Репозиторий Университета

© 2018 Denisenko et al. Background: Proton pump inhibitors (PPIs) are metabolized by cytochrome P450. CYP2C19 is the main isoenzyme for the majority of PPI, whereas CYP3A family is a secondary enzyme for PPI biotransformation. Purpose: The aim of the study was to find if CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17 genotypes are connected with CYP3A and CYP2C19 activities in Russian peptic ulcer patients taking omeprazole. Patients and methods: Forty-eight gastric or duodenal ulcer patients (15 men, 33 women; mean age 55.0±15.3 years, age range 18–91 years) from Moscow region of Russia were enrolled. Peripheral venous blood was collected for DNA extraction, and real-time polymerase chain reaction was performed for CYP3A5*3A6986G (rs776746), CYP3A4*22 C>T in intron 6 (rs35599367), CYP2C19*2G681A (rs4244285), CYP2C19*3G636A (rs4986893), and CYP2C19*17C-806T (rs12248560) polymorphism analyses. Urine samples of patients were collected in the morning between 6 and 9 am before food or drug intake. Urine cortisol and 6β-hydroxycortisol concentrations (for CYP3A activity) and omeprazole and 5-hydroxyomeprazole concentrations (for CYP2C19 activity) were measured using high-performance liquid chromatography/mass spectroscopy. Results: We found a connection between CYP2C19 genotypes and CYP3A activity. Median metabolic ratios 6β-hydroxycortisol/cortisol (25%–75% percentiles) were 2.84 (1.99–4.39) for CYP2C19 extensive metabolizers (EMs), 2.51 (1.86–4.73) for CYP2C19 ultra-rapid metabolizers (UMs), and 1.45 (1.12–2.16) for CYP2C19 intermediate metabolizers (IMs) + poor metabolizers (PMs). A statistically significant difference in CYP3A activity (Mann–Whitney test) was found between CYP2C19 EMs vs CYP2C19 IMs+PMs (p=0.006), between CYP2C19 UMs vs CYP2C19 IMs+PMs (p=0.018), and in multiple comparison Kruskal–Wallis test (p=0.014). Conclusion: In CYP2C19 IMs+PMs, CYP3A activity was significantly lower than in CYP2C19 EMs and UMs.

© 2018 Media Sphera Publishing Group. All rights reserved. The review analyzes the main etiological and pathogenetic mechanisms of the development of NSAID-enteropathy. Particular attention is paid to the role of intestinal microbiota in the manifestation and progression of NSAID-enteropathy. The special role of probiotics in the prevention and treatment of NSAIDs enteropathy is considered.

© 2018 Media Sphera Publishing Group. All rights reserved. Purpose of the review to present up-to-date data on the causes, methods of diagnosis and treatment of the refractory form of gastroesophageal reflux disease (GERD). Refractory GERD is the preservation of typical symptoms of the disease and/or incomplete healing of the esophageal mucosa against the background of taking a standard dose of proton pump inhibitors (PPI) once a day for 8 weeks. The reasons for the lack of response to the treatment are divided into related to the patient, related to therapy, and not related to GERD. Diagnostic approaches include x-ray examination of the esophagus and stomach, endoscopy with biopsy, 24-hour Impedance-pH monitoring, esophageal manometry. Depending on the reasons for the lack of response to the therapy, treatment may include lifestyle changes, doubling the dose of PPI, replacing PPI with another, adding H2-receptor antagonists, prokinetics, antacids, alginates and adsorbents. If conservative treatment is ineffective, it is possible to consider alternative methods, such as surgical treatment. Refractory GERD is a serious clinical problem. The absence of an answer to 8-week therapy with PPI requires a thorough differential diagnosis using additional examination methods. The identification of the causes of refractory to the therapy allows to optimize the approaches to its overcoming and to choose the optimal treatment.