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Gastroenterology Mar 2022The protozoa Giardia duodenalis is a major cause of gastrointestinal illness worldwide, but underlying pathophysiological mechanisms remain obscure, partly due to the...
BACKGROUND & AIMS
The protozoa Giardia duodenalis is a major cause of gastrointestinal illness worldwide, but underlying pathophysiological mechanisms remain obscure, partly due to the absence of adequate cellular models. We aimed at overcoming these limitations and recapitulating the authentic series of pathogenic events in the primary human duodenal tissue by using the human organoid system.
METHODS
We established a compartmentalized cellular transwell system with electrophysiological and barrier properties akin to duodenal mucosa and dissected the events leading to G. duodenalis-induced barrier breakdown by functional analysis of transcriptional, electrophysiological, and tight junction components.
RESULTS
Organoid-derived cell layers of different donors showed a time- and parasite load-dependent leak flux indicated by collapse of the epithelial barrier upon G. duodenalis infection. Gene set enrichment analysis suggested major expression changes, including gene sets contributing to ion transport and tight junction structure. Solute carrier family 12 member 2 and cystic fibrosis transmembrane conductance regulator-dependent chloride secretion was reduced early after infection, while changes in the tight junction composition, localization, and structural organization occurred later as revealed by immunofluorescence analysis and freeze fracture electron microscopy. Functionally, barrier loss was linked to the adenosine 3',5'-cyclic monophosphate (cAMP)/protein kinase A-cAMP response element-binding protein signaling pathway.
CONCLUSIONS
Data suggest a previously unknown sequence of events culminating in intestinal barrier dysfunction upon G. duodenalis infection during which alterations of cellular ion transport were followed by breakdown of the tight junctional complex and loss of epithelial integrity, events involving a cAMP/protein kinase A-cAMP response element-binding protein mechanism. These findings and the newly established organoid-derived model to study G. duodenalis infection may help to explore new options for intervening with disease and infection, in particular relevant for chronic cases of giardiasis.
Topics: Apoptosis; Caco-2 Cells; Chlorides; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cystic Fibrosis Transmembrane Conductance Regulator; Duodenum; Electric Impedance; Giardia lamblia; Giardiasis; Humans; Interleukin-1; Intestinal Mucosa; Ion Transport; NF-kappa B; Organoids; Parasite Load; Signal Transduction; Solute Carrier Family 12, Member 2; Tight Junctions; Transcriptome; Tumor Necrosis Factor-alpha
PubMed: 34822802
DOI: 10.1053/j.gastro.2021.11.022 -
World Journal of Gastroenterology Jul 2014The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world's population. H. pylori that establishes life-long infection in the stomach is... (Review)
Review
The bacterial pathogen Helicobacter pylori (H. pylori) colonizes in over half of the world's population. H. pylori that establishes life-long infection in the stomach is definitely associated with gastro-duodenal diseases and a wide variety of non-gastrointestinal tract conditions such as immune thrombocytopenia. Triple therapy which consists of a proton pump inhibitor and combinations of two antibiotics (amoxicillin, clarithromycin or amoxicillin, metronidazol) is commonly used for H. pylori eradication. Recently, the occurrence of drug-resistant H. pylori and the adverse effect of antibiotics have severely weakened eradication therapy. Generally antibiotics induce the disturbance of human gastrointestinal microflora. Furthermore, there are inappropriate cases of triple therapy such as allergy to antibiotics, severe complications (liver and/or kidney dysfunction), the aged and people who reject the triple therapy. These prompt us to seek alterative agents instead of antibiotics and to develop more effective and safe therapy with these agents. The combination of these agents actually may result in lower a dose of antibiotics. There are many reports world-wide that non-antibiotic substances from natural products potentially have an anti-H. pylori agent. We briefly review the constituents derived from nature that fight against H. pylori in the literature with our studies.
Topics: Animals; Anti-Bacterial Agents; Complementary Therapies; Dietary Supplements; Drug Resistance, Bacterial; Drug Therapy, Combination; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Phytotherapy; Plant Extracts; Plants, Medicinal; Proton Pump Inhibitors; Treatment Outcome
PubMed: 25083070
DOI: 10.3748/wjg.v20.i27.8971 -
The Korean Journal of Internal Medicine May 2016One in 10 people suffer from functional dyspepsia (FD), a clinical syndrome comprising chronic bothersome early satiety, or postprandial fullness, or epigastric pain or... (Review)
Review
One in 10 people suffer from functional dyspepsia (FD), a clinical syndrome comprising chronic bothersome early satiety, or postprandial fullness, or epigastric pain or burning. Postprandial distress syndrome (PDS, comprising early satiety and/or postprandial fullness) and epigastric pain syndrome (EPS) are increasingly accepted as valid clinical entities, based on new insights into the pathophysiology and the results of clinical trials. Diagnosis is based on the clinical history, and exclusion of peptic ulcer and cancer by endoscopy. Evidence is accumulating FD and gastroesophageal ref lux disease are part of the same disease spectrum in a major subset. The causes of FD remain to be established, but accumulating data suggest infections and possibly food may play an important role in subsets. FD does not equate with no pathology; duodenal eosinophilia is now an accepted association, and Helicobacter pylori infection is considered to be causally linked to dyspepsia although only a minority will respond to eradication. In those with EPS, acid suppression therapy is a first line therapy; consider a H2 blocker even if proton pump inhibitor fails. In PDS, a prokinetic is preferred. Second line therapy includes administration of a tricyclic antidepressant in low doses, or mirtazapine, but not a selective serotonin reuptake inhibitor.
Topics: Anti-Bacterial Agents; Antidepressive Agents, Tricyclic; Dyspepsia; Gastrointestinal Agents; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Predictive Value of Tests; Proton Pump Inhibitors; Risk Factors; Treatment Outcome
PubMed: 27048251
DOI: 10.3904/kjim.2016.091 -
The Journal of Clinical Endocrinology... May 2022SARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19...
CONTEXT
SARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19 are more likely to have severe disease is unknown.
OBJECTIVE
We aimed to compare the duodenal mucosal expression of SARS-CoV-2 and inflammation-related genes in diabetes gastroenteropathy (DGE), functional dyspepsia (FD), and healthy controls.
METHODS
Gastrointestinal transit, and duodenal mucosal mRNA expression of selected genes were compared in 21 controls, 39 DGE patients, and 37 FD patients from a tertiary referral center. Pathway analyses were performed.
RESULTS
Patients had normal, delayed (5 FD [13%] and 13 DGE patients [33%]; P = 0.03 vs controls), or rapid (5 FD [12%] and 5 DGE [12%]) gastric emptying (GE). Compared with control participants, 100 SARS-CoV-2-related genes were increased in DGE (FDR < 0.05) vs 13 genes in FD; 71 of these 100 genes were differentially expressed in DGE vs FD but only 3 between DGE patients with normal vs delayed GE. Upregulated genes in DGE include the SARS-CoV2 viral entry genes CTSL (|Fold change [FC]|=1.16; FDR < 0.05) and CTSB (|FC|=1.24; FDR < 0.05) and selected genes involved in viral replication (eg, EIF2 pathways) and inflammation (CCR2, CXCL2, and LCN2, but not other inflammation-related pathways eg, IL-2 and IL-6 signaling).
CONCLUSION
Several SARS-CoV-2-related genes were differentially expressed between DGE vs healthy controls and vs FD but not between DGE patients with normal vs delayed GE, suggesting that the differential expression is related to diabetes per se. The upregulation of CTSL and CTSB and replication genes may predispose to SARS-CoV2 infection of the gastrointestinal tract in diabetes.
Topics: COVID-19; Diabetes Mellitus; Diabetic Neuropathies; Dyspepsia; Gastric Emptying; Gastrointestinal Diseases; Humans; Inflammation; RNA, Viral; SARS-CoV-2
PubMed: 35090021
DOI: 10.1210/clinem/dgac038 -
Journal of Pediatric Surgery Sep 2021Surgical site infections (SSI) are a frequent and significant problem understudied in infants operated for abdominal birth defects. Different forms of SSIs exist, namely... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical site infections (SSI) are a frequent and significant problem understudied in infants operated for abdominal birth defects. Different forms of SSIs exist, namely wound infection, wound dehiscence, anastomotic leakage, post-operative peritonitis and fistula development. These complications can extend hospital stay, surge medical costs and increase mortality. If the incidence was known, it would provide context for clinical decision making and aid future research. Therefore, this review aims to aggregate the available literature on the incidence of different SSIs forms in infants who needed surgery for abdominal birth defects.
METHOD
The electronic databases Pubmed, EMBASE, and Cochrane library were searched in February 2020. Studies describing infectious complications in infants (under three years of age) were considered eligible. Primary outcome was the incidence of SSIs in infants. SSIs were categorized in wound infection, wound dehiscence, anastomotic leakage, postoperative peritonitis, and fistula development. Secondary outcome was the incidence of different forms of SSIs depending on the type of birth defect. Meta-analysis was performed pooling reported incidences in total and per birth defect separately.
RESULTS
154 studies, representing 11,786 patients were included. The overall pooled percentage of wound infections after abdominal birth defect surgery was 6% (95%-CI:0.05-0.07) ranging from 1% (95% CI:0.00-0.05) for choledochal cyst surgery to 10% (95%-CI:0.06-0.15) after gastroschisis surgery. Wound dehiscence occurred in 4% (95%-CI:0.03-0.07) of the infants, ranging from 1% (95%-CI:0.00-0.03) after surgery for duodenal obstruction to 6% (95%-CI:0.04-0.08) after surgery for gastroschisis. Anastomotic leakage had an overall pooled percentage of 3% (95%-CI:0.02-0.05), ranging from 1% (95%-CI:0.00-0.04) after surgery for duodenal obstruction to 14% (95% CI:0.06-0.27) after colon atresia surgery. Postoperative peritonitis and fistula development could not be specified per birth defect and had an overall pooled percentage of 3% (95%-CI:0.01-0.09) and 2% (95%-CI:0.01-0.04).
CONCLUSIONS
This review has systematically shown that SSIs are common after correction for abdominal birth defects and that the distribution of SSI differs between birth defects.
Topics: Abdomen; Digestive System Surgical Procedures; Humans; Incidence; Infant; Surgical Wound Dehiscence; Surgical Wound Infection
PubMed: 33485614
DOI: 10.1016/j.jpedsurg.2021.01.018 -
World Journal of Gastroenterology Jul 2016Endoscopic papillary balloon dilatation (EPBD) is useful for decreasing early complications of endoscopic retrograde cholangio-pancreatography (ERCP), including... (Review)
Review
Endoscopic papillary balloon dilatation (EPBD) is useful for decreasing early complications of endoscopic retrograde cholangio-pancreatography (ERCP), including bleeding, biliary infection, and perforation, but it is generally avoided in Western countries because of a relatively high reported incidence of post-ERCP pancreatitis (PEP). However, as the efficacy of endoscopic papillary large-balloon dilatation (EPLBD) becomes widely recognized, EPBD is attracting attention. Here we investigate whether EPBD is truly a risk factor for PEP, and seek safer and more effective EPBD procedures by reviewing past studies. We reviewed thirteen randomised control trials comparing EPBD and endoscopic sphincterotomy (EST) and ten studies comparing direct EPLBD and EST. Three randomized controlled trials of EPBD showed significantly higher incidence of PEP than EST, but no study of EPLBD did. Careful analysis of these studies suggested that longer and higher-pressure inflation of balloons might decrease PEP incidence. The paradoxical result that EPBD with small-calibre balloons increases PEP incidence while EPLBD does not may be due to insufficient papillary dilatation in the former. Insufficient dilatation could cause the high incidence of PEP through the use of mechanical lithotripsy and stress on the papilla at the time of stone removal. Sufficient dilation of the papilla may be useful in preventing PEP.
Topics: Ampulla of Vater; Cholangiopancreatography, Endoscopic Retrograde; Choledocholithiasis; Dilatation; Humans; Lithotripsy; Pancreatitis; Postoperative Complications; Risk Factors; Sphincterotomy, Endoscopic
PubMed: 27468185
DOI: 10.3748/wjg.v22.i26.5909 -
Medicina (Kaunas, Lithuania) Dec 2022: To determine the antibiotic resistance rate of among patients with peptic ulcer. : A cross-sectional monocentric study was conducted from January to December 2021...
: To determine the antibiotic resistance rate of among patients with peptic ulcer. : A cross-sectional monocentric study was conducted from January to December 2021 among patients aged from 16 years with gastrointestinal symptoms and esophagogastroduodenoscopy. Gastric mucosa biopsies were collected at the edges of the ulcer or at lesion sites for culture. Five antibiotics (amoxicillin (AMX), clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LEV), and tetracycline (TET)) were selected for antibiotic susceptibility testing. : One hundred and twenty-five patients were included, and the sex ratio was 0.6. Their mean age was 47.3 ± 14.2 years. All of the participants had gastritis, and 24.0% had duodenitis. A total of 21.6% of patients had a duodenal ulcer, and 12.8% had an antral ulcer. A total of 40 specimens have grown in culture. The proportion of resistance to AMX, CLR, MTZ, LEV, and TET was 27.5%, 50%, 67.5%, 35%, and 5%, respectively. The proportion of multidrug resistance was 22.5%. The proportion of double resistance to AMX + CLR was 20.0%, AMX + MTZ was 15.0%, AMX + LEV was 2.5%, CLR + MTZ was 32.5%, and TET + MTZ was 5.0%. : Our research results show that the treatment with MTX-TET or LVX-AMOX has the highest sensitivity rate. Therefore, practitioners should refer to these regimes to eradicate in patients with gastric and duodenal ulcers. The reports on eradication from different geographic areas show heterogeneous results. Therefore, continuous monitoring of antibiotic resistance of in each population is very important. Having evidence helps clinicians to treat patients most effectively, reduce treatment costs, and limit the rate of antibiotic resistance.
Topics: Humans; Adult; Middle Aged; Adolescent; Helicobacter pylori; Ulcer; Cross-Sectional Studies; Microbial Sensitivity Tests; Anti-Bacterial Agents; Peptic Ulcer; Drug Resistance, Microbial; Clarithromycin; Metronidazole; Amoxicillin; Duodenal Ulcer; Tetracycline; Gastritis; Helicobacter Infections
PubMed: 36676631
DOI: 10.3390/medicina59010006 -
World Journal of Gastroenterology Jul 2023Schistosomiasis (bilharziasis) is a major neglected tropical disease. It is endemic in many tropical and subtropical communities. Schistosomal polyps (S. polyps) are not... (Review)
Review
Schistosomiasis (bilharziasis) is a major neglected tropical disease. It is endemic in many tropical and subtropical communities. Schistosomal polyps (S. polyps) are not uncommon presentation of this infection. Although the colon is the most commonly affected organ, many other organs are affected. S. polyps are associated with a variable range of morbidity independent of the Schistosomal infection. S. polyps are frequently described in endemic areas and increasingly reported in non-endemic areas mainly among immigrants and visitors to the endemic areas. This review aimed to increase awareness of practitioners, especially gastroenterologists, for this peculiar type of polyps caused by this neglected infection hence improving patient outcomes. Web-based search of different databases was conducted for the literature focusing the development of S. polyps in the colon and other organs with analysis of the clinical manifestations, diagnosis and treatment. The following key words were used in the search, "Schistosomiasis" OR "Bilharziasis" AND "Polyps" OR "Polyp" AND "Colon" OR "Small intestine" OR " Duodenum" OR " Stomach" OR "Esophagus" OR " Gallbladder" OR" Pharynx" OR "Larynx" OR "Trachea" OR "Urinary bladder" OR " Ureter" OR "Renal Pelvis" OR "Urethra". All publication types including case reports, case series, original research, and review articles were retrieved and analyzed. S. polyps are not infrequent presentation of acute or chronic Schistosomal infection. S. polyps are described in many organs including the bowel, genitourinary tract, skin, gallbladder and the larynx. Presentation of S. polyps is variable and depends on the site, number as well as the polyp size. The relationship of to malignant transformation is a matter of discussion. Presence of S. polyps is sometimes the only manifestation of Schistosomiasis. Small polyps can be treated medically with praziquantel, while large accessible polyps are amendable for endoscopic excision through different polyp resection techniques. However, huge, complicated, non-accessible and suspicious polyps are indicated for surgical management or advanced endoscopic resection when appropriate. Clinicians and endoscopists should be aware about these facts when treating patients living in, immigrated from or visiting endemic areas.
Topics: Humans; Schistosomiasis; Praziquantel; Colon; Polyps
PubMed: 37475844
DOI: 10.3748/wjg.v29.i26.4156 -
The Turkish Journal of Gastroenterology... Jul 2020This study aimed to investigate the differences and relevance of various common duodenal diseases in different parts in the aspects of age, gender, helicobacter pylori... (Comparative Study)
Comparative Study
BACKGROUND/AIMS
This study aimed to investigate the differences and relevance of various common duodenal diseases in different parts in the aspects of age, gender, helicobacter pylori (H. pylori) infection, application of nonsteroidal anti-inflammatory drugs (NSAIDs), smoking, or alcohol consumption.
MATERIALS AND METHODS
The medical records of various duodenal diseases were collected and tested for difference using the χ2 test or the Fisher exact probability method.
RESULTS
1) The proportions of duodenal ulcer (DU), inflammation, and duodenal bulb diseases in the adult group (A) (47.98%, 36.70%, and 66.63%) were higher than those in the elderly group (E) (41.38%, 29.83%, and 56.82%), but the proportions of duodenal diverticulum (DD) and tumor diseases in the descending and ascending segments (2.95%, 1.43%, 9.14%, and 0.14%) were lower than those in group E (13.73%, 3.69%, 19.41%, and 0.76%) (p<0.001). 2) The positive rate of H. pylori (63.64%) in the duodenal bulb diseases was higher than that in the bulb-descending segment (53.75%), but the application rate of NSAIDs (16.44%) in the duodenal bulb-descending diseases was lower than that in the descending segment (24.81%) (p<0.001).
CONCLUSION
1) DU, inflammation, and duodenal bulb diseases are common in adults, but DD and tumor diseases in the descending and ascending segments are more common in the elderly. 2) Compared with the duodenal bulb-descending diseases, the application of NSAIDs has greater impact on the diseases in the descending segment, and the rate of H. pylori infection is higher in duodenal bulb diseases.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; Anti-Inflammatory Agents, Non-Steroidal; Chi-Square Distribution; China; Duodenal Diseases; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Sex Factors; Smoking; Young Adult
PubMed: 32897221
DOI: 10.5152/tjg.2020.18712 -
The Korean Journal of Gastroenterology... Jul 2022Symptom-based subtyping of functional dyspepsia (FD) is used to segregate patients into groups with homogenous pathophysiological mechanisms. This study examined whether...
BACKGROUND/AIMS
Symptom-based subtyping of functional dyspepsia (FD) is used to segregate patients into groups with homogenous pathophysiological mechanisms. This study examined whether subtyping could reflect the duodenal and gastric microinflammation in FD patients.
METHODS
Twenty-one FD patients without infection were recruited. An endoscopic biopsy was performed in the duodenum 2nd portion, stomach antrum, and body. The eosinophil and mast cell counts per high-power field (×40) were investigated by H&E and c-kit staining, respectively. The degree of inflammatory cell infiltration, atrophy, and intestinal metaplasia was also determined by H&E staining in the stomach. The baseline characteristics and eosinophil and mast cell infiltrations were compared among the three groups (epigastric pain syndrome, postprandial distress syndrome, and overlap).
RESULTS
According to the symptom assessment, seven subjects were classified into the epigastric pain syndrome group, 10 into the postprandial syndrome group, and four into the overlap group. The baseline variables were similar in the three groups. Eosinophil infiltration was more prominent in the duodenum than in the stomach. In contrast, mast cell infiltration was similar in the duodenum and stomach. The eosinophil counts in the duodenum were similar in the three groups. The eosinophil counts in the stomach and mast cell counts in the duodenum and stomach were also similar in the three groups.
CONCLUSIONS
Duodenal eosinophil infiltration was prominent in FD patients, but the eosinophil counts were similar regardless of the symptom-based subtypes of FD. Hence, the current symptom-based subtyping of FD does not reflect duodenal eosinophil and mast cell infiltration.
Topics: Abdominal Pain; Cell Count; Duodenum; Dyspepsia; Eosinophilia; Eosinophils; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Mast Cells
PubMed: 35879060
DOI: 10.4166/kjg.2022.036