L'évolution de la gastrite et des lésions précancéreuses suit une cascade de plusieurs étapes. Les modifications des tissus pathologiques affichent de faibles variations par rapport à la muqueuse normale d'un point de vue macroscopique. Même si certaines variations pourraient être identifiées, cela reste fortement subjectif. Le diagnostic classique des maladies de l'estomac est divisé en deux procédures. Le premier est une gastroendoscopie où l'estomac est visuellement exploré sous une lumière blanche. Le second est la biopsie pour l'analyse histologique. Cette procédure a une forte probabilité d'établir le diagnostic correct mais il dépend fortement de la sélection correcte des échantillons de tissus endommagés. Ce travail porte sur l'étude de la muqueuse gastrique par imagerie multispectrale. La contribution principale est l'étude clinique de l'imagerie multispectrale afin de différencier les pathologies mal diagnostiquées ou qui ne peuvent être diagnostiquées que par l'analyse histologique. A cet effet, nous avons effectué (1) une étude ex-vivo dans un modèle de souris de l'infection de Helicobacter pylori dans le but d'identifier les longueurs d'onde qui pourraient être utilisées pour le diagnostic. (2) Nous proposons deux prototypes compatibles avec les gastroendoscopes actuels pour acquérir des images multispectrales du tissu gastrique : le premièr est basé sur une roue à filtres et le second sur une caméra multispectrale avec sept canaux. De plus, (3) nous présentons une méthodologie pour identifier les tissus pathologiques, qui est basé sur des caractéristiques statistiques extraites des spectres acquis, classées en fonction de leur pouvoir discriminants et une classification supervisée, où nous cherchons la meilleure performance de trois algorithmes de classification: le plus proche voisin, un réseaux de neurones et une Support Vector Machine avec une évaluation de la performance rigoureuse en utilisant une validation de type Leave One Patient Out Cross Validation. Les résultats démontrent la pertinence de l’imagerie multispectrale comme un outil supplémentaire pour un diagnostic objectif. / The evolution of gastritis into precancerous lesions follows a cascade of multiplestages. The modifications of the pathological tissues display low variations with respect to normal mucosa from a macroscopical point of view. Even though some features could be identified, they remain strongly subjective. The current gold standard for diagnosis of gastric diseases is divided in two procedures. The first one is gastroendoscopy where the stomach is visually explored under white light. The second one is biopsy collection for histological analysis. This procedure has a high probability of establishing the correct diagnosis but it strongly depends on the accurate collection of samples from damaged tissues. This doctoral work focuses on the study of gastric mucosa by multispectral imaging. The main contribution is the clinical study of multispectral imaging to differentiate pathologies poorly diagnosed or that can only be diagnosed by histological analysis. For this purpose, we performed (1) ex vivo studies in a mice model of infection of Helicobacter pylori in order to identify the wavelengths which could be used for diagnosis. (2) We propose two prototypes compatible with current gastroendoscopes to acquire multispectral images from gastric tissue: the first one is based on a filter wheel and the second one on a multispectral camera with seven channels. Additionally, (3) we present a methodology to identify pathological tissues, which is based on statistical features extracted from the acquired spectra, ranked according to their discriminative power and a supervised classification, where we search for the best performance of three classification algorithms: Nearest Neighbor, Neural Networks and Support Vector Machine with a rigorous performance evaluation by using leave one patient out cross validation. The results demonstrate the relevance of multispectral imaging as an additional tool for an objective diagnosis.

Die kontinuierliche Rezirkulation von Immunzellen durch periphere und sekundäre lymphatische Organe (SLOs) ist Bestandteil der Immunüberwachung und wichtig für die Aufrechterhaltung und Funktionsbereitschaft des Immunsystems. Der homöostatische Chemokinrezeptor CCR7 vermittelt dabei nicht nur die Rezirkulation von Lymphozyten durch SLOs, sondern scheint auch an der homöostatischen Rezirkulation von Lymphozyten durch nicht-lymphoide periphere Gewebe beteiligt zu sein. Im Rahmen dieser Arbeit wurde mithilfe von CCR7-defizienten Mäusen die funktionale Bedeutung von CCR7 für die homöostatische Rezirkulation von Lymphozyten durch das Peritoneum untersucht und nachgewiesen, dass CCR7 der dominante Chemokinrezeptor ist, der unter physiologischen Bedingungen die Transitzeit von Lymphozyten durch das Peritoneum festlegt. Die gestörte Rezirkulation von Lymphozyten begünstigte außerdem die Entstehung von tertiären lymphoiden Organen (TLOs) in der Magenschleimhaut von CCR7-defizienten Mäusen. Untersuchungen zur zellulären und molekularen Grundlage dieser und weiterer pathomorphologischer Veränderungen in der Magenschleimhaut von CCR7-defizienten Mäusen verdeutlichten die Funktion von CCR7 für die Etablierung von zentraler und peripherer Toleranz gegenüber gastrischen Antigenen. Fehlt CCR7, dann entwickelten Mäuse eine spontane Autoimmungastritis, welche durch gastritogene CD4+ T-Zellen verursacht wurde, deren Aktivierung auch unabhängig von Lymphknoten und TLOs erfolgte. Die Entstehung von TLOs wird auch bei einer durch Helicobacter pylori ausgelösten chronischen Gastritis beobachtet. Die Expression des homöostatischen Chemokinrezeptors CXCR5 und seines Liganden CXCL13 ist mit der Entwicklung dieser TLOs korreliert worden. Unter Verwendung eines Mausmodells für H. pylori-induzierte chronische Gastritis konnte gezeigt werden, dass CXCR5 die Ausbildung von TLOs vermittelt und eine Rolle für die Induktion von H. pylori-spezifischen T-Zell- sowie humoralen Immunantworten spielt. / Homeostatic recirculation of immune cells through peripheral and secondary lympoid organs (SLOs) is required for immune surveillance and the maintenance and functionality of the immune system. The homeostatic chemokine receptor CCR7 controls not only lymphoid cell trafficking to and within SLOs, but also seems to be involved in the homeostatic recirculation of lymphocytes through non-lymphoid peripheral tissues. Within the scope of this work we investigated the functional relevance of CCR7 for the homeostatic recirculation of lymphocytes through the peritoneal cavity and could show, that CCR7 is the dominant chemokine receptor which defines the transit time of lymphocytes in the peritoneal cavity under physiological conditions. Impaired recirculation of lymphocytes also promoted the development of tertiary lymphoid organs (TLOs) in the gastric mucosa of CCR7-deficient mice. Analysis of the cellular and molecular mechanisms underlying these and other pathomorphological alterations in the gastric mucosa of CCR7-deficient mice provided further evidence regarding the function of CCR7 for the establishment of central and peripheral tolerance towards gastric antigens. Mice that lack CCR7 spontaneously developed autoimmune gastritis, which was caused by gastritogenic CD4+ T-cells. Such autoreactive T cell responses were also initiated in the absence of lymph nodes and TLOs in CCR7/LT-alpha double-deficient mice. Development of TLOs is also observed during chronic gastritis induced by Helicobacter pylori. The expression of the homeostatic chemokine receptor CXCR5 and its ligand CXCL13 has been correlated with the development of these TLOs. Using a mouse model for H. pylori-induced chronic gastritis, we could show that CXCR5 is responsible for the development of TLOs and also plays a role for the induction of H. pylori-specific T and B cell responses.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A infecÃÃo pelo Helicobacter pylori acomete mais da metade da populaÃÃo mundial, sendo esta bactÃria reconhecida como carcinÃgeno do grupo I pela OrganizaÃÃo Mundial de SaÃde-OMS. Familiares em primeiro grau de pacientes com cÃncer gÃstrico tÃm um maior risco de desenvolver cÃncer gÃstrico. Avaliamos a prevalÃncia de lesÃes precursoras do cÃncer gÃstrico e do Helicobacter pylori nos familiares em primeiro grau de pacientes com cÃncer gÃstrico, quando comparado a controles sem histÃria familiar. Cento e quatro familiares foram recrutados à partir de 40 casos de cÃncer gÃstrico tipo nÃo-cÃrdia e foram comparados com cento e dezoito controles, nÃo havendo diferenÃas estatisticamente significantes entre os dois grupos com relaÃÃo a idade, sexo, tabagismo, etilismo e condiÃÃes socioeconÃmicas garantindo a homogeneidade da amostra. Todos os pacientes foram submetidos a avaliaÃÃo endoscÃpica e biÃpsias seguindo o protocolo de Sydney. A anÃlise histopatolÃgica foi realizada pÃr um Ãnico patologista experiente e mascarado quanto a origem das amostras. Ainda que a prevalÃncia da atrofia e da metaplasia intestinal tenha ocorrida de forma similar nos dois grupos, a associaÃÃo destas lesÃes foi mais encontrada nos familiares que nos controles (p=0,021). A metaplasia intestinal tipo incompleta foi mais significante nos familiares (p=0,001), assim como a displasia (p=0,025). O padrÃo de gastrite encontrado nos familiares foi o de pangastrite associada a presenÃa de folÃculos linfÃides, padrÃo este jà definido como o de fenotÃpico de maior risco para a carcinogÃnese gÃstrica. NÃo houve diferenÃa estatisticamente significante entre os dois grupos com relaÃÃo a prevalÃncia do H. pylori , porÃm a topografia da infecÃÃo envolvendo antro e corpo foi maior nos familiares (p=0,001). De acordo com os resultados obtidos neste estudo, encontramos que familiares de pacientes com cÃncer gÃstrico tÃm uma maior prevalÃncia de alteraÃÃes histopatolÃgicas, estando estas alteraÃÃes confinadas a presenÃa do Helicobacter pylori / Infection by Helicobacter pylori, a bacterial species classified by WHO as being carcinogenic (group I) affects more than half the world population. First-degree relatives to patients with gastric cancer are at increased risk of developing gastric cancer. The present study evaluated the prevalence of precursor lesions of gastric cancer and infection by Helicobacter pylori in first-degree relatives to patients with gastric cancer as compared to controls with no family history of gastric cancer. One hundred four first-degree relatives to 40 patients with noncardiac gastric cancer were enrolled in the study and compared to 108 controls. The groups were statistically homogenous in terms of age. All patients were submitted to endoscopic evaluation and biopsy as described in the Sydney protocol. The histopathological analysis was carried out by a single, experienced pathologist blinded to the origin of the samples. Although the prevalence of atrophy and intestinal metaplasia was similar for the two groups, association with these lesions was more common among relatives than controls (p=0.021). Incomplete intestinal metaplasia was also more significant among relatives (p=0.001), as was displasia (p=0.025). The group of relatives presented a pattern of pangastritis associated with lymphoid follicles characteristic of increased risk for gastric carcinogenesis. There was no statistically significant difference between the groups with regard to the prevalence of H. pylori, though infection involving body and antrum was more prevalent among relatives (p=0.001). Our findings suggest that relatives to patients with gastric cancer present a greater prevalence of histopathological changes associated with the presence of H. pylori

Helicobacter spp é uma bactéria espiralada gram negativa que pode fazer parte da microbiota gástrica de cães e gatos domésticos, e sua associação com as gastropatias ainda é amplamente discutida na Medicina Veterinária. O objetivo do estudo foi avaliar a frequência de ocorrência da helicobacteriose gástrica em cães e gatos necropsiados no HOVET-USP e comparar quatro métodos de diagnóstico para a identificação do agente. Fragmentos da mucosa gástrica foram destinados ao TRU, citologia, histopatologia por hematoxilina e eosina (HE) com coloração de Warthin Starry (WS) e imuno-histoquímica (IHQ). Para a análise comparativa, de concordância e de desempenho dos testes, entre os métodos de diagnóstico com o padrão ouro (HE), foram utilizados o teorema de Bayes, o índice Kappa e o índice Youden respectivamente. Nos cães a frequência de ocorrência da helicobacteriose gástrica ficou em 57%, com associação entre a infecção e a faixa etária dos animais. Nos gatos esta frequência de ocorrência foi de 87% pelo método padrão ouro (HE) de diagnóstico escolhido sem associação entre infecção, raça, gênero e idade dos animais. A imunohistoquímica obteve maiores índices de Youden e Kappa nos cães. Nos gatos, a coloração específica a base de prata, Warthin Starry, obteve maior índice Youden e Kappa do que os outros diagnósticos. A determinação da frequência de ocorrência do Helicobacter spp varia conforme o método de diagnóstico adotado. A escolha do método depende dos recursos financeiros disponíveis, das amostras que se pretende estudar, do tempo necessário, da praticidade do método e da sua performance. / Helicobacter spp are gram negative spiral bacterium that can be part of the gastric microbiota of domestic dogs and cats, and its association with gastropathies is still widely discussed in Veterinary Medicine. The aim of the study was to evaluate the frequency of occurrence of gastric helicobacteriose in dogs and cats necropsied at HOVET - USP and compare four diagnostic methods for the identification of the agent. Fragments of gastric mucosa were sent to the rapid urease test (RUT), cytology, histopathology by hematoxylin and eosin (HE) staining with Warthin Starry (WS) and immunohistochemistry (IHC). For comparative analysis, and concordance and performance between diagnostic methods with the gold standard (HE) were used respectively the Bayes\' theorem, the Kappa index and Youden index. In dogs the frequency of occurrence of gastric helicobacteriose stood at 57 %, with an association between infection and the age of the animals. In cats this frequency of occurrence was 87 % for the gold standard method (HE) and no association between infection, race, gender and age of the animals was found. Immunohistochemistry showed higher Youden index and Kappa in dogs. In cats, the specific staining based on silver, Warthin Starry, demonstrated the highest Youden and Kappa indexes among the other diagnostic methods. The determination of the frequency of occurrence of Helicobacter spp varies according to the diagnostic method adopted. The choice of method depends on the financial resources available, the samples under study, the time required, the practicality of the method and its performance.

O Helicobacter pylori, é tido como o principal fator de risco para o carcinoma gástrico. Diferentes estudos experimentais em animais procuram relacionar essa carcinogênese a outros fatores carcinógenos sem sucesso. Neste estudo, procurou-se avaliar-se em ratos, se há correlação entre o refluxo duodenogástrico, o Helicobacter pylori e o desenvolvimento do câncer gástrico ou de seus precursores. Para tal, realizou-se nos três grupos de ratos (n de dez por grupo) as técnicas de: piloroplastia precedida de infecção, gastrectomia subtotal precedida de infecção e um grupo no qual foi praticada apenas a infecção. Apois seis meses, analisou-se as alterações da mucosa, comparando-se os três grupos. As alterações da mucosa pesquisadas foram as seguintes: gastrites, metaplasias, displasias e neoplasias epiteliais. Ao término do estudo, foi encontrado, no grupo submetido a piloroplastia precedida de infecção um alto percentual de alterações epiteliais. Conclui-se que, no rato, a operação de piloroplastia, levou ao maior desenvolvimento da população do Helicobacter pylori, que se relaciona com as lesões pré- malignas e o adenocarcinoma gástrico. / Helicobacter pylori is considered the main risk factor for gastric carcinoma. Different experimental studies in animals seek to relate this carcinogenesis to other carcinogenic factors without success. This study sought to evaluate in rats, if there was a correlation between duodenogastric reflux, Helicobacter pylori and the development of gastric cancer or its precursors. To this end, it was carried out in three groups of rats the techniques: pyloroplasty, subtotal gastrectomy and only infection. After six months, the changes in mucosa were analyzed comparing the three groups. The mucosal changes reseached were: gastritis, metaplasia, dysplasia and epithelial neoplasms. At the end of the study, was found in the group that underwent pyloroplasty a high percentage of epithelial alterations and these correlated with the population of Helicobacter pylori. It is concluded that in the rat, the operation of pyloroplasty led to increased colonization of the population of Helicobacter pylori and is related with the development of benign lesions and gastric cancer.

Helicobacter spp é uma bactéria espiralada gram negativa que pode fazer parte da microbiota gástrica de cães e gatos domésticos, e sua associação com as gastropatias ainda é amplamente discutida na Medicina Veterinária. O objetivo do estudo foi avaliar a frequência de ocorrência da helicobacteriose gástrica em cães e gatos necropsiados no HOVET-USP e comparar quatro métodos de diagnóstico para a identificação do agente. Fragmentos da mucosa gástrica foram destinados ao TRU, citologia, histopatologia por hematoxilina e eosina (HE) com coloração de Warthin Starry (WS) e imuno-histoquímica (IHQ). Para a análise comparativa, de concordância e de desempenho dos testes, entre os métodos de diagnóstico com o padrão ouro (HE), foram utilizados o teorema de Bayes, o índice Kappa e o índice Youden respectivamente. Nos cães a frequência de ocorrência da helicobacteriose gástrica ficou em 57%, com associação entre a infecção e a faixa etária dos animais. Nos gatos esta frequência de ocorrência foi de 87% pelo método padrão ouro (HE) de diagnóstico escolhido sem associação entre infecção, raça, gênero e idade dos animais. A imunohistoquímica obteve maiores índices de Youden e Kappa nos cães. Nos gatos, a coloração específica a base de prata, Warthin Starry, obteve maior índice Youden e Kappa do que os outros diagnósticos. A determinação da frequência de ocorrência do Helicobacter spp varia conforme o método de diagnóstico adotado. A escolha do método depende dos recursos financeiros disponíveis, das amostras que se pretende estudar, do tempo necessário, da praticidade do método e da sua performance. / Helicobacter spp are gram negative spiral bacterium that can be part of the gastric microbiota of domestic dogs and cats, and its association with gastropathies is still widely discussed in Veterinary Medicine. The aim of the study was to evaluate the frequency of occurrence of gastric helicobacteriose in dogs and cats necropsied at HOVET - USP and compare four diagnostic methods for the identification of the agent. Fragments of gastric mucosa were sent to the rapid urease test (RUT), cytology, histopathology by hematoxylin and eosin (HE) staining with Warthin Starry (WS) and immunohistochemistry (IHC). For comparative analysis, and concordance and performance between diagnostic methods with the gold standard (HE) were used respectively the Bayes\' theorem, the Kappa index and Youden index. In dogs the frequency of occurrence of gastric helicobacteriose stood at 57 %, with an association between infection and the age of the animals. In cats this frequency of occurrence was 87 % for the gold standard method (HE) and no association between infection, race, gender and age of the animals was found. Immunohistochemistry showed higher Youden index and Kappa in dogs. In cats, the specific staining based on silver, Warthin Starry, demonstrated the highest Youden and Kappa indexes among the other diagnostic methods. The determination of the frequency of occurrence of Helicobacter spp varies according to the diagnostic method adopted. The choice of method depends on the financial resources available, the samples under study, the time required, the practicality of the method and its performance.

El Helicobater pylori, principal agente causal de la gastritis, condiciona el estrés oxidativo debido a la producción de radicales libres. La Satureja brevicalyx, es usada para tratar problemas gastrointestinales, como la gastritis. El objetivo del presente trabajo fue caracterizar los componentes químicos, la actividad anti-Helicobacter pylori y antioxidante del aceite esencial de Satureja brevicalyx. El aceite esencial reportó un rendimiento (1.80%v/p), rotación óptica (-2 a +4º), densidad (0.9047 g/mL) e índice de refracción (1.475). Mediante CG-SM y CG-FID se elucidó 35 compuestos al 97.1%: monoterpenos oxigenados (74.8%), como componentes mayoritarios la pulegona (27.2%), linalol (20.3%), mentona (11.1%), isomentona (8.3%), cis-isopulegona (2.7%), trans-isopulegona (0.9%), carvacrol (0.6%), timol (0.6%) y α-terpineol (0.5%); hidrocarburos sesquiterpénicos (16%), destacando biciclogermacreno (8.2%), β-cariofileno (6.5%) y bicicloelemeno (0.5%); hidrocarburos monoterpénicos (4.1%), con el p-cimeno (2.0%), limoneno (0.7%) y γ-terpineno (0.6%); y sesquiterpenos oxigenados (1.5%), con el espatulenol (0.8%). Por el método de Artemia salina mostró una bioactividad significativa, con una CL50 de 13.35 μg/mL, y por el método de Dosis Fija, en ratones albinos, presenta una DL50 de 655.26 mg/kg, siendo ligeramente tóxica. Por el método de Difusión de Discos, tiene un efecto antibacteriano frente al H. pylori, con un halo de inhibición de 33.33 % en comparación con la amoxicilina a una concentración de 10 μg/mL; por el método de Difusión en Microplacas, la concentración mínima inhibitoria es de 1.00 μg/mL, y la concentración mínima bactericida de 2.00 μg/mL. Se determinó en 3 modelos la actividad antioxidante a concentraciones de 10, 50 y 100 μg/mL: 1) El aceite inhibió al radical DPPH en 67.76, 75.33 y 86.84%, frente al trolox que inhibió en 80.59, 87.17 y 93.09%; 2) secuestró al radical hidroxilo en 28.95, 51.57 y 76.84%; y 3) inhibió de la peroxidación lipídica en 16.4x10-8, 9.8x10-8 y 8.5x10-8 moles x cm, comparado con el trolox que lo hizo en 14.9x10-8, 8.0x10-8 y 7.5 x10-8 moles x cm, frente a 53.9x10-8 moles x cm para el control negativo. Las estructuras químicas del aceite esencial de la S. brevicalyx justifican su actividad anti-Helicobacter pylori y antioxidante. Palabras Clave: Satureja brevicalyx, gastritis, radicales libres, anti-Helicobacter pylori, antioxidante / --- The Helicobacter pylori is the main causal agent of gastritis, it conditions the oxidative stress due to the fact that it produces free radicals. The Satureja brevicalyx is used to treat gastrointestinal problems as gastritis. The objective of this work was to characterize the chemical components, the anti-Helicobacter pylori activity and the antioxidant of the main oil of Satureja brevicalyx. Te main oil reported a performance (1.80%v/p), optical rotation (- 2 to + 4º), density (0,9047 g/mL) and index of refraction (1.475). By means of CG-SM and CG-FID elucidated 35 compounds at 97,1%: oxygenated monoterpens (74,8%) as majority compound the pulegone (27,2%), linalool (20,3%), menthone (11,1%), isomenthone (8,3%), cis-isopulegone (2,7%), trans-isopulegone (0,9%), carvacrol (0,6%), thymol (0,6%) and α-terpineol (0,5%); sesquiterpenes hydrocarbons (16%), emphasizing biciclogermacrone (8,2%), β-caryophyllene (6,5%) and bicicloelemene (0,5%); monoterpenic hydrocarbons (4,1%), with the p-cymene (2,0%), limonene (0,7%) and γ-terpineno (0,6%); and sesquiterpenes (1,5%), with espatulenol (0,8%). By the method of Artemia salina it showed a significant bioactivity, with a CL50 of 13,35 μg/mL, and by the method of Fixed Dose, in albinae mice shows a DL50 of 655,26 mg/kg being slightly toxic. By the method of the Diffusion of Discs, it has an antibacterial effect of the H. pylori, with an halo of inhibition of 33,33% in comparation with the amoxiciline in a concentration of 10 μg/mL; by the method of Diffusion in Microplacas, the minimum inhibitory concentration is of 1,00 μg/mL, and the minimum bactericide concentration is of 2,00 μg/mL. The antioxidant activity to concentrations was determined in three models the concentrations must be of 10, 50 and 100 μg/mL: 1) The oil inhibited the radical DPPH in 67.76, 75,33 and 86,84%, in relation with trolox which inhibited in 80.59, 87,17 and 93,09%; 2) kidnapped the hidroxile radical in 28.95, 51,57 and 76,84%; and 3) inhibited the lipidic peroxidation in 16.4x10-8, 9.8x10-8 and 8.5x10-8 moles x cm, in relation with trolox which inhibited in 14.9x10-8, 8.0x10-8 and 7.5 x10-8 moles x cm, in relation to a 53.9x10-8 moles x cm for the negative control. The chemical structures of the main oil of the S. brevicalyx justify its activity as an anti-Helicobacter pylori and as an antioxidant. Key Words: Satureja brevicalyx, gastritis, free radicals, anti-Helicobacter pylori, antioxidant / Tesis

Abstract not available

El Helicobater pylori, principal agente causal de la gastritis, condiciona el estrés oxidativo debido a la producción de radicales libres. La Satureja brevicalyx, es usada para tratar problemas gastrointestinales, como la gastritis. El objetivo del presente trabajo fue caracterizar los componentes químicos, la actividad anti-Helicobacter pylori y antioxidante del aceite esencial de Satureja brevicalyx. El aceite esencial reportó un rendimiento (1.80%v/p), rotación óptica (-2 a +4º), densidad (0.9047 g/mL) e índice de refracción (1.475). Mediante CG-SM y CG-FID se elucidó 35 compuestos al 97.1%: monoterpenos oxigenados (74.8%), como componentes mayoritarios la pulegona (27.2%), linalol (20.3%), mentona (11.1%), isomentona (8.3%), cis-isopulegona (2.7%), trans-isopulegona (0.9%), carvacrol (0.6%), timol (0.6%) y α-terpineol (0.5%); hidrocarburos sesquiterpénicos (16%), destacando biciclogermacreno (8.2%), β-cariofileno (6.5%) y bicicloelemeno (0.5%); hidrocarburos monoterpénicos (4.1%), con el p-cimeno (2.0%), limoneno (0.7%) y γ-terpineno (0.6%); y sesquiterpenos oxigenados (1.5%), con el espatulenol (0.8%). Por el método de Artemia salina mostró una bioactividad significativa, con una CL50 de 13.35 μg/mL, y por el método de Dosis Fija, en ratones albinos, presenta una DL50 de 655.26 mg/kg, siendo ligeramente tóxica. Por el método de Difusión de Discos, tiene un efecto antibacteriano frente al H. pylori, con un halo de inhibición de 33.33 % en comparación con la amoxicilina a una concentración de 10 μg/mL; por el método de Difusión en Microplacas, la concentración mínima inhibitoria es de 1.00 μg/mL, y la concentración mínima bactericida de 2.00 μg/mL. Se determinó en 3 modelos la actividad antioxidante a concentraciones de 10, 50 y 100 μg/mL: 1) El aceite inhibió al radical DPPH en 67.76, 75.33 y 86.84%, frente al trolox que inhibió en 80.59, 87.17 y 93.09%; 2) secuestró al radical hidroxilo en 28.95, 51.57 y 76.84%; y 3) inhibió de la peroxidación lipídica en 16.4x10-8, 9.8x10-8 y 8.5x10-8 moles x cm, comparado con el trolox que lo hizo en 14.9x10-8, 8.0x10-8 y 7.5 x10-8 moles x cm, frente a 53.9x10-8 moles x cm para el control negativo. Las estructuras químicas del aceite esencial de la S. brevicalyx justifican su actividad anti-Helicobacter pylori y antioxidante. Palabras Clave: Satureja brevicalyx, gastritis, radicales libres, anti-Helicobacter pylori, antioxidante / The Helicobacter pylori is the main causal agent of gastritis, it conditions the oxidative stress due to the fact that it produces free radicals. The Satureja brevicalyx is used to treat gastrointestinal problems as gastritis. The objective of this work was to characterize the chemical components, the anti-Helicobacter pylori activity and the antioxidant of the main oil of Satureja brevicalyx. Te main oil reported a performance (1.80%v/p), optical rotation (- 2 to + 4º), density (0,9047 g/mL) and index of refraction (1.475). By means of CG-SM and CG-FID elucidated 35 compounds at 97,1%: oxygenated monoterpens (74,8%) as majority compound the pulegone (27,2%), linalool (20,3%), menthone (11,1%), isomenthone (8,3%), cis-isopulegone (2,7%), trans-isopulegone (0,9%), carvacrol (0,6%), thymol (0,6%) and α-terpineol (0,5%); sesquiterpenes hydrocarbons (16%), emphasizing biciclogermacrone (8,2%), β-caryophyllene (6,5%) and bicicloelemene (0,5%); monoterpenic hydrocarbons (4,1%), with the p-cymene (2,0%), limonene (0,7%) and γ-terpineno (0,6%); and sesquiterpenes (1,5%), with espatulenol (0,8%). By the method of Artemia salina it showed a significant bioactivity, with a CL50 of 13,35 μg/mL, and by the method of Fixed Dose, in albinae mice shows a DL50 of 655,26 mg/kg being slightly toxic. By the method of the Diffusion of Discs, it has an antibacterial effect of the H. pylori, with an halo of inhibition of 33,33% in comparation with the amoxiciline in a concentration of 10 μg/mL; by the method of Diffusion in Microplacas, the minimum inhibitory concentration is of 1,00 μg/mL, and the minimum bactericide concentration is of 2,00 μg/mL. The antioxidant activity to concentrations was determined in three models the concentrations must be of 10, 50 and 100 μg/mL: 1) The oil inhibited the radical DPPH in 67.76, 75,33 and 86,84%, in relation with trolox which inhibited in 80.59, 87,17 and 93,09%; 2) kidnapped the hidroxile radical in 28.95, 51,57 and 76,84%; and 3) inhibited the lipidic peroxidation in 16.4x10-8, 9.8x10-8 and 8.5x10-8 moles x cm, in relation with trolox which inhibited in 14.9x10-8, 8.0x10-8 and 7.5 x10-8 moles x cm, in relation to a 53.9x10-8 moles x cm for the negative control. The chemical structures of the main oil of the S. brevicalyx justify its activity as an anti-Helicobacter pylori and as an antioxidant. Key Words: Satureja brevicalyx, gastritis, free radicals, anti-Helicobacter pylori, antioxidant

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 5 uppsatser.