[Comparative analysis of the development mechanisms of cryoglobulinemic vasculitis and Sjögren's syndrome]. / Sravnitel'nyi analiz mekhanizmov razvitiya krioglobulinemicheskogo vaskulita i sindroma Shegrena.

Cryoglobulinemic vasculitis is a disease characterized by damage of small vessels and in some cases can be a manifestation of mixed cryoglobulinemia. Mixed cryoglobulinemia is a condition in which immunoglobulins in the blood serum form precipitates at temperatures below 37 °C and dissolve again when it rises. Currently, hepatitis C (HCV) is considered the most common etiological factor of mixed cryoglobulinemia. In addition, mixed cryoglobulinemia may be associated with other infectious agents, as well as autoimmune and lymphoproliferative diseases. In the absence of such association, we can talk about essential mixed cryoglobulinemia. To understand how different nosologies in their clinical and morphological picture lead to the development of mixed cryoglobulinemia, it is necessary to carefully analyze the mechanisms of the development of some of them, namely, HCV-associated cryoglobulinemic vasculitis and Sjögren's syndrome. It is noteworthy that mixed cryoglobulinemia in relation to Sjögren's syndrome can be perceived both as its consequence and as a manifestation of the underlying disease. Such an ambiguous nature of mixed cryoglobulinemia makes it currently impossible to select clear diagnostic criteria. For this reason, it is necessary to carry out a comparison between different immunopathogenesis of mixed cryoglobulinemia in order to identify the features that form its classical manifestations.

[Ferroptosis-associated lesion as a potential target for cardiovascular disease: A review].

Cell death is an important feature of the development of multicellular organisms, a critical factor in the occurrence of cardiovascular diseases. Understanding the mechanisms that control cell death is crucial to determine its role in the development of the pathological process. However, the most well-known types of cell death cannot fully explain the pathophysiology of heart disease. Understanding how cardiomyocytes die and why their regeneration is limited is an important area of research. Ferroptosis is an iron-dependent cell death that differs from apoptosis, necrosis, autophagy, and other forms of cell death in terms of morphology, metabolism, and protein expression. Ferroptotic cell death is characterized by the accumulation of reactive oxygen species resulting from lipid peroxidation and subsequent oxidative stress, which can be prevented by iron chelates (eg, deferoxamine) and small lipophilic antioxidants (eg, ferrostatin, liproхstatin). In recent years, many studies have been carried out on ferroptosis in the context of the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In addition to cardiovascular diseases, the review also presents data on the role of ferroptosis in the development of other socially significant diseases, such as COVID-19, chronic obstructive pulmonary disease. With the study of ferroptosis, it turned out that ferroptosis participates in the development of bacterial infection associated with the persistence in the host body of Pseudomonas aeruginosa. The review summarizes the recent advances in the study of ferroptosis, characterizing this type of cell death as a novel therapeutic target.

Difficulties in Goodpasture's syndrome diagnosing.

The article analyzes the diagnosis and treatment of anti-GBM antibody disease (Goodpasture's syndrome) - a rare, severe progressive disease, associated with anti-glomerular basement membrane antibody-induced pulmonary hemorrhage and glomerulonephritis. The main problem of this pathology is late diagnosis, resulted in ineffective treatment. The article provides current information on the epidemiology, etiology and pathogenesis, diagnosis, and treatment of Goodpasture's syndrome, as well as clinical case of a patient with this rare disease.

Autoimmune liver disease (primary biliary cholangitis/autoimmune hepatitis-overlap) associated with sarcoidosis (clinical cases and literature review).

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.

Clinical features of cardiac lesion in patients with generalized sarcoidosis.

The article presents a clinical observation of two patients with generalized sarcoidosis. The woman typical granulomatous changes in the lungs and lymph nodes combined with atrial fibrillation, kidney failure and hereditary thrombophilia, men with atherosclerotic coronary arteries, re-myocardial infarction, cholestasis, tubulointerstitial nephritis. The accession of systemic manifestations was accompanied by increase of level of angiotensin-converting enzyme in the blood serum, morphological examination of lung tissue in both cases there were high histological activity of vasculitis and granulomatous inflammation. Extrapulmonary symptoms regressed when conducting immunosuppressive therapy. Discusses modern aspects of diagnosis of sarcoidosis in clinical practice.

Clinical significance of the determination of surfactant proteins A and D in assessing the activity of lung sarcoidosis.

AIM: To study the clinical significance of SP-A, SP-D in assessing the activity of idiopathic pulmonary fibrosis and sarcoidosis. We examined 81 patients with morphologically confirmed diagnoses of idiopathic pulmonary fibrosis (ILF) and sarcoidosis, a control group of 20 healthy individuals. The MSCT of the thoracic organs of the chest was performed, the diffusivity of the lungs was examined, oxygen saturation was determined. In the serum, the surfactant proteins SP-A and SP-D were determined by the enzyme-linked immunosorbent assay. RESULTS: A significant increase in SP-A and SP-D (p<0.05) was observed in patients compared with patients in the control group, a direct correlation was found with signs of activity: SP-A with alveolitis (p<0.05), SP- D with progressive fibrosis (p<0.05), inverse correlation of surfactant proteins with respiratory function indices (p<0.05). CONCLUSION: Serological parameters of SP-A and SP-D reflect the activity of alveolitis and the progression of pulmonary fibrosis in patients with ILF and sarcoidosis.

[Computer technologies in teaching pathological anatomy].

The paper gives experience with personal computers used at the Academician A.L. Strukov Department of Pathological Anatomy for more than 20 years. It shows the objective necessity of introducing computer technologies at all stages of acquiring skills in anatomical pathology, including lectures, students' free work, test check, etc.

[Interstitial pulmonary fibrosis: the role of angiogenic factors, the inhibitory pathways of progression].

AIM: To assess the role of angiogenic factors (vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in interstitial lung diseases (ILD), such as fibrosing alveolitis, sarcoidosis. SUBJECTS AND METHODS: The blood levels of endothelial dysfunction and neoangiogenesis markers (ET-1 and VEGF) were investigated in 96 patients with different clinical forms of ILD at it different stages; the found changes were compared with the clinical and morphological manifestations of the disease. RESULTS: It has been ascertained that regardless of the clinical type of ILD, there is a correlation between the blood levels of VEGF and ET-1 and the intensity of lung neoangiogenesis, the expression of VEGF by the endothelium of newly formed blood vessels, the production of angiogenic factors, the degree of endothelial dysfunction, the extent of pulmonary fibrosis, the degree of pulmonary vascular remodeling, and the severity of pulmonary hypertension. The findings suggest that the markers of neoangiogenesis play an important role in the mechanisms of ILD progression. CONCLUSION: The study of these parameters in the blood may be used to clarify the activity and prognosis of ILD.

[Clinical significance of markers of endothelial dysfunction and angiogenesis in progressing of the lung interstitial diseases].

The data obtained suggest an important role of the FRES and ET-1 in progressing of the lung interstitial diseases; they can be used as diagnostic criteria of the disease activity, risk of pulmonary hypertension, and extra-pulmonary manifestations.

[Experience in using information-computer technologies during teaching students at the Department of Human Pathology, I. M. Sechenov Moscow Medical Academy].

On implementing the innovational educational program of the I. M. Sechenov Moscow Medical Academy, supported by the National Educational Project, the Department of Human Pathology has developed the hardware-software complex "Virtual Operating-Room" that is used to teach a biopsy-section course. The "Virtual Operating-Room" comprises three objects: a digital operating-room, a digital workplace, and digital study audience. Due to the use of the hard-software complex, the students take a direct part when examining the intraoperative biopsy material.

[Surgical treatment of thymomas in patients with generalized myasthenia gravis]. / Khirurgicheskoe lechenie timom u bol'nykh generalizovannoi miasteniei.

Experience in surgical treatment of 2977 patients with generalized myasthenia is presented, 386 (13%) of them have undergone surgeries for thymus tumors. Organo-specific tumors (thymoma) were diagnosed in 370 (95.9%) of them. Computed and magnetic-resonance tomography has the highest sensitivity and specificity in diagnosis of thymus tumors. Thymomthymectomy was performed in 317 patients including extended one in 117 (36.9%). Postoperative lethality in thymic tumor in the last years was 0.5%, general lethality over all period--5.1%. According to used classification (WHO, 1999) types of thymoma were the following: type A--2.1%, type B--86.3%, type AB--9.6%. Prognosis of surgical treatment depends of tumor type (it is worse in type B than in types A and AB), duration of the disease and severity of myasthenia.

[Sjogren's syndrome in chronic hepatitis C: clinical features and diagnosis]. / Sindroma Shegrena pri khronicheskom gepatite C: kliknicheskie osobennosti i diagnostika.

AIM: To examine clinical features of Sjogren's syndrome (SS) and morphological picture of the lesser salivary glands (LSG) in chronic hepatitis C (CHC). MATERIAL AND METHODS: The examination of 42 patients with SS and chronic HCV infection (mean age 44.3 +/- 13.7 years) has detected signs of chronic hepatitis and hepatic cirrhosis, respectively, in 31 (71.4%) and 11 (26.2%) patients. "Dry syndrome" was diagnosed by criteria of European SS Study Group. LSG biopsy of the lower lip was conducted in 23 (54.7%) of 42 patients. RESULTS: The "dry" syndrome in CHC ran subclinically in 73.8% patients. Apparent symptoms of SS were seen primarily in middle-aged and aged women with CHC history over 10 years. The first signs of SS occurred in 25 (59.5%) patients 2.9 +/- 3.1 years prior to diagnosis of hepatic disease. All the patients had xerostomy. Xerophthalmia was recorded 1.5 times less frequently. In 16 (47.1%) patients with CHC "dry eye" and in 6 (17.6%) patients dry keratoconjunctivitis were detected. Pathohistological changes of LSG were diagnosed in 21 (91.3%) of 23 patients with CHC. In the majority of cases (86.9%) the glands exhibited insignificant inflammatory infiltration and advanced fibrosis. LSG in CHC is characterized by fibrosis prevalence over cell infiltration. 83.3% CHC patients had SS and other extrahepatic lesions. SS was most evident in 28.6% CHC patients with cryoglobulinemia. CONCLUSION: Registration of SS symptoms in CHC patients depends on targeted examination of patients with chronic HCV infection. The severity of the symptoms correlates directly with the infection duration and age of the patient. LSG lesions in CHC patients with SS are characterized by fibrosis pre-domination over cell infiltration.

[Thymomas with a myasthenic syndrome]. / Timomy s miastenicheskim sindromom.

2560 patients with generalized myasthenia (Gm) were operated during 1960-1996. Tumors of the thymus (TT) which are the most often neoplastic masses of anterior mediastinum were revealed in 312 patients. Among them organ-specific tumors (thymomas, cancers) were detected in 252 patients (95.8%). Comparative analysis of effectiveness of a number of special methods of diagnostics of TT showed that CT and magnetic resonance tomography are the most sensitive and specific methods. Thymoma-thymectomy was carried out in 247 patients, among them in 93 (37.7%)--extended one. Postoperative lethality made up 5.1%, last years (1990-1996) there were no fatal outcomes. Among early postoperative complications wound infection was observed in 2.5% of patients, pneumonia--in 1.3%, myasthenic crisis--in 1.6%. Basing on histogenetic classification, following kinds of thymomas were singled out: in 58.9% cortical ("light cellular"), in 2.2%--medullar ("dark cellular") and in 38.9%--mixed cellular thymomas. Long-term results of thymectomy in patients with Gm in various kinds of thymomas were different: at the 5th year of follow-up they are worse in cortical cellular types and much better in medullar--cellular and mixed cellular thymomas with prevalence of medullar component.

[Diffuse cholangiocarcinoma in the context of multilobular liver cirrhosis as a manifestation of Wilson-Konovalov disease]. / Diffuznaia kholangiokartsinoma na fone mul'tilobuliarnogo tsirroza pecheni kak proiavleniia bolezni Vil'sona-Konovalova.

A 31-year-old female had a hepatolenticular degeneration. Multilobular cirrhosis and cholangiocellular liver carcinoma responsible for a rapid disease progression were found at necropsy. This is the first report of cholangiocarcinoma in Wilson-Konovalov disease.

[Diabetic glomerulonephritis--the first stage of diabetic glomerulopathy]. / Diabeticheskii glomerulonefrit--pervaia stadiia diabeticheskoi glomerulopatii.

20 puncture renal biopsies and 16 pancreatic biopsies from patients with insulin-dependent diabetes mellitus were studied ultrastructurally. The stages in the development of kidney changes depending on the functional state of Langerhans islands B-cells were established. The 1st stage includes signs of segmentary mesangioproliferative glomerulonephritis- segmentary increase of the mesangium due to the hypercellularity, variability of the basal membrane thickness in the glomeruli capillaries, leucocytes in the lumen, subendothelial deposits. This stage may be due to the persistence of the etiologic factors(virus), formation of circulating immune complexes, antibodies excess and relative preservation of B-cells and their function. Thinning of the capillary basal membrane, decrease of the mesangial matrix surface, cell destruction are characteristic for the 2nd stage- stage of the mesangiolysis. The duration of disease up to 15 years has no influence on the formation of glomerulosclerosis.

[Diabetic glomerulosclerosis--a prolonged stage of diabetic glomerulopathy]. / Diabeticheskii glomeruloskleroz--prolongirovannaia stadiia diabeticheskoi glomerulopatii.

Formation of diabetic glomerulosclerosis was followed by the electron microscopy of 21 puncture renal biopsy and 12 incisive pancreatic biopsies from patients with insulin-dependent diabetes mellitus. The influence of the B-cell destruction and the decrease or absence of their activity (the presence of serum C-peptide) on the degree of renal damage and clinical symptoms of the diabetic nephropathy (proteinuria, hypertension) is noted. Dynamics of the diabetic glomerulosclerosis formation is as follows: 1st group--thickening of capillary basal membrane in the glomeruli, mesangial ectopy, formation of nodules at the periphery of loops; 2nd group--increase of the mesangial matrix, doubling of the glomerular capillary basal membrane, hyalin droplets in the capsule membrane. 4 stages in the development of diabetic glomerulopathy are distinguished: diabetic segmentary mesangioproliferative glomerulonephritis, mesangiolysis, two stages of glomerulosclerosis progression. Duration of the disease more than 15 years predetermines the development of diabetic glomerulosclerosis.

[Duodenal gastrinoma with the development of Zollinger-Ellison syndrome]. / Gastrinoma dvenadtsatiperstnoi kishki s razvitiem sindroma Zollingera-Ellisona.

Gastrinoma consisting of eosinophilic gastrin--producing cells (this was proven electron--microscopically and immunohistochemically) was found in a 32-year-old female. The tumour, 1 x 1 x 1.5 cm in size, was located in the submucosa of the horizontal part of the duodenum. This was the cause of Zollinger--Ellison syndrome in the above patient.