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.

[THE CLINICAL COURSE OF THE ISOLATED EFFECTS OF EXTENSIVE SMALL INTESTINE RESECTION IN THE LATE POSTOPERATIVE PERIOD].

UNLABELLED: The purpose is the postoperative period study of clinical and functional status of patients after small intestine resection, which was performed in different volume MATERIAL AND METHODS: 91 patients with sequelae of small intestine resection in different terms after the operation were surveyed. Patients were assessed for clinical symptoms on a scale "Method of evaluating intestinal failure after gastric resection", in our own modifications, clinical-laboratory and biochemical blood examination, ultrasound examination of abdominal cavity and kidneys, x-ray examination of the gastrointestinal tract, esophagogastroduodenoscopy with histological examination of the mucosa. We determined the scatology, the consistency of the feces on the Bristol scale, concentration and profile of short chain fatty acids in coprofiltrates. Blood serum Citrulline was determined using high performance liquid chromatography on the chromatograph "Stayer". The degree of nutritional risk was assessed using screen questionnaire NRS-2002 RESULTS: Analysis of clinical, anthropometric and laboratory data showed that patients with residual stumps of the small intestine more than 2 meters have a distinct tendency to stabilize their condition, confirmed by the level of citrulline in the serum. At the same time complete adaptation does not occur, because the main reason of the operation is adhesive intestinal obstruction with chronic relapsing course. Patients with stumps of the small intestine less than 2 m have highly individual adaptation, which may be due to a small sample of patients in this group. The detected changes in the concentration and profile of coprofiltrat short-chain fatty acids allow differentiated approach to therapy of diarrhea syndrome as the main clinical manifestations of the effects of isolated small intestine resection.

Experimental osteoporosis and its correction.

Osteoporosis was modeled in rats by chronic (6 months) treatment with omeprazole or serotonin, and bone tissue status was studied in experimental hepatic fibrosis and during serotonin treatment under conditions of hepatic fibrosis. Serum levels of calcium, phosphorus, alkaline phosphatase, albumins, and creatinine and bone tissue levels of calcium, phosphorus, magnesium, and iron were measured. Treatment with mesenchymal stem cells over 6 months reduced the severity of osteoporosis.

[Diagnostic value of serum markers of fibrosis in chronic liver diseases].

AIM: To estimate the diagnostic value (DV) of direct markers of liver fibrosis, such as type IV collagen (C-IV), hyaluronic acid (HA), tissue inhibitor of metalloproteinases-1 (TIMP-1) in combination with indirect markers of fibrosis, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (gamma-GTP), alkaline phosphatase (ALP), platelets, tumor necrosis factor-alpha (TNF-alpha) in evaluating liver fibrosis. SUBJECTS AND METHODS: Sixty-seven patients with chronic diffuse liver diseases were examined. ALT, AST, gamma-GTP, and ALP were determined as indirect indicators of fibrosis. The levels of TIMP-1, HA, C-IV, and TNF-alpha were estimated by ELISA; the stage of fibrosis was determined by the results of indirect liver ultrasound fibroelastography (FE). RESULTS: According to the results of FE, the patients were divided into 2 groups: 1) (n = 25) F < or = 2 METAVIR and 2) (n = 42) F3-F4. While estimating DV of severe fibrosis stages (F3-F4), the area under the ROC curve (AUC) increased for platelets, HA, and C-IV. DV of ALT, AST declined with the higher degree of fibrosis. The highest ratio of test specificity and sensitivity (TSp and TSen) and AUC were observed for AST and HA. ALT and platelets showed low TSen, and TNF-alpha and TIMP-1 had no TSp. For evaluation of fibrosis (F4), a HA increase of over 57.7 ng/ml had 92.6% TSen and 67.5% TSp; for a C-IV elevation of above 133.1mkg/l, TSen was 85.2%, TSp was 57.5%; for a TIMP-1 rise from 24.4 ng/ml, TSen was 74.1% and TSp was 62.5%. For the diagnosis of fibrosis (F4) with a HA rise of more than 57.7 ng/ml, DV of a positive test was 65.8 (48.65-80.4; 95% CI) and that of a negative test was 93.1 (76.8-99.2; 95% CI). Thus, the negative rather than positive test results are of great diagnostic value for evaluation of the degree of fibrosis. CONCLUSION: The results of the investigation convincingly suggest that examination of the serum markers of fibrosis allows one to estimate with a high probability its presence and severity in patients with hepatic cirrhosis. The so-called direct markers (substances reflecting the biochemistry and regulation of fibrogenesis) are undoubtedly of great diagnostic value.

[Dynamics of antipirin test at patients with alcoholic liver disease on the background of metadoksin drug receiving].

AIM: To study the effect of the drug metadoxin on drug-metabolizing liver function in patients with liver lesions alcoholic etiology (ALD). MATERIALS AND METHODS: 36 patients with ALD, of which 16 patients were diagnosed with hepatitis, while 20 - with the liver cirrhosis. All the patients underwent biochemical blood analysis and the study of drug-metabolizing liver function according to the pharmacokinetics of antipyrine in saliva before and after treatment with metadoxin. Metadoxin was administered at a dose of 500 mg once a day for 28 days. Concentrations of antipyrine in saliva samples were determined by HPLC. RESULTS. It was shown that of 36 patients examined in the 28-patients with ALD (group 2) there was a significant decrease in activity of liver enzymes according to the test with antipyrine (T1/2 = 28.7 +/- 3.4, CL = 17,9 +/- 5.2; p < 0,01 vs normal), whereas in 8 patients (group 1) was noted the typical for alcohol inductive influence on the activity of liver monooxygenases (T1/2 = 7.8 +/- 1.5, CL = 39.1 +/- 6.8; p < 0,05 vs normal). As a result of the 28-day therapy with metadoxin was a normalization of the pharmacokinetic parameters of AP in Gr. 1 (12.6 +/- 1.8; p < 0.05; NS vs normal) and a significant improvement of it in patients of Gr. 2 (17.9 +/- 5.2, vs N, p <0.05). Biochemical markers of ALD (AST/ALT, GGT, ALP) also demonstrated a positive dynamics in patients of both study groups. Correlation analysis of changes in CL and GGT (r1) and changes in AST/ALT and T1/2 (r2) showed a fairly high degree of correlation between these parameters (r1 = 0.58, r2 = 0.65). CONCLUSION: The results showed marked improvement of drug-metabolizing liver function according to the test with antipyrine in patients with ALD after treatment with metadoxin.

[Spontaneous bacterial peritonitis: scientific and practical achievements and prospects].

We presented the results of our research in comparison with the literature on the etiology, pathogenesis and diagnosis of spontaneous bacterial peritonitis (SBP) at liver cirrhosis (LC), complicated by ascites. Based on these data, was proposed a classification of SBP. Were identified criteria for early diagnosis of SBP on the basis of clinical manifestations of bacterial peritonitis, systemic inflammatory response, results of studies of ascitic fluid (AF) using gas chromatography-mass spectrometry (GC-MS). In accordance with the proposed criteria was proposed a scheme for the diagnosis, treatment and prevention of STDs. Presents data on the effectiveness of therapy and prevention of SBP. Denote the potential major long-term trends in the treatment of SBP in cirrhosis.

[Intrahepatic cholestasis in chronic liver diseases].

The syndrome of cholestasis is a common manifestation of chronic liver disease (CLD) of any etiology: alcoholic, viral, drug, metabolic, etc. The basis of the formation of cholestasis is a violation of the synthesis, secretion or bile outflow. Accession intrahepatic cholestasis (field surgery) for chronic liver disease alters its course, aggravates the condition of the patient, reduces the immune system, leads to development of severe septic complications, significantly reduces the quality of life (QoL) and worsens the prognosis. In published data, as well as the results of original research aimed at improving the diagnosis and treatment of syndrome of field surgery. Was given the definition of the severity of field surgery, defined the criteria for severity, identified the severity of field surgery. Clarified the influence of field surgery in the state of the plasma level of coagulation, as well as the phosphorus-calcium metabolism in CLD of various etiologies. The advantages and versatility combined antiholestaticheskoy field surgery therapy for moderate and severe degree of different etiologies. An algorithm for treatment of field surgery, suggesting a differential approach to therapy depending on the severity of field surgery.

[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.

[Diagnosis and treatment of intrahepatic cholestasis in chronic diseases of the liver].

AIM: To improve diagnosis of intrahepatic cholestasis (IHC) basing on clinicobiochemical picture in chronic hepatic diseases (CHD) of different etiology with cholestasis and to develop a differential approach to treatment. MATERIAL AND METHODS: We examined 875 CHD patients with IHC with evaluation of the levels of the enzymes, biliary acids (BA), lipids, characteristics of hemostasis and phosphocalcium metabolism in blood. We also studied correlations and changes of the above parameters in IHC of different etiology. A comparative analysis of efficacy of mono- and combined treatment of CHD patients with IHC was made. RESULTS: We revealed correlations between the levels of the enzymes, bilirubin, lipids and BA concentration in blood serum; unfavourable prognostic value of aggravating cholemia; no correlations between content of serum BA, duration of IHC and intensity of skin itching (SI). We propose to establish "the degree of IHC severity" with 4 degrees of this severity. Characteristics of impairment of hemostasis and phosphocalcium metabolism in IHC of different etiology depending on the degree of IHC severity are presented. Efficacy and universality of combined treatment with ursodeoxicholic acid and ademetionin in moderate and severe IHC of different etiology are shown. CONCLUSION: Introduction of the definition "the degree of IHC severity" allowed us to classify IHC by severity. This enables adequate assessment of the patient's condition, prognosis the risk of complications and their severity, a differential approach to treatment and, finally, improvement of the disease outcome prognosis.

[Syndrome of iron overload and its impact on the clinical course and risk of complications in patients with liver cirrhosis].

The paper presents the results of a study of iron metabolism in 185 patients with cirrhosis of different etiologies. The frequency of iron deficiency in 28.6% of patients and the syndrome of iron overload - 18.9%. The gender and etiology of cirrhosis role in the frequency of occurrence of the syndrome of iron overload and iron deficiency. The iron metabolism disorders in relationship with the frequency of complicated cirrhosis, the severity of liver cirrhosis, according to Child-Pugh's grade of severity of liver disease, the severity of cytolytic syndrome.

[Pharmacokinetics of iron medication and efficacy of therapy with oral iron supplementation].

The pharmacokinetics of iron oral medication in was studied in patients with liver cirhorosis. In patients with hepatocellular insufficiency and high level of gepsidin found a decrease of the iron absorption constant, which led to a change in pharmacokinetic parameters. Tests on the absorption of iron have been conducted in 25 patients with liver cirrhosis, 36% of them showed a decrease of iron absorption, which led to the decrease in the efficiency of subsequent iron therapy. Found that elevated levels of gepsidin that lead to violation of iron metabolism and absorption and reduce the effectiveness of the treatment of iron deficiency.

[Effectiveness of the new plant hepatoprotector--Ropren in patients with non-alcoholic steatohepatitis].

Liver damage causes serious metabolic disorders, immune response, detoxification functions and antimicrobial protection. Therefore, the problem of finding new high effective drugs for the restoration and normalization of liver function is extremely urgent. This article presents a new domestic plant hepatoprotector Ropren, which is a biopolymer polyprenols isolated from the green of pine and spruce, and an analog of the endogenous lipid--dolichol. Presented the Ropren efficiency in patients with nonalcoholic steatohepatitis. The drug reduces the clinical and biochemical disease activity, contributes to the normalization of lipid profile. The resulting decrease in the index treatment of fibrosis, determined by indirect transient elastometry, indicates an increase in the elasticity of the liver and reducing the risk of developing cirrhosis.

[Modeling osteoporosis].

The authors propose a method for simulation of systemic osteoporosis by means of bilateral ovariectomy and administration of proton pump inhibitors. The model is applicable to the development of new technologies for the treatment of osteoporosis.

[The damaging role of endogenous nitric oxide in the development of the experimental DSS-induced colitis in rats].

An experimental study on rats to determine the role of inducible NO production in the pathogenesis of inflammation of the mucous membrane of the colon. The introduction of DSS induces the formation of lesions of the colon mucosa of different severity, which is accompanied by increased synthesis of NO and the stable metabolite of NO - citrulline. Inhibition of NO-synthase reduces the release of NO and the formation of lesions of the colon. The Conduct of experimental research on animals will allow further study of the role of NO in the dynamics of damage development and the medication protective role of inhibition of NO-synthase.

[Bone mineral density in patients with gluten-sensitivity celiac disease].

AIM: to determine the frequency of development of osteopenia/ostoporosis (OP) vitamin D deficiency, some population risk factors, and the effects of alpha-calcidol and calcitriol on bone mineral density (BMD) in patients with gluten-sensitivity celiac disease (GSCD). SUBJECTS AND METHODS: Densitometry of the lumbar vertebra and femoral neck (FN) was carried out in 47 patients with GSCD. Their sera were tested for 25OHD3, 1,25(OH)2D3, total alkaline phosphatase, calcium, phosphorus, parathyroid hormone (PTH), type 1 collagen type C-telopeptides (CrossLaps) and tumor necrosis factor-a (TNF-alpha), as well as urinary creatinine and calcium. RESULTS: The T score below -1 was found in 37 (78.7%) of the patients. BMD reduced to the level of osteopenia in 51.1% of the patients; OP was detected in 27.7%. Lower BMD was noted in 19 (95%) of the 20 menopausal women and in 15 (68.2%) of the 22 females with preserved menstrual function (p = 0.047). The mean value of 250 HD3 was 47.8 +/- 5.0 in patients with OP patients and 85.6 +/- 7.1 ng/l in those with normal BMD (p < 0.001). The latter had no decreased level of vitamin D, suggesting its deficiency, but 11 (30%) osteopenic patients were found to have vitamin D deficiency (25OHD3 < 30 ng/l). Impaired calcitriol synthesis (69.9 +/- 24.0 ng/l) was observed only in patients with OP; the level of calcitriol was 85.6 +/- 31.2 ng/ml in those with normal BMD. Decreased BMD was accompanied by elevated PTH levels in 25 (67%) patients with GSCD. There were increases in the bone resorption marker CrossLaps and in the level of TNF-alpha in 28 (76%) and 8 (22%) osteopenic patients, respectively. A more significant BMD reduction was seen in the presence of antibodies to gliadin and tissue transglutaminase. A significant correlation was found between the titer of immunoglobulin A antibodies to gliadin and TNF-alpha (rho = -0.57; p = 0.035), CrossLaps (rho = -0.58; p = 0.035), Tscores in the vertebral column and FN (rho = -0.62; p = 0.030) and (rho = -0 37; p = 0.06), respectively. CONCLUSION: The risk for OP in patients with GSCD is affected by menopause and the clinical features of the disease: secondary hyperparathyroidism due to impaired calcium and vitamin D absorption, by the activity of immunological inflammation and the compliance with a gluten-free diet. The immunological activity of inflammation is closely related to the activation of bone resorption and enhances a BMT reduction in patients with celiac disease. The use of vitamin D preparations (alpha-calcidol and calcitriol) in combination with calcium salts lowers BMD in patients with celiac disease just within the first 6 months.

[Pharmacokinetics of the proton pump inhibitors and psychological status in patients as factors that influence the efficiency of treatment of GERD with pantoprazole].

Was made an investigation of the effectiveness of pantoprazole (sanpraz, "SanFarma", India) at gastroesophageal reflux disease (GERD). 53 patients with GERD, including 20--with reflux esophagitis, received a daily dose of pantoprazole 40 mg to 28 days. To the 7 day of treatment heartburn was broke in 63.3%, regurgitation--in 65% of patients initially experiencing these symptoms. The 14-th day of treatment heartburn was broke in 83.7%, regurgitation--in 90%. Endoscopic remission in 28-th day of treatment was obtained in 85% of patients with reflux esophagitis. Broking of symptoms was accompanied by significant improvement in well-being and quality of life of patients. Treatment of a standard dose of pantoprazole was ineffective in 16.3% of patients. The reasons for the conservation of heartburn in 4.1% of the cases was an individual characteristics of the pharmacokinetics drug, in 12.2%--non-reflux mechanisms of symptoms in the face of mental status.

[Role of cholestasis in development of copper metabolism disorder in patients with chronic liver disease].

In this article was evaluated correlation between violations of copper exchange and the severity cholestasis at 162 of the patients with chronic liver diseases. There was high correlation between the level of AF and copper content in the blood. Also it was shown that patients with cholestasis significantly more frequently have observed hypercopperemy.