THE ROLE OF BILE ACIDS IN THE REGULATION OF LIPID AND CARBOHYDRATE METABOLISM IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE AND DIABETES TYPE2.

Bile acids regulate glucose and lipid metabolism. Aim -determination of total serum bile acids in patients with NAFLD and in combination with type 2 diabetes. To determine the inflammatory markers (nitric oxide, endotoxin, phospholipase A2, malondialdehyde) effects role for the synthesis and transport of bile acids. NAFLD patients with type 2 diabetes observed decrease in synthesis and disruption of transport of bile acids, which is associated with the cell membrane damage by inhibition of enzyme systems, and inflammation.

[Nitric oxide and indicators of oxidative stress in patients with exacerbation of chronic pancreatitis].

The aim of the study was to compare the level of nitric oxide to clinical and laboratory criteria for acute CP, and indicators of oxidative stress in CP. A total of 129 patients with CP (96 males and 33 females), mean age 46,9 +/- 9,2 years, were distributed to the groups with uncomplicated and complicated course. A study of nitric oxide in the blood as an additional criterion for acute CP. Found it significantly increased in patients with CP compared with control values. The content of nitric oxide in the blood during uncomplicated CP was 149,07 +/- 15,4 umol/l, with complicated course increased to 211,5 +/- 17,7 umol/l, which is significantly higher than that in uncomplicated CP (p = 0,042). A significant increase of NO level in the amplification of pain intensity (10-point analogue scale), and also obtained a direct correlation between these criteria (r = 0,69, p = 0,01). Received a significant increase in levels of nitric oxide with an increase in pancreas head size, revealed a direct correlation between these parameters (r = 0,59, p = 0,04). The obtained results allowed using nitric oxide as a criterion of acute HP. For diagnostic levels of nitric oxide made its rise above 120 mmol/liter. Sensitivity and specificity improvement of nitric oxide above 120 umol/L were 97% and 57% respectively when compared with the pain syndrome and 42% and 62% respectively when compared to pancreas head size. Were studied AAO and MDA indices. A significant increase in MDA (t = 2,58, p = 0,012), indicating that activation of LPO. There was a significant increase of MDA in the amplification of the intensity of pain, and also obtained a direct correlation between these criteria (r = 0,30, p = 0,03). Identified a direct correlation between levels of MDA and nitric oxide (r = 0,63, p = 0,01). Study of the level of nitric oxide can be used as an additional criterion of exacerbation of CP. In patients with CP enhanced LPO processes, as evidenced by the increase of MDA in patients with high levels of nitric oxide in the blood. Growth of LP may be an additional pathophysiological factor amplifying damaged pancreas.

[Advisability of using probiotics in the treatment of atherogenic dyslipidemia].

One of the main components of the metabolic syndrome is a non-alcoholic fatty liver disease (NAFLD). Currently, NAFLD is recognized as one of the main factors for cardiovascular disease because cholesterol synthesis is carried out mainly in the liver. In connection with this selection of lipid-lowering therapy, which has a known hepatotoxic effect, is a challenge. In the pathogenesis of NAFLD important role played by the violation of the colon microflora and, consequently, elevated levels of metabolic products of microorganisms (short chain fatty acids, endotoxin, nitric oxide), which must also be considered in the treatment of atherogenic dyslipidemia. In patients with NAFLD and atherogenic dyslipidemia appointment of combination therapy of statins and probiotics are more effective in lowering cholesterol and products of metabolism of intestinal microflora compared with monotherapy.

[Diagnostic value of nitric oxide and endotoxins at non-alcoholic fatty liver disease].

The aim of this examination was investigation of the nitrogen oxide (NO) role for the inflammation forming in the patients with nonalcoholic fat disease of the liver. 90 patients (male--25, women--65) were examined: steatohepatitis (SH)--60 patients, liver steatosis--30 patients). Index of body mass was increased on 40-45%. NO metabolites blood level was examined by Metelskaya V.A. (2005) method. The trustworthy increase of NO production in the SH patients in comparison in patients with steatosis liver and was increasing together with aminotransferases and GGTP. NO as inflammation marker may be real criterion of the liver inflammation in the patients with the early stage transformation of liver steatosis to SH.

[Structural changes of esophageal mucosa at metabolic syndrome].

In metabolic syndrome including the connection with gastro-esophageal rephlux it was detected some equal dystrophic changes in esophageal mucosa. These changes are: horny epithelium, destruction in epithelial-stromal interactions, a special form of papilla, some spherical structures with dystrophic epithelial cells and groups of epitheliocytes with nuclear absence. These changes occurred against a background of NO increased level.

[Features of chronic pancreatitis in the elderly patients].

The aim of this study was to determine the severity of the exocrine and endocrine insufficiency of the pancreas, HC composition and state of homeostasis in the elderly patients. Was obsercved 76 patients with CP (46 females, 30 males), of whom 20 patients diagnosed alcoholic pancreatitis (AP) aged 30 to 55 years. At 26 patients was marked biliary pancreatitis (BP), age of patients was 35-60 years and at 30 was found involutional pancreatitis (IP) from 60 to 74 years, 15 people (with no signs of lesions of the gastrointestinal tract) consisted the control group. The diagnosis of CP was made on the basis of clinical data, laboratory and instrumental investigations. Depending on the etiology of chronic pancreatitis was revealed a different degree of impairment of exocrine and endocrine functions of pancreas. These changes were more pronounced in patients with AP, which depended on the severity of the disease and the presence of complications. In duodenal bile of patients was significantly progressive decrease in the total content of the HC, which depended on the reduction of the total content of the conjugates. Revealed a qualitative change in HC composition may reduce absorption of exogenous cholesterol in the intestine of patients with CP, and is one of the reasons affecting the state of the exocrine pancreas. These changes are especially pronounced in patients with IP. All patients with CP were observed on blood hypercoagulation, which was accompanied by a decrease in the overall constant blood clotting, increasing content of F, an increase in the index of coagulation and clot elasticity. Especially pronounced these changes were in patients with complicated disease and the elderly patients.

[Taurine in the treatment of non-alcoholic fatty liver disease].

Non-alcoholic fatty liver disease (NAFLD) has several phases of flow: from simple steatosis, steatohepatitis, and ending with fibrosis and cirrhosis. NAFLD characterized by elevated liver enzymes in blood serum, the morphological changes in biopsies of the liver often associated with metabolic disorders. Metabolic syndrome represents a complex of many linked to pathobiochemical and pathophysiological factors levels influencing the extremely high risk of developing coronary heart disease (CHD), diabetes mellitus type 2 and other diseases associated with atherosclerosis. NAFLD proceeds favorably without significant morphological changes in most of the patients. In connection with this treatment is given only to patients with high risk of progression of this disease or the presence of marked changes in biochemical liver tests. Therefore, prevention and treatment of these conditions should be conducted before the complications and lead to improvement of the liver.

[Change of nitric oxide metabolites in patients with chronic pancreatitis].

72 patients with chronic pancreatitis were investigated. The levels of nitrogen oxide in the blood and urine were examined in the patients with chronic pancreatitis depend on the disease's stage and its complications. The nitrogen oxide metabolites were determined to all patients (by method of V. A. Metelskaya, 2005) The trustworthy differences of NO levels were revealed depend on the chronic pancreatitis complications presence. The patients with the pancreatic hypertension due to pancreatic calcinosis, that was accompanied persistent painful syndrome and relativelly high blood amylase level (amylase increase 3-4 times in comparison with its normal level) were demonstrated the high NO levels. The tendency to the lowering of level NO and painful syndrome with blood amylase activity reduce were revealed in the patients with surgical treatment of the complicated chronic pancreatitis. The lowering of the painful syndrome and the blood amylase activity follow to normalisaton of pancreatic juice outflow and reduce of the inflammation in parenchyma pancreas. So, the revealed connection increase of NO level and pancreatic inflammation may be the additional criterions for the surgical treatment of such patients.

[Implication of serotonin in the regulation of hemostasis in the experiment].

The role of serotonin in the regulation of hemostasis was studied. The administration of serotonin was ascertained to result in enhanced blood clot elasticity. Its readministration led to the development of disseminated intravascular coagulation.

[Hepatic lesion in patients with hepatocerebral dystrophy].

AIM: To study hepatic affection in hepatocerebral dystrophy (HCD) regarding clinical course and duration of the disease. MATERIAL AND METHODS: The records on 63 HCD patients were studied retrospectively as to early clinical symptoms, onset dynamics, biochemical tests for hepatic function, morphological changes of the liver, immune and cytokine status, markers of hepatotropic viruses. RESULTS: Six variants of HCD course were identified: hepatic (24 patients), endocrine (17 patients), neurological (12 patients), psychoemotional (5 patients), hemolytic (3 patients), renal (1 patient). Early hepatitis and hepatic cirrhosis progress were characteristic for the hepatic variant. The other variants were characterized by hepatic fibrosis, lipofuscinosis, fat dystrophy of the liver. Markers of viral hepatitides B, C, G, TT were detected primarily in patients with a hepatic variant of HCD. A moderate rise of aminotransferases, immunoglobulins, cytokines level indicate weak inflammation in hepatic tissue. Disorders in proteins synthesis, hepatic detoxication function reflect changes in the microsomal system and endoplasmic network. CONCLUSION: Hepatic lesions in HCD are different. Clinical, biochemical, morphological activity and immune status affections were most severe in patients with hepatic and endocrine variants of HCD, being the least severe in neurological, psychoemotional and hemolytic variants. Hepatotropic viruses in some patients deteriorate hepatic lesion caused by copper imbalance.

[Pancreatic insufficiency in chronic pancreatitis of various etiology].

The goal of this study was to examine the severity of exocrinous and endocrinous pancreatic incompetence, composition of bile acids (BA) and hemostasis state depending on the etiologic form of chronic pancreatitis (CP). The study comprised 76 patients with CP at the age of 33-74 (46 females and 30 males), 20 of them having alcoholic pancreatitis (AP), 26 --biliary pancreatitis (BP), and 30--involutional pancreatitis (IP); 15 people (without any signs of gastrointestinal tract lesions) made up the control group. CP was diagnosed based on clinical data, laboratory and instrumental assessments. Various degrees of severity of exocrinous and endocrinous pancreatic incompetence were revealed depending on the CP etiology. AP patients had more marked alterations of this type depending on the severity and presence of complications. The study revealed changes in the quantitative and qualitative BA composition, which can cause reduced absorption of exogenous cholesterol in the CP patients' bowels and be one of the reasons affecting the exocrinous function of the pancreas. IP patients had more marked alterations of this type. All CP patients had blood hypercoagulation accompanied by a reduction of the public constant of blood coagulation, increase of the coagulation index and clot elasticity. Patients with the complicated course of the disease had more marked alteration of this type.

[Nicotinamide in combined treatment of chronic pancreatitis]. / Primenenie nikotinamida v kompleksnom lechenii bol'nykh khronicheskim pankreatitom.

AIM: To evaluate effects of nicotinamide on insulin secretion in glucose tolerance test and on blood clotting in patients with chronic pancreatitis (CP). MATERIALS AND METHODS: 30 patients with CP of alcoholic etiology received combined treatment with enzyme medicines. In addition, some of them were administered nicotinamide as 2.5% solution for 2 weeks (1 ml twice a day). Before the treatment and during its course, measurements were made of fasting and post glucose test values of insulin secretion and thromboelastogram. RESULTS: Both basal and stimulated insulin secretion in CP patients was low compared to control subjects. Nicotinamide significantly increased basal secretion of insulin and insignificantly aroused its glucose-stimulated secretion. Nicotinamide promoted reduction of hypercoagulation and time to remission. CONCLUSION: Nicotinamide administration is thought valid for correction of endocrine pancreatic function and hemocoagulation in patients with alcoholic CP.

[The characteristics of peptic ulcer in subjects with concomitant ischemic heart disease]. / Osobennosti iazvennoi bolezni u lits s soputstvuiushchei ishemicheskoi bolezn'iu serdtsa.

AIM: The study of clinical running of gastric or duodenal ulcer in associated coronary heart disease (CHD). MATERIALS AND METHODS: 209 CHD patients with gastric ulcer (GU) or duodenal ulcer (DU) were examined clinically plus histological examination of gastric or duodenal mucosa biopsies was made. RESULTS: In CHD patients GU occurred more frequently (56%) than DU. The lesions involved more frequently lesser curvature of the stomach and pyloric part of the stomach. Males developed ulcers 3.5 times more frequently than females. Ulcers tended to a painless course without season exacerbations. The disease manifested first with gastric bleeding in 52% of the patients. GU and DU ran with frequent recurrences and long-term exacerbations (76% of patients) which coincided in time with CHD exacerbations. 68% of patients developed exacerbations within 10 days after myocardial infarction or aortocoronary bypass operation. Helicobacter pylori was present as a resolving factor in arising ulcer in 26% of patients. Microcirculatory disorders, reduced blood flow speed in gastric or duodenal mucosa, hypocoagulation syndrome, dyslipidemia provoked exacerbations in 62% of patients. Examinations of biopsies from gastric and duodenal mucosa showed marked dystrophic changes in the mucosa, its connective tissue basis in the vessels in the presence of mild inflammation at ulcer site. CONCLUSION: The onset of ulcers and erosions in the mucosa of the gastrointestinal tract in CHD may be due to circulatory disorders in gastric mucosa. The main factors of aggression are hypoxia, hypoxia-induced trophic defects in gastric and duodenal mucosa, circulatory disorders.

[A trial of the use of sandostatin in patients with chronic pancreatitis]. / Opyt primeneniia sandostatina u bol'nykh khronicheskim pankreatition.

Out of 15 patients with chronic pancreatitis (CP) treated with sandostatin, 8 patients demonstrated a complete and 6 partial response. One patient did not respond. Pain relief occurred in all of them. Side effects were registered in 3 patients (doughy stools 4 times a day throughout treatment). Normal blood levels of pancreatic enzymes, insulin secretion, parameters of blood inhibitory system did not change much because of sandostatin administration, whereas hypercoagulation got diminished. Rat experiments have revealed a trend to trypsin lowering in tissues of unaffected pancreas and more intensive inhibition of active trypsin by tissue inhibitors.

[Oxidase activity of ceruloplasmin and the state of hemocoagulation in patients with chronic pancreatitis]. / Oksidaznaia aktivnost' tseruloplazmina i sostoianie gemokoaguliatsii u bol'nykh khronicheskim pankreatitom.

We examined oxidase activity of ceruloplasmin, fibrinogen content in the blood serum and the state of hemocoagulation in 80 patients with chronic pancreatitis of different etiology. The presence of ceruloplasmin was considered to be paraphenylenediamine oxidase. It was shown that at the acute stage of the disease oxidase activity of ceruloplasmin is increased and depends on the severity, duration and presence of complications. An increase of the anti-oxidant action protein content is accompanied by hypercoagulation and an increase of the fibrinogen content. Data are given on the availability of correlation relationship between the fibrinogen content and general blood coagulation constant.

[Features of insulin secretion and thromboelastography values in chronic pancreatitis]. / Osobennosti sekretsii insulina i pokazateli tromboélastografii pri khronicheskom pankreatite.

The function of pancreatic beta-cells in patients with chronic pancreatitis is insufficient, which manifests by hyposecretion of basal and stimulated insulin into the blood. Moreover, blood-clotting activity is increased in chronic pancreatitis. A conclusion is made that timely prevention of exacerbations of this disease should include laboratory check-ups of insulin production and assessment of blood coagulation in the patients.

[Role of stress in the etiopathogenesis of duodenal ulcer in young patients]. / Rol' stressa v étiopatogeneze iazvennoi bolezni dvenadtsatiperstnoi kishki u bol'nykh molodogo vozrasta.

The analysis of the acid-forming function of the stomach, both basal and stimulated with insulin, atropine test, tests for the content of the adrenocorticotropic hormone, somatotropic hormone, thyrotropic hormone, triiodothyronine, thyroxin, cortisol in the blood and the content of gastrin in the blood and gastric juice, activity of the processes of lipid peroxidation, content of ceruloplasmin in the blood, content of Helicobacter pylori (Hp) in the gastric mucosa were conducted in 68 men and 64 women at the age from 18 to 40 years suffering from gastroduodenal ulcer in order to examine the role of stress in ulcer formation. 38 patients with duodenal ulcer took proton pump blockers and antioxidants for 3 years whenever they were in a stress situation. The research revealed that young patients with duodenal ulcer show enhanced sensitivity of parietal cells and sympathoadrenal system to stressful situations, and stimulation of the acid-forming stomach function takes place under the effect of both catecholamines and gastrin. Men can have both Hp-dependent and Hp-independent duodenal ulcers, while women have mostly Hp-dependent duodenal ulcers. Prescription of proton pump blockers of and antioxidants for patients with duodenal ulcer, who are in a stressful situation, reduces the frequency of duodenal ulcer recurrences.

[Interconnection in activity of lipid peroxidation reactions and functional status of the liver in patients with chronic hepatitis of viral etiology]. / Vzaimosviaz' aktivnosti reaktsii perekisnogo okisleniia lipidov i funktsional'nogo sostoianiia pecheni u bol'nykh khronicheskim gepatitom virusnoi étiologii.

There was a study of lipid peroxidation activity, ceruloplasmin level, bile acids content, and the liver detoxifying function state in 37 patients with chronic hepatitis types B and C of viral etiology. Changes of the indices under study were most apparent in patients with HCV. It was revealed that the degree of impairment of detoxifying and bile-producing functions of the liver are closely interrelated to the activity of the inflammatory reaction and lipid peroxidation processes. The increasing ceruloplasmin level in this category of patients hampers the reduction of the activity of lipid peroxidation processes, which is apparently related not only to the direct cytotoxic viral effect but also to the negative effect of superoxide ions on the cell membrane. Along with this, in cases of viral lesions of hepatocytes there are changes in the synthesis and conjugation of bile acids leading to the derangement of their correlation, their increased aggregate content and accumulation in tissues, which can also enhance the intensity of destruction of liver tissues and is an extra factor contributing to the intensification of lipid peroxidation processes.