[NON-ALCOHOLIC FATTY PANCREATIC DISEASE (NAFPD) AND THE METABOLIC SYNDROME: INITIATING FACTOR OR ADDITIONAL COMPONENT?].

Nonalcoholic fatty pancreatic disease (NAFPD) integrates the spectrum of chronic clinical and morphological pancreatic changes: steatosis and nonalcoholic steatopancreatitis. NAFPD prevalence in USA was 27.8%, in China--12.9-16%. According to our data, 51.8% of patients with chronic pancreatitis was diagnosed MS. Association NAFPD with MS has been confirmed in most studies, the presence of any components of MS increases the prevalence NAFPD by 37 %. In the NAFPD pathogenesis is important not only excessive intake of free fatty acids (FFA), which leads to the pancreatic parenchyma inflammation and fibrosis, but also "glucolipotoxicity" (i.e., the combined toxicity of hyperglycemia and increased FFA level) for ß-cells. It is shown that NAFPD is an initial index ofectopic fat deposition, and the earlier manifestation of MS than NAFLD. Most likely, a stage (or degree) of the MS is usefully to determine as the pancreatic status--its exo- and endocrine functions, and fat deposition. This approach will allow us to develop new therapeutic approaches not only to treatment but also to the primary prevention of metabolic syndrome.

[Genetic aspects of pancreatic cancer].

The purpose of the review--to analyze the basic data on modifiable and genetic risk factors of pancreatic cancer (PC). PC is the most fatal disease that kills about 95% of patients. Among the known risk factors for PC only for smoking, obesity, and family history a positive association with the PC risk in meta-analyzes confirmed. The PC etiology remains unclear, more than 90% of patients acquire it sporadically. Currently, the most significant genes for PC include KRAS2, p16/CDKN2, TP53, SMAD4/DPC4. Mutations in the KRAS noted in 90% of cases of pancreatic ducts adenocarcinoma. p16/CDKN2A mutation is accompanied by a 38-fold increased risk of PC compared with the general population. TP53 mutations are associated not only with carcinogenesis but also PC metastasis, as well as SMAD4/DPC4 mutations. Study of the role of genetic aspects in the PC development is necessary both to identify individuals with high PC risk, as well as for the development of gene-specific treatments, such as inhibitors of proteins, histone deacetylase, and histone acetyltransferase (vorinostat, belinostat, entinostat, panobinostat, curcumin) are in clinical trials.

[Pancreatitis, pancreatic cancer and obesity: hypothesis and facts].

THE PURPOSE OF THE REVIEW: Analyze the basic data on the role of obesity in the pathogenesis of pancreatic cancer (PC) and the modern mechanisms of this association. RECENT LITERATURE DATA: In the European Union and in Russia incidence of pancreatic diseases increases, such pancreatic cancer (PC) ranks 10th among cancer diseases. Obesity is a risk factor for not only of severe acute pancreatitis, but also PC at that independently of diabetes. In a meta-analysis the PC risk in obese increased by 47%, while the person with a central obesity have a higher PC risk compared to those with a peripheral type of obesity (odds ratio = 1,45, 95% CI: 1,02-2,07), but association between BMI and PC risk in this Japanese population may be different from that in Western populations, sometimes inversely. The link between obesity and PC is explained by insulin resistance and hyperinsulinemia: was proved a direct correlation between the level of circulating C-peptide and PC, low levels of serum adiponektin and leptin increase the PC risk. There are also genetic risk factors for PC: a statistically significant interaction between IVS1-27777C> and IVS1-23525A>T genotypes of the FTO gene with obesity and the PC risk: AA genotype in patients with BMI < 25 kg/m2 reduced PC risk by 22%-28% (p < 0,0001), and with BMI ≥ 25 kg/m2 was associated with 54%-60% increased PC risk (p < 0,0015). Lifestyle factors (smoking, consumption of saturated fats, etc.) increase the PC risk.

[Vessel-platelet and coagulation components of hemostasis in patients with chronic tubulointerstitial nephritis].

AIM: To study vessel-platelet and coagulation parts of hemostasis system, their correlation with clinical characteristics and activity of chronic tubulointerstitial nephritis (CTIN). MATERIAL AND METHODS: 128 patients 15 to 65 years of age with CTIN were included in the study. The diagnosis was confirmed morphologically in 42 patients. The patients were divided into subgroups by activity of the disease at the moment of examination (active and inactive CTIN), by arterial pressure (normotensive and hypertensive patients), intact and low renal function, by duration of the disease (up to 60 months, 61-120 months, more than 120 months). Complex study of hemostasis system was carried out by a set of standard techniques. RESULTS: CTIN runs with activation of vessel-platelet hemostasis characterised by a decrease in platelets count (p < 0.001), persistent platelet hyperaggregation and activation (p < 0.001). Severity of platelet aggregative activity is related with endothelial affection manifesting with high level and activity of Willebrand factor (p < 0.001). The most typical changes of coagulation in CTIN were acceleration of activated partial thrombin time (p < 0.001) closely related with activation of thrombocytic hemostasis and background thrombinemia the presence of which was confirmed by elevated blood level of soluble fibrin-monomeric complexes (SFMC). THE CONCLUSION: Hypercoagulation, suppression of fibrinolytic plasma activity, increase of SFMC and fibrinogen levels in the blood as well as detected enhancement of platelet aggregation testify to a latent course of renal intravascular blood coagulation in CTIN. Hemostasis system activation in CTIN helps assessment of the disease activity.

Ultrastructural and biosynthetic changes in epitheliocytes of renal tubules during the development of chronic renal failure.

Structural and functional studies of changes in the tubular compartment during progressive renal dysfunction showed that the major types of damage to tubular cells include dystrophy, degeneration, and atrophy. These changes were associated with inhibition of biosynthetic processes in the tubular epithelium, progressive interstitial fibrosis, and disturbances in the structure and function of peritubular microvessels.

Ultrastructure of kidney cell population in patients with markers of HCV- and HBV-infections (analysis of biopsy specimens).

Changes in the glomerular, tubular, and interstitial compartments were revealed in kidney biopsy specimens from patients with serological markers of HCV and HBV infections. The dominant change was destruction of the tubular apparatus and atrophy of the tubular epithelium associated with progressive interstitial fibrosis. Our results indicate that kidney disorders constitute patho- and morphogenesis of systemic infection in HCV- and HBV-infected patients.

[Plasmic activity of phospholipid membranes in nephritis]. / Plazmennaia aktivnost' fosfolipidnykh membran pri nefritakh.

AIM: To study activity of plasmic phospholipid membranes (PPM) in patients with chronic nephritis (CN) as regards clinical-laboratory and morphological characteristics of the disease. MATERIAL AND METHODS: 10 patients with chronic mesangial glomerulonephritis (CMG) and 4 patients with chronic drug-induced tubulointerstitial nephritis were examined. All the patients had moderate arterial hypertension including 5 patients with CMG combined with nephrotic syndrome. 9 patients had elevated blood creatinine (up to 500 mcmol/l). Measurements were made of routine laboratory indices, blood coagulation and paracoagulation, Willebrand's factor (WF), aggregation time (AT), phospholipid activation of blood coagulation (FABC), morphological indices of activity and sclerosis. RESULTS: In spite of chronic latent intravascular blood coagulation, CN was characterized by apparent lowering of FABC which was more evident in CMG. There was a weak correlation between a FABC fall and the level of proteinuria, lipidemia, AT of platelets, indices of activity. Some parallels exist between creatininemia and activity of PPM. A close reverse relationship was found between FABC and WF, and a direct one between FABC and sclerosis index. CONCLUSION: Subnormal PPM activity in CN correlates with organic microthrombi formation and promotes the discussion of both mechanisms of FABC formation disturbances and possible ways of PPM consumption including enhanced diffusion into the mesangium in progressing nephrosclerosis.

[Evolutionary trends in symptoms of acute glomerulonephritis in adult population of the Novosibirsk region]. / Evoliutivnye tendentsii v klinike ostrogo glomerulonefrite vzroslogo naseleniia Novosibirskoi oblasti.

Acute glomerulonephritis (AGN) trends in the last 3 decades in the Novosibirsk Region have been analysed basing on the data from 308 AGN case histories. The results of the analysis demonstrate that AGN occurs not often but with stable rate. It is encountered more frequently in young men. The last decade is characterized by higher morbidity after streptococcal infection, high percentage of women at reproductive age, aggravation of the clinical course with marked edemas, severe arterial hypertension, renal dysfunction (acute renal failure in 10.4%), cases of left ventricular failure (5.2%) and eclampsia (1.7%) not registered earlier.

[Role of the hemostatic system in the progression of acute glomerulonephritis]. / Rol' sistemy gemostaza v progressirovanii ostrogo glomerulonefrita.

AIM: To study basic parameters of hemostasis in the course of acute poststreptococcal glomerulonephritis (APSGN). MATERIAL AND METHODS: Platelets number and aggregation 4-platelet factor, Willebrand's factor, activated partial thromboplatelet time, antithrombin III, fibrin-monomeric complexes and products of degradation fibrinogen/fibrin were studied in 127 APSGN patients. Autocoagulation, prothrombin and thrombin tests were made. RESULTS: Progredient thrombinemia, stable elevation of Willebrand's factor, high aggregation activity of platelets and content of their degradation products evidence for intrarenal microthrombogenesis in APSGN, confirms direct involvement of platelet hemostasis in long-term inflammation in this disease. CONCLUSION: Mechanisms of APSGN development operate also through changes in hemostatic system.

[The immediate results of using plasmapheresis in patients with chronic glomerulonephritis]. / Blizhaishie rezul'taty primeneniia plazmafereza u bol'nykh khronicheskim glomerulonefritom.

A study was made of the effect produced by a short-term course of plasmapheresis (PA) combined with cytostatic, glucocorticoid and deaggregation therapy on the clinico-laboratory characteristics in 45 patients suffering from chronic glomerulonephritis (CGN). It has been established that PA rapidly normalizes the characteristics such as the level of circulating immune complexes and fibrinogen in the blood, ESR. Exerting no effect on renal function, PA led to a significant lowering of proteinuria and erythrocyturia, with its beneficial effects being preserved after discontinuation of the sessions. The best results were attained in associated CGN and nephrotic syndrome, in mesangioproliferative and mesangiocapillary CGN. The effectiveness of the short-term course of PA in patients with membranous and diffuse fibroplastic CGN turned out questionable.

[Functional properties of B-lymphocytes of patients with a B-cell variant of chronic lymphocytic leukemia and chronic glomerulonephritis]. / Funktsional'nye svoistva B-limfotsitov bol'nykh B-kletochnym variantom khronicheskogo limfoleikoza i khronicheskim glomerulonefritom.

The common features of the pathogenesis of chronic lymphocytic leukemia (CLL) and chronic glomerulonephritis (CGN) have been shown as a result of a comprehensive study of the functional properties of B cells. Both CLL and CGN are accompanied by the appearance and accumulation of different types of activated B cells characterized by high spontaneous proliferation and/or Ig secretion; or sensitivity to T cell growth and differentiation factors; or capacity for Ig secretion; in mitomycin C treated B cell cultures (i.e. without previous proliferation). The present data may be useful in the integral evaluation of B cell function in health and in immunopathologies (lymphoproliferative and autoimmune/immune complex diseases).

[Effect of therapeutic plasmapheresis on the system of hemostasis in patients with chronic glomerulonephritis]. / Vliianie lechebnogo plazmafereza na sistemu gemostaza u bol'nykh khronicheskim glomerulonefritom.

Coagulative and thrombocytic hemostasis as well as the fibrinolytic system were studied in 20 patients with chronic glomerulonephritis on plasmapheresis (PA). It is shown that PA promotes activation of platelet aggregation which can be related to their contact activation. Coagulation enhances, antithrombic potential reduces, fibrinogen is mechanically removed as well as fibrin-monomer soluble complexes, fibrin degradation products. In view of the importance of the fibrinolytic system in chronic glomerulonephritis, measures should be taken to correct the disturbances detected.

[The outcomes and prognosis of a course of acute glomerulonephritis]. / Iskhody i prognozirovanie techeniia ostrogo glomerulonefrita.

Observation of 131 patients with acute glomerulonephritis (AGN) experiencing the first year of disease made it possible to distinguish, by the 4th month of disease, the lingering disease patterns encountered in 100% of cases with the nephrotic form and typical for pronounced and little symptomatic AGN (96.1-78.8%). As compared to the catamnestic data, 83 patients manifested (after 5.8 +/- 0.7 yr.) an unfavourable influence of the lingering disease course on AGN outcomes (the probability of convalescence dropped to 30.8-33.3% in pronounced and little symptomatic forms and was completely excluded in the nephrotic one) and a high diagnostic significance of the dynamics of the urinary syndrome for prognosis determination. The constancy of proteinuria at a level of over 1 g/day and hematuria at a level over 50.0 x 10(3)/ml within 4 to 6 months significantly deteriorated the prognosis. Virus nature of pronounced AGN can be indicated among other prognostic criteria. The other characteristics of the debut produced no significant effect on the disease outcome. The morphological signs of the chronic disease corresponded to mesangiomembranous glomerulonephritis whereas fibroplastic alterations were only observed in special forms of AGN marked by rapid progress.

[A clinico-pathogenetic approach to choosing the therapeutic procedure in chronic glomerulonephritis]. / Kliniko-patogeneticheskii podkhod k vyboru terapevticheskoi taktiki pri khronicheskom glomerulonefrite.

The results have been compared of the use of two schedules (continuous and cyclic) of multimodality therapy of chronic glomerulonephritis (CGN) including cytostatics, corticosteroids, anticoagulants and deaggregation agents. Continuous therapy was carried out for 12.9 +/- 0.41 months on the average, with the drug dosage being corrected depending on the clinico-laboratory and immunological findings as well as on the parameters of the hemostatic system. Cyclic therapy was conducted for 6 months according to a strictly unified program. It has been shown that continuous individualized treatment compares very favourably with the cyclic schedule, which is particularly marked in mesangiocapillary CGN and CGN with a tubulointerstitial component. It is concluded that continuous multimodality treatment chosen with regard to the clinico-pathogenetic disease characteristics allows CGN prognosis to be improved.

[Study of the blood coagulation and fibrinolysis systems in evaluating the activity of glomerulonephritis]. / Koaguliatsionnaia i fibrinoliticheskaia sistema krovi v otsenke aktivnosti glomerulonefrita.

Certain parameters of blood coagulation and fibrinolysis were studied in 84 patients suffering from different variants of chronic glomerulonephritis. The disease is characterized by various conditions of the coagulation system, and acceleration of the initial stages of coagulation; the most typical are disturbances of thrombin inactivation. Simultaneous accumulation in the blood of products of degradation of fibrin and monomeric fibrin complexes is observed. The degree of manifestation of changes in blood coagulation and fibrinolytic systems corresponds to disease activity. The tests used are more sensitive than the traditional clinicolaboratory tests and reveal not only manifested by also latent disease activity.

[Precursor thymus-dependent lymphocytes in variants of chronic glomerulonephritis]. / Prekursornye timuszavisimye limfotsity pri raznykh variantakh khronicheskogo glomerulonefrita.

Altogether 67 patients with chronic glomerulonephritis (CGN) were examined for the content of thymus-dependent precursor lymphocytes (auto-RFC, pre-T-cells). The patients suffering from CGN were characterized by the high content of the young post-thymic T-cells (auto-RFC) and high affinity T lymphocytes carrying a receptor for the Fc fragment of IgM as compared to normal donors. In patients with different clinical patterns of CGN, an analysis was made of the content of precursor thymus-dependent lymphocytes. A relationship was discovered between the content of pre-T-cells and the activity of the nephritic process. The activity of the pathological process was associated with the high content of precursor lymphocytes. The inactive course of nephritis was characterized by a well-defined reduction of the number of precursor cells. This might be regarded as depletion of the amount of precursor lymphocytes.

[Clinico-pathogenetic characteristics of hematuric glomerulonephritis]. / Kliniko-patogeneticheskaia kharkteristika gematuricheskogo glomerulonefrita.

Criteria for the diagnosis of hematuric nephritis (HemN) are proposed. Based on these criteria a group of patients (n = 157) was formed. As a result of the observation of many years, the main variants of HemN were characterized and its etiological polymorphism was demonstrated. The investigation of the immune status of the patients with HemN, of hemostasis and fibrinolysis and the data of light, optic and electron microscopy of the renal tissue made it possible to demonstrate the pathogenetic originality of HemN and thus to regard it as a separate clinical pattern of chronic glomerulonephritis.

[Myeloma-related nephropathy (incidence, clinical aspects and morphology). Analysis of 95 cases of multiple myeloma]. / Mielomnaia nefropatiia (chastota razvitiia, klinika, morfologiia). Analiz 95 sluchaev mnozhestvennoi mielomy.

The authors provided the results of observations of 95 patients with multiple myeloma (MM). Signs of renal involvement in that period were detected in 79% of the patients. The authors analyzed the frequency of various symptoms of myelogenic nephropathy (MN) and its evolution. The comparison of clinicolaboratory findings and the nature of morphological changes of the renal tissue in the MN patients made it possible to define 3 stages in MN development. When the predominance of renal symptomatology made the diagnosis of MM difficult, puncture nephrobiopsy was recommended. It can be performed in the absence of marked hyperproteinemia and hemostatic disorders.