The article presents a detailed literature review on the role of intestinal dysbiosis, including bacterial overgrowth syndrome, as well as increasing intestinal permeability in the pathogenesis of the main pancreatic diseases: acute and chronic pancreatitis (AP and CP), autoimmune pancreatitis, pancreatic cancer. Thus, according to the results of meta-analysis, populations of Enterobacteriaceae and Enterococcus were larger in all patients with AP as compared with healthy. There was no difference between the groups with severe and mild AP. Number of Bifidobacterium was lower in all patients with AP as compared with healthy. In severe AP, level of endotoxin and cytokines in blood was higher than in mild AP and in healthy. Participation of Helicobacter pylori in pathogenesis of autoimmune pancreatitis via molecular mimicry is assumed. In addition, Helicobacter pylori may have significance in development of pancreatic adenocarcinoma. In CP, rate of syndrome of bacterial overgrowth has been studied in numerous studies, since dysbiosis halts the effect of enzyme preparations, causes worsening of clinical manifestations. According to the results of meta-analysis, patients with CP are characterized by quantitative and qualitative changes in the composition of intestinal microbiome: decrease of Bifidobacterium and Lactobacillus, and increase of Enterobacteriaceae. The authors also preseented their own data. Recent data suggest a connection between the oral microbiota, tongue plaque and pancreatic adenocarcinoma. Pancreatic cancer is characterized by decrease of Neisseria elongate, Streptococcus mitis, and increase of Porphyromonas gingivalis and Granulicatella adiacens. Recent reports have found that oral microbiota may be important in increasing the risk of pancreatic cancer. The conclusion is drawn on the prospects of studying the intestinal microbiota in pancreatic diseases and the need for its participation in the pathogenesis of this disease.
The article presents data on classification, pathogenesis, clinical picture, diagnosis and differentiated treatment tactics, as well as practical algorithm for recognizing and preventing the development of drug-induced liver injury. Pathogenesis of drug-induced liver injury is analyzed, mechanisms of drug metabolism are explained, metabolism phases are described. Four main mechanisms of the pathological effect of drugs on the liver are identified: direct toxic effect on hepatocytes; toxic effect of drug metabolites; immunoallergic liver injury; idiosyncrasy. Peculiar attention is paid to the pathogenesis of drug-induced cholestasis. Direct hepatotoxic reactions develop according to the cytolytic (hepatocellular, parenchymal), cholestatic or mixed option. The most commonly diagnosed clinical variant of drug-induced liver injury is drug-induced hepatitis. Five forms of hepatitis induced by the use of pharmacological agents are distinguished: drug-induced hepatitis with an isolated increase in transaminases (anti-TB drugs, methyldopa, amiodarone, statins); acute hepatitis with jaundice; pseudo-surgical form of acute hepatitis: abdominal pain, fever, jaundice, enlarged gall bladder (cytostatics, antidepressants, antiarrhythmic drugs); severe forms of acute hepatitis with liver failure; chronic drug hepatitis. International diagnostic criteria, basic data on morphological liver changes are presented. Action of ursodeoxycholic acid is explained. It has a litholytic, anticholestatic, cytoprotective, immunomodulating, anti-inflammatory, antitoxic, hypocholesterolemic effect, modulates apoptosis, has a differentiated effect on the regeneration of hepatocytes.
Vasyl Parmenovich Obraztsov (1849 — 1920) was an outstanding therapist, Professor of Medicine, and innovator in the field of techniques for diagnosing diseases of the cardiovascular and digestive systems. The research interests of V. P. Obraztsov were mainly focused on studying the most important issues in general and specific gastroenterology and cardiology. At the same time, he aimed to invent reliable techniques for the physical diagnosis of diseases of the abdominal organs and heart. Palpation of the abdominal organs, invented and introduced into clinical practice by V. P. Obraztsov, is based on four principles. During deep breathing, especially when the patient is lying down, the abdominal press occasionally relaxes. During the exhalation phase, the researcher tries to reach deep into the abdominal cavity with a palpating hand and press an organ that needs to be felt against the posterior abdominal wall. The first principle of the research technique that V. P. Obraztsov came up with is deep palpation. It is usually possible to palpate any organ in the abdomen when the fingertips of the palpating hand slide off the edge of the organ being examined. The palpable part of the gastrointestinal tract is pressed against the posterior abdominal wall with a strong downward movement of the hand that is perpendicular to the organ’s long axis. When the fingers slip from the organ, the localization of the organ, as well as its consistency, shape, width, and mobility, can be determined; at the same time, the patient may report unpleasant or painful sensations. Sliding palpation is the second principle of the research technique by V. P. Obraztsov. According to topographic anatomy, each organ in the abdominal cavity has its own normal localization. Now, X‑rays confirm this, but V. P. Obraztsov had to do experiments to develop a typical topography of certain segments of the digestive tract in the abdominal cavity of a healthy person and find typical projections of internal organs on the anterior wall of the abdomen. Further studies by his students proved the correctness of his description of the topography of the abdominal organs. Of course, both V. P. Obraztsov and his students repeatedly emphasized the possibility of individual differences or physiological variants in the localization of the digestive tract organs in patients. Topographic palpation has become the third guiding principle of the research technique developed by V. P. Obraztsov. V. P. Obraztsov suggested that a study of the organs in the abdomen be done in a certain sequence. First, the sigmoid colon is examined, then the cecum, the terminal segment of the small intestine, the appendix, the stomach, with an attempt to palpate its small and large curvatures, and the pylorus. After that, the palpation of the transverse colon and the ascending and descending sections of the large intestine starts. The examination is completed by determining the localization, consistency, shape, mobility, and other features of the parenchymal organs — the liver, spleen, and kidneys. Thus, systematic palpation is the fourth principle of the examination of the abdominal organs. V. P. Obraztsov made a significant contribution to the history of cardiology. Systematic cardiac auscultation with a stethoscope and directly with the ear let him describe some features of the tone I, report the presence of a normal tone III, and point out the relatively frequent detection of bifurcation and splitting of heart tones. A series of works by V. P. Obraztsov on the study of the gallop rhythm is of particular importance for cardiology. In 1950, on the centenary of his birth, the government of the Ukrainian SSR decided to publish his «Selected Works», build a monument, and assign his name to the Department of Internal Diseases No. 1 of the Kyiv Medical Institute. By the same date, the country’s medical journals had published his students’ memoirs, as well as articles and essays about his life path.
This article presents an overview of the results of practical and basic research in the field of pancreatology, which were presented during the 51st Meeting of the European Pancreatic Club (2019). Achievements of leading European pancreatologists in the study of the etiology, pathogenesis, diagnosis, treatment of pancreatitis, pancreatic tumors are briefly described. The article presents clinical features of acute and chronic pancreatitis, depending on the variety of concomitant pathology, genetic characteristics, bad habits, drugs taken. New opportunities for the differential diagnosis of chronic pancreatitis and pancreatic cancer using miRNA are considered, as well as the feasibility of determining the soluble urokinase-type plasminogen activator receptor (suPAR) in order to differentiate benign and malignant pancreatic tumors. Approaches to the diagnosis of abdominal pain, use of computed tomography for the diagnosis of sarcopenia are described. Results of basic research analyzing the mechanisms of pancreatic cancer development are presented. Modern theory on the role of microbiota and syndrome of bacterial overgrowth in the pancreatic oncogenesis processes is revealed. Pathogenetic features of the formation of exocrine pancreatic insufficiency and effectiveness of its correction via enzyme replacement therapy with the use of modern drugs are emphasized. Results of randomized controlled studies that proved effectiveness and safety of microtablet preparation in correction of exocrine pancreatic insufficiency in patients undergoing pancreatoduodenectomy are presented.
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreatic disease (NAFPD) develop against the background of metabolic syndrome, systemic insulin resistance, oxidative stress, changes in lipid and carbohydrate metabolism. There are a number of similarities between NAFLD and NAFPD: the natural course of diseases proceeds from steatosis through inflammation to fibrosis and cancer, one of the etiopathogenetic factors is the disbalance of bile acids synthesis and low expression of farnesoid receptor X (FXR). One of the possible methods of treatment NAFLD and NAFPD is a correction of the biosynthesis of bile acids and increase FXR expression with FXR agonists. Ursodeoxycholic acid (UDCA) is a selective FXR agonist. It has a multipled spectrum of actions: anticholestatic, anti-apoptic, antioxidant, cytoprotective, antifibrotic, hypocholesterolemic, immunomodulatory, hepatoprotective. The ability of UDCA correct lipid and carbohydrate metabolism in combination with anti-inflammatory and antiapoptic effects may be of great importance for the treatment of NAFLD and NAFPD. The article reviews the results of clinical and experimental studies describing the efficacy of UDCA in NAFLD and some pancreatic diseases. It has been suggested that the therapy of UDCA can reduce the severity of NAFLD and NAFPDand improve the functional activity of hepatocytes and β cells. The need for randomized clinical trials was emphasized in order to make an informed decision on the expediency of including UDCA in the treatment of NAFLD and NAFPD.
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