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Gut Jun 1989The actions of hydrochloric acid, natural PGE1, PGE2 and a synthetic commercial PGE1 preparation, Enisoprost (Searle) on pepsinogen synthesis and secretion were studied...
The actions of hydrochloric acid, natural PGE1, PGE2 and a synthetic commercial PGE1 preparation, Enisoprost (Searle) on pepsinogen synthesis and secretion were studied in canine chief cell monolayer cultures. Hydrochloric acid, applied directly to the apical surface of chief cells using culture plate inserts (Millipore) had no effect on secretion, nor did it affect the action of any secretagogue in the basolateral medium. All prostaglandins tested showed significant stimulation of pepsinogen secretion. Basal secretion of pepsinogen after 90 min was 9.4 (1.3)% to total initial monolayer content. At 10(-6) M, PGE1 stimulated secretion was 26.1 (3.8)%; PGE2 27.9 (4)% and Enisoprost 28.8 (4.2)% of initial pepsinogen content. Stimulations by all tested prostaglandins were additive with carbachol (10(-4) M) and CCK (10(-9) M), but not with VIP (10(-6) M), dbcAMP (10(-3) M) or forskolin (10(-6) M) responses. All three prostaglandins stimulated pepsinogen synthesis as measured by 14C labelled amino acid incorporation into pepsinogen. Time course experiments were similar to those for forskolin and showed shorter time delays between stimulus and increased synthesis rate than carbachol but longer than dbcAMP. Stimulated pepsinogen secretion was inhibited by high pepsin concentrations (greater than 800 micrograms/ml) in the medium. The inhibited abolished simultaneous carbachol induced stimulation of synthesis but prostaglandin or forskolin stimulation only after two hours. Combined with the shorter response time, as compared with carbachol, these data support our previous findings that potent stimulators of cAMP production can stimulate pepsinogen synthesis directly by stimulation of mRNA synthesis, independently from an increased secretion. The additivity of effects with carbachol or CCK and similarity with forskolin stimulated synthesis supports the suggestion that the actions of prostaglandins are mediated by cAMP.
Topics: Animals; Cells, Cultured; Dogs; Gastric Mucosa; Hydrochloric Acid; Pepsinogens; Prostaglandins E
PubMed: 2753400
DOI: 10.1136/gut.30.6.774 -
BMC Cardiovascular Disorders Nov 2023Existing research has established the pepsinogen ratio (PGR) as a complex biomarker, not only as an independent predictor for various gastrointestinal diseases but also...
BACKGROUND
Existing research has established the pepsinogen ratio (PGR) as a complex biomarker, not only as an independent predictor for various gastrointestinal diseases but also in its association with atherosclerotic cardiovascular diseases. However, the precise mechanism linking changes in PGR to cardiovascular pathologies remains unclear. The objective of this study is to quantitatively elucidate the association between PGR and brachial-ankle pulse wave velocity (baPWV) as an indicator of atherosclerotic progression.
METHODS
We conducted a cross-sectional study that analyzed clinical data from 465 patients who underwent health screenings. One-way Analysis of Variance (ANOVA) identified potential risk factors affecting baPWV. Multiple logistic regression was employed to evaluate if PGR serves as an independent risk factor for elevated baPWV after accounting for these variables. Generalized additive models and smoothed curve fitting were utilized to investigate the possibility of a nonlinear association between PGR and baPWV. When such nonlinearity was found, threshold effect analysis pinpointed the inflection point in this relationship, followed by segmented correlation analyses.
RESULTS
PGR negatively correlated with both right baPWV (RbaPWV) and left baPWV (LbaPWV) after adjusting for confounders. Smoothed curve analyses revealed nonlinear relationships, with inflection points at 22.5 for RbaPWV and 22.3 for LbaPWV. For PGR values below 22.5, a significant negative correlation with RbaPWV was observed (β = - 6.3 cm/s, P < 0.001). Conversely, for PGR values above 22.5, no significant linear relationship was found (P = 0.141). Similarly, when PGR was below 22.3, a strong negative correlation with LbaPWV was detected (β = - 7.0 cm/s, P < 0.001), but such correlation was absent for higher PGR levels (P = 0.273).
CONCLUSION
The study reveals that PGR is associated with RbaPWV and LbaPWV in a nonlinear manner. Specifically, lower levels of PGR were linearly and inversely correlated with baPWV, but this relationship became nonlinear at higher PGR levels. These findings suggest that modulating PGR levels may offer a therapeutic strategy for managing atherosclerosis.
Topics: Humans; Ankle Brachial Index; Cross-Sectional Studies; Pepsinogen A; Pulse Wave Analysis; Atherosclerosis; Risk Factors; Vascular Stiffness
PubMed: 37986148
DOI: 10.1186/s12872-023-03618-9 -
International Journal of Cancer Apr 2012The correlation between low serum PG level and H. pylori infection with the development of gastric cancer has caused considerable concerns all over the world. Some...
Low serum pepsinogen I and pepsinogen I/II ratio and Helicobacter pylori infection are associated with increased risk of gastric cancer: 14-year follow up result in a rural Chinese community.
The correlation between low serum PG level and H. pylori infection with the development of gastric cancer has caused considerable concerns all over the world. Some authors exclaimed that gastric cancer developed only in patients infected with H. pylori, whereas the other had different findings. In this study, 1,501 adult local residents with determined serum PG levels and anti H. pylori IgG status were followed for 14 years for the development of gastric cancer in a rural community with high risk of gastric cancer in Hebei Province, China. The results showed the accumulated gastric cancer incidence in the subjects with abnormal PG level and those with H. pylori infection were all significantly higher than that in the corresponding normal controls (53.9‰ vs. 12.7‰, p < 0.05 and 23.1‰ vs. 5.93‰, p < 0.05). The highest gastric cancer incidence was seen in the subjects with both abnormal serum PG and positive H. pylori (56.0‰), and followed by the subjects with abnormal PG and negative H. pylori (47.6‰) and those with normal serum PG and positive H. pylori (18.4‰). The abnormal serum PG level (OR 3.029) and H. pylori infection (OR 4.345) were all risk factors for the development of gastric cancer. The results suggested that the subjects with abnormal serum PG level and/or positive H. pylori infection in the rural area of China were all high risk population for gastric carcinoma and the subjects with both abnormal serum PG and positive H. pylori infection were at especially high risk for the development of gastric carcinoma.
Topics: Adult; Asian People; Biomarkers, Tumor; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Risk Factors; Rural Population; Stomach Neoplasms
PubMed: 21547904
DOI: 10.1002/ijc.26172 -
Medicine Jan 2019Serum pepsinogen assay (sPGA) combining concentration of pepsinogen I (PG I), and the ratio of PG I/II is the noninvasive biomarker for predicting chronic atrophic...
BACKGROUND
Serum pepsinogen assay (sPGA) combining concentration of pepsinogen I (PG I), and the ratio of PG I/II is the noninvasive biomarker for predicting chronic atrophic gastritis (CAG) and neoplasms reflecting mucosal secretory status. Although various cut-off values have been suggested, PG I ≤70 ng/mL and PG I/II ≤3 have been widely accepted. However, previous studies for diagnostic test accuracy presented only pooled outcomes, which cannot discriminate the diagnostic validity of sPGA with cut-off of PG I ≤70 ng/mL and PG I/II ≤3.
METHODS
We will search the core databases [MEDLINE (through PubMed), the Cochrane Library, and Embase] from their inception to December 2018 by 2 independent evaluators. The P.I.C.O. is as follows; Patients: who have histologically proven CAG or gastric neoplasms, Intervention: sPGA with cut-off of PG I ≤70 ng/mL and/or PG I/II ≤3, Comparison: none, Outcome: diagnostic performance indices of sPGA for CAG and gastric neoplasms (sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios) (if, true/false positive, true/false negative values are presented, diagnostic performance indices will be calculated). All types of study design with full text will be sought and included. The risk of bias will be assessed using the QUADAS-2 tool. Descriptive data synthesis is planned and quantitative synthesis (bivariate and HSROC model) will be used if the included studies are sufficiently homogenous. Publication bias will be assessed.
RESULTS
The results will provide clinical evidence for diagnostic validity of sPGA.
CONCLUSION
This study will provide evidence of sPGA for predicting CAG and gastric neoplasms.
Topics: Biomarkers; Gastritis, Atrophic; Hematologic Tests; Humans; Meta-Analysis as Topic; Pepsinogen A; Pepsinogen C; Predictive Value of Tests; Research Design; Sensitivity and Specificity; Stomach Neoplasms; Systematic Reviews as Topic
PubMed: 30681610
DOI: 10.1097/MD.0000000000014240 -
PloS One 2022To investigate the clinical characteristics, risk factors, and predictors of esophagogastric variceal bleeding in patients with hepatitis C virus (HCV)-induced liver... (Comparative Study)
Comparative Study Observational Study
OBJECTIVES
To investigate the clinical characteristics, risk factors, and predictors of esophagogastric variceal bleeding in patients with hepatitis C virus (HCV)-induced liver cirrhosis.
METHODS
This comparative observational study was carried out on 100 patients suffering from post hepatitis cirrhosis and portal hypertension who were admitted to the Internal Medicine Department, Al-Azhar University Hospital, Damietta Egypt. Patients were classified into two groups: 50 of them presented with esophagogastric varices with acute variceal bleeding, and 50 patients presented without bleeding. Data were collected, coded, revised, and entered into the Stata software version 16.
RESULTS
The mean age of patients with bleeding was slightly higher than those without bleeding (55.58 ± 5.89 vs. 52.54 ± 9.01 years), p = 0.049. Mild ascites, positive H.Pylori, and Child-Pugh score B and C were an independent predictors of esophagogastric variceal bleeding (OR = 0.036, 95% CI: 0.0004-0.36; p = 0.005), (OR = 7.36, 95% CI: 1.44-37.59; p = 0.016), (OR = 19.0, 95% CI: 2.02-186.3; p = 0.010), and (OR = 40.51, 95% CI: 2.18-751.31; p = 0.013). The sensitivity of this model was 93.88%, specificity was 53.85%, PPV was 88.46%, NPV was 70.0%, correctly classified patients were 85.48%, and AUC was 90.27%. In the second model, pepsinogen level higher than 43.5 μg/l, AST (>54.5), Bilirubin (>1.45), and Hemoglobin (>11.5) were a significant independent predictors of esophagogastric variceal bleeding (OR = 1.18, 95% CI: 1.09-1.27; p<0.001), (OR = 1.14, 95% CI: 1.03-1.27; p = 0.007), (OR = 5.55, 95% CI: 1.21-25.43; p = 0.027), and (OR = 0.05, 95% CI: 0.008-0.32; p = 0.002), respectively. The sensitivity of this model was 92%, specificity was 98%, PPV was 97.87%, NPV was 92.45%, correctly classified patients were 95%, and AUC was 98.68%.
CONCLUSION
The independent predictors of esophagogastric variceal bleeding were ascites, positive H. pylori, Child-Pugh score B and C, pepsinogen level higher than 43.5 μg/l, AST (>54.5), bilirubin (>1.45), and hemoglobin (>11.5). Laboratory investigations are more reliable in predicting variceal bleeding and excluding non-variceal bleeding; however, clinical symptoms should not be neglected, especially H. pylori infection, ascites, and Child-Pugh score.
Topics: Ascites; Bilirubin; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Hepacivirus; Hepatitis C; Humans; Liver Cirrhosis; Pepsinogen A
PubMed: 36227871
DOI: 10.1371/journal.pone.0275373 -
Proceedings of the Japan Academy.... 2011The current status of screening for gastric cancer-risk (gastritis A, B, C, D) method using combined assay for serum anti-Helicobacter pylori (Hp) IgG antibody and serum... (Review)
Review
The current status of screening for gastric cancer-risk (gastritis A, B, C, D) method using combined assay for serum anti-Helicobacter pylori (Hp) IgG antibody and serum pepsinogen (PG) levels, "ABC method", was reviewed and the latest results of our ongoing trial are reported. It was performed using the following strategy: Subjects were classified into 1 of 4 risk groups based on the results of the two serologic tests, anti-Hp IgG antibody titers and the PG I and II levels: Group A [Hp(-)PG(-)], infection-free subjects; Group B [Hp(+)PG(-)], chronic atrophic gastritis (CAG) free or mild; Group C [Hp(+)PG(+)], CAG; Group D [Hp(-)PG(+)]), severe CAG with extensive intestinal metaplasia. Continuous endoscopic follow-up examinations are required to detect early stages of gastric cancer. Asymptomatic Group A, which accounts for 50-80% of all the subjects may be excluded from the secondary endoscopic examination, from the viewpoint of efficiency. Hp-infected subjects should be administered eradication treatment aimed at the prevention of gastric cancer.
Topics: Antibodies, Bacterial; Early Detection of Cancer; Helicobacter pylori; Humans; Immunoglobulin G; Pepsinogen A; Stomach Neoplasms
PubMed: 21785258
DOI: 10.2183/pjab.87.405 -
Journal of Epidemiology Apr 2019Practical criteria for the use of serum pepsinogen (PG) values in diagnosing Helicobacter pylori infection have not yet been determined.
BACKGROUND
Practical criteria for the use of serum pepsinogen (PG) values in diagnosing Helicobacter pylori infection have not yet been determined.
METHODS
The results of gastric endoscopies, H. pylori infection tests, and PG values were retrospectively reviewed. Subjects were assigned to groups, including never-infected (with neither infection nor gastric mucosal atrophy), infected (with atrophy or findings indicating infection in endoscopy and positive infection tests except for antibody tests), and ex-infected (with gastric mucosal atrophy and negative infection tests, except for antibody tests). The optimal criteria with combined use of the PG II concentrations and the PG I/PG II ratio were investigated separately for PG measurements obtained with the chemiluminescent magnetic particle immunoassay (CLIA) and latex agglutination (LA) methods, such that the specificity was greater than 70% and the sensitivity was no less than 95% among the never-infected and infected subjects. Similar analyses were performed by combining the data from ex-infected and infected subjects.
RESULTS
For the CLIA (LA) method, the optimal criterion among 349 (397) never-infected and 748 (863) infected subjects was a PG II value of at least 10 (12) ng/mL or a PG I/PG II ratio no more than 5.0 (4.0), which produced 96.3% (95.1%) sensitivity and 82.8% (72.8%) specificity. When 172 (236) ex-infected subjects were included, the optimal criterion was the same, and the sensitivity was 89.1% (86.9%).
CONCLUSIONS
The above criteria may be practical for clinical use, and PG tests using these criteria might prevent unnecessary endoscopic examinations for never-infected subjects.
Topics: Adult; Aged; Biomarkers; Case-Control Studies; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Pepsinogen A; Pepsinogen C; Retrospective Studies; Sensitivity and Specificity
PubMed: 30249942
DOI: 10.2188/jea.JE20170094 -
The Korean Journal of Internal Medicine May 2020
Topics: Atrophy; Early Detection of Cancer; Gastritis, Atrophic; Humans; Pepsinogen A; Stomach Neoplasms
PubMed: 32392661
DOI: 10.3904/kjim.2020.139 -
The Biochemical Journal Nov 1998The gastric aspartic proteinases (pepsin A, pepsin B, gastricsin and chymosin) are synthesized in the gastric mucosa as inactive precursors, known as zymogens. The... (Review)
Review
The gastric aspartic proteinases (pepsin A, pepsin B, gastricsin and chymosin) are synthesized in the gastric mucosa as inactive precursors, known as zymogens. The gastric zymogens each contain a prosegment (i.e. additional residues at the N-terminus of the active enzyme) that serves to stabilize the inactive form and prevent entry of the substrate to the active site. Upon ingestion of food, each of the zymogens is released into the gastric lumen and undergoes conversion into active enzyme in the acidic gastric juice. This activation reaction is initiated by the disruption of electrostatic interactions between the prosegment and the active enzyme moiety at acidic pH values. The conversion of the zymogen into its active form is a complex process, involving a series of conformational changes and bond cleavage steps that lead to the unveiling of the active site and ultimately the removal and dissociation of the prosegment from the active centre of the enzyme. During this activation reaction, both the prosegment and the active enzyme undergo changes in conformation, and the proteolytic cleavage of the prosegment can occur in one or more steps by either an intra- or inter-molecular reaction. This variability in the mechanism of proteolysis appears to be attributable in part to the structure of the prosegment. Because of the differences in the activation mechanisms among the four types of gastric zymogens and between species of the same zymogen type, no single model of activation can be proposed. The mechanism of activation of the gastric aspartic proteinases and the contribution of the prosegment to this mechanism are discussed, along with future directions for research.
Topics: Amino Acid Sequence; Animals; Chymosin; Digestion; Enzyme Precursors; Gastric Mucosa; Humans; Models, Molecular; Molecular Sequence Data; Pepsinogen A; Pepsinogen C; Protein Structure, Tertiary; Sequence Alignment; Sequence Homology, Amino Acid
PubMed: 9794784
DOI: 10.1042/bj3350481 -
Clinical and Translational... Oct 2020Noninvasive assessment of corpus atrophic gastritis (CAG), a condition at increased risk of gastric cancer, is based on the measurement of pepsinogens, gastrin, and... (Observational Study)
Observational Study
INTRODUCTION
Noninvasive assessment of corpus atrophic gastritis (CAG), a condition at increased risk of gastric cancer, is based on the measurement of pepsinogens, gastrin, and Helicobacter pylori antibodies. Parietal cell autoantibodies (PCAs) against the gastric proton pump (ATP4) are potential serological biomarkers of CAG. The purpose of this study was to compare the diagnostic performance of PCA and pepsinogen I tests in patients with clinical suspicion of CAG with the histopathological evaluation of gastric biopsies as reference standard.
METHODS
A prospective case-finding study was performed on 218 naive adult patients (131 women, median age 65 years) who underwent gastric biopsies to confirm/exclude CAG. Patients with histopathological CAG were defined as cases, conversely as controls. Autoantibodies against the individual alpha (ATP4A) and beta (ATP4B) subunits of ATP4 were measured by luciferase immunoprecipitation, and global PCA and pepsinogen I by enzyme-linked immunosorbent assay.
RESULTS
Histopathology classified 107 subjects (49%) as cases (CAG+, autoimmune 81.2%, and multifocal extensive 18.8%) and 111 subjects (51%) as controls (CAG-). In cases, ATP4A, ATP4B, and PCA titers were increased compared with controls, whereas pepsinogen I was reduced (P < 0.0001 for all). ATP4B, ATP4A, and pepsinogen I tests showed sensitivities of 77%, 75%, and 73% and specificities of 88%, 88%, and 80%, respectively. The receiver operating characteristic (ROC) area under the ROC curve (AUC) of these serological biomarkers confirmed their ability to discriminate cases from controls (ATP4B = 0.838, ATP4A = 0.826, pepsinogen I = 0.775, and PCA = 0.805), whereas the partial ROC-pAUC90 analysis showed that the ATP4B test had the best diagnostic performance (P = 0.008 vs ATP4; P = 0.0002 vs pepsinogen I). The presence of autoimmune or extensive gastritis was not significantly different between ATP4B positive or negative cases (P = 0.217).
DISCUSSION
PCAs are promising serological biomarkers for the identification of CAG in high-risk individuals, particularly in an autoimmune pattern but also in an extensive-multifocal atrophy pattern.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers; Biopsy; Case-Control Studies; Female; Gastric Mucosa; Gastritis, Atrophic; Gastroscopy; H(+)-K(+)-Exchanging ATPase; Humans; Male; Middle Aged; Parietal Cells, Gastric; Pepsinogen A; Prospective Studies; Young Adult
PubMed: 33031196
DOI: 10.14309/ctg.0000000000000240