1. Gastric Mucosal Defense and Cytoprotection: Bench to Bedside
Loren Laine, Koji Takeuchi, Andrzej Tarnawski 
Gastroenterology 
Volume 135, Issue 1, Pages (July 2008)
DOI: /j.gastro
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2. Figure 1
Diagrammatic representation of gastric mucosal defense, modified and updated from Tarnawski.9
Gastroenterology  , 41-60DOI: ( /j.gastro )
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3. Figure 2
Structural elements of gastric mucosal defense. (A) Histology of upper part of human gastric mucosa visualizing surface epithelial cells (SEC), foveoli (F), and upper gland area. (H&E staining; original magnification, ×50). Blood microvessels with erythrocytes in the lumen are present in the lamina propria (arrows). (B) Scanning electromicrograph of human gastric mucosal luminal surface. The unstirred mucus gel layer is not seen because of dissolution during fixation. Individual surface epithelial cells (SEC) are clearly visible as are lumina of the gastric pits (arrows). Reproduced with permission from Tarnawski A, Krause WJ, Ivey KJ. The effect of glucagon on aspirin-induced gastric mucosal damage in man. Gastroenterology 1978;74:240–245. (C) Immunostaining of human gastric mucosa with survivin (antiapoptosis protein) antibody. Survivin is strongly expressed (brown-red staining) in the progenitor cells located in the foverolar/neck area (arrowheads). Reproduced with permission from Tarnawski et al.159 (D) Vascular cast study of capillary blood vessels in the gastric mucosa. The remaining components of the mucosa were dissolved in concentrated NaOH Reproduced with permission from Ichikawa et al.165 (E) Transmission electronmicrograph of normal human gastric mucosa. Surface epithelial cells (SEC) contain prominent, dark mucus granules. Below the surface epithelial cells, a capillary blood vessel (CAP) with erythrocytes (E) in the lumen is present in the lamina propia. N, nucleus of endothelial cell lining capillary vessel (original magnification, ×2000). Reproduced with permission from Tarnawski et al.172 (F) Transmission electronmicrograph of a portion of human gastric capillary blood vessel. The structure of the capillary wall and endothelial cell cytoplasm is normal with a characteristic fenestration (arrows) and presence of endothelial vesicles. BM, basement membrane; E, erythrocytes in the capillary lumen; J, junction between 2 neighboring endothelial cells; CF, collagen fibers. Original magnification, ×17,400. Reproduced with permission from Tarnawski et al.172
Gastroenterology  , 41-60DOI: ( /j.gastro )
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4. Figure 3
Sensory innervation of gastric mucosa. Photomicrographs of rat gastric specimens immunostained with calcitonin gene-related peptide (CGRP) antibody demonstrate the distribution of CGRP immunoreactivity reflecting sensory nerves. CGRP-immunoreactive fibers are present in the submucosa, often close to the blood vessels (A; arrowheads). The nerve fibers form a dense plexus at the mucosal base (A; arrows). From this plexus, sensory nerves enter the lamina propria and together with microvessels penetrate toward the mucosal surface (B; arrowheads), ending just beneath the basement membrane of the surface epithelial cells. Through the acid sensing ion channels, these nerve endings sense luminal contents such as acid and other irritants. Reproduced with permission from Tarnawski et al.48
Gastroenterology  , 41-60DOI: ( /j.gastro )
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5. Figure 4
Current hypotheses for roles of COX-1 and COX-2 in the pathogenic mechanism of NSAID-induced gastric damage. The motility hypothesis suggests that gastric motility plays an important role in NSAID damage. NSAIDs induce vagal-dependent gastric hypermotility via inhibition in COX-1-mediated prostaglandin (PG) production and CNS actions. Subsequent microvascular disturbances lead sequentially to neutrophil-endothelial interaction and oxyradical production. Inhibition of COX-1 leads to up-regulation of COX-2 expression. PG production mediated by COX-2, which may suppress the neutrophil-endothelial interaction, is also decreased by COX-2 selective or nonselective NSAIDs. The neutrophil-endothelial interaction plays a major role in the neutrophil hypothesis, which suggests that NSAIDs activate the neutrophil through alteration of arachidonic acid metabolites (eg, PGs), enhancing neutrophil-endothelial cell adhesion.
Gastroenterology  , 41-60DOI: ( /j.gastro )
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6. Figure 5
Results of a double-blind randomized trial of ranitidine intravenously vs. sucralfate via nasogastric tube in 1200 intensive care unit patients requiring mechanical ventilation ≥48 hours.162
Gastroenterology  , 41-60DOI: ( /j.gastro )
Copyright © 2008 AGA Institute Terms and Conditions