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Concept on the pathogenesis and treatment of primary biliarycirrhosis

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World Journal of Gastroenterology 2006年第45期12卷 7250-7262页

作者： vasiliy Ivanovich Reshetnyak Scientific Research Institute of General Reaniamatology Russia Academy of Medical SciencesMoscowRussia

Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic, progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis, leading to liver failure in the absence of treatment. Little is known about the etiology of PBC. PBC is characterized by anti-mitochondrial antibodies and destruction of intrahepatic bile ducts. The serologic hallmark of PBC is the presence of auto-antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex (PDC). Current theories on the pathogenesis of PBC favor the hypothesis that the disease develops as a result of an inappropriate immune response following stimulation by an environmental or infectious agent. Some reports suggest that xenobiotics and viral infections may induce PBC. The pathogenetic mechanism is believed to be caused by a defect in immunologic tolerance, resulting in the activation and expansion of self-antigen specific T and B lymphocyte clones and the production of circulating autoantibodies in addition to a myriad of cytokines and other inflammatory mediators. This leads to ductulopenia and persistent cholestasis, by developing end-stage hepatic-cell failure. In this review are given our own and literary data about mechanisms of development of intrahepatic cholestasis and possible ways of its correction.

关键词： Primary biliary cirrhosis Pathogenesis Treatment

Physiological and molecular biochemical mechanisms of bile formation

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World Journal of Gastroenterology 2013年第42期19卷 7341-7360页

作者： vasiliy Ivanovich Reshetnyak V.A. Negovsky Scientific Research Institute of General Reanimatology Russian Academy of Medical Sciences107031 MoscowRussia

This review considers the physiological and molecular biochemical mechanisms of bile *** composition of bile and structure of a bile canaliculus,biosynthesis and conjugation of bile acids,bile phospholipids,formation of bile micellar structures,and enterohepatic circulation of bile acids are *** general,the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical *** of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes,associated with diseases of the liver and biliary tract.

关键词： Bile acids Bile phospholipids Bile micelle structures Bile salt transporters

Primary biliary cirrhosis: Clinical and laboratory criteria for its diagnosis

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World Journal of Gastroenterology 2015年第25期21卷 7683-7708页

作者： vasiliy Ivanovich Reshetnyak V.A. Negovsky Research Institute of General Reanimatology

Primary biliary cirrhosis(PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts, which is likely to be caused by an autoimmune mechanism with a the presence of serum antimitochondrial antibodies and a potential tendency to progress to cirrhosis. Despite the fact that the etiology of this disease has beenunknown so far, there has been a considerable body of scientific evidence that can reveal the clinical and laboratory signs of PBC and the individual components of its pathogenesis and elaborate diagnostic criteria for the disease and its symptomatic therapy. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease. The purpose of this review is to summarize the data available in the literature and the author's findings on clinical and laboratory criteria for the diagnosis of PBC. This review describes the major clinical manifestations of the disease and the mechanisms of its development. It presents the immunological, biochemical, and morphological signs of PBC and their significance for its diagnosis. A great deal of novel scientific evidence for the problem of PBC has been accumulated. However, the inadequate efficiency of therapy for the disease lends impetus to the quest for its etiological factors and to further investigations of its pathogenetic mechanisms and, on this basis, to searches for new methods for its early diagnosis.

关键词： Primary biliary cirrhosis Clinical criteria Laboratory criteria Immunological signs Biochemicalsigns Morphological signs

Magnetic cycles of Sun-like stars with different levels of coronal and chromospheric activity——comparison with the Sun

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Research in Astronomy and Astrophysics 2016年第9期16卷 123-136页

作者： Elena Shimanovskaya vasiliy Bruevich Elena Bruevich Sternberg Astronomical Institute Moscow State University

The atmospheric activity of the Sun and Sun-like stars is analyzed involving observations from the HK-project at the Mount Wilson Observatory, the California and Carnegie Planet Search Program at the Keck and Lick Observatories and the Magellan Planet Search Program at the Las Campanas Observatory. We show that for stars of E G and K spectral classes, the cyclic activity, similar to the 11-yr solar cycle, is different： it becomes more prominent in K-stars. Comparative study of Sun-like stars with different levels of chromospheric and coronal activity confirms that the Sun belongs to stars with a low level of chromospheric activity and stands apart among these stars by its minimum level of coronal radiation and minimum level of variations in photospheric flux.

关键词： Sun activity -- Sun-like stars activity

New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage

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World Journal of Gastroenterology 2023年第37期29卷 5292-5304页

作者： vasiliy Ivanovich Reshetnyak Igor Veniaminovich Maev Department of Propaedeutics of Internal Diseases and Gastroenterology A.I.Yevdokimov Moscow State University of Medicine and DentistryMoscow 127473Russia

Primary biliary cholangitis(PBC)is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in *** to cholangiocytes triggers the development of intrahepatic cholestasis,which progresses to cirrhosis in the terminal stage of the *** data indicate that damage to biliary epithelial cells[(BECs),cholangiocytes]is most likely associated with the intracellular accumulation of bile acids,which have potent detergent properties and damaging effects on cell *** mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen,which is controlled by the bicarbonate(HCO3-)buffer system“biliary HCO3-umbrella”.The impaired production and entry of HCO3-from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA *** on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC,we propose a hypothesis explaining the pathogenesis of the first morphologic(ductulopenia),immunologic(antimitochondrial autoantibodies)and clinical(weakness,malaise,rapid fatigue)signs of the disease in the asymptomatic *** review focuses on the consideration of these mechanisms.

关键词： Primary biliary cholangitis Antimitochondrial autoantibodies MicroRNA 506 Inositol-1,4,5-trisphosphate receptor type 3 Chloride/bicarbonate anion exchanger 2 Biliary bicarbonate umbrella Dihydrolipoyl transacetylase(E2 subunit) Pyruvate dehydrogenase complex

Significance of dormant forms of Helicobacter pylori in ulcerogenesis

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World Journal of Gastroenterology 2017年第27期23卷 4867-4878页

作者： vasiliy Ivanovich Reshetnyak Tatiana Magomedalievna Reshetnyak VA Negovsky Research Institute of General Reanimatology of Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology Department of Systemic Connective Tissue Diseases VA Nasonova Research Institute of Rheumatology

Nearly half of the global population are carriers of Helicobacter pylori(H. pylori),a Gram-negative bacterium that persists in the healthy human stomach. H. pylori can be a pathogen and causes development of peptic ulcer disease in a certain state of the macroorganism. It is well established that H. pylori infection is the main cause of chronic gastritis and peptic ulcer disease(PUD). Decontamination of the gastric mucosa with various antibiotics leads to H. pylori elimination and longer remission in this disease. However,the reasons for repeated detection of H. pylori in recurrent PUD after its successful eradication remain unclear. The reason for the redetection of H. pylori in recurrent PUD can be either reinfection or ineffective anti-Helicobacter therapy. The administration of antibacterial drugs can lead not only to the emergence of resistant strains of microorganisms,but also contribute to the conversion of H. pylori into the resting(dormant) state. The dormant forms of H. pylori have been shown to play a potential role in the development of relapses of PUD. The paper discusses morphological H. pylori forms,such as S-shaped,C-shaped,U-shaped,and coccoid ones. The authors proposes the classification of H. pylori according to its morphological forms and viability.

关键词： Helicobacter pylori Forms of H. pylori Dormant forms of H. pylori Viable forms of H. pylori Non-viable forms of H. pylori Physiological states of H. pylori Culturable forms of H. pylori Unculturable forms of H. pylor Resuscitation of dormant H. pylori Ulcerogenesis

Concept of the pathogenesis and treatment of cholelithiasis

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World Journal of Hepatology 2012年第2期4卷 18-34页

作者： vasiliy Ivanovich Reshetnyak VA Negovsky Scientific Research Institute of General Reanimatology Russia Academy of Medical Sciences

Gallstone disease(GD) is a chronic recurrent hepatobiliary disease,the basis for which is the impaired metabolism of cholesterol,bilirubin and bile acids,which is characterized by the formation of gallstones in the hepatic bile duct,common bile duct,or *** is one of the most prevalent gastrointestinal diseases with a substantial burden to health care *** can result in serious outcomes,such as acute gallstone pancreatitis and gallbladder *** epidemiology,pathogenesis and treatment of GD are discussed in this *** prevalence of GD varies widely by *** prevalence of gallstone disease has increased in recent *** is connected with a change in lifestyle:reduction of motor activity,reduction of the physical load and changes to *** of the important benefits of early screening for gallstone disease is that ultrasonography can detect asymptomatic cases,which results in early treatment and the prevention of serious *** pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental *** suggests that corticosteroids and oral contraceptives,which contain hormones related to steroid hormones,may be regarded as a model system of cholelithiasis development in *** achievement in the study of the physiology of bile formation and the pathogenesis of GD has allowed expanding indications for therapeutic treatment of GD.

关键词： Gallstone disease:Epidemiology Pathogenesis of cholesterol stones Treatment

Design and experimental testing of a gas cluster ion accelerator

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Chinese Physics C 2017年第8期41卷 143-146页

作者：曾晓梅 vasiliy Pelenovich 刘传胜付德君 Key Laboratory of Artificial Micro-and Nano-Materials of Ministry of Education and Hubei Nuclear Solid Physics Key Laboratory School of Physics and TechnologyWuhan UniversityWuhan 430072China

A gas cluster ion beam（GCIB） system with cluster energy up to 12 keV has been designed. To facilitate pumping of the nozzle chamber and increased pressure of the gas source up to 10 atm, pulse mode was used for the gas feeding. Argon was employed as the working gas. To separate monomers from clusters, both electromagnet and retarding electrode were utilized. A maximal pulsed cluster current of 90 nA has been achieved. The shape of pulsed ion beam currents has been analyzed in detail at different applied magnetic and retarding electric fields.

关键词： gas cluster ion beam flow visualization cluster mass separation retarding electrode

Helicobacter pylori:Commensal,symbiont or pathogen?

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World Journal of Gastroenterology 2021年第7期27卷 545-560页

作者： vasiliy Ivanovich Reshetnyak Alexandr Igorevich Burmistrov Igor Veniaminovich Maev Department of Propaedeutic of Internal Diseases and Gastroenterology A.I.Yevdokimov Moscow State University of Medicine and DentistryMoscow 127473Russia

This review considers the data on Helicobacter pylori(***),which have been accumulated over 40 years since its description as an etiological factor in gastrointestinal *** majority of modern publications are devoted to the study of the pathogenic properties of the microorganism in the development of chronic gastritis,peptic ulcer disease,and gastric cancer,as well as methods for its ***,in recent years,there have been more and more studies which have suggested that *** has a beneficial,or potentially positive,effect on the human *** authors have attempted to objectively analyze the information accumulated in the literature on *** studies consider it as one of the recently identified human bacterial pathogens,and special attention is paid to the evidence suggesting that it is probably part of the composition of the human microbiome as a commensal(commensal from French to English is a table companion)or even a *** presented data discussing the presence or absence of the effect of *** on human health suggest that there is an apparent ambiguity of the *** re-assessment of the data available on *** infection is important in order to answer the question of whether it is necessary to create a program of mass *** eradication or to apply a more personalized approach to treating patients with ***-associated gastrointestinal diseases and to perform eradication therapy.

关键词： Helicobacter pylori Pathogen Commensal Microbiome Peptic ulcer Gastric cancer Asthma Inflammatory bowel diseases