[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.

[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.