Heterologous expression and function evaluation of Gloeobacter violaceus rhodopsin in Escherichia coli / 生物工程学报

Proton-pumping rhodopsin (PPR) is a simple photosystem widely distributed in nature. By binding to retinal, PPR can transfer protons from the cytoplasmic to the extracellular side of the membrane under illumination, creating a proton motive force (PMF) to synthesize ATP. The conversion of light into chemical energy by introducing rhodopsin into nonphotosynthetic engineered strains could contribute to promoting growth, increasing production and improving cell tolerance of microbial hosts. Gloeorhodopsin (GR) is a PPR from Gloeobacter violaceus PCC 7421. We expressed GR heterologously in Escherichia coli and verified its functional activity. GR could properly function as a light-driven proton pump and its absorption maximum was at 539 nm. We observed that GR was mainly located on the cell membrane and no inclusion body could be found. After increasing expression level by ribosome binding site optimization, intracellular ATP increased, suggesting that GR could supply additional energy to heterologous hosts under given conditions.

Comparison of 7- and 14-Day Eradication Therapy for Helicobacter pylori with First- and Second-Line Regimen: Randomized Clinical Trial

Efficacy of Dairy Free Diet and 6-Food Elimination Diet as Initial Therapy for Pediatric Eosinophilic Esophagitis: A Retrospective Single-Center Study / 대한소아소화기영양학회지

12 weeks) were 81.8%, 50.0%, and 55.1% for DFD, and 68.8%, 50.0%, and 40.0% for SFED. Response based on age ( 12 years) were 59.3%, 42.9%, and 67.5% for DFD, and 36.4%, 58.8%, and 72.7% for SFED. In patients treated with DFD, concomitant proton pump inhibitor (PPI) administration resulted in improved outcomes (p=0.0177). Bivariate regression analysis showed that PPI with diet is the only predictor of response (p=0.0491), however, there were no significant predictors on multiple regression analysis.CONCLUSION: DFD and SFED are effective first line therapies for EoE. DFD should be tried first before extensive elimination diets. Concomitant therapy with PPI's may be helpful.

Chronic use of proton pump inhibitors and the quantity of g, d, and ecl cells in the stomach / Uso crônico de inibidores de bomba de prótons e a quantidade de células g, d e ecl no estômago

ABSTRACT Background: Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells. Aim: To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection. Methods: Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands. Results: Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls. Conclusion: Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.

RESUMO Racional: A inibição ácida pelo uso crônico de inibidores de bomba de prótons e o possível aumento da gastrina podem ser seguidos de alterações na regulação da produção do ácido clorídrico. Ainda não está definido se o uso crônico altera a quantidade de células G, D e ECL no estômago ou a razão células G/D. Objetivo: Avaliar o número de células G - produtoras de gastrina -, células D - produtoras de somatostatina - e células ECL - produtoras de histamina -, em pacientes com uso crônico de inibidores de bomba de prótons, com ou sem infecção pelo Helicobacter pylori. Método: Trata-se de estudo retrospectivo avaliando 105 pacientes, 81 usadores crônicos de inibidores de bomba de prótons e 24 controles, através de biópsias com contagem das células G, D e ECL por estudo imunoistoquímico, de forma quantitativa onde havia maior número de células positivas por campo microscópico de grande aumento e em 10 glândulas. Resultados: Não houve diferença estatística comparando-se o número de células G, D e ECL. A razão entre as células G e D foi maior nos pacientes usadores crônicos de inibidores de bomba de prótons. Conclusão: O uso crônico de inibidores de prótons parece não interferir na contagem das células G, D e ECL, porém, interfere na razão entre as células G e D.

Risk of Peptic Ulcer Bleeding Associated with Helicobacter pylori Infection, Nonsteroidal Anti-inflammatory Drugs, and Low-dose Aspirin Therapy in Peptic Ulcer Disease: A Case-control Study

BACKGROUND/AIMS: The association between Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin therapy as a risk factor for peptic ulcer bleeding (PUB) remains unclear. This study investigated the risk of PUB associated with H. pylori infection and NSAID or low-dose aspirin therapy in patients with PUD. MATERIALS AND METHODS: This case-control study investigated 340 patients with PUB between 2012 and 2016. The control group comprised age and sex-matched patients with endoscopically documented non-bleeding ulcers. Using logistic regression analysis, the adjusted odds ratio (AOR) was calculated for the risk of PUB. RESULTS: Of the patients investigated, 57.9% in the study group and 51.8% in the control group were diagnosed with H. pylori infection (P=0.106). Logistic regression analysis showed synergistic interaction between H. pylori infection and low-dose aspirin therapy. Multivariate analysis showed that low-dose aspirin (AOR 3.92, P < 0.001), NSAIDs (AOR 2.98, P=0.001), warfarin (AOR 14.57, P=0.011), gastric ulcer (compared with duodenal ulcer) (AOR 1.65, P=0.01), and smoking (AOR 1.97, P=0.004) increased the risk of PUB compared with the risk of PUD. CONCLUSIONS: Both NSAIDs and aspirin are independent risk factors for bleeding in patients with PUD. Additionally, low-dose aspirin therapy concomitant with H. pylori infection produced a synergistic effect. Therefore, H. pylori eradication may be crucial in aspirin users. Moreover, a proton pump inhibitor should be prescribed in patients with a history of bleeding ulcers who need long-term NSAID treatment.

Is the Diagnostic Trial with Proton Pump Inhibitors Reasonable for School Age Children with Gastroesophageal Reflux Symptoms? / 대한소아소화기영양학회지

PURPOSE: On the basis of evidence, we aimed to reevaluate the necessity of the empirical proton pump inhibitor (PPI) trial for children with suspected gastroesophageal reflux disease (GERD). METHODS: We analyzed the frequency of GERD in 85 school-age children with gastroesophageal reflux (GER) symptoms, who received 24-hour esophageal pH monitoring and/or upper endoscopy. According to the reflux index (RI), the children were classified into normal (RI <5%), intermediate (5%≤ RI <10%), or abnormal (RI ≥10%) groups. RESULTS: Fifty six were female and 29 were male. Their mean age was 12.6±0.5 (±standard deviation) years (range: 6.8–18.6). The RI analysis showed that the normal group included 76 patients (89.4%), the intermediate group included 6 patients (7.1%), and the abnormal group included 3 patients (3.5%). The DeMeester score was 5.93±4.65, 14.68±7.86 and 40.37±12.96 for the normal, intermediate and abnormal group, respectively (p=0.001). The longest reflux time was 5.56±6.00 minutes, 9.53±7.84 minutes, and 19.46±8.35 minutes in the normal, intermediate, and abnormal group, respectively (p=0.031). Endoscopic findings showed reflux esophagitis in 7 patients. On the basis of the Los Angeles Classification of Esophagitis, 5 of these patients were included in group A, 1 patient, in group B and 1 patient, in group C. CONCLUSION: The incidence of GERD was very low in school-age children with GER symptoms. Therefore, injudicious diagnostic PPI trials would be postponed until the actual prevalence of GERD is verified in future prospective studies.

Validation of the Korean Version of the Gastroesophageal Reflux Disease Questionnaire for the Diagnosis of Gastroesophageal Reflux Disease

BACKGROUND/AIMS: The Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed and validated as a tool for the diagnosis of gastroesophageal reflux disease (GERD) in patients with gastrointestinal symptoms. However, the GerdQ and the cutoff value for determining GERD has not been validated in Korea. METHODS: Patients with symptoms suggestive of GERD were consecutively recruited. The Korean version of GerdQ was developed through a forward-backward translation process according to the cross-cultural adaptation method. Endoscopically documented esophagitis, abnormal results on 24-hour ambulatory pH recording with symptom association monitoring, or response to proton pump inhibitor treatment were used as diagnostic references for GERD. The reproducibility and test characteristics of the Korean version of GerdQ were assessed. RESULTS: A total of 149 patients with a median age of 55 years were analyzed. The intra-class correlation coefficient of 2 subsequently measured GerdQ scores was 0.651 (95% CI, 0.518–0.748). The cutoff value of 8 was found to have the highest sensitivity (64.9%; 95% CI, 56.2–73.7) and specificity (71.4%; 95% CI, 56.5–86.4) for the diagnosis of GERD. The questionnaire had a high positive predictive value (88.1%; 95% CI, 81.2–95.0), but a low negative predictive value (38.5%; 95% CI, 26.2–50.3) for GERD. Any symptom improvement on proton pump inhibitor treatment showed a sensitivity of 93.0% (95% CI, 88.3–97.7) and a specificity of 48.6% (95% CI, 32.0–65.1) for GERD. CONCLUSION: The Korean version of GerdQ is a useful complementary tool in the diagnosis of GERD.

Can proton pump inhibitors cause intestinal inflammation in children? / 소아과

No abstract available.

Influence of proton pump inhibitor therapy on intestinal inflammation assessed by fecal calprotectin in pediatric patients / 소아과

BACKGROUND: An increase in the numbers of patients with gastrointestinal symptoms has recently been observed. PURPOSE: To investigate the effects of proton pump inhibitor (PPI) therapy on intestinal inflammation in children and adolescents as confirmed by clinical manifestations and objectively assessed by fecal calprotectin (FC) level measurement. METHODS: Consecutive children (aged 3–18 years) who presented with gastrointestinal symptoms and were treated with or without PPI for at least 1 month were enrolled. Patients were divided into PPI and non-PPI groups. The PPI group was further subdivided by treatment duration and type of PPI used. Stool samples were collected for FC evaluation at baseline and after treatment and clinical data and FC levels were compared between the groups. RESULTS: Fifty-one patients (15 boys, 36 girls) were enrolled in the study. The PPI group included 37 patients, while the non-PPI group included 14 patients. Clinical symptoms were not significantly different. FC levels and laboratory results, including C-reactive protein levels, white blood cell count, and absolute neutrophil count, were not statistically different before versus after PPI treatment. After treatment, FC levels decreased to 8.1 mg/kg (-575.4 to 340.3 mg/kg) in the PPI group and increased to 5.6 mg/kg (-460.0 to 186.9 mg/kg) in the non-PPI group compared to those before treatment (P=0.841). The number of patients with increased FC levels was not significantly different between the 2 groups (48.6% vs. 64.3%, P=0.363), similar to that observed in patients with an FC level > 50 mg/kg (24.3% and 7.1%, P=0.250). PPI therapy type and duration did not affect the FC levels (P=0.811 and P=0.502, respectively). CONCLUSION: Although we aimed to confirm the evidence of intestinal inflammation due to PPI use in children and adolescents through clinical symptoms and FC measurement, no significant changes were observed.

Effects of Proton Pump Inhibitor for Laryngopharyngeal Reflux and Comorbid Chronic Rhinosinusitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Laryngopharyngeal reflux (LPR) is a prevalent condition with an increasing incidence, and several recent studies have reported the association of LPR with chronic rhinosinusitis (CRS). In this study, we studied the effect of proton-pump inhibitors (PPIs) on symptom improvement for LPR and comorbid CRS. SUBJECTS AND METHOD: Enrolled in the study from January 2017 to December 2017 were 164 patients (54 male, 110 female, mean age 48.8 years) who were diagnosed as LPR by reflux symptom index (RSI) or reflux finding scores (RFS) and comorbid CRS. Sino-Nasal Outcome Test (SNOT)-20 and Lund-Kennedy endoscopic scores were evaluated for CRS severity. The study group was divided into PPI treatment group (Ilaprazole 20 mg, once a day for 8 weeks) and non-treatment group. The RSI, RFS, SNOT-20, and Lund-Kennedy endoscopic scores were repeated at the end of treatment. RESULTS: Ninety-two patients were prescribed PPI and 72 patients were not. Initial RSI, RFS, SNOT-20, and Lund-Kennedy score did not differ between the two groups. RSI and RFS decreased significantly after eight weeks of PPI medication (p=0.002 and p<0.001, respectively). In the non-treatment group, only RFS showed statistically significant decrease. SNOT-20 and Lund-Kennedy endoscopic scores decreased significantly in the treatment group (p=0.005 and p<0.001, respectively) compared to the non-treatment group. CONCLUSION: The results of our study suggest that PPI treatment for 8 weeks was effective in reducing signs and symptoms of both LPR and CRS.

Gastro Oesophageal Reflux Disease Shadowing Anxiety Disorder Causing Prolonged Exposure to Proton Pump Inhibitor / 가정의학회지

Anxiety disorders are the most prevalent psychiatric disorders in the general population. The relationship between dyspepsia and particularly gastroesophageal reflux disease (GERD) and psychiatric comorbidity such as anxiety is poorly defined. However, GERD was noted to be strongly associated and often coincident in onset with generalized anxiety disorder in the community. In this paper, we report the case of an adult man who presented with severe weight loss and underlying GERD, and was later found to have an anxiety disorder as the cause of both.

Association of Proton Pump Inhibitor Use and Risk of Fracture Based on the National Health Insurance Sample Cohort Database (2002~2013)

OBJECTIVES: The purpose of this study was to investigate the association between fracture risk and proton pump inhibitor (PPI) use to establish evidence for defining high-risk groups of fracture among PPI users. METHODS: A case-control study was performed using the National Health Insurance Sample Cohort Database from January 2002 to December 2013. The cases included all incidences of major fractures identified from January 2011 to December 2013, and up to four controls were matched to each case by age, gender, osteoporosis, and Charlson comorbidity index. Conditional logistic regression was used to calculate the adjusted odds ratio (aOR) and associated 95% confidence interval (CI). RESULTS: Overall, 14,295 cases were identified, and 63,435 controls were matched to the cases. The aOR of fractures related to the use of PPIs was 1.06 (95% CI: 1.01–1.11). There was a statistically significant association between fracture and PPI use within 3 months of the last dose, and a trend of increasing fracture risk with increasing cumulative PPI dose. The risk of fracture was significantly higher in patients who took PPIs for more than 1 year during the 2-year observation period. CONCLUSION: Patients who have been using PPIs for more than 1 year should be warned about the risk of fracture during or at least 3 months after discontinuing the PPI.

Issues on the Stress Ulcer Prophylaxis Using Proton Pump Inhibitor in Intensive Care Unit / 대한소화기학회지

No abstract available.

Risk Factors of Multiple Gastric Polyps according to the Histologic Classification: Prospective Observational Cohort Study / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to determine the risk factors of multiple gastric polyps according to the histological classification of gastric polyps. METHODS: Subjects with multiple gastric polyps (at least three) during endoscopy were enrolled prospectively. They were assigned to a fundic gland polyp (FGP) group and hyperplastic polyp (HP) group based on a histological classification of gastric polyps. Helicobacter pylori (H. pylori) was confirmed by its histology. Serum gastrin was measured using the radioimmunoassay method. A questionnaire was taken regarding the intake of proton pump inhibitor and nonsteroidal anti-inflammatory drugs, alcohol, smoking history, and diet. RESULTS: Among the 60 subjects enrolled from 2015 to 2018 at Seoul National University Bungdang Hospital, 47 and 13 subjects were assigned to the FGP and HP groups, respectively. The H. pylori infection rate was 12.8% in the FGP group, which is lower than that in the HP group (69.2%, p<0.001). The gastrin level was higher in the HP group (194.7 pg/dL, range 50.6–387.8 pg/dL) than in the FGP group (57.4 pg/dL, range 24.8–79.0 pg/dL) (p=0.007). Histologically, neutrophil infiltration in the antrum and body of the stomach were higher in the HP group than in the FGP group (p=0.022 and p=0.030, respectively). In contrast, monocyte infiltration in the antrum and body of the stomach were higher in the FGP group than in the HP group (p=0.018 and p<0.001, respectively). CONCLUSIONS: HPs arise from inflammation caused by H. pylori. On the other hand, the FGP was not associated with H. pylori or environmental factors.

Virulence genes of Streptococcus mutans and dental caries

Streptococcus mutans is one of the important bacteria that forms dental biofilm and cause dental caries. Virulence genes in S. mutans can be classified into the genes involved in bacterial adhesion, extracellular polysaccharide formation, biofilm formation, sugar uptake and metabolism, acid tolerance, and regulation. The genes involved in bacterial adhesion are gbps (gbpA, gbpB, and gbpC) and spaP. The gbp genes encode glucan-binding protein (GBP) A, GBP B, and GBP C. The spaP gene encodes cell surface antigen, SpaP. The genes involved in extracellular polysaccharide formation are gtfs (gtfB, gtfC, and gtfD) and ftf, which encode glycosyltransferase (GTF) B, GTF C, and GTF D and fructosyltransferase, respectively. The genes involved in biofilm formation are smu630, relA, and comDE. The smu630 gene is important for biofilm formation. The relA and comDE genes contribute to quorum-sensing and biofilm formation. The genes involved in sugar uptake and metabolism are eno, ldh, and relA. The eno gene encodes bacterial enolase, which catalyzes the formation of phosphoenolpyruvate. The ldh gene encodes lactic acid dehydrogenase. The relA gene contributes to the regulation of the glucose phosphotransferase system. The genes related to acid tolerance are atpD, aguD, brpA, and relA. The atpD gene encodes F1F0-ATPase, a proton pump that discharges H⁺ from within the bacterium to the outside. The aguD gene encodes agmatine deiminase system and produces alkali to overcome acid stress. The genes involved in regulation are vicR, brpA, and relA.

Effectiveness of Autologous Platelet-Rich Plasma for the Healing of Ulcers after Endoscopic Submucosal Dissection

BACKGROUND/AIMS: Platelet-rich plasma (PRP) has been used for wound healing in various medical fields. The aim of this study was to evaluate the clinical efficacy and safety of local PRP injections after endoscopic submucosal dissection (ESD). METHODS: Patients were non-randomly divided into the following two groups: (1) control group in which patients were administered only an intravenous proton pump inhibitor (PPI), and (2) a study group in which patients were administered an intravenous PPI and a topical PRP injection. We assessed the reduction in the ulcer area and stage of the ulcer after the procedure (24 hours, 48 hours, and 28 days after endoscopic surgery). RESULTS: We enrolled 7 study and 7 control patients. In the study group, the rate of ulcer reduction was 59% compared to 52% in the control group (p=0.372), 28 days after ESD. There were 5 patients in the S stage and 2 patients in the H stage in the study group compared to no patient in the S stage and 7 patients in the H stage in the control group (p=0.05), 28 days after ESD. There were no serious complications in either group. CONCLUSIONS: The local injection of PRP is a safe and effective procedure for ulcer healing after ESD.

IgE-mediated allergy to proton pump inhibitors with both delayed and immediate onset

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. Incidence of drug hypersensitivity reactions (DHRs) to PPIs has been rising, presumably because of their increased consumption. Most DHR are IgE-mediated, with half of the reactions being anaphylactic. We describe the case of a Caucasian 50-year-old female patient referred to our allergy department after 2 episodes of anaphylaxis. The allergy work-up distinguished PPI as a cause of delayed onset (14 hours) and immediate onset (45 minutes) IgE-mediated DHR.

Proton pump inhibitor intake negatively affects the osseointegration of dental implants: a retrospective study

OBJECTIVES: This study sought to investigate the association between the systemic intake of proton pump inhibitors (PPI) and the early failure of dental implants. MATERIALS AND METHODS: A retrospective cohort study involving 1,918 dental implants in 592 patients (69 implants in 24 PPI users and 1,849 implants in 568 nonusers, respectively) was conducted. The effect of PPI intake on the osseointegration of dental implants was evaluated using patient- and implant-level models. RESULTS: Among 24 PPI users, two patients experienced implant failure, one of whom had three and the other of whom had one failed implant, respectively. Thus, the rate of failure for this population was 8.3%. Separately, 11 nonusers each experienced one implant failure, and the failure rate for these patients was 1.9%. Fisher's exact test revealed statistically significant differences between PPI users and nonusers at the implant level (P=0.002) but failed to show any significance at the patient level (P=0.094). The odds of implant failure were 4.60 times greater among PPI users versus nonusers. Dental implants that were placed in patients using PPIs were found to be 4.30 times more likely to fail prior to loading. CONCLUSION: The findings of this study suggest that PPI intake may be associated with an increased risk of early dental implant failure.

Diagnosis and Management of Functional Chest Pain in the Rome IV Era

Functional chest pain accounts for about a third of the patients with noncardiac chest pain. It is a very common functional esophageal disorder that remains even today a management challenge to the practicing physician. Based on the definition offered by the Rome IV criteria, diagnosis of functional chest pain requires a negative workup of noncardiac chest pain patients that includes, proton pump inhibitor test or empirical proton pump inhibitor trial, endoscopy with esophageal mucosal biopsies, reflux testing, and esophageal manometry. The mainstay of treatment are neuromodulators that are primarily composed of anti-depressants. Alternative medicine and psychological interventions may be provided alone or in combination with other therapeutic modalities.

Multicenter Prospective Study of Laparoscopic Nissen Fundoplication for Gastroesophageal Reflux Disease in Korea

BACKGROUNDS/AIMS: This multicenter study aims to evaluate the effect and feasibility of anti-reflux surgery compared with medical treatment for gastroesophageal reflux disease (GERD). METHODS: Patients with GERD who were undergoing medical treatment with proton pump inhibitors for more than 8 weeks and those who were scheduled to undergo anti-reflux surgery were enrolled. Efficacy of pre-operative medical treatment was evaluated retrospectively and effect of anti-reflux surgery was prospectively evaluated at 1 week and 3 months after surgery. Quality of life (QOL) was also investigated before and after surgery. RESULTS: Between February and October 2018, 51 patients underwent laparoscopic Nissen fundoplication for treating GERD at 5 hospitals in Korea. Thirty-four patients (66.7%) showed poor proton pump inhibitor response. At 3 months after surgery, heartburn was completely resolved in 87.9% patients and partially improved in 9.1%. Acid regurgitation was completely resolved in 82.9% and partially improved in 11.4%. Atypical extraesophageal symptoms were completely controlled in 45.5% and partially controlled in 36.4%. GERD-related QOL scores at 1 week after surgery significantly improved compared with pre-operative scores. There was no difference in GERD-related QOL scores between 1 week and 3 months after surgery. General QOL measured with European QOL-5 dimensions and health-related QOL instrument with 8 items significantly improved after anti-reflux surgery. Satisfaction with treatment was significantly higher after surgery than before surgery (72.5% vs 11.8%, P < 0.001). CONCLUSION: Anti-reflux surgery improved GERD symptoms and QOL in patients. Anti-reflux surgery is an effective treatment option compared with medical treatment for GERD patients selected for surgical treatment.