Activation level of JNK and Akt/ERK signaling pathways determinates extent of DNA damage in the liver of diabetic rats.

AIMS: Diabetes-related oxidative stress conditions lead to progressive tissue damage and disfunctionality. Mechanisms underlying liver pathophysiology during diabetes are not fully understood. The aim of this study was to find relationship between diabetes-related DNA damage in the rat liver and activities of prosurvival signaling pathways. METHODS: Effect of diabetes was analyzed two (development stage) and eight weeks (stable diabetes) after single intraperitoneal injection of streptozotocin. Extent of DNA damage, analysed by comet assay, was corelated with oxidative status (plasma level of ROS, liver antioxidant capacity) and activity/abundance of kinases (Akt, p38, ERK1, JNK, JAK) and transcription factors NF-κB p65 and STAT3. RESULTS: Significant DNA damage in development stage is accompanied by elevated plasma levels of O(2)(-) and H(2)O(2), decreased activities of CAT, MnSOD, and GST in the liver and increased activation of proapoptotic JNK signal pathway. Lower DNA damage in stable diabetes, is accompanied by elevated plasma level of O(2)(-), restored antioxidative liver enzyme activity, decreased activation of JNK and increased activation of prosurvival Akt and ERK signal pathways. CONCLUSION: These findings indicate that level of DNA damage in diabetic liver depends on the extent of oxidative stress, antioxidant activity and balance between JNK and Akt/ERK signal pathways activation .

Prospective evaluation of the prevalence of Helicobacter pylori in abdominal surgery patients.

BACKGROUND/AIMS: Helicobacter pylori infection is accepted to be associated with two mutually exclusive diseases duodenal ulcer and gastric cancer. The aim of this study was to explore the relationship and prevalence of Helicobacter pylori infection in different surgical diseases. METHODOLOGY: With use of simple serologic assays for detecting IgA and IgG antibodies to HP antigen, we studied the association of infection with HP and 15 surgical diseases. RESULTS: The prevalence of HP was 68.60% (results of assays were positive for 142 patients out of 207). This study confirmed statistically significant correlation between HP seropositivity and pancreatic cancer (p = 0.02), hepatocellular cancer (p = 0.000), gastric cancer (p = 0.01), colon cancer (p = 0.002), rectal cancer (p = 0.001), intestinal cancer (p = 0.026), stenosis pylori (p = 0.01), ulcer diseases (p = 0.004), jaundice (p = 0.002); statistically significant inverse association between HP seropositivity and the acute appendicitis (p = 0.013) and no correlation with HP infection and cholecystitis (p = 0.716), cholelithiasis (p = 0.06), and ulcer hemorrhage (p = 0.064). CONCLUSION: The use of simple serological tests to identify patients with HP infection could help to calculate the risk of development of severe gastrointestinal diseases.

Plasminogen activator inhibitor in patients with acute myocardial infarction and re-infarction in syndrome X.

Plasminogen activator inhibitor was determined in myocardial infarction and re-infarction patients along with other parameters relevant for the Syndrome X, such as triglycerides, HDL-cholesterol and body mass index. Plasminogen activator inhibitor was determined in 58 patients with myocardial infarction and 18 patients with re-infarction as well as in 57 healthy individuals. Significantly higher plasminogen activator inhibitor values were found in re-infarction patients (6.53 +/- 0.39 U/mL) than in myocardial infarction patients (4.32 +/- 0.19 U/mL), whereas the values were significantly higher in both groups in comparison to healthy individuals (2.81 +/- 0.74 U/mL). Triglyceride values were also significantly higher in myocardial infarction (2.05 +/- 0.1 mmmi/L) and re-infarction patients (2.02 +/- 0.99 mmol/L) than in healthy individuals (1.35 +/- 0.58 mmol/L), although the difference between the triglyceride values obtained for myocardial infarction and re-infarction patients was not statistically significant. HDL-cholesterol values for myocardial infarction (1.18 +/- 0.04 mmol/L) and re-infarction (1.14 +/- 0.18 mmol/L) patients were significantly lower than in healthy individuals (1.46 +/- 0.5 mmol/L). However, the difference was not statistically significant between the myocardial infarction and the re-infarction group. The difference in body mass index between myocardial infarction (26.65 +/- 0.39 kg/m2) and re-infarction (25.49 +/- 0.39 kg/m2) patients and healthy individuals (24.45 +/- 3.41 kg/m2) was evidenced.

Prevalence of Helicobacter Pylori in Different Surgical Diseases: A Preliminary Report.

The aim of this study was to explore the prevalence of Helicobacter pylori infection in different surgical diseases in patients with six different cancer types. We analyzed sixty consecutive patients with malignancy (gastric cancer, pancreatic cancer, hepatocellular cancer, intestinal cancer, colon cancer, rectal cancer). Detection of specific IgA and IgG antibodies to Helicobacter pylori in human serum was determined by Enzygnost Anti-Helicobacter pylori II/IgA (IgG) using ELISA processor (Siemens, Germany). This study confirmed statistically significant association between Helicobacter pylori seropositivity and all types of cancer included in the study. All patients had elevated levels of Helicobacter pylori IgA and IgG antibodies. Patients with examined cancer types that underwent abdominal surgery exibited a strong antibody reaction to Helicobacter pylori.

The effect of nutritional status, body composition, inflammation and serum iron on the developement of insulin resistance among patients on long-term hemodialysis.

We investigated the effect of body composition, nutrition, inflammation and iron status on insulin resistance in patients with long-term hemodialysis. We selected 43 stable end-stage chronic renal failure patients, on maintenance hemodialysis. We evaluated the nutritional status, body composition by subjective global assessment (SGA), anthropometric measurements (BMI and waist circumference), bioelectrical impedance analysis and biochemical parameters measurements [serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein]. All parameters were evaluated by comparisons between HOMA-IR tertiles, and after simple regression analysis, by backward multivariate regression analysis we identified independent variables for IR. As the tertile of HOMA-IR increased, serum level of glucose, insulin, and waist increascd, whereas HDL-cholesterol level decreased, or the prevalence of the metabolic syndrome increased across the tertiles of HOMA-IR. After adjustment for gender, age, hemodialysis duration, ferritin, phosphorus, waist and total fat percentages, multivariate regression analysis was performed and the association with HOMA-IR was still strong only for serum levels of iron and TNF-alpha. That explains 16% of the total variation in HOMA-IR. Our results suggest that the increase of IR in end-stage chronic renal failure patients on hemodialysis could be related to anemia and particularly to iron overload. Moreover, chronic inflammatory status with over-production of adipokine TNF-alpha participate in the pathogenesis of IR too. The present study demonstrated that adipokine TNF-alpha and serum iron participated as independent predictors in the pathogenesis of insulin resistance on long-term hemodialysis patients.

[Inflammatory markers, nutritional parameters and polyunsaturated fatty acids in hemodialysis patients].

INTRODUCTION: Malnutrition and inflammation are associated with end-stage renal disease. Inflammation leads to reduced synthesis of albumin, transferin, and other negative acute-phase proteins and increases their catabolic rates. The causes of inflammation are multifactorial, including oxidative modification of plasma proteins, interaction of blood with nonbiocompatible membranes, and other infectious processes. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) powerfully predict death from cardiovascular disease in dialysis patients as well as progression of vascular injury. The aim of our study was to establish a correlation between markers of inflammation and parameters of malnutrition in hemodialysis patients. MATERIAL AND METHODS: We examined 42 hemodialysis patients at the mean age of 55+/-8 with dialysis duration 52.6+/-42. For nutritional assessment subjective global assessment (SGA), anthropometric parameters, bio-electric impedance (BIA), and biochemical nutritional parameters were used. We measured their plasma levels of inflammatory markers: C-reactive protein, IL-6 and TNF-alpha. Patients with severe malnutrition had higher level of IL-6 and TNF-alpha. RESULTS AND DISCUSSION: The following correlations between measured parameters emerged. There was a negative correlations between serum albumin concentration and inflammatory markers (r=-0.31; p=0.05). Anthropometric parameters in hemodialysis patients were lower when inflammatory markers were higher and correlation was significant (p=0.05). A statistically significant negative correlation between TNF-alpha and EPA (r=-0.497; p<0.05) and IL-6 and EPA (r=-468; p=0.03) was found in hemodialysis patients. CONCLUSION: The main findings of this study were that the decrease of nutritional parameters in hemodialysis patients were related to the degree of inflammation. Nutritional factors, as essential fatty acids, could lead to permanent changes in the inflammatory process.

Metabolic syndrome in HD patients: association with body composition, nutritional status, inflammation and serum iron.

OBJECTIVE: Insulin resistance and metabolic syndrome (MeS) are common in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Such metabolic and clinical abnormalities may lead to an increased risk for cardiovascular disease. METHODS: The study group included 22 well-nourished and 20 middle- to moderate-malnourished, stable ESRD patients, with median dialysis duration of 48 months (IQR 24.5-82.0). To determine nutritional status, body composition, inflammatory biomarkers and the presence of MeS subjective global assessment (SGA), anthropometrical measurements (BMI and waist circumference), bioelectrical impedance analysis (BIA), and biochemical parameters [the levels of serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, TIBC, transferrin saturation (TSAT), ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein (hs-CRP)] were used. All parameters were evaluated by comparisons between two groups, with MeS (Group 2) and without it (Group 1). Logistical regression analysis was used to evaluate the correlation between measured variables and the presence of MeS in HD patients. Independent variables for MeS were identified by backward multivariate regression analysis. To identify the independent predictors for insulin resistance index (HOMA-IR) multivariate regression analysis was conducted, after linear regression analysis. RESULTS: After adjustment for confounding variables, a model consisting of serum levels of iron, transferrin saturation (TSAT), and BMI which accounted for 62% of the variance in MeS, determined only BMI as an independent marker (according to ATP-III criteria). But, serum glucose level, iron, waist and total fat mass accounted for 68% of the variance in MeS, according to IDF criteria. Glucose level was an independent predictor. BMI and iron, as independent variables, contributed to 29% of the variance in IR HOMA, the sensitive marker of MeS. CONCLUSION: The present study demonstrated that serum iron participated together with independent predictors, glucose and BMI, in the pathogenesis of IR and MeS of ESRD patients on maintenance HD.

[Plasminogen activator inhibitor-1 in the evolution of stroke]. / Inhibitor 1 aktivatora plazminogena u evoluciji mozdanog udara.

Fibrinolytic activity in the acute stroke was examined by monitoring the level of plasminogen activator inhibitor-1 (PAI-1), as one of the indicators of fibrinolytic activity. Given the role of PAI-1 in the processes of atherogenesis and thrombogenesis, plasma PAI-1 level was measured in 59 patients (up to 50 years of age) with atherothrombotic stroke (verified by computed tomography scanning or magnetic resonance imaging of brain) in the period from 12 to 24 hours (I analysis) and 30 days after the onset of stroke (II analysis); then, it was correlated with plasma PAI-1 level in the control group (57 healthy subjects), which was 2.86 +/- 0.70 U/ml. It was found that PAI-1 level was significantly higher in the acute stroke (I analysis: PAI-1 = 4.10 +/- 1.40 U/ml, p < 0.001; II analysis: PAI-1 = 3.64 +/- 0.90 U/ml, p < 0.001), while fibrinolytic activity was lower, especially on the first day from the stroke that was not completely increased even after 30 days. There was no difference in PAI-1 levels between the subgroups of patients with infarction and lacunar cerebral ischemia (p > 0.05), as well as between females and males (p > 0.05). Along with significantly increased fibrinogen level (4.65 +/- 1 g/l, in the controls--2.83 +/- 0.64 g/l, p < 0.001), significantly higher triglycerides (2.04 +/- 0.76 mmol/l, in the controls--1.38 +/- 0.54 mmol/l, p < 0.001) and lipoproteins(a) (0.405 +/- 0.29 g/l, in the controls--0.172 +/- 0.14 g/l, p < 0.001) were found, correlating with higher plasma PAI-1 level in these patients. The increased plasma level of PAI-1 pointed to possibility of decreased fibrinolytic activity in pathogenesis of ischemic stroke, as well as, risk of reinsult, which had been the greatest after the onset of stroke and declined gradually within several weeks.