Bile Acids and Their Value for Central Nervous System

Aim. A review to highlight the bile acids importance as steroid mediators of nervous system activity and show the nervous system involvement in cholesterol metabolism and bile acids production.Key points. Presence of bile acid membrane and nuclear receptors and their activation role in mediating manifold metabolic processes have been established in various organs and tissues. Bile acid transporters are discovered in CNS. The animal brain under physiological conditions was found to contain about 20 bile acid types of likely innate origin suggested by their high contents; the bile acids spectrum in CNS differs significantly from blood plasma. Clinical and experimental works are conclusive about the CNS bile acids influence on mitochondrial membrane, their antioxidative role and, probably, steroid-mediator involvement in indirect regulation of memory, attention, motor functions and appetite.Conclusion. Bile acids act as pleiotropic signalling molecules affecting various tissues. The presence in CNS of various bile acid synthesis-related receptors and enzymes indicates their value in brain functioning and warrants research into their metabolism

A 19-year-old Patient with Recurrent Pruritus and Jaundice

Аim: to highlight the importance of broad differential diagnosis and possibility of conversion of benign recurrent intrahepatic cholestasis type 2 into more aggressive clinical phenotype.Key points. A 19-year-old female patient was admitted to the Clinic with skin pruritus, jaundice, dark urine, clay-colored stool, and general fatigue. Past medical history was significant for recurrent aforementioned symptoms since 3 years old, that relapsed every 1–2 years and were usually ameliorated with conservative therapy. During recent years, frequency of relapses and recovery period increased, at the same time effectiveness of medical therapy decreased. Blood chemistry results revealed an elevation of total bilirubin (up to 634 μmol/L), direct bilirubin (up to 354 μmol/L), bile acids (up to 510 μmol/L) and normal gamma glutamyl transferase level. Workup was negative for viral hepatitis, autoimmune liver diseases, obstructive choledochal lesions, storage diseases, although mutation in gene ABCB11 was found. Benign recurrent intrahepatic cholestasis type 2 was diagnosed. Following conservative therapy and plasmapheresis, jaundice and skin pruritus significantly diminished, levels of bilirubin and bile acids normalized. Regular follow up, liver biopsy and measures for relapse prevention given clinical features of aggressive phenotype were recommended.Conclusion. Identification of etiology of cholestatic liver diseases requires broad differential diagnosis. Clinical course of patients with benign recurrent intrahepatic cholestasis may transform into aggressive phenotype, reminiscent of progressive familial intrahepatic cholestasis

Современный взгляд на проблему постхолецистэктомического синдрома (по материалам Экспертного совета, состоявшегося 4 мая 2019 г. в городе Алматы, Казахстан)

Gallstone disease is revealed in 10–20% of the population with a clear tendency to affect the younger population. In a clinically manifested course, cholecystectomy remains the treatment of choice. Symptoms and signs persist or even become more severe after gallbladder surgery in 10-15% of cases (“postcholecystectomy syndrome”). Postcholecystectomy syndrome includes heterogeneous disorders of liver, pancreas, duodenum, sphincter of Oddi, etc. that can be associated with errors or negative consequences of surgical intervention. Often, symptoms may persist because of previously unrecognized chronic diseases of neighboring organs. The spectrum of effective conservative measures is rather limited. The Advisory Board was held on May 4, 2019, in Almaty (Kazakhstan) to re-estimate the definitions and categories related to the issue of the postcholecystectomy syndrome and to develop the diagnostic and treatment algorithm for patients with the postcholecystectomy dysfunction of the sphincter of Oddi. The statements discussed by the interdisciplinary team of gastroenterologists and surgeons were addressed to general practitioners, therapists, gastroenterologists, and surgeons. The Advisory Board emphasized that organic and functional biliary diseases manifest mainly by biliary pain, main characteristics of which were defined in the Rome IV consensus based on the statistical analysis of a large pool of clinical data. For a more accurate bile duct system assessment and the exclusion of cholelithiasis, the examination algorithm was proposed, which included abdominal ultrasound investigation, endoscopic ultrasound investigation of the pancreatobiliary area, and magnetic resonance cholangiopancreatography. Diagnostic algorithm for differentiation of functional biliary disorders from organic gastrointestinal pathology was developed. Sphincter of Oddi dysfunction may be considered as a postcholecystectomy syndrome manifestation in 1.5-3% of cases. Apart from rational nutrition, conservative management of functional gastrointestinal diseases implies  pharmacological therapy. The efficacy of non-steroidal anti-inflammatory drugs, prokinetics, nitrates, antispasmodics, calcium channel antagonists, botulinum toxin, and hymecromone was demonstrated in previous studies. Papillosphincterotomy is not effective in relieving biliary pain in cases of the sphincter of Oddi dysfunction. The proposed algorithm for the management of patients with the postcholecystectomy syndrome was presented.Желчнокаменная болезнь выявляется у 10–20% населения и имеет четкую тенденцию к «омоложению». При наличии клинических симптомов основным методом лечения остается холецистэктомия, после которой у 10–15% пациентов клинические проявления сохраняются либо усиливаются (для обозначения таких ситуаций применяют термин «постхолецистэктомический  синдром»). Постхолецистэктомический синдром объединяет неоднородные расстройства, включая  нарушения функции печени, поджелудочной железы, двенадцатиперстной кишки, сфинктера Одди  пр., которые могут быть связаны с погрешностями или последствиями хирургических манипуляций. Зачастую причиной сохранения жалоб оказываются ранее нераспознанные хронические заболевания других органов. Арсенал эффективных средств медикаментозной и  немедикаментозной коррекции относительно невелик. С целью стандартизировать определения и  категории, касающиеся проблемы постхолецистэктомического синдрома, и разработать алгоритм обследования и лечения пациентов с постхолецистэктомической дисфункцией сфинктера  Одди 4 мая 2019 г. в городе Алматы (Казахстан) состоялся совет экспертов – представителей  междисциплинарной команды из гастроэнтерологов и хирургов. Целевая аудитория – врачи общей  практики, терапевты, гастроэнтерологи, хирурги. Согласно решению Экспертного совета, основным  клиническим проявлением органических и функциональных заболеваний желчных путей  является билиарная боль, подробные характеристики которой были выделены в материалах IV Римского консенсуса на основании статистического анализа большого объема клинических данных. Для более точной оценки состояния протоковой системы и исключения желчнокаменной болезни в план обследования включают ультразвуковое исследование органов брюшной полости,  эндоскопическое ультразвуковое исследование панкреато-билиарной зоны, магнитно-резонансную  холангиопанкреатографию. Функциональные билиарные расстройства необходимо дифференцировать с органическими заболеваниями органов пищеварения; с этой целью  рекомендован план обследования пациентов. Дисфункцию сфинктера Одди можно рассматривать как вариант постхолецистэктомического синдрома; на долю таких случаев приходится 1,5–3%. Консервативное ведение при функциональных заболеваниях органов пищеварения, помимо  рационального питания, подразумевает лекарственную терапию. Показана эффективность  нестероидных противовоспалительных препаратов, прокинетиков, нитратов, спазмолитиков, антагонистов кальциевых каналов, ботулотоксина и гимекромона. Папиллосфинктеротомия при  дисфункции сфинктера Одди не обладает должной эффективностью в купировании билиарной  боли. Разработан алгоритм ведения пациентов при появлении билиарной боли и другой  симптоматики после холецистэктомии

Principles of Rational Nutrition for Managing Constipation

Aim. The aim of this work was to investigate the problem of constipation associated with a deficiency in dietary fibre and to develop principles for the nutritional management of this condition.  Main findings. In countries characterized by the Western-style diet, only about 10% of people consume an optimal amount of fibre daily. As a result, primary normal-transit constipation is a common problem. A special role in maintaining the function of the colon belongs to carbohydrates. Keeping a food diary helps to choose an optimal type of nutrition for a patient and reduce the likelihood of flatulence. Food fibres (oligosaccharides and polysaccharides) play an especially important role. Viscous fibres are most capable of swelling, thus exhibiting metabolic effects at the level of the small intestine. Non-viscous and insoluble fibres increase the volume of feces, stimulate peristalsis and exert a prebiotic effect. A low content of fibre in the diet is a factor provoking intestinal dysbiosis followed by a decrease in  Bacteroides and Ruminococcus populations. Flavonoids also play an important role in the regulation of intestinal peristalsis and secretion. Under constipation of functional origin, the microbiota contains a significantly reduced amount of Bifidobacterium and Bacteroides. Changes in the composition of microflora correlate with psychopathological symptoms. Strains capable of exhibiting a therapeutic effect in constipation include Escherichia coli Nissle 1917, a probiotic mixture of VSL#3, Florasan-D combined bacterium, DN-173 010 Bifidobacterium lactis (B. lactis), HN019 Bifidobacterium lactis and Lactobacillus rhamnosus GG. For the prevention and management of constipation, functional food products enriched with oligo-, polysaccharides and probiotics are developed. Thus, various products of the Activia brand contain DN-173 010 Bifidobacterium lactis (ActiRegularis) at a concentration of at least 108 CFU / g. The consumption of fermented milk products with DN-173-010 Bifidobacterium lactis contributes to the elimination of subclinical discomfort in the abdomen in practically healthy people, reduces the time of colon transit and helps to normalise the frequency of defecation.Conclusion. In most cases, the first stage in managing constipation is the normalisation of the diet by means of adding dietary fibre and probiotics into the composition of functional foods or medical preparations

Intestine motility, secretion, and constipation treatment principles

Introduction. Constipation is a derangement of the motor, secretory and/or evacuation function of the colon. The same symptoms are recorded in at least 20% of the population in the developed countries – as those occurring sporadically or for a long period.Basic content. The secretory function of the colon significantly affects stool consistency and its free movement. The secretion increases by 8–10 times in the presence of local mechanical irritation.  Intestinal mucus is produced by colonic goblet cells. The frequency, time of defecation and stool consistency is in large part determined by the motor function of the colon. The relation of various types of contraction varies depending on the main function – propulsion or mixing. Rhythmic phasic contractions in the colon generate a pendular movement with slow propulsion of the contents and absorption of water. The tonic contractions enhance the mixing effect of weak rhythmic contractions. The propulsive contractions are specifically attributed to the lower gastrointestinal tract and occur spontaneously. They occur quite regularly, from 2 to 10 times a day, and ensure the propulsion of intestinal contents over great distances in the colon. When reaching the sphincter area, such wave causes its relaxation by mechanisms of descending inhibition. The dietary regime and adequate intake of carbohydrates with various chain lengths, including dietary fiber, as well as flavonoids and other components that modify peristaltic activity and secretion, play an important role in the regulation of intestinal secretion and peristalsis. The drugs enhancing intestinal secretion and peristalsis, such as bisacodyl and sodium picosulfate, are also used to treat constipation. These substances hydrolyse into bis-(p-hydroxyphenyl)-pyridyl-2-methane in the intestine, which, upon contact with the receptors in colonic mucosa, stimulates propulsive activity and increases intestinal secretion. The selective action of sodium picosulfate is confined to the colon.Conclusion. Pharmacological and non-pharmacological treatments for constipation are aimed at maintaining and enhancing the natural propulsive contractions of the colon and intestinal secretion

Combination of functional disorders of the digestive organs

Many publications and major population studies have been devoted to the problem of combination of two or more functional disorders (FD) of digestive organs. The Rome Consensus IV applies the term “overlapping of FD” to cases of combinations within a single organ and stresses that the irritable bowel syndrome in any form should rather be regarded as a “continuum of different clinical variants” according to modern ideas. As a possible explanation for the existence of the overlap of FD the increase of visceral hypersensitivity, the expansion of the hypersensitivity zone, the progression of motor disorders are considered. With a combination of FD the number and intensity of complaints increases, the quality of life indicators decrease, the average number of concomitant somatic symptoms and drugs taken increases. Functional dyspepsia is more common in combinations of FD. At the same time, postprandial distress syndrome is more often combined with irritable bowel syndrome with constipation, epigastric pain syndrome with irritable bowel syndrome with diarrhea, and endoscopic-negative gastro-esopha-geal reflux disease. In addition to food components, a special role in the development of visceral sensitization is given to the persistence of inflammation after infection, gluten exposure, disorders of the intestinal microbiome, conditions of depression and anxiety. When two or more digestive organ FDs combine, it is advisable to choose the methods of treatment aimed at eliminating the action of intraluminal stimuli and the formation of “pain memory”. Drugs that normalize intestinal peristalsis and secretion are used, the choice of which is determined by the clinical version of the course, probiotics, as well as the means that affect the state of the central nervous system. When two or more digestive organ FDs combine, it is advisable to choose medications that affect their general pathogenetic mechanisms

Principles of Rational Nutrition for Managing Constipation

Aim. The aim of this work was to investigate the problem of constipation associated with a deficiency in dietary fibre and to develop principles for the nutritional management of this condition.  Main findings. In countries characterized by the Western-style diet, only about 10% of people consume an optimal amount of fibre daily. As a result, primary normal-transit constipation is a common problem. A special role in maintaining the function of the colon belongs to carbohydrates. Keeping a food diary helps to choose an optimal type of nutrition for a patient and reduce the likelihood of flatulence. Food fibres (oligosaccharides and polysaccharides) play an especially important role. Viscous fibres are most capable of swelling, thus exhibiting metabolic effects at the level of the small intestine. Non-viscous and insoluble fibres increase the volume of feces, stimulate peristalsis and exert a prebiotic effect. A low content of fibre in the diet is a factor provoking intestinal dysbiosis followed by a decrease in  Bacteroides and Ruminococcus populations. Flavonoids also play an important role in the regulation of intestinal peristalsis and secretion. Under constipation of functional origin, the microbiota contains a significantly reduced amount of Bifidobacterium and Bacteroides. Changes in the composition of microflora correlate with psychopathological symptoms. Strains capable of exhibiting a therapeutic effect in constipation include Escherichia coli Nissle 1917, a probiotic mixture of VSL#3, Florasan-D combined bacterium, DN-173 010 Bifidobacterium lactis (B. lactis), HN019 Bifidobacterium lactis and Lactobacillus rhamnosus GG. For the prevention and management of constipation, functional food products enriched with oligo-, polysaccharides and probiotics are developed. Thus, various products of the Activia brand contain DN-173 010 Bifidobacterium lactis (ActiRegularis) at a concentration of at least 108 CFU / g. The consumption of fermented milk products with DN-173-010 Bifidobacterium lactis contributes to the elimination of subclinical discomfort in the abdomen in practically healthy people, reduces the time of colon transit and helps to normalise the frequency of defecation.Conclusion. In most cases, the first stage in managing constipation is the normalisation of the diet by means of adding dietary fibre and probiotics into the composition of functional foods or medical preparations

Rabeprazole in the treatment of duodenal ulcer desease and functional dyspepsia

The review aims to provide a contemporary view of the pathogenesis and treatment of the most common duodenum diseases – duodenal ulcer disease (DUD) and functional dyspepsia (FD). Due to its unique structure and functions, the duodenum that anatomically represents the initial section of the small intestine differentiates itself from others. The prevalence of DUD is declining in many Western countries due to the widespread introduction of effective anti-Helicobacter therapy and a significant decrease in the prevalence of H pylori infection. However, the ideas about the poly-biological nature of DUD persists and additional risk factors continue to be studied. DUD is manifested by pain/burning feeling in the epigastric region, as well as by symptoms such as early satiety, epigastric filling after eating in the absence of obvious organic changes in the digestive system. The diagnosis of FD is based on the Rome IV criteria. The duodenum plays an important role in its pathogenesis (disorders of gastric accommodation, motor and visceral hypersensitivity). Most patients with FD have microscopic signs of inflammation of the mucous membrane of the postbulbar part of the duodenum - an increased amount of intraepithelial lymphocytes, eosinophils, and signs of increased permeability of the mucous membrane. In all likelihood, these changes are provoked by infection and / or nutritional factors, as well as by exposure to hydrochloric acid. Proton pump inhibitors (prokinetics in postprandial distress syndrome) form the basis of treatment of peptic ulcer and epigastric pain syndrome; all patients with DUD and dyspepsia syndrome infected with H. pylori receive antihelicobacter therapy. Rabeprazole that is characterized by a long and powerful effect and minimal interaction with the cytochrome 2C19 system stands out from the proton pump inhibitors. Conclusion: acid aggression plays a very important role in the pathogenesis of duodenal ulcers diseases and FD; proton pump inhibitors form the basis for the treatment of such patients both in the form of monotherapy and as part of eradication regimens

TREATMENT OF HCV INFECTION BY A COMBINATION OF SOFOSBUVIR AND DACLATASVIR

The purpose of the review is to evaluate the efficacy and safety of using pangenotypic combination «of Sofosbuvir/Daclatasvir» — the direct action antiviral drugs in the treatment of chronic HCV infection at different stages of liver damage.Main provisions: Sofosbuvir is the antisense nucleotide, inhibiting RNA-dependent RNA-polymerase NS5B, this drug has earned a reputation as one of the strongest anti-replication drugs, including when there is interferon resistance. Daclatasvir is a powerful non-nucleotide inhibitor of NS5А protein, catalyzing formation of replicative complexes. Both components are proven to be effect against HCV genotypes 1-6. Their combination provides pangenotypic activity, and the mutual strengthening effect diminishes the risk of development of drug resistance. Indications for the administration of a combination «Sofosbuvir/Daclatasvi» are: treatment of HCV infection at the stage of acute hepatitis (for genotypes 1–6 of the virus), treatment for HCV infection at the stage of chronic hepatitis (for genotypes 1–6 of the virus), treatment of HCV infection in co-infection with HIV, treatment of HCV infection at the stage of liver cirrhosis, treatment of recurrent HCV infection after liver transplantation, treatment of HCV infection with immune manifestations.Conclusion: the combination «Sofosbuvir/Daclatasvir» is shown to be highly effective in the treatment of HCV infection of genotypes 1-6 with a frequency of SVR 93—97% at the stage of the hepatitis and 88—95% — at the stage of cirrhosis. Good tolerance and high efficiency has led to active use of this combination фе the stage of cirrhosis. This combination has been successfully used for the treatment of recurrence of HCV infection in the liver graft, including co-infection with HIV

First Russian Gastroenterology Olympiad

On October 21, 22, 23, 2022, within the framework of the 122nd International Session of the National School of Gastroenterology, Hepatology (NSGH) of the Russian Gastroenterological Association (RGA), the First Russian Gastroenterology Olympiad was held