The Experts below are selected from a list of 17880 Experts worldwide ranked by ideXlab platform
Andrzej S Tarnawski - One of the best experts on this subject based on the ideXlab platform.
-
angiogenesis in gastric mucosa an important component of gastric erosion and Ulcer Healing and its impairment in aging
Journal of Gastroenterology and Hepatology, 2014Co-Authors: Andrzej S Tarnawski, Amrita Ahluwalia, Michael K JonesAbstract:Angiogenesis (also referred to as neovascularization-formation of new blood vessels from existing vessels) is a fundamental process essential for Healing of tissue injury and Ulcers because regeneration of blood microvessels is a critical requirement for oxygen and nutrient delivery to the Healing site. This review article updates the current views on angiogenesis in gastric mucosa following injury and during Ulcer Healing, its sequential events, the underlying mechanisms, and the impairment of angiogenesis in aging gastric mucosa. We focus on the time sequence and ultrastructural features of angiogenesis, hypoxia as a trigger, role of vascular endothelial growth factor signaling (VEGF), serum response factor, Cox2 and prostaglandins, nitric oxide, and importin. Recent reports indicate that gastric mucosa of aging humans and experimental animals exhibits increased susceptibility to injury and delayed Healing. Gastric mucosa of aging rats has increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin, and other non-steroidal anti-inflammatory drugs because of structural and functional abnormalities including: reduced gastric mucosal blood flow, hypoxia, reduced expression of vascular endothelial growth factor and survivin, and increased expression of early growth response protein 1 (egr-1) and phosphatase and tensin homolog (PTEN). Until recently, postnatal neovascularization was assumed to occur solely through angiogenesis sprouting of endothelial cells and formation of new blood vessels from pre-existing blood vessels. New studies in the last decade have challenged this paradigm and indicate that in some tissues, including gastric mucosa, the homing of bone marrow-derived endothelial progenitor cells to the site of injury can also contribute to neovascularization by a process termed vasculogenesis.
-
gastric cytoprotection beyond prostaglandins cellular and molecular mechanisms of gastroprotective and Ulcer Healing actions of antacids
Current Pharmaceutical Design, 2012Co-Authors: Andrzej S Tarnawski, Amrita Ahluwalia, Michael K JonesAbstract:This article updates current views on gastric mucosal defense, injury, protection and Ulcer Healing with a focus on mucosal protective and Ulcer Healing actions of antacids. The gastric mucosa is continuously exposed to a variety of noxious factors, both endogenous such as: 0.1N hydrochloric acid, pepsin, bile acids, lysolecithin, H. pylori toxins and exogenous such as NSAIDs, ethanol and others. Gastric mucosal integrity is maintained by pre-epithelial, epithelial and post-epithelial defense mechanisms permitting the mucosa to withstand exposure to the above damaging factors. When mucosal defense is weakened or overwhelmed by injurious factors, injury develops in the form of erosions or Ulcers. In the late 1970s Andre Robert and coworkers discovered that microgram amounts of a prostaglandin E2 analog protects the gastric mucosa against a variety of Ulcerogenic and necrotizing agents - even such strong inducers of injury as 100p ethanol and boiling water. They proposed a new concept of cytoprotection. Subsequently, other compounds, such as sulfhydryls, sucralfate and epidermal growth factor were shown to exert protective action on gastric mucosa. Additionally, some antacids have been shown to exert a potent mucosal protective action against a variety of injurious factors and accelerate Healing of erosions and gastric Ulcers. These actions of antacids, especially hydrotalcite - the newest and the most extensively studied antacid - are due to activation of prostaglandin synthesis; binding to and inactivation of pepsin, bile acids and H. pylori toxins; induction of heat shock proteins; and, activation of genes encoding growth factors and their receptors.
-
cellular and molecular mechanisms of gastrointestinal Ulcer Healing
Digestive Diseases and Sciences, 2005Co-Authors: Andrzej S TarnawskiAbstract:This paper reviews cellular and molecular mechanisms of gastrointestinal Ulcer Healing. Ulcer Healing, a genetically programmed repair process, includes inflammation, cell proliferation, re-epithelialization, formation of granulation tissue, angiogenesis, interactions between various cells and the matrix and tissue remodeling, all resulting in scar formation. All these events are controlled by the cytokines and growth factors (EGF, PDGF, KGF, HGF, TGFbeta, VEGF, angiopoietins) and transcription factors activated by tissue injury in spatially and temporally coordinated manner. These growth factors trigger mitogenic, motogenic and survival pathways utilizing Ras, MAPK, PI-3K/Akt, PLC-gamma and Rho/Rac/actin signaling. Hypoxia activates pro-angiogenic genes (e.g., VEGF, angiopoietins) via HIF, while serum response factor (SRF) is critical for VEGF-induced angiogenesis, re-epithelialization and muscle restoration. EGF, its receptor, HGF and Cox2 are important for epithelial cell proliferation, migration re-epithelializaton and reconstruction of gastric glands. VEGF, angiopoietins, nitric oxide, endothelin and metalloproteinases are important for angiogenesis, vascular remodeling and mucosal regeneration within Ulcer scar. Circulating progenitor cells are also important for Ulcer Healing. Local gene therapy with VEGF + Ang1 and/or SRF cDNAs dramatically accelerates esophageal and gastric Ulcer Healing and improves quality of mucosal restoration within Ulcer scar. Future directions to accelerate and improve Healing include the use of stem cells and tissue engineering.
-
cyclooxygenase 2 implications on maintenance of gastric mucosal integrity and Ulcer Healing controversial issues and perspectives
Gut, 2001Co-Authors: F Halter, Andrzej S Tarnawski, A Schmassmann, B M PeskarAbstract:Cyclooxygenase (COX), the key enzyme for synthesis of prostaglandins, exists in two isoforms (COX-1 and COX-2). COX-1 is constitutively expressed in the gastrointestinal tract in large quantities and has been suggested to maintain mucosal integrity through continuous generation of prostaglandins. COX-2 is induced predominantly during inflammation. On this premise selective COX-2 inhibitors not affecting COX-1 in the gastrointestinal tract mucosa have been developed as gastrointestinal sparing anti-inflammatory drugs. They appear to be well tolerated by experimental animals and humans following acute and chronic (three or more months) administration. However, there is increasing evidence that COX-2 has a greater physiological role than merely mediating pain and inflammation. Thus gastric and intestinal lesions do not develop when COX-1 is inhibited but only when the activity of both COX-1 and COX-2 is suppressed. Selective COX-2 inhibitors delay the Healing of experimental gastric Ulcers to the same extent as non-COX-2 specific non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, when given chronically to experimental animals, they can activate experimental colitis and cause intestinal perforation. The direct involvement of COX-2 in Ulcer Healing has been supported by observations that expression of COX-2 mRNA and protein is upregulated at the Ulcer margin in a temporal and spatial relation to enhanced epithelial cell proliferation and increased expression of growth factors. Moreover, there is increasing evidence that upregulation of COX-2 mRNA and protein occurs during exposure of the gastric mucosa to noxious agents or to ischaemia-reperfusion. These observations support the concept that COX-2 represents (in addition to COX-1) a further line of defence for the gastrointestinal mucosa necessary for maintenance of mucosal integrity and Ulcer Healing.
-
regeneration of gastric mucosa during Ulcer Healing is triggered by growth factors and signal transduction pathways
Journal of Physiology-paris, 2001Co-Authors: Andrzej S Tarnawski, Imre Szabo, Syeda S Husain, Brian SoreghanAbstract:An Ulcer is a deep necrotic lesion penetrating through the entire thickness of the gastrointestinal mucosa and muscularis mucosae. Ulcer Healing is a complex and tightly regulated process of filling the mucosal defect with proliferating and migrating epithelial and connective tissue cells. This process includes the re-establishment of the continuous surface epithelial layer, glandular epithelial structures, microvessels and connective tissue within the scar. Epithelial cells in the mucosa of the Ulcer margin proliferate and migrate onto the granulation tissue to re-epithelialize the Ulcer. Growth factors, such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), trefoil peptides (TP), platelet derived growth factor (PDGF) and other cytokines produced locally by regenerating cells, control re-epithelialization and the reconstruction of glandular structures. These growth factors, most notably EGF, trigger epithelial cell proliferation via signal transduction pathways involving EGF-R- MAP (Erk1/Erk2) kinases. Granulation tissue, which develops at the Ulcer base, consists of fibroblasts, macrophages and proliferating endothelial cells, which form microvessels under the control of angiogenic growth factors. These growth factors [bFGF, vascular endothelial growth factor (VEGF) and angiopoietins] promote angiogenesis--capillary vessel formation--thereby allowing for the reconstruction of microvasculature in the mucosal scar, which is essential for delivery of oxygen and nutrients to the Healing site. The primary trigger to activate expression of angiogenic growth factors and their receptors appears to be hypoxia. During Ulcer Healing expression of growth factor genes is tightly regulated in a temporally and spatially ordered manner.
Kazuhide Higuchi - One of the best experts on this subject based on the ideXlab platform.
-
gastric Ulcer Healing after treatment of endoscopic submucosal dissection in japanese comparison of h2 receptor antagonist and proton pump inhibitor administration
Journal of Clinical Biochemistry and Nutrition, 2011Co-Authors: Nozomi Takeuchi, Eiji Umegaki, Toshihisa Takeuchi, Mitsuyuki Murano, Yukiko Yoda, Satoshi Tokioka, Kazuhide HiguchiAbstract:Endoscopic submucosal dissection has made it possible to resect large lesions during a single operation. The present study was undertaken to compare the time taken for recovery from artificial Ulcers after endoscopic submucosal dissection between an H2 Receptor Antagonist treatment group and a Proton Pump Inhibitor treatment group, focusing on analysis of the time course of reduction rate in Ulcer area. The powerful acid suppression by Proton Pump Inhibitor may not be needed to treat Japanese post-endoscopic submucosal dissection Ulcer which usually develops after early gastric carcinoma in the mucosa of low acid secretory capacity. The study involved 60 patients with 69 artificial Ulcers following endoscopic submucosal dissection for the treatment of tumors remaining in the gastric mucosa. Of all lesions, 36 were allocated to the H2 Receptor Antagonist group and 33 to the Proton Pump Inhibitor group. Patients in both groups underwent endoscopy at 4 and 8 weeks after the start of administration. There were no significant differences between two groups and Ulcer Healing rates were similar in the two groups. The efficacy of H2 Receptor Antagonists in curing this type of Ulcer can thus be expected to be comparable to that of Proton Pump Inhibitors.
-
sofalcone a gastroprotective drug promotes gastric Ulcer Healing following eradication therapy for helicobacter pylori a randomized controlled comparative trial with cimetidine an h2 receptor antagonist
Journal of Gastroenterology and Hepatology, 2010Co-Authors: Kazuhide Higuchi, Toshio Watanabe, Tetsuya Tanigawa, Kazunari Tominaga, Yasuhiro Fujiwara, Tetsuo ArakawaAbstract:Background and Aims: According to reports in Japanese patients, 1 week of Helicobacter pylori eradication therapy alone is not adequate for Healing of gastric Ulcers; 7–8 weeks of anti-Ulcer therapy are subsequently required. We compared a gastroprotective drug, sofalcone, and an H2-receptor antagonist, cimetidine, in terms of promoting Ulcer Healing after 7 weeks of administration following 1 week of eradication therapy. Methods: Eradication therapy was administered to 64 patients with H. pylori-positive active gastric Ulcer at least 10 mm in diameter, after which 32 patients each received 7 weeks of Ulcer treatment with sofalcone (300 mg/day) or cimetidine (800 mg/day). Results: The H. pylori eradication rate was 81.3% (intention-to-treat: ITT) and 81.3% (per protocol: PP) in the sofalcone group, and 62.5% (ITT) and 64.5% (PP) in the cimetidine group. The Ulcer Healing rate after 8 weeks was 71.9% (ITT) and 71.9% (PP) in the sofalcone group, and 71.9% (ITT) and 71.0% (PP) in the cimetidine group. The rate of a flat pattern of scarred mucosa was 43.5% (ITT) and 43.5% (PP) in the sofalcone group, and 47.8% (ITT) and 50.0% (PP) in the cimetidine group. No significant differences were seen between the two groups in terms of H. pylori eradication rate, Ulcer Healing rate and flat pattern rate. Conclusion: Sofalcone promoted gastric Ulcer Healing during 7 weeks of treatment following 1 week of eradication therapy, and the Healing rate was equivalent to that of cimetidine. Symptom disappearance rates were significantly better in the sofalcone group than in the cimetidine group. This may be a useful way of using a gastroprotective drug in the H. pylori era.
-
rebamipide a gastro protective and anti inflammatory drug promotes gastric Ulcer Healing following eradication therapy for helicobacter pylori in a japanese population a randomized double blind placebo controlled trial
Journal of Gastroenterology, 2007Co-Authors: Akira Terano, Kazuhide Higuchi, Tetsuo Arakawa, Toshiro Sugiyama, Hidekazu Suzuki, Takashi Joh, Toshikazu Yoshikawa, Ken Haruma, Kazunari Murakami, Kenzo KobayashiAbstract:Background One week of Helicobacter pylori eradication therapy is insufficient for Healing of gastric Ulcers. We examined the efficacy of rebamipide in gastric Ulcer Healing following 1 week of eradication therapy in a randomized, double-blind, placebo-controlled trial.
John L Wallace - One of the best experts on this subject based on the ideXlab platform.
-
divergent effects of new cyclooxygenase inhibitors on gastric Ulcer Healing shifting the angiogenic balance
Proceedings of the National Academy of Sciences of the United States of America, 2002Co-Authors: Piero Del Soldato, John L WallaceAbstract:Delayed gastric Ulcer Healing is a well recognized problem associated with the use of cyclooxygenase (COX) inhibitors. In contrast, NO-releasing COX inhibitors do not interfere with Ulcer Healing. These divergent effects may in part be due to differences in their effects on platelets, which are known to influence Ulcer Healing. Therefore, we compared the effects of a nonselective COX inhibitor (flurbiprofen), a nitric oxide-releasing COX inhibitor (HCT-1026), and a selective COX-2 inhibitor (celecoxib) on gastric Ulcer Healing, angiogenesis, and platelet/serum levels of vascular endothelial growth factor (VEGF) and endostatin. Gastric Ulcers were induced in rats by serosal application of acetic acid. Daily treatment with the test drugs was started 3 days later and continued for 1 week. Celecoxib and flurbiprofen impaired angiogenesis and delayed Ulcer Healing, as well as increasing serum endostatin levels relative to those of VEGF. HCT-1026 did not delay Ulcer Healing nor impair angiogenesis, and also did not change the ratio of serum endostatin to VEGF. Incubation of human umbilical vein endothelial cells with serum from celecoxib- or flurbiprofen-treated rats resulted in suppressed proliferation and increased apoptosis, effects that were reversed by an antiendostatin antibody. These results demonstrate a previously unrecognized mechanism through which nonsteroidal antiinflammatory drugs can delay Ulcer Healing, namely, through altering the balance of anti- and proangiogenic factors in the serum. The absence of a delaying effect of HCT-1026 on Ulcer Healing may be related to the maintenance of a more favorable balance in serum levels of pro- and antiangiogenic growth factors.
-
platelets modulate gastric Ulcer Healing role of endostatin and vascular endothelial growth factor release
Proceedings of the National Academy of Sciences of the United States of America, 2001Co-Authors: Susan N Elliott, Giuseppe Cirino, Andre G Buret, Louis J Ignarro, John L WallaceAbstract:Bleeding and delayed Healing of Ulcers are well recognized clinical problems associated with the use of aspirin and other nonsteroidal antiinflammatory drugs, which have been attributed to their antiaggregatory effects on platelets. We hypothesized that antiplatelet drugs might interfere with gastric Ulcer Healing by suppressing the release of growth factors, such as vascular endothelial growth factor (VEGF), from platelets. Gastric Ulcers were induced in rats by serosal application of acetic acid. Daily oral treatment with vehicle, aspirin, or ticlopidine (an ADP receptor antagonist) was started 3 days later and continued for 1 week. Ulcer induction resulted in a significant increase in serum levels of VEGF and a significant decrease in serum levels of endostatin (an antiangiogenic factor). Although both aspirin and ticlopidine markedly suppressed platelet aggregation, only ticlopidine impaired gastric Ulcer Healing and angiogenesis as well as reversing the Ulcer-associated changes in serum levels of VEGF and endostatin. The effects of ticlopidine on Ulcer Healing and angiogenesis were mimicked by immunodepletion of circulating platelets, and ticlopidine did not influence Ulcer Healing when given to thrombocytopenic rats. Incubation of human umbilical vein endothelial cells with serum from ticlopidine-treated rats significantly reduced proliferation and increased apoptosis, effects reversed by an antibody directed against endostatin. Ticlopidine treatment resulted in increased platelet endostatin content and release. These results demonstrate a previously unrecognized contribution of platelets to the regulation of gastric Ulcer Healing. Such effects likely are mediated through the release from platelets of endostatin and possibly VEGF. As shown with ticlopidine, drugs that influence gastric Ulcer Healing may do so in part through altering the ability of platelets to release growth factors.
-
a nitric oxide releasing nonsteroidal anti inflammatory drug accelerates gastric Ulcer Healing in rats
Gastroenterology, 1995Co-Authors: Susan N Elliott, Giuseppe Cirino, Webb Mcknight, John L WallaceAbstract:Abstract Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) have well-characterized inhibitory effects on gastric Ulcer Healing. A new class of gastrointestinal-sparing, nitric oxide-releasing NSAID derivatives has been recently described. This study was performed to determine if one of these compounds (nitrofenac) would influence Healing of a preexisting Ulcer. Methods: Seven days after induction of gastric Ulcer with serosal acetic acid, daily oral treatment with antiinflammatory doses of diclofenac, nitrofenac, or vehicle was started. After 7 days of treatment, the Ulcer area was measured. The effects of misoprostol and two drugs that show in vitro selectivity for inhibiting cyclooxygenase 2 (nabumetone and L745,337) were also assessed. Results: Diclofenac, nabumetone, and L745,337 had no effect on Ulcer Healing when compared with vehicle. Only diclofenac significantly decreased hematocrit and weight gain. On the other hand, nitrofenac significantly accelerated Healing. Glyceryl trinitrate also significantly and dose dependently accelerated Healing. Nitrofenac suppressed cyclooxygenase 1 activity to a similar extent as diclofenac. Conclusions: These results show that an NO-releasing NSAID derivative and an NO donor could accelerate Ulcer Healing, whereas a standard NSAID, misoprostol, and two inhibitors of cyclooxygenase 2 had no effect. In addition to sparing the gastrointestinal tract, NO-releasing NSAIDs, despite suppressing cyclooxygenase activity, are capable of accelerating tissue repair.
Michael K Jones - One of the best experts on this subject based on the ideXlab platform.
-
angiogenesis in gastric mucosa an important component of gastric erosion and Ulcer Healing and its impairment in aging
Journal of Gastroenterology and Hepatology, 2014Co-Authors: Andrzej S Tarnawski, Amrita Ahluwalia, Michael K JonesAbstract:Angiogenesis (also referred to as neovascularization-formation of new blood vessels from existing vessels) is a fundamental process essential for Healing of tissue injury and Ulcers because regeneration of blood microvessels is a critical requirement for oxygen and nutrient delivery to the Healing site. This review article updates the current views on angiogenesis in gastric mucosa following injury and during Ulcer Healing, its sequential events, the underlying mechanisms, and the impairment of angiogenesis in aging gastric mucosa. We focus on the time sequence and ultrastructural features of angiogenesis, hypoxia as a trigger, role of vascular endothelial growth factor signaling (VEGF), serum response factor, Cox2 and prostaglandins, nitric oxide, and importin. Recent reports indicate that gastric mucosa of aging humans and experimental animals exhibits increased susceptibility to injury and delayed Healing. Gastric mucosa of aging rats has increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin, and other non-steroidal anti-inflammatory drugs because of structural and functional abnormalities including: reduced gastric mucosal blood flow, hypoxia, reduced expression of vascular endothelial growth factor and survivin, and increased expression of early growth response protein 1 (egr-1) and phosphatase and tensin homolog (PTEN). Until recently, postnatal neovascularization was assumed to occur solely through angiogenesis sprouting of endothelial cells and formation of new blood vessels from pre-existing blood vessels. New studies in the last decade have challenged this paradigm and indicate that in some tissues, including gastric mucosa, the homing of bone marrow-derived endothelial progenitor cells to the site of injury can also contribute to neovascularization by a process termed vasculogenesis.
-
gastric cytoprotection beyond prostaglandins cellular and molecular mechanisms of gastroprotective and Ulcer Healing actions of antacids
Current Pharmaceutical Design, 2012Co-Authors: Andrzej S Tarnawski, Amrita Ahluwalia, Michael K JonesAbstract:This article updates current views on gastric mucosal defense, injury, protection and Ulcer Healing with a focus on mucosal protective and Ulcer Healing actions of antacids. The gastric mucosa is continuously exposed to a variety of noxious factors, both endogenous such as: 0.1N hydrochloric acid, pepsin, bile acids, lysolecithin, H. pylori toxins and exogenous such as NSAIDs, ethanol and others. Gastric mucosal integrity is maintained by pre-epithelial, epithelial and post-epithelial defense mechanisms permitting the mucosa to withstand exposure to the above damaging factors. When mucosal defense is weakened or overwhelmed by injurious factors, injury develops in the form of erosions or Ulcers. In the late 1970s Andre Robert and coworkers discovered that microgram amounts of a prostaglandin E2 analog protects the gastric mucosa against a variety of Ulcerogenic and necrotizing agents - even such strong inducers of injury as 100p ethanol and boiling water. They proposed a new concept of cytoprotection. Subsequently, other compounds, such as sulfhydryls, sucralfate and epidermal growth factor were shown to exert protective action on gastric mucosa. Additionally, some antacids have been shown to exert a potent mucosal protective action against a variety of injurious factors and accelerate Healing of erosions and gastric Ulcers. These actions of antacids, especially hydrotalcite - the newest and the most extensively studied antacid - are due to activation of prostaglandin synthesis; binding to and inactivation of pepsin, bile acids and H. pylori toxins; induction of heat shock proteins; and, activation of genes encoding growth factors and their receptors.
-
inhibition of angiogenesis by nonsteroidal anti inflammatory drugs insight into mechanisms and implications for cancer growth and Ulcer Healing
Nature Medicine, 1999Co-Authors: Michael K Jones, Andrzej S Tarnawski, B M Peskar, H Wang, E Levin, R M Itani, I J SarfehAbstract:Angiogenesis, the formation of new capillary blood vessels, is essential not only for the growth and metastasis of solid tumors, but also for wound and Ulcer Healing, because without the restoration of blood flow, oxygen and nutrients cannot be delivered to the Healing site1,2. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin and ibuprofen are the most widely used drugs for pain, arthritis, cardiovascular diseases and, more recently, the prevention of colon cancer and Alzheimer disease3,4,5,6,7. However, NSAIDs produce gastroduodenal Ulcers in about 25% of users (often with bleeding and/or perforations) and delay Ulcer Healing8,9, presumably by blocking prostaglandin synthesis from cyclooxygenase (COX)-1 and COX-2 (ref. 10). The hypothesis that the gastrointestinal side effects of NSAIDs result from inhibition of COX-1, but not COX-2 (ref. 11), prompted the development of NSAIDs that selectively inhibit only COX-2 (such as celecoxib and rofecoxib). Our study demonstrates that both selective and nonselective NSAIDs inhibit angiogenesis through direct effects on endothelial cells. We also show that this action involves inhibition of mitogen-activated protein (MAP) kinase (ERK2) activity, interference with ERK nuclear translocation, is independent of protein kinase C and has prostaglandin-dependent and prostaglandin-independent components. Finally, we show that both COX-1 and COX-2 are important for the regulation of angiogenesis. These findings challenge the premise that selective COX-2 inhibitors will not affect the gastrointestinal tract and Ulcer/wound Healing.
Tetsuo Arakawa - One of the best experts on this subject based on the ideXlab platform.
-
quality of Ulcer Healing in gastrointestinal tract its pathophysiology and clinical relevance
World Journal of Gastroenterology, 2012Co-Authors: Tetsuo Arakawa, Toshio Watanabe, Tetsuya Tanigawa, Kazunari Tominaga, Yasuhiro Fujiwara, Kenichi MorimotoAbstract:In this paper, we review the concept of quality of Ulcer Healing (QOUH) in the gastrointestinal tract and its role in the Ulcer recurrence. In the past, peptic Ulcer disease (PUD) has been a chronic disease with a cycle of repeated Healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori (H. pylori), which is also the cause of Ulcer recurrence. However, H. pylori-negative Ulcers are present in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within Ulcer scars are incompletely regenerated. Within the scars of healed Ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for Ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in Ulcer recurrence. Our studies in a rat model of Ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macrophages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in Ulcer recurrence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a deficiency and/or an imbalance of endogenous growth factors. Topically active mucosal protective and antiUlcer drugs promote high QOUH and reduce inflammatory cell infiltration in the Ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn’s disease and Ulcerative colitis.
-
sofalcone a gastroprotective drug promotes gastric Ulcer Healing following eradication therapy for helicobacter pylori a randomized controlled comparative trial with cimetidine an h2 receptor antagonist
Journal of Gastroenterology and Hepatology, 2010Co-Authors: Kazuhide Higuchi, Toshio Watanabe, Tetsuya Tanigawa, Kazunari Tominaga, Yasuhiro Fujiwara, Tetsuo ArakawaAbstract:Background and Aims: According to reports in Japanese patients, 1 week of Helicobacter pylori eradication therapy alone is not adequate for Healing of gastric Ulcers; 7–8 weeks of anti-Ulcer therapy are subsequently required. We compared a gastroprotective drug, sofalcone, and an H2-receptor antagonist, cimetidine, in terms of promoting Ulcer Healing after 7 weeks of administration following 1 week of eradication therapy. Methods: Eradication therapy was administered to 64 patients with H. pylori-positive active gastric Ulcer at least 10 mm in diameter, after which 32 patients each received 7 weeks of Ulcer treatment with sofalcone (300 mg/day) or cimetidine (800 mg/day). Results: The H. pylori eradication rate was 81.3% (intention-to-treat: ITT) and 81.3% (per protocol: PP) in the sofalcone group, and 62.5% (ITT) and 64.5% (PP) in the cimetidine group. The Ulcer Healing rate after 8 weeks was 71.9% (ITT) and 71.9% (PP) in the sofalcone group, and 71.9% (ITT) and 71.0% (PP) in the cimetidine group. The rate of a flat pattern of scarred mucosa was 43.5% (ITT) and 43.5% (PP) in the sofalcone group, and 47.8% (ITT) and 50.0% (PP) in the cimetidine group. No significant differences were seen between the two groups in terms of H. pylori eradication rate, Ulcer Healing rate and flat pattern rate. Conclusion: Sofalcone promoted gastric Ulcer Healing during 7 weeks of treatment following 1 week of eradication therapy, and the Healing rate was equivalent to that of cimetidine. Symptom disappearance rates were significantly better in the sofalcone group than in the cimetidine group. This may be a useful way of using a gastroprotective drug in the H. pylori era.
-
rebamipide a gastro protective and anti inflammatory drug promotes gastric Ulcer Healing following eradication therapy for helicobacter pylori in a japanese population a randomized double blind placebo controlled trial
Journal of Gastroenterology, 2007Co-Authors: Akira Terano, Kazuhide Higuchi, Tetsuo Arakawa, Toshiro Sugiyama, Hidekazu Suzuki, Takashi Joh, Toshikazu Yoshikawa, Ken Haruma, Kazunari Murakami, Kenzo KobayashiAbstract:Background One week of Helicobacter pylori eradication therapy is insufficient for Healing of gastric Ulcers. We examined the efficacy of rebamipide in gastric Ulcer Healing following 1 week of eradication therapy in a randomized, double-blind, placebo-controlled trial.
