Daily probiotics: benefits and reasonable application

This article reviewed the mechanisms of action of probiotics and the possible effects of individual strains on the general wellbeing if they are taken daily.The content and activity of bacteria in food products should be regulated by special guidelines. The balanced nutrition allows us to get healthy strains in a natural way. Daily consumption of certain strains as part of functional food products is promising for the prevention of obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, functional intestinal disorders, colon cancer, cardiovascular diseases and depression. The issues of safety of novel probiotic strains newly introduced in clinical practice require careful consideration. Synbiotics can comprise probiotic strains of bacteria (Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32, Bifidobacterium lactis Bl-04) with tolerance to acid, pepsin and bile salts, as well as the prebiotic inulin and vitamins B1, B2, B6 and B12 contributing to survival of beneficial bacteria. L. acidophilus is a common probiotic that occurs in the natural environment and food products, no cases of antibiotic resistance of this species have been established. Strains Lactobacillus acidophilus La-14, Lactobacillus rhamnosus Lr-32, Bifidobacterium lactis Bl-04 have a high adhesion capacity, strong inhibitory effects on intestinal pathogens, including fungi, anti-inflammatory effects, help to eliminate oxalates. As can be seen from the above, the use of probiotics and synbiotics is one of the most promising preventive fields of medicine

Duodenal Eosinophilia in Functional Dyspepsia

Aim: to present observation of a patient diagnosed with functional dyspepsia based on current guidelines, and having increased eosinophil counts in the biopsy specimen of duodenal mucosa. To consider possible causes of duodenal eosinophilia in the light of present-day concepts.Highlights. Patient K., 40 years old, complained of dyspeptic phenomena, the first appearance of which she had noted at the age of 18. The patient noted poor tolerance to canned and fermented foods, which provoked an increase in dyspepsia and sometimes caused watery diarrhea. The examination excluded “symptoms of concern”. Successful antihelicobacter eradication therapy was carried out. Morphological examination of the stomach showed phenomena of mild chronic inflammation without intestinal metaplasia or glandular atrophy. A biopsy of the mucosa of the descending part of the duodenum showed a moderate increase in the levels of mononuclears and eosinophils in its lamina propria without penetration into the epithelium of the villi or formation of clusters. The patient suffers from pollinosis; sensitization to birch pollen was diagnosed by a skin prick test. However, she has no oral allergy symptoms, which does not allow linking duodenal eosinophilia to food allergy. Based on current guidelines, the patient was diagnosed with functional dyspepsia. In addition to dietary restrictions, treatment courses with a proton pump inhibitor, itopride, and S-methylmethionine sulfonium chloride, which has an antihistamine effect, were recommended for periods of worsening dyspepsia.Conclusion. The clinical significance of duodenal eosinophilia and local histamine production in patients with a clinical diagnosis of functional dyspepsia deserves special attention. Triggering factors provoking the worsening of symptoms should be analyzed; in particular, a food diary and exclusion of food allergies are recommended. Histamine-neutralizing drugs may play a role in the treatment of FD with duodenal eosinophilia in the future

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

Technologically-Treated Polyclonal Affinity-Purified Antibodies to the Tumor Necrosis Factor-α, Brain Specific S-100 Protein and Histamine in Treatment of Functional Dyspepsia: Results of the Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

The aim of the study was to evaluate the efficacy and safety of Kolofort® (a complex medicine containing technologically processed forms of antibodies to S-100 protein, tumor necrosis factor-α and histamine) in the management of functional dyspepsia (FD) in outpatient clinical practice.Methods: Outpatients (N = 309) at the age of 18–45 in whom FD was diagnosed according to the Rome IV criteria were enrolled in a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients were randomized in two groups receiving Kolofort® or placebo 2 tablets tid for 8 weeks. The primary endpoint of the study was a change in the FD symptoms severity score according to the Gastrointestinal symptom score (GIS) at week 8. ITT and [PP] analysis were performed.Results: at week 8 the reduction in GIS sum score was observed in Kolofort® group and placebo group (by 7.2 ± 3.3 [7.2 ± 3.4] and 6.3 ± 4.6 [6.2 ± 4.5], respectively, p = 0.041 [0.039]). The proportion of cases with GIS score reduction by ≥4 was 88,1 % [88.6 %] and 79.1 % [79.6 %] in Kolofort® group and placebo group, respectively (p = 0.046 [p = 0.051]). None of the patients in Kolofort® group had progression of FD symptoms or required additional therapy. There were 29 adverse events (AEs) recorded in 25 patients including 16 cases in 13 (8.6 %) patients in Kolofort® group and 13 AEs in 12 (7.6 %) patients in placebo group.Conclusion: the clinical trial demonstrates the positive effect of Kolofort® in FD with a favorable safety profile

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

Reassessment of disease severity routine laboratory tests in the COVID-19 infection

Introduction. Publications demonstrate some limitations of National Early Warning Score 2 (NEWS-2) accuracy in assessment on coronavirus infection severity.The purpose of this study was to determine the value of the patient’s age and routine laboratory parameters in the assessment of patient’s general condition in coronavirus pneumonia and their relation to NEWS-2 scale parameters.Materials and methods. 50 case reports of patients with COVID-19 infection observed in the Sechenov University in January–March 2021 were analyzed. 34 % of patients were males aged 31 to 89 years (average age 55 years) and 66 % — females aged 40 to 91 (mean age 63). The diagnosis of pneumonia was confirmed by computed tomography. NEWS-2 scale total score was assessed.Results. According to the physician’s subjective assessment the condition was significantly more often assessed as moderate and severe. There was only a weak correlation between the blood oxygen saturation and the total NEWS-2 score (r = 0.165, α = 0.1). We found a mild correlation (r = 0.341, α = 0.1) between the patient’s age and NEWS2 score. Among the most significantly interrelated parameters were age, neutrophil count, serum creatinine, CRP, fibrinogen level. Seven interrelated parameters (age, body temperature, blood oxygen saturation, the neutrophils count, creatinine, CRP, fibrinogen), for which a reliable relation with other tests has been shown, were assigned with its special index according to their contribution to the assessment of the overall condition severity. An aggregated score (criterion X) was proposed for assessment of disease severity according to equation. The proportions of mild, moderate, and severe cases according to criterion X were 12 %, 64 % and 24 %.Conclusion. The preliminary results obtained in the study emphasize the importance of routine laboratory tests in assessment of coronavirus infection severity. An evident discrepancy between NEWS-2 score and X criterion may be very important for practice

Hymecromone Administration in Real Clinical Practice: Results of the Prospective Multicentre Observational Study in the Republic of Kazakhstan

Introduction. This multicentre prospective non-interventional observational study was conducted to obtain additional data about Odeston efficacy and safety in routine clinical practice. The objectives of the study included collection of clinical characteristics of patients, evaluation of Odeston effects in treatment of biliary pain and changes in the gallbladder emptying, evaluation of compliance to therapy, and treatment effect satisfaction.Materials and methods. The study was conducted from July 2020 to April 2021 at the premises of 60 study sites in 4 cities of the Republic of Kazakhstan. Patients having indications for Odeston administration according to the patient leaflet were enrolled. The study included 2 patient visits and an intermediate telephone contact. A visual analogue scale and RAPID questionnaire were used to characterise biliary pain; severity of associated symptoms, bowel habit and a quality of life according the SF-12 were also assessed. A rate of a ≥50 % reduction in symptom severity was used as a primary efficacy criterion; a rate of a ≥10 improvement in the SF-12 quality of life score was used as a secondary efficacy criterion. Compliance to treatment was evaluated using a number of days on Odeston. Treatment satisfaction was assessed using 5 grades.Results. 877 patients, 68.2 % of females and 31.8 % of males, were included in the study; the mean age was 46.0 ± 14.9 years. Primary functional biliary disorder was diagnosed in 65.3 % of patients, chronic non-calculous cholecystitis — 51.4 %, uncomplicated gallbladder disease — in 8.9 %, biliary sludge — 38.4 %, sphincter of Oddi functional disorder — 5.3 % of patients. A dose of Odeston was prescribed at the discretion of the physician. Group A patients received 600 mg (n = 89), group B received 1200 mg of Odeston a day (n = 788). In group B, an incidence of pronounced pain interference with daily living activities was higher. In both groups, the mean VAS scores were reduced to 1 point on treatment, a primary efficacy criterion was achieved in 77.3 % of patients in group A and in 79.8 % of patients in group B, р < 0.05. In both groups, a reduction in the incidence of constipation and diarrhea (р < 0,001) and an increase in the mean scores of physical and mental functioning were noted (р < 0.001, though a secondary efficacy criterion was not achieved (a ≥10 change in the SF-12 score). A prevalence of ultrasonographic sings of biliary sludge was reduced, and an increased gallbladder emptying was observed (p < 0.001). 77.4 % of patients in a total group of patients reported about drug administration for 21 days. A number of patients who were completely satisfied with treatment was higher in group B (p = 0.027).Conclusions. It was found that biliary pain interfered with daily living activities and commonly accompanied by other symptoms of gastrointestinal dysmotility. Odeston effectively reduces the severity of biliary pain, corrects dyspeptic disorders and normalizes stool pattern in patients with functional and organic diseases of the biliary system. Treatment satisfaction was higher with a dose of 1200 mg a day, particularly in more pronounced interference of pain with daily living activities

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