Plantas medicinais e óleos essenciais representam um importante papel na terapêutica, tanto na cura como também na prevenção de diferentes enfermidades, sendo esta prática medicinal uma das mais antigas formas de tratamento. Devido à utilização dos óleos essenciais na terapêutica e a importância do conhecimento do pontencial de toxicidade destes, objetivou-se: (i) identificar os principais componentes químicos dos óleos essenciais de Origanum vulgare (orégano), Origanum majorana (manjerona) e Rosmarinus officinalis (alecrim); (ii) avaliar a atividade antifúngica in vitro destes óleos essenciais frente a leveduras isoladas de animais hígidos e casos clínicos; (iii) avaliar a irritação/corrosão cutânea e ocular aguda dos três óleos essenciais e (iv) avaliar a sensibilização cutânea do óleo essencial de orégano. O material vegetal foi adquirido de distribuidor comercial e encaminhado para extração do óleo essencial por hidrodestilação em Clevenger e, para análise cromatográfica através da cromatografia gasosa. Para realização dos testes in vitro foi utilizado o método de microdiluição em caldo, documento M27A3 do Clinical and Laboratory Standards Institute (CLSI) com adaptações para fitofármacos e Malassezia pachydermatis. Os óleos essenciais de orégano, manjerona e alecrim foram testados nas concentrações de 28 a 0,87mg/mL, 60 a 1,87mg/mL e 112,8 a 3,52mg/mL, respectivamente. Os testes de toxicidade in vivo foram realizados conforme a Organisation for Economic Co-operation and Development (OECD). Para os testes de irritação/corrosão cutânea (OECD 404, 2002) e ocular aguda (OECD 405, 2002) foram utilizados 24 coelhos albinos (Oryctolagus cuniculus), Nova Zelândia, machos, adultos e hígidos. Na sensibilização cutânea (OECD 406, 1992) utilizaram-se 33 cobaios (Cavia porcellus), fêmeas, adultas e hígidas. Os compostos majoritários do orégano foram timol, -terpineno e 4-terpineol; da manjerona timol, 4-terpineol e p-cimeno e; do alecrim α-pineno e 1,8 cineol. A Concentração Inibitória Mínima (CIM) e Concentração Fungicida Mínima (CFM) do óleo essencial de orégano para M. pachydermatis variaram de ≤0,87 a 7mg/mL. Para manjerona a CIM e a CFM foram de ≤1,87 a 30mg/mL e de ≤3,52 a 112,8mg/mL para o alecrim nos isolados de M. pachydermatis, Candida spp e T. asahii. Nas avaliações da irritação/corrosão cutânea do óleo essencial de orégano 3% somente um animal apresentou eritema leve nas 24h com regressão aos sete dias e, edema leve nas 72h com regressão aos sete dias. Na irritação/corrosão ocular, apenas um animal apresentou reação inflamatória nas avaliações de 24 e 48h, regredindo nas 72h. Na sensibilização cutânea, os animais responderam à indução, mas nenhum respondeu ao desafio. Nos animais tratados com óleo essencial de manjerona 6% nas 24, 48 e 72h apresentaram eritema leve, regredindo em até sete dias. Dois animais apresentaram edema leve nas 24 e 48h com remissão nas 72h e um animal permaneceu sem alterações Em dois animais do grupo alecrim 24% as lesões de eritema/escara regrediram em 21 dias. Quanto ao edema, as lesões foram consideradas reversíveis aos sete dias. Conclui-se que M. pachydermatis é sensível ao óleo essencial de orégano; que os óleos essenciais de manjerona e alecrim possuem atividade antifúngica in vitro frente a isolados de animais; o óleo essencial de orégano 3% causa irritação cutânea e ocular aguda leve e, não causa sensibilização cutânea na concentração testada. O óleo essencial de manjerona 6% causa irritação cutânea e ocular aguda leve e, o óleo essencial de alecrim 24% causa irritação cutânea e ocular aguda moderada. / Medicinal plants and essential oils represent an important therapeutic role in the cure and diseases different prevention both, this medical practice is one the oldest treatment forms. Thus, the aim was: (i) identify the main chemical components of essential oils from Origanum vulgare (oregano), Origanum majorana (marjoram) and Rosmarinus officinalis (rosemary), (ii) evaluate the in vitro antifungal activity of essential oils against yeasts isolated from healthy animals and clinical cases, (iii) evaluate the irritation/skin corrosion and acute eye of the three essential oils and (iv) assess the skin sensitization of the oregano essential oil. The plant material was purchased from commercial distributor and referred for essential oil extraction and gas chromatography. We used the method of microdilution M27-A3 with adaptations for phytochemicals and Malassezia pachydermatis. The oregano essential oils, marjoram and rosemary were tested at concentrations from 28 to 0.87 mg/mL, 60 to 1.87 mg/mL and 112.8 to 3.52 mg/mL, respectively. The in vivo toxicity tests were performed according to the Organization for Economic Co-operation and Development (OECD). The twenty-four males, adults and healthy rabbits (Oryctolagus cuniculus) were used for irritation/corrosion skin (OECD 404, 2002) and eye acute (OECD 405, 2002) tests. The thirty-three adults, females and healthy guinea pigs (Cavia porcellus) were used for sensitization skin test (OECD 406, 1992). The major compounds in oregano were thymol, α-terpinene and 4-terpineol, in marjoram were thymol, 4-terpineol, and p-cymene and in rosemary were α-pinene and 1,8 cineole. The Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of the oregano essential oil against to M. pachydermatis were ≤ 0.87 to 7mg/mL, while the MIC and MFC of the marjoram were ≤ 1.87 to 30mg/mL. The MIC and CFM of the rosemary were ≤ 3.52 to 112.8 mg/mL against to M. pachydermatis, Candida spp and T. asahii. In the irritation/skin corrosion test, only one animal at 24h had slight erythema with regression at 7 days and slight edema at 72 h with regression to 7 days against to oregano essential oil at 3%. In the eye irritation/corrosion test, only one animal showed inflammatory reaction signs at 24 and 48h evaluates, but the assessments 72h had regressed. In the skin sensitization test, the animals responded, but anyone responded to the challenge. The treated with marjoram essential oils at 6%, the animals showed slight erythema at 24, 48 and 72h evaluate, with regression to 7 days. About to edema presentation, two animals showed moderate at 24 and 48h, with regression at 72h, only one animal without signs. The group rosemary at 24%, the erythema/eschar lesions in two animals were regression at 21 days. About the edema, the lesions were reversible for seven days. The conclusion was the sensibility of M. pachydermatis against to oregano essential oil, antifungal activity in vitro of marjoram and rosemary essential oils against animals isolates, the oregano essential oil at 3% induces skin and eye irritation slight acute and doesn’t induce skin sensitization. The marjoram essential oil at 6% induces skin and eye irritation slight acute, the rosemary essential oil at 24% induces skin and eye irritation moderate acute.

Plantas medicinais e óleos essenciais representam um importante papel na terapêutica, tanto na cura como também na prevenção de diferentes enfermidades, sendo esta prática medicinal uma das mais antigas formas de tratamento. Devido à utilização dos óleos essenciais na terapêutica e a importância do conhecimento do pontencial de toxicidade destes, objetivou-se: (i) identificar os principais componentes químicos dos óleos essenciais de Origanum vulgare (orégano), Origanum majorana (manjerona) e Rosmarinus officinalis (alecrim); (ii) avaliar a atividade antifúngica in vitro destes óleos essenciais frente a leveduras isoladas de animais hígidos e casos clínicos; (iii) avaliar a irritação/corrosão cutânea e ocular aguda dos três óleos essenciais e (iv) avaliar a sensibilização cutânea do óleo essencial de orégano. O material vegetal foi adquirido de distribuidor comercial e encaminhado para extração do óleo essencial por hidrodestilação em Clevenger e, para análise cromatográfica através da cromatografia gasosa. Para realização dos testes in vitro foi utilizado o método de microdiluição em caldo, documento M27A3 do Clinical and Laboratory Standards Institute (CLSI) com adaptações para fitofármacos e Malassezia pachydermatis. Os óleos essenciais de orégano, manjerona e alecrim foram testados nas concentrações de 28 a 0,87mg/mL, 60 a 1,87mg/mL e 112,8 a 3,52mg/mL, respectivamente. Os testes de toxicidade in vivo foram realizados conforme a Organisation for Economic Co-operation and Development (OECD). Para os testes de irritação/corrosão cutânea (OECD 404, 2002) e ocular aguda (OECD 405, 2002) foram utilizados 24 coelhos albinos (Oryctolagus cuniculus), Nova Zelândia, machos, adultos e hígidos. Na sensibilização cutânea (OECD 406, 1992) utilizaram-se 33 cobaios (Cavia porcellus), fêmeas, adultas e hígidas. Os compostos majoritários do orégano foram timol, -terpineno e 4-terpineol; da manjerona timol, 4-terpineol e p-cimeno e; do alecrim α-pineno e 1,8 cineol. A Concentração Inibitória Mínima (CIM) e Concentração Fungicida Mínima (CFM) do óleo essencial de orégano para M. pachydermatis variaram de ≤0,87 a 7mg/mL. Para manjerona a CIM e a CFM foram de ≤1,87 a 30mg/mL e de ≤3,52 a 112,8mg/mL para o alecrim nos isolados de M. pachydermatis, Candida spp e T. asahii. Nas avaliações da irritação/corrosão cutânea do óleo essencial de orégano 3% somente um animal apresentou eritema leve nas 24h com regressão aos sete dias e, edema leve nas 72h com regressão aos sete dias. Na irritação/corrosão ocular, apenas um animal apresentou reação inflamatória nas avaliações de 24 e 48h, regredindo nas 72h. Na sensibilização cutânea, os animais responderam à indução, mas nenhum respondeu ao desafio. Nos animais tratados com óleo essencial de manjerona 6% nas 24, 48 e 72h apresentaram eritema leve, regredindo em até sete dias. Dois animais apresentaram edema leve nas 24 e 48h com remissão nas 72h e um animal permaneceu sem alterações Em dois animais do grupo alecrim 24% as lesões de eritema/escara regrediram em 21 dias. Quanto ao edema, as lesões foram consideradas reversíveis aos sete dias. Conclui-se que M. pachydermatis é sensível ao óleo essencial de orégano; que os óleos essenciais de manjerona e alecrim possuem atividade antifúngica in vitro frente a isolados de animais; o óleo essencial de orégano 3% causa irritação cutânea e ocular aguda leve e, não causa sensibilização cutânea na concentração testada. O óleo essencial de manjerona 6% causa irritação cutânea e ocular aguda leve e, o óleo essencial de alecrim 24% causa irritação cutânea e ocular aguda moderada. / Medicinal plants and essential oils represent an important therapeutic role in the cure and diseases different prevention both, this medical practice is one the oldest treatment forms. Thus, the aim was: (i) identify the main chemical components of essential oils from Origanum vulgare (oregano), Origanum majorana (marjoram) and Rosmarinus officinalis (rosemary), (ii) evaluate the in vitro antifungal activity of essential oils against yeasts isolated from healthy animals and clinical cases, (iii) evaluate the irritation/skin corrosion and acute eye of the three essential oils and (iv) assess the skin sensitization of the oregano essential oil. The plant material was purchased from commercial distributor and referred for essential oil extraction and gas chromatography. We used the method of microdilution M27-A3 with adaptations for phytochemicals and Malassezia pachydermatis. The oregano essential oils, marjoram and rosemary were tested at concentrations from 28 to 0.87 mg/mL, 60 to 1.87 mg/mL and 112.8 to 3.52 mg/mL, respectively. The in vivo toxicity tests were performed according to the Organization for Economic Co-operation and Development (OECD). The twenty-four males, adults and healthy rabbits (Oryctolagus cuniculus) were used for irritation/corrosion skin (OECD 404, 2002) and eye acute (OECD 405, 2002) tests. The thirty-three adults, females and healthy guinea pigs (Cavia porcellus) were used for sensitization skin test (OECD 406, 1992). The major compounds in oregano were thymol, α-terpinene and 4-terpineol, in marjoram were thymol, 4-terpineol, and p-cymene and in rosemary were α-pinene and 1,8 cineole. The Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of the oregano essential oil against to M. pachydermatis were ≤ 0.87 to 7mg/mL, while the MIC and MFC of the marjoram were ≤ 1.87 to 30mg/mL. The MIC and CFM of the rosemary were ≤ 3.52 to 112.8 mg/mL against to M. pachydermatis, Candida spp and T. asahii. In the irritation/skin corrosion test, only one animal at 24h had slight erythema with regression at 7 days and slight edema at 72 h with regression to 7 days against to oregano essential oil at 3%. In the eye irritation/corrosion test, only one animal showed inflammatory reaction signs at 24 and 48h evaluates, but the assessments 72h had regressed. In the skin sensitization test, the animals responded, but anyone responded to the challenge. The treated with marjoram essential oils at 6%, the animals showed slight erythema at 24, 48 and 72h evaluate, with regression to 7 days. About to edema presentation, two animals showed moderate at 24 and 48h, with regression at 72h, only one animal without signs. The group rosemary at 24%, the erythema/eschar lesions in two animals were regression at 21 days. About the edema, the lesions were reversible for seven days. The conclusion was the sensibility of M. pachydermatis against to oregano essential oil, antifungal activity in vitro of marjoram and rosemary essential oils against animals isolates, the oregano essential oil at 3% induces skin and eye irritation slight acute and doesn’t induce skin sensitization. The marjoram essential oil at 6% induces skin and eye irritation slight acute, the rosemary essential oil at 24% induces skin and eye irritation moderate acute.

Submitted by Ubirajara Cruz (ubirajara.cruz@gmail.com) on 2017-03-27T15:20:13Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_Anelise_Fonseca.pdf: 3465232 bytes, checksum: f05a9c58180cb611f7817c4afa026cba (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2017-03-27T20:50:38Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_Anelise_Fonseca.pdf: 3465232 bytes, checksum: f05a9c58180cb611f7817c4afa026cba (MD5) / Made available in DSpace on 2017-03-27T20:50:38Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_Anelise_Fonseca.pdf: 3465232 bytes, checksum: f05a9c58180cb611f7817c4afa026cba (MD5) Previous issue date: 2015-02-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Pythium insidiosum é um oomiceto aquático e agente etiológico da pitiose, uma doença infecciosa, não contagiosa, de difícil tratamento e prognóstico desfavorável, que acomete mamíferos que habitam áreas pantanosas e alagadas. O presente estudo teve como objetivos: a) avaliar e padronizar um inóculo a partir de cultivo micelial de P. insidiosum; b) avaliar a suscetibilidade in vitro de P. insidiosum aos óleos essenciais de Origanum vulgare, Origanum majorana, Mentha piperita e Rosmarinus officinalis; c) investigar a ação antimicrobiana dos óleos essenciais de O. vulgare e M. piperita sozinhos, associados e em combinação com imunoterapia no tratamento da pitiose experimental. O inóculo foi confeccionado a partir de cultura micelial de P. insidiosum e testado frente a antifúngicos azólicos. Os resultados foram comparados aos testes de suscetibilidade empregando o inóculo padrão de zoósporos frente aos mesmos antifúngicos. O inóculo proposto mostrou padrões de suscetibilidade comparáveis ao inoculo padrão, indicando, portanto, que pode ser um método adequado para avaliar-se a suscetibilidade deste oomiceto, particularmente quando não é possível obter-se o inóculo padrão. Os óleos foram analisados por cromatografia gasosa acoplada a espectrometria de massa. Os componentes majoritários dos óleos essenciais foram os seguintes: O. vulgare: carvacrol (93,10%) e beta; O. majorana: 1,4-terpineol (34,34%); M. piperita: mentona (57,53%); R. officinalis: 1,8-cineol (64,53%). A atividade antimicrobiana foi determinada pelo método de microdiluição em caldo frente a 22 isolados de P. insidiosum. Os óleos foram submetidos a uma série de diluições, obtendo-se concentrações de 14 a 0,025mg/mL. As concentrações inibitórias mínimas para O. majorana, M. piperita e R. officinallis variaram de 0,11 a 3,5mg/mL e para O. vulgare de 0,05 a 1,75mg/mL. Os resultados evidenciaram que os óleos essenciais avaliados apresentaram ação antimicrobiana sobre P. insidiosum, ressaltando-se a melhor atividade do óleo essencial de O. vulgare. A partir destes dados delineou-se o experimento in vivo, no qual foram utilizados 18 coelhos com pitiose experimental, divididos em seis grupos de três animais sendo: grupo 1 controle; grupo 2 tratados com óleo essencial de M. piperita; grupo 3 tratados com óleo essencial de O. vulgare; grupo 4 tratados com imunoterápico Pitium Vac®; grupo 5 tratados com associação dos óleos de M. piperita e O. vulgare e grupo 6 tratados com associação dos óleos plus imunoterápico. Os óleos foram formulados em creme tópico e as lesões foram tratadas diariamente por 45 dias; os animais dos grupos 4 e 6 receberam uma dose do imunoterápico a cada 14 dias. Os resultados revelaram que a evolução das lesões dos grupos 5 e 6, não diferiram entre si, porém diferiram dos demais grupos. Evidenciou-se que as lesões do grupo 5 aumentaram 3.16 vezes a cada dia, enquanto àquelas do grupo 6, aumentaram 1.83 vezes, indicando o menor crescimento das lesões quando o tratamento empregou a combinação das terapias. Este estudo é pioneiro no tratamento da pitiose experimental empregando óleos essenciais de plantas e combinação de terapias com óleos em pitiose. Demonstrou que o emprego de óleos essenciais pode se constituir numa alternativa viável de tratamento da pitiose cutânea, particularmente quando utilizados em combinação ou em associação com imunoterapia. / Pythium insidiosum is an aquatic oomycete and etiological agent of Pythiosis, an infectious, non-contagious, difficult-to-treat disease. It affects mammals that inhabit marshy and flooded areas. This study aimed to: a) evaluate and standardize an inoculum from P. insidiosum mycelial culture; b) evaluate P. insidiosum in vitro susceptibility to Origanum vulgare, Origanum majorana, Mentha piperita and Rosmarinus officinalis essential oils; c) investigate the antimicrobial activity of O. vulgare and M. piperita essential oils separately, associated and in combination with immunotherapy in the treatment of experimental Pythiosis. The inoculum was prepared from P. insidiosum mycelial culture and tested against azole antifungals. The results were compared to susceptibility tests by using zoospore standard inoculum against the same antifungals. The proposed inoculum showed susceptibility patterns comparable to standard inoculum, thus indicating that it can be a suitable method to evaluate oomycete susceptibility, particularly when it is not possible to obtain standard inoculum. The oils were analyzed by gas chromatography mass spectrometry. Essential oils main components were as follows: O. vulgare: carvacrol (93.10%); O. majorana: 4-terpineol (34.34%); M. piperita: menthone (57.53%); A. officinalis: 1.8-cineole (64.53%). Antimicrobial activity was determined by the broth microdilution method against 22 P. insidiosum isolates. The oils were subjected to serial dilutions, and 14-0.025mg/mL concentrations were obtained. O. marjorana, M. piperita and R. officinalis minimum inhibitory concentrations ranged from 0.11 to 3.5 mg/mL, and those for O. vulgare, from 0.05 to 1.75 mg/mL. The results showed that the tested essential oils had antimicrobial effect on P. insidiosum, with O. vulgare essential oil being the most active. The in vivo experiment was outlined from these results. Eighteen rabbits with experimental Pythiosis, divided into six groups of three animals, were used: group 1 control; group 2 was treated with Mentha piperita essential oil; group 3 was treated with Origanum vulgare essential oil; group 4 was treated with commercial immunotherapic; group 5 was treated with a combination of Mentha piperita and Origanum vulgare oils, and group 6 was treated with a combination of immunotherapy plus oils. The oils were formulated as topical cream and lesions were treated daily for 45 days; animals in groups 4 and 6 received an immunotherapy dose every 14 days. The results revealed that the evolution of lesions in groups 5 and 6 did not differ between each other, but differed from the other groups. Group 5 lesions increased 3.16 fold every day, whereas those in group 6 increased 1.83 fold, thus showing that the smallest lesion growth occurred when an combination of therapies was employed. This is the first study to use essential oils from plants and a combined oil therapy in theexperimental treatment of Pythiosis. It was demonstrated that the use of essential oils can be a viable alternative for skin Pythiosis treatment, particularly when used in combination with or associated to immunotherapy.

This dissertation is the collection of a progressive research on the topic of topological quantum computation and information with the focus on the error threshold of the well-known models such as the unpaired Majorana, the toric code, and the planar code. We study the basics of quantum computation and quantum information, and in particular quantum error correction. Quantum error correction provides a tool for enhancing the quantum computation fidelity in the noisy environment of a real world. We begin with a brief introduction to stabilizer codes. The stabilizer formalism of the theory of quantum error correction gives a well-defined description of quantum codes that is used throughout this dissertation. Then, we turn our attention to a quite new subject, namely, topological quantum codes. Topological quantum codes take advantage of the topological characteristics of a physical many-body system. The physical many-body systems studied in the context of topological quantum codes are of two essential natures: they either have intrinsic interaction that self-corrects errors, or are actively corrected to be maintained in a desired quantum state. Examples of the former are the toric code and the unpaired Majorana, while an example for the latter is the surface code. A brief introduction and history of topological phenomena in condensed matter is provided. The unpaired Majorana and the Kitaev toy model are briefly explained. Later we introduce a spin model that maps onto the Kitaev toy model through a sequence of transformations. We show how this model is robust and tolerates local perturbations. The research on this topic, at the time of writing this dissertation, is still incomplete and only preliminary results are represented. As another example of passive error correcting codes with intrinsic Hamiltonian, the toric code is introduced. We also analyze the dynamics of the errors in the toric code known as anyons. We show numerically how the addition of disorder to the physical system underlying the toric code slows down the dynamics of the anyons. We go further and numerically analyze the presence of time-dependent noise and the consequent delocalization of localized errors. The main portion of this dissertation is dedicated to the surface code. We study the surface code coupled to a non-interacting bosonic bath. We show how the interaction between the code and the bosonic bath can effectively induce correlated errors. These correlated errors may be corrected up to some extend. The extension beyond which quantum error correction seems impossible is the error threshold of the code. This threshold is analyzed by mapping the effective correlated error model onto a statistical model. We then study the phase transition in the statistical model. The analysis is in two parts. First, we carry out derivation of the effective correlated model, its mapping onto a statistical model, and perform an exact numerical analysis. Second, we employ a Monte Carlo method to extend the numerical analysis to large system size. We also tackle the problem of surface code with correlated and single-qubit errors by an exact mapping onto a two-dimensional Ising model with boundary fields. We show how the phase transition point in one model, the Ising model, coincides with the intrinsic error threshold of the other model, the surface code.

Submitted by Luciclea Silva (luci@ufpa.br) on 2018-11-01T17:20:15Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EstadosligadosMajorana.pdf: 5157889 bytes, checksum: a697f1a4428dbb52f1b3046f7b793221 (MD5) / Approved for entry into archive by Luciclea Silva (luci@ufpa.br) on 2018-11-01T17:20:40Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EstadosligadosMajorana.pdf: 5157889 bytes, checksum: a697f1a4428dbb52f1b3046f7b793221 (MD5) / Made available in DSpace on 2018-11-01T17:20:40Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EstadosligadosMajorana.pdf: 5157889 bytes, checksum: a697f1a4428dbb52f1b3046f7b793221 (MD5) Previous issue date: 2018-10-11 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A pesquisa em física da matéria condensada com isolantes e supercondutores topológicos tem contribuído muito para a caracterização das propriedades de superfície e de modos zero em nanofios. Investigamos teoricamente o transporte de elétrons através do ponto quântico em forma de T (PQ) com um único nível e spinless, conectado a uma cadeia em zigue zague e acoplado a um supercondutor p-wave, utilizando o método analítico recursivo de funções de green no equilíbrio. Este modelo é uma extensão da cadeia de Kitaev para uma rede triangular de tamanho finito com três, quatro e cinco sitios. Observamos que modos zero de Majorana podem ser sintonizados através dos parâmetros de acoplamento do dispositivo e a condutância linear mostra ambos os Estados Ligados de Majorana (MBS) na fase topológica e na fase topológica geral maximamente robusta. Este modelo mais realista permite a detecção de MBS através do controle dos parâmetros que governam o tunelamento eletrônico e pode ser útil para experimentos relevantes. / The research in condensed matter physics with insulators and superconductors topological has contributed greatly to the characterization of the surface properties and modes zero in nanowires. We investigate theoretically, through the recursive Green’s function approach, the electron transport through the T-shaped quantum dot (PQ) with a single level and spinless, connected to a zigue zague chain and coupled to a p-wave superconductor. This model is an extension of the Kitaev chain for a network triangular of finite-size with for three, four, and five sites. We find that the Majorana zero modes can be tuned through the coupling parameters of the device and the linear conductance show both the Majorana Bound States (MBS) in topological phase and in the general topological phase maximally robust. This more realistic model allows the detection of MBS through of the control of the parameters governing the electronic tunneling and can be helpful for relevant experiments. Keywords: Majorana Fermions, recursive Green’s function approach, Kitaev chain, class of electronic nanodevices, Quantum Dot, T-shaped, Qubit, Majorana Bound States (MBS).

As propriedades terapêuticas das plantas medicinais são cada vez mais estudadas, principalmente devido aos crescentes casos de resistência antimicrobiana, como observado em cepas do Complexo Sporothrix. As plantas da família Lamiaceae são conhecidas por suas propriedades antifúngicas, entretanto, são escassos seus estudos contra agentes causadores da esporotricose. Devido ao potencial promissor dessas plantas, objetivou-se (1) avaliar a atividade anti-Sporothrix spp. in vitro de Origanum vulgare L. (orégano), Origanum majorana L. (manjerona) e Rosmarinus officinalis L. (alecrim) nas formas de óleos essenciais, extratos aquosos de infusão e decocção e extratos hidroalcoólicos contra isolados clínicos de Sporothrix spp. obtidos de casos clínicos de esporotricose humana, canina e felina; (2) avaliar os principais constituintes químicos presentes nos óleos essenciais das plantas; e (3) avaliar a atividade citotóxica in vitro. Extratos aquosos e hidroalcoólicos foram preparados a partir de partes aéreas das plantas. Em óleos essenciais, produtos comerciais e produtos extraídos de partes aéreas por hidrodestilação em Clevenger foram testados. Ambos óleos foram analisados quimicamente por cromatografia gasosa. Testes in vitro foram realizados pela técnica de Microdiluição em Caldo contra isolados clínicos de Sporothrix spp. oriundos de humanos, caninos e felinos, bem como ambiental nas fases leveduriforme (CLSIM27A3) e filamentosa (CLSI-M38A2), sendo testados entre 72 a 0.07 mg/mL. Os efeitos citotóxicos foram avaliados através do ensaio MTT em células VERO (78 a 5000 μg/mL). Na fase leveduriforme, os óleos essenciais extraído e comercial de orégano apresentaram atividade anti-Sporothrix spp. nas concentrações inibitórias mínimas (CIM) e concentrações fungicidas mínimas (CFM) de 36 a ≤2.25 mg/mL e de alecrim entre 72 a≤2.25 mg/mL, não havendo diferença estatística entre os tipos de óleos. Por sua vez, óleo comercial de manjerona apresentou CIM/CFM de 18 a ≤2.25 mg/mL. Na fase micelial, 100% dos isolados felinos e caninos foram sensíveis aos óleos essenciais de orégano (0.14 a ≤0.07 mg/mL), alecrim (18 a ≤0,07 mg/mL) e manjerona (4.5 a ≤0.07 mg/mL). Extratos aquosos e hidroalcoólicos de orégano apresentaram atividade inibitória e fungicida, respectivamente, em 100% e entre 90% a 35% dos isolados animais (40 a ≤0.07 mg/mL). Nas mesmas concentrações, o extrato hidroalcoólico de manjerona inibiu de 90% a 100% dos isolados. Entretanto, os demais extratos de manjerona e de alecrim apresentaram fraca atividade anti-Sporothrix spp. sobre 40% a 5% dos isolados, não havendo atividade antifúngica sobre as infusões de alecrim preparadas em 10 e 60 minutos. Sobre itraconazol, Sporothrix spp. foi sensível na fase leveduriforme (16 a ≤0.03 μg/mL) e filamentosa (64 a ≤0.12 μg/mL), entretanto, 5 foi observada resistência antifúngica em 4% e 28% (CIM e CFM >16 μg/mL, respectivamente) dos isolados na fase leveduriforme, ao passo que, na fase filamentosa, a resistência ocorreu em 12,5% e 85% dos isolados (CIM e CFM >64 μg/mL, respectivamente). Os óleos essenciais de orégano e manjerona apresentaram maior atividade citotóxica com 80% de inviabilidade celular, ao passo que os extratos aquosos e hidroalcoólico de manjerona foram os menos citotóxicos. A análise química foi similar nos produtos das plantas Lamiaceae, diferindo a concentração dos compostos, os quais α-pineno e 1,8-cineol foram majoritários para o óleo extraído do alecrim e α- terpineno, terpineol-4 e timol para o óleo extraído de orégano, ao passo que 1,8-cineol foi majoritário para os produtos comerciais de alecrim e manjerona, e carvacrol para orégano. A boa atividade anti-Sporothrix spp. in vitro das plantas da família Lamiaceae, em especial ao Origanum vulgare L., é promissora para o tratamento da esporotricose, inclusive sobre isolados clínicos resistentes. / Therapeutics properties of medicinal plants are increasingly studied, mainly due to increasing cases of antimicrobial cases, as observed in strains of Sporothrix Complex. Plants of Lamiaceae family are known for their antifungal properties, but studies in causative agents of sporotrichosis are scarces. Due to the promising potential of these plants, aimed to (1) evaluate the in vitro anti-Sporothrix spp. activity of aqueous extracts of infusion and decoction, hydroalcoholic extract and essential oils os Origanum vulgare L. (oregano), Origanum majorana L. (marjoram) and Rosmarinus officinalis L. (rosemary); (2) evaluate the main chemical constituents present in essential oils; and (3) evaluate the in vitro cytotoxic activity. Aqueous and hydroalcoholic extracts were prepared from the aerial parts of the plants. In essential oils, commercial products and extracted products from aerial parts through hydrodistillation in Clevenger were tested. Both essential oils were chemically analyzed by gas chromatography. In vitro tests were performed by broth microdilution technique against clinical isolates of Sporothrix spp. from humans, dogs and cats with sporotrichosis, as well as environmental soil, in yeast (CLSI-M27A3) and mycelial (CLSI-M38A2) phases and tested from 72 to 0.07 mg/mL. Cytotoxic effects were assessed by MTT assay on VERO cells (78 to 5000 μg/mL). In yeast phase, the extracted and commercial essential oils of oregano showed anti-Sporothrix spp. activity in the minimum inhibitory concentrations (MIC) and minimum fungicidal concentration (MFC) of 36 to ≤2.25 mg/mL and rosemary between 72 to ≤2.25 mg/mL, with no statistical difference between the types of oils. In turn, commercial marjoram oil showed MIC/MFC of ≤2.25 to 18 mg/mL. In the mycelial phase, 100% of feline and canine isolates were sensibles to essential oils of oregano (0.14 to ≤0.07 mg/mL), rosemary (18 to ≤0,07 mg/mL) and marjoram (4.5 to ≤0.07 mg/ml). Aqueous and hydroalcoholic extracts of oregano showed inhibitory and fungicidal activity, respectively, 100% and between 90% and 35% of animal isolates (40 to ≤0.07 mg/mL). In the same concentrations, hydroalcoholic extract of marjoram inhibited 90% to 100% of the isolates. However, other extracts of marjoram and rosemary showed weak activity anti- Sporothrix spp. about 40% to 5% of the isolates, with no antifungal activity by INF10 and INF60 rosemary. About itraconazole, Sporothrix spp. was sensitive in the yeast phase (16 to ≤0.03 mg/mL) and filamentous (64 to ≤0.12 mg/mL), however, antifungal resistance was observed in 4% and 28% (MIC and MFC > 16 μg/mL, respectively) in fungal isolates in the yeast form, and in the mycelial form, the resistence occurred in 12.5% and 85% of isolates (MIC and MFC > 64 μg/mL, respectively). Essential oils of oregano and marjoram exhibited greater cytotoxic activity with 80% cell inviability, while hydroalcoholic and aqueous extracts of marjoram were less cytotoxic. The chemical analysis was similar for the products of Lamiaceae plants and differed in the concentration of the compounds, which α-pinene and 1,8-cineole were majoritary for extracted oil of rosemary and α-terpinene, terpineol-4 and thymol for extracted oil of 7 oregano, while 1,8-cineole was majoritary for commercial products of rosemaru and marjoram, and carvacrol for oregano. The good in vitro anti-Sporothrix spp. activity of the plants of Lamiaceae family, mainly to Origanum vulgare L., is promising for the treatment of sporotrichosis, including against clinical isolates resistant.

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as PEGylated bioconjugate of OME with TPP (P-OME-TPP) against human breast epithelial and cancer cell lines was investigated. Initially, TPP, a lipophilic cation, was used to check whether an imbalance in mitochondrial bioenergetics, in part, may be responsible for estrogen induced growth of breast cancer. The results showed that exposure of estrogen-dependent MCF-7 cells to 17 β-estradiol (E2) induced the metabolic activity, proliferation, mitochondrial bioenergetics, DNA damage, and formation of cellular and mitochondrial reactive oxidant species (ROS). These E2-induced endpoints were inhibited by co-treatment with TPP, indicating mitochondrial mechanisms, in part, may contribute to the development of breast cancer. Furthermore, O. majorana, widely used in the Middle East as a culinary aromatic medicinal herb, has been shown to possess an extensive range of biological activity including antioxidant, anti-inflammatory, and anti-tumor growth effects. Interestingly, the anticancer potential of O. majorana against breast cancer remains largely unexplored; therefore, the anticancer effect of O. majorana on breast cell lines was investigated. The results showed that E2-induced metabolic activity and growth were inhibited by OME in MCF-7 cells. The results also demonstrated that synthesized P-OME-TPP conjugate, compared to OME, was far more effective in exerting its cytotoxic effect through the inhibition of growth and mitochondrial metabolic activity in both highly metastatic, triple negative MDA-MB-231 and estrogen-dependent MCF-7 breast cancer cells. Altogether, these findings offer a new perspective on the utility of mitochondria-targeted lipophilic TPP cation and the potential of O. majorana extract to be developed as a new therapy against breast tumors.

As propriedades terapêuticas das plantas medicinais são cada vez mais estudadas, principalmente devido aos crescentes casos de resistência antimicrobiana, como observado em cepas do Complexo Sporothrix. As plantas da família Lamiaceae são conhecidas por suas propriedades antifúngicas, entretanto, são escassos seus estudos contra agentes causadores da esporotricose. Devido ao potencial promissor dessas plantas, objetivou-se (1) avaliar a atividade anti-Sporothrix spp. in vitro de Origanum vulgare L. (orégano), Origanum majorana L. (manjerona) e Rosmarinus officinalis L. (alecrim) nas formas de óleos essenciais, extratos aquosos de infusão e decocção e extratos hidroalcoólicos contra isolados clínicos de Sporothrix spp. obtidos de casos clínicos de esporotricose humana, canina e felina; (2) avaliar os principais constituintes químicos presentes nos óleos essenciais das plantas; e (3) avaliar a atividade citotóxica in vitro. Extratos aquosos e hidroalcoólicos foram preparados a partir de partes aéreas das plantas. Em óleos essenciais, produtos comerciais e produtos extraídos de partes aéreas por hidrodestilação em Clevenger foram testados. Ambos óleos foram analisados quimicamente por cromatografia gasosa. Testes in vitro foram realizados pela técnica de Microdiluição em Caldo contra isolados clínicos de Sporothrix spp. oriundos de humanos, caninos e felinos, bem como ambiental nas fases leveduriforme (CLSIM27A3) e filamentosa (CLSI-M38A2), sendo testados entre 72 a 0.07 mg/mL. Os efeitos citotóxicos foram avaliados através do ensaio MTT em células VERO (78 a 5000 μg/mL). Na fase leveduriforme, os óleos essenciais extraído e comercial de orégano apresentaram atividade anti-Sporothrix spp. nas concentrações inibitórias mínimas (CIM) e concentrações fungicidas mínimas (CFM) de 36 a ≤2.25 mg/mL e de alecrim entre 72 a≤2.25 mg/mL, não havendo diferença estatística entre os tipos de óleos. Por sua vez, óleo comercial de manjerona apresentou CIM/CFM de 18 a ≤2.25 mg/mL. Na fase micelial, 100% dos isolados felinos e caninos foram sensíveis aos óleos essenciais de orégano (0.14 a ≤0.07 mg/mL), alecrim (18 a ≤0,07 mg/mL) e manjerona (4.5 a ≤0.07 mg/mL). Extratos aquosos e hidroalcoólicos de orégano apresentaram atividade inibitória e fungicida, respectivamente, em 100% e entre 90% a 35% dos isolados animais (40 a ≤0.07 mg/mL). Nas mesmas concentrações, o extrato hidroalcoólico de manjerona inibiu de 90% a 100% dos isolados. Entretanto, os demais extratos de manjerona e de alecrim apresentaram fraca atividade anti-Sporothrix spp. sobre 40% a 5% dos isolados, não havendo atividade antifúngica sobre as infusões de alecrim preparadas em 10 e 60 minutos. Sobre itraconazol, Sporothrix spp. foi sensível na fase leveduriforme (16 a ≤0.03 μg/mL) e filamentosa (64 a ≤0.12 μg/mL), entretanto, 5 foi observada resistência antifúngica em 4% e 28% (CIM e CFM >16 μg/mL, respectivamente) dos isolados na fase leveduriforme, ao passo que, na fase filamentosa, a resistência ocorreu em 12,5% e 85% dos isolados (CIM e CFM >64 μg/mL, respectivamente). Os óleos essenciais de orégano e manjerona apresentaram maior atividade citotóxica com 80% de inviabilidade celular, ao passo que os extratos aquosos e hidroalcoólico de manjerona foram os menos citotóxicos. A análise química foi similar nos produtos das plantas Lamiaceae, diferindo a concentração dos compostos, os quais α-pineno e 1,8-cineol foram majoritários para o óleo extraído do alecrim e α- terpineno, terpineol-4 e timol para o óleo extraído de orégano, ao passo que 1,8-cineol foi majoritário para os produtos comerciais de alecrim e manjerona, e carvacrol para orégano. A boa atividade anti-Sporothrix spp. in vitro das plantas da família Lamiaceae, em especial ao Origanum vulgare L., é promissora para o tratamento da esporotricose, inclusive sobre isolados clínicos resistentes. / Therapeutics properties of medicinal plants are increasingly studied, mainly due to increasing cases of antimicrobial cases, as observed in strains of Sporothrix Complex. Plants of Lamiaceae family are known for their antifungal properties, but studies in causative agents of sporotrichosis are scarces. Due to the promising potential of these plants, aimed to (1) evaluate the in vitro anti-Sporothrix spp. activity of aqueous extracts of infusion and decoction, hydroalcoholic extract and essential oils os Origanum vulgare L. (oregano), Origanum majorana L. (marjoram) and Rosmarinus officinalis L. (rosemary); (2) evaluate the main chemical constituents present in essential oils; and (3) evaluate the in vitro cytotoxic activity. Aqueous and hydroalcoholic extracts were prepared from the aerial parts of the plants. In essential oils, commercial products and extracted products from aerial parts through hydrodistillation in Clevenger were tested. Both essential oils were chemically analyzed by gas chromatography. In vitro tests were performed by broth microdilution technique against clinical isolates of Sporothrix spp. from humans, dogs and cats with sporotrichosis, as well as environmental soil, in yeast (CLSI-M27A3) and mycelial (CLSI-M38A2) phases and tested from 72 to 0.07 mg/mL. Cytotoxic effects were assessed by MTT assay on VERO cells (78 to 5000 μg/mL). In yeast phase, the extracted and commercial essential oils of oregano showed anti-Sporothrix spp. activity in the minimum inhibitory concentrations (MIC) and minimum fungicidal concentration (MFC) of 36 to ≤2.25 mg/mL and rosemary between 72 to ≤2.25 mg/mL, with no statistical difference between the types of oils. In turn, commercial marjoram oil showed MIC/MFC of ≤2.25 to 18 mg/mL. In the mycelial phase, 100% of feline and canine isolates were sensibles to essential oils of oregano (0.14 to ≤0.07 mg/mL), rosemary (18 to ≤0,07 mg/mL) and marjoram (4.5 to ≤0.07 mg/ml). Aqueous and hydroalcoholic extracts of oregano showed inhibitory and fungicidal activity, respectively, 100% and between 90% and 35% of animal isolates (40 to ≤0.07 mg/mL). In the same concentrations, hydroalcoholic extract of marjoram inhibited 90% to 100% of the isolates. However, other extracts of marjoram and rosemary showed weak activity anti- Sporothrix spp. about 40% to 5% of the isolates, with no antifungal activity by INF10 and INF60 rosemary. About itraconazole, Sporothrix spp. was sensitive in the yeast phase (16 to ≤0.03 mg/mL) and filamentous (64 to ≤0.12 mg/mL), however, antifungal resistance was observed in 4% and 28% (MIC and MFC > 16 μg/mL, respectively) in fungal isolates in the yeast form, and in the mycelial form, the resistence occurred in 12.5% and 85% of isolates (MIC and MFC > 64 μg/mL, respectively). Essential oils of oregano and marjoram exhibited greater cytotoxic activity with 80% cell inviability, while hydroalcoholic and aqueous extracts of marjoram were less cytotoxic. The chemical analysis was similar for the products of Lamiaceae plants and differed in the concentration of the compounds, which α-pinene and 1,8-cineole were majoritary for extracted oil of rosemary and α-terpinene, terpineol-4 and thymol for extracted oil of 7 oregano, while 1,8-cineole was majoritary for commercial products of rosemaru and marjoram, and carvacrol for oregano. The good in vitro anti-Sporothrix spp. activity of the plants of Lamiaceae family, mainly to Origanum vulgare L., is promising for the treatment of sporotrichosis, including against clinical isolates resistant.

As propriedades terapêuticas das plantas medicinais são cada vez mais estudadas, principalmente devido aos crescentes casos de resistência antimicrobiana, como observado em cepas do Complexo Sporothrix. As plantas da família Lamiaceae são conhecidas por suas propriedades antifúngicas, entretanto, são escassos seus estudos contra agentes causadores da esporotricose. Devido ao potencial promissor dessas plantas, objetivou-se (1) avaliar a atividade anti-Sporothrix spp. in vitro de Origanum vulgare L. (orégano), Origanum majorana L. (manjerona) e Rosmarinus officinalis L. (alecrim) nas formas de óleos essenciais, extratos aquosos de infusão e decocção e extratos hidroalcoólicos contra isolados clínicos de Sporothrix spp. obtidos de casos clínicos de esporotricose humana, canina e felina; (2) avaliar os principais constituintes químicos presentes nos óleos essenciais das plantas; e (3) avaliar a atividade citotóxica in vitro. Extratos aquosos e hidroalcoólicos foram preparados a partir de partes aéreas das plantas. Em óleos essenciais, produtos comerciais e produtos extraídos de partes aéreas por hidrodestilação em Clevenger foram testados. Ambos óleos foram analisados quimicamente por cromatografia gasosa. Testes in vitro foram realizados pela técnica de Microdiluição em Caldo contra isolados clínicos de Sporothrix spp. oriundos de humanos, caninos e felinos, bem como ambiental nas fases leveduriforme (CLSIM27A3) e filamentosa (CLSI-M38A2), sendo testados entre 72 a 0.07 mg/mL. Os efeitos citotóxicos foram avaliados através do ensaio MTT em células VERO (78 a 5000 μg/mL). Na fase leveduriforme, os óleos essenciais extraído e comercial de orégano apresentaram atividade anti-Sporothrix spp. nas concentrações inibitórias mínimas (CIM) e concentrações fungicidas mínimas (CFM) de 36 a ≤2.25 mg/mL e de alecrim entre 72 a≤2.25 mg/mL, não havendo diferença estatística entre os tipos de óleos. Por sua vez, óleo comercial de manjerona apresentou CIM/CFM de 18 a ≤2.25 mg/mL. Na fase micelial, 100% dos isolados felinos e caninos foram sensíveis aos óleos essenciais de orégano (0.14 a ≤0.07 mg/mL), alecrim (18 a ≤0,07 mg/mL) e manjerona (4.5 a ≤0.07 mg/mL). Extratos aquosos e hidroalcoólicos de orégano apresentaram atividade inibitória e fungicida, respectivamente, em 100% e entre 90% a 35% dos isolados animais (40 a ≤0.07 mg/mL). Nas mesmas concentrações, o extrato hidroalcoólico de manjerona inibiu de 90% a 100% dos isolados. Entretanto, os demais extratos de manjerona e de alecrim apresentaram fraca atividade anti-Sporothrix spp. sobre 40% a 5% dos isolados, não havendo atividade antifúngica sobre as infusões de alecrim preparadas em 10 e 60 minutos. Sobre itraconazol, Sporothrix spp. foi sensível na fase leveduriforme (16 a ≤0.03 μg/mL) e filamentosa (64 a ≤0.12 μg/mL), entretanto, 5 foi observada resistência antifúngica em 4% e 28% (CIM e CFM >16 μg/mL, respectivamente) dos isolados na fase leveduriforme, ao passo que, na fase filamentosa, a resistência ocorreu em 12,5% e 85% dos isolados (CIM e CFM >64 μg/mL, respectivamente). Os óleos essenciais de orégano e manjerona apresentaram maior atividade citotóxica com 80% de inviabilidade celular, ao passo que os extratos aquosos e hidroalcoólico de manjerona foram os menos citotóxicos. A análise química foi similar nos produtos das plantas Lamiaceae, diferindo a concentração dos compostos, os quais α-pineno e 1,8-cineol foram majoritários para o óleo extraído do alecrim e α- terpineno, terpineol-4 e timol para o óleo extraído de orégano, ao passo que 1,8-cineol foi majoritário para os produtos comerciais de alecrim e manjerona, e carvacrol para orégano. A boa atividade anti-Sporothrix spp. in vitro das plantas da família Lamiaceae, em especial ao Origanum vulgare L., é promissora para o tratamento da esporotricose, inclusive sobre isolados clínicos resistentes. / Therapeutics properties of medicinal plants are increasingly studied, mainly due to increasing cases of antimicrobial cases, as observed in strains of Sporothrix Complex. Plants of Lamiaceae family are known for their antifungal properties, but studies in causative agents of sporotrichosis are scarces. Due to the promising potential of these plants, aimed to (1) evaluate the in vitro anti-Sporothrix spp. activity of aqueous extracts of infusion and decoction, hydroalcoholic extract and essential oils os Origanum vulgare L. (oregano), Origanum majorana L. (marjoram) and Rosmarinus officinalis L. (rosemary); (2) evaluate the main chemical constituents present in essential oils; and (3) evaluate the in vitro cytotoxic activity. Aqueous and hydroalcoholic extracts were prepared from the aerial parts of the plants. In essential oils, commercial products and extracted products from aerial parts through hydrodistillation in Clevenger were tested. Both essential oils were chemically analyzed by gas chromatography. In vitro tests were performed by broth microdilution technique against clinical isolates of Sporothrix spp. from humans, dogs and cats with sporotrichosis, as well as environmental soil, in yeast (CLSI-M27A3) and mycelial (CLSI-M38A2) phases and tested from 72 to 0.07 mg/mL. Cytotoxic effects were assessed by MTT assay on VERO cells (78 to 5000 μg/mL). In yeast phase, the extracted and commercial essential oils of oregano showed anti-Sporothrix spp. activity in the minimum inhibitory concentrations (MIC) and minimum fungicidal concentration (MFC) of 36 to ≤2.25 mg/mL and rosemary between 72 to ≤2.25 mg/mL, with no statistical difference between the types of oils. In turn, commercial marjoram oil showed MIC/MFC of ≤2.25 to 18 mg/mL. In the mycelial phase, 100% of feline and canine isolates were sensibles to essential oils of oregano (0.14 to ≤0.07 mg/mL), rosemary (18 to ≤0,07 mg/mL) and marjoram (4.5 to ≤0.07 mg/ml). Aqueous and hydroalcoholic extracts of oregano showed inhibitory and fungicidal activity, respectively, 100% and between 90% and 35% of animal isolates (40 to ≤0.07 mg/mL). In the same concentrations, hydroalcoholic extract of marjoram inhibited 90% to 100% of the isolates. However, other extracts of marjoram and rosemary showed weak activity anti- Sporothrix spp. about 40% to 5% of the isolates, with no antifungal activity by INF10 and INF60 rosemary. About itraconazole, Sporothrix spp. was sensitive in the yeast phase (16 to ≤0.03 mg/mL) and filamentous (64 to ≤0.12 mg/mL), however, antifungal resistance was observed in 4% and 28% (MIC and MFC > 16 μg/mL, respectively) in fungal isolates in the yeast form, and in the mycelial form, the resistence occurred in 12.5% and 85% of isolates (MIC and MFC > 64 μg/mL, respectively). Essential oils of oregano and marjoram exhibited greater cytotoxic activity with 80% cell inviability, while hydroalcoholic and aqueous extracts of marjoram were less cytotoxic. The chemical analysis was similar for the products of Lamiaceae plants and differed in the concentration of the compounds, which α-pinene and 1,8-cineole were majoritary for extracted oil of rosemary and α-terpinene, terpineol-4 and thymol for extracted oil of 7 oregano, while 1,8-cineole was majoritary for commercial products of rosemaru and marjoram, and carvacrol for oregano. The good in vitro anti-Sporothrix spp. activity of the plants of Lamiaceae family, mainly to Origanum vulgare L., is promising for the treatment of sporotrichosis, including against clinical isolates resistant.

The GERDA experiment is searching for the neutrinoless double beta (0vbb) decay of Ge-76. By that, it tries to answer two long standing questions about the neutrino: 'How large is the neutrino mass?' and 'Is the neutrino either Dirac or Majorana particle?'. Additionally, an observation would imply that lepton number is not conserved, which is an important puzzle piece for theories explaining the asymmetry between matter and anti-matter in the universe. The effective Majorana electron neutrino mass can be extracted from the half-life of the 0vbb -decay. However, during that conversion large uncertainties are added through nuclear matrix elements, that are calculated by a variety of theoretical models. Experimental input is required to constrain such models and their parameters to improve the reliability of the calculations. Additional input can be obtained by comparing the model predictions for the two neutrino double beta (2vbb) decay to the ground state, but also for decay modes to excited states of the daughter nuclide with measurements. The latter decay modes have not yet been observed in the case of Ge-76. The event signature of transitions to excited states is enhanced by de-excitation gamma-rays. The GERDA experiment employs an array of bare germanium semi-conductor detectors in a liquid argon cryostat. This array is suited to search for excited state transition in the 2vbb and 0vbb -decay modes using data with coincident energy depositions in multiple detectors. This work presents the preparation and characterisation of this data set, which includes the evaluation and correction of crosstalk between detector channels, the determination of the energy resolution of the detectors and the modelling of background. In an analysis combining 22 kgyr of Phase I data with the first 35 kgyr of Phase II data of GERDA, no signal has been observed for 2/0vbb -decays of Ge-76 to the energetically lowest three excited states in Se-76. New limits have been set for the two neutrino decay modes at T1/2(2v)(0+g.s. to 0+1) > 3.1x10^23 yr, T1/2(2v)(0+g.s. to 2+1) > 3.4x10^23 yr T1/2(2v)(0+g.s. to 2+2) > 2.5x10^23 yr with 90% credibility using a Bayesian approach, improving upon the limits obtained in Phase I. The corresponding sensitivities are 3.6x10^23 yr, 6.7x10^23 yr and 3.7x10^23 yr, respectively. First limits are set for the neutrinoless decay modes in the order of (10^24-10^25) yr. Reaching the desired Phase II exposure of 100 kgyr, the sensitivities will increase by up to 50%.