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World Journal of Gastroenterology Apr 2019Upper gastrointestinal (UGI) tract involvement of inflammatory bowel disease (IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine... (Review)
Review
Upper gastrointestinal (UGI) tract involvement of inflammatory bowel disease (IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis (UC), atypical UC, Crohn's disease (CD) and IBD unclassified. Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid (non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD, is histologically characterized by increased intraepithelial lymphocytes (> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis, villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.
Topics: Child; Diagnosis, Differential; Duodenitis; Endoscopy, Gastrointestinal; Esophagitis; Gastric Mucosa; Gastritis; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Intraepithelial Lymphocytes; Upper Gastrointestinal Tract
PubMed: 31086461
DOI: 10.3748/wjg.v25.i16.1928 -
Scientific Reports Jul 2020Celiac disease (CD) is an enteropathy triggered by the ingestion of gluten proteins in genetically predisposed individuals and characterized by excessive activation of...
Celiac disease (CD) is an enteropathy triggered by the ingestion of gluten proteins in genetically predisposed individuals and characterized by excessive activation of effector immune cells and enhanced production of inflammatory cytokines. However, factors/mechanisms that amplify the ongoing mucosal inflammation in CD are not fully understood. In this study, we assessed whether mammalian target of Rapamycin (mTOR), a pathway that combines intra- and extra-cellular signals and acts as a central regulator for the metabolism, growth, and function of immune and non-immune cells, sustains CD-associated immune response. Our findings indicate that expression of phosphorylated (p)/active form of mTOR is increased in protein lysates of duodenal biopsy samples taken from patients with active CD (ACD) as compared to normal controls. In ACD, activation of mTOR occurs mainly in the epithelial compartment and associates with enhanced expression of p-4EBP, a downstream target of mTOR complex (mTORC)1, while expression of p-Rictor, a component of mTORC2, is not increased. Stimulation of mucosal explants of inactive CD patients with pepsin-trypsin-digested (PT)-gliadin or IFN-γ/IL-21, two cytokines produced in CD by gluten-specific T cells, increases p-4EBP expression. Consistently, blockade of such cytokines in cultures of ACD mucosal explants reduces p-4EBP. Finally, we show that inhibition of mTORC1 with rapamycin in ACD mucosal explants reduces p-4EBP and production of IL-15, a master cytokine produced by epithelial cells in this disorder. Our data suggest that ACD inflammation is marked by activation of mTORC1 in the epithelial compartment.
Topics: Biopsy; Celiac Disease; Duodenum; Female; Gliadin; Humans; Inflammation; Interferon-gamma; Interleukins; Intestinal Mucosa; Male; Mechanistic Target of Rapamycin Complex 1; Mechanistic Target of Rapamycin Complex 2; Phosphorylation; T-Lymphocytes; TOR Serine-Threonine Kinases
PubMed: 32612145
DOI: 10.1038/s41598-020-67889-4 -
Cell Reports Jan 2016The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and...
The cargo receptor NCOA4 mediates autophagic ferritin degradation. Here we show that NCOA4 deficiency in a knockout mouse model causes iron accumulation in the liver and spleen, increased levels of transferrin saturation, serum ferritin, and liver hepcidin, and decreased levels of duodenal ferroportin. Despite signs of iron overload, NCOA4-null mice had mild microcytic hypochromic anemia. Under an iron-deprived diet (2-3 mg/kg), mice failed to release iron from ferritin storage and developed severe microcytic hypochromic anemia and ineffective erythropoiesis associated with increased erythropoietin levels. When fed an iron-enriched diet (2 g/kg), mice died prematurely and showed signs of liver damage. Ferritin accumulated in primary embryonic fibroblasts from NCOA4-null mice consequent to impaired autophagic targeting. Adoptive expression of the NCOA4 COOH terminus (aa 239-614) restored this function. In conclusion, NCOA4 prevents iron accumulation and ensures efficient erythropoiesis, playing a central role in balancing iron levels in vivo.
Topics: Anemia, Hypochromic; Animals; Autophagy; Cell Line; Duodenum; Erythrocytes; Erythropoiesis; Female; Ferritins; Hepcidins; Iron; Iron Overload; Iron, Dietary; Liver; Male; Mice; Mice, Knockout; Nuclear Receptor Coactivators; Oxidoreductases; Reactive Oxygen Species; Spleen; Up-Regulation
PubMed: 26776506
DOI: 10.1016/j.celrep.2015.12.065 -
Revista Espanola de Enfermedades... Aug 2022A 79-year-old male, with a past medical history of hypertension, dyslipidemia and type 2 diabetes, underwent routine esophagogastroduodenoscopy and colonoscopy. The...
A 79-year-old male, with a past medical history of hypertension, dyslipidemia and type 2 diabetes, underwent routine esophagogastroduodenoscopy and colonoscopy. The patient was asymptomatic, with unremarkable blood tests. Upper gastrointestinal endoscopy showed multiple whitish nodular lesions in the first part of the duodenum.
Topics: Aged; Diabetes Mellitus, Type 2; Duodenal Neoplasms; Duodenum; Endoscopy, Gastrointestinal; Humans; Lymphoma, Follicular; Male
PubMed: 34517710
DOI: 10.17235/reed.2021.8149/2021 -
Physiology & Behavior May 2018Cholecystokinin (CCK) and apolipoprotein A-IV (ApoA-IV) are gastrointestinal peptides that play an important role in controlling energy homeostasis. Lymphatic ApoA-IV...
Cholecystokinin (CCK) and apolipoprotein A-IV (ApoA-IV) are gastrointestinal peptides that play an important role in controlling energy homeostasis. Lymphatic ApoA-IV and plasma CCK secretion are mediated via a chylomicron formation-dependent pathway during a dietary lipid infusion. Given their similar roles as satiating proteins, the present study examines how the two peptides interact in their function. Specifically, this study sought to understand how ApoA-IV regulates CCK secretion. For this purpose, Cck gene expression in the small intestines of ApoA-IV knockout (ApoA-IV-KO) and wild-type (WT) mice were compared under an array of feeding conditions. When fed with a chow or high-fat diet (HFD), basal levels of Cck transcripts were significantly reduced in the duodenum of ApoA-IV-KO mice compared to WT mice. Furthermore, after an oral gavage of a lipid mixture, Cck gene expression in the duodenum was significantly reduced in ApoA-IV-KO mice relative to the change seen in WT mice. To determine the mechanism by which ApoA-IV modulates Cck gene expression, STC-1 cells were transfected with predesigned mouse lysophosphatidic acid receptor 5 (LPAR5) small interfering RNA (siRNA) to knockdown Lpar5 gene expression. In this in-vitro study, mouse recombinant ApoA-IV protein increased Cck gene expression in enteroendocrine STC-1 cells and stimulated CCK release from the STC-1 cells. However, the levels of CCK protein and Cck expression were attenuated when Lpar5 was knocked down in the STC-1 cells. Together these observations suggest that dietary lipid-induced ApoA-IV is associated with Cck synthesis in the duodenum and that ApoA-IV protein directly enhances CCK release through the activation of a LPAR5-dependent pathway.
Topics: Animals; Antioxidants; Apolipoproteins A; Cell Line, Transformed; Cholecystokinin; Dietary Fats; Dose-Response Relationship, Drug; Duodenum; Gene Expression Regulation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; RNA, Messenger; Receptors, Lysophosphatidic Acid; Time Factors; Triglycerides
PubMed: 29378187
DOI: 10.1016/j.physbeh.2018.01.019 -
The American Journal of Case Reports Nov 2022BACKGROUND Spontaneous oropharyngeal hemorrhage is rare and is often associated with other predisposing factors. This can result in hemodynamic instability in the...
BACKGROUND Spontaneous oropharyngeal hemorrhage is rare and is often associated with other predisposing factors. This can result in hemodynamic instability in the presence of other bleeding sources. It is oftentimes difficult to diagnose due to its limitations to visual inspection of the oropharyngeal structures. It is commonly mistaken for hemoptysis or hematemesis upon initial evaluation. Trauma, infection, pulmonary pathologies (ie, lung cancer or tuberculosis), gastrointestinal pathologies (ie, esophageal/gastric varices, Mallory-Weiss tears, esophagitis), coagulopathies, medications, and prolonged intubation have been shown to increase the risk of oropharyngeal hemorrhage. CASE REPORT A 54-year-old man with a medical history of alcohol use disorder, liver cirrhosis, portal hypertension, and gastric varices presented with altered mental status. He was subsequently intubated for airway protection. Bleeding from the oropharynx was later found. Esophagogastroduodenoscopy (EGD) and bronchoscopy were unrevealing. Computed tomography angiography (CTA) of the head and neck revealed active bleeding of the right posterior pharyngeal artery, which was emergently embolized. Over the next few days, he continued to bleed from the oropharynx and became hemodynamically unstable. CTA abdomen showed bleeding from gastric varices and large-volume hemoperitoneum with multiple sources of active bleeding from the liver, duodenum, and jejunum. CONCLUSIONS We present a rare case of spontaneous oropharyngeal hemorrhage and gastric variceal bleeding resulting in hemorrhagic shock in a cirrhotic patient with multiple predisposing factors. If a patient presents with spontaneous oropharyngeal hemorrhage, clinicians should consider bleeding from the oropharynx if EGD and bronchoscopy are unrevealing. Thus, an emergent CTA of the head and neck should be strongly considered to further evaluate a potential source of active bleeding, as delayed diagnosis can be life-threatening.
Topics: Male; Humans; Middle Aged; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Shock, Hemorrhagic; Liver Cirrhosis; Causality; Oropharynx
PubMed: 36322511
DOI: 10.12659/AJCR.937582 -
BMC Gastroenterology May 2022Primary duodenal cancer (PDC) is rare, especially signet-ring cell carcinoma (SRCC) of the duodenal bulb, and it is commonly misdiagnosed as an ulceration. Here, we... (Review)
Review
BACKGROUND
Primary duodenal cancer (PDC) is rare, especially signet-ring cell carcinoma (SRCC) of the duodenal bulb, and it is commonly misdiagnosed as an ulceration. Here, we report a rare case of SRCC of the duodenal bulb presenting with gastrointestinal hemorrhage in an 82-year-old man.
CASE PRESENTATION
An 82-year-old man was admitted for gastrointestinal hemorrhage. Physical examination revealed upper abdominal tenderness and pale appearance, but was otherwise unrevealing. Laboratory workup was significant for anemia. Imaging showed no abnormalities. Two endoscopic evaluations along with interventional embolization were attempted and, unfortunately, adequate hemostasis was not achieved, resulting in distal subtotal gastrectomy, including the duodenal bulb. SRCC of the duodenal bulb was diagnosed based on pathology after surgery. Post-operatively, the patient experienced persistent gastrointestinal bleeding. Family declined further intervention and the patient eventually died one month post-resection.
CONCLUSIONS
SRCC in the duodenal bulb is difficult to diagnose. For those with high-risk factors, endoscopic examination and biopsy are recommended. For patients who can receive radical tumor resection, pancreaticoduodenectomy (PD) is considered a first-line option. Early diagnosis and resection have been shown to improve prognosis.
Topics: Aged, 80 and over; Carcinoma, Signet Ring Cell; Duodenum; Embolization, Therapeutic; Endoscopy; Gastrointestinal Hemorrhage; Humans; Male
PubMed: 35534806
DOI: 10.1186/s12876-022-02267-0 -
Nutrients Sep 2021Zinc (Zn) deficiency is estimated to affect over one billion (17%) of the world's population. Zn plays a key role in various cellular processes such as differentiation,...
Zinc (Zn) deficiency is estimated to affect over one billion (17%) of the world's population. Zn plays a key role in various cellular processes such as differentiation, apoptosis, and proliferation, and is used for vital biochemical and structural processes in the body. Widely used biomarkers of Zn status include plasma, whole blood, and urine Zn, which decrease in severe Zn deficiency; however, accurate assessment of Zn status, especially in mild to moderate deficiency, is difficult, as studies with these biomarkers are often contradictory and inconsistent. Thus, sensitive and specific biological markers of Zn physiological status are still needed. In this communication, we provide the Zn status index (ZSI) concept, which consists of a three-pillar formula: (1) the LA:DGLA ratio, (2) mRNA gene expression of Zn-related proteins, and (3) gut microbiome profiling to provide a clear assessment of Zn physiological status and degree of Zn deficiency with respect to assessing dietary Zn manipulation. Analysis of five selected studies found that with lower dietary Zn intake, erythrocyte LA:DGLA ratio increased, mRNA gene expression of Zn-related proteins in duodenal and liver tissues was altered, and gut microbiota populations differed, where the ZSI, a statistical model trained on data from these studies, was built to give an accurate estimation of Zn physiological status. However, the ZSI needs to be tested and refined further to determine its full potential.
Topics: 8,11,14-Eicosatrienoic Acid; Animals; Biomarkers; Cation Transport Proteins; Chickens; Diet; Duodenum; Erythrocytes; Food, Fortified; Gastrointestinal Microbiome; Gene Expression Regulation; Linoleic Acid; Liver; Models, Animal; Zinc
PubMed: 34684398
DOI: 10.3390/nu13103399 -
World Journal of Gastroenterology Nov 2017To evaluate selected intestinal parameters of oxidative stress, and antioxidant capacity in adult celiac disease patients with extraintestinal manifestations.
AIM
To evaluate selected intestinal parameters of oxidative stress, and antioxidant capacity in adult celiac disease patients with extraintestinal manifestations.
METHODS
The study involved 85 adult patients divided into the following subgroups: (1) patients with newly diagnosed celiac disease (CD) ( = 7); (2) celiac patients not adhering to a gluten-free diet (GFD) ( = 22); (3) patients with CD on the GFD ( = 31); and (4) patients with functional disorders of the gastrointestinal tract, serving as controls ( = 25). Celiac patients presented with non-classic symptoms or extraintestinal manifestations. Standard blood tests including serum antioxidant levels (uric acid, bilirubin, and vitamin D), celiac antibody levels, and histopathological status of duodenal biopsy specimens have been determined. The expression of mRNA for tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 10 (IL-10), superoxide dismutase (SOD), heat-shock protein 70 (HSP-70), hypoxia-inducible factor 1 (HIF-1α), and BAX in the duodenal mucosa of patients was analyzed by reverse transcriptase-polymerase chain reaction.
RESULTS
The mean plasma uric acid level in patients with active CD (newly diagnosed and nonadherent patients) and treated celiac patients was significantly higher than in controls (260.17 ± 53.65 190.8 ± 22.98, < 0.001, and 261.7 ± 51.79 190.8 ± 22.98, < 0.001, respectively). The mean bilirubin concentration in active and treated celiac patients was significantly lower than in controls (8.23 ± 5.04 10.48 ± 4.08, < 0.05 and 8.06 ± 3.31 10.48 ± 4.08, < 0.05, respectively). The mean plasma vitamin D level was significantly lower in active celiac patients than in treated celiac patients and controls (19.37 ± 9.03 25.15 ± 11.2, < 0.05 and 19.37 ± 9.03 29.67 ± 5.12, < 0.001, respectively). The expression of TNF-α, IL-10, and HSP-70 mRNAs was significantly elevated in the celiac groups regardless of the diet when compared with controls. Patients on the GFD presented a significantly lower mRNA expression of TNF-α and IL-10 than in newly diagnosed and nonadherent patients ( < 0.05). The expression of SOD mRNA was significantly elevated in celiac patients compared with controls ( < 0.05), with a significant difference between treated and untreated patients ( < 0.05). The expression of HIF-1α mRNA and BAX mRNA was significantly higher in patients with active CD compared with controls and patients on GFD, while no difference was observed between the latter two groups.
CONCLUSION
Increased intestinal expression of HSP-70 despite GFD indicates that GFD only partially reduced oxidative stress. CD patients exhibited an oxidative imbalance and inflammatory response despite GFD. Uric acid may act as an important antioxidant in CD.
Topics: Adult; Aged; Biomarkers; Case-Control Studies; Celiac Disease; Diet, Gluten-Free; Duodenum; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Oxidative Stress; RNA, Messenger; Uric Acid; Young Adult
PubMed: 29209126
DOI: 10.3748/wjg.v23.i44.7849 -
The American Journal of Clinical... Jul 2015We re-evaluated the old hypothesis that gastritis-induced achlorhydria is a cause of iron deficiency anemia (IDA) in humans. First, we analyzed the currently available... (Review)
Review
We re-evaluated the old hypothesis that gastritis-induced achlorhydria is a cause of iron deficiency anemia (IDA) in humans. First, we analyzed the currently available research on the association between achlorhydria and IDA. When gastric acid secretion was measured after maximal stimulation, the frequency of achlorhydria (or severe hypochlorhydria) was 44% in patients with idiopathic IDA and 1.8% in healthy controls. In some patients with pernicious anemia, presumed achlorhydria preceded the development of IDA in time. However, we found no credible evidence that IDA caused gastritis or that IDA preceded the development of achlorhydria. Thus, correlational results favor achlorhydria as the causal factor in the association between achlorhydria and IDA. Second, we sought to determine whether gastritis and achlorhydria cause negative iron balance. When biosynthetic methods were used to isotopically label iron in food, achlorhydric patients were found to have severe malabsorption of nonheme iron, which persisted after the development of IDA. In 1 study, achlorhydria reduced the normal increase in heme-iron absorption from hemoglobin in response to iron deficiency. After an injection of isotopic iron into normal men, the physiologic loss of iron from the body was found to be 1 mg/d. Patients with chronic gastritis had excess fecal loss of isotopically tagged plasma iron. Calculations based on these results indicate that the absorption of iron from a typical Western diet by achlorhydric patients would be less than physiologic iron losses, creating a negative iron balance that could not be overcome by the adaptive increase in duodenal iron absorptive capacity that occurs in response to iron deficiency. The combination of results from these correlational and pathophysiologic studies supports the hypothesis that gastritis-induced achlorhydria can be an independent cause of IDA.
Topics: Achlorhydria; Anemia, Iron-Deficiency; Duodenum; Gastritis; Hemoglobins; Humans; Iron, Dietary
PubMed: 25994564
DOI: 10.3945/ajcn.114.097394