Inhibitory Effects and Mechanisms of Three Benzodiazepines on Helicobacter pylori / 中国医学科学院学报

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.

Research progress of Helicobacter pylori vaccine / 细胞与分子免疫学杂志

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.

Determinación de Helicobacter spp. en mucosa gástrica glandular de muías a través de la prueba de la actividad de la ureasa e histopatología / Determination of Helicobacter spp. in glandular gastric mucosa of mules through the test of urease activity and histopathology

RESUMEN La información sobre la presentación y los factores predisponentes del síndrome de úlcera gástrica en mulas (SUGM) es escasa en comparación con el síndrome de úlcera gástrica en equinos (SUGE) y asnales. Debido a la naturaleza multifactorial de este síndrome, la helicobacteriosis ha sido estudiada en otras especies. El objetivo de este trabajo fue establecer la presencia de Helicobacter spp. en mucosa gástrica de mulas a través de la prueba rápida de la ureasa (PRU) y de análisis histopatológico. Menos del 27% de las muestras reaccionaron a la PRU, con tiempos prolongados de reacción, y al Agar Urea (prueba de oro), con menor porcentaje de positividad. La histopatología reveló procesos inflamatorios crónicos, sin presencia de bacterias curvoespiraladas. Las PRU no fueron conclusivas en la determinación de Helicobacter spp., comportamiento similar reportado en equinos. Se requieren exámenes diagnósticos más específicos y procedimientos complementarios orientados a explorar por regiones del estómago en la consideración del número de muestras representativas.

ABSTRACT Information on the presentation and predisposing factors of Mule Gastric Ulcer Syndrome (MGUS) is scarce, compared to Equine Gastric Ulcer Syndrome (EGUS) and donkeys. Within the multifactorial nature of this syndrome, helicobacteriosis has been studied in other species. The objective of this work was to establish the presence of Helicobacter spp. in gastric mucosa of mules, through the rapid urease test (RUT) and histopathological analysis. Less than 27% of the samples reacted to RUTs, with prolonged reaction times, and Urea Agar (gold test), with a lower percentage of positivity. Histopathology revealed chronic inflammatory processes, without the presence of curved-spiral bacteria. The RUTs were not conclusive in the determination of Helicobacter spp., a similar behavior reported in horses. More specific diagnostic tests and complementary procedures are required to explore the regions of the stomach in consideration of the number of representative samples.

Advances of enzymes related to microbial cement / 生物工程学报

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.

Amplification of urea detection based on pH-sensitive liposomes

BACKGROUND: This study aimed to develop an amplification method of urea detection based on pHsensitive liposomes. RESULTS: The urease covalently immobilized on the magnetic particles and the pH-sensitive liposomes encapsulating ferricyanide were added to the cyclic-voltammeter cell solution where urea was distributed. The conversion of urea into carbonic acid seemed to induce a pH decrease that caused a reduction in the electrostatic repulsion between the headgroups of weakly acidic 1,2-dipalmitoyl-sn-glycero3-succinate. The reduction induced the liposomes to release potassium ferricyanide that was encapsulated inside. The effects of urea concentration and pH value were investigated. A specific concentration (0.5 mg/mL) of the urea solution was set to observe the response. The activity of urease was reversible with respect to the pH change between 7 and 5. The sensitivity of this detection was almost identical to the comparable techniques such as an enzyme-linked immunosorbent assay and a field-effect transistor. CONCLUSIONS: In summary, the methodology developed in this study was feasible as a portable, rapid, and sensitive method.

First genome sequence of Chilean Brucella canis SCL strain provides insights on the epidemiology and virulence factors, explaining differences between geographical origins

BACKGROUND: Brucella canis is the etiological agent of canine brucellosis, a worldwide neglected zoonosis that constitutes one of the major infectious causes of infertility and reproductive failure in dogs. Although genomic information available for this pathogen has increased in recent years, here we report the first genome sequencing of a B. canis strain in Chile, and the differences in virulence genes with other B. canis strains. RESULTS: Genome assembly produced a total length of 3,289,216 bp, N50 of 95,163 and GC% of 57.27, organized in 54 contigs in chromosome I, and 21 contigs in chromosome II. The genome annotation identified a total of 1981 CDS, 3 rRNA and 36 tRNA in chromosome I, and 1113 CDS and 10 tRNA in chromosome II. There is little variation between the different strains and the SCL isolate. Phylogenetic analysis showed that the Chilean SCL strain is closely related to B. canis and B. suis strains. Small differences were found when compared to the Serbian isolate, but all strains shared the same recent common ancestor. Finally, changes in the sequence of some virulence factors showed that the SCL strain is similar to other South American B. canis strains. CONCLUSIONS: This work sequenced and characterized the complete genome of B. canis strain SCL, evidencing the complete presence of all the genes of the virB operon, and minor changes in outer membrane proteins and in the urease operon. Our data suggest that B. canis was introduced from North America and then spread throughout the South American continent.

Acurácia diagnóstica entre teste rápido da urease e estudo histopatológico para detecção de Helicobacter pylori / Diagnostic accuracy of urease quick test compared to histopathological study for Helicobacter pylori detection

Objetivo: Analisar a acurácia do teste rápido da urease para detecção de Helicobacter pylori comparado com o exame histopatológico. Métodos: Estudo prospectivo e descritivo realizado de abril de 2018 a maio de 2019 em um Serviço de Endoscopia e Biliopancreática e em um laboratório de patologia. A amostra foi composta de 64 pacientes, de ambos os sexos, com idade de 35 a 81 anos, que apresentavam queixas dispépticas. Foram realizados exame histopatológico e teste rápido da urease. Os dados foram analisados pelo R Core team 2019 e submetidos a análises descritivas (variáveis categóricas) e inferenciais (teste de associação de qui-quadrado de Pearson e teste de Mann-Whitney). O nível de significância adotado foi de 5%. Resultados: O teste rápido da urease demonstrou que dez pacientes foram verdadeiros-positivos, 39 verdadeiros-negativos, três falsos-positivos, 12 falsos-negativos, com sensibilidade de 45,4% (25,1% a 67,3%), especificidade de 92,9% (79,4% a 98,1%), valor preditivo positivo de 76,9% (45,9% a 93,8%), valor preditivo negativo de 76,5% (62,2% a 86,7%), acurácia de 76,6% (64,0% a 85,9%), razão de chance diagnóstica 10,8 (2,56 a 45,9), índice de Youden 0,38 (0,16 a 0,60) e taxa de erro de 23,4% (14,1% a 36,0%). Conclusão: O teste rápido da urease apresentou baixa capacidade de detectar pacientes infectados, menor acurácia em relação ao estudo anatomopatológico e alta especificidade. O teste pode ser útil no momento da realização da endoscopia, por fornecer resultado rápido e barato para detectar H. pylori. O diagnóstico da bactéria apresenta maior confiabilidade com a realização dos dois métodos para pesquisa de H. pylori.

Objective: To analyze the accuracy of the rapid urease test for Helicobacter pylori detection when compared with the histopathological examination. Methods: This is a prospective and descriptive study conducted from April 2018 to May 2019, at an Endoscopy and Biliopancreatic Service and in a pathology laboratory. The sample consisted of 64 male and female patients aged 35 to 81 years old with dyspeptic complaints. Histopathological examination and rapid urease test were performed. Data were analyzed by R Corel team 2019 and underwent descriptive (categorical variables) and inferential (Pearson's Chi-squared association test and Mann-Whitney test) analyzes. The significance level adopted was 5%. Results: The rapid urease test showed that ten patients were true positive, 39 true negative, three false-positive, and 12 false-negative, and sensitivity was of 45.4% (25.1% to 67.3%), specificity 92.9% (79.4% to 98.1), positive predictive value of 76.9% (45.9-93.8%), negative predictive value of 76.5% (62.2% to 86.7%), accuracy of 76.6% (64.0% to 85.9%), diagnostic odds ratio of 10.8 (2.56% to 45.9), Youden index 0.38 (0.38% to 0.60), and error rate 23.4 (14.1% to 36.0%). Conclusion: The rapid urease test showed low ability to detect infected patients, lower accuracy compared to the pathological study, and high specificity. The test may be useful at the time of endoscopy, as it provides a quick and inexpensive result to detect H. pylori. The diagnosis of the bacterium is more reliable when both methods for H. pylori investigation are performed

Fatores de virulência e susceptibilidade a antifúngicos de Cryptococcus Spp / Virulence factors and susceptibility to Cryptococcus Spp. antifungals

Criptococose é uma doença grave que afeta tanto imunocomprometidos quanto imunocompetentes, com isso analisar a virulência é fundamental para novas terapêuticas. Objetivo: Analisar a capacidade de virulência e susceptibilidade aos antifúngicos de Cryptococcus spp. isolados de líquor de pacientes de hospital do norte do Paraná. Métodos: A partir de dois isolados clínicos C. neoformans e C. gattii, realizou-se a confirmação da identificação. Para a virulência, avaliou-se o tamanho da cápsula, capacidade de sobrevivência após exposição a neutrófilos, produção de melanina e urease. No antifungigrama por difusão em disco utilizou-se: anfotericina B, cetoconazol, voriconazol, itraconazol e miconazol. Resultados: C. gattii destaca-se por maior desenvolvimento da cápsula além da melhor capacidade de sobreviver a fagocitose em relação ao C. neoformans. No antifungigrama, ambos os isolados se apresentam sensíveis às drogas estudadas. Conclusão: Esses achados contribuem para a compreensão das diferentes patogêneses entre C. gattii e C. neoformans.

Cryptococcosis is a serious disease that can affect both immunocompromised and immunocompetent individuals, thus the virulence analysis is fundamental for the development of new treatments. Objective: To analyze the virulence and susceptibility of Cryptococcus spp. isolated from cerebrospinal fluid of patients from a hospital in the north of Paraná. Methods: From two clinical isolates, C. neoformans and C. gattii were confirmed and identified. For virulence, capsule size, survival capacity after exposure to neutrophils, melanin production and urease were evaluated. In the disc-diffusion method, the following antifungals were used: amphotericin B, ketoconazole, voriconazole, itraconazole and miconazole Results: It was observed that C. gattii presents greater results for development of the capsule beside presenting the best ability to survive phagocytosis in relation to C. neoformans. In the disc-diffusion method, both isolates presented sensitivity to the studied drugs. Conclusion: These findings contribute to the understanding of the different pathogens between C. gattii and C. neoformans.

Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Enzyme inhibition and antibacterial potential of 4-Hydroxycoumarin derivatives

The 4-Hydroxycoumarin derivatives are known to show a broad spectrum of pharmacological applications. In this paper we are reporting the synthesis of a new series of 4-Hydroxycoumarin derivatives synthesized through Knovenegal condensation; they were characterized by using UV-Vis, FT-IR, NMR spectroscopies. The synthesized compounds were evaluated for antibacterial activity against Staphylococcus aureus and Salmonella typhimurium strains. The compounds (2), (3) and (8) showed favorable antibacterial activity with zone of inhibitions 26.5± 0.84, 26.0 ± 0.56 and 26.0 ± 0.26 against Staphylococcus aureus (Gram-positive) respectively. However, the compounds (5) and (9) were found more active with 19.5 ± 0.59 and 19.5 ± 0.32 zone of inhibitions against Salmonella typhimurium (Gram-negative). Whereas, in urease inhibition assay, none of the synthesized derivatives showed significant anti-urease activity; although, in carbonic anhydrase-II inhibition assay, the compound (2) and (6) showed enzyme inhibition activity with IC50 values 263±0.3 and 456±0.1, respectively.

Diagnóstico de infección por Helicobacter pylori mediante test de aliento con urea C-14 en población ecuatoriana / Diagnosis of Helicobacter pylori infection by C-14 urea breath test in Ecuadorian population

siendo el test de aliento con urea carbono-14 (C-14) uno de los métodos de diagnóstico no invasivos; sin embar-go, no ha sido comprobada su utilidad en la población ecuatoriana.Objetivo: Evaluar la sensibilidad y especificidad del test de aliento con urea C-14 para predecir la infección por HP en la población ecuatoriana.Métodos: Estudio de Pruebas Diagnósticas realizado en pacientes que acudieron a la consulta externa del servicio de gastroenterología del Hospital Teófilo Dávila de la ciudad de Machala, en el periodo abril 2018 a marzo 2019. Los pacientes se sometieron a una endoscopia superior de luz blanca (ES) con toma de biopsias para investigar la infec-ción por HP; además, se realizó un test de aliento con urea C-14, para compararla con los resultados de las biopsias.Resultados: Se estudiaron 78 pacientes con una edad media de 33.76±11.2 años. El diagnóstico de gastritis se confirmó a través de la ES e histopatología en el 100% de los pacientes. El test de aliento con urea C-14 fue positi-va en 47/78 (60.3%) pacientes. Se demostró evidencia de infección por HP en biopsias gástricas de 50/78 (64.1%) pacientes. La sensibilidad, especificidad, VPP, VPN, observada y la concordancia entre evaluadores fue de 94%, 100%, 100%, 90%, 96% y 92% (P <0.001), respectivamente.Conclusiones: El test de aliento con urea C-14, es una herramienta útil para predecir infección por HP en la población ecuatoriana

Background: Early detection of Helicobacter pylori infection has become more relevant, with urea carbon-14 (C-14) breath test as one of the non-invasive diagnostic methods; however, it has not been proven in Ecuadorian population.Objective: To evaluate the sensitivity and specificity of the C-14 urea breath test to predict HP infection in the Ecuadorian population.Methods: : Study of diagnostic tests performed on patients who attended the outpatient gastroenterology service of the Hospital Teófilo Dávila in the city of Machala, in the period April 2018 to March 2019. The patients underwent an upper endoscopy of white light (WLE) with biopsies taken to investigate HP infection. In addition, a breath test with C-14 urea was performed to compare it with the biopsies results.Results: 78 patients with a mean age of 33.76±11.2 years were studied. The diagnosis of gastritis was confirmed through endoscopy and histopathology in 100% of the patients. The breath test with urea C-14 was positive in 47/78 (60.3%) patients. Evidence of HP infection was demonstrated in gastric biopsies from 50/78 (64.1%) pa-tients. Sensitivity, specificity, PPV, NPV, and inter-rater reliability were 94%, 100%, 100%, 90%, 96%, and 92% (P <0.001), respectively.Conclusions: The C-14 urea breath test is a useful tool for predicting HP infection in the Ecuadorian population

Gênero, idade, achados endoscópicos, urease e Helicobacter pylori: ausência de correlação dentro de uma amostra de população com alta prevalência de câncer gástrico na Amazônia / Gender, age, endoscopic findings, urease and helicobacter pylori: all uncorrelated within a sample of a high gastric cancer prevalence population in amazon

ABSTRACT BACKGROUND: It is widely assumed that gender, age, gastritis and Helicobacter pylori , all have some degree of correlation and, therefore, can synergistically lead to the development of gastric cancer. OBJECTIVE: In this cross-sectional study, we expected to observe the above mentioned correlation in the analysis of medical records of 67 patients of both sexes (female, n=44), mean age ± standard deviation: 41±12 years old, all from Belém (capital of Pará State, Brazilian Amazon), a city historically known as one with the highest gastric cancer prevalence in this country. METHODS: All patients were submitted to upper gastrointestinal endoscopy for gastric biopsy histopathological analysis and rapid urease test. All diagnoses of gastritis were recorded considering its topography, category and the degree of inflammatory activity, being associated or not associated with H. pylori infection. RESULTS: The results show that no statistically relevant associations were found among the prevalences of the observed variables. CONCLUSION: The authors hypothesize that observed risk factors associated to gastric cancer might be lesser synergistic than is usually expected.

RESUMO CONTEXTO: É amplamente assumido que gênero, idade, gastrite e Helicobacter pylori , todos têm algum grau de correlação e, portanto, podem sinergicamente levar ao desenvolvimento de câncer gástrico. OBJETIVO: Neste estudo transversal, esperamos observar a correlação acima mencionada na análise de prontuários de 67 pacientes de ambos os sexos (sexo feminino, n=44), média de idade ± desvio padrão: 41±12 anos, todos de Belém (capital do Estado do Pará, Amazônia Brasileira), uma cidade historicamente conhecida como sendo uma das que apresenta maior prevalência de câncer gástrico no país. MÉTODOS: Todos os pacientes foram submetidos à endoscopia digestiva alta para análise histopatológica da biópsia gástrica e teste rápido da urease. Todos os diagnósticos de gastrite foram registrados considerando sua topografia, categoria e grau de atividade inflamatória, sendo associada ou não associada à infecção por H. pylori . RESULTADOS: Os resultados mostram que não foram encontradas associações estatisticamente relevantes entre as prevalências das variáveis observadas. CONCLUSÃO: Os autores levantam a hipótese de que os fatores de risco associados ao câncer gástrico podem ser menos sinérgicos do que o esperado.

Eradication Rates of 10-day Sequential Therapy for Helicobacter pylori: Results of an 8-year Prospective Study Conducted at a Tertiary Korean Hospital / 대한소화기학회지

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.

Roles of Ureaplasma Species in Idiopathic Chronic Prostatitis: A Case-Control Study

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.

Changes in the Clinical and Pathological Characteristics of Gastric Cancer during the Last 16 Years: A Study of a Single Institution in Korea

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.

Progress in bacterial urease complexes and their activation mechanisms / 生物工程学报

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.

Advances in microbial enzymatic elimination of ethyl carbamate in Chinese rice wine / 生物工程学报

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.

Effect of 7-day Bismuth Quadruple Therapy versus 14-day Moxifloxacin Triple Therapy for Second-line Helicobacter pylori Eradication Therapy / 대한소화기학회지

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.

Usefulness of rapid urease test samples for molecular analysis of clarithromycin resistance in Helicobacter pylori / Utilidad de las muestras de test rápido de ureasa para el análisis molecular de resistencia a claritromicina en Helicobacter pylori

Helicobacter pylori is a gastric pathogen that is widely recognized as a causative agent of gastric disease. Its eradication is variable, mainly due to increased resistance to clarithromycin. Our objective was: to evaluate (i) if the biopsy specimen used for the rapid urease test is a useful sample to detect resistance to clarithromycin by PCR-RFLP and (ii) the distribution of A2142G and A2143G point mutations in the 23S rRNA gene, in relation to virulence factors in our region. Gastric specimens were collected from adult dyspeptic patients (n = 141) and H. pylori was investigated by the rapid urease test, histopathological analysis and PCR for the hsp60 gene. Clarithromycin resistance was detected by PCR-RFLP in 62 H. pylori (+) paired biopsy specimens submitted to molecular analysis and the rapid urease test. H. pylori virulence factors were analyzed by multiplex PCR using specific primers for the cagA, vacA and babA2 genes. Thirteen out of 62 strains (20.9%) were resistant to clarithromycin: 6/13 (46.2%) harbored the A2143G mutation whereas 7/13 (53.8%) carried the A2142G point mutation. vacA m1s1 was the most frequent genotype among the resistant strains. In conclusion, the biopsy specimens used for the rapid urease test were suitable samples for clarithromycin resistance detection in patients infected with H. pylori, which became especially useful in cases where the number or size of the biopsies is limited. In addition, this is the first report of a molecular analysis for clarithromycin resistance performed directly from gastric biopsies in our region.

Helicobacter pylori es un patógeno ampliamente reconocido como causante de enfermedad gástrica. Su erradicación es variable, principalmente debido al incremento de la resistencia a claritromicina. Nuestros objetivos fueron evaluar la utilidad de la biopsia usada para realizar el test rápido de ureasa en la detección de resistencia a claritromicina por PCR-RFLP y conocer la distribución de las mutaciones puntuales A2142G y A2143G en el gen ARNr 23S, en relación con los factores de virulencia en nuestra región. Se recolectaron muestras gástricas (n=141) provenientes de pacientes adultos dispépticos y se investigó la presencia de H. pylori mediante el test rápido de ureasa, análisis histopatológico y PCR para el gen hsp60. La resistencia a claritromicina se analizó por PCR-RFLP en 62 muestras pareadas de biopsias gástricas H. pylori+ destinadas al análisis molecular y al test rápido de ureasa. Los factores de virulencia de H. pylori fueron analizados mediante PCR multiplex usando oligonucleótidos específicos para los genes cagA, vacA y babA2. Trece de 62 cepas (20,9%) fueron resistentes a claritromicina, 6/13 (46,2%) llevaron la mutación A2143G, mientras que 7/13 (53,8%) presentaron la mutación A2142G. El genotipo vacA s1m1 fue el más frecuente entre las cepas resistentes a claritromicina. En conclusión, las biopsias destinadas al test rápido de ureasa fueron muestras apropiadas para la detección de la resistencia a claritromicina en pacientes infectados con H. pylori. Esto es especialmente útil en aquellos casos en los que el número o el tamaño de las muestras son limitados. Además, este es el primer reporte de estudio de resistencia a claritromicina (mediante técnicas moleculares), directamente de biopsias gástricas en nuestra región.

Is It More Effective to Prescribe a Proton Pump Inhibitor Separately before a Meal for the Eradication of Helicobacter pylori?

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.