Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K⁺ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T₀)and 1(T₁),2(T₂),3(T₃),4(T₄),5(T₅),6(T₆),and 7 h(T₇)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K⁺ in the diazepam,midazolam,and control groups increased during T₁-T₇ compared with those at T₀(all P<0.01).The concentration of K⁺ in diazepam and midazolam groups during T₁-T₄ was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.
Midazolam ; Helicobacter pylori ; Urease ; Clarithromycin/pharmacology* ; Benzodiazepines/pharmacology* ; Diazepam/pharmacology* ; Amoxicillin ; Water ; Anti-Bacterial Agents/pharmacology*

Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.
Animals ; Helicobacter pylori ; Urease/genetics* ; Helicobacter Infections/prevention & control* ; Vaccines ; Membrane Proteins

Microbial induced calcium carbonate precipitation (MICP) refers to the natural biological process of calcium carbonate precipitation induced by microbial metabolism in its surrounding environment. Based on the principles of MICP, microbial cement has been developed and has received widespread attention in the field of biology, civil engineering, and environment owing to the merits of environmental friendliness and economic competence. Urease and carbonic anhydrase are the key enzymes closely related to microbial cement. This review summarizes the genes, protein structures, regulatory mechanisms, engineering strains and mutual synergistic relationship of these two enzymes. The application of bioinformatics and synthetic biology is expected to develop biocement with a wide range of environmental adaptability and high performance, and will bring the MICP research to a new height.
Calcium Carbonate/metabolism* ; Chemical Precipitation ; Urease/metabolism*

BACKGROUND/AIMS: The incidence of gastric cancer (GC) in Korea is very high compared to that in other countries. The aim of this study was to investigate the trends of GC in patients for over 16 years. MATERIALS AND METHODS: A total of 1,227 patients with GC were prospectively enrolled at Seoul National University Bundang Hospital between 2003 and 2018. Age, sex, histologic type (Lauren classification), and Helicobacter pylori (H. pylori) infection status were compared between three periods (2003~2007, 2008~2012, and 2013~2018). H. pylori infection status was evaluated based on histology, rapid urease test, culture, serology, and history of H. pylori eradication. Patients with severe atrophy or intestinal metaplasia based on histology were assumed to have previous H. pylori infection. RESULTS: Most patients with GC underwent endoscopic mucosal resection/endoscopic submucosal dissection or another type of surgery. Early GC (EGC) and advanced GC (AGC) were detected in 769 (62.7%) and 458 (37.3%) patients, respectively, and intestinal and diffuse types were detected in 714 (58.2%) and 485 (39.5%) patients, respectively. The prevalence of EGC increased from 54.0% (252/467) to 63.5% (359/565) to 81.0% (158/195) in 2003~2007, 2008~2012, and 2013~2018, respectively. The prevalence of H. pylori-positive GC decreased from 93.4% (436/467) to 88.5% (500/565) to 82.1% (160/195) during these three periods, respectively (P<0.001). Multivariate logistic analysis showed that diffuse-type GC was continuously more prevalent in those who were younger than 50 years, who were female, and who harbored the predominant AGC type. CONCLUSIONS: Over 16 years, the prevalence of EGC increased with a decrease in H. pylori infection rate. Diffuse-type GC was continuously more common in young and female patients.
Atrophy ; Female ; Helicobacter pylori ; Humans ; Incidence ; Korea ; Metaplasia ; Prevalence ; Prospective Studies ; Seoul ; Stomach Neoplasms ; Urease

PURPOSE: Because of the inconsistent symptoms associated with Ureaplasma infections, their clinical significances in genitourinary tracts are under debate. Therefore, we evaluated the presence of Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) in urine samples and examined their associations with chronic prostatitis (CP) through a case and control study. MATERIALS AND METHODS: We included 696 nonchlamydial nongonococcal (NCNG) urine samples from men; 350 were categorized into non-inflammatory CP, 88 in inflammatory CP, and 258 in non-CP group. We amplified a region in the Ureaplasma urease areas from these samples and determined their biovars using the Sanger method. RESULTS: Among the NCNG population, the rates of UU, UP, and non-UU/UP were 3.88%, 6.46%, and 89.66%, respectively. The overall infection rates of non-CP, inflammatory CP, and non-inflammatory CP groups were 4.15%, 6.10%, and 3.65% in UU (p=0.612) and 6.85%, 7.22%, and 6.50% in UP (p=0.968), respectively. UU infection increased the risk of white blood cell (WBC) counts (≥5) in urine (p=0.005). In contrast, UP infections did not increase the risks of urethritis. Re-analysis from the 633 men who were excluded from urethritis effects did not reveal the associations between UU infection and the clinical characteristics of CP. Furthermore, the profiles from the National Institutes of Health-Chronic Prostatitis Symptom Index questionnaire and WBC counts in expressed prostatic secretion were similar among the non-CP and the two CP groups in each Ureaplasma infection. CONCLUSIONS: We found that UU may induce male urethritis. However, Ureapalsma species in urine were not definitively associated with the occurrence of CP.
Academies and Institutes ; Case-Control Studies ; Humans ; Leukocytes ; Male ; Methods ; Prostate ; Prostatitis ; Ureaplasma Infections ; Ureaplasma urealyticum ; Ureaplasma ; Urease ; Urethritis

Ethyl carbamate (EC), a carcinogenic and teratogenic chemical that is widely distributed in various alcoholic beverages, has attracted much attention. Microbial enzymatic degradation of EC in rice wine is always efficient and attractive. In this review, we summarize the research progress and problems of microbial enzymatic elimination of EC in rice wine from three aspects: the mechanisms of EC formation in rice wine, the research progress of acid urease, and the research progress of urethanase. Then, we propose the corresponding strategies to solve the problems: screening new urethanase with satisfied enzyme properties, food-grade expression and directed evolution of the bifunctional Fe³⁺-dependent acid urease and acid urease used in combination with urethanase to eliminate both urea and EC in rice wine.
Oryza ; Urea ; Urease ; Urethane ; Wine

Urease decomposes urea to ammonia, and has application potential in agriculture and medical treatment. Urease proteins include structural proteins (UreA, UreB and UreC) and accessory proteins (UreD/UreH, UreE, UreF and UreG), each of them has its own unique role in urease maturation. The structural proteins form the active center of urease, and the accessory proteins are responsible for the delivery of nickel. We review here the structure and function of bacterial urease complexes, and how each protein interacts to complete the activation process. We hope to provide theoretical basis for the regulation of urease activity and the development of urease inhibitors.
Bacterial Proteins ; Nickel ; Urease ; metabolism

BACKGROUND/AIMS: The Helicobacter pylori (H. pylori) eradication rate of standard triple therapy is unsatisfactory in Korea, and sequential therapy (SQT) has been suggested to be a practical first-line alternative regimen. The aim of this prospective study was to document changes in annual eradication rates of SQT. METHODS: A total of 983 H. pylori-positive subjects were enrolled from 2010 to 2018 and their data were subjected to intention-to-treat (ITT) and per-protocol (PP) analysis. All subjects received 10-day sequential therapy consisting of 40 mg esomeprazole and 1 g amoxicillin b.i.d for 5 days followed by 40 mg esomeprazole b.i.d, 500 mg clarithromycin b.i.d and 500 mg metronidazole t.i.d for 5 days. The 13C-urea breath test, rapid urease test (CLO test®), and histology were used to confirm eradication. Compliance and side effects were also investigated. RESULTS: ITT and PP eradication rates of SQT were 69.9% (687 of 983) and 87.1% (657 of 754), respectively. The annual eradication rate of ITT remained consistent over the 8-year study period (p for trend=0.167), whereas PP analysis showed the eradication rate increased (p for trend=0.042). The overall adverse event rate for SQT was 41.7% (410 subjects). CONCLUSIONS: Despite high antibiotic resistance rates in Korea, the eradication rate of SQT did not decrease over the 8-year study period.
Amoxicillin ; Breath Tests ; Clarithromycin ; Compliance ; Drug Resistance, Microbial ; Esomeprazole ; Helicobacter pylori ; Helicobacter ; Intention to Treat Analysis ; Korea ; Metronidazole ; Prospective Studies ; Urease

BACKGROUND/AIMS: Both bismuth-containing quadruple therapy and moxifloxacin-containing triple therapy have been suggested as second-line eradication therapy for Helicobacter pylori (H. pylori) infection. We aimed to evaluate the efficacy of 14-day moxifloxacin-containing triple therapy (14-EAM) in second-line H. pylori eradication in comparison to 7-day bismuth-containing quadruple therapy (7-RBMT). METHODS: From January 2011 to December 2015, a total of 569 patients who failed to respond to first-line triple therapy and who subsequently received second-line 7-RBMT or 14-EAM were retrospectively enrolled. The eradication rates were identified using per-protocol (PP) analysis. H. pylori eradication was confirmed by a 13C-urea breath test (UBiT-IR300®; Otsuka Electronics, Co., Ltd., Osaka, Japan) or a rapid urease test (CLOtest®; Delta West, Bentley, Australia) at least 4 weeks after completion of eradication therapy. RESULTS: A total of 487 and 82 patients received 7-RBMT and 14-EAM, respectively. PP eradication rates were 93.6% (366/391; 95% CI, 91.0–95.9%) with 7-RBMT and 73.8% (48/65; 95% CI, 63.1–84.6%) with14-EAM (p < 0.001). Therefore, the eradication rates with 7-RBMT were significantly higher than with 14-EAM according to the PP analysis. The adverse event rate was 17.1% (67/391) with 7-RBMT and 7.7% (5/65) with 14-EAM (p=0.065). In terms of risk factors, multivariate analysis revealed that 14-EAM (OR, 5.47; 95% CI, 2.74–10.93) was related to H. pylori eradication failure. CONCLUSIONS: 7-RBMT may be an effective second-line therapy in patients who failed to respond to first-line triple therapy in Korea, where there is a high prevalence of H. pylori infection.
Bismuth* ; Breath Tests ; Disease Eradication ; Helicobacter pylori* ; Helicobacter* ; Humans ; Korea ; Multivariate Analysis ; Prevalence ; Retrospective Studies ; Risk Factors ; Urease

BACKGROUND/AIMS: The current standard regimen for the treatment of Helicobacter pylori infection is a combination of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin. The aim of this study was to determine the effectiveness of PPIs taken separately before a meal for the treatment of H. pylori infection. MATERIALS AND METHODS: This retrospective study included 160 patients who were tested positive for rapid urease in Kosin Unversity Gospel Hospital between January 2008 and December 2012. The patients were divided into two groups (n=80 in each group) based on the method of administration of the H. pylori triple therapy. Group A took a PPI before a meal and amoxicillin and clarithromycin after a meal. Group B took all three medications together after a meal. The 13C-urea breath test was performed after 4 weeks to assess the eradication of H. pylori. RESULTS: H. pylori was eradicated in 58/80 (72.5%) patients in group A and 60/80 (75.0%) patients in group B, with no significant difference between the groups (P=0.719). Adverse effects occurred in 4 patients of group A and 7 patients of group B (5.0% and 8.8%, respectively); however, the difference between the groups was not significant (P=0.232). CONCLUSIONS: Administration of all medicines at once after a meal may be the better prescription for treatment, considering patient convenience and improved likelihood of compliance.
Amoxicillin ; Breath Tests ; Clarithromycin ; Compliance ; Helicobacter pylori ; Helicobacter ; Humans ; Meals ; Methods ; Prescriptions ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Retrospective Studies ; Urease