Asymmetric Dimethylarginine Is a Marker of Endothelial Dysfunction in Thrombotic Antiphospholipid Syndrome Patients.

Objective: The potential contribution of asymmetric dimethylarginine (ADMA) and high-sensitivity C reactive protein (hsCRP) to endothelial dysfunction in APS patients has not been studied in detail, until now. The study involved 105 APS patients (59 diagnosed with primary APS (PAPS) and 46 APS associated with systemic lupus erythematosus (SAPS)) who were compared to 40 controls. Endothelial dysfunction was assessed by measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate dilatation (NMD) of the brachial artery. ADMA (micromol/L) was analyzed by ELISA. Results: FMD in patients with APS was significantly lower than that of the controls (p < 0.001), with no difference between the PAPS and the SAPS groups. ADMA and hsCRP concentrations were significantly higher in the patient cohort than in the control group (p < 0.001, p = 0.006, respectively), as was the case with the SAPS group as compared to the PAPS group (p < 0.001, p = 0.022, respectively). FMD impairment correlated to ADMA (ρ 0.472, p < 0.001) and to hsCRP (ρ 0.181, p = 0.033). In the regression model, the ADMA concentration confirmed the strength of its association (B 0.518, SE 0.183, Wald 8.041, p = 0.005, Exp(B) 1.679, 95% CI 1.174−2.402) to FMD impairment. The synergistic probability model of ADMA and hsCRP caused FMD impairment when the positivity of ß2GPIIgG was added. ADMA may be used as a simple and low-cost tool for verifying the presence of endothelial dysfunction in APS patients. According to the results of the study, we could presume that hsCRP, together with aPL, has a preparatory effect on the endothelium in causing endothelial dysfunction.

A Simple Index for Nonalcoholic Steatohepatitis-HUFA-Based on Routinely Performed Blood Tests.

Background and objectives: Data suggests that nearly 30% of the general population have steatosis and up to 5% of this population develops nonalcoholic steatohepatitis (NASH). Liver biopsy is still considered to be the gold standard for the diagnosis of NASH. Great effort is being made toward the identification of sensitive diagnostic tests that do not involve invasive procedures to address a common concern in patients with the nonalcoholic fatty liver disease-whether they have NASH or simple steatosis. We aimed to investigate the independent predictors and develop a non-invasive, easy-to-perform, low-cost set of parameters that may be used in clinical practice to differentiate simple steatosis from NASH. Methods: А cross-sectional study of nonalcoholic fatty liver disease (NAFLD) patients divided into two groups: group I-simple steatosis (SS) and group II-biopsy-proven NASH. Strict inclusion criteria and stepwise analysis allowed the evaluation of a vast number of measured/estimated parameters. Results: One hundred and eleven patients were included-82 with simple steatosis and 29 with biopsy-proven NASH. The probability of NASH was the highest when homeostatic model assessment of insulin resistance (HOMA-IR) was above 2.5, uric acid above 380 µmol/L, ferritin above 100 µg/L and ALT above 45 U/L. An acronym of using first letters was created and named the HUFA index. This combined model resulted in an area under the receiver operator characteristic curve (AUROC) of 0.94, provided sensitivity, specificity, positive predictive value and a negative predictive value for NASH of 70.3%, 95.1%, 83.1% and 90.0%, respectively. Conclusion: We suggest a simple non-invasive predictive index HUFA that encompasses four easily available parameters (HOMA-IR, uric acid, ferritin and ALT) to identify patients with NASH, which may reduce the need for a liver biopsy on a routine basis in patients with NAFLD.

Comparison of two laboratory assays in monitoring the efficacy of different prophylaxis regimens for severe haemophilia.

BACKGROUND: The goal of this study was to compare the validity of two laboratory assays, rotation thromboelastometry (ROTEM) and endogenous thrombin potential (ETP), in monitoring and evaluating different prophylactic treatment regimens in patients with severe haemophilia. METHODS: Twenty adult patients with severe haemophilia were divided into three groups according to treatment regimen with concentrate of factor (F) VIII/IX: full-dose prophylaxis (5 patients), intermediate-dose prophylaxis (5 patients), and on demand treatment (10 patients). RESULTS: The ROTEM for the group treated with full-dose prophylaxis was significantly lower than ROTEM for the group treated with intermediate-dose prophylaxis (p = 0.025). Among the patients given full-dose prophylaxis, 40% (2 patients) had prolonged ROTEM after 3 months of treatment, while among those given intermediate-dose prophylaxis all patients (100%, 5 patients) had prolonged ROTEM (p = 0.038). The ETP was significantly improved after 3 months of full-dose in comparison with intermediate-dose prophylaxis (p = 0.042). CONCLUSIONS: ROTEM and ETP are useful laboratory assays for monitoring efficacy of different prophylaxis regimens with concentrate of FVIII/IX in patients with severe haemophilia, helping in making decisions regarding optimal dose-regimen prophylaxis.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

BACKGROUND: The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. METHODS: We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. RESULTS: Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. CONCLUSIONS: NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Hematological, oxidative stress, and immune status profiling in elite combat sport athletes.

The aim of this study was to profile hematological, oxidative stress, and immunological parameters in male athletes who practiced combat sports and to determine whether the type of combat sport influenced the measured parameters. Eighteen karate professionals, 15 wrestlers, and 14 kickboxers participated in the study. Hematological, iron-related, oxidative stress, and immunological parameters were measured at the beginning of a precompetitive period. The general linear model showed significant differences between the karate professionals, wrestlers, and kickboxers with respect to their hematological and iron status parameters (Wilks' Lambda = 0.270, F = 2.186, p < 0.05) and oxidative stress status (Wilks' Lambda = 0.529, F = 1.940, p < 0.05). The immature reticulocyte fraction was significantly higher in wrestlers (0.30 ± 0.03) compared with kickboxers (0.24 ± 0.04; p < 0.05) and karate professionals (0.26 ± 0.04; p < 0.05). Low hemoglobin density was significantly lower in wrestlers and kickboxers (p < 0.05) compared with karate professionals (karate: 3.51 ± 1.19, wrestlers: 1.95 ± 1.10, and kickboxers: 1.77 ± 0.76). Significant differences were observed between the karate professionals and wrestlers with respect to their pro-oxidant-antioxidant balance (437 ± 103 vs. 323 ± 148, p < 0.05) and superoxide-dismutase activity (SOD) (73 ± 37 vs. 103 ± 30, p < 0.05). All the measured parameters (with the exception of SOD activity) fell within their physiological ranges, indicating that the study participants represented a young and healthy male population. Hematological parameters differed between kickboxers and karate professionals. The low pro-oxidant-antioxidant balance and high SOD activity in wrestlers could be associated with the long-term impact of wrestling as a type of strenuous exercise.

Iron deficiency in nonanaemic COPD patients-Could Low haemoglobin density and Microcytic anaemia factor be usefull?

INTRODUCTION: Erythrocyte indices LHD and Maf are complementary parameters to complete blood count and have been shown as reliable iron deficiency markers in different clinical settings. The aim of the study was to assess diagnostic performances of LHD and Maf in detecting iron deficiency in nonanaemic stable COPD patients. METHODS: A total of 93 nonanaemic stable COPD patients were classified as either iron deficient (ID, N = 15) or non-iron deficient (non-ID, N = 78). Iron deficiency was defined as a ferritin level < 100 µg/L with a transferrin saturation (TSAT) <20%. A complete blood count, including LHD and Maf as well as other relevant inflammation and iron status parameters were obtained for all participants. RESULTS: Both LHD and Maf have shown significant differences between the ID and non-ID group with p = .003 and p = .007 respectively. The AUC for LHD was .744 (95% CI: .626-.863, p = .003) with the best cut-off of 5.85 and sensitivity of 80% (95% CI: 76.0-84.0) and specificity of 61.5% (95% CI: 58.4-64.6). The AUC for Maf was .707 with optimal cut-off value 12.65 and sensitivity of 83.3% (95% CI: 79.1-87.5) and specificity of 60.0% (95% CI: 57.0-63.0). Furthermore, LHD performance was not affected by vitamin B12 status. CONCLUSION: LHD and Maf are useful for iron deficiency diagnosis in stable COPD patients. LHD was shown to be resistant to vitamin B12 deficiency, which is of substantial importance in specific patient subpopulations. Both parameters are not technology-dependant and do not require additional sample and/or reagent volume, which makes them cost-effective and convenient for everyday use.

How Supplementation with SOD-Rich Plant Extract, Combined with Gliadin, Can Affect Oxidative Stress Markers and Zonulin Levels in Exercise-Induced Oxidative Stress.

A randomized, double-blind, placebo-controlled study was conducted to investigate the influence of supplementation with a superoxide dismutase (SOD)-rich plant extract on markers of oxidative stress, zonulin levels and the performance of elite athletes. Participants were 30 international-level rowers, divided into an experimental group (n = 15) and a control group (n = 15). The rowers performed a maximal effort incremental test on a rowing ergometer at the beginning and at the end of the study. Markers of oxidative stress (total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), superoxide dismutase (SOD), glutathione peroxidase (GPx), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), sulfhydryl (SH) groups, bilirubin, uric acid, albumin and zonulin) were determined in serum. A lower TOS (p = 0.010) and OSI (p = 0.004), a lower MDA (p = 0.001) and a higher level of SH groups (p = 0.031) were observed in the experimental group after supplementation. Physical performance was evaluated through metabolic efficiency, taking lactate levels and power output on the ergometer into account. After 6 weeks of supplementation, the relative increase in metabolic efficiency at a 4 mmol/L lactate concentration and maximal effort was significantly higher in the experimental group (p = 0.004 and p = 0.015, respectively). These results suggest that supplementation with a SOD-rich extract promotes lower oxidative stress, better antioxidant protection and, consequently, the better work performance of athletes.

Risk factors associated with coronary artery calcification should be examined before kidney transplantation.

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p < 0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.

Effects of 6-Week Supplementation with GliSODin on Parameters of Muscle Damages, Metabolic, and Work Performance at International Level Rowers after Specific Maximal Effort.

This study aimed to investigate the effect of supplementation with plant origin superoxide dismutase (SOD), GliSODin, on parameters of muscle damage, metabolic, and work performance at international level rowers. Twenty-eight rowers were included in a randomized, double-blind study. The study was conducted during a 6-week preparation period. At the beginning of the study and after 6 weeks of the supplementation period, all rowers were tested on a rowing ergometer. Blood samples were taken from the antecubital vein before and after every ergometer testing. Muscle damage markers creatine kinase (CK) and lactate dehydrogenase (LDH), total antioxidant capacity (TAC), inflammation parameters interleukin-6 (IL-6), and C-reactive protein (CRP) were measured. Rowing performance was assessed by lactate level in capillary blood and power output on the rowing ergometer. After supplementation, experimental group had significantly lower CK (p = 0.049) and IL-6 (p = 0.035) before and IL-6 (p = 0.050) after exhausting exercise on ergometer. Relative change of power output at 4 mmol/L concentration of lactate in blood, considering the initial and final test, was significantly higher (p = 0.020) in the supplemented group. It was concluded that GliSODin could be considered a good supplement in preventing some deleterious effects of intensive physical activity, including inflammation and muscle damage, and consequently, to enable a better rowing performance of elite rowers.

Veno-occlusive disease in pediatric patients after hematopoietic stem cell transplantation: relevance of activated coagulation and fibrinolysis markers and natural anticoagulants.

Prediction of veno-occlusive disease (VOD), its precise diagnosis, and treatment have been the subject of various studies, but still remain unclear. Our goal was to investigate the levels of activated coagulation and fibrinolysis markers and natural anticoagulants in pediatric patients with VOD after hematopoietic stem cell transplantation (HSCT). We investigated 47 pediatric patients: 20 with neuroblastoma, 17 with leukemias, and 10 with lymphomas and measured the values of antithrombin (AT), protein C (PC), fibrinogen (FI), thrombin AT complex, prothrombin fragments 1+2 (F1+2), and D-dimer from day -7 to day +30 post-HSCT. Patients were monitored for the occurrence of VOD, and it occurred in 10 patients at a median post-HSCT day of 17.5 (range: 2 to 28 d). In the VOD group, at baseline the levels of FI were significantly lower, and on days +7 and +14 a relevant difference existed in F1+2 levels. The levels of PC were significantly lower on day +14. Logistic multivariate regression analysis between the groups showed significantly different D-dimer levels on day +14. On day +30, the levels of PC, AT, and F1+2 were different between these 2 groups of patients. The levels of D-dimer and F1+2 were increased, and PC and FI decreased before the clinical onset of VOD. The parameter differences may have a predictive value in VOD onset, which makes them candidates to be routinely monitored in patients after HSCT.

Haematological and iron-related parameters in male and female athletes according to different metabolic energy demands.

We investigated the iron-related haematological parameters in both male and female athletes participating in different sporting disciplines necessitating different metabolic energy demands. A total of 873 athletes (514 males, mean age: 22.08 ± 4.95 years and 359 females, mean age: 21.38 ± 3.88 years) were divided according to gender and to the predominant energy system required for participation in sport (aerobic, anaerobic or mixed) and haematological and iron-related parameters were measured. For both male and female athletes, significant differences related to the predominant energy system were found at a general level: male (Wilks' λ = 0.798, F = 3.047, p < 0.001) and female (Wilks' λ = 0.762, F = 2.591, p < 0.001). According to the ferritin cutoff value of 35 µg/L, whole body iron and sTfR significantly differed in all three groups of male and female athletes (p < 0.001). The percentage of hypochromic erythrocytes in male athletes was significantly higher only in those who required an anaerobic energy source (p < 0.001), whilst in the females hypochromic erythrocytes (p < 0.001) and haemoglobin (anaerobic, p = 0.042; mixed, p = 0.006) were significantly different only in anaerobic and mixed energy source athletes. According to the ferritin cutoff value of 22 µg/L, in females, whole body iron, sTfR and hypochromic erythrocytes were significantly higher in all three groups of athletes than those below the aforementioned cutoff value (p < 0.001). We conclude that the predominant energy system required for participation in sport affects haematological parameters. sTfR and body iron proved to be reliable parameters for monitoring the dynamics of iron metabolism and could contribute to successful iron-deficiency prevention.

Oxidative stress biomarker monitoring in elite women volleyball athletes during a 6-week training period.

The objectives of this study were to determine (a) if reactive oxygen metabolites (ROMs) are a reliable parameter for monitoring oxidative stress in athletes alone or in association with other parameters of oxidative stress and depending on whether antioxidant supplements are taken or not; (b) the level of oxidative stress in athletes before the competition season; and (c) if oxidative status could be improved in volleyball athletes. Sixteen women athletes (supplemented group) received an antioxidant cocktail containing vitamin E, vitamin C, zinc gluconate, and selenium as a dietary supplement during a 6-week training period, whereas 12 of them (control group) received no dietary supplement. Blood samples were taken before and after the training period. The following parameters were measured: ROMs, superoxide anion (O2⁻2), malondialdehyde (MDA), advanced oxidation protein products (AOPP), lipid hydroperoxide (LOOH), biological antioxidative potential (BAP), paraoxonase activity toward paraoxon (POase) and diazoxon (DZOase), superoxide dismutase(SOD), total sulfydryl group concentration (SH groups), and lipid status. Reactive oxygen metabolites were taken as the dependent variable and MDA, O2⁻2, AOPP, and LOOH as independent variables. In the group of athletes who have received supplementation, linear regression analysis revealed that the implemented model had a lower influence on dROMs (70.4 vs. 27.9%) after the training period. The general linear model showed significant differences between parameters before and after training/supplementation (Wilks' lambda = 0.074, F = 11.76, p < 0.01). At the partial level, significant increases in ROM levels (p <0.05, 95% confidence interval [CI]: 286-337), SOD activity (CI: 113-144), and BAP (CI: 2,388-2,580) (p < 0.01) were observed. The association between ROMs and other parameters of oxidative stress was reduced in athletes who received supplements. During the precompetition training period, treatment with dietary supplements prevented the depletion of antioxidative defense in volleyball athletes.

Factors associated with hepcidin-25 levels in maintenance hemodialysis patients.

This study aimed to investigate the factors that are independently associated with hepcidin-25 and its relationship with doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron in stable maintenance hemodialysis patients (smHD) stratified by ESAs administration. In 103 adult smHD (ESAs therapy (N = 64) and ESAs-free (N = 39)), median values of biologically active hepcidin-25 (chemiluminescent direct ELISA assay) and ferritin levels were significantly higher whereas red blood cell count, hemoglobin, and hematocrit values were lower in ESAs therapy compared to ESAs-free group (P < .001, for all). Our results suggest that ESAs-independent smHD exhibit supposedly normal hepcidin-25 levels and preserved iron homeostasis, with a lower degree of anemia. The results of our multivariable model indicate that hepcidin-25 levels are independently and positively associated with iron stores and inflammation, and inversely with active erythropoiesis, regardless of ESAs administration. Maintenance ESAs and the intravenous iron dose were not related to hepcidin-25 levels.

Assessment of positive iron balance in end-stage renal disease: Could hepcidin-25 be useful?

INTRODUCTION: The aim of our study was to examine the relationship of hepcidin-25 with red blood cell and reticulocyte indices and to evaluate the diagnostic properties of hepcidin-25 in the assessment of positive iron balance in end-stage renal disease (ESRD) patients. METHODS: Eighty anemic ESRD patients (hemoglobin < 110 g/L) were classified as having iron deficiency (ID, N = 20), iron sufficiency (IS, N = 29), and positive iron balance (PB, N = 31) using the conventional biomarkers for iron status evaluation. Hepcidin-25 was determined by a chemiluminescent direct ELISA. RESULTS: Hepcidin-25 was significantly negatively correlated with the proportion of hypochromic erythrocytes (%HYPO) (P = .034) and immature reticulocyte fraction (P = .010) in ID and with the absolute reticulocyte concentration in ID (P = .048) and PB (P = .040). In multivariate models, hepcidin-25 was independently negatively associated with the mean reticulocyte hemoglobin content (CHr; ß = -0.493, P = .004) and red blood cell size factor (RSf) (ß = -0.334, P = .036) only in the PB group. The best hepcidin-25 value to exclude PB was 66.13 µg/L, showing a sensitivity of 61.3%, a specificity of 75.5%, and an AUC of 0.808. CONCLUSION: Our results suggest that hepcidin-25 levels are independently negatively associated with the iron demand for the most recent erythropoiesis only in PB. Hepcidin-25 performed acceptable in discriminating anemic ESRD patients with positive iron balance and may prove to be a useful additional tool in the evaluation of iron status.

Phosphatidylserine Exposing Extracellular Vesicles in Pre-eclamptic Patients.

Background: Pre-eclampsia (P-EC) is associated with systemic inflammation, endothelial dysfunction and hypercoagulability. The role of extracellular vesicles (EVs) in coagulation disturbances affecting the development and severity of P-EC remains elusive. We aimed to evaluate the concentration of EVs expressing phosphatidylserine (PS) and specific markers in relation to the thrombin and fibrin formation as well as fibrin clot properties, in pregnant women with P-EC in comparison to healthy pregnant women of similar gestational age. Methods: Blood samples of 30 pregnant women diagnosed with P-EC were collected on the morning following admission to hospital and after delivery (mean duration 5 days). The concentration of the PS-exposing EVs (PS+ EVs) from platelets (CD42a+, endothelial cells (CD62E+), and PS+ EVs expressing tissue factor (TF) and vascular cell adhesion molecule 1 (VCAM-1) were measured by flow cytometry. Further phenotyping of EVs also included expression of PlGF. Markers of maternal haemostasis were correlated with EVs concentration in plasma. Results: Preeclamptic pregnancy was associated with significantly higher plasma levels of PS+ CD42a+ EVs and PS+ VCAM-1+ EVs in comparison with normotensive pregnancy. P-EC patients after delivery had markedly elevated concentration of PS+ CD42a+ EVs, CD62E+ EVs, TF+ EVs, and VCAM-1+ EVs compared to those before delivery. Inverse correlation was observed between EVs concentrations (PS+, PS+ TF+, and PlGF+) and parameters of overall haemostatic potential (OHP) and fibrin formation, while PS+ VCAM-1+ EVs directly correlated with FVIII activity in plasma. Conclusion: Increased levels of PS+ EVs subpopulations in P-EC and their association with global haemostatic parameters, as well as with fibrin clot properties may suggest EVs involvement in intravascular fibrin deposition leading to subsequent microcirculation disorders.

Indicators of Absolute and Relative Changes in Skeletal Muscle Mass during Adulthood and Ageing.

This study aimed to explore the set of variables related to skeletal muscle mass (SMM) in both sexes, and to create age- and sex-related models of changes in SMM, using the most representative indicator of muscular status. Body composition was assessed in 8733 subjects (♀ = 3370 and ♂ = 5363), allocated into subsamples according to age: 18-29.9, 30-39.9, 40-49.9, 50-59.9, 60-69.9, and 70.0-79.9 years. Nine variables were used: protein mass, protein percent, protein mass index, SMM, percent of SMM, SMM index, fat-free mass, fat-free mass index, and protein/fat index. Univariate and multivariate analysis of variance (ANOVA and MANOVA) were used to determine between- and within-sex difference in all variables by age. Correlation analysis established the relationship between age and muscularity variables. Principal Component Analysis extracted the variables that loaded highest in explaining muscularity, while regression analysis determined the linearity of association between the age and indicators of muscular status. Variables SMMI and PSMM were extracted as the most sensitive to age, with SMMI being gender-independent while showing the parabolic and sinusoidal form of change as function of ageing in males and females, respectively; and PSMM being sex-dependent while showing a linear trend of decrease in both sexes.

Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis.

BACKGROUND: The progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with Nash. Setting: Outpatient hepatology clinic. METHODS: A prospective trial was conducted. The first cohort included patients with biopsy-proven Nash, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in Nash group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications. RESULTS: All 33 Nash patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 mmol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA - IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase by 24.0 U/L, 9.1 U/L, 10.8 U/L respectively, was noted. CONCLUSIONS: Pentoxifylline and Metformin may provide possible treatment option in Nash. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.

Evaluation of global haemostatic assays and fibrin structure in patients with pre-eclampsia.

INTRODUCTION: Haemostatic balance shifted towards hypercoagulability in normal pregnancy is even more pronounced in pre-eclampsia (P-EC). The aim of this study was to analyse haemostatic disturbances and fibrin clot properties in women with pre-eclampsia and to investigate their association with maternal and foetal outcomes. METHODS: Forty-six pregnant women diagnosed with pre-eclampsia were included in the study, with blood sampling done on the morning following admission to hospital, as well as after delivery (mean duration 4.8 days). Two global haemostatic assays-endogenous thrombin potential (ETP) and assay of overall haemostatic potential (OHP)-were employed, including fibrin clot turbidity measurements and scanning electron microscopy (SEM) of representative samples. RESULTS: Three thrombin generation parameters (ETP, t_lag and peak height) and OHP were significantly increased in pre-eclampsia compared with controls, whereas overall fibrinolytic potential (OFP-determined as a parameter of the OHP assay) had significantly lower values. Clot lysis time was significantly prolonged in patients with pre-eclampsia. In the pre-eclamptic group after delivery, we observed a significant elevation in the peak height and a reduction in the time to peak and OFP compared with values before delivery. Pre-eclamptic patients with renal complications had significantly higher values for ETP, peak height and D-dimer. Turbidity measurements and SEM revealed dense fibrin structure in patients with pre-eclampsia. CONCLUSION: Patients with pre-eclampsia have enhanced coagulation and impaired fibrinolysis before, and even after, delivery. In particular, the presence of multi-organ dysfunction, such as renal dysfunction, may be associated with increased thrombin generation in pre-eclampsia.

Serum amyloid-A rather than C-reactive protein is a better predictor of mortality in hemodialysis patients.

The most frequent cause of death in hemodialysis patients is cardiovascular disease with chronic inflammation being an epidemiologically proved risk factor. Many studies have shown C-reactive protein (CRP) as the strongest predictor of long-term mortality of hemodialysis patients, while other reports have indicated acute phase proteins as potential predictors of the mortality. The present study therefore aimed to evaluate the prevalence of chronic inflammation in hemodialysis patients and the role of acute phase proteins together with lipids and divalent ions for predicting mortality in hemodialysis patients. Chronic inflammation was defined, based on the serum level of high sensitive CRP > 8.4 mg/L and/or serum amyloid-A (SAA) > 8.9 mg/L. Acute phase proteins are defined as one whose plasma concentration increase (positive) or decreases (negative) by at least 25% during inflammation. High sensitive CRP and SAA were positive acute phase proteins measured, while albumin and fetuin-A, a calcification inhibitor, were selected as negative acute phase proteins. This prospective 36-month follow-up study included 130 patients (60 males and 70 females, aged 55.1 +/- 12.9 years) maintained by hemodialysis for 107.2 +/- 54.72 months at a Nephrology Clinic in Belgrade. The prevalence of chronic inflammation was 35.4% (46 patients). During the follow-up period, 24 patients (18.5%) died and 2 patients received transplants. In multivariate analysis, potential independent predictors of mortality in hemodialysis patients are hyperphosphatemia, hypoalbuminemia, and high SAA. Considering that assays for SAA are widely used, we propose that SAA is the best predictor for outcomes of end-stage renal disease.

Associations of Common Variants in HFE and TMPRSS6 Genes with Hepcidin-25 and Iron Status Parameters in Patients with End-Stage Renal Disease.

BACKGROUND: Influence of TMPRSS6 A736V and HFE (C282Y and H63D) polymorphisms on serum hepcidin-25 levels and iron status parameters in end-stage renal disease (ESRD) patients stratified according to gender has not been previously investigated. In addition, we aimed to evaluate the diagnostic accuracy of the parameters to separate iron-deficiency anemia (IDA) from anemia of chronic disease. MATERIALS AND METHODS: Iron status parameters and genetic analysis were performed in 126 ESRD patients and in 31 IDA patients as the control group. RESULTS: ESRD patients had significantly higher ferritin and hepcidin-25 (<0.001) relative to IDA patients. Cut-off values with the best diagnostic accuracy were found for hepcidin ≥9.32 ng/mL, ferritin ≥48.2 µg/L, transferrin saturation ≥16.8%, and MCV ≥81 fL. Interaction between gender and HFE haplotypes for the hepcidin-25 and ferritin levels in ESRD patients (p = 0.005, partial eta squared = 0.09; p = 0.027, partial eta squared = 0.06, respectively) was found. Serum transferrin was influenced by the combined effect of gender and TMPRSS6 A736V polymorphism in ESRD patients (p = 0.002, partial eta squared = 0.07). CONCLUSION: Our findings could contribute to the further investigation of mechanisms involved in the pathophysiology and important gender-related involvement of the TMPRSS6 and HFE polymorphisms on anemia in ESRD patients.