, have been associated with elevated levels of lipid peroxidation products. Hence, our interest in the evaluation of the antioxidant capacity of Melissa officinalis and Rosmarinus officinalis and the anxiolytic effect of the administration of these herbal extracts in murine model. Induced lipid peroxidation of microsomes of rat liver was performed by oxidant Cu2+/ascorbate system. Both extracts prevented lipid peroxidation and were able to prevent depletion of the protein thiols induced by Cu2+ in both the presence and absence of ascorbate. This indicates that the active ingredients present in these extracts may exert its antioxidant action at least by two mechanisms: trapping of oxygen free radicals and chelating metal ions that generate ROS through the Haber-Weiss reactions and/or Fenton. Moreover, both extracts were able to inhibit the N-demethylating activity of aminopyrine by cytochrome P450, which metabolizes lipophilic substrates. Behavioral experiments on rats showed that dried extracts of both plants produced a significant effect on motor and exploratory activity, indicating anxiolytic activity. These preliminary results allow making way for the development of new safe and effective herbal medicines to treat psychiatric diseases

Memoria para optar al título de Químico Farmacéutico / Los polifenoles herbales están representados por un grupo de compuestos que incluyen moléculas lipofílicas y polares. Plantas medicinales utilizadas para mitigar patologías psicotrópicas deben contener principios activos lipofílicos que sean capaces de atravesar la barrera hemato-encefálica. Diversos estudios demuestran la asociación de la enfermedad de Alzheimer´s y la de Parkinson´s a estrés oxidativo, fenómeno que parece estar relacionado con concentraciones elevadas de hierro y cobre que se han descrito en neuronas de estos pacientes. De aquí nuestro interés en evaluar la capacidad antioxidante de extractos secos estandarizados de hojas de Melissa officinalis (melisa) y Rosmarinus officinalis (romero), plantas utilizadas para mitigar efectos psicotrópicos como ansiedad y depresión. Para ello, se utilizó como sistema biológico una preparación enriquecida en retículo endoplásmico hepático de rata (microsomas) y como sistema oxidante, Cu2+/ascorbato. Ambos extractos previnieron la lipoperoxidación microsómica inducida por Cu2+/ascorbato. Además, ellos fueron capaces de prevenir la disminución de los tioles proteicos inducida por Cu2+ ya sea en presencia como en ausencia de ascorbato. Esto indica que los principios activos presentes en estos extractos podrían ejercer su acción antioxidante al menos a través de dos mecanismos: a) atrapamiento de radicales libres del oxígeno y b) quelación de iones metálicos que generan ROS a través de las reacciones de Haber-Weiss y/o Fenton. Más aún, ambos extractos fueron capaces de inhibir la actividad N-desmetilante de aminopirina del sistema CYP450, el cual metaboliza sustratos lipofílicos. Cabe resaltar que los efectos de romero fueron significativamente superiores a los de melisa. Estos resultados aunque preliminares, son promisorios y nuevos experimentos están en curso conducentes a evaluar en modelos animales la eficacia y seguridad de estos extractos / Herbal polyphenols are represented by a group of compound that includes lipophilic and polar compounds. Medicinal plants used to mitigate psychotropic pathologies must contain active lipophilic principles capable of crossing the blood-brain barrier. Studies have shown the association of Parkinson's and Alzheimer's diseases to oxidative stress, phenomenon that seem to be related with elevated concentrations of iron and copper In the neurons of these patients. Hence our interest in evaluating the antioxidant capacity of standardized dry extracts of Melissa officinalis (lemon balm) and Rosmarinus officinalis (rosemary) leaves, plants used to mitigate psychotropic effects such as anxiety and depression. An enriched preparation of rat liver endoplasmic reticulum (microsomes) was used as a biological system in and Cu2+/ascorbate, as oxidant system. Both extracts prevented microsomal lipid peroxidation induced by Cu2+/ascorbate. Furthermore, they were able to prevent the decrease of protein thiols induced by Cu2+ either in the presence or absence of ascorbate. This indicates that the principles antioxidants in rosemary and lemon balm extract may exert its cellular antioxidant activity through at least two mechanisms: a) trapping of oxygen free radicals and b) chelation of metals ions, which generate ROS through Haber-Weiss and/or Fenton reactions. Moreover, both extracts were able to inhibit the aminopyrine N-demethylating activity of CYP450 system, which metabolizes lipophilic compounds. It necessary to point out that the effects of rosemary were significantly higher than balm. These results, though preliminary, are promising and further experiments are underway leading in animal models to evaluate the efficacy and safety of these extracts

No description available.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, 2014. / Submitted by Josina da Silva Vieira (josinasv1990@gmail.com) on 2014-07-17T14:08:19Z No. of bitstreams: 1 2014_JoaoEudesFilho.pdf: 1504476 bytes, checksum: 6cef4e660ebfa17a50ad271150d08065 (MD5) / Approved for entry into archive by Guimaraes Jacqueline(jacqueline.guimaraes@bce.unb.br) on 2014-07-18T15:53:40Z (GMT) No. of bitstreams: 1 2014_JoaoEudesFilho.pdf: 1504476 bytes, checksum: 6cef4e660ebfa17a50ad271150d08065 (MD5) / Made available in DSpace on 2014-07-18T15:53:40Z (GMT). No. of bitstreams: 1 2014_JoaoEudesFilho.pdf: 1504476 bytes, checksum: 6cef4e660ebfa17a50ad271150d08065 (MD5) / A Melissa officinalis, popularmente conhecida como erva-cidreira, tem sido usada predominantemente em desordens relacionadas ao cérebro. Está bem documentado que os diferentes componentes dessa erva podem interferir no humor e na cognição de humanos e animais experimentais. Considerando esses aspectos, o objetivo deste estudo foi analisar os efeitos comportamentais e cognitivos do extrato de Melissa officinalis em dois modelos experimentais com possibilidade de traumas neurológicos: sepse experimental e administração de metil mercúrio (MeHg). Para tal, foram usados ratos machos Wistar (n= 150),conforme as recomendações do Comitê de Ética no Uso Animal (CEUA). Para a indução de sepse, os animais foram anestesiados com uma mistura de ketamina(80mg/kg) e xilazina (10mg/kg), seguida das cirurgias e exposição do ceco, comou sem perfuração para o extravasamento das fezes. Ao final dos procedimentos cirúrgicos, todos os animais receberam ceftriaxona (30 mg/kg) e clindamicina (25mg/kg). No segundo modelo experimental, os animais foram administrados comsalina ou MeHg (100 mg/kg). O extrato de M. officinalis (100 mg/kg) foi administrado por via oral, durante uma semana após os procedimentos mencionados, quando os animais foram avaliados nos seguintes testes experimentais: campo aberto (locomoção), Labirinto em cruz elevado (LCE,ansiedade), nado forçado (depressão) e esquiva inibitória (memória).Considerando os resultados com sepse, observou-se que os animais que sobreviveram à perfuração cecal apresentaram uma redução no percentual de entradas nos braços abertos do LCE, enquanto aqueles administrados com MeHgreduziram o percentual de tempo nos braços abertos do LCE. Ambos procedimentos, não alteraram as locomoções dos animais no teste do campo aberto e na frequência nos braços fechados do LCE. Além disso, esses mesmos animais apresentaram um aumento no tempo de imobilidade no teste do nado forçado, enquanto que no teste de esquiva inibitória eles reduziram o tempo de permanência na plataforma do equipamento. O extrato de M. officinalis interferiu,de forma positiva, no bloqueio dessas respostas, aumentando os parâmetros das entradas e/ou tempo de permanência dos animais nos braços abertos do LCE e reduzindo o tempo de imobilidade no nado forçado. No teste da esquiva inibitória,os melhores resultados com M. officinalis foram observados com o grupo de animais que sobreviveram à sepse, visto que o extrato melhorou a memória de curta e longa duração dos referidos animais. Nos ratos que foram expostos ao MeHg somente a memória de longa duração melhorou com a administração do extrato. Considerando esses resultados conclui-se que a M. officinalis parece ter propriedades ansiolíticas, antidepressivas e mnemônicas relacionadas a possíveis traumas neurológicos decorrentes de processos infecciosos e também devido à exposição de contaminante ambiental. ___________________________________________________________________________________ ABSTRACT / Melissa officinalis, commonly known as lemon balm has been used predominantlyin the brain related disorders. It is well documented that different components ofthis herb may interfere with mood and cognition in humans and experimentalanimals. Considering these aspects, the aim of this study was to analyze thebehavioral and cognitive effects of this ethanolic extract of M. officinalis in twoexperimental models with possibility of neurological trauma: experimental sepsisand administration of methylmercury (MeHg). For this purpose, male Wistar rats(n= 150) were used, as recommended by the Ethics Committee on Animal Use. Toinduce experimental sepsis, the animals were anesthetized with a mixture ofketamine (80mg/kg) and xylazine (10mg/kg), followed by surgery and exposure ofthe cecum, with or without perforation area for overflow of feces. At the end of thesurgery, all animals received ceftriaxone (30 mg/kg) and clindamycin (25 mg/kg).In second experimental model, the animals were administered with saline or MeHg(100 mg/kg). M. officinalis ethanolic extract (100 mg/kg) was administered by oralroute for one week after those mentioned procedures, when the animals wereevaluated in the following experimental tests: open field (locomotion), elevatedplus maze – EPM (anxiety), forced swimming (depression) or inhibitory avoidance(memory) tests. Considering the results with sepsis, we observed that sepsissurvivor animals showed a decrease in the percentage of open arms entries of theEPM, while those administered with MeHg showed decrease in the percentage ofopen arms time of the EPM. Both procedures did not change the locomotion of theanimals in the open field test and frequency in the enclosed arms of the EPM.Furthermore, the same animals belonging to these two experimental protocolsalso showed an increase in immobility time in the forced swimming test, whereasin the inhibitory avoidance test they reduced the latency in the platform of theequipment. M. officinalis interfered positively in blocking almost all theseresponses, increasing the parameters of entries and/or time spent in the openarms of the EPM and reduced the immobility time in the forced swimming. At theinhibitory avoidance test, the best result with M. officinalis was observed in sepsis procedures, since the extract improved short- and long-term memories of those animals. In rats that were exposed to MeHg only long-term memory was improved with the extract administration. Considering these results it is concluded that M.officinalis appears to have anxiolytic, antidepressant and mnemonic propertiesrelated to possible neurological traumas resulting from infectious processes andalso due to exposure to environmental contaminants.

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2007. / Submitted by Raquel Viana (tempestade_b@hotmail.com) on 2009-11-18T16:17:38Z No. of bitstreams: 1 2007_AdefunmilayoEbotTaiwo.pdf: 2007828 bytes, checksum: 176308b596148cf6f12825f6d3519f2c (MD5) / Approved for entry into archive by Marília Freitas(marilia@bce.unb.br) on 2010-01-13T16:52:05Z (GMT) No. of bitstreams: 1 2007_AdefunmilayoEbotTaiwo.pdf: 2007828 bytes, checksum: 176308b596148cf6f12825f6d3519f2c (MD5) / Made available in DSpace on 2010-01-13T16:52:05Z (GMT). No. of bitstreams: 1 2007_AdefunmilayoEbotTaiwo.pdf: 2007828 bytes, checksum: 176308b596148cf6f12825f6d3519f2c (MD5) Previous issue date: 2007 / A Melissa officinalis tem despertado interesse de alguns pesquisadores nos últimos anos devido a algumas particularidades terapêuticas, em especial às relacionadas ao Sistema Nervoso Central (SNC). O objetivo deste trabalho foi avaliar diferentes doses do extrato dessa planta no comportamento de ratos adultos, machos e fêmeas. Os efeitos da administração oral, por gavagem, do extrato alcoólico de Melissa officinalis sobre o comportamento de ratos, após o tratamento agudo ou subcrônico (10 dias), foram avaliados no teste da atividade locomotora (ambulação), teste do Labirinto em cruz elevado (ansiedade) e teste do nado forçado (depressão). Para o tratamento agudo foram usados 50 ratos machos e 50 ratos fêmeas, que foram subdivididos em 5 subgrupos de 10 animais, para receberem: 1) o diluente do extrato (animais controles), 2) diferentes doses do extrato (30, 100 ou 300 mg/kg) por via oral, 3) controle positivo (1 mg/kg de diazepam ou 10 mg/kg de fluoxetina, conforme o teste). Para o tratamento subcrônico (10 dias de tratamento), foram utilizados 50 ratos machos, que foram administrados, diariamente, as mesmas doses mencionadas anteriormente. As fêmeas, por sua vez, foram administradas as doses de 10, 30, 100 ou 300 mg/kg. Os testes foram realizados uma hora após o último dia de administração. Para a avaliação experimental, os animais foram levados cobertos do Biotério Setorial da Faculdade de Ciências da Saúde/Faculdade de Medicina para o Laboratório de Cirurgia Experimental, da Faculdade de Medicina, e foram mantidos na sala por um período de 1 hora para habituação ao ambiente do teste, onde esses foram realizados 1 hora após a administração dos extratos. Os resultados obtidos não mostraram nenhuma alteração comportamental quando o extrato de Melissa officinalis foi administrado agudamente. No entanto, quando administrado subcronicamente por 10 dias, o extrato modificou o comportamento dos animais, que demonstraram uma resposta sugestiva de atividade ansiolítica, tendo em vista que os animais avaliados no teste do LCE aumentaram a freqüência de entradas e o tempo de permanência nos braços abertos, sem que fosse alterada a freqüência de entradas dos animais nos braços fechados daquele Labirinto. Além disso, o extrato também favoreceu a redução do tempo de imobilidade no teste do nado forçado, sem que fossem observadas quaisquer alterações no número de ambulações avaliado nesses mesmos animais. Diante dos resultados mencionados, esse estudo reforça outros dados experimentais, mostrando que o extrato de Melissa officinalis pode se constituir em uma boa alternativa terapêutica medicinal para o tratamento de algumas alterações comportamentais relacionadas à ansiedade e depressão. _______________________________________________________________________________________ ABSTRACT / In recent past, the plant Melissa officinalis has received much attention from researchers due to its peculiar therapeutic benefits particularly in relation to the Central Nervous System (CNS). The aim of this work was thus to evaluate the effect of different doses of an alcoholic extract of Melissa officinalis on the behavior of adult male and female Wistar rats. The effects of oral administrations, by gavage, of the alcoholic extract of Melissa officinalis on the rats’ behavior after an acute and subchronic (ten days) treatment were evaluated using the Open field (locomotion), Elevated plus-maze (anxiety) and Forced swimming (depression) tests. For acute treatment, one hundred rats were used (50 male and 50 females); divided into subgroups of 10 animals per treatment (control solution, 30, 100, 300 mg/kg of extract and 1 mg/kg of diazepam or 10 mg/kg of fluoxetine as positive controls, by oral route. During the subchronic treatment, 50 male rats were used; different doses of the extract or control solution or the positive controls were administered daily for ten days, and on the tenth day animals were tested. On the other hand, female rats received doses of 10, 30, 100 or 300 mg/kg of extract or controls. The tests were carried out one hour after administration of the various treatments on the tenth day. For the experimental procedures, animal were covered and carried from the Animal Facility of Healthy Sciences Faculty/Faculty of Medicine to the Experimental Surgery Laboratory of the Faculty of Medicine. Animals were left in their cages and maintained in the experimental room for at least one hour before beginning the administration of the various treatments, in order to be habituated to the experimental environment. Results obtained after acute administration of the extract indicated that the rats' behavior was not altered. However, subchronic administration of the extract for 10 days modified the animals’ behavior, suggestive of an anxiolytic effect. This was indicated by an increase in the frequency of entries and the time spent in the open arms without a corresponding change in the frequency of enclosed arm entries in the Elevated plus maze. In addition, the extract also reduced immobility time in the forced swimming test, without changing locomotion in the Open field test. Despite the results mentioned above, this study requires further experimental data demonstrating that extracts of Melissa officinalis can be a good therapeutic or medicinal alternative for the treatment of certain behavioral conditions related to anxiety and depression.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-06-21T18:22:06Z No. of bitstreams: 1 Carolina Carvalho Bortoletto.pdf: 1150113 bytes, checksum: 3c91f95731b94e62999602e9c5b9f44f (MD5) / Made available in DSpace on 2018-06-21T18:22:06Z (GMT). No. of bitstreams: 1 Carolina Carvalho Bortoletto.pdf: 1150113 bytes, checksum: 3c91f95731b94e62999602e9c5b9f44f (MD5) Previous issue date: 2015-12-14 / Bruxism is defined as parafunctional habit of grinding or clenching, which may occur during sleep or wakefulness and headache is any pain related to the brain segment, being an extremely common manifestation. The objective of this research was to evaluate the association between bruxism and headache in children and the effect of therapy with Melissa officinalis L in muscle activity of children with bruxism. Children were assessed in the Early Childhood Center "Noemia Fabricio dos Santos Gatto" in the city of Araras, SP and Children's Clinic, Faculty of Dentistry, Nove de Julho University. Those responsible were asked to answer a questionnaire about sleep, and children subjected to clinical examination for diagnosis of bruxism, 24 children considered bruxism were selected and randomly divided into 2 groups: GI (n = 12) received oral ingestion of Melissa officinalis L. 20%, 15 drops of the dye, 2 times a day, 1 hour and 1 hour after lunch, after dinner, for 30 days and GII (n = 12) received plabebo solution in the same dosage group 1. The groups were evaluated for initial muscle activity and end by Bitestrip®. The results were computed and statistical analysis by adopting the 95% significance level, and there was no statistical difference in muscle activity, regardless of the therapy used. Data analysis showed a strong association between bruxism and headache (OR: 3.07). It follows that there is a strong association between bruxism and headache in children and that Melissa officinalis L, the dose used, did not show therapeutic effect in children bruxism. / O bruxismo é definido como hábito parafuncional de ranger ou apertar os dentes, podendo ocorrer durante o sono ou em vigília. A cefaleia consiste em qualquer dor referida no segmento cefálico, sendo uma manifestação extremamente comum. O objetivo dessa pesquisa foi avaliar a associação entre bruxismo e cefaleia em crianças e o efeito da terapia com Melissa officinalis L na atividade muscular de crianças com bruxismo. Foram avaliadas crianças matriculadas no Centro de Educação Infantil “Noemia Fabrício dos Santos Gatto” na cidade de Araras-SP e na Clínica Infantil da Faculdade de Odontologia da Universidade Nove de Julho. Os responsáveis foram instruídos a responder questionário sobre o sono, e as crianças submetidas a exame clínico para diagnóstico do bruxismo, 24 crianças consideradas bruxistas foram selecionadas e divididas aleatoriamente em 2 grupos: GI (n=12) recebeu ingestão oral de Melissa officinalis L. a 20%, 15 gotas da tintura, 2 vezes ao dia, 1 hora após almoço e 1 hora após o jantar, durante 30 dias e o GII (n=12) recebeu solução plabebo, na mesma posologia do grupo 1. Os grupos foram submetidos à avaliação da atividade muscular inicial e final por meio da Bitestrip®. Os resultados obtidos foram computados e análise estatística realizada adotando-se nível de significância de 95%, sendo que não houve diferença estatística na atividade muscular, independente da terapia utilizada. A análise dos dados demonstrou uma forte associação entre bruxismo e cefaleia (OR: 3,07). Concluiu-se que existe uma forte associação entre bruxismo e cefaleia em crianças e que a Melissa officinalis L, na posologia utilizada, não apresentou efeito terapêutico para o bruxismo em crianças.

A creative nonfiction thesis, Luke's Mama is a memoir of personal essays that explore how the birth of my son has affected the ways that I relate within and interpret different areas of my life. Chapter I, Introduction, identifies personal and ethical concerns involved in telling my story and explores how others have handled similar issues. Chapter II, Family, illustrates how my relationship with my family of origin has changed since I've become a parent and also how my new family and I interact with society. Chapter III, Calling, depicts my struggle in finding a balance between work and family priorities. Chapter IV, Partner, presents a contrast between my relationship with my partner before and after my son's birth. Chapter V, Parent, displays the beginning of my ever-growing relationship with my son and sense of parenthood.

My thesis work includes 10 large drawings that explore the narrative qualities of line movement. I use line in these drawings as a recording device to document both the physical activity of the process and the personal experience that the lines represent. Through this work I attempt to develop a language of visual imagery that is autobiographical in nature. A system of personal symbols and recurring forms make up the structure of this visual vocabulary. Line movement and rhythm provides a sense of the dialog.

The objective of this study is to extract phenolic compounds from nettle and melissa by using microwave and ultrasound and to compare these methods with conventional extraction and maceration, respectively. Extraction of melissa essential oil was also studied. In extraction of phenolics, effects of extraction time (5-20 min for microwave / 5-30 min for ultrasound) and solid to solvent ratio (1:10, 1:20, 1:30 g/ml) on total phenolic content (TPC) were investigated for microwave and ultrasound extractions. Different powers were also studied for ultrasound extraction. In addition, effect of solvent type (water, ethanol, ethanol-water mixture at 50:50 v/v) was analyzed and water was found as better solvent. Optimum conditions for microwave extraction of phenolics were determined as 10 min and 1:30 solid to solvent ratio for nettle, and as 5 min and 1:30 solid to solvent ratio for melissa. TPC at these conditions for nettle and melissa extracts were 24.6 and 145.8 mg GAE/g dry material, respectively. Optimum conditions for ultrasound extraction was 30 min, 1:30 solid to solvent ratio, and 80% power for nettle and 20 min, 1:30 solid to solvent ratio, and 50% power for melissa. TPC at these conditions for nettle and melissa were 23.9 and 105.5 mg GAE/g dry material, respectively. Major phenolic acids were determined as naringenin in nettle and rosmarinic acid in melissa. Major aromatic compounds in melissa essential oil were found as limonene, citral, and caryophyllene oxide. Yields of essential oil obtained by microwave and hydrodistillation were 4.1 and 1.8 mg oil/g dry sample, respectively.

Inaug.-Diss.--Berlin. / Vita.