O objetivo deste estudo foi analisar a participação do PCV2 no desenvolvimento de ulcerações gástricas em suínos. Descrevem-se as lesões macroscópicas e histopatológicas nas diferentes zonas do estômago de suínos naturalmente infectados pelo PCV2 e H. pylori. As lesões foram descritas nas diferentes zonas do estômago. Os estômagos coletados eram provenientes de granjas com diagnóstico prévio de infecção pelo PCV2 durante os anos de 2006 à 2008. A presença dos agentes foi verificada por técnicas de imunoistoquímica (IHQ). Dentre os 63 estômagos processados, 30 não apresentavam ulcerações no quadrilátero, sendo que 16 deles apresentavam marcação anti-PCV2 positiva em alguma das regiões analisadas. Apenas 06 casos não apresentavam marcação anti-PCV2 nos dos tecidos testados (estômago e linfonodo). Marcação positiva anti-PCV2 foi verificada em 56 linfonodos, dos quais 28 estômagos foram positivos para PCV2 em alguma zona da mucosa glandular. Grandes quantidades de antígeno do PCV2 foram observadas pela IHQ no citoplasma, núcleo e restos necróticos de células intralesionais das glândulas gástricas nas regiões do antro e cárdia; entretanto, na região do fundo, a marcação de IHQ anti-PCV2 foi restrita às células da superfície mucosa e fossetas gástricas. Marcação de IHQ anti-H. pylori foi identificada em 27 casos, principalmente, na superfície mucosa e fossetas gástricas no antro. A associação de antígenos PCV2 com células produtoras de muco lesadas na zona glandular gástrica sugere o envolvimento de PCV2 como um fator adicional para o desenvolvimento de úlceras gástricas em suínos. / The aim of this study was to describe macroscopical and histopathological found in different zones of stomachs collected from pigs naturally infected with PCV2 and H. pylori. lesions were described in the different zones of the stomach. Stomachs were collected during the years of 2006 to 2008 from herds previously diagnosed as positive for PCV2 infection. The presence of the agents was determined by immunohistochemical techniques. Among 63 stomachs examined, ulceration of the Pars oesophagica was not observed in 30 stomachs, although, 16 of them showed positive PCV2 immunostaining in some of the areas tested. PCV2 immunostaining was not observed in only six cases in any of the tested tissues (stomach and lymph node). PCV2 positive immunostaining was observed in 56 lymph nodes and in some zones of the glandular mucosa, in 28 stomachs. Large amounts of PCV2 antigen were observed in the cytoplasm and nucleus of intralesional cells and in debris of gastric glands of antrum and cardia. However, anti-PCV2 immunostaining was restricted to superficial mucosal cells and gastric pits, in the fundus. H. pylori immunostaining was observed in 27 cases, mainly pn the mucosal surface and gastric pits of the antrum. The association of PCV2 antigen with damaged glandular mucus-producing cells in the gastric glandular zone suggests a role of PCV2 as an additional factor for the development of swine gastric ulcers.

Caesalpinia pyramidalis Tul. (Fabaceae), known as catingueira , have been used in folk medicine for the treatment of various disorders such as gastritis, heartburn, indigestion, and stomach ache. However, the gastroprotective properties of this species have not yet been studied. The ethanol extract of C. pyramidalis inner bark was used in rats via oral, at the doses of 30, 100, and 300 mg/kg. The antiulcer assays were performed using the ethanol- and nonsteroidal anti-inflammatory drug-induced ulcer protocols. Gastric secretion parameters (volume, pH, and total acidity) were also evaluated by the pylorus ligated model, and the mucus in the gastric content was determined. The anti-Helicobacter pylori activity of the ethanol extract of Caesalpinia pyramidalis was performed using the agar-well diffusion and broth microdilution methods to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values. The ethanol extract (30, 100, and 300 mg/kg) produced dose dependent inhibition (p < 0.01) on the ulcer lesion index in the ethanol-induced ulcer model. The ethanol extract (30, 100, and 300 mg/kg) also reduced (p < 0.001) the ulcer index in the indomethacin-induced ulcer model. In the model ligature pylorus, the treatment with C. pyramidalis ethanol extract failed to significantly change the gastric secretion parameters. However, after treatment with the ethanol extract of C. pyramidalis (30, 100, and 300 mg/kg), there was a significant increase (p < 0.05) in mucus production. The ethanol extract of Caesalpinia pyramidalis had an anti-Helicobacter pylori activity with a MIC of 625 ìg/mL and a MBC of 10.000 ìg/mL. Collectively, the present results suggest that the ethanol extract of C. pyramidalis display gastroprotective actions, supporting the folkloric usage of the plant to treat various gastrointestinal disturbances. / Caesalpinia pyramidalis Tul. (Fabaceae), conhecida popularmente como gcatingueira h, tem sido usada pela medicina popular para tratamento de diversas desordens fisiologicas como gastrite, indigestao e dores estomacais. Entretanto, a acao gastroprotetora dessa especie ainda nao foi estudada. O extrato etanolico da entrecasca (EEE) da Caesalpinia pyramidalis foi administrado em ratos pela via oral, nas doses de 30, 100 e 300 mg/kg. Para avaliacao da atividade gastroprotetora foram utilizados os modelos de ulceras agudas induzidas por etanol e anti-inflamatorio nao esteroidal (AINE). Parametros da secrecao gastrica (volume, pH e acidez total) e producao de muco gastrico tambem foram avaliados pela tecnica de ligadura de piloro. A atividade antimicrobiana do EEE da Caesalpinia pyramidalis foi mensurada atraves da tecnica de difusao em agar e calculados os valores da concentracao inibitoria minima (CIM) e da concentracao bactericida minima (CBM) pela tecnica de microdiluicao em placa. O EEE da Caesalpinia pyramidalis nas doses de 30, 100 e 300 mg/kg inibiu de maneira dose dependente (p < 0,01) o indice de lesoes ulcerativas no modelo de ulceras induzidas por etanol. No modelo de ulceras induzidas por AINE, o extrato em todas as doses utilizadas, tambem reduziu o indice de lesoes ulcerativas (p < 0,001). No modelo de ligadura de piloro, o tratamento com o EEE da Caesalpinia pyramidalis nao foi capaz de modificar os parametros da secrecao gastrica. Entretanto, apos tratamento com o EEE da Caesalpinia pyramidalis (30, 100 e 300 mg/kg) observou-se um aumento significativo (p < 0,05) na producao do muco gastrico. O EEE da Caesalpinia pyramidalis possui atividade antimicrobiana contra o Helicobacter pylori com CIM de 625 Êg/mL e CBM de 10.000 Êg/mL. Os resultados deste estudo sugerem que o EEE da Caesalpinia pyramidalis possui acao gastroprotetora, desta forma validando a utilizacao popular desta planta no tratamento de disturbios gastrointestinais.

Orientador: Alba Regina Monteiro Souza Brito / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-08T13:29:12Z (GMT). No. of bitstreams: 1 Barbastefano_Victor_D.pdf: 8030940 bytes, checksum: fafb57fc17a39a72e222df9d06055b31 (MD5) Previous issue date: 2007 / Resumo: O gênero Vernonia (Asteraceae) compreende cerca de 1000 espécies, figurando como o gênero mais representativo da sua família. Do ponto de vista sistemático, Vernonia é um dos gêneros mais complexos da família Asteraceae, principalmente pela extrema diversidade de formas biológicas que exibe, desde pequenas ervas até grandes árvores. O gênero possui um grande potencial farmacológico e é sempre mencionado em trabalhos etnofarmacológicos. Só no banco de dados Pubmed o termo ¿Vernonia¿ foi citado 126 vezes até Dezembro de 2006. No presente trabalho, a atividade antiulcerogênica de duas espécies do gênero Vernonia (Vernonia polyanthes Less. e Vernonia ferruginea Less.) foi investigada. Ambas as espécies estão presentes no cerrado, embora possuam ampla distribuição pelo território brasileiro, e são empregadas popularmente para o tratamento de bronquite, tosse, asma, cálculo renal, etc. Inicialmente foram realizados ensaios fitoquímicos e farmacológicos nos extratos brutos, clorofórmico e metanólico, de cada espécie. Foi identificada a presença de flavonóides e terpenóides em ambas as espécies, além da presença de atividade antiulcerogênica em todos os extratos brutos avaliados. Investigamos a seguir alguns dos possíveis mecanismos de ação dos extratos mais eficazes de cada espécie, do extrato metanólico da V. ferruginea (EMVF), rico em flavonóides e do extrato clorofórmico da V. polyanthes (ECVP), rico em terpenóides. Concluímos que eles estão relacionados a um aumento na produção de muco aderido à mucosa gástrica e dependem em parte da presença de óxido nítrico (NO) e radicais sulfidríla (SHs). O extrato ECVP foi então fracionado em fração clorofórmica (FCVP) e metanólica (FMVP) e o extrato EMVF foi particionado em fração acetato (FAVF) para avaliação farmacológica em modelos de úlcera crônica e aguda induzida. A fração FMVP, a mais eficaz dentre as duas espécies estudadas, foi então submetida a ensaios fitoquímicos objetivando a identificação da sua substância majoritária. O lupeol, triterpeno pentacíclico da família dos lupanos, foi identificado como o princípio ativo da espécie V. polyanthes e novos ensaios farmacológicos foram então realizados para elucidação dos seus mecanismos de ação. Foi identificado um aumento na produção de muco em animais pré-tratados com o lupeol, relacionado à presença de NO. Observou-se também uma boa atividade antiinflamatória na mucosa gástrica, através da diminuição da infiltração de neutrófilos, relacionada a uma diminuição na produção de PGE2. O lupeol, na dose investigada, não promoveu aumento significativo no pH do suco gástrico, o que descarta uma possível atividade anti-secretória. Por fim, nos estudos crônicos de indução de úlcera, o lupeol não apresentou toxicidade in vivo e demonstrou possuir uma grande atividade cicatrizante das lesões gástricas, provavelmente não relacionada à presença da Heat Shock Protein 70 (HSP70) e proliferação celular (PCNA) na borda da lesão. No presente trabalho, através do fracionamento biomonitorado das espécies V. polyanthes e V. ferruginea, identificamos a substância antiulcerogênica lupeol. A sua alta atividade gastroprotetora aliada à sua baixa toxicidade in vivo fazem do lupeol um fármaco potencial para o tratamento de úlceras gástricas / Abstract: The genus Vernonia (Asteraceae), which includes about 1.000 species, figures as the most representative from its family. From a systematic point of view, Vernonia is one of the most complex genus of its family, mainly because of its diverse biological forms, from small herbs through big trees. This genus possesses a great pharmacological potential and is always mentioned by ethnopharmacological works. Evidence for the interest in this genus is the number of citations in the database Pubmed. This exceeds 126 for the keyword ¿Vernonia¿, as of December, 2006. In the present work, the antiulcerogenic effect of two species from genus Vernonia (Vernonia polyanthes Less. and Vernonia ferruginea Less.) was evaluated. Both species are found predominately in Brazilian savannah, although they are widespread over Brazilian territory. They are used in traditional medicine for the treatment of bronchitis, cough, asthma and renal calculus. Initially, phytochemical and pharmacological assays were done with the crude methanolic and chloroformic extracts from each species. Flavonoids and terpenoids were identified in both species, and all crude extracts presented an antiulcerogenic effect. Soon afterward we evaluated some of the action mechanisms from the most effective crude extracts, the methanolic extract from V. ferruginea (EMVF), a flavonoid rich extract, and the chloroformic extract from V. polyanthes (ECVP), a terpenoid rich extract. They both presented an increase in gastric mucus content, and depended in part of the nitric oxide (NO) and sulfhydryls (SHs) presence. ECVP was then fractionated in a chloroformic (FCVP) and methanolic fraction (FMVP), while EMVF was partitioned in an acetate fraction (FAVF) for pharmacological approaches in chronic and acute models. FMVP, the most effective fraction, had its majority compound identified. Lupeol, a lupane pentacyclic triterpene, was identified as the active compound from V. polyanthes, and new assays were done to evaluate its action mechanisms. Lupeol increased gastric mucus content in rats, probably mediated by NO presence. It also presented anti-inflammatory properties in gastric mucosa, reducing PGE2 production and neutrophil infiltration. On its effective dose, it didn¿t decreased the gastric acid output. On the other hand, Lupeol showed on a chronic model of ulcer induction a great healing effect with no toxicity in vivo, probably not related to the presence of Heat Shock Protein 70 (HSP70) and cellular proliferation (PCNA) on the ulcer border. In the present work, in a biomonitored fractionation process of the species V. polyanthes and V. ferruginea, we identified the antiulcerogenic compound lupeol. Its high gastroprotective effect allied to its low toxicity in vivo, turns it a potential drug for treating gastric ulcers / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular

Orientadores: Fabio Husemann Menezes, João Poterio Filho / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-09T07:32:33Z (GMT). No. of bitstreams: 1 Viarengo_LuizMarceloAiello_D.pdf: 5372848 bytes, checksum: 053f8a2b3ec69d775d15f4e631b7f2c9 (MD5) Previous issue date: 2007 / Resumo: Este estudo foi desenvolvido para avaliar, prospectivamente, os resultados do tratamento de varizes com úlcera em atividade com laser endovenoso (EVL), comparando com um grupo sob tratamento clínico, durante um ano. Foram estudados 52 pacientes consecutivos portadores de varizes com úlcera em atividade há mais de um ano, divididos em dois grupos aleatórios. O Grupo I, tratamento clínico, formado por 25 indivíduos; o Grupo II, tratamento com EVL, constituído por 27 indivíduos. Todos os pacientes foram estudados com ultra-som no início e término do estudo. Os pacientes do Grupo II foram seguidos com ultra-som com 7 dias, 30 dias e a cada 3 meses. As áreas das feridas foram avaliadas a cada 3 meses. O laser utilizado para o tratamento endovenoso das varizes tronculares foi um laser de diodo, com comprimento de onda de 980 nanômetros, com potência nominal de 15W com fibra óptica condutora de laser de 600 microns, introduzida endovenosamente por punção percutânea dirigida por ultra-som e com emprego de anestesia local por infiltração intumescente associado a sedação leve por via oral com 15mg de Midazolam®. As medidas de temperaturas intra e perivenosa foram realizadas com um termômetro digital acoplado ao computador. Em 12 meses, 81,5% das feridas dos pacientes do Grupo II estavam cicatrizadas enquanto no Grupo I apenas 24% estavam cicatrizadas. A recorrência de úlcera foi de 44,4% no Grupo I, sem nenhuma recorrência no Grupo II. A área média das feridas no Grupo I reduziu de 18,04cm² para 13,16cm² ao final de um ano, enquanto no Grupo II reduziu de 22,7cm² para 3,64cm² (p<0,05). A temperatura média registrada foi de 79,3ºC no intravenoso e de 43,0ºC nos tecidos perivenosos. Não houve efeito adverso importante. O tratamento de varizes com laser endovenoso em pacientes com úlcera venosa em atividade mostrou-se seguro, com taxa de cicatrização das feridas superior à dos pacientes com tratamento clínico no prazo de um ano, e não houve recorrência / Abstract: Conventional saphenous vein stripping is difficult to be indicated for the treatment of varicose veins in patients classified as CEAP C4, C5 or C6. This study was developed to consecutively evaluate treatment results for varicose veins with active ulcers using endovenous laser (EVL), compared to a groupundergoing clinical treatment, during a year. Fifty-two consecutive patients presenting with varicose veins with active ulcers for more than a year were divided for treatment into two randomized groups: Group I, clinical treatment, composed of 25 subjects, were submitted to elastic or inelastic compression therapy according to individual medical recommendation; Group II, EVL treatment, composed of 27 subjects, were submitted to great and or small saphenous vein ablation with a 980 nm diode endovenous laser, plus the clinical treatment. Intravenous and perivenous temperatures were measured continuously with a digital thermometer connected to a computer during the EVL treatment. All patients were followed for 12 months and studied with ultrasound at the beginning and end of the study. The ulcers¿areas were evaluated initially and at every 3 months. In 12 months, 81.5% of the wounds in patients in Group II and only 24% in patients in Group I had healed. Ulcer recurrence rate was 44.4% in Group I. The average wound area in Group I decreased from 18.04cm² to 13.16cm² at the end of the year. In Group II, the wound area decreased from 22.7cm² to 3,64cm² (p<0,05). Mean intravenous and perivenous temperatures of 79.3ºC and 43.0ºC were recorded. In conclusion, the treatment for varicose veins with endovenous laser (EVL) as described is safe in patients with active ulcers. Wounds healed faster than in patients undergoing clinical treatment alone during a one-year period. There was no ulcer recurrence in patients treated with EVL / Doutorado / Cirurgia / Doutor em Cirurgia

Orientador: Alba Regina Monteiro Souza Brito / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T09:46:43Z (GMT). No. of bitstreams: 1 Silva_MariaSileneda_D.pdf: 4656721 bytes, checksum: 56e7845f0f3f5782cd1555e890bb08cc (MD5) Previous issue date: 2010 / Abstract: Abarema cochliacarpos (Gomes) Barneby & Grimes, which belongs the Mimosaceae family, is popularly known as "barbatimao" by the tradicional communities in Northeastern Brazil that use its bark in the treatment of gastric ulcer and inflammation, among other uses. In this work, the antiulcerogenic activity of its extracts and fractions was screened, using the gastric ulcer model induced by absolute ethanol in rats and selecting of the butanolic fraction of the methanolic extracts at dosis of 150 mg/kg as being in the most effective one. The action mechanisms of this fraction were studied based on the mucus gastric content and gastric secretion models. We have also decided to test it in anti-inflammatory intestinal activity model. Acute toxicity of AC150 was evaluated in Swiss mice, and no symptoms or visible toxicity signs were observed. Wistar rats were used in the others experiments. The intraduodenal pathway was utilized only in the pylorus ligature model; in the other models the oral pathway was employed. The AC 150 was able to significantly increased the mucus production, as well as to change the biochemical parameters of the acid gastric secretion, reducing the gastric volume and increasing the pH, suggesting a cytoprotection and anti-secretory activity. AC150 showed healing activity in the chronic model of gastric ulcer induced by 30 % acetic acid. This was demonstrated by the reduction of lesion area, in agreement with HE histological analysis. The induction of cellular proliferation was indicated by the PCNA results. The immunolocation of HSP-70, COX-2 and VEGF in the gastric tissue suggested that the ulcer cicatrization activity was induced by the increased of the expression of these factors, as well as the increase of the mucus production highlightened in the PAS results. In the acute ulcerative colitis model induced by intra-colonic administration of trinitrobenzensulfonic acid (TNBS) (10 mg/animal) AC 100 and 150 mg/kg were able to significantly decrease the lesion and the mieloperoxidase (MPO) levels in the colonic mucosa. However, only AC150 decreased the levels of the tumour necrosis factor-alpha (TNF-a). The western blot analysis showed that AC 150 mg/kg induced the down-regulation of both cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression, and the involvement of signaling also demonstrated a reduction in the JNK activation in this dosis. In the chronic colitis model (TNBS, 30 mg/animal) AC 150 showed the same inhibition profile of the inflammatory parameters; nevertheless, the increase of the antiinflammatory cytokine production IL-10 was highlightened only in this model. These data suggested a significant protective effect of the chronic administration of AC during the chronic phase of the inflammatory response associated with TNBS induced colitis. Phytochemical studies by mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) revealed that catechins were a major component into condensate class of tannins. Taken as a whole, these data allow us to conclude that the AC150 of Abarema cochliacarpos has chemical compounds that present antiulcerogenic gastric and anti-inflammatory activities, which may be attributed to the tannins and (+)-catechins of this fraction. / Abstract: Abarema cochliacarpos (Gomes) Barneby & Grimes, which belongs the Mimosaceae family, is popularly known as "barbatimao" by the tradicional communities in Northeastern Brazil that use its bark in the treatment of gastric ulcer and inflammation, among other uses. In this work, the antiulcerogenic activity of its extracts and fractions was screened, using the gastric ulcer model induced by absolute ethanol in rats and selecting of the butanolic fraction of the methanolic extracts at dosis of 150 mg/kg as being in the most effective one. The action mechanisms of this fraction were studied based on the mucus gastric content and gastric secretion models. We have also decided to test it in anti-inflammatory intestinal activity model. Acute toxicity of AC150 was evaluated in Swiss mice, and no symptoms or visible toxicity signs were observed. Wistar rats were used in the others experiments. The intraduodenal pathway was utilized only in the pylorus ligature model; in the other models the oral pathway was employed. The AC 150 was able to significantly increased the mucus production, as well as to change the biochemical parameters of the acid gastric secretion, reducing the gastric volume and increasing the pH, suggesting a cytoprotection and anti-secretory activity. AC150 showed healing activity in the chronic model of gastric ulcer induced by 30 % acetic acid. This was demonstrated by the reduction of lesion area, in agreement with HE histological analysis. The induction of cellular proliferation was indicated by the PCNA results. The immunolocation of HSP-70, COX-2 and VEGF in the gastric tissue suggested that the ulcer cicatrization activity was induced by the increased of the expression of these factors, as well as the increase of the mucus production highlightened in the PAS results. In the acute ulcerative colitis model induced by intra-colonic administration of trinitrobenzensulfonic acid (TNBS) (10 mg/animal) AC 100 and 150 mg/kg were able to significantly decrease the lesion and the mieloperoxidase (MPO) levels in the colonic mucosa. However, only AC150 decreased the levels of the tumour necrosis factor-alpha (TNF-a). The western blot analysis showed that AC 150 mg/kg induced the down-regulation of both cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression, and the involvement of signaling also demonstrated a reduction in the JNK activation in this dosis. In the chronic colitis model (TNBS, 30 mg/animal) AC 150 showed the same inhibition profile of the inflammatory parameters; nevertheless, the increase of the antiinflammatory cytokine production IL-10 was highlightened only in this model. These data suggested a significant protective effect of the chronic administration of AC during the chronic phase of the inflammatory response associated with TNBS induced colitis. Phytochemical studies by mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) revealed that catechins were a major component into condensate class of tannins. Taken as a whole, these data allow us to conclude that the AC150 of Abarema cochliacarpos has chemical compounds that present antiulcerogenic gastric and anti-inflammatory activities, which may be attributed to the tannins and (+)-catechins of this fraction. / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular

Orientador: Alba Regina Monteiro Souza Brito / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T09:47:10Z (GMT). No. of bitstreams: 1 Pimentel_FabianadeOliveira_M.pdf: 870212 bytes, checksum: 8e570716c925b38a3a354b49a0ae575c (MD5) Previous issue date: 2006 / Resumo: A úlcera péptica afeta cerca de 10% da população ocidental. Estudos relatam a participação de espécies reativas do oxigênio (EROs) na etiologia e patofisiologia das doenças humanas; como o processo inflamatório, infecção viral, doenças auto-imunes, doenças gastrointestinais e na úlcera gástrica. Alterações bioquímicas são constatadas durante a formação da úlcera, indicando que os radicais livres estão envolvidos com o processo ulceroso. Na úlcera por etanol ocorre formação de edema, liberação de substâncias vasoativas, infiltração de células inflamatórias e aumento da permeabilidade da mucosa. Há uma maior formação de EROs a partir das células inflamatórias, devido a alterações na cadeia respiratória ou a atividade da xantina oxidase, utilizando acetaldeído como substrato. Na úlcera gástrica por de isquemia e reperfusão, a liberação de EROs é relatada como um evento patológico central, sendo a mesma por si só capaz de provocar lesões no tecido gástrico; entretanto, é após a reperfusão que ocorrem os principais eventos lesivos. Neste trabalho foi avaliada a possível atividade antioxidante da fração acetato de etila (FAc) de Byrsonima crassa e Byrsonima fagifolia em úlcera induzida por etanol e por isquemia e reperfusão em ratos machos Wistar. Sob nossas condições experimentais, os modelos de indução de úlcera por etanol e por isquemia e reperfusão provocaram alterações no sistema antioxidante da mucosa gástrica de ratos, como nos níveis de grupamentos sulfidrila (GSH), glutationa peroxidase (GPx) e glutationa redutase (GR). Também observamos aumento na atividade da superóxido dismutase (SOD) e da concentração de espécies que reagem com o ácido tiobarbitúrico (TBARs), como índice de peroxidação lipídica (LPO). As FAc de B. crassa e FAc de B. fagifolia no modelo de etanol permitiram o restabelecimento dos níveis de GSH, de LPO e da atividade da SOD. Com relação as GPx e GR apenas o tratamento com FAc de B.crassa permitiu o seu restabelecimento. O tratamento com FAc de B. crassa e FAc de B. fagifolia no modelo de isquemia e reperfusão não restabeleceu nenhum dos parâmetros estudados. A atividade antiulcerogênica da FAc de B. crassa e B. de fagifolia pode estar envolvida com atividade antioxidante através do seqüestro de radicais livres aliado a outros mecanismos de proteção / Abstract: The gastric ulcer is a pathology that affects about 10% of the world-wide population. There is evidence concerning the participation of reactive oxygen species (ROS) in the etiology and pathophysiology of human diseases, such as inflammation, viral infections, autoimmune pathologies, and digestive system disorders such as gastrointestinal inflammation and gastric ulcer. Studies have shown alterations in the antioxidant status following ulceration, indicating that free radicals seem to be associated with the ethanol-induced and ischaemia-reperfusion-induced ulceration in rats. Ethanol promotes a strong and quick venoconstriction, which is followed by arteriolar dilatation. The oxyradicals generated during the episodes of ethanol can provoke severe changes leading to cell death. In the ischaemia and reperfusion the release of ROS is reported as a central pathological event. Thus, the objective of this work was to evaluate the antioxidant activity of the ethila acetate fraction (FAc) of gross Byrsonima crassa Nied. and Byrsonima fagifolia Nied. in the induced ulcer by absolute ethanol and ischaemia and reperfusion in male rats Wistar. We observed the reduction of the levels the sulfhydryl compounds (GSH), the increase in the concentration of species that react with the tiobarbitúrico (TBARS), as index of lipid peroxidation (LPO), beyond the reduction in the activity in the activity of glutathione peroxidase (GPX), glutathione reductase (GR.) and increase in superoxide dismutase (SOD). The FAc B. crassa and FAc B. fagifolia administration in the ethanol induced the reestablishment of the levels of GSH, LPO and activity of the SOD. Regarding to the GPx and GR activities only the treatment with FAc B.crassa allowed its reestablishment. In ischaemia and reperfusion -induced gastric lesions, were observed the increase of LPO, the reduction of the activity of the GPx and GR., and the increase of SOD. The treatment with FAc B. crassa and Fac B. fagifolia in ischaemia and reperfusion -induced gastric lesions did not reestablish none of the studied parameters. The antiulcerogenic activity of gross FAc B. crassa and FAc B. fagifolia can be involved with antioxidant activity, through the free radicals kidnapping associated with other mechanisms of protection / Mestrado / Mestre em Farmacologia

Orientador: Sandra Cecilia Botelho Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T12:19:53Z (GMT). No. of bitstreams: 1 Roesler_BrunaMaria_M.pdf: 3428404 bytes, checksum: ee37171bd6740210c88477c4839317fb (MD5) Previous issue date: 2006 / Resumo: O Helicobacter pylori é uma bactéria gram-negativa que está estritamente relacionada com o desenvolvimento de doenças gástricas, inclusive malignas, sendo classificada como carcinógeno do grupo I pela Agência Internacional para Pesquisa do Câncer. Apesar de grande parte da população mundial estar contaminada pela bactéria, a maioria dos indivíduos permanece assintomática. Muitas abordagens são sugeridas para diferenciar os isolados de H. pylori e diversas técnicas de biologia molecular têm sido aplicadas para caracterizar as amostras clínicas de diferentes pacientes. A análise de restrição (RFLP) usada em conjunto com a PCR tem sido amplamente utilizada para a tipagem de isolados clínicos, utilizando vários genes do genoma do H. pylori como alvos para esse método. Padrões de eletroforese da nested PCR e da PCR para as regiões dos genes urease C e urease B do H. pylori foram obtidos com enzimas de restrição e comparados entre pacientes com úlcera péptica e gastrite crônica. Os produtos da nested PCR para urease C foram digeridos com a enzima Mbo I e os produtos da PCR para urease B com a enzima Hae III, sendo os fragmentos obtidos analisados por eletroforese em gel de agarose. Foram encontrados 7 padrões de genotipagem para urease B e 17 padrões para urease C. O grupo prevalente para gastrite crônica obtido com essa última genotipagem foi o denominado grupo ureC MboI G, com fragmentos de 110, 120, 250 e 310 pares de bases, ocorrendo em 13 pacientes (15,7% dos casos). Em relação aos casos de úlcera péptica, o grupo de genotipagem mais prevalente foi o denominado ureC MboI E, com 110, 180 e 500 pares de bases, ocorrendo em 11 pacientes (24,4% do total de casos). O grupo prevalente obtido com a genotipagem para urease B foi o denominado ureB I, com um fragmento único de 750 pares de bases. Esse grupo foi o prevalente tanto para os casos de úlcera péptica (27), com 60,0%, quanto para os de gastrite crônica (53), com 63,9%. Não foram observadas diferenças significativas entre os padrões encontrados para ambas as doenças. A nested PCR para detecção prévia do DNA do H. pylori também foi realizada, obtendo-se 100% de concordância. Os métodos de tipagem dos produtos obtidos por nested PCR e PCR proporcionam um esquema funcional e de grande reprodutibilidade para estudos epidemiológicos e de caracterização de cepas / Abstract: Helicobacter pylori is a gram-negative bacterium that has been implicated as a major human gastric pathogen responsible for gastritis and peptic ulcer disease. It has been classified as a group I carcinogen by the International Agency for Research on Cancer and is regarded as a primary factor for gastric cancer. A significant proportion of the world population is infected with H. pylori, even though most infections are asymptomatic. To isolate H. pylori, many approaches have been presented and several molecular techniques have been applied to separate clinical isolates from different patients. PCR-RFLP analysis has been widely developed for the typing of clinical isolates, with several genes within H. pylori having been targeted by this method. Eletroforesis patterns of nested PCR and PCR to urease C and urease B gene regions of H. pylori were obtained by restriction fragment length polymorphism and compared among patients with peptic ulcer and chronic gastritis. Nested PCR products for urease C were digested with MboI enzyme and PCR products for urease B with Hae III enzyme, and the obtained fragments were analyzed by eletroforesis in agarosis gel. We have encountered 7 genotyping patterns for urease B and 17 patterns for urease C. The prevalent group for chronic gastritis which was obtained with this last genotyping was named ureC MboI G group, with fragments of 110, 120, 250 and 310 base pairs, occurring in 13 patients (15,7% of the cases). Regarding the peptic ulcer cases, the most prevalent genotyping group was named ureC MboI E group, with 110, 180 and 500 base pairs, occurring in 11 patients (24,4% of the cases). The prevalent group obtained with the genotyping for urease B was named ureB I, with only one fragment of 750 base pairs. This group was the prevalent one both in peptic ulcer cases (27) with 60,0%, and in chronic gastritis case (53), with 63,9%. We haven¿t found meaningful differences among the encountered patterns for both diseases. Nested PCR for previous detection of H. pylori DNA has also been performed, and we have obtained 100% of concordance. The typing methods of the products obtained by nested PCR and PCR show a functional scheme and of great reproduction for epidemiologic studies and of H. pylori strains characterization / Mestrado / Mestre em Farmacologia

Orientadores: Maria Aparecida Mesquita, Ciro Garia Montes / Dissertação (mestrado profissional) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T06:48:46Z (GMT). No. of bitstreams: 1 CustodioLima_Juliana_M.pdf: 1668374 bytes, checksum: ee0f2db5e25a3f2b8735d67b17331357 (MD5) Previous issue date: 2013 / Resumo: A hemorragia digestiva alta (HDA) é a emergência gastrointestinal mais frequente em todo o mundo. De acordo com a etiologia, a HDA se divide em varicosa e não varicosa. Existem poucos dados recentes da literatura nacional com relação à evolução dos pacientes com HDA, especialmente no que se refere à população idosa. Além disso, o uso de escalas prognósticas para avaliar o risco dos pacientes, como o escore de Rockall, embora recomendado por várias diretrizes, ainda não foi incorporado na prática clínica da maior parte dos hospitais brasileiros. Os objetivos do presente estudo foram avaliar as características clínicas, os achados endoscópicos e a evolução em 30 dias de pacientes com HDA não varicosa, e identificar os principais aspectos associados com a idade avançada...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Upper gastrointestinal bleeding (UGIB) is the most frequent gastrointestinal emergency worldwide. According to the etiology, UGIB is classified into variceal and non variceal bleeding. There is a lack of recent data regarding the outcomes of non variceal UGIB in Brazil, specially in the elderly. Furthermore, although recommended by several guidelines, the use of prognostic scales for risk assessment, such as the Rockall score, has not yet been included in the daily practice of most Brazilian hospitals. The aims of this study were to evaluate the clinical features, endoscopic findings and outcomes within 30 days in patients with non variceal UGIB, and to identify the main characteristics related to advanced age...Note: The complete abstract is available with the full electronic document / Mestrado / Clinica Medica / Mestra em Clínica Médica

Orientadores: Alba Regina Monteiro Souza Brito, Everardo Magalhães Carneiro / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-03T15:44:26Z (GMT). No. of bitstreams: 1 Paula_AnaClaudiaBensuaskide_D.pdf: 11340456 bytes, checksum: b5246f89983fbde44c817f7181e3eda4 (MD5) Previous issue date: 2003 / Resumo: É conhecido que a desnutrição protéica pode afetar o metabolismo de humanos, roedores e outros animais. É aceito que úlceras pépticas são causadas por um desequilíbrio entre fatores agressivos e fatores protetores da mucosa gástrica. Então, o objetivo primário deste trabalho foi verificar a correlação entre a desnutrição protéica e a formação de úlceras gástricas em ratos alimentados com baixo (6%) e regular (17%). Croton cajucara Benth (Euphorbiaceae) é uma planta usada na medicina tradicional da Amazônia no tratamento das doenças do trato gastrointestinal. Assim, nós também investigamos a ação anti-ulcerogênica de C. cajucara no tratamento de úlceras gástricas em ratos controles e desnutridos. É observado que animais desnutridos apresentam. um menor número de lesões gástricas quando comparado aos animais normais submetidos ao processo de úlcera gástrica induzida por etanol e indometacina. Isto se deve ao fato dos animais desnutridos produzirem uma maior quantidade de muco aderido a parede gástrica e de prostaglandina E2 (pGEz), quando comparado aos animais normais mesmo na ausência de droga anti-ulcerogênica. Na indução de úlcera pôr ligadura de piloro, os animais desnutridos tratados com o controle negativo 12% tween 80, mostraram um aumento significativo no volume do suco gástrico quando comparado aos animais normais. Após a administração (via intra-duodenal) do óleo essencial de sacaca, houve uma redução significativa na concentração de íons Ir do conteúdo gástrico de ambos os grupos animais. O volume do suco gástrico esteve aumentado no grupo de animais normais, entretanto em ratos desnutridos o volume do suco gástrico manteve-se constante após o tratamento com sacaca, porém permanecendo com seus valores altos. Em experimentos crônicos, onde os animais foram tratados por 14 dias com o veículo, com a droga padrão (cimetidina) e com o óleo essencial de Croton cajucara, verificou-se que os animais desnutridos apresentaram sérias lesões na mucosa gástrica quando comparado às lesões gástricas dos animais normais. Em ambos os casos (ulceração aguda e crônica), o óleo essencial de sacaca revelou-se eficiente em impedir e em cicatrizar estas lesões gástricas em ambos os grupos animais. Observou-se desta forma, que o efeito anti-ulcergênico do óleo essencial de C. cajucara se deve ao aumento de PGE2 e muco aderido à parede gástrica conferindo a citoproteção do estômago. Aliado a isto, houve um aumento do fator de crescimento epidermal da mucosa gástrica, dos níveis de somatostatina e de corticosterona; e baixos níveis de gastrina, que favoreceram a cicatrização da mucosa gástrica de ambos os grupos animais. Todos estes fatores parecem agir conjuntamente no sentido de produzir um efeito anti-ulcerogênico do óleo essencial cicatrizando a mucosa gástrica de animais normais e desnutridos. Os resultados deste trabalho confirmaram o efeito cicatrizante do óleo essencial de C. cajucara obtido previamente com ratos normais. Adicionalmente, foi possível concluir que os animais com desnutrição protéica mostraram uma melhor prevenção da mucosa gástrica frente aos agentes ulcerogênicos, devido às alterações fisiológicas encontradas em seus organismos / Abstract: It is known that the protein malnutrition can affect metabolism rates in humans, rodents and other animals. It is generally accepted that peptic ulcers are caused by a failure in the balance between gastric aggressive factors and mucosal defensive factors. Thus, the primary aim of this work was to verify the correlation between protein malnutrition and the gastric ulcer formation in rats fed diets with low (6%) or regular (17%) content of proteins. Croton cajucara Benth (Euphorbiaceae) is a specie widely used in Amazonian folk medicine for the treatment of a wide range of gastrointestinal symptoms. Thus, we also investigated the anti-ulcerogenic action of C. cajucara in the treatment of gastric ulcers in control and protein undernourished rats. It was observed that undernourished animals presented lower number of gastric injuries when compared with control animals in ethanol- and indomethacin-induced acute gastric ulcer. This may have occurred because undernourished animals produced greater amount of mucus and prostaglandin E2 (PGE2) when compared with the values obtained in control animals, even in the absence of the anti-ulcerogenic drugs. Besides, in placebo treated (12% Tween 80) undernourished rats submitted to pylorus ligature, a significant increase in gastric juice volume was observed when compared with control animals. After administration of essential oil from C. cajucara by intra-duodenal route, there was a significant reduction in the total acid content of both animal groups. The gastric juice volume was increased in the control group; however in undernourished rats, the gastric juice volume was higher before and remained high after treatment. In chronic experiments, where the animals were treated for 14 days with vehicle, standard drug (cimetidine) and with Croton cajucara essential oil, undernourished animals showed serious injuries in the gastric mucosa when compared with the gastric lesions of control animals. In acute and chronic ulceration, the essential oil was efficient in both animal groups to prevent and to heal these kinds of injuries. It was observed that C. cajucara essential oil caused citoprotection of the gastric mucosa of control and undernourished rats due to the increase of PGE2 release and gastric mucus content. It was also detected an increase of epidermal growth factor more pronounced in the gastric mucosa of control rats than malnourished rats that probably helped the healing of the gastric lesions. An increase in somatostatin and corticosterone levels and the decrease in gastrin levels were observed in both groups, control and undernourished animals.However, the latter showed high levels of somatostatin and corticosterone hormones and low gastrin levels when compared to control rats. All these factors appear to contribute with the anti-ulcerogenic effect of the essential oil preventing and healing the gastric mucosal damage of both control and undernourished animals. The results of this work confirmed healing effects previously obtained with C. cajucara essential oil in control rats. Additionally, it was possible to demonstrate that undernourished animals showed a resistance of the gastric mucosa against to ulcerogenic agents due to physiological changes found in their organisms / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular

L'ulcère de Buruli (UB), ou infection à Mycobacterium ulcerans, est une maladie tropicale négligée qui se manifeste par des lésions cutanées, responsable d'une morbidité importante et de lourdes incapacités chez les personnes atteintes. Cette maladie touche surtout des populations rurales en Afrique de l'Ouest et Afrique Centrale, où elle sévit dans des foyers localisés. Le mode de transmission de M. ulcerans à l'humain est inconnu et les connaissances épidémiologiques limitées, ce qui restreint les possibilités de contrôle de la maladie. Les objectifs de cette thèse étaient d'identifier les circonstances associées au risque d'UB, et d'améliorer la compréhension de la chaîne de transmission de M. ulcerans, à partir de l'étude de deux foyers d'UB situés au Cameroun. Nos travaux ont permis d'identifier des environnements, saisons et activités à risque d'UB à l'échelle individuelle, et à celle du territoire. Un travail d'entomologie de terrain a permis de compléter ces analyses en vérifiant l'existence d'une circulation de M. ulcerans dans l'environnement domestique : plusieurs groupes d'arthropodes porteurs de M. ulcerans ont été identifiés dans l'environnement domestique, parmi lesquels plusieurs possibles candidats vecteurs. Ces travaux apportent des précisions sur l'épidémiologie de d'UB au Cameroun, qui sont transposables à d'autres foyers endémiques africains présentant des environnements similaires. Ces résultats permettront de cibler les populations, zones et périodes à risque, afin de rendre plus efficace les activités de santé publique de contrôle de l'UB. Ces résultats proposent enfin de nouvelles approches pour la recherche du mode de transmission de M. ulcerans / Buruli ulcer (BU) is a tropical disease caused by Mycobacterium ulcerans. It appears as cutaneous lesions causing severe morbidity and permanent incapacities in affected populations. BU occurs mainly in West and Central Africa, where it is found endemic in very localized regions. The transmission mode of M. ulcerans to humans remains mysterious, which, combined with the lack of basic epidemiological knowledge on the disease, hampers considerably the design of effective control strategies. The goals of this thesis were to identify the different risks associated with Buruli ulcer, and to contribute to the improvement of knowledge on the circulation and transmission of M. ulcerans. We studied two Buruli ulcer foci in Cameroon, and analyzed the individual, behavioral, spatial and temporal risk factors for BU. We described populations groups, environments and seasons at higher risk. We also engaged in entomological fieldwork to verify if M. ulcerans was circulating in the domestic environment, an hypothesis never tested in African endemic regions. We identified several taxa carrying M. ulcerans, and possible vector candidates among them.This work proposes an update of the knowledge on Buruli ulcer epidemiology in Cameroon, and several results can be transposed to other endemic regions, especially in Central or West Africa, where endemic areas present similar environments. These results could provide useful elements to design more efficient public health strategies against Buruli ulcer and to target them accurately to populations, places and persons at highest risk. These results finally suggest new leads for future research on the mode of transmission of M. ulcerans.