Orientador: Madileine Francely Américo / Resumo: A contratilidade do músculo liso e o trânsito gastrintestinal (GI) são importantes parâmetros da motilidade, cujas alterações podem comprometer a absorção de nutrientes e a biodisponibilidade de fármacos. Diversos fármacos apresentam efeitos adversos associados ao trato GI e, mesmo aqueles utilizados para controlar esses efeitos, podem provocar alterações importantes na motilidade ainda pouco conhecidas. Camundongos das linhagens C57BL/6 e BALB/c são amplamente utilizados nas pesquisas biomédicas, entretanto poucos estudos consideram os parâmetros motores GI. Diante de métodos escassos para avaliar a motilidade in vivo e da importância de conhecer a fisiologia básica dos camundongos, bem como o efeito de fármacos sobre o trato GI, objetivou-se: 1) desenvolver protocolo para avaliação da contratilidade duodenal e trânsito gastrintestinal por meio da Biosusceptometria de Corrente Alternada (BAC), e avaliar comparativamente a morfologia e função gastrintestinal de camundongos das linhagens BALB/c e C57BL/6J e, 2) avaliar o efeito GI do tratamento com cisplatina e a influência da dexametasona como antiemético. A partir deste trabalho foi possível implementar um protocolo experimental inédito, por meio da BAC, para avaliar a contratilidade duodenal e o trânsito gastrintestinal em camundongos. Após prévia implantação de marcador magnético no duodeno de camundongos, observou-se uma alta e uma baixa frequência de contração, expressas em ciclos por minuto (cpm). BALB/c e C57BL/6J apre... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The smooth muscle contractility and gastrointestinal (GI) transit are important parameters of motility, whose alterations may compromise nutrient absorption and bioavailability of drugs. Several drugs have side effects associated with the GI tract and, even those used to control these effects may cause significant changes in motility that are still poorly understood. Mice C57BL/6 and BALB/c strains are widely used in biomedical research, but a few studies consider the GI motor parameters. In front of scarce methods to evaluate the in vivo motility and the importance of knowing the basic physiology of the mice, as well as the effect of drugs on the GI tract. Then, the objectives of this study were 1) to develop protocol for the evaluation of duodenal contractility and gastrointestinal transit through Alternating Current Biosusceptometry (ACB), and comparing the morphology and gastrointestinal function of BALB/c and C57BL/6J mice, and 2) to evaluate the GI effect of cisplatin treatment and the influence of dexamethasone as an antiemetic. From this work, it was possible to implement an original experimental protocol, through the BAC, to evaluate the duodenal contractility and the gastrointestinal transit in mice. After the previous implantation of a magnetic marker in the duodenum of mice, a high and low frequency of contraction, expressed in cycles per minute (cpm), was observed. BALB/c and C57BL/6J presented a high frequency of 40 cpm, while the low frequency in BALB/c was 29 ... (Complete abstract click electronic access below) / Doutor

Includes bibliographical references. / 59 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Various articles published by John Robin Warren on the discovery and pathology of Helicobacter pylori. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 2000

<p>After drinking water, the fluid quickly leaves the stomach thereby creating a hypotonic luminal environment in the duodenum. This in turn constitutes a potential threat to the integrity of the duodenal epithelium. It therefore seems highly likely that luminal hypotonicity activates physiological mechanisms that aim to increase luminal osmolality. One such physiological mechanism may be to increase mucosal permeability thereby facilitating the transport of osmolytes into the lumen.</p><p>A draw-back of performing experiments in anesthetized animals is that surgery <i>per se</i> depresses gut functions, such as peristalsis, by mechanisms involving endogenous prostaglandins. In this thesis it is shown that inhibition of cyclooxygenase-2 (COX-2), in animals subjected to an abdominal operation, restore and/or improve duodenal functions such as motility, mucosal bicarbonate secretion, hypotonicity-induced increase in mucosal permeability and the osmolality-adjusting capability.</p><p>Experiments revealed that the stomach is resistant to hypotonic challenge while the jejunum is more sensitive to hypotonicity-induced increase in mucosal permeability than the duodenum. The hypotonicity-induced increase in duodenal mucosal permeability is not due to injury but possibly reflects physiological dilatation of paracellular shunts.</p><p>Luminal perfusion of the duodenum with an isotonic solution lacking Cl^- decreased bicarbonate secretion while the lack of luminal Na⁺ increased mucosal permeability. Stimulation of bicarbonate secretion by COX-2 inhibition is to a large extent dependent on luminal Cl^- while that induced by vasoactive intestinal peptide is not.</p><p>The hypotonicity-induced increase in mucosal permeability involves the release and action of serotonin (5-HT) on 5-HT₃ and 5-HT₄ receptors and stimulation of enteric nerves strongly implicating physiological regulation of this process.</p>

After drinking water, the fluid quickly leaves the stomach thereby creating a hypotonic luminal environment in the duodenum. This in turn constitutes a potential threat to the integrity of the duodenal epithelium. It therefore seems highly likely that luminal hypotonicity activates physiological mechanisms that aim to increase luminal osmolality. One such physiological mechanism may be to increase mucosal permeability thereby facilitating the transport of osmolytes into the lumen. A draw-back of performing experiments in anesthetized animals is that surgery per se depresses gut functions, such as peristalsis, by mechanisms involving endogenous prostaglandins. In this thesis it is shown that inhibition of cyclooxygenase-2 (COX-2), in animals subjected to an abdominal operation, restore and/or improve duodenal functions such as motility, mucosal bicarbonate secretion, hypotonicity-induced increase in mucosal permeability and the osmolality-adjusting capability. Experiments revealed that the stomach is resistant to hypotonic challenge while the jejunum is more sensitive to hypotonicity-induced increase in mucosal permeability than the duodenum. The hypotonicity-induced increase in duodenal mucosal permeability is not due to injury but possibly reflects physiological dilatation of paracellular shunts. Luminal perfusion of the duodenum with an isotonic solution lacking Cl- decreased bicarbonate secretion while the lack of luminal Na+ increased mucosal permeability. Stimulation of bicarbonate secretion by COX-2 inhibition is to a large extent dependent on luminal Cl- while that induced by vasoactive intestinal peptide is not. The hypotonicity-induced increase in mucosal permeability involves the release and action of serotonin (5-HT) on 5-HT3 and 5-HT4 receptors and stimulation of enteric nerves strongly implicating physiological regulation of this process.

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

A study was undertaken of the stressful life situations of 87 duodenal ulcer patients (50 Indian and 37 Black males) and a control group of 75 non-ulcer patients (43 Indian and 32 Black males). The majority of the control group were orthopaedic patients selected on the grounds that they were not hospitalised for a psychosomatic complaint. The group emerged, however, as highly stressed in relation to possible work and income loss, because of their injuries. The duodenal ulcer and non-ulcer groups were similar in many demographic details and in several stressful life situations. There was a significantly higher reporting of stress in family life, in the work situation and as a result of the illness itself, by duodenal ulcer patients compared with the controls. The initial hypothesis that there would be more areas perceived of as stressful in the case of duodenal ulcer patients than controls was confirmed in the study. A minor hypothesis that there would be cross-cultural differences in the perception of stress was also confirmed. The follow-up study of Indian duodenal ulcer patients demonstrated the development of an "illness career" consisting of a periodic response to stress with onset or recurrence of duodenal ulcer symptoms accompanied by changes in the individual's family system. Minuchin's (1978) concept of enmeshment or disengagement in family systems was found to be applicable to the duodenal ulcer patient. The symptom served to maintain family homeostasis by transforming family conflict into care and concern, or by legitamising the under-functioning of the sick person. The role of social work intervention in relation to duodenal ulcer disease was explored through the establishment of a medical social work programme at the Gastro-Intestinal Unit, King Edward VIII Hospital, Durban. It was shown that the psychosocial aspects of duodenal ulcer disease must receive attention, together with medical treatment, if comprehensive patient care is to be achieved. Intervention should emphasise self management of stress through behaviour modification and cognitive restructuring. Family therapy is essential in cases where the symptom has a function in the family system. Many systems are involved in the aetiology and treatment of duodenal ulcer disease. A general systems approach is therefore useful in promoting a holistic view of the person and the illness. / Thesis (Ph.D.)-University of Durban-Westville, 1983.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

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

Introdução e objetivos: Eosinofilia duodenal está associada com parasitoses intestinais e com alergias alimentares, e tem sido sugerida como possível fator etiológico da dispepsia funcional, pela capacidade de causar alterações na motilidade e na sensibilidade do aparelho digestivo. Sua relação com o Helicobacter pylori é pouco conhecida, tendo sido avaliada apenas como achado secundário em alguns estudos, com resultados controversos. Esse estudo tem como objetivos avaliar o papel da infecção gástrica pelo H. pylori no número de eosinófilos duodenais e avaliar a relação dos eosinófilos duodenais com os sintomas da dispepsia funcional. Métodos: foram avaliados 100 pacientes dispépticos funcionais, de acordo com os critérios de Roma III, dos quais 50 foram H. pylori positivos e 50 negativos. Os pacientes foram submetidos à endoscopia digestiva alta com biópsias gástricas e duodenais. A positividade do H. pylori foi avaliada pelo teste de urease e pelo exame histológico (Hematoxilina-eosina e Giemsa). As biópsias duodenais foram avaliadas com hematoxilina-eosina e a número de eosinófilos duodenais foi quantificada pela média de eosinófilos por 5 campos de grande aumento (CGA) aleatórios e não sobrepostos. Eosinofilia duodenal foi definida pela presença de >22 eosinófilos/CGA. As medianas das médias aritméticas dos eosinófilos duodenais por cinco CGA foram comparadas entre os pacientes H. pylori positivos e negativos. Também foi avaliada a relação do número de eosinófilos duodenais com a intensidade e tipo de sintomas dispépticos, determinados por questionário validado (PADYQ). Os eosinófilos duodenais foram avaliados para variáveis demográficas e endoscópicas. Resultados: Pacientes do sexo feminino representaram 88% da amostra e a idade média foi de 41,7 anos As características basais dos pacientes H. pylori positivos e H. pylori negativos foram semelhantes. Apenas um paciente, no grupo H. pylori positivo, apresentou eosinofilia duodenal. As medianas dos eosinófilos duodenais/CGA foram 4,6 [P25-75: 2,8-7,2] nos pacientes H. pylori negativos e 4,7 [P25-75: 3,4-8,4] nos H. pylori positivos (p= 0,403). O número de eosinófilos 8 duodenais foi significativamente maior em pacientes com sintomas mais intensos: pacientes com escore do PADYQ >22 (>50% da pontuação máxima) apresentaram mediana de eosinófilos duodenais/CGA de 5,4 [P25-75: 3,4–7,6] e pacientes com escore ≤22 de 3,4 [P25-75: 2,2–6,0] (p= 0,018). Os pacientes foram divididos em tercis, de acordo com a intensidade dos sintomas: grupo 1 com 31 pacientes (sintomas leves); grupo 2 com 30 pacientes (sintomas moderados); e grupo 3 com 31 pacientes (sintomas acentuados). A mediana dos eosinófilos duodenais/CGA no grupo 1 foi de 3,4 [P25-75: 2,2 -6,0]; no grupo 2 de 4,7 [P25-75: 3,2-6,4]; e o grupo 3 de 5,8 [P25-75: 3,6-8,2] (P=0,033). Houve diferença estatisticamente significativa no número de eosinófilos duodenais entre fumantes e não fumantes (p= 0,030) e entre pacientes com índice de massa corporal (IMC) <25 kg/m2 e IMC ≥ 25 kg/m2 (p= 0,035). Na análise multivariada por regressão linear, os fatores que tiveram influência sobre o número de eosinófilos duodenais foram o tabagismo (p= 0,026) e a intensidade dos sintomas dispépticos (p= 0,039). Conclusões: Esse estudo não mostrou associação entre a infecção pelo H. pylori e a contagem de eosinófilos duodenais, nessa população de pacientes dispépticos funcionais. Entretanto, foi demonstrada uma relação diretamente proporcional e estatisticamente significativa entre o número de eosinófilos duodenais e a intensidade dos sintomas dispépticos. / Background and Aims: Duodenal eosinophilia is associated with intestinal parasitosis and food allergies. It has also been implicated as a potential factor on the etiology of functional dyspepsia, probably by causing changes in digestive tract motility and sensitivity. The association with Helicobacter pylori is poorly understood, and has been only evaluated as a secondary finding in 9 previous studies, with conflicting results. This study aims to evaluate the potential role of gastric H. pylori infection in the duodenal eosinophil count, and the influence of duodenal eosinophils on symptoms in functional dyspeptic subjects. Methods: One hundred functional dyspeptic subjects, according to Rome III criteria, were evaluated, and 50 were H. pylori positive and 50 H. pylori negative. Patients were submitted to upper gastrointestinal endoscopy with gastric and duodenal biopsies. H. pylori positivity was evaluated by urease test and gastric histology (Hematoxylin-eosin and Giemsa). Duodenal biopsies were evaluated with Hematoxylin-Eosin staining, and the duodenal eosinophil count was determined by the mean of eosinophil by 5 random nonoverlapping high power fields (HPF). Duodenal eosinophilia was defined as >22 eosinophils/HPF. The median of the arithmetic means of the duodenal eosinophils counts per high power field were compared between H. pylori positive and H. pylori negative subjects. The relationship between the number of duodenal eosinophils and the intensity and type of dyspeptic symptoms was determined by validated questionnaire (PADYQ). Duodenal eosinophils counts were also evaluated by demographic variables and endoscopic findings. Results: 88% of the subjects were female and the mean age was 41.7 years. Baseline characteristics were similar between H. pylori positive and H. pylori negative subjects. Only one patient, in the H. pylori positive group, had duodenal eosinophilia. The median duodenal eosinophils/HPF were 4.6 [Percentiles 25-75(P25-75): 2.8-7.2] in H. pylori negative and 4.7 [P25-75: 3.4-8.4] in H. pylori positive subjects (p= 0.403). The duodenal eosinophil count was greater in subjects with higher symptoms severity: patients with PADYQ score more than 22 (>50% of the maximum score) had median duodenal eosinophil/HPF of 5.4 [P25-75: 3,4–7,6] and subjects with PADYQ score ≤22 of 3.4 [P25-75: 2.2–6.0] (p= 0.018). The patients were divided into terciles, according to symptoms severity: group 1 with 31 subjects (mild symptoms); group 2 with 30 subjects (moderate symptoms); and group 3 with 31 subjects (severe symptoms). 10 The median duodenal eosinophils/HPF was 3.4 [P25-75: 2.2-6.0] in group 1; 4.7 [P25-75: 3.2-6.4] in group 2; and 5.8 [P25-75: 3.6-8.2] in group 3 (p=0.033). There was a higher duodenal eosinophils count in smokers (current or former) (p=0.030), and subjects with BMI ≥ 25 kg/m2 (p=0.035). In the multivariate analysis by linear regression, the duodenal eosinophil count were influenced by smoking (p = 0.026) and dyspeptic symptoms severity (p= 0.039). Conclusion: This study did not show an association between H. pylori infection and the number of duodenal eosinophils, in this population of functional dyspeptic patients. However, a directly proportional and statistically significant relationship between the number of duodenal eosinophils and the intensity of dyspeptic symptoms has been demonstrated.

Made available in DSpace on 2014-06-11T19:33:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-14Bitstream added on 2014-06-13T19:44:13Z : No. of bitstreams: 1 pereira_jg_dr_jabo.pdf: 2012412 bytes, checksum: a771199b8c53c2ad3c164715147a19cf (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O Kinosternon scorpioides é uma tartaruga de água doce conhecida como jurará. O objetivo do presente trabalho foi identificar serotonina, gastrina, enteroglucagon e motilina em esôfago, estômago e duodeno de K.scorpioides por meio da técnica de imunohistoquímica. Os resultados mostraram que as células imunorreativas à serotonina estavam presentes no epitélio na região caudal do esôfago, nas glândulas gástricas das regiões cárdica, fúndica e pilórica. As células produtoras de gastrina foram identificadas em grande quantidade entre as células da região pilórica e no epitélio de revestimento do duodeno, e em número reduzido na região cárdica. O enteroglucagon foi identificado na superfície dos cílios, no epitélio de revestimento da mucosa esofágica, nas fibras nervosas da lâmina própria e submucosa; no estômago estava localizado entre as células das glândulas cárdicas e fúndicas em número moderado, e aparentemente em maior quantidade nas pilóricas. No duodeno, o enteroglucagon foi identificado na superfície dos microvilos, no epitélio de revestimento, nas fibras nervosas da lâmina própria e submucosa. A motilina foi identificada apenas entre as fibras nervosas dos órgãos estudados. Em conclusão, as células imunorreativas à serotonina, gastrina, enteroglucagon e motilina foram identificadas em todos os órgãos estudados. Entretanto, nos diferentes segmentos houve diferença quanto à distribuição e frequência dessas células / Kinosternon scorpioides is a freshwater turtle known as “jurará”. The aim of this work was to identify peptides serotonin, enteroglucagon, gastrin and motilin in esophagus, stomach and duodenum by immunohistochemical techniques. The results showed that immunoreactive cells for serotonin were presented in the epthitelium of distal region of the esophagus, in glands of cardiac, fundic and pyloric region of the stomach and in the surface of duodenum epithelium. These cells were classified as open and closed type. The cells immunoreactive for gastrin were abundant in pyloric region and duodenum epitheliun, few numerous in cardiac region and absent in the esophagus. Cells rich in enteroglugagon were identified in the cilia surface, in the epithelium of esophagus, among nervous fibers of lamina propria and submucosa; in the stomach, these cells were observed in small number cardiac and fundic glands, however in pyloric region they were abundant. In duodenum, they were observed in microvillus surface, epithelium and nervous fibers of both lamina propria and submucosa. On the other hand, cells that produce motilin were observed just among lamina propia and submucosa. In conclusion, cells rich in serotonin, gastrin, enteroglugagon and motilin were found in all studied organs. However it was observed differences in the segments regarding distribution and frequency of these cells