Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

nÃo hà / O presente ensaio clÃnico avaliou o efeito gastroprotetor do Myracrodruon urundeuva AllemÃo (Aroeira-do-sertÃo) frente à gastropatia reativa (GR) secundÃria ao uso oral de aspirina (Ãcido acetil salicÃlico â AAS) em baixa dose (100 mg/dia). O Myracrodruon urundeuva AllemÃo, à planta nativa do Nordeste brasileiro, usada na medicina popular, como infusos ou decoctos da entrecasca de seu tronco, para afeÃÃes dermatolÃgicas, respiratÃrias, gastrointestinais e ginecolÃgicas. Seus extratos hidroalcÃolico e aquoso, submetidos a ensaios farmacolÃgicos prÃ-clÃnicos, demonstraram efeitos anti-inflamatÃrio, analgÃsico, cicatrizante, antiÃlcera, anti-histamÃnico e antibradicinÃnico e a ensaios clÃnicos preliminares, efeitos terapÃuticos sobre Ãlceras pÃpticas e cervicites. A GR por AAS, identificÃvel e classificÃvel endoscopicamente, foi escolhida como modelo de lesÃes gastroduodenais. Utilizou-se o elixir de Aroeira-do-sertÃo, obtido de brotos da planta jovem. O estudo, prospectivo, randomizado, duplo cego e comparativo com placebo, avaliou a ocorrÃncia da GR por AAS em dois grupos de participantes tratados por 04 semanas, respectivamente com: AAS e Elixir de Aroeira (Grupo Aroeira) e AAS e Placebo (Grupo Placebo). Antes do tratamento (prÃ-estudo), os participantes, de ambos os sexos, com 21 a 65 anos, demonstraram normalidade gastroduodenal por endoscopia digestiva alta (EDA); responderam a questionÃrio sobre sinais e sintomas digestivos, com escores de frequÃncia e de intensidade, e submeteram-se a anÃlises laboratoriais (hemograma completo, glicose, creatinina, TGO, TGP, TAP e TPTA). Doze sujeitos incluÃram o Grupo Aroeira e 11 o Grupo Placebo. ApÃs 04 semanas, nova EDA foi realizada, o questionÃrio sintomÃtico foi reaplicado e os exames laboratoriais foram repetidos (pÃs-estudo). As EDAs do pÃs-estudo evidenciaram GR por AAS em 100% dos sujeitos do Grupo Aroeira e em 82% dos sujeitos do Grupo Placebo (p = 0,2160). A anÃlise dos questionÃrios prà e pÃs-estudo, evidenciou ausÃncia de variaÃÃes clÃnicas significantes na comparaÃÃo intragrupo (Grupo Aroeira, p = 0,2907; Grupo Placebo, p = 0,8880) e na comparaÃÃo intergrupo (PrÃ-estudo, p = 0,7951 vs PÃs-estudo, p = 0,6809). Em relaÃÃo aos exames laboratoriais, apenas poucas variaÃÃes estatÃsticas em comparaÃÃes intragrupos foram verificadas em parÃmetros do hemograma, os quais, contudo, se mantiveram nas faixas de normalidade. TambÃm foram registradas elevaÃÃes discretas nas mÃdias das glicemias (alteraÃÃes justificÃveis pelo perfil da populaÃÃo estudada). Estas nÃo foram estatisticamente significantes nas comparaÃÃes prà e pÃs-estudo. Todos os demais parÃmetros laboratoriais se mantiveram dentro das faixas de normalidade e nÃo sofreram variaÃÃes estatÃsticas significantes nas comparaÃÃes prà e pÃs-estudo. Em conclusÃo, este estudo demonstrou que o Myracrodruon urundeuva AllemÃo, na formulaÃÃo estudada, nÃo oferece gastroproteÃÃo frente ao uso oral de AAS, mas tambÃm nÃo se associa a eventos adversos gastrointestinais ou a efeitos tÃxicos hematolÃgicos ou bioquÃmicos. Em relaÃÃo ao uso de AAS em baixas doses, o estudo demonstrou elevada incidÃncia de GR oligossintomÃtica nas semanas iniciais de tratamento. / This clinical trial evaluated the gastroprotective effect of the Myracrodruon urundeuva AllemÃo (Aroeira-do-sertÃo) in face of the reactive gastropathy (RG) due to the oral usage of low-dose (100 mg/day) of aspirin (acetyl salicylic acid â ASA). The Myracrodruon urundeuva AllemÃo, is a native plant of the Brazilian Northeast, used in popular medicine, as infusions or decoctos of its trunk bark, for dermatologic, respiratory, gastrointestinal and gynecologic disorders. Its hydroalcoholic and aqueous extracts were submitted to pre-clinical pharmacologic assays which showed anti-inflammatory, analgesic, healing, anti-ulcer, antihistaminic and antibradicininic effects. As well, preliminary clinical assays showed its therapeutic effects to peptic ulcers and to cervicitis. The RG due to ASA, which is identifiable and classifiable endoscopically, were chosen as gastroduodenal lesions model. It was employed the Aroeira-do-sertÃo elixir, obtained from burgeons of the young plant. The study was prospective, randomized, double-blind and placebo comparative and evaluated the occurrence of RG due to ASA in 2 groups of participants treated for 4 weeks, respectively with: ASA and Aroeira Elixir (Aroeira Group) and ASA and Placebo (Placebo Group). Before treatments (pre-study), the participants, from both sexes, with 21 to 65 years old, showed gastroduodenal normality by upper digestive endoscopy (UDE); answered a digestive signs and symptoms questionnaire, with frequency and intensity scores, and submitted to laboratory tests (CBC, Glucose, Creatinine, AST, ALT, PT and PTT). Twelve participants were included in the Aroeira Group and 11 in the Placebo Group. After 4 weeks of treatment, new UDEs were performed, the symptomatic questionnaire was reapplied and the laboratory tests were repeated (post-study). The post-studies UDEs showed ASA RG in 100% of the Aroeira Group participants and in 82% of the Placebo Group participants (p = 0.2160). The pre and post-study questionnaires analysis showed no significant clinical variations in the intragroup comparison (Aroeira Group, p = 0.2907; Placebo Group, p = 0.8880) or in the intergroup comparison (Pre-study, p = 0.7951 vs Post-study, p = 0.6809). The laboratory tests showed a few statistically significant variations in the intragroups comparisons of CBC parameters, which, however, stayed within the normal range values. As well, there were discrete elevations of the medium glucose dosages (alterations justifiable by the profile of the participantsâ population). However, these data were not statistically significant in the pre and post-study variations comparisons. All the other laboratory parameters stayed within the normal range values and did not show statistically significant variations in the pre and post-study comparisons. In conclusion, this study demonstrated that the Myracrodruon urundeuva AllemÃo, in the formulation studied, do not offer gastroprotection to the lesions resulting by the oral ASA usage, but neither it was associated to adverse gastrointestinal events nor to toxic hematologic or biochemical effects. In relation to the low-dose ASA therapy, the study demonstrated a high incidence of oligosymptomatic RG during the initial weeks of treatment.

Submitted in partial fulfillment of the requirement for the Degree of Master of Technology: Biological Sciences, ML Sultan Technikon, 1999. / Today, the number one income-generating drugs are remedies prescribed for gastric disorders, in particular dyspepsia. These clinical conditions have a multi-faceted aetiology and pathology of dysfunction. One likely causal factor is the entero-pathogen Helicobacter pylori. It has been shown to be more than just a commensal related to gastric diseases like dyspepsia (80-90% incidence) and duodenal ulcer sufferers (100% incidence), with a total estimated world-wide population infection of 50%. The current therapy offered to dyspepsia sufferers is a triple regimen of an anti-bacterial, an Ir proton-pump inhibitor, and bismuth colloidal salts. / M

Cathelicidin, a pleiotropic host defense peptide, has been shown to promote cutaneous wound repair and reaches high levels in the gastric mucosa during acute Helicobacter pylori-associated inflammation. The expression of cathelicidin, nevertheless, has also been found to be down-regulated in gastric hyperplastic polyps, tubular adenomas, and adenocarcinomas. We therefore hypothesized that cathelicidin might contribute to gastric ulcer healing and suppress gastric cancer growth. In this study, the role of this peptide in gastric tissue repair and carcinogenesis was investigated. / Collectively, this study demonstrates for the first time that cathelicidin can promote tissue repair and suppress cancer growth in stomachs by eliciting differential cellular signaling and responses in normal and cancerous gastric epithelial cells. These unique biological activities may open up a novel therapeutic avenue for the treatment of these diseases. / Concerning gastric carcinogenesis, the human cathelicidin LL-37 lowered gastric cancer cell proliferation and delayed G1-S transition in vitro and inhibited the growth of gastric cancer xenograft in vivo. Knockdown or induction of endogenous LL-37 by RNA interference or 1alpha,25-dihydroxylvitamin D3, respectively, increased or suppressed cell proliferation. In this connection, LL-37 increased bone morphogenetic protein (BMP) signaling, manifested as increases in BMP4 expression and the subsequent Smad1/5 phosphorylation and the induction of Smad6 and Smad7. Moreover, LL-37 increased the expression of p21Waf1/Cip1, whose induction was abolished by the knockdown of BMP receptor II. Knockdown of BMP receptor II or p21Waf1/Cip1 also abrogated the anti-mitogenic action of LL-37. The activation of BMP signaling by LL-37 was accompanied with the inhibition of chymotrypsin-like and caspase-like activity of proteasome. In this regard, proteasome inhibitor MG-132 mimicked the effect of LL-37 by increasing BMP4 mRNA expression and Smad1/5 phosphorylation. In addition, cyclin E 2 was down-regulated by LL-37 via a BMP-independent mechanism. Further analysis of clinical samples revealed that LL-37 and p21Waf1/Cip1 mRNA expression were both down-regulated in gastric cancer tissues and their expression were positively correlated. These findings indicate that LL-37 inhibits gastric cancer cell proliferation through activation of BMP signaling via a proteasome-dependent mechanism. / In relation to gastric ulcer healing, results revealed that ulcer induction in rats increased the expression of rat cathelicidin rCRAMP in the gastric mucosa. Further increase in expression of rCRAMP by local injection of rCRAMP-encoding plasmid promoted ulcer healing by enhancing cell proliferation and angiogenesis. rCRAMP directly stimulated proliferation of cultured rat gastric epithelial cells (RGM-1), which was abolished by inhibitors of matrix metalloproteinase (MMP), epidermal growth factor receptors (EGFR) tyrosine kinase, or mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase. rCRAMP also increased EGFR and ERK1/2 phosphorylation via an MMP-dependent mechanism. Knockdown of transforming growth factor alpha (TGFalpha), which is a ligand of EGFR, by small interfering RNA completely nullified the mitogenic signals evoked by rCRAMP in RGM-1 cells. These findings suggest that rCRAMP exhibits pro-healing activity in stomachs through TGFalpha-dependent transactivation of EGFR and its related signaling pathway to induce proliferation of gastric epithelial cells. / Wu, Ka Kei. / Adviser: Joseph J. Y. Sung. / Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0252. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 153-178). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Orientador: Marcelo Brocchi / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-09T02:57:32Z (GMT). No. of bitstreams: 1 Pacheco_AllineRoberta_M.pdf: 1095930 bytes, checksum: a6051845b7780b11eec360d1641c464c (MD5) Previous issue date: 2007 / Resumo: Helicobacter pylori é um bacilo Gram-negativo, espiralado, microaerófilo, e flagelado, incluído na família Helicobacteraceae. Essa bactéria infecta cronicamente a mucosa gastroduodenal de uma grande parcela da população mundial. A infecção por H. pylori está associada ao desenvolvimento de diversas doenças gastroduodenais em humanos, entre elas a gastrite, a úlcera péptica (PUD) e seus subtipos, úlcera gástrica (GU) e duodenal (DU), e o adenocarcinoma gástrico. Embora a porcentagem de infectados seja alta, podendo chegar a 90% nos países em desenvolvimento como o Brasil, somente uma pequena parcela dos indivíduos infectados desenvolve patologias graves. O desenvolvimento de doenças gástricas em indivíduos infectados por H. pylori parece ser o resultado da interação entre características do hospedeiro, influências ambientais e fatores de virulência produzidos pela bactéria. Muitos fatores de virulência prováveis, que contribuem para a patogênese, tem sido identificados em H. pylori, dentre os quais temos os genes da Ilha de Patogenicidade cag (PAIcag), e genes da zona de plasticidade de H. pylori. Embora sabe-se que muitos dos fatores de virulência descritos (cagA, cagE, vacA) estejam associados, universalmente, a um aumento no risco de desenvolvimento de quadros clínicos graves como úlcera péptica e câncer gástrico, nenhum deles pôde ser ligado a uma doença específica causada pela infecção persistente por H. pylori, e portanto ainda não foi descrito um gene marcador universal para uma doença resultante da infecção por essa bactéria. Dados da literatura mostram uma associação entre o gene cagT da PAIcag e o desenvolvimento de PUD. Um trabalho recente descreveu o locus dupA e sua associação com o desenvolvimento de DU, e dupA foi sugerido como marcador universal para DU. Neste trabalho, investigou-se a presença dos genes virB11 e cagT, localizados na PAIcag, e dos genes jhp917 e jhp918, integrantes do locus dupA encontrado zona de plasticidade de H.pylori, em isolados brasileiros dessa bactéria. Além disso, investigou-se uma possível associação entre tais genes e algumas doenças decorrentes da infecção por H. pylori, tais como a gastrite, PUD, GU, DU e a doença do refluxo gastroesofágico (GERD), na tentativa de encontrar um gene marcador para alguma dessas doenças. Nossos resultados mostram que o gene cagT foi associado com PUD; o gene virB11 foi detectado em quase todas as amostras; o locus dupA não foi associado a DU ou nenhuma outra doença gastroduodenal. Dessa forma, nossos resultados sugerem que o gene cagT pode ser usado como marcador para o desenvolvimento de PUD no Estado de São Paulo, Brasil; o gene virB11 pode representar um gene de virulência essencial para a patogênese da infecção causada por H. pylori no desenvolvimento de gastrite, PUD e GERD; o locus dupA não é um marcador universal para o desenvolvimento de DU / Abstract: Helicobacter pylori is a Gram-negative, spiral-shaped, flagellated, micro-aerophilic bacterium, included in the Helicobacteraceae family, which infects the human stomach cronically. H. pylori infection has a worldwide distribution and is associated with the development of several gastroduodenal diseases, such as gastritis, peptic ulcer disease (PUD) and its subtypes, gastric ulcer (GU) and duodenal ulcer (DU), and gastric adenocarcinomas. The number of infected individuals are high but only a minority of them will develop serious gastroduodenal diseases. Disease outcome depends on many factors, including host physiology, environmental influences and bacterial genotype. Although a number of putative virulence factors had been reported (cagA, cagE and vacA) for H. pylori, their presence has tipically been associated with an increased risk of both gastric cancer and peptic ulcer disease, and none can be clearly linked to one specific H. pylori related-disease. So the identification of a disease-specific H. pylori virulence factors predictive of the outcome of infection remains unachieved. Several of the H. pylori putative virulence genes that may play a role in its pathogenicity have been identified, many of them located in the cag pathogenicity island (PAIcag) and in the plasticity zone of the H. pylori genome. Data from the literature shows an association between cagT and PUD development, as well as dupA and DU. The latter has been suggested as an universal marker for the development of duodenal ulcers. In this work, we investigated the presence of virB11 and cagT, located in the left half of PAIcag, and the genes jhp917-jhp918, components of the dupA locus, which is located in the plasticity zone region of H. pylori, in brazilian isolates. In addition, we investigated a possible association between these genes and some H. pylori relateddiseases, such as gastritis, PUD, GU, DU and gastroesophageal-reflux (GERD), in an attempt to find a gene marker for a clinical outcome resulted from H. pylori infection. The cagT gene was associated with PUD; virB11 gene was detected in nearly all the samples; dupA locus was not associated with development of DU neither any gastroduodenal disease. In this way, our results suggest that cagT can be used as a marker for the developmentof PUD in State of São Paulo, Brazil; virB11 can be an essential virulence gene for H. pylori pathogenesis on the development of gastritis, PUD and GERD; dupA locus is not an universal marker for the development of DU / Mestrado / Microbiologia / Mestre em Genética e Biologia Molecular

Thesis--Odense. / Summary in Danish. Includes bibliographical references (p. 136-[147]) and index.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis--Odense. / Summary in Danish. Includes index. Bibliography: p. 136-[147]

目的：全面而系統的評價中醫藥對慢性萎縮性胃炎伴腸上皮化生的臨床總體療效、胃鏡療效、病理療效，及中醫藥對腸上皮化生的逆轉率。 方法：電腦檢索中國期刊全文資料庫、重慶維普中文科技期刊資料庫、中國知網資料庫、中國生物醫學文獻資料庫網路版、萬方資料庫、PUBMED 和中國中醫藥期刊文獻資料庫，查找有關中醫藥治療，慢性萎縮性胃炎伴腸上皮他生的隨機對照試驗，檢索從2006 年至2015 年12 月發表的論文。按照納入標準、排除標準及結局指標的統計進行文獻篩查，採用Jadad 評分標準對文獻進行評估，採用Review Manager5 軟體進行Meta分析。 結果： 共納入的項臨床研究，未發現隨機雙盲實驗。共納入1559 例慢性萎縮性胃炎伴腸上皮化生患者，未發現嚴重不良反應。Meta 分析結果顯示，在臨床有效性方面， 中醫藥個體化方案治療組與中成藥治療組相比OR=5.18,95%CI(3.59, 7.64)]，中醫藥個體化方案治療組與單純西醫西藥治療組相比OR=5.46, 95%CI (3.42,8.70），中醫中藥合輔助治療組與此外其他療法治療組OR=6.66 , 95%CI (2.69,16.49），試驗組療效均優於對照組。在胃鏡療效和病理療效方面，中醫中藥治療組與此外其他療法治療名且對胃粘膜萎縮改善情況對比結果OR=2.81，95%CI(1.76,4.47）, 對腸上皮化生改善情況的對比結果OR=4.14, 95%CI (2.87, 5.99 ）中醫中藥治療組與中成藥治療組對綜合胃鏡結果改善情況的對比結果OR =2.68, 95%CI (0.96, 6.8），對綜合病理結果改善情況的對比結果OR=2.80, 95%CI(1.79, 4.38）, 試驗組優於對照在且。中醫中藥治療組與此外其他方法治療組對腸上皮化生逆轉情況的對比結果，共在內人病例數1552 例，結果顯示OR=3.61, 95%CI(2.76, 4.72）,試驗組優於對照組。 結論：中醫藥治療慢性萎縮性胃炎伴腸上皮化生具有很好的臨床療效，主要體現在改善綜合胃鏡情況， 改善綜合病理情況以及逆轉腸上皮他生的情況。但由於臨床試驗設計的局限，不能對中醫藥對該疾病的作用進行全面的判斷，故仍需嚴謹的大樣本多中心的隨機雙盲試驗加以驗證。

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-13T14:23:21Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado Augusto - Versão Final - 05.07.16.pdf: 2539433 bytes, checksum: 5317f34435773775b8fcf0c7526d78d5 (MD5) / Made available in DSpace on 2017-07-13T14:23:21Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado Augusto - Versão Final - 05.07.16.pdf: 2539433 bytes, checksum: 5317f34435773775b8fcf0c7526d78d5 (MD5) Previous issue date: 2016-05-27 / O pantoprazol é, atualmente, um dos medicamentos mais utilizados para tratamento das doenças gástricas por seu mecanismo de ação conhecido e eficácia comprovada na inibição da secreção de ácido no lúmen estomacal, contudo o tratamento prolongado e os efeitos causados pelas gastropatias exigem tratamentos específicos e mais abrangentes. O material Vegetal Schinus terebinthifolius Raddi, conhecida como Aroeira, já é utilizada popularmente em feridas cutâneas pelos seus efeitos cicatrizantes e anti-inflamatórios, possui vários estudos comprovando sua eficácia na diminuição das lesões promovidas pelas doenças gástricas. Sabendo-se da existência das formulações Associação em Dose Fixa (ADF), que integram em uma mesma fórmula farmacêutica um insumo farmacêutico sintético e um insumo farmacêutico fitoterápico, o objetivo deste trabalho foi elaborar um forma farmacêutica sólida ADF utilizando doses terapêuticas do pantoprazol e do extrato da Aroeira. Para isto, foi realizada a obtenção do granulado seco de aroeira pela metodologia de secagem por convecção. Assim, os ativos foram misturados a excipientes e transformados em comprimidos, por compressão direta. Os comprimidos obtidos foram submetidos a controle físico-químico e foram realizados testes de doseamento, dissolução e estabilidade acelerada que avaliaram as condições da formulação. Como esperado a dissolução demonstrou liberação do pantoprazol em meio básico e degradação em meio ácido, levando a necessidade de utilização do fármaco em formato de grânulos gastroresistentes. Já os testes de estabilidade realizados nos tempos 0, 3 e 6 meses atestou no curto período a manutenção das características básicas de liberação e teor dos comprimidos que foram mantidos durante o estudo em câmara climática de zona IV. Foi possível, desta forma, estabelecer os parâmetros básicos para o desenvolvimento desta formulação ADF contribuindo para a descoberta de alternativas terapêuticas aos tratamentos convencionais. / Pantoprazole is today one of the most used drugs for the treatment of gastric diseases because its known mechanism of action and proven effectiveness in inhibiting acid secretion in the stomach lumen, but prolonged treatment and the effects caused by gastropathy require specific treatments and more extensive. Schinus terebinthifolius Raddi plant, known as Aroeira, is already commonly used in skin healing by its anti-inflammatory effects, having several studies showing efficacy in reducing gastric lesions promoted by the disease. Knowing the existence of the formulations Association-Dose-Fixed (ADF), which are part of the same pharmaceutical form, a synthetic active ingredient and an active herbal principle, the objective of this study was to develop a solid dosage form ADF using therapeutic doses of pantoprazole and the Aroeira extract. For to obtain the dry granulated were used the method for drying by convection, where the active excipients were mixed and tableted by direct compression. The tablets obtained were subjected to physic-chemical control and tests to determinate their concentrations, their accelerated stability and their dissolution quality who served to evaluate the conditions of the formulation. The obtained values maintained their therapeutic range described in the literature. As expected the dissolution demonstrated release of pantoprazole in basic medium and degradation in acid medium that leads to the need to use the drug in gastroresistant granules format. Since the stability testing at 0, 3 and 6 months attested short period maintaining the basic characteristics of release and content of the tablets that were maintained during the study in climate zone IV camera. It was thus possible to establish the basic parameters for the development of this formulation ADF contributing to the discovery of therapeutic alternatives to conventional treatments.