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Ivan Mikhailovich Sechenov is a Russian physiologist, a natural scientist, and the creator of the Russian physiological school. The classic work «Reflexes of the Brain», published in 1863, became revolutionary in its own way for medicine and society, since the reflex nature of conscious and unconscious activity was proved. Along with numerous well-known scientific works, there is an early student publication in the Moscow Medical Journal published by A. I. Polunin. It describes the medical history of a patient with a tumor who was unsuccessfully treated for a long time in accordance with the humoral theory of pathology. This publication makes it possible to understand why I. M. Sechenov became disillusioned with practical medicine, but found his vocation in the study of physiology. The article is devoted to the 195th anniversary of the birth of I. M. Sechenov.

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.

The paper presents an update on the epidemiology, main clinical manifestations, and diagnostic methods in IgG 4 -associated sclerosing cholangitis. It highlights the importance of morphological and immunohistochemical studies in the diagnosis of the disease. It describes a case of diagnosing IgG 4 -associated sclerosing cholangitis when examining the surgical material from a patient with suspected cholangiocellular carcinoma of the hepatic hilus.

Leishmaniasis is a vector-born parasitic disease characterized by predominant cutaneous or visceral involvement with fever, hepatosplenomegaly and anemia. Leishmaniasis has relatively high prevalence in tropical and subtropical areas. Several sporadic and mostly imported cases are detected in Russian Federation. Nevertheless, some local incidents are noted in southern areas (Crimea, Dagestan). Lack of epidemiological alertness hampers confirmation of diagnosis and may lead to incorrect treatment. The article summarizes current state of knowledge in epidemiology, diagnostic approach and treatment of leishmaniasis. Particular clinical case is discussed.

The paper presents a unique case of an autopsy study of the concurrence of two diseases, such as liver alveococcosis and hepatocellular carcinoma, in a 46-year-old woman with obvious hypercoagulability syndrome caused by parasitic invasion. It gives the macroscopic and histological characteristics of this case.

The article is published based on the results of the Russian Consensus on the diagnosis and treatment of primary sclerosing cholangitis (PSC), discussed at the 44th annual Scientific Session of the CNIIG "Personalized Medicine in the Era of Standards" (March 1, 2018). The aim of the review is to highlight the current issues of classification of diagnosis and treatment of patients with PSC, which causes the greatest interest of specialists. The urgency of the problem is determined by the multivariate nature of the clinical manifestations, by often asymptomatic flow, severe prognosis, complexity of diagnosis and insufficient study of PSC, the natural course of which in some cases can be considered as a function with many variables in terms of the nature and speed of progression with numerous possible clinical outcomes. In addition to progression to portal hypertension, cirrhosis and its complications, PSC can be accompanied by clinical manifestations of obstructive jaundice, bacterial cholangitis, cholangiocarcinoma and colorectal cancer. Magnetic resonance cholangiography is the main method of radial diagnostics of PSC, which allows to obtain an image of bile ducts in an un-invasive way. The use of liver biopsy is best justified when there is a suspicion of small-diameter PSC, autoimmune cross-syndrome PSC-AIG, IgG4-sclerosing cholangitis. Currently, a drug registered to treat primary sclerosing cholangitis which can significantly change the course and prognosis of the disease does not exist. There is no unified view on the effectiveness and usefulness of ursodeoxycholic acid and its dosage in PSC. Early diagnosis and determination of the phenotype of PSC is of clinical importance. It allows to determine the tactics of treatment, detection and prevention of complications.

Clinical features of overlap autoimmune hepatitis/primary biliary cholangitis and morphological-proved sarcoid lesions (lungs, lymph nodes, skin) were performed. Data of long-term clinical observation presented in comparison with the results of laboratory datas, instrumental and morphological studies of liver tissue, lungs, skin. The modern aspects of pathogenesis of association autoimmune and granulomatous diseases arediscussed on the example of clinical cases of combination of cholestatic variants of autoimmune hepatitis and generalized sarcoidosis. Keywords: sarcoidosis, autoimmune hepatitis, primary biliary cholangitis, primary biliary cholangitis-autoimmune hepatitis-overlap, extrahepatic manifestations.

The paper gives an update on the pathogenesis and main clinical manifestations of primary (hereditary) hemochromatosis and its diagnostic methods. It emphasizes the importance of genetic research in the diagnosis of the disease. Its clinical manifestations are associated with iron deposition in organs, such as the liver, pancreas, joints, skin, and heart. The paper points out the importance of liver biopsy using Perls' reaction for the diagnosis of liver damage with the development of fibrosis, cirrhosis, and cancer as the main cause of death in patients with hereditary hemochromatosis and presents the results of examining liver biopsy specimens in patients with hemochromatosis.

Aim: To summarize the experience of a multidisciplinary therapy hospital in treating patients with hepatitis C virus (HCV)-associated cryoglobulinemic vasculitis (CV)., Subjects and Methods: Seventy-two patients (mean age, 49.4±10.3 years) with HCV-associated CV were examined and followed up for an average period of 2.8±3.6 years. The efficiency of traditional (corticosteroids ± cyclophosphamide) and selective (rituximab) immunosuppressive therapy (IST) was estimated in 31 and 15 observations, respectively, and that of antiviral therapy (AVT) in 25. Vasculitis activity was assessed using the Birmingham vasculitis activity score (BVAS). The patients' survival was studied; multivariate logistic regression analysis was carried out., Results: 24 (33.4%) of the 72 patients had a stage of liver cirrhosis (LC). The pretreatment mean BVAS was 11.9±7.2 (range 2 to 36). Severe CV (BVAS ≥15) was present in 30.6% of the patients. AVT was accompanied by achievement of sustained virologic response in 48% of the patients, clinical remission in 68% and had an advantage over IST in relation to long-term treatment results. Rituximab was significantly more effective than traditional immunosuppressants (remission rates of 73 and 13%, respectively). Combined therapy (rituximab and AVT) was most effective in patients with severe forms of vasculitis. Sixteen patients died from complications of vasculitis (37.5%), infection (37.5%), and LC (25%). The factors adversely affecting prognosis were age >55 years (odds ratio (OR), 4.49), the presence of LC (OR, 3.68), renal failure (OR, 4.66) and the use of glucocorticosteroids (OR, 3.91)., Conclusion: HCV-associated CV can determine the prognosis of chronic HСV infection. AVT is the treatment of choice in all patients with HСV-associated CV. AVT must be combined with rituximab therapy in patients with severe forms of vasculitis.

Background: Schnitzler syndrome (SS) is a rare clinical entity characterized by chronic recurrent urticarial rash, monoclonal IgM gammopathy, intermittent fever and other symptoms. In this report, we present the cases of two patients with SS: a male and a female aged 50 and 49 years, respectively. Both patients had hyperimmunoglobulinemia E and showed good response to elimination diet., Methods: The patients had chronic urticaria, IgM gammopathy and an elevation of the serum levels of inflammation markers. Total IgE levels were found to be high (2000 U/ml and 540 U/ml, respectively). No underlying causes for hyperimmunoglobulinemia E (allergy, parasites, etc.) were revealed. The first patient did not respond to the treatment with antihistamines, while the second one responded only to high doses. The response to prednisolone in the second patient was incomplete., Results: Following a strict elimination diet resulted in marked improvement in skin lesions in both patients. In one of our patients we observed a decrease in IgE and IgM levels after a 3 week diet. The systemic symptoms persisted and improved only after adding pefloxacin, followed by a 3-day empirical course of intravenous prednisone in the first patient and a course of plasmapheresis in the second one., Conclusion: The high serum levels of total IgE may be associated with chronic urticaria activity, severe disease course and a poor response to treatment with antihistamines, and may be considered a possible marker of a subset of patients with SS showing a good response to the restriction diet. In general, we can assume that elimination diet can have an influence on the skin lesions and other symptoms of SS as well as on total IgE and IgM levels, but such association, the underlying mechanisms and the reasons for excessive IgE synthesis should be investigated in further studies.

The stimulatory effect of cryoprecipitate on liver regeneration was studied in rabbits with cirrhosis of the liver induced by subcutaneous injection of tetrachloromethane. Cryoprecipitate stimulated the hepatocyte regeneration (appearance of binuclear and proliferating cells) in liver tissue in cirrhosis, but the initial structure of the liver was not restored. The newly formed focus of regeneration with proper girder structure of hepatocytes forced back the connective tissue. Highly concentrated solution of fibrinogen, injected by puncture method into cirrhotic hepatic tissue, stimulated its regeneration.

The aim of this prospective study was too asses the frequency and clinical significance of metabolic syndrome (MS), insulin resistance (IR) and hepatic steatosis in 114 patients with chronic hepatitis C (HCV) genotype 1. MS was found in 47% and IR in 50% of the cases. Diagnosis of IR in patients without MC and marked fibrosis supported the role of HCV in the development of metabolic abnormalities. Hepatic steatosis was found in 38% of the patients and the degree of steatosis significantly correlated with that of fibrosis. Obesity, IR, steatosis and liver cirrhosis were independent negative predictors of the response to the treatment with peginterferon alpha and ribavirin.

Aim: To estimate the incidence and clinical value of metabolic syndrome, insulin resistance, and steatosis in patients with chronic hepatitis C (CHC) caused by its virus genotype 1., Subjects and Methods: One hundred and fourteen patients (67 men and 47 women; mean age 44.9 +/- 13.3 years) were examined., Results: There were high incidence rates of metabolic syndrome (47.2%) and insulin resistance (50%), in the genesis of which the host-virus interaction is discussed. There was an independent correlation of the insulin resistance and elevated leptin levels with abdominal obesity and hepatic steatosis; however, these indicators did not correlate with the stage of fibrosis. At the same time hepatic steatosis (found in 38% of the patients) and its degree correlated with the stage of fibrosis. Thirty-four of 66 (54.5%) patients receiving antiviral therapy achieved a stable virological response., Conclusion: Obesity, hyperglycemia, and significant insulin resistance along with the stage of hepatic cirrhosis are independent cofactors that determine no treatment response.

A case of a lesion of the central nervous system in Wegener's granulomatosis with neuritis of craniocerebral nerves, granulomas, vasculitis and foci of ishemic necrosis and hemorrhages in the brain tissue is reported. Diagnosis of Wegener's granulomatosis in a female aged 48 years was confirmed morphologically and by detection of specific antibodies. In spite of prednisolone (20 mg/day) and cyclophosphamide treatment (200 mg per week), hemiplegia, aphasia appeared which progressed and resulted in a death of the patient. Histologically lesions in many organs were found: middle ear, lungs, kidneys, brain, destructive vasculitis, necrotic foci and polymorphic lung granulomas, fibrosing alveolitis, polymorphocellular granulomas, multiple infarctions in the kidneys, endothrombovasculitis, necrotic foci and granulomas with glial reaction in the brain tissue.

The study results related with the rate of vascular purpura in 660 patients with different-type chronic diffusive hepatic pathologies both of the viral and other natures are described in the paper. The main regularities characterizing the phenomenon (spread and possible cause of purpura development) are defined. According to an analysis of actual materials, dermal vasculitis is not an exclusive feature of virus-associated hepatitis or liver cirrhosis. Vascular purpura can be regarded, on the basis of the obtained data, as a universal sign typical of any liver pathologies.

To study clinicomorphological characteristics and a course of chronic HbeAg-negative HBV-infection with a normal level of aminotransferases, 38 patients whose blood contained HbsAg, HBVDNA and anti-Hbe were divided into 2 groups: with normal (20 patients, test group) and elevated (18 patients, control group) level is of aminotransferases. All the patients' livers were studied morphologically and semiquantitative test for viremia was made. Compared to the controls, the test group patients had low morphological activity (3.4 +/- 1.1 and 8.7 +/- 3.2, respectively, p < 0.005), a fibrosis degree (1.1 +/- 0.4 and 2.3 +/- 1.4 score, respectively p < 0.01) and viremia (log 10 - 3.7 +/- 1.2 vs 6.1 +/- 2.4, p < 0.05). The monofactor analysis has established that viremia 10(5) cop/ml maximum significantly associates with a normal level of aminotransferases (chi-square = 7.89, p = 0.005) while viremia higher than 10(7) cop/ml strongly correlates with a high level of aminotransferases (chi-square = 4.11, p = 0.043). Follow-up of patients with a normal level of aminotransferases for 28 +/- 24 months (6-72 months) showed neither deterioration of the clinical status nor laboratory changes. Thus, patients having anti-HBe and no HbeAg with a normal level of ALT and low viremia (under 10(5) cop/ml) can be considered inactive carriers of HbsAg. In spite of a relatively favourable prognosis, these patients should be followed up for a long time.

A case of microscopic polyarteritis in a male aged 45 years having hypertension for 22 years is reported. There were clinical manifestations (hemorrhages, subfebrile temperature, arthralgias and others) and damages in many organs: productive-necrotic alveolitis, capillaritis of various organs, morphological features of hypertension, atherosclerosis, subendocardial myocardial infarction. The leading clinical feature was rapid progression of renal and pulmonary-heart failure.

A rare disease in a female of 60 is reported. Telangiectasias of skin venules, brain, mediastinum, stomach, duodenum and jejunum were found. The disease manifested with repeated massive intestinal bleedings. Elastic fibers alterations were found in the ectatic vessels and surrounding connective tissue.

28 liver biopsies from patients with sarcoidosis were studied with the use of multifactor mathematical methods. Granuloma morphogenesis in the liver results from the effect of the antigen (which is realized possibly through cytokines), "scarring" and "lymphoidization". Non-linear dependence between the morphogenesis factors is revealed and thus the hypothesis about the presence in the sarcoidosis liver of the three types of granulomas and their transformation from one type into another is confirmed.

Protein kinase C (PK C) activity in cells of two ethidium bromide (EB) resistant clones with different proliferating rates, derived from CHO-K1 cell line, was assayed. After selection in the presence of 1 mkg/ml EB cells of isolated clones acquired cross-resistance also to some unrelated drugs of different structure. It is shown that resistant cells after the first step of selection elevated PK C activity level in membrane fractions. Subsequent increase in resistance (from 1 to 10 mkg/ml EB) led to a further elevated enzyme activity both in cytosolic and membrane fractions in cells of both variants. The effect of EB presence in cultural media on the enzyme activity was tested. EB at a subtoxic concentration was shown to cause an increased PK C activity both in cytosolic and membrane fractions from resistant cells sublines.

Granulomatous hepatitis with non-caseous epithelioid-cell granulomas (43 cases, 86%) and non-specific reactive hepatitis (7 cases, 14%) were observed in liver biopsies of 50 patients with sarcoidosis. Three types of granulomas are distinguished: macrophagal, florid and fading epithelioid-cell granulomas which are consequent stages of the granuloma transformation. Fibrosis arises in the macrophagal granuloma, is increasing in both epithelioid-cell granulomas and is ended by a formation of a small scar. Nonspecific liver changes were also found (hydropic and fat hepatocyte degeneration, hypertrophy and proliferation of the stellate reticulo-endotheliocytes, sinuses capillarization, lymphoid-histiocytic infiltration of the intralobular stroma and portal tract, step-like necrosis which are probably induced by the action of the sarcoidosis unknown etiological factor.

The ability of the mouse neuroblastoma cell line NTR to proliferate at 40 degrees C correlates with the position of the temperature optimum of protein kinases A and C activities in the region of higher temperatures compared to those for cells of the original line N18AI, and with higher thermostability of protein kinase A after its heating at various elevated temperatures. The found changes in protein kinases A and C in the cells of NTR line mean that the selection of variants, capable of growing at elevated temperatures, is accompanied with conformational protein changes.

The protein kinase C (PK C) activity was determined in the cytosolic and membrane fractions of L- and CHO-K1-cells, both sensitive and resistant to ethidium bromide (EB). In the resistant cells (Lebr-25 and Cebr) a decreased enzyme activity was found in addition to alteration of the enzyme elution profile in the membrane preparations purified by DE-52 cellulose column chromatography. Methyltestosterone treated cells had a decreased enzyme activity in nonpurified membrane preparations in Lebr-25 cells, whereas the enzyme quantity in purified preparations remained the same. The decreased PK C activity on membranes correlates with the rapid proliferation of the resistant cells. The differences found between Lebr-25 and Cebr-cell lines in proliferation response to methyltestosterone correspond to the change of PK C developed due to hormone treatment.

Data are reviewed on protein kinase C (PK-C) and its function in phosphorylation and regulation of different cellular proteins--enzymes, receptors, contractile and cytoskeletal proteins, as well as expression of cellular oncogenes. Besides, interactions between PK-C and cAMP-dependent PK are discussed. The evidence provided suggests that PK-C-phosphorylation may be one of the mechanisms of transformation of extracellular transmembrane signals (hormones, neuromediators, growth factors) into responsive biochemical cell reactions.

The content of cholesterol (Chl) and phospholipids (Phl) in cell lines L and CHO-K1, sensitive and resistant to the toxic action of ethidium bromide, has been studied. EB-resistant cells were shown to have lower amounts of Chl and Phl, and the ratio Chl/Phl in these cells was decreased too. EB-resistant cells, grown in serum-free medium, have dramatically decreased contents of Chl, while compared with the cells growing with serum. Treatment of EB-resistant cells with methyltestosterone in concentration of 3 X 10(-7) M caused the increase in Chl and Phl contents, thus approximating these indices to those of EB-sensitive ones.