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Objective: In functional dyspepsia patients, duodenal mucosal eosinophilia has been associated with early satiety but is not present in all patients suggesting varied pathways to symptom generation. The objective of the current study was to explore metabolic differences comparing those with duodenal mucosal eosinophilia to those without eosinophilia., Methods: This study was conducted utilizing an existing biorepository. Patients had plasma samples obtained at the time of endoscopy. All had undergone endoscopy for dyspepsia and reported early satiety. Two groups were identified including those with peak duodenal mucosal eosinophil densities above 30/high power field (N = 28) and those below 30 (N = 16). The fasting plasma samples were analyzed by liquid chromatography/high-resolution mass spectrometry. Significant differences between groups were determined., Results: The eosinophilia group demonstrated significant elevations in several gamma-glutamyl amino acids. The eosinophilia group had elevations of metabolites associated with oxidative stress including glutathione metabolites (cysteinlyglycine and cys-gly oxidized), and metabolites related to nitric oxide synthesis (arginine, citrulline, ornithine, and dimethylarginine). Eosinophilia was also associated with alterations in lipid metabolism including several long-chain acylcarnitine conjugated fatty acids. Carnitine levels were lower in the eosinophilia group. Lastly, vanillymandelate, a derivative of norepinephrine and epinephrine was elevated in the eosinophilia group., Conclusions: In patients with dyspepsia and early satiety, duodenal mucosal eosinophilia is associated with metabolites levels which are consistent with increased oxidative stress and alterations in lipid metabolism. Eosinophilia was also associated with lower carnitine levels. These alterations may contribute to pathophysiology and represent therapeutic targets., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background & Aims: Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs)., Methods: We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells and permeability were quantified. Luminal pH and bile salts were determined in duodenal aspirates. Procedures were also performed in PPI-refractory patients with FD ("FD-stoppers") before and 8 weeks after PPI withdrawal. Between- and within-group changes from baseline and associations with duodenal or systemic factors were analyzed using linear mixed models., Results: The study was completed by 30 HV, 27 FD-starters, and 18 FD-stoppers. Symptoms and duodenal eosinophils, mast cells (all, P < .0001), and paracellular passage (P = .02) were significantly higher in FD-starters vs HVs and reduced with PPI therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off PPIs. In contrast, immune cells and permeability increased in HVs on PPIs. Dyspeptic symptoms correlated with eosinophils before and during PPI therapy, and increased eosinophils and permeability in HVs on PPIs were associated with changes in bile salts., Conclusions: We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPIs in FD, with differential effects in HVs pointing to a role of luminal changes. ClinicalTrials.gov, Number: NCT03545243., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Although the type 4 secretion system of the integrating and conjugative elements (tfs ICE) is common in Helicobacter pylori, its clinical association with the cag pathogenicity island (cagPAI) have not yet been well-investigated. In this study, Vietnamese patient H. pylori samples (46 duodenal ulcer (DU), 51 non-cardia gastric cancer (NCGC), 39 chronic gastritis (CG)) were fully sequenced using next-generation sequencing and assembled into contigs. tfs3, tfs4, and cagPAI genes were compared with the public database. Most (94%) H. pylori strains possessed a complete cagPAI, which was the greatest risk factor for clinical outcomes, while the prevalences of tfs3 and tfs4 were 45% and 77%, respectively. Complete tfs3 and tfs4 were found in 18.3% and 17.6% of strains, respectively. The prevalence of H. pylori strains with complete tfs3 ICE in DU patients was significantly higher than that in NCGC patients (30.4% vs 11.7%, P < 0.05). In addition, the prevalence of strains with complete tfs3 ICE and cagPAI was significantly higher in DU patients than that in NCGC (28.4% vs 9.8%, P = 0.038) and CG patients (28.2% vs 7.7%, P = 0.024). cagPAI and complete tfs3 increased the risk of DU compared to NCGC (OR = 3.56, 95%CI: 1.1-14.1, P = 0.038) and CG (OR = 4.64, 95%CI: 1.1-27.6, P = 0.024). A complete cluster of tfs3 ICE was associated with gastroduodenal diseases in Vietnam. However, there was a low prevalence of the dupA/complete dupA cluster (15.4%) in the Vietnam strains. The prevalence of cagPAI in Vietnam strains was significantly higher than in US (P = 0.01) and Indonesia (P < 0.0001); the prevalence of the dupA cluster was also higher in the Vietnam strains than in the Indonesian strains (P < 0.05). In addition, the prevalence of ctkA, an accessory gene of tfs3, was significantly different between Vietnam and US strains (28% vs 2%, P = 0.0002). In summary, the acquisition of tfs3/4 ICE was common in H. pylori strains in patients with gastroduodenal disease in Vietnam, and the complete cluster of tfs3 ICE was a reliable marker for the severity of disease in the H. pylori infected population.

Background/aims: Transient receptor potential ankyrin 1 (TRPA1) and substance P (SP), both expression in sensory neurons, have important roles in stress-induced duodenal lesions. The possible contribution of TRPA1 and SP to stress-induced duodenal lesions was explored by using the water immersion restraint stress (WIRS) rat model., Materials and Methods: Western blotting, Real-time polymerase chain reaction (RT-PCR), and immunohistochemistry assay were used to evaluate the changes of TRPA1and SP expression in the dorsal root ganglia (DRG, T8-11), the corresponding segment of the spinal cord (T8-11), and the duodenum in a duodenal lesions rat model. The SP concentrations of duodenal mucosa were investigated using an enzyme-linked immunosorbent assay (ELISA). Duodenal lesions were assessed according to histopathological changes. TRPA1 specific antagonist HC-030031 was intrathecally or intraperitoneally performed to suppress the expression of both TRPA1 and SP for evaluating the roles of TRPA1 and SP in duodenal lesions., Results: In contrast to the control group, TRPA1 and substance P in the DRG (T8-11) and duodenum were up-regulated, and concentrations of SP in the duodenal mucosa were increased after WIRS (p<0.05), which are closely associated with duodenal lesions. SP concentrations in the duodenal mucosa were decreased and duodenal lesions were alleviated by pretreatment with TRPA1 antagonist HC-030031. We identified a protective role for HC-030031 in WIRS-induced duodenal lesions. Furthermore, we demonstrated that WIRS increased the concentrations of SP in the duodenal mucosa in a TRPA1-dependent manner. However, WIRS caused no significant changes of TRPA1 and SP in the spinal cord (T8-11) compared with the control group (p>0.05)., Conclusion: Our study indicates that TRPA1 antagonist HC-030031 alleviates duodenal lesions. TRPA1 is activated and sensitized, therefore concomitant neuropeptide SP is released, which exerts a critical role in inducing and maintaining duodenal lesions following WIRS in rats. This provides evidence that neuroimmune interactions may control duodenal injury. TRPA1 may be a potential drug target to inhibit the development of duodenal lesions by stress-induced in patients.

Amyloid tends to deposit in the gastrointestinal tract, which, being easily accessible, is often the target organ for a pathological diagnostic examination. Although a mucosal biopsy is necessary for a definitive diagnosis and several studies have reported positive results for each possible biopsy site, there remain many unclear features in various aspects. This review focuses on the current literature to determine a better understanding of the diagnosis from endoscopic and histological views in patients with systemic amyloidosis with gastrointestinal involvement. A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed. Endoscopic findings vary based on the organ and the depositing amyloids. A fine granular appearance or polypoid protrusions are likely to occur in the duodenum. AL, Aβ2M, and ATTR amyloids are likely to deposit submucosally, while AA amyloid is easily deposited in the superficial layer of the mucous membrane. Furthermore, it is necessary to consider the collection of biopsy specimens from the duodenum, which has high positive biopsy rates. However, the difference in the positive biopsy rates depends on whether endoscopic findings are available or whether the appropriate number has not been fully elucidated. A duodenal biopsy is strongly recommended to confirm the deposition of amyloid in patients with systemic amyloidosis having gastrointestinal involvement. Because amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are required; gastroenterologists and endoscopists play important roles., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Cell proliferation in the intestine is commonly occurred during infection and inflammation to replace damaged enterocytes, and cholesterol as an essential constituent of cell membrane, is required for cell proliferation and growth. Here we found that coccidium-challenged (CC) chickens showed severe damages in intestinal structure, a significant increase of cell proliferation, and an activation of genes expression involved in the innate immune response. Compared to control (CON), CC chickens showed a marked decrease of cholesterol (Tch) level in the circulating system, but a significant increase in local duodenum epithelium. Increase of LDLR protein combined with a significant decrease of CYP27A1 protein expression in duodenum epithelium may contribute to intestinal cholesterol accumulation in CC chickens. Moreover, we found miRNAs targeting to CYP27A1 gene participating in post-transcriptional regulation. Hence, these results provide a new insight for the intervention of epithelial proliferation and cholesterol metabolism in the gastrointestinal tracts., Competing Interests: The authors have no conflicts of interest to declare.

The article summarizes clinical features of the course when chronic pancreatitis goes in combination with diseases of gastroduodenal and hepatobiliary systems and features of functional and morphological changes. The article also represents justification of need to include the combined medicine Doktovit (combination of Dexpanthenol and S-methylmethionine) into complex treatment of the pathology, describes mechanism of its gastro protective and reparative action.

Objective: We prospectively studied children with portal hypertension (PHT) for portal hypertensive duodenopathy (PHTD) and small bowel intestinal permeability (SIP) with the objectives of defining histopathological parameters for PHTD and to find out whether any association existed among structural changes, SIP, and nutritional status., Method: SIP was assessed by using lactulose and mannitol sugar probes in 31 children with PHT (cirrhosis n = 15 and extrahepatic portal venous obstruction n = 16) and 15 healthy children as controls. Morphometric assessment from duodenal biopsies was done in children with PHT. SIP and morphometric parameters were correlated with nutritional status and dietary intake., Results: Among children with PHT, 48% had PHTD defined as presence of villous atrophy (villous to crypt ratio < 2.5:1), dilated capillaries (capillary diameter > 16.8 μm, capillary area > 151 μm, capillary perimeter > 56 μm), and thickened muscularis mucosae (>22.2 μm). Lactulose excretion alone was increased in children with PHT as compared with healthy children (median %: 0.03, 0.02, and 0.01 for cirrhosis, extrahepatic portal venous obstruction, and controls, respectively [P < 0.01]) signifying increased paracellular permeability in PHT. Children with PHT had significantly lower z scores for height, weight, and triceps skin-fold thickness (<-2SD), whereas no differences were found in dietary intake between patients and controls. Increased SIP, nutritional compromise, and PHTD in our patients had no correlation., Conclusions: PHT is often associated with duodenopathy. SIP does occur as a result of increased paracellular permeability. Factors of increased SIP, undernutrition, and PHTD do not have correlation in childhood PHT.

Pseudomelanosis is a rare finding during upper gastrointestinal endoscopy, and is most commonly seen in the duodenum. Involvement of other organs in the upper gastrointestinal tract is extremely rare, with only 1 reported case involving the stomach, duodenum, and jejunum. We present a case of a 60-year-old woman with mild anemia and hematemesis, who was found to have characteristic speckled pattern of gray-black pigmentation on endoscopic examination. To the best of our knowledge, this is the second reported case of pseudomelanosis involving the stomach, duodenum, and jejunum.

Recent developments in the field of diabetes and obesity management have established the central role of the gut in glucose homeostasis; not only is the gut the primary absorptive site, but it also triggers neurohumoral feedback responses that regulate the pre- and post-absorptive phases of glucose metabolism. Structural and/or functional disorders of the intestine have the capacity to enhance (e.g.: diabetes) or inhibit (e.g.: short-gut syndrome, critical illness) glucose absorption, with potentially detrimental outcomes. In this review, we first describe the normal physiology of glucose absorption and outline the methods by which it can be quantified. Then we focus on the structural and functional changes in the small intestine associated with obesity, critical illness, short gut syndrome and other malabsorptive states, and particularly Type 2 diabetes, which can impact upon carbohydrate absorption and overall glucose homeostasis.

A 32-month-old male common marmoset had a firm and white-colored mass in the duodenal wall. The cut surface was smooth and grayish white in color. Histologically, the mass consisted of a proliferation of spindle cells with an oval to spindle-shaped nucleus and scant eosinophilic cytoplasm in a loose myxoid or fibrotic background. Most of the lesion displayed no specific growth pattern whereas some of the cells concentrated around the vessels and created an onion-bulb structure. Additionally, marked inflammatory cellular infiltration, mainly eosinophils, was observed throughout the lesion. Immunohistochemically, the spindle cells were positive for vimentin, α-smooth muscle actin, fascin, and cyclin D1, and negative for S-100, factor VIII-related antigen, and c-kit. These histological and immunohistochemical features did not meet any differential diagnoses such as gastrointestinal stromal tumor, inflammatory myofibroblastic tumor, solitary fibrous tumor/hemangiopericytoma, smooth muscle tumor, schwannoma, and hemangiosarcoma. Collectively, the authors diagnosed the mass as a lesion that corresponded to an inflammatory fibroid polyp (IFP) in humans. IFP is defined as a mesenchymal proliferation composed of spindle stromal cells, small blood vessels, and inflammatory cells, particularly eosinophils, and is currently classified as a nonneoplastic lesion. To the best of our knowledge, this is the first case of spontaneous IFP in nonhuman primates.

Gastric hypersecretion occurrence in patients, suffering chronic renal insufficiency (CHRI), creates conditions for acido-peptic gastroduodenal zone affection with possible formation of erosive-ulcerative defects, complicated by hemorrhage. In 116 patients, suffering CHRI, the state of gastric mucosa secretory function was studied up. In patients with an acute gastrointestinal hemorrhage and CHRI in conservative and terminal stages the analysis of acidity was conducted.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory disease of the stomach, the small intestine and/or the large intestine. Loss of integrity of the intestinal barrier may be an important factor in the pathogenesis of IBD. In dogs, lymphoplasmacytic enteritis (LPE) is one of the recognized forms of IBD. P-glycoprotein (P-gp) is a membrane-bound efflux pump constituting an important component of the intestinal barrier. Changes in P-gp expression at the level of the intestinal barrier may be important in the pathogenesis of canine LPE, as this may lead to variable protection against xenobiotics and bacterial products in the intestine. The aim of the present study was to evaluate the expression of epithelial P-gp in the intestine in dogs with LPE compared with disease-free animals. Formalin-fixed intestinal biopsy samples from 57 dogs with histopathological evidence of LPE were immunolabelled with anti-P-gp antibodies (C494 and C219). Endoscopic biopsy samples of the duodenum and colon from 16 healthy beagles were used as controls. None of the control dogs had P-gp expression in the apical membrane of duodenal enterocytes, but all had P-gp labelling at the colonic epithelial surface. Twenty out of 57 dogs with LPE had P-gp expression at the apical surface membrane of villus epithelial cells in the duodenum, jejunum and/or ileum. Six out of 16 colonic samples from dogs with LPE had decreased P-gp expression at the epithelial surface compared with controls. It is unclear whether these changes in P-gp expression in dogs with LPE are a cause or a consequence of the inflammation. The observed changes could affect bioavailability of therapeutic drugs used in LPE., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Familial adenomatous polyposis (FAP) provides a model for sporadic colorectal cancer development. Cyclooxygenase (COX) inhibition may ameliorate polyp development, but rofecoxib was withdrawn due to cardiovascular side effects. Although this selective COX-2 inhibitor, like diet, may alter the fatty acid and eicosanoid pattern, data on the potential alteration in tissues after use, are scarce. The aims were to study if rofecoxib might influence the fatty acid distribution in serum phospholipids and duodenal lesions, mRNA for COX-1 and COX-2 in leucocytes and duodenal lesions, and finally plasma levels of PGE(2) in a randomized, double-blind, placebo controlled study (n = 38). Significant reductions were found for essential fatty acid index both in serum phospholipids (P = 0.01, 95% CI = -0.9; -0.1), and in duodenal lesions (P = 0.04, 95 CI % = -0.9; -0.1) after treatment. No treatment effects were found on the COX mRNA expression, or in the plasma PGE(2) levels. Dietary AA/EPA ratio was inversely associated with all the indicators of EFA status (all P < 0.01). These findings suggest that the effects of COX chemoprevention should be further investigated in FAP and that dietary needs should be included in the treatment of FAP.

Aim: to study the time course of changes in the gastric juice levels of nitric oxide (NO) in patients with esophagogastroduonenal diseases (EGDD)., Subjects and Methods: One hundred and seventy-four patients with EGDD were examined., Results: In patients with chronic atrophic gastritis, the level of NO was significantly lower than the normal levels and correlated with the magnitude of mucosal atrophy. Elevated gastric juice NO levels were noted at exacerbations of gastroesophageal reflux disease (GERD), chronic nonatrophic gastritis (CNAG), and duodenal ulcer disease (DUD). At the end of a therapy course, the gastric juice levels of NO did not achieve the control values in patients with GERD, reduced to the normal values in those with CNAG, although became lower, but remained above the normal values in DUD in a remission phase., Conclusion: The patients with EGDD were observed to have heterodirectional changes in the content of NO in gastric juice. In the patients with DUD, the remaining gastric juice NO levels above the normal values after ulcerative defect cicatrization are indicative of incomplete reparative processes in the gastric mucosa, i.e., delayed morphological remission. In chronic atrophic gastritis, the gastric juice levels of NO did not achieve normal values after treatment despite the onset of clinical remission which may be caused by a continuous gastric mucosal atrophic process.

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in the regulation of coagulation and inflammation. In addition to inhibiting the fibrinolytic system, TAFI may also regulate the bradykinin and complement systems. We hypothesized that TAFI also plays a role in defense mechanisms of the gastric mucosa during Helicobacter pylori infection. This study comprised 65 patients with gastroduodenal disorders: 41 patients with H. pylori infection, 13 without, and 11 patients with cured H. pylori infection. The gastric intramucosal concentrations of TAFI were measured by enzyme immunoassay. The gastric levels of TAFI and plasminogen activator inhibitor-1 were significantly increased in patients with H. pylori compared to those without infection or cured H. pylori. The presence of TAFI was detected in gastric mucosal epithelial cells. The concentration of TAFI was correlated with the degree of gastric mucosal atrophy, inflammation, and disease activity. These results show that TAFI is present in the gastric mucosa and that it may play a role in the pathogenesis of H. pylori infection-associated gastroduodenal disorders.

We have found out the clinical presentations and peculiarities of endoscopic and morphologic view of pathologies of mucous membrane of gastroduodenal zone caused by liver cirrhosis. We have examined 74 patients with liver cirrhosis of viral and nonviral etiology using the clinical, endoscopic, morphologic and immunohistochemical methods.We have found that during liver cirrhosis morphometric rates of epithelial cells of mucous coat of stomach that produce somatostatin and endothelin-1 decrease and morphometric rates of epithelial cells that produce nitrogen oxide synthase increase. We have also found out that during liver cirrhosis proliferate activity decrease and apoptosis of epithelial cell of mucous coat of stomach increase.

Aim: To measure content of neuromediators (acetylcholine-Ach, serotonin-5-NT) and gastrointestinal hormones (cholecystokinine-CCK and secretin) in the blood serum of patients with chronic pancreatitis (CP); to study protective properties of the mucus in the duodenum in CP., Material and Methods: CCK and secretin concentrations were estimated by enzyme immunoassay, Ach and 5-NT were measured biochemically basally and after standard meal in 65 CP patients and in the control group. Proteolytic activity of the mucus was assessed by Anson's method. An inhibitory property of the mucus was studied by residual proteolytic activity of pepsine after its incubation with mucus., Results: In AP patients the response of biologically active substrates to standard meal changed: 5-NT concentration rose from 0.40 +/- 0.07 to 0.55 +/- 0.05 mcg/ml (p < 0.05) while Ach dropped from 1.7 +/- 0.3 to 1.6 +/- 0.3 mmol/l (p > 0.05). BP patients responded to the standard meal with 5-HT concentration rise from 0.28 +/- 0.04 to 0.43 +/- 0.05 mcg/ml (p < 0.05), Ach changed insignificantly (from 1.5 +/- 0.12 to 1.45 +/- 0.21 mmol/l, p > 0.05, reselectively). CCK after standard meal significantly rose both in AP and BP. AP and BP patients had strong direct correlation between concentrations of 5-HT and CCK (r = 0.875439) and weak negative correlation with Ach level (r = -0.2209). In AP and BP patients secretin level weakly negatively correlated both with 5-NT and Ach levels (r = -0.4839 and r = -0.33207, respectively). Reduction of secretin secretion diminished secretion of bicarbonates and mucus with simultaneous change in the quality of mucous gel., Conclusion: In CP of various etiology there are changes in the level and proportions of neuromediators and hormones causing alterations in the regulation system. These disorders correlate with disturbances in pancreatic excretory function and destructive tissue changes. Bicarbonates secretion decreases and changes quality of the secreted mucus.

Purpose of Review: The gastrointestinal tract has developed multiple mechanisms of protection from intrinsic and extrinsic sources of injury, including but not limited to drugs, ischemic/reperfusion injuries, and infections such as Helicobacter pylori. We review recent developments in host defense against Helicobacter pylori, duodenal bicarbonate secretion, protection from nonsteroidal anti-inflammatory drug induced gastrointestinal injury, and apoptosis, as well as newer therapies., Recent Findings: Leptin and survivin confer protection against ethanol and indomethacin induced injury. Mucin-1, a cell surface mucin, is an important barrier to gastrointestinal infection. Prostaglandin E(2), Escherichia coli heat-stable enterotoxin, orexins, and carbonated beverages stimulate duodenal bicarbonate secretion., Summary: Gastroduodenal mucosal defense is a dynamic process, and further insights into these defense mechanisms have and will lead to safer and more effective treatments.

Helicobacter pylori colonize the stomach of over half the world's population. While 80-90% H. pylori-infected individuals have clinically asymptomatic gastritis, 10-15% develop peptic ulcer, and 1-2% gastric malignancies. These variable clinical outcomes have led to an interest in prognostic indicators. The current disease paradigm suggests that host genetics and bacterial virulence both play important roles in modulating the final outcome of H. pylori infection. Elucidation of the interaction between host and bacterium is essential to clarify pathogenesis and to develop new strategies for prevention and treatment. Proteomic technology is a powerful tool for simultaneously monitoring proteins and protein variation on a large scale in biological samples. It has provided an unprecedented opportunity to survey a cell's translational landscape comprehensively, and the results may allow in-depth analyses of host and pathogen interactions. Using this high-throughput platform and taking advantage of complete sequences for both the H. pylori and the human genome in available databases, we have identified several crucial proteins that have pathogenic and prognostic potential. Among them, antibodies to AhpC and GroEs of H. pylori could be utilized for identification of patients who are at high risk of disease complications after H. pylori infection. Evolving proteomic technologies, together with appropriate clinical phenotyping and genotype information should enhance understanding of disease pathogenesis and lead to more precise prediction of variable disease outcomes. It will also facilitate development of biomarkers for diagnosis, treatment, and prevention of H. pylori infection.

Because human duodenal mucosal bicarbonate secretion (DMBS) protects duodenum against acid-peptic injury, we hypothesize that estrogen stimulates DMBS, thereby attributing to the clinically observed lower incidence of duodenal ulcer in premenopausal women than the age-matched men. We found that basal and acid-stimulated DMBS responses were 1.5 and 2.4-fold higher in female than male mice in vivo, respectively. Acid-stimulated DMBS in both genders was abolished by ICI 182,780 and tamoxifen. Estradiol-17beta (E2) and the selective estrogen receptor (ER) agonists of ERalpha [1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole] and ERbeta [2,3-bis(4-hydroxyphenyl) propionitrile], but not progesterone, rapidly stimulated ER-dependent murine DMBS in vivo. E2 dose dependently stimulated murine DMBS, which was attenuated by a Cl(-)/HCO3(-) anion exchanger inhibitor 4,4'-didsothio- cyanostilbene-2, 2'-disulfonic acid, removal of extracellular Cl(-), and in cystic fibrosis transmembrane conductance regulator knockout female mice. E2 stimulated murine DMBS in vitro in both genders with significantly greater response in female than male mice (female to male ratio = 4.3). ERalpha and ERbeta mRNAs and proteins were detected in murine duodenal epithelium of both genders; however, neither ERalpha nor ERbeta mRNA and protein expression levels differed according to gender. E2 rapidly mobilized intracellular calcium in a duodenal epithelial SCBN cell line that expresses ERalpha and ERbeta, whereas BAPTA-AM abolished E2-stimulated murine DMBS. Thus, our data show that E2 stimulates DMBS via ER dependent mechanisms linked to intracellular calcium, cystic fibrosis transmembrane conductance regulator, and Cl(-)/HCO3(-) anion exchanger. Gender-associated differences in basal, acid- and E2-stimulated DMBS may have offered a reasonable explanation for the clinically observed lower incidence of duodenal ulcer in premenopausal women than age-matched men.

Clinical presentation, endoscopic picture and morphological changes of gastric and duodenal mucosa were evaluated in 75 patients with chronic hepatitis of different (viral and non-viral) etiology. Endoscopic, morphological, and immunohistochemical studies revealed deterioration of morphometric characteristics of somatostatin-immunopositive epitheliocytes in gastric mucosa and their improvement in epitheliocytes producing endothelin-1 and nitric oxide synthase. These changes were associated with decreased proliferative activity and enhanced apoptosis of epitheliocytes in gastric mucosa.

Morphologic, clinical, and genetic evidence suggests that pancreatic intraepithelial neoplasia (PanIN) is a precursor to ductal adenocarcinoma. But understanding precursor lesions in a pancreas with existing tumor is hampered by the fact that chronic pancreatitis often accompanies carcinoma, and the possible interactions between tumor, chronic pancreatitis, and PanIN are complex. Furthermore, cancerization of ducts can mimic high-grade PanIN. Heterotopic pancreas has a genetic make-up, physiologic function, and local environmental exposure similar to that of the pancreas. It offers an opportunity to study putative precursor lesions in a setting with fewer confounding factors. We identified 6 pancreatic cancer patients who had heterotopic pancreas removed at the time of surgery. All 6 cases were immunostained for p53, cyclin D1, and p16. Molecular analysis of K-ras mutation was also done. All 6 cancer-associated heterotopias had PanIN-1A or 1B; 5 had PanIN-2 and 1 had PanIN-3. Three of 6 cases harbored the same K-ras codon 12 mutation as the PanINs in orthotopic pancreas, and a similar pattern of p53, cyclin D1, and p16 expression was observed between heterotopic and orthotopic pancreas in all 6 cases. There was no chronic pancreatitis in the cancer-associated heterotopias, but chronic pancreatitis was seen adjacent to carcinoma in 5 of 6 cases. The presence of PanIN in heterotopic pancreas from patients with ductal adenocarcinoma supports the progression model.

Using the duodenal bleeding and its early recurrence modelling on 48 mongrel dogs the dynamics of content of general protein, urea and glucose in duodenal mucosa were investigated. There was established that the dynamics of investigated indices of anterior and posterior duodenal wall appeared different and that the level of urea while early recurrence of duodenal bleeding owes consistent tendency for lowering, especially in posterior duodenal wall. The glucose level in these both walls is merely stable.

We describe a 55-year-old man with isolated duodenal and jejunal amyloidosis producing rare endoscopic and histologic findings. The patient had no specific gastrointestinal complaints but underwent esophagogastroduodenoscopy and colonoscopy because of progressive microcytic anemia. Endoscopy revealed multiple polyps, some filiform and measuring up to 3 cm in length, in the duodenum and proximal jejunum. Microscopically, the polyps resulted from amyloid deposition, predominantly within the submucosa, but also focally involving muscularis mucosae and lamina propria. The amyloid formed multiple globular submucosal deposits with a lamellated appearance reminiscent of corpora amylacea; linear amyloid deposition was also present in a perivascular distribution and within the overlying mucosa. Immunophenotyping confirmed AL amyloidosis with lambda immunoglobulin light chain restriction. There was no clinical evidence of visceral amyloidosis. The source of lambda light chain production was unclear as bone marrow biopsy and multiple gastrointestinal biopsies revealed normal numbers of polyclonal plasma cells. Further, immunoglobulin-free light chain assay was normal, as were serum and urine protein electrophoreses with immunofixation. This endoscopic presentation of isolated small bowel polyposis is an uncommon association with AL amyloidosis and to our knowledge this represents the first case of globular gastrointestinal amyloidosis resulting from AL amyloid.

Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein) that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.

Ectopic pancreas is a developmental anomaly occasionally found in humans. Hes1, a main effector of Notch signaling, regulates the fate and differentiation of many cell types during development. To gain insights into the role of the Notch pathway in pancreatic fate determination, we combined the use of Hes1-knockout mice and lineage tracing employing the Cre/loxP system to specifically mark pancreatic precursor cells and their progeny in Ptf1a-cre and Rosa26 reporter mice. We show that inactivation of Hes1 induces misexpression of Ptf1a in discrete regions of the primitive stomach and duodenum and throughout the common bile duct. All ectopic Ptf1a-expressing cells were reprogrammed, or transcommitted, to multipotent pancreatic progenitor status and subsequently differentiated into mature pancreatic exocrine, endocrine, and duct cells. This process recapitulated normal pancreatogenesis in terms of morphological and genetic features. Furthermore, analysis of Hes1/Ptf1a double mutants revealed that ectopic Ptf1a-cre lineage-labeled cells adopted the fate of region-appropriate gut epithelium or endocrine cells similarly to Ptf1a-inactivated cells in the native pancreatic buds. Our data demonstrate that the Hes1-mediated Notch pathway is required for region-appropriate specification of pancreas in the developing foregut endoderm through regulation of Ptf1a expression, providing novel insight into the pathogenesis of ectopic pancreas development in a mouse model.

Background and Aim: The role of juxtapapillary diverticulum ( JPD) in biliary stone formation is controversial. This study was designed to understand the relationship between the size of JPD, hepatic clearance and recurrent bile duct stones in patients after endoscopic sphincterotomy., Methods: Five hundred and twenty patients with choledocholithiasis who had received endoscopic sphincterotomy were enrolled. They were divided into three groups: group A (n = 268) without diverticula; group B (n = 156) with small diverticula; and group C (n = 96) with large diverticula. All patients were regularly followed with interviews, liver function test and sonogram to detect the recurrent bile duct stones. Quantitative cholescintigraphy was performed in 176 cholecystectomized patients to evaluate the hepatic clearance. Sphincter of Oddi manometry was performed to exclude incomplete sphincterotomy if quantitative cholescintigraphy was abnormal., Results: After 9-111 months of follow-up, 76 patients had recurrent bile duct stones. There was a significant higher bile duct stone recurrence in group C than in group A (P < 0.01), but no statistical difference was noted between group B and group A (P = 0.2). Patients with JPD were older than those without (P < 0.05). Of 176 cholecystectomized patients, two were excluded because sphincter of Oddi basal pressure was more than 10 mmHg. In the remaining 174 patients, the E45' was significantly lower in group C than in group A (41.2% +/- 18.6%vs 49.1% +/- 14.1%; P < 0.05), and there was no significant difference between group B and group A., Conclusions: JPD is a predisposing factor of delayed biliary emptying and it increases the chance and incidence of recurrent bile duct stones.

Aim: To determine the concentration of alpha- and beta-defensins in gastric juice of patients with various gastroduodenal diseases., Methods: Concentrations of human neutrophil peptides (HNPs) 1-3, the major forms of alpha-defensins, and human beta-defensin (HBD)-1 and HBD-2 were measured by radioimmunoassay in plasma and gastric juice of 84 subjects, consisting of 54 Helicobacter pylori-infected and 30 uninfected subjects. They included 33 patients with chronic gastritis (CG), 12 with gastric ulcer (GU), 11 with duodenal ulcer (DU), 11 with benign gastric polyp (BGP) and 16 with normal mucosa (N group) on upper endoscopy. Plasma pepsinogen I and II levels, biomarkers for gastric mucosal inflammation and atrophy, were also measured., Results: Gastric juice HNPs 1-3 levels in patients with CG, GU and BGP were significantly higher than those in patients with DU and N. Gastric juice HBD-2 concentrations in patients with CG and GU were significantly higher than those in the N group, but were significantly lower in DU patients than in GU patients. Gastric juice HBD-1 levels and plasma levels of these peptides were similar in the patient groups. Concentrations of gastric juice HNPs 1-3 and HBD-2 of in H pylori-infected patients were significantly different from those in uninfected subjects. HNPs 1-3 concentrations in gastric juice correlated negatively with plasma pepsinogen I levels and I/II ratios. HBD-2 levels in gastric juice correlated positively and negatively with plasma pepsinogen II concentrations and I/II ratios, respectively., Conclusion: HNPs 1-3 and HBD-2 levels in gastric juice are diverse among various gastrointestinal diseases, reflecting the inflammatory and atrophic events of the background gastric mucosa affected by H pylori.

The pathogenesis of the gastroduodenal lesions induced by non-steroidal anti-inflammatory drugs and aspirin is primarily caused by a reduction in mucosal blood flow, which is the consequence of inhibition of cyclooxygenase-producing vasodilator prostaglandins. The subsequent phase is adherence of leukocytes to the endothelium, which may depend on cyclooxygenase-2. Endothelial lesions accentuate the fall of mucosal blood flow and promote the inflammatory process in the gastric mucosa. The inflammatory process is amplified by expression of TNFalpha in polymorphonuclears induced by non-steroidal anti-inflammatory drugs. A few days after starting treatment, epithelial proliferation and increased mucosal blood flow, partly dependent on cyclooxygenase-2 and nitric oxide expression, compensates for the damaging process. Selective inhibitors of inducible cyclooxygenase-2 have reduced gastrointestinal toxicity, which could partially be explained by the protection effect of cyclooxygenase-2 on the gastrointestinal mucosa during inflammation or epithelial repair. Selective inhibitors may worsen inflammatory bowel disease. Non-steroidal inflammatory drugs and aspirin, but perhaps not selective inhibitors, increase the mucosal lesions associated with Helicobacter pylori-induced gastritis. Co-administration of selective inhibitors and aspirin leads to gastrointestinal toxicity equivalent to that of non-specific anti-inflammatory drugs.

Background: Montelukast, a competitive cysteinyl leucotriene-1 receptor antagonist, reduces airway eosinophilia in asthmatics. We evaluated the effect of this drug in children with eosinophilic duodenitis, defined histologically as duodenal mucosa with peak eosinophil count of more than 10 eosinophils/hpf., Methods: Forty children and adolescents (6-18 yr) with dyspepsia and duodenal eosinophilia were enrolled in a double blind, randomized, placebo-controlled, cross-over study of monteleukast therapy. Subjects were randomized to receive either 10 mg montelukast or an identical placebo once daily and were evaluated on day 14 for symptomatic and biochemical responses. Subjects were also randomized to one of two blood sampling schemes to evaluate montelukast pharmacokinetics., Results: Using a post treatment global pain assessment, a positive clinical response was observed in 62.1% of patients receiving montelukast compared with 32.4% on placebo (p < 0.02). Pain assessment score deteriorated in 45% of montelukast responders (5/11) after cross-over to placebo and improved in 62% (8/13) of placebo non-responders on cross-over to montelukast. In patients with peak duodenal eosinophil counts between 20-29/hpf (n=19), a positive pain assessment response was observed in 84% of patients receiving montelukast compared to 42% receiving placebo (p < 0.01). Response rate did not differ by age, gender or histologic findings at baseline. Pharmacokinetic analysis yielded parameter estimates for absorption rate constant (Ka), apparent volume of distribution (Vd/F) and elimination rate constant (Kel) of 0.42 h, 0.19 L/kg and 0.26 h, respectively. The relative extent of systemic drug exposure was comparable to that observed in previous pediatric investigations with similar weight-adjusted montelukast doses. Neither dose nor calculated drug exposure were associated with the level of post treatment pain assessment or the change in biochemical markers., Conclusions: These data suggest a beneficial role for montelukast in the treatment of pediatric patients with dyspepsia associated with duodenal eosinophilia.

Objectives: Whether gastric infection with Helicobacter pylori increases the risk of gastric mucosal injury during long term/low dose aspirin therapy is unknown. We examined whether H. pylori infection enhances upper GI mucosal damage, assessed endoscopically, in volunteers given low dose aspirin. We studied 61 healthy men and women, 29 with and 32 without active H. pylori infection., Methods: We treated volunteers for 45 days with a placebo or aspirin (either 81 mg every day or 325 mg every 3 days). Gastroduodenal mucosal damage was then assessed by endoscopy, as was gastric histology and ex vivo gastric mucosal prostaglandin E2 and F2alpha synthesis rates., Results: Erosive disease from low dose aspirin (erosions and/or ulcers) occurred in 50% of H. pylori-infected volunteers and in 16% of their noninfected counterparts (p = 0.02). Aspirin caused a significantly higher average mucosal injury score in the gastric antrum in H. pylori-infected participants than in noninfected subjects (p = 0.03), and two H. pylori-infected subjects developed antral gastric ulcers. Subjects with H. pylori gastritis treated with the placebo had nearly 50% higher gastric mucosal prostaglandin (E2 plus F2alpha) synthesis rates than their noninfected counterparts (108 +/- 6 ng/g/min versus 75 +/- 6 ng/g/min, p < 0.001). Aspirin reduced mucosal prostaglandin synthesis to similar levels in infected and noninfected participants., Conclusions: Long term/low dose aspirin therapy led to more gastric mucosal damage when H. pylori gastritis was present than when it was absent, despite similar degrees of gastric mucosal prostaglandin depletion.

It is highly probable that nutritionally-related geographic and socioeconomic factors may modulate the conversion of early stages of Helicobacter pylori-associated chronic active gastritis (chronic superficial gastritis [CSG] and chronic deep gastritis [CDG]) to chronic atrophic gastritis (CAG). The factors would be diets low in antioxidant vitamins and other micronutrients. In regions of the world and population groups with high socioeconomic level in which these modulating factors are absent, chronic active gastritis tends to stay in its early stages of CSG or CDG and to predispose to duodenal ulcer. On the contrary, in regions and population groups with low socioeconomic level in which the modulating factors are present, the frequency of CAG increases markedly. When CAG becomes severe and diffuse, hypochlorhydria ensues. Hypochlorhydria decreases the predisposition to duodenal ulcer, while CAG, a precancerous lesion, predisposes to gastric cancer of the intestinal type. The real role of the modulating factors already mentioned could be elucidated doing a multicentric study to determine endoscopically and histologically, in large series of dyspeptic patients from various regions of the world and with different socioeconomic levels, prevalence rates of duodenal ulcer, gastric ulcer, gastric cancer, Helicobacter pylori-associated CAG and intestinal metaplasia of the gastric mucosa, and to correlate these prevalence rates with blood levels of antioxidant capacity and related micronutrients. Latin America, because of its diversity in regions, geographic characteristics and population socioeconomic levels, seems to be the ideal place to conduct a study of that type. If the study could be performed, it would undoubtedly constitute an important contribution to a better understanding of Helicobacter pylori-associated gastroduodenal pathology.

The striking similarities between microvillus inclusions (MIs) in enterocytes in microvillus inclusion disease (MID) and vacuolar apical compartment in tissue culture epithelial cells, led us to analyze endoscopic biopsies of duodenal mucosa of a patient after the samples were used for diagnostic procedures. Samples from another patient with an unrelated disease were used as controls. The MID enterocytes showed a decrease in the thickness of the apical F-actin layer, and normal microtubules. The immunofluorescence analysis of the distribution of five apical membrane markers (sucrase isomaltase, alkaline phosphatase, NHE-3 Na+/H+ exchanger, cGMP-dependent protein kinase, and cystic fibrosis trans-membrane conductance regulator), showed low levels of these proteins in their standard localization at the apical membrane as compared with normal duodenal epithelium processed in parallel. Instead, four of these markers were found in a diffuse distribution in the apical cytoplasm, below the terminal web (as indicated by co-localization with F-actin and cytokeratin 19), and in MIs as well. The basolateral protein Na(+)-K+ATPase, in contrast, was normally localized. These results support the hypothesis that MID may represent the first genetic defect affecting apical membrane traffic, possibly in a late step of apical exocytosis.

Oxygen metabolism disturbances are the pathogenetic factors of many diseases, including digestive tract diseases. Last time much attention was given to importance of active oxygen form, oxygen free radicals. Free radicals are one of the tissue aggressive factors and they are the pathogenic factor of gastritis and duodenitis, stress ulcer, gastric and duodenal ulcer disease and gastric cancer. In this paper the review of investigations of oxygen metabolism in gastric and duodenal diseases was presented.

A case of primary non-Hodgkin's T-cell lymphoma of the duodenum is presented. A 41-year-old man was hospitalized in 1984 complaining of abdominal distention and vomiting. Hypotonic duodenography showed an encircling filling defect in the second portion of the duodenum, and a biopsy specimen revealed features of malignancy suggestive of either undifferentiated carcinoma or malignant lymphoma. Radical surgery (pancreaticoduodenectomy) was performed, after which chemotherapy was administered. A histological evaluation of the duodenal tumor showed it to be non-Hodgkin's lymphoma. It was a diffuse, large-cell type, which immunohistochemically suggested it to be of T-cell origin. Currently the patient is doing well, with no evidence of disease recurrence 13 years after surgery.

Background: Severe intra-abdominal sepsis continues to carry a high mortality rate. The physiological response to sepsis in this condition and its relationship with proinflammatory mediators and their endogenous antagonists require further clarification., Methods: Fifty-seven patients were stratified by Acute Physiology And Chronic Health Evaluation (APACHE) II score at the time of admission to an intensive care unit (group 1, score of less than 20; group 2, score of 20 or more). Serial measurements of clinical and immunological variables were made., Results: Non-survivors from group 2 had a raised acute physiology score (P = 0.01), a higher peak serum interleukin (IL) 6 concentration (P = 0.03) and a depressed level of endogenous immunoglobulin (Ig) G class antiendotoxin core antibody (P = 0.005). In group 1, although organ failure score increased progressively in non-survivors, physiology score and peak IL-6 level were similar to those in survivors, and endogenous IgG class antiendotoxin core antibody titre rose (P = 0.02). In both groups IL-1 and tumour necrosis factor alpha were detected infrequently, but their natural antagonists were present in much higher concentrations in both survivors and non-survivors. Levels of C-reactive protein were raised in both but were not significantly different between survivors and non-survivors., Conclusion: During the development of organ failure and death, the pattern of proinflammatory mediators and their endogenous antagonists can vary markedly and may in part be determined by the extent of the initial physiological disturbance.

The results of examining the mechanisms of development of neurogenic visceral abnormalities induced by the body's extreme exposures, search for modes of its pharmacological correction are presented. Experiments have provided evidence for that the neutropic agents recovering the functional activity of the sympathetic nervous system, normalizing energy and plastic exchange have a positive effect in the treatment of the cardiovascular and gastroduodenal diseases which are caused by a neurogenic agent. A basically new approach to treating peptic ulcer, coronary heart diseases, and myocardial infarction is proposed depending on the stage of a disease.

It is unclear why Helicobacter pylori produces different diseases in different persons. High and low acid secretion rates probably contribute to duodenal ulceration and gastric carcinogenesis, respectively. Both of these changes seem to be corrected by eradicating Helicobacter pylori. We are therefore exploring the basic mechanisms and asking why patients react differently? Helicobacter pylori products and certain cytokines released in Helicobacter pylori gastritis release gastrin from G-cells but inhibit parietal cells. Also tumour necrosis factor alpha inhibits somatostatin-cells and interleukin 1 beta inhibits enterochromaffin-like cells. The net result is that antral gastritis tends to increase, whilst corpus gastritis tends to decrease acid secretion. Corpus atrophy further lowers acid through loss of parietal cells. Factors postulated to increase corpus gastritis include host genetics, early acquisition of Helicobacter pylori, more aggressive strains, poor general health and diets high in salt or lacking in antioxidant vitamins. Further research should address the interaction of bacterium, host and environment with a view to preventing the serious clinical outcomes.

Pseudomelanosis duodeni is rarely seen in children. It manifests endoscopically as peppery speckles in the duodenal mucosa. This pigment corresponds principally to accumulation of ferrous sulfide in macrophages within the lamina propria. We report the case of a 16-year-old boy with ectodermal dysplasia who underwent renal transplantation for vesicoureteral reflux and later developed epigastric pain. Endoscopic and pathologic findings in the duodenal mucosa were typical of pseudomelanosis duodeni. A review of the literature reveals shared clinical features among reported adult and pediatric cases, including chronic renal failure, use of antihypertensive medication and oral iron supplementation, and/or presence of gastric hemorrhage.

Since the intubation study of B. Borgstrom, A. Dahlqvist, and G. Lundh (J. Clin. Invest. 36: 1521-1536, 1957) in humans, the completion of fat absorption within the proximal small intestine has been widely accepted. Based on this report, it has been assumed that the distal small intestine is exposed to fat only in the setting of pathology. This concept may be flawed, since completeness of fat absorption was calculated from the recovery of a water-soluble marker but the aqueous phase is now known to move independently from fat. To reexamine the question of whether fat absorption is complete by midgut, we measured the recovery of a fat-specific marker, 99mTc-thiocyanate, in a canine model equipped with duodenal and midgut fistulas. The fistulous output allowed for the measurement of the amount of fat entering the small intestine and the amount of fat entering the distal one-half of the small intestine. Emulsion meals containing 15 or 60 g of corn oil were tested. The importance of fat exposure of the distal one-half of the small intestine was further confirmed by comparing the fistulous fat recovery under two different patterns of exposure [allowing (ALL) or denying (150 cm) access to the distal small intestine]. We found that fat recovery depended on 1) the dose of fat (15 vs. 60 g; P < 0.0005), 2) the pattern of exposure (150 cm vs. ALL; P < 0.01), and 3) the fistulous position (duodenal vs. midgut; P < 0.005). Specifically, under a 150-cm exposure pattern, whereas 8.8 +/- 1.8 g (means +/- SE) of fat emptied into the duodenum after the 15-g fat meal, 32.6 +/- 3.2 g emptied after the 60-g fat meal. Correspondingly, although 3.5 +/- 1.5 g of fat were recoverable from the midgut fistulous output after the 15-g meal, a much larger amount, 17.1 +/- 5.6 g of fat, was recoverable and therefore not absorbed by the proximal one-half of the small intestine after the 60-g meal. The amount of fat recovery at each fistula was reduced when chyme was allowed access to the whole gut (by triggering fat-induced ileal brake). We conclude that the intestinal length required for fat absorption depends on the load of fat in the meal so that, even after usual meals, absorption of fat is not complete by midgut.

Pseudomelanosis duodeni is an uncommon endoscopic sign characterized by diffuse small black spots on the first and second portions of the duodenum. It occurs predominantly in female and elderly patients and is linked to chronic illnesses and related medications. Between 1988 and 1994, the authors saw eight patients with pseudomelanosis duodeni. To evaluate the nature of the pigments, special staining was performed in seven cases. Iron stain was strongly positive in three cases. Electron microscopy was performed in two cases. This revealed amorphous bodies within macrophage lysosomes in one case and angular crystals in another case. These tests suggest that in pseudomelanosis duodeni iron metabolism may be impaired and iron is pooled within macrophages.

Two male patients with mild gastrointestinal bleeding had peculiar dark pigmentation of their duodenum on upper endoscopy. These pigmented lesions were still present 3 months after the original endoscopy and after resolution of all other mucosal lesions. Both patients had other medical problems, including hypertension. They have been on multiple antihypertensive medications for many years. Biopsies of these duodenal lesions showed the pigment to be present inside the macrophages found in the lamina propria and in between the epithelial cells. Electron microscopy revealed a lysosomal localization of this pigment. This melanin-like pigment proved to contain varying amounts of iron, sulfur, and calcium. This pigmentation is closely associated with systemic hypertension, even in the pediatric population.

We report a case of brown-black pigmentation of the duodenum found in an elderly female during endoscopy for unrelated reasons. Melanin-like pigmentation of the duodenum is a rare endoscopic entity of uncertain etiology and significance. Various theories related to the etiology and pathogenesis, as well as histochemical and electron microscopic characteristics, are discussed.