Vol 93, No 2 (2021)

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Full Issue


Enteropathy with impaired membrane digestion and the prospects for cytoprotective therapy

Parfenov A.I., Akhmadullina O.V., Belostotsky N.I., Sabelnikova E.A., Novikov A.A., Bykova S.V., Dbar S.R.


The article describes enteropathy with impaired membrane digestion (EIMD) as a new nosological form. The main clinical manifestation of EIMD is the poor tolerance of food products, in particular carbohydrates and a decrease in the activity of membrane enzymes, in particular, carbohydrates, in the mucous membrane of the small intestine. The cause of the disease can be acute intestinal infections, viruses, drugs and other agents that damage the small intestine. The pathophysiology, clinical picture and diagnosis of EIMD are described. The basis of therapy is rebamipide, which has the ability to reduce the symptoms of carbohydrate intolerance and increase the activity of disaccharidases.

Terapevticheskii arkhiv. 2021;93(2):129-137
pages 129-137 views

Original articles

Screening for celiac disease among patients of the gastroenterological profile

Bykova S.V., Sabelnikova E.A., Gudkova R.B., Noskova K.K., Krums L.M., Parfenov A.I.


Aim. To determine the frequency of celiac disease (CD) among gastroenterological patients and criteria for its active detection.

Materials and methods. 1.358 patients referred for gastroenterologist consultation from 2016 to 2019 was conducted, of which 140 had CD (339 males – 24.9%; 1019 females – 75.1%). The average age was 40.4±15.4 (18–86 years). All patients were determined anti-TTG IgA, IgG, and analyzed the clinical symptoms and analysis. The results were subjected to statistical processing Statistica 13.3 (StatSoft Inc., USA).

Results. In patients without CD (1218 people), high level of anti-TTG IgA and IgG was observed in 59 (4.8%), an increase in anti-TTG IgA – in 54 (4.4%), and anti-TTG IgG – in 38 patients (3.1%). The CD diagnosis confirmed in 51 patients (4.2%). The main symptoms were diarrhea (88%), abdominal pain (60.7%), bloating (73.8%), nausea (40.3%), weight loss (44.3%). Anemia was determined in 31.6%, serum iron – 33%, hypoproteinemia – 12.6%, hypoalbuminemia – 12%, hypokalemia – 5.48%, hypocalcemia – 21.9%. An increase in the level of AST – 14.5%, ALT – 14.6%. Comparative analysis showed that in the group with newly detected CD, anemia, malabsorption syndrome, increase AST, ALT were significantly more frequent than in patients with normal antibodies, which confirms the need to detect CD among patients with these laboratory abnormalities.

Conclusion. The incidence of CD among patients with a gastroenterological symptoms was 4.2%. Analysis of clinical and laboratory data has shown that a comprehensive analysis of clinical symptoms and laboratory indicators at the stage of primary treatment will allow timely identification of CD patients and prescribe GFD.

Terapevticheskii arkhiv. 2021;93(2):145-149
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Loss of response and frequency of adverse events in patients with ulcerative colitis and Crohn’s disease when switching from the original infliximab to its biosimilars

Knyazev O.V., Zvyaglova M.Y., Kagramanova A.V., Li I.A., Sabelnikova E.A., Lishchinskaya A.A., Kulakov D.S., Parfenov A.I.


Aim. To define the frequency of adverse events and loss of the response in patients with ulcerative colitis (UC) and Crohn’s disease (CD), treated with original medicine infliximab (IFX) “Remicaide” and its biosimilars.

Materials and methods. We included 154 patients with IBD: 78 UC patients (50.6%) и 76 CD patients (49.4%), treated with original medicine IFX Remicade and its biosimilars. In our study we did not include patients, who previously underwent induction treatment with IFX and its biosimilar.

Results. Among 78 UC patients, IFX was cancelled in 25 (32.0%) patients and they were switched to the other anti-TNF inhibitor or medicine with the another mechanism of action; in patients group, treated with biosimilar – 16 (20.5%) and 9 (11.5%) patients, who were interchanged biosimilar and/or original IFX. Among 76 CD patients IFX was cancelled in 20 (26.3%) patients: 11 (14.5%) patients in group, treated with similar trade name biosimilar, 8 (10.5%) patients, who were interchanged biosimilar and/or original IFX and 1 patient (1,3%), receiving original IFX. We found no difference in the secondary loss of response and adverse events in patients with CD and UC, switched from original IFX to biosimilar (p=0.6257 and p=0.6635, correspondingly). The frequency of the secondary loss of response or adverse events in patients with UC and CD, switched from original IFX to IFX biosimilar, was similar (p>0.05).

Conclusion. Approximately 30% of IBD patients, receiving IFX biosimilar, will be switched to the other anti-TNF therapy or medicine with the another mechanism of action because of secondary loss of response or adverse events.

Terapevticheskii arkhiv. 2021;93(2):150-157
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Efficacy of butyric acid inclusion in eradication regimens for Helicobacter pylori infection: a meta-analysis of controlled trials

Andreev D.N., Kucheryavyy Y.A., Maev I.V.


Aim. Systematization of data on the efficacy and safety of butyric acid inclusion in eradication therapy (ET) regimens for Helicobacter pylori infection.

Methods. Research searches were carried out in the electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, the Russian Science Citation Index (RSCI) until November 2020. All controlled studies comparing the efficacy and/or safety of including butyric acid in ET regimens for H. pylori infection were included in the final analysis.

Results. The meta-analysis included 6 controlled studies (1 – Italy, 5 – Russia) involving 736 patients (381 in the ET groups with butyric acid; 355 in the comparison groups). The pooled eradication efficiency in the butyric acid groups was 90.23% (95% confidence interval – CI 86.734–93.069), while in the comparison groups it was 65.69% (95% CI 60.441–70.669). Meta-analysis showed that the addition of butyric acid to ET regimens significantly increased the eradication efficiency (odds ratio – OR 5.355, 95% CI 3.504–8.184; p<0.001). There was no significant heterogeneity between results (p=0.1408; I2=42.1%). The addition of butyric acid to ET regimens significantly reduces the risk of diarrhea (OR 0.225, 95% CI 0.0923–0.549; p=0.001; I2=34.21%) and abdominal distention (OR 0.357, 95% CI 0.155–0.818; p=0.015; I2=80.13%) by the end of the 1st week of treatment.

Conclusion. The present meta-analysis demonstrated that the inclusion of butyric acid in ET regimens for H. pylori infection significantly increases the effectiveness of treatment and reduce the incidence of side effects. Apparently, the increase in the effectiveness of eradication is due to an increase in patient compliance with treatment due to an improvement in the safety profile of therapy.

Terapevticheskii arkhiv. 2021;93(2):158-163
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Disorders of carbohydrate-lipid metabolism and galectin-3 level as factors of liver fibrosis progression in chronic hepatitis C

Kovalevа V.A., Zhevnerova N.S., Antonova T.V.


Aim. To assess the effect of metabolic disorders and galectin-3 levels on the progression of liver fibrosis in chronic hepatitis C.

Materials and methods. 106 patients with HCV without decompensated liver cirrhosis were examined. Exclusion criteria: age younger than 20 and older than 65 years, diabetes, coronary heart disease, hypertension, alcoholism, drug addiction. Laboratory examination (biochemical blood test, enzyme immunoassay (ELISA) with determination of HCV-Ab antibodies, viral load) was supplemented with liver elastometry (Fibroscan®) with fibrosis assessment (kPa, METAVIR scale). The body mass index of Quetelet (kg/m2), the presence of abdominal obesity, insulin resistance were evaluated. Serum levels of insulin and galectin-3 were determined by ELISA.

Results. In 45% of patients, an increase in ITM was revealed, in 44% – abdominal obesity, in 62% – insulin resistance. In 75% abdominal obesity was determined in patients with liver fibrosis F3–F4. Insulin resistance was found more often in patients with fibrosis F0–1 – 56.7%. Significant correlations between the level of galectin-3 and the degree of liver fibrosis (in kPa) [r=0,206, p=0,034], as well as the stage of liver fibrosis (on the METAVIR scale) [r=0,247, p=0,01] were obtained. The level of galectin-3 in liver cirrhosis was 6.32 (4.57; 9.64) ng/ml, which is significantly higher than in F0 – 3.96 (1.45; 5.30) ng/ml (p=0.002) and F1 – 3.85 (2.20; 5.83) ng/ml (p=0.002). By calculating the specificity and sensitivity of isolated for F4 stage of liver fibrosis (ROC-curve, the level of galectin-3 is 5.21 ng/ml), the level of specificity of 74.7%, sensitivity of 74% was established.

Conclusion. We found a significant relationship between the disturbances of carbohydrate-lipid metabolism and liver fibrosis, the level of galectin-3 and fibrosis stage of the liver. The prognostic value of increasing the level of galectin-3 for predicting the cirrhotic stage of liver fibrosis is substantiated.

Terapevticheskii arkhiv. 2021;93(2):164-168
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The importance of the bacterial overgrowth syndrome in the development of disorders metabolic functions of the liver in non-alcoholic fatty liver disease

Vakhrushev Y.M., Lukashevich A.P.


Aim. To study the basic metabolic functions of the liver in patients with non-alcoholic fatty liver disease and to assess the relationship of these disorders with the bacterial overgrowth syndrome.

Materials and methods. 50 patients with non-alcoholic fatty liver disease at the stage of steatosis were examined. In the verification of the diagnosis, hepatobiliary system ultrasound and FibroMax test data were used. A study was conducted of indicators of lipid, carbohydrate, protein, pigment, mineral metabolism and the exchange of enzymes in the blood. The bacterial overgrowth syndrome was studied by the results of a hydrogen breath test with lactulose using a LactofаH2 analyzer.

Results. Patients with non-alcoholic fatty liver disease showed a significant increase in total cholesterol (median 5.9 mmol/l vs 5.0 mmol/l, p=0.000013), triglycerides (1.35 g/l vs 0.9 g/l, p=0.014), glucose (5.65 mmol/l against 5.1 mmol/l, p=0.000001) of blood serum compared with the control group. An increase in total protein and a tendency to decrease in albumin, an increase in serum sodium and calcium were detected. In patients with non-alcoholic fatty liver disease there is a significant increase in the markers of cytolysis and cholestasis compared with the control group. The bacterial overgrowth syndrome was detected in 72% of cases, with ileocecal valve function impaired in 50% of patients, gastrointestinal motility slowed down, or colon dysbiosis occurred. A correlation analysis revealed positive relationships between the bacterial overgrowth syndrome on the one hand and glucose (r=0.83, p<0.05), total protein (r=0.35, p<0.05), calcium (r=0.5, p<0.05) on the other hand; negative relationship between the bacterial overgrowth syndrome and albumin (r=-0.8, p<0.05). In this case, a positive relationship between the bacterial overgrowth syndrome and the increase in glycemia after glucose loading, that is, absorption in the small intestine, was revealed.

Conclusion. The established violations of the metabolic functions of the liver with non-alcoholic fatty liver disease are closely related to the bacterial overgrowth syndrome.

Terapevticheskii arkhiv. 2021;93(2):169-173
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The role of fibroblast growth factor 19 in pathogenesis of bile acid diarrhea of the patients who underwent cholecystectomy

Indeykina L.К., Sabelnikova Е.А., Varvanina G.G., Silvestrova S.U., Smirnova А.V., Krums L.М., Viaznikova A.A., Parfenov А.I.


The occurrence of chronic diarrhea after cholecystectomy (CCY) has been described by many researchers. However, the main mechanisms of the development of this diarrhea are not fully understood. Supposed that dysregulation of the bile acids (ВA) absorption in the ileum is played a significant role in the development of diarrhea syndrome.

Aim. To determine the role of the fibroblast growth factor 19 (FGF19) level in the serum and BA concentration in feces in pathogenesis of bile acid diarrhea (ВАD) in patients after CCY.

Materials and methods. Sixty-one patients were examined at various times after CCY: 30 patients with chronic diarrhea that appeared after CCY (group 1) and 31 patients with normal stools (group 2). In all patients, the level of FGF19 in the blood serum, and the daily excretion of BA in the feces were studied. The control group consisted of 28 healthy individuals.

Results. In the 1st group we found lower concentrations of FGF19 in the blood serum 86.2 ng/ml (67.8; 117.8) compared with concentrations in the 2nd group – 259 ng/ml (170.6; 318.8), p<0.001. The daily excretion of bile acids with feces in the 1st group was 657.4 mg/day (524.6; 830.1), which was twice more than in the 2nd group and the control group. It was established an inverse correlation between serum concentration of the FGF19 and the BA excretion in the feces in all examined patients. It indicates a possible relationship between the low concentration of FGF19 in blood serum and malabsorption of the BA.

Conclusion. Low level of FGF19 in the blood serum and a high excretion of BA in the feces may be one of the causes of BAD in patients undergoing cholecystectomy. Our results indicate the important role of FGF19 in the development of chronic diarrhea, which can be considered as one of the variants of postcholecystectomy syndrome.

Terapevticheskii arkhiv. 2021;93(2):174-178
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Biliary sludge: pathogenesis, etiology and drug therapy

Bakulin I.G., Avalueva E.B., Serkova M.U., Skvortsova T.E., Seliverstov P.V., Shevyakov M.A., Sitkin S.I.


Aim. To evaluate the effectiveness of the use of ursodeoxycholic acid (UDCA) for the treatment of biliary sludge (BS) and to compare the therapeutic effectiveness of the German substance UDCA and generic drugs from other manufacturers.

Materials and methods. The study involved 65 patients diagnosed with BS (K80.8). To assess the severity of BS, ultrasound of the gallbladder was performed before treatment, after 1, 3, 6 months during therapy, as well as an assessment of its contractility. All patients were randomized into 2 groups. Patients of the main group received UDCA Ursofalk (Germany) at a dose of 10 mg/kg for at least 6 months. Patients in the comparison group received UDCA (another manufacturer) at a dose of 10 mg/kg for at least 6 months.

Results. After 3 months of follow-up, the number of patients with dissolved sludge in the main group was 87.1%, while in the comparison group – 50%. In 71% of patients, the normalization of the lean volume of the gallbladder was noted, and in the comparison group only in 47.1%. After 6 months of follow-up, complete resolution of BS in the main group was observed in 93.5% of cases, and in the comparison group in 73.6% of cases.

Conclusion. As a result of the study, the high effectiveness of Ursofalk during oral litolysis in patients with stage I GI (BS) in the first 3 months of therapy, as well as the normalization of the contractile function of the gallbladder, were noted.

Terapevticheskii arkhiv. 2021;93(2):179-186
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Assessment of individual risk of food interactions while taking warfarin

Skirdenko Y.P., Nikolaev N.A.


Aim. To develop a questionnaire to assess the individual risk of food interactions in a patient taking warfarin.

Materials and methods. Based on the review of 159 literature sources, a test version of the questionnaire was formed. 196 respondents took part in the pilot part of the study to assess the multiplicity and volume of food consumption. For the initial assessment of the risk limit of the diet, complications of warfarin therapy were registered no earlier than 24 weeks later.

Results. The final version of the questionnaire included 25 products that are most frequently consumed and significant in relation to the risk of alimentary interactions. The questionnaire contains 2 groups of products: increasing and decreasing the activity of warfarin. The volume and frequency of use of each product is evaluated in points that are calculated as the simple product of weights of frequency and volume, with a minimum value of 0 and maximum of 12. The number of points for each product is calculated separately. The points obtained are summed for a group of products that increase the activity of warfarin, and for a group of products that reduce it, and the overall risk score is calculated. The average number of points for the use of products that affect the activity of warfarin in patients with AF with complications of therapy was 75.78±31.97 b. The calculation of the design validity of the questionnaire (Cronbach’s a=0.864) showed a good level for confirmation purposes.

Conclusion. A specialized questionnaire was developed, implemented as a computer program, to assess the significance of food preferences in ensuring the safety and effectiveness of warfarin therapy. Further research is required to determine the risk limit of alimentary interactions of warfarin, but now this questionnaire can be used to monitor the uniformity of consumption of products that affect its activity. The authors suggested using a questionnaire for assessing the risk of food interactions as one of the factors influencing the decision to prescribe warfarin to patients with insufficient adherence to lifestyle modification.

Terapevticheskii arkhiv. 2021;93(2):187-192
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Diagnostic and conservative treatment nuances in patients with obstructive jaundice: in the wake of Russian consensus

Khatkov I.E., Avanesyan R.G., Akhaladze G.G., Beburishvili A.G., Bulanov A.Y., Bykov M.I., Vinnitskaia E.V., Virshke E.R., Gabriel S.A., Granov D.A., Darvin V.V., Dolgushin B.I., Dyuzheva T.G., Efanov M.G., Korobka V.L., Korolev M.P., Kulabukhov V.V., Maystrenko N.A., Melekhina O.V., Nedoluzhko I.Y., Okhotnikov O.I., Pogrebnyakov V.Y., Polikarpov A.A., Prudkov M.I., Ratnikov V.A., Solodinina E.N., Stepanova Y.A., Subbotin V.V., Fedorov E.D., Shabunin A.V., Shapovalyants S.G., Shulutko A.M., Shishin K.V., Tsvirkun V.V., Chzhao A.V., Kulezneva Y.V.


The research was performed at the Loginov Moscow Clinical Scientific Center. It is based on Russian obstructive jaundice (OJ) consensus results, considered at the 45th annual Central Research Institute of Gastroenterology Scientific session “Oncological issues in the gastroenterologist practice” (1 March 2019). The article objective is to note the diagnostic and conservative treatment current issues in patients with OJ. The increase in the number of patients with OJ of different etiology provides problem actuality. In a large number of cases, medical treatment is delayed due to inadequate diagnostic and management, while correct patients routing today can be provided regardless of medical institution level. In this article the examination steps and conservative treatment role in patients with biliary obstruction management are presented.

Terapevticheskii arkhiv. 2021;93(2):138-144
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Clinical notes

Sarcoidosis and primary biliary cholangitis in a patient with cholestasis

Brovko M.Y., Akulkina L.A., Kalashnikov M.V., Rozina T.P., Nekrasova T.P., Sholomova V.I., Konovalov D.V., Yanakayeva A.S., Moiseev S.V.


Primary biliary cholangitis and sarcoidosis are both cholestatic liver diseases. Currently, there are no established specific criteria for distinguishing the diseases from each other; diagnosis is based on the anamnesis, as well as the results of physical, laboratory and instrumental examination. The case report presents a female patient with a rare combination of histologically verified liver sarcoidosis and primary biliary cholangitis. Despite the similar clinical manifestations, the approaches to the treatment of these diseases are completely different, that underlines the importance of the differential diagnosis to exclude combined liver damage.

Terapevticheskii arkhiv. 2021;93(2):193-198
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Lung disease/pneumonitis in a patient with ulcerative colitis due to mesalazine

Sablin O.A., Chernousova V.V., Komlev A.D.


Mesalazine is a main medicine for treatment of ulcerative colitis. Most patience of left-sides and total colitis receive oral mesalazine for many years. Currently, there is a little information about the tolerability and safety of long-term use of mesalazine. The eosinophilic pneumonia, organizing pneumonia, and nonspecific interstitial pneumonia are very rare adverse effects of ulcerative colitis treatment with mesalazine. The article presents case of the development interstitial lung disease induced by mesalazine under long-term maintenance treatment for three years in the young patient with ulcerative colitis. It shows the difficulties in diagnosing this disease due to the work-long low-grade fever in manifestation of pneumonitis, the similarity of clinical and radiological manifestations (diffuse bilateral pattern in chest imaging). The article demonstrates the limitations of modern laboratory and instrumental diagnostic methods for the differentiation of disseminated lesions of the lung tissue, and shows the importance of elimination treatment of mesalazine-induced pneumonitis.

Terapevticheskii arkhiv. 2021;93(2):199-203
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Molecular factors associated with regression of liver fibrosis of alcoholic etiology

Kiseleva Y.V., Zharikov Y.O., Maslennikov R.V., Pavlov C.S., Nikolenko V.N.


Liver fibrosis develops as a result of chronic liver damage of various etiologies, is characterized by excessive synthesis of connective tissue by activated stellate liver cells. The toxic effect of alcohol is one of the most significant and common etiological factors worldwide. Stellate cell activation results from the interaction of multiple molecular fibrogenic pathways triggered by intracellular and extracellular, hepatic and extrahepatic stimuli. Data analysis showed that knowledge about these abnormal pathways and biomolecular processes may further contribute to the improvement of approaches to assessment of disease prognosis and treatment of alcoholic liver disease.

Terapevticheskii arkhiv. 2021;93(2):204-208
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Pathogenetic aspects of the development of cholelithiasis in patients with metabolic syndrome

Uspenskiy Y.P., Fominykh Y.A., Nadzhafova K.N., Vovk A.V., Koshcheev A.V.


Nowadays there is a steady tendency to increase the number of patients with gallstone disease and metabolic syndrome. Increasingly, gallstone disease is called a non-canonical cluster of metabolic syndrome, because the main components of metabolic syndrome are also modifiable risk factors for gallstone disease. This article discusses the pathogenetic parallels in the development of gallstone disease and metabolic syndrome - insulin resistance and hormones of adipose tissue, lipid metabolism disorders, immune factors and the cytokine system. There are described possible effects of cholecystectomy on metabolism in patients with metabolic syndrome.

Terapevticheskii arkhiv. 2021;93(2):209-214
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Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)

Iakupova A.A., Abdulkhakov S.R., Safin A.G., Alieva I.M., Oslopova J.V., Abdulkhakov R.A.


Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.

Terapevticheskii arkhiv. 2021;93(2):215-221
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Features of intestinal microbiota disorders in the development of metabolic disorders in non-alcoholic fatty liver disease

Livzan M.A., Krolevets T.S., Mozgovoy S.I., Nikolaev N.A., Nelidova A.V.


We discussed about the term “intestinal permeability” like as the mucosal barrier – a single structural and functional conception that includes the layer of mucus, the indigenous microbiota and the epithelium of the mucosa in this publication. Information was presented about the role of the microbiota, the composition of intestinal mucus, epithelial cells and proteins of tight junctions which lead to various metabolic diseases. The complex pathogenetic interactions are formed between the intestinal mucosal barrier, metabolic disorders such as non-alcoholic fatty liver disease and cardiovascular diseases. The complex researches and modification of this interactions will allow to create personalized approaches and to prevent of these diseases.

Terapevticheskii arkhiv. 2021;93(2):222-227
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Clinical value of antibodies in inflammatory bowel diseases

Aleksandrova E.N., Novikov A.A., Lukina G.V., Parfenov A.I.


Inflammatory bowel disease – IBD (Crohn’s disease – CD, ulcerative colitis – UC) – immune-mediated diseases of the digestive tract of unknown etiology. The basis of the pathogenesis of IBD is a violation of the protective mechanisms of the intestinal barrier as a result of a complex interaction of environmental factors, a genetic predisposition and defects in the activation of the immune response in the lymphoid tissue of the intestinal mucosa. Three groups of antibodies are detected in the sera of IBD patients: autoantibodies, antimicrobial antibodies and antibodies to peptide antigens. In CD, the most useful diagnostic markers are ASCA; in UC patients – pANCA. Antibodies are not among the diagnostic criteria for CD and UC, the diagnosis of which is traditionally made on the basis of a complex of clinical, radiological, endoscopic and histological signs, but can be used as useful additional non-invasive markers for early diagnosis, assessment of clinical phenotypes, prognosis and effectiveness of treatment of these diseases.

Terapevticheskii arkhiv. 2021;93(2):228-235
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New approaches to the pathogenesis, clinic, and treatment of hepatic encephalopathy

Podymova S.D.


This review article presents new approaches to the assessment of key pathogenesis factors, clinical features, and treatment of hepatic encephalopathy (HE) associated with liver cirrhosis. Various clinical variants of the course of HE in patients with cirrhosis of the liver areconsidered, which are important for the choice of treatment and prevention of repeated relapses of HE. Analyzed the ammonia hypothesis of pathogenesis and associated hyperammonemia, which is the basis of most modern treatment methods. These data on the activation of the adaptive pathway for removing ammonia in the form of glutamine are used in the further study of drugs that enhance the clearance of ammonia. The possibility of reducing GABA-ergic tone due to the effect of the antagonist on the neurosteroid site in the GABA receptor complex is emphasized.

Terapevticheskii arkhiv. 2021;93(2):236-242
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History of medicine

Historical milestones in the knowledge of celiac disease: on the 80th anniversary of the discovery of W.-K. Dike of the аgluten diet

Parfenov A.I.


The article describes the main achievements in the knowledge of celiac disease – a mysterious disease known since the time of Hippocrates. The most important discovery was made by Willem-Karel Dicke, in 1941 linking the cause of the disease with the consumption of bread. Dicke is recognized as an outstanding medical worker in Holland. His memory and contribution to medicine is embodied in the Dicke Medal, the most prestigious award of the Dutch Society of Gastroenterology.

Terapevticheskii arkhiv. 2021;93(2):243-248
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