Abstract. A sexual dimorphism in hypertension has been observed in both human and laboratory animal studies. The mechanisms by which male sex hormones regulate cardiovascular homeostasis are still not yet fully understood and represent the subject of this study. The possible involvement of androgen receptors in the development of hypertension and end-organ damage in transgenic rats harboring the mouse Ren-2 renin gene [TGR(mREN2)27] was studied. Male TGR(mREN2)27 rats were treated with the androgen receptor antagonist Flutamide starting at 4 wk of age. Also, an androgen receptor mutation (testicular feminization mutation [tfm]) was introduced in these rats by crossbreeding male TGR(m-REN2)27 rats with tfm rats. The resulting offspring male rats that contain the tfm mutation are insensitive to androgens.Flutamide treatment or tfm mutation produced a significant attenuation of the development of hypertension. Besides a reduction in cardiac hypertrophy, urinary albumin excretion was blunted and no histologic characteristics of end-organ damage were observed in the kidney after Flutamide treatment. Testosterone levels increased 15-fold after Flutamide treatment and 2.7-fold by the tfm mutation. Also, plasma estrogens and luteinizing and follicle-stimulating hormones were significantly increased. Plasma renin concentrations and activity but not plasma angiotensinogen were reduced. Our results indicate that androgens contribute not only to the development of hypertension, but even more importantly to end-organ damage in TGR(mREN2)27 rats.Men are predisposed to hypertension and cardiovascular diseases more than age-matched, premenopausal women (1). A sexual dimorphism in hypertension has been observed both in human and laboratory animal studies (2). The mechanisms responsible for the gender differences in BP control are not yet clear and continue to be subject of active investigation (3). Evidence is accumulating that androgens may play an important role in gender-associated differences in BP regulation. Several studies have indicated that androgens may mediate hypertension and renal injury (4 -8). However, the mechanisms by which male sex hormones regulate cardiovascular homeostasis are not yet fully understood (3) and represent the subject of this study. There are indications for an interrelation between androgens and the renin-angiotensin system (RAS) (3); therefore, we studied the consequences of androgen receptor blockade on the development of malignant hypertension in transgenic TGR(mREN2)27 rats with overactive RAS (9,10). Androgen receptor inhibition was achieved by treatment with the antagonist Flutamide or by introducing a testicular feminization mutation (tfm) mutation, and BP as well as end-organ damage and RAS and pituitary-gonadal hormones were evaluated. Materials and Methods Rat StrainsMale transgenic heterozygous rats [TGR(mREN2)27] (n ϭ 24 rats) were obtained from the animal facilities of the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. Female Long-Evans rats carrying the X-linked rece...
The high prevalence of Helicobacter pylori and the variety of gastroduodenal diseases caused by this pathogen necessitate the use of only accurate methods both for the primary diagnosis and for monitoring the eradication effectiveness. There is a broad spectrum of diagnostic methods available for detecting H. pylori. All methods can be classified as invasive or non-invasive. The need for upper endoscopy, different clinical circumstances, sensitivity and specificity, and accessibility defines the method chosen. This article reviews the advantages and disadvantages of the current options and novel developments in diagnostic tests for H. pylori detection. The progress in endoscopic modalities has made it possible not only to diagnose precancerous lesions and early gastric cancer but also to predict H. pylori infection in real time. The contribution of novel endoscopic evaluation technologies in the diagnosis of H. pylori such as visual endoscopy using blue laser imaging (BLI), linked color imaging (LCI), and magnifying endoscopy is discussed. Recent studies have demonstrated the capability of artificial intelligence to predict H. pylori status based on endoscopic images. Non-invasive diagnostic tests such as the urea breathing test and stool antigen test are recommended for primary diagnosis of H. pylori infection. Serology can be used for initial screening and epidemiological studies. The histology showed its value in detecting H. pylori and provided more information about the degree of gastric mucosa inflammation and precancerous lesions. Molecular methods are mainly used in detecting antibiotic resistance of H. pylori. Cultures from gastric biopsies are the gold standard and recommended for antibiotic susceptibility tests.
Цель представления клинических рекомендаций, предназначенных для врачей-гастроэнтерологов, врачей общей практики (семейных врачей), врачей-терапевтов, заключается в изложении современных методов диагностики и лечения язвенной болезни. Основное содержание. Язвенная болезнь (ЯБ) представляет собой хроническое рецидивирующее заболевание, протекающее с чередованием периодов обострения и ремиссии, ведущим проявлением которого служит образование дефекта (язвы) в стенке желудка и двенадцатиперстной кишки. Большинство случаев ЯБ патогенетически связано с инфекцией Н. pylori. Различают ЯБ как самостоятельное заболевание и симптоматические язвы желудка и двенадцатиперстной кишки (лекарственные, «стрессовые», при эндокринной патологии, при других хронических заболеваниях внутренних органов). Всем пациентам с подозрением на ЯБ, при отсутствии противопоказаний, с целью подтверждения диагноза рекомендуется проведение эзофагогастродуоденоскопии. Всем пациентам с ЯБ с целью определения показаний к эрадикационной терапии рекомендуется проведение тестирования на наличие инфекции Н. рylori с помощью 13 С-дыхательного теста или определения антигена H. pylori в кале, а при одновременном проведении ЭГДС-с помощью быстрого уреазного теста. Всем пациентам с ЯБ с положительными результатами тестирования на инфекцию H. рylori с целью профилактики последующих рецидивов ЯБ рекомендуется проведение эрадикационной терапии, с целью достижения заживления язв рекомендуется проведение антисекреторной терапии ингибиторами протонного насоса в течение 4-6 недель. Клинические рекомендации содержат критерии оценки качества оказания медицинской помощи, алгоритм действия врача, а также информацию для пациента. Заключение. В клинических рекомендациях даются современные представления об этиологии и патогенезе язвенной болезни, ее клинических проявлениях, методах лабораторной и инструментальной диагностики, основных подходах к консервативному и хирургическому лечению. Ключевые слова: язвенная болезнь, язвенное кровотечение, перфорация, стеноз, H. pylori, эрадикационная терапия H. pylori, ингибиторы протонной помпы Конфликт интересов: авторы заявляют об отсутствии конфликта интересов.
Abstract-We aimed at studying the role of androgens in the development of cardiovascular pathology in hypertensive female rats. Female TGR(mREN2)27 rats harboring the mouse Ren-2 renin gene were treated with Flutamide (specific antagonist of the androgen receptor, 30 mg/kg per day) starting at 4 weeks of age. Flutamide treatment significantly attenuated the development of hypertension in female rats (systolic blood pressure: treated, 134.5Ϯ5.4 versus control, 165.4Ϯ3.8 mm Hg). Heart hypertrophy was significantly reduced by the treatment (treated, 0.37Ϯ0.008 versus control, 0.45Ϯ0.01 g/100 g body wt). Urinary albumin excretion was blunted (treated, 0.4Ϯ0.1 versus control, 23.1Ϯ7.5 mg/24 hours), collagen III mRNA was significantly decreased, and no histological characteristics of end-organ damage were observed in the kidney after treatment. Flutamide treatment significantly reduced plasma renin concentrations and rat renin mRNA in kidney but not plasma angiotensinogen levels. Plasma levels of estrogens, testosterone, and luteinizing hormone were not altered. These results demonstrate that the androgen receptor antagonist Flutamide protects against hypertension and end-organ damage not only in male but also in female TGR (mREN2) Gender differences have been observed in various hypertensive animal models, with male rats having higher blood pressure than female rats, 2-6 including the transgenic rat TGR(mREN2)27 with an overactive renin-angiotensin system (RAS). 7,8 Evidence is accumulating that androgens may play an important role in gender-associated differences in cardiovascular pathology. We have previously demonstrated that androgens contribute not only to the development of malignant hypertension but also to the associated end-organ damage in transgenic male TGR(mREN2)27 rats with overactive RAS. 9 Females produce androgens as well, which act on specific receptors. 10 Women with hyperandrogenism are considered to be at increased risk for cardiovascular disease. 11-15 Based on a prospective literature survey, it has been recently hypothesized that relative androgen excess is a key factor explaining the increased risk of cardiovascular disease in interpausal women. 16 In the present study, we hypothesized that endogenous androgens may participate in the development of hypertension and end-organ damage in female TGR(mREN2)27 rats. Androgen blockade was achieved by treatment with the antagonist Flutamide, and blood pressure (BP) as well as end-organ damage, RAS, and sex hormones were evaluated. Methods Rat StrainsFemale transgenic heterozygous rats [TGR(mREN2)27] (nϭ24 rats) were obtained from the animal facilities of the Max-Delbrück-Center for Molecular Medicine, Berlin, Germany. The rats were housed individually, synchronized to a 12-hour light-dark cycle, at ambient temperature 23Ϯ2°C. A standard rat diet (ssniff R-ZUCHT) and tap water were supplied at libitum. Study DesignAll experimental protocols were performed in accordance with the guidelines for the use of laboratory animals by the Max-Delbrück-Center for...
Background Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn’s disease (CD). The phylogeny of E. coli isolated from Crohn’s disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related.ResultsWe performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons.ConclusionsOur findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3917-x) contains supplementary material, which is available to authorized users.
A steady decline in the effectiveness of standard eradication therapy (ET) regimens for Helicobacter pylori infection necessitates a search for ways of their optimization, by enhancing the efficiency of treatment protocols and by improving their safety and tolerability. The review systematizes the data available in the literature on main accessible methods for optimizing ET regimens. Among the optimization methods that can considerably enhance the efficiency of ET regimens, one may identify their addition of a bismuth agent (by 10—20%), the use of rebamipide (by 11.9%), adjuvant therapy with probiotics (by 8.1—13%), or double-dose proton pump inhibitors (by 8%). Only adjuvant therapy with probiotics results in a significant decrease in the incidence of side effects from ET. In posteradication period, rebamipide should be used to potentiate gastric mucosal repair and to regress inflammatory processes.
Background: There has been a negative trend in the effectiveness of classic eradication therapy regimens for Helicobacter pylori (H. pylori), which has largely been determined from the emergence and spread of antibiotic resistance. Several studies have shown that adding rebamipide to eradication regimens leads to an increase in the effectiveness of treatment. Aim: To evaluate the efficacy and safety of including rebamipide in the eradication regimens for H. pylori infection. Methods: The literature search was conducted in the MEDLINE/PubMed, EMBASE, Cochrane Central Register, Korean Medical Citation Index, and Russian Science Citation Index databases. All identified randomized controlled trials comparing rebamipide supplementation with non-rebamipide-containing eradication regimens for the treatment of H. pylori infection were included in the final analysis. Results: We identified 11 randomized controlled trials (RCTs) involving 1227 patients (631 in groups with rebamipide and 596 in groups without rebamipide). The meta-analysis showed that the addition of rebamipide to eradication regimens significantly increased the effectiveness of treatment (odds ratio (OR) 1.753, 95% confidence interval (CI) 1.312–2.333, p < 0.001). The subgroup analysis demonstrated that rebamipide significantly increased the effectiveness of eradication when added to a dual therapy regimen (OR 1.766, 95% CI: 1.167–2.495, p = 0.006); however, no significant improvement in effectiveness was observed when it was added to the triple therapy regimen (OR 1.638, 95% CI 0.833–3.219, p = 0.152). Conclusion: This meta-analysis demonstrated that the addition of rebamipide to H. pylori eradication regimens significantly increases the effectiveness of treatment.
Ключевые слова: гастроэзофагеальная рефлюксная болезнь, гастроэзофагеальный рефлюкс, неэрозивная рефлюксная болезнь, рефлюкс-эзофагит, пищевод Баррета, манометрия высокого разрешения, pH-импедансометрия Конфликт интересов: авторы заявляют об отсутствии конфликта интересов.
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