Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.

This thesis presents work designed to study the effects of acid secretagogues upon the parietal cell, in order to gain a greater understanding of their modes of action, and interaction and the role of circulating secretagogues in the mediation of parietal cell function, with the aim of increasing the understanding of the pathophysiology of the world-wide problem of peptic ulcer disease.

Familial Amyloidosis with Polyneuropathy was first recognized in Portugal and reported by Andrade in 1952. The disease is rare, but clustering of the patients has been reported from Portugal, Japan and northern Sweden. The gastrointestinal involvement in the Swedish form of the disease was studied in this investigation. In a study of 52 patients on their first admission 47 displayed gastrointestinal symptoms in the form of severely altered bowel habits (intractable diarrhea and/or constipation). Steatorrhea was found in 30 out of 52 patients (58%) and an impaired d-xylose absorption in 26 out of 50 patients (52%). The steatorrhea was correlated to the degree of peripheral polyneuropathy as expressed by EMG-score. No relation could be established between steatorrhea or impaired d-xylose absorption with oral lactose and glucose tolerance tests indicating an intact entero- cyte function. A follow-up study comprising 21 patients demonstrated that all patients ultimately developed gastrointestinal symptoms and that the prevalence of diarrhea became higher with the duration of the disease. In this study steatorrhea became more frequent and was significantly related to the duration. Bile acid breath test, fecal fat determination and d-xylose tests were performed on 13 patients. Six patients with results indicating an increased bile acid deconjugation in the small bowel were treated with antibiotics for one week, after which the results had returned to normal in all. Four out of five patients with impaired d-xylose absorption before treatment also returned to normal after antibiotics. Three patients with diarrhea 3-7 times daily were considerably relieved after treatment both concerning general well-being and bowel movements. The results give strong evidence that bacterial overgrowth of the small intestine is important in causing gastrointestinal dysfunction in this disease. A histopathological study of the small intestinal mucosa on 27 patients showed that 84 percent were amyloid positive. The degree of amyloid infiltration did not correlate to the symptomatic state, steatorrhea or impaired d-xylose absorption. The surface ultrastructure was normal in all of 21 investigated cases. Radiographical and endoscopi cal studies were performed on 43 patients altogether. Evidence of gastric stasis was found in 7 out of 37 patients investigated by means of gastric x-ray and in 7 out of 28 patients at gastroscopy. No characteristic radiological appearance of the disease could be shown in the small intestine, the colon or the gall bladder. Nine patients who were operated on with the construction of an enterostomy were reported. The diversion of the fecal stream when the patients had diarrhea and were incontinent meant a considerable relief. / <p>S. 1-46: sammanfattning, s. 47-128: 6 uppsatser</p> / digitalisering@umu

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

Part I Inhibition of Gastric Acid Secretion Fat in the small bowel is a powerful inhibitor of gastric acid secretion. The gastric inhibitory agent(s) liberated from intestinal mucosa by the presence of fat has been named enterogastrone. Gastric inhibitory polypeptide (GIP), has been considered a candidate for enterogastrone. GIP is released into the circulation by infusion of fat into the proximal small bowel and inhibits gastric acid secretion under select experimental conditions. It has been proposed that the release of somatostatin, a potent inhibitor of acid secretion, may mediate the gastric inhibitory action of GIP. Recently, monoclonal antibodies raised to both GIP and somatostatin have been produced. The suitability of these antibodies for the study of the physiological roles proposed for their respective peptides is not known. This study examined the inhibitory action of GIP and somatostatin on gastric acid secretion in the rat and in man. GIP was found to be a weak inhibitor of meal-stimulated gastric acid secretion in man when given in supraphysiological doses. When administered at a dose which produces less than the normal maximal physiological plasma level, GIP had little effect on the acid secretory response to the meal and no effect on either plasma gastrin or plasma SLI concentrations. In the rat, infusion of GIP produced a 60% reduction of meal-stimulated acid secretion, independent of changes in serum gastrin release. Intraduodenal infusion of oleic acid in the rat reduced the gastric acid secretory response to a liver extract meal by 80% without affecting serum gastrin levels. A humoral gastric inhibitory agent, or "enterogastrone", was demonstrated in the portal blood of the rat following fat infusion. Intravenous infusion of portal serum, which had been collected during an intraduodenal infusion of fat, reduced meal-stimulated acid secretion in a second animal. A comparison of the inhibition of gastric acid secretion produced by intraduodenal infusion of either glucose or oleic acid with the release of IR-GIP in the portal serum was performed. The inhibitory effect of an intraduodenal fat infusion could not be explained by plasma IR-GIP. The release of GIP was not found to play a significant role in the mechanism for gastric inhibition by intestinal fat. Part II Monoclonal antibodies as Probes of Humoral Inhibitors of Gastric acid secretion The ability of recently produced monoclonal antibodies to block in vivo the inhibitory action of exogenous GIP and somatostatin on gastric acid secretion was examined. Anti-GIP monoclonal antibody demonstrated a high affinity for GIP when compared to the polyclonal rabbit antiserum R07 in the ELISA. When administered either as an intravenous bolus, or after incubation with GIP for 1 hour at 37°C, the antibody was unable to block the inhibitory effect of a GIP infusion on meal-stimulated gastric acid secretion in the rat. Monoclonal antibody 3.65H may not be suitable for the study of the role of endogenously released GIP. Two anti-somatostatin monoclonal antibody clones 58 and 510, when given as intravenous boluses, blocked the inhibitory action of exogenous somatostatin on meal-stimulated gastric acid secretion in the rat. The antibody clone S10 however, had no effect on the inhibitory action of exogenous GIP on gastric acid secretion. Although both monoclonal antibodies S8 and SIO effectively prevented the gastric inhibitory effect of infused somatostatin, the ability to block the physiological action of endogenously released gastric somatostatin remains to be determined. / Surgery, Department of / Medicine, Faculty of / Graduate

No description available.

O autor estudou prospectivamente a evolução clínica e a função secretora e hormonal 90 estômago em quinze pacientes portadores de rnegaesôfago chagásico avançado, antes e seis meses após o tratamento cirúrgico pela esofagectornia subtotal associada a esofagogastroplastia com anastomose esofa gogástrica cervical e piloroplastia. A evolução clínica pós-operatória, foi segui- da com avaliaçôes a cada dois meses, durante os seis meses es tudados neste tratabalho. Houve resolução da síndrome disfágicã, apos o tratamento cirúrgico, com exceção de um paciente em que ape- sar da melhora evidente, persistiu disfagia discreta. Consta tou-se ainda aumento significativo do peso corporeo, notada- mente nos pacientes que apresentavam maior dãficit ponderal. A diarrãia,que não esteve presente no período pré-operatório, foi constatada no pós-operatório, em nível si~ nificante, até os seis meses considerados neste estudo, porem com discreta intensidade, a partir do terceiro mês de evolução. Esta manifestação foi interpretada como conseqüência da VT e piloroplastia. No período pós-operatório, o estômago trans- posto ao mediastino, tomou forma alongada com pregas mucosas de disposição longitudinal, porém com moderada dilatação na porção distal em três casos. Houve redução significativa do TEG, no período pós-operatório. Os valores médios da acidimetria, em condição basal e apos estimulação com pentagastrina, no período pré-operatório, foram inferiores aos valores obtidos em indivíduos DOr mais, nas mesmas condições. Seis meses após a realização do tratamento cirúrgico, houve diminuição significativa dos valo- res médios da acidimetria após estimulação com pentagastrina, sem no entanto- se alterarem significativamente os referidos va lores, em condição basal. Os valores médios da acidimetria, apos estimulação com pentagastrina,apresentavam aumento significativo quan do comparados aos valores médios obtidos em condição tanto antes- como após o tratamento cirúrgico. Os valores médios dos niveis séricos do pepsnogênio, tanto em condição basal, como após estimulação com Betazole R aos 60, 90 e 120 minutos, diminuiram significativa- mente no período pós-operatórioíquando comparados às médias dos niveis pré-operatórios. Os valores médios dos niveis séricos do pepsnogênio, obtidos após estimulação com BetazoleR aos 60, 90 e 120 minutos, apresentaram aumento significativo quando compara dos aos valores obtidos em condição basal, tanto no pre como no pós-operatório período. No periodo pré-operatório, os valores médios dos niveis séricos da gastrina, em condição basal, apresenta- ram aumento significativo quando comparados aos valores obti dos em individuos normais, nas mesmas condições. o valor médio da gastrinemia, em condição basal, mostrou-se significativamente aumentado no periodo pós-operatório, quando comparado ao valor obtido no pré-operatório, nas mesmas condições / Clinical evolution and secretory and hormonal gastric functions were prospectively studied in fifteen - patients with advanced megaesophagus consequent to Chagas disease. Stu dies were carried out before and up to six months after surgi- cal treatment by subtotal esophagectomy associated with gastr9 plasty, cervical gastroesophageal anastomosis and pyloroplasty. Complete postoperative resolution of the dis phagic syndrome was observed in alI patients except one, who was evidently relieved but still complained of some disphagia. Significant postoperative body weight increase was also registered, specially in those patients who exhibited preoperative larger body weight deficit. Diarrhea was never present before the opera- tion. Postoperative diarrhea, however, occurred significantly up to the six months included in this study, but i t was of mild degree from the third month on. This symptom was atributed to vagatomy and pyloroplasty. In the radiological postoperative studies the stomach in mediastinal position assumed an alongated shape, with longitudinal mucosal folds, but with moderate distal enlargement in three cases. There was significant reduction in the time of gastric emptying after the operation. Preoperative mean vaIues of gastric acid secretion in basal condition and after stimuIation with pentaga trin were Iower than observed in normal controls in the same conditions. Six months after surgery there was significant reduction of the mean values after stimulation, with pentagastrin. However, no significant variation was observed in basal condition. Mean values after stimulation with pentagastrin w re significantly higher than in basal condition before as well as after the operation. Mean values of serum pepsinogen levels in basal condition, as well as after, stimuIation with Betazole, at 60, 90 and 120 minutes, were significantIy reduced in the post operative period when compared to the preoperative correspon- dents Ievels. Mean values after stimuIation with Betazole we re siginificantly higher than in basal condition, before as weIl as after the operation. Preoperative mean values of ser um gastrin levels in basal condition were significantly higher than in normal controls in the same conditions. The mean value of basaI serum gastrin increased significantly after the operation, in comparison:with preoperative vaIue in the same condition

<p>The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. </p><p>In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows:</p><p>Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pH_jm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. </p><p>Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. </p><p>Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pH_jm. </p><p>Removal of the loosely adherent mucus layer did not influence the maintenance of the pH_jm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pH_jm. </p><p>Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. </p><p>Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. </p><p>It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.</p>

The gastric mucosa is frequently exposed to endogenously secreted hydrochloric acid of high acidity. Gastric mucosal defense mechanisms are arranged at different levels of the gastric mucosa and must work in unison to maintain its integrity. In this thesis, several mechanisms underlying gastric mucosal resistance to strong acid were investigated in anesthetized rats and mice. The main findings were as follows: Only when acid secretion occurred did the pH gradient in the mucus gel withstand back-diffusion of luminal acid (100 mM or 155 mM HCl), and keep the juxtamucosal pH (pHjm) neutral. Thus, when no acid secretion occurred and the luminal pH was 0.8-1, the pH gradient was destroyed. Bicarbonate ions, produced concomitant with hydrogen ions in the parietal cells during acid secretion and blood-borne to the surface epithelium, were carried transepithelially through a DIDS-sensitive transport. Prostaglandin-dependent bicarbonate secretion seemed to be less important in maintaining a neutral pHjm. Removal of the loosely adherent mucus layer did not influence the maintenance of the pHjm. Hence, only the firmly adherent mucus gel layer, approximately 80µm thick, seemed to be important for the pHjm. Staining of the mucus gel with a pH-sensitive dye revealed that secreted acid penetrated the mucus gel from the crypt openings toward the gastric lumen only in restricted paths (channels). One crypt opening was attached to one channel, and the channel was irreversibly formed during acid secretion. Gastric mucosal blood flow increased on application of strong luminal acid (155 mM HCl). This acid-induced hyperemia involved the inducible but not the neural isoform of nitric oxide synthase. These results suggest a novel role for iNOS in gastric mucosal protection and indicate that iNOS is constitutively expressed in the gastric mucosa. It is concluded that a pH gradient in the gastric mucus gel can be maintained during ongoing acid secretion, since the acid penetrates the mucus only in restricted channels and bicarbonate is carried from the blood to the lumen via a DIDS-sensitive transporter.