PEPTIC ULCER DISEASE Edited by Jianyuan Chai Peptic Ulcer Disease Edited by Jianyuan Chai Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. 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ISBN 978-953-307-976-9 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Pathogenesis of Peptic Ulcer 1 Chapter 1 Gastric Ulcer Etiology 3 Maria Izabel Gomes Silva and Francisca Cléa Florenço de Sousa Chapter 2 Effects of Helicobacter pylori and Non-Steroidal Anti-Inflammatory Drugs on Peptic Ulcer 29 Wang G.Z. and Wang J.F. Chapter 3 Helicobacter Pylori Infection in Peptic Ulcer Disease 39 Tat-Kin Tsang and Manish Prasad Shrestha Chapter 4 NSAIDs and Peptic Ulcer Disease 75 Iván Ferraz-Amaro and Federico Díaz-González Chapter 5 The Etiological Factors of Duodenal and Gastric Ulcers 93 Ahmet Uyanıkoğlu, Ahmet Danalıoğlu, Filiz Akyüz, Binnur Pınarbaşı, Mine Güllüoğlu, Yersu Kapran, Kadir Demir, Sadakat Özdil, Fatih Beşışık, Güngör Boztaş, Zeynel Mungan and Sabahattin Kaymakoğlu Chapter 6 Helicobacter pylori – Not Only a Gastric Pathogene? 99 Petr Lukes, Jaromir Astl, Emil Pavlik, Bela Potuznikova, Jan Plzak, Martin Chovanec and Jan Betka Part 2 Molecular Mechanisms of Peptic Ulcer Development and Healing 111 Chapter 7 Pathophysiology of Gastric Ulcer Development and Healing: Molecular Mechanisms and Novel Therapeutic Options 113 Matteo Fornai, Luca Antonioli, Rocchina Colucci, Marco Tuccori and Corrado Blandizzi Chapter 8 Gastric Ulcer Healing – Role of Serum Response Factor 143 Jianyuan Chai VI Contents Chapter 9 Helicobacter pylori and Peptic Ulcer – Role of Reactive Oxygen Species and Apoptosis 165 Trinidad Parra-Cid, Miryam Calvino-Fernández and Javier P. Gisbert Chapter 10 Role of New Appetite Hormones Ghrelin, Orexin-A and Obestatin in the Mechanism of Healing of Chronic Gastric Ulcers 187 Thomas Brzozowski, Aleksandra Szlachcic, Robert Pajdo, Zbigniew Sliwowski, Danuta Drozdowicz, Jolanta Majka, Wladyslaw Bielanski, Peter. C. Konturek, Stanislaw J. Konturek and Wieslaw W. Pawlik Chapter 11 Activation of the Hypothalamic-Pituitary-Adrenocortical Axis as a Gastroprotective Component of Stress Response 209 Ludmila Filaretova Chapter 12 Helicobacter pylori Suppresses Serum Immunoglobulin Levels in Smokers with Peptic Ulcer: Probable Interaction Between Smoking and H. pylori Infection in the Induction of Th1 Predominant Immune Response and Peptic Ulceration 225 Yoshihiro Matsukawa and Kimitoshi Kato Chapter 13 Helicobacter pylori and Host Response 239 Mario M. D’Elios and Marina de Bernard Part 3 Clinical Management of Peptic Ulcer Patients 253 Chapter 14 Helicobacter pylori Infection in Elderly Patients 255 Nathalie Salles Chapter 15 Perforated Duodenal Ulcer in High Risk Patients 271 Aly Saber Chapter 16 Management of Acute Gastric Ulcer Bleeding 285 Christo van Rensburg and Monique Marais Chapter 17 Case Study in Optimal Dosing in Duodenal Ulcer 303 Karl E. Peace Part 4 Treatment and Prevention Strategies of Peptic Ulcer 321 Chapter 18 Conventional and Novel Pharmaceutical Dosage Forms on Prevention of Gastric Ulcers 323 Işık Özgüney Chapter 19 Spices as Alternative Agents for Gastric Ulcer Prevention and Treatment 351 Ibrahim Abdulkarim Al Mofleh Contents VII Chapter 20 Ethnopharmacology as Current Strategy in the Search of Novel Anti-Ulcerogenic Drugs: Case of a Brazilian Medicinal Plant (Maytenus ilicifolia Mart. ex. Reissek) 375 Rômulo Dias Novaes and João Paulo Viana Leite Chapter 21 Anti-Ulcerative Potential of Some Fruits and the Extracts 401 Yasunori Hamauzu Chapter 22 Herbal Treatment of Peptic Ulcer: Guilty or Innocent 419 Khaled A. Abdel-Sater Chapter 23 In Vitro and In Vivo Anti-Helicobacter pylori Activity of Natural Products 427 Maria do Carmo Souza Chapter 24 Prevention of Gastric Ulcers 437 Mohamed Morsy and Azza El-Sheikh Part 5 Peptic Ulcer Management in Animals 461 Chapter 25 Association Between Nonsteroidal Anti-Inflammatory Drugs and Gastric Ulceration in Horses and Ponies 463 Maria Verônica de Souza and José de Oliveira Pinto Preface Our knowledge about peptic ulcer can be traced back at least to the medieval era (~ 11 th century) when the great Iranian physician, Avicenna, described the association between stomachache and mealtimes in his book, The Cannon of Medicine, and suggested that the pain could be all due to the presence of a gastric ulcer. Later it was the invention of microscope (~ 16 th century) that gave the early investigators the edge to draw a connection between gastric ulcers and the bacteria living in the stomach. Nowadays, when you search the literature for the cause of peptic ulcers, almost every article tells you that it is the bacterium Helicobacter pylori that is responsible for the vast majority of ulcers. The main argument for this notion is the high frequency of H. pylori found in ulcer patients. However, we should not ignore the fact that although more than half of the world population is infected by H. pylori, only less than 10% of them develop peptic ulcer disease. We should also remember that peptic ulcers sometimes occur in the absence of the bacteria. Use of NSAIDs is an example. Some estimate that more than 16,000 people die of NSAIDs-induced ulcers each year. The common effect of H. pylori and NSAIDs on the stomach is that both can disarm the mucosal protection, exposing the epithelium directly to the gastric fluid that is highly acidic (~ pH 1-2). As early as in 1940s, scientists already learned through animal experiments that exposure of any living tissues, including the stomach wall, to this fluid is detrimental. The reason that our stomach can normally tolerate such hostile environment is the mucus overlaid on the surface of the gastric epithelium, which shields gastric tissue from gastric acid. In addition, both the stomach and the duodenum contain cells that can produce bicarbonate to neutralize the acid intimate to the mucosal surface. When H. pylori dwells in the stomach or duodenum, it produces toxins that trigger the inflammatory response from the host, which can lead to mucosal atrophy, making the epithelial cells prone to the acidic damage. Similarly, NSAIDs inhibit production of mucus and bicarbonate, which can result in epithelial denudation. In both cases, the ultimate cause of peptic ulcers is the acid. Zollinger- Ellison Syndrome is an extreme case in which peptic ulcers are simply induced by over secretion of gastric acid. This book is a snapshot of the current view of peptic ulcer disease. Although the book is divided into five sections, it is only for the convenience of the readers and the content of each section is tightly connected to the rest of the book. Peptic Ulcer Disease opens with a discussion on the causes of the disease. The first chapter by Silva & de X Preface Souza (Federal University of Ceará, Brazil) introduces the offense-defense mechanisms that protect mucosal integrity and discusses each factor that is known to jeopardize this balance. Out of all the offensive factors, H. pylori infection and NSAID use are two most common ones. The chapter by Wang & Wang (Zhejiang University, China) analyze these two major etiologies, debate on their relationship whether synergistic, antagonistic or independent, and point out several elements that may influence the outcome of this interaction, such as age of the patient, type of NSAIDs, strain of the bacteria, etc. The following two chapters examine each one of these two causes in more detail respectively. Tsang (Northwestern University, USA) focuses his attention on the No. 1 factor – H. pylori, thoroughly describes what is known about this bacterium, including its microbiology, pathophysiology, epidemiology and eventually the methods of clinical testing. The large body of references provides further readings for those who are eager to know more about H. pylori. Whereas, Ferraz-Amaro & Diaz- Gonzalez (Hospital Universitario de Canarias, Spain) give a systematic review on the second cause of peptic ulcer disease – NSAIDs. They unfold a complete picture of NSAIDs including their history, pharmacological features and their effects on gastrointestinal system. In Chapter 5, a group of clinical researchers (Istanbul University, Turkey) present an actual set of data that shows a consistent association of peptic ulcers with H. pylori infection and NSAID use. The last chapter of this section by Lukes et al (Charles University in Prague, Czech) reports an unusual location of H. pylori infection, the oral cavity, which is outside its common gastro-duodenal territory and a little beyond our central topic of this book – peptic ulcer disease, however, the paper raises an interesting question: is H. pylori really interested only in acidic environments? After all, the oral cavity is just the upper end of the gastro-duodenal tract. The second part of the book collects seven chapters devoting to the molecular mechanisms of peptic ulcer development and healing. Chapter 7 by Fornai et al (University of Pisa, Italy) explains how mucosal defense system at the molecular level protects gastric tissue from gastric acid damage in normal people, then discusses how NSAIDs break down this barrier and induce ulceration, and finally describes how ulcer healing proceeds. The next chapter (Chapter 8) by Chai (Department of Veterans Affairs, USA) gives a systematic review on the molecular and cellular mechanisms of ulcer healing and introduces a powerful regulator – SRF, a transcription factor that has influence on hundreds and possibly thousands of genes, many of which are important to ulcer healing. Chapter 9 by Gisbert group (Hospital Universitario de la Princesa, Spain) takes a look at peptic ulcer from a very different point of view – oxidative stress and apoptosis, and presents strong evidence that ulceration, regardless of the cause, is mediated through excessive production of reactive oxygen species, and therefore, therapeutic strategies to eliminate the oxidative stress should benefit the ulcer patients. The following two chapters (Chapter 10 & 11) provide strong data that elucidate hormonal involvement in ulcer healing. Brzozowski group (Jagiellonian University Medical College, Poland) studied ghrelin, orexin-A and obestatin and found that these newly discovered gastrointestinal hormones all have positive effects on gastric ulcer [...]... potentially serious acid-related clinical conditions occur, including gastroesophageal reflux disease, Barrett's esophagus, where the 14 Peptic Ulcer Disease usual squamous mucosal lining becomes replaced by columnar epithelial cells of putative specific aspect, peptic ulcer disease, and stress-related erosion /ulcer disease (Schubert & Peura, 2008; Schubert, 2008) Acid is thought to gain access to the lumen... therapy delay the healing of active peptic ulcers, the best way to prevent mucosal injury is to avoid the use of NSAIDs or replace it with an agent less toxic to the gastroduodenal mucosa (Sostres et al., 2010) 3.3 Gastric acid secretion For decades, surgeons were taught and believed that peptic ulcer disease was caused by acid, since the cure rate of peptic ulcer disease by acid-reduction operations... (Georgia Southern University, USA), which shows negative associations of duodenal ulcer healing vs smoking status, as well as duodenal ulcer healing vs ulcer size Peptic ulcer treatment usually involves a combination of antibiotics, acid suppressors, and mucosa protectors The next section includes eight chapters dealing with peptic ulcer treatment and prevention strategies The first chapter (Chapter 18), prepared... better understand and treat peptic ulcer disease, the major clinical challenge at that time (Dotevall & Walan, 1971) In this sense, when pharmacologic means were developed such as histamine-2 blockers drugs (like cimetidine), which effectively eliminated acid and thus many patients found that their ulcer disease was healed, these observations validated the dictum “no acid, no ulcer (Gustafson and Welling,... of peptic ulcer patients In the first article (Chapter 14), Salles (Hospital Xavier Arnozan, France) discusses peptic ulcer in elderly patients, which is the population suffered mostly from the disease because both H pylori infection and NSAID use increase with age This chapter also puts together a list of common methods for diagnosis and treatment of H pylori infection Although the prevalence of peptic. .. of GI Injury and Cancer VA Long Beach Healthcare System Long Beach, California USA Part 1 Pathogenesis of Peptic Ulcer 1 Gastric Ulcer Etiology Maria Izabel Gomes Silva and Francisca Cléa Florenço de Sousa Federal University of Ceará Brazil 1 Introduction A gastric ulcer, also called stomach ulcer, is a break in the normal gastric mucosa integrity that extends through the muscularis mucosa into the... increased acid load ulcerations the duodenum (El-Omar, 2006; Schubert & Peura, 2008) Thus, dosed before mealtime, proton pump inhibitors drugs are the most effective acid inhibitors currently available and are the most widely prescribed class of gastrointestinal Gastric Ulcer Etiology 15 medications Not only can peptic ulcers be healed more rapidly with these agents, but refractory ulcers have all but... mechanisms are impaired Thus, much importance is attached to interactions and relationships among various ulcer- related factors, as well as to the individuality of the patients, including infections by H pylori, alcohol and NSAIDs consume, and even smoking use, or stress-related disease 18 Peptic Ulcer Disease Significant knowledge over the past three decades regarding gastric mucosal attack and defense... Gastroduodenal ulcers: causes, diagnosis, prevention and treatment Comprehensive Therapy, Vol.25, No.1 (January), pp 30-38, ISSN 0098-8243 Brzozowski, T.; Konturek, S.J.; Drozdowicz, D.; Dembinski, A & Stachura, J (1995) Healing of chronic gastric ulcerations by L-arginine Role of nitric oxide, prostaglandins, gastrin and polyamines Digestion 56, No.6, pp 463–471, ISSN 0012-2823 20 Peptic Ulcer Disease Brzozowski,T.;... consequences, as referred above, the presence of this pathogen is associated with an increased risk of several diseases, including peptic ulcers, noncardia gastric adenocarcinoma, and gastric mucosa associated lymphoid tissue (MALT) lymphoma (Cover & Blaser, 2009) The risks of developing gastric diseases are determined in part by the presence or absence of specific genotypes of the H pylori strains with . on Peptic Ulcer 29 Wang G.Z. and Wang J.F. Chapter 3 Helicobacter Pylori Infection in Peptic Ulcer Disease 39 Tat-Kin Tsang and Manish Prasad Shrestha Chapter 4 NSAIDs and Peptic Ulcer Disease. PEPTIC ULCER DISEASE Edited by Jianyuan Chai Peptic Ulcer Disease Edited by Jianyuan Chai Published by InTech. USA), which shows negative associations of duodenal ulcer healing vs. smoking status, as well as duodenal ulcer healing vs. ulcer size. Peptic ulcer treatment usually involves a combination of