The coincidence of low vitamin K status and high expression of growth differentiation factor 15 may indicate increased mortality risk in stable coronary heart disease patients.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification critically dependent on circulating vitamin K status. Growth differentiation factor 15 (GDF-15) is a regulatory cytokine mainly of the inflammatory and angiogenesis pathways, but potentially also involved in bone mineralization. We sought to determine whether these two circulating biomarkers jointly influenced morbidity and mortality risk in patients with chronic coronary heart disease (CHD). METHODS AND RESULTS: 894 patients ≥6 months after myocardial infarction and/or coronary revascularization at baseline were followed in a prospective study. All-cause and cardiovascular mortality, non-fatal cardiovascular events (myocardial infarction, stroke, any revascularization), and hospitalization for heart failure (HF) were followed as outcomes. Desphospho-uncarboxylated MGP (dp-ucMGP) was used as a biomarker of vitamin K status. Both, increased concentrations of dp-ucMGP (≥884 pmol/L) and GDF-15 (≥1339 pg/mL) were identified as independent predictors of 5-year all-cause or cardiovascular mortality. However, their coincidence further increased mortality risk. The highest risk was observed in patients with high dp-ucMGP plus high GDF-15, not only when compared with those with "normal" concentrations of both biomarkers [HR 5.51 (95% CI 2.91-10.44), p < 0.0001 and 6.79 (95% CI 3.06-15.08), p < 0.0001 for all-cause and cardiovascular mortality, respectively], but even when compared with patients with only one factor increased. This pattern was less convincing with non-fatal cardiovascular events or hospitalization for HF. CONCLUSIONS: The individual coincidence of low vitamin K status (high dp-ucMGP) and high GDF-15 expression predicts poor survival of stable CHD patients.

Effect of n-3 fatty acids supplementation during life style modification in women with overweight.

OBJECTIVE: The marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to defend against development of peripheral insulin resistance of healthy person with overweight remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the lifestyle modification (LSM) in women with overweight. METHOD: In a parallel-group, three-arm, randomized trial (UMIN Clinical Trials Registry - R000031131), 34 women were assigned to a 12-week-intervention using corn oil (1.5 g/day; placebo); LSM and corn oil (1.5 g/day; LSM); or LSM and EPA + DHA concentrate (1.5 g/day, containing ~ 0.6 g EPA + DHA; LSM & n-3). At baseline and after intervention, anthropometric measurements including bioelectrical impedance analysis, spiroergometry, 24-hours dietary recall, and various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures. Data from 29 women were used for the final evaluation. Wilcoxon two-sided rank-sum test was used to inspect the differences between LSM and LSM & n-3, and placebo groups, with a p-value of ≤ 0.05. All computations were performed with MATLAB Statistics Toolbox. RESULTS: In comparison with placebo, LSM and LSM & n-3 decreased body weight, waist circumference, and body fat, and increased VO2max/kg. LSM & n-3 increased adiponectin levels in comparison to LSM. Fasting insulin, IL8, and cholesterol were decreased by LSM, but were unchanged by LSM & n-3. IL6 was not affected in LSM & n-3, while it was increased in LSM. Other inflammatory markers, as well as leptin, LIF, follistatin, BDNF, and fasting triacylglycerol were not significantly affected by any of the interventions. CONCLUSION: Besides preventing a modest negative effect of LSM on IL6 and adiponectin level, the combination of LSM and EPA + DHA supplementation could be probably used to improve the functional capacity of adipose tissue in women with overweight.

Citrate-Buffered Dialysis Solution (Citrasate) Allows Avoidance of Anticoagulation During Intermittent Hemodiafiltration-At the Cost of Decreased Performance and Systemic Biocompatibility.

Reportedly, citrate-based dialysis solution enables heparin dose tapering or even complete exclusion, particularly in postdilution hemodiafiltration (HDF). The aim of the study was to verify this strategy in predilution setting and to assess its short-term safety, efficacy, and biocompatibility. Ten regular hemodialysis patients were assigned to predilution HDF on acetate- and citrate-based dialysis solutions (0.8 mmol/l trisodium citrate) at random order. Acetate HDF was performed using routine dose of heparin while citrate HDF was heparin free. Plasma calcium, thrombin-antithrombin complexes (TAT), and citrate levels were measured at 0, 30, 60, 120, and 240 min. Following each session, a semiquantitative dialyzer clotting score (DCT 1-5) was assessed and HDF adequacy was determined as spKt/V. Statistical relevance was tested by ANOVA with pP < 0.05 held significant, data are given as means ± standard deviations. All sessions were accomplished successfully, premature termination or circuit re-setting was not necessary. However, DCT was significantly higher in citrate-HDF compared to acetate-HDF regimen (3.4 ± 0.65 and 1.8 ± 0.79, respectively, P = 0.002) as well as TAT generation rate (increase per session by factor 11.0 ± 8.43 and 2.1 ± 1.26, respectively, P = 0.004 between regimens). Ionized calcium declined only by the end of citrate-HDF (from 1.09 ± 0.086 to 0.99 ± 0.030 mmol/L, P = 0.002) yet without accompanying clinical symptoms. Systemic citrate levels increased along the citrate-HDF session but stayed an order of magnitude below concentrations needed to establish citrate anticoagulation (peak at 0.276 ± 0.112 mmol/L). Dialysis adequacy estimated by spKt/V was found lower in citrate-HDF vs. acetate-HDF (1.48 ± 0.163 and 1.58 ± 0.165, respectively, P = 0.006). Although predilution HDF using citrate-based dialysate is feasible without heparin, both dialysis adequacy and biocompatibility is significantly compromised. Therefore, this approach can be adopted for a single procedure but is not acceptable on a regular basis.

Comparison of two methods for dimethylarginines quantification.

Objectives: Both dimethylarginines are widely bound to chronic kidney disease (CKD). This study was focused to validate published LC-MS/MS method and compared the measured data with an immunoassay. Design and methods: The analysis was performed on a Dionex UltiMate 3000 UHPLC-Standard (Thermo Fisher Scientific, Waltham, Massachusetts, USA) with an amaZon SL ion trap (Bruker, Billerica, Massachusetts, USA). Comparison was evaluated by using Passing Bablok regression and Bland Altman plot. Healthy volunteers (n = 40) were used for validation and as control group to patients group (n = 40) with different stages of CKD. Results: The results in healthy controls determined by the LC-MS/MS (ELISA) method were 0.52 ± 0.0892 with 95 % CI: 0.49-0.55 (0.61 ± 0.1213 with 95 % CI: 0.57-0.64) µmol/L for AD MA and 0.56 ± 0.0810 with 95 % CI: 0.53-0.58 (0.62 ± 0.0752 with 95 % CI: 0.57-0.65) µmol/L for SDMA. In the same way, the patient group values determined by the LC-MS/MS (ELISA) method were 0.82 ± 0.1604 with 95 % CI: 0.75-0.88 (1.06 ± 0.3002 with 95 % CI: 0.94-1.19) µmol/L and 2.14 ± 0.8778 with 95 % CI: 1.47-2.58 (1.65 ± 0.5160 with 95 % CI: 1.40-1.98) µmol/L for ADMA and SDMA, respectively. The correlation between the methods, expressed as the Spearman correlation coefficient (R), was 0.858 (0.8059) for ADMA (p < 0.0001) and 0.895 (0.9607) for SDMA (p < 0.0001). Conclusions: ADMA levels determined by the immunoassay were almost 30 % overestimated, in contrast to SDMA levels, which were 3 % underestimated. According to our findings, a better correlation could be obtained by simple sample dilution.

Serum citrulline levels as a marker of enterocyte function in patients after allogeneic hematopoietic stem cells transplantation - a pilot study.

BACKGROUND: Citrulline is an amino acid produced by enterocytes. Serum citrulline concentration has been proposed as a marker of enterocyte mass and function. Our study focused on evaluation of citrulline levels in patients with diarrhea related to toxic intestinal damage (mucositis), intestinal graft versus host disease (GVHD), and other etiology of diarrhea (e.g., dysmicrobia) after allogeneic stem cells transplantation (SCT). MATERIAL AND METHODS: This was a prospective study in 11 adults (18 blood samples) with diarrhea developed after allogeneic SCT in 4/2011-1/2012 compared to twenty healthy control samples. RESULTS: The median (interquartile range) of citrulline levels was significantly lower in the transplanted patients group compared to healthy controls: 9.3 (3.62-15.38) vs. 33.3 (26.82-36.23) µmol/L, p<0.0001. The median values of citrulline in patients with post-transplant toxic intestinal mucositis (n=8, days 1-22 post-transplant) vs. intestinal GVHD (n=7, day 43-142) vs. other etiology of diarrhea (e.g., dysmicrobia) (n=3, day 120-127) were: 9.55 (2.95-12.03) vs. 5 (3.85-9.05) vs. 15.6 (15.45-18.3) mol/L resp. Serum citrulline levels were significantly higher in other (eg, dysmicrobic) etiology of diarrhea in comparison with mucositis (p=0.0336) and GVHD (p=0.0152). CONCLUSIONS: Citrulline levels are very low shortly after the myeloablative FLU/MEL or BuCY2 conditioning allogeneic SCT due to the toxic intestinal damage. Significantly low levels of citrulline were also in patients with intestinal GVHD later on. Other observations in larger groups of patients are necessary before any specific recommendation for citrulline levels monitoring in intestinal GVHD can be made.

Macrotroponins cause discrepancy in high-sensitivity examination.

AIM: We present two cases with clearly discrepant results of clinical examination and cardiac troponin I (cTnI) and cardiac troponin T (cTnT) concentrations. In similar cases with discrepant results, the possibility of interference should be considered. METHODS: Due to the suspicion of the presence of macrotroponin I in both of the presented cases, the patients were invited to our laboratory and both cTnI (Architect i1000, Abbott) and cTnT (Cobas 8000, Roche) concentrations were analysed. The samples were treated by preincubation in a heterophilic antibodies blocking tube (HBT) and analysed. Precipitation with polyethylene glycol solution (PEG) and molecular weight separation by gel filtration on Sephadex G100 was performed and concentrations of cTnI were analysed. RESULTS: In the same blood sample, the cTnT and cTnI concentrations were 7 and 1782 ng/L, respectively, in Case 1, and 6 and 96 ng/L, respectively, in Case 2. Incubation of samples in HBT had no significant effect. CTnI concentrations after precipitation with PEG - presented as the percentage of initial concentrations - were 7.4% in Case 1 (and 26.8% in the control sample) and 1.4% in Case 2 (and 56.0% in the control sample). These results indicate a significant decrease in both cases, supporting presence of macrotroponin I. Finally, analyses of cTnI concentrations after gel filtration also supported the presence of macrotroponin I. CONCLUSION: The present cases show that the presence of macrotroponin can lead to unnecessary investigation of the patient. When the possibility of interference is suspected, cooperation with laboratory staff to help with interpretation or to perform more detailed analysis is crucial.

False positive result of human chorionic gonadotropin caused by human anti-mouse antibodies.

Immunochemical reactions are fast, can be automated, and generally do not require pretreatment of biological material. Based on these advantages, they are widely used. On the other hand, they are susceptible to analytical interference that can lead to inaccurate results. These factors include the presence of anti-mouse antibodies, causing false positive (or sometimes false negative) results. Although the anti-mouse antibodies over many decades have been repeatedly identified to be the causative source but due to the rarity of such encounters they remain insufficiently considered. Here we show a case, a 45 year-old female who was mis-diagnosed with pregnancy due to falsely elevated human chorionic gonadotropin (hCG) due to anti-mouse antibodies. This led to the patient undergoing two ultrasound examinations and laparoscopy before the hCG was repeated on alternative assays which showed negative results, preventing the patient from methotrexate treatment. Here we describe the details of the case, outline the assay principal, supporting the finding from literature and outlining a process on how to identify such interferences in timely manner.

Tumour necrosis factor-alpha stimulates liver regeneration in porcine model of partial portal vein ligation.

BACKGROUND/AIMS: Portal vein ligation (PVL) could multiply the future liver remnant volume (FLRV). Tumor necrosis factor- alpha (TNF-α) is a pleiotropic cytokine that is connected with initial phase of liver regeneration. The aim of this basic pilot study was to accelerate regeneration of liver parenchyma after PVL. The experimental porcine model was developed to be as much compatible as possible with portal vein embolization (PVE) in human medicine. METHODOLOGY: After ligation of portal branches of caudate and right lateral and right medial liver lobes recombinant porcine TNF-α (TNF-α group) or physiological solution (control group) were applied into non-occluded portal vein branches. The biochemical and immunoanalytical parameters were assessed. The compensatory hypertrophy was evaluated by periodic ultrasonography. The histological examination of liver was performed. RESULTS: The acceleration of growth of hypertrophic liver lobes was maximal at the 7th postoperative day in comparison with the control group (p<0.05); nevertheless this stimulating effect was lost at the end of experiment. The important differences in biochemical or histological studied parametres between study groups were not proved. CONCLUSIONS: The achieved acceleration of growth of hypertrophic liver lobes after application of TNF-α confirms the role of studied cytokine in priming of liver regeneration.

Bronchial Asthma as a Cardiovascular Risk Factor: A Prospective Observational Study.

Introduction: Asthma as a chronic inflammatory disorder has been suggested as a risk factor for endothelial dysfunction (ED), but studies on the association between asthma and cardiovascular disease (CVD) risk are limited. Background: We assessed associations of ED with the severity of asthma, eosinophilic inflammation, lung function, and asthma control. Methods: 52 young asthmatics (median age of 25.22 years) and 45 healthy individuals were included. Demographic, clinical, and laboratory findings were recorded. We evaluated microvascular responsiveness by recording the reactive hyperemia index (RHI) indicating post-occlusive peripheral endothelium-dependent changes in vascular tone using the Itamar Medical EndoPAT2000. VCAM-1, ADMA, high-sensitive CRP (hsCRP), and E-selectin were measured. Results: Asthmatics had considerably lower RHI values (p < 0.001) with a dynamic decreasing trend by asthma severity and higher hsCRP levels (p < 0.001). A substantial increase in hsCRP and E-selectin with asthma severity (p < 0.05) was also observed. We confirmed a higher body mass index (BMI) in asthmatics (p < 0.001), especially in women and in severe asthma. Conclusions: We demonstrated the progression of CVD in asthmatics and the association of the ongoing deterioration of ED with the inflammatory severity, suggesting that the increased risk of CVD in young asthmatics is dependent on disease severity. The underlying mechanisms of risk factors for CVD and disease control require further study.

Serum biomarkers, skin autofluorescence and other methods. Which parameter better illustrates the relationship between advanced glycation end products and arterial stiffness in the general population?

Stiffening of large arteries, clinically manifesting as increased aortic pulse wave velocity (PWV), is an inevitable outcome of aging. Among other mechanisms, impaired glucose metabolism plays an important role, leading to the deposition of advanced glycation end products (AGEs). This process is counterbalanced by the circulating soluble receptor for AGEs (sRAGE). We investigated the association between arterial stiffness on one side and multiple circulating biomarkers and the degree of skin deposition of AGEs on the other. In a cross-sectional design, 867 participants based on a general population sample (Czech post-MONICA studies) were examined. PWV was measured by SphygmoCor device (AtCor Medical Ltd.), while skin AGEs were measured using a dedicated autofluorescence method (AGE Reader mu®). To quantify the circulating status of AGEs, carboxymethyl lysine (CML) and sRAGE concentrations were assessed by ELISA, along with conventional glucose metabolism indicators. When analyzing the whole sample using multiple linear or logistic regression models and after adjustment for potential covariates, a significant association with PWV was found for fasting glycemia, HbA1c, sRAGE, skin AGEs, and the skin AGE-to-sRAGE ratio. Among these parameters, stepwise models identified the strongest association for the skin AGEs and AGE-to-sRAGE ratio, and this was also true when diabetic subjects were excluded. In contrast, neither CML nor its ratio relative to sRAGE showed any association with arterial stiffness. In conclusion, skin AGEs along with their ratio relative to sRAGE were closely associated with arterial stiffness and is a better indicator of the current status of deposited AGEs than other relevant factors.

The role of advanced glycation end products in vascular aging: which parameter is the most suitable as a biomarker?

Advanced glycation end products (AGEs) are involved in several pathophysiologic processes in vascular diseases, including progressive loss of elasticity of the vessel wall (arterial stiffness). Circulating soluble receptors for AGEs (sRAGE) act as a decoy and counterbalanced the harmful properties of AGEs as the natural protective factor. We compared the role of circulating or skin-deposed AGEs and sRAGE regarding the natural course of arterial stiffening. In a prospective cohort study, we longitudinally followed 536 general population-based subjects (subsample of Czech post-MONICA study). Aortic pulse-wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE and carboxymethyl lysine (circulating AGEs) were assessed at the follow-up visit by ELISA, while skin AGEs were measured using the autofluorescence-based device AGE Reader. Using multiple regressions, we found significant association between ∆PWV/year as a dependent variable, and both, sRAGE and skin AGEs as independent ones (each on its own model). However, the closest associations to ∆PWV/year were found for the ratio of these two factors (skin AGEs/sRAGE) [ß coeff = 0.0747 (SE 0.0189), p < 0.0001]. In a categorized manner, subjects with skin AGEs/sRAGE ratio ≥ 3.3 showed about twofold higher risk having ΔPWV/year ≥ 0.2 m/s [adjusted odds ratio was 2.09 (95% CI: 1.35-3.22), p = 0.001]. In contrast, neither circulating AGEs nor circulating AGEs/sRAGE showed any significant relation to ΔPWV/year. In conclusion, skin AGEs/sRAGE ratio seems to be a more sensitive biomarker of vascular aging than these single factors themselves or circulation status of AGEs.

Asymmetric dimethylarginine in hemodialysis, hemodiafiltration, and peritoneal dialysis.

Asymmetric dimethylarginine (ADMA) is a mediator of endothelial dysfunction. Production and elimination of ADMA may be affected by the type of renal replacement therapy used and oxidative stress. Plasma ADMA, advanced glycation end products (AGE), and homocysteine were assessed in 59 subjects: 20 hemodialysis (HD) patients, 19 patients undergoing peritoneal dialysis (PD), and 20 controls. Results were compared between the groups. The effect of 8 weeks of HD and high-volume predilution hemodiafiltration (HDF) was compared in a randomized study. HD patients showed higher ADMA (1.20 [0.90-1.39 micromol/L]) compared to controls (0.89 [0.77-0.98], P < 0.01), while ADMA in PD did not differ from controls (0.96 [0.88-1.28]). AGE and homocysteine were highest in HD, lower in PD (P < 0.01 vs. HD), and lowest in controls (P < 0.001 vs. HD and PD). PD patients had higher residual renal function than HD (P < 0.01). The decrease in ADMA at the end of HD (from 1.25 [0.97-1.33] to 0.66 [0.57-0.73], P < 0.001) was comparable to that of HDF. Switching from HD to HDF led to a decrease in predialysis homocysteine level in 8 weeks (P < 0.05), while ADMA and AGE did not change. Increased ADMA levels in patients undergoing HD, as compared to PD, may be caused by higher oxidative stress and lower residual renal function in HD. Other factors, such as diabetes and statin therapy, may also be at play. The decrease in ADMA at the end of HD and HDF is comparable. Switching from HD to HDF decreases in 8 weeks the predialysis levels of homocysteine without affecting ADMA.

Soluble receptor for advanced glycation end-products independently influences individual age-dependent increase of arterial stiffness.

Circulating levels of soluble receptor for advanced glycation end-products (sRAGE) have been suggested to have a protective role in neutralizing advanced glycation end-products (AGEs) and their pathological effects on vessel walls. We aimed to investigate the association between the circulating concentration of sRAGE and the dynamics of arterial wall stiffening as a manifestation of vascular aging in the general population. In a prospective cohort study, we longitudinally followed 530 general-population-based subjects (subsample of Czech post-MONICA study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE were assessed at baseline by ELISA (R&D Systems). The average ∆PWV/year significantly decreased across the sRAGE quintiles (p = 0.048), and a drop by one sRAGE quintile was associated with an ~21% increase in the relative risk of accelerated age-dependent stiffening (∆PWV/year ≥ 0.2 m/s). Subjects in the bottom quintile of sRAGE (<889.74 pg/mL) had a fully adjusted odds ratio of accelerated stiffening of 1.72 (95% CI: 1.06-2.79), p = 0.028, while those with high sRAGE concentrations (≥1695.2 pg/mL) showed the opposite effect [odds ratio 0.55 (95% CI: 0.33-0.90), p = 0.017]. In conclusion, the circulating status of sRAGE independently influenced the individual progression of arterial stiffness over time. This finding strongly supports the hypothesis that high sRAGE has a protective role against vascular aging.

N-terminal pro B-type natriuretic peptide as prognostic marker for mortality in coronary patients without clinically manifest heart failure.

Brain natriuretic peptide (BNP) and its inactive N-terminal fragment (NT-proBNP) are strong prognostic markers in patients with manifest heart failure and acute coronary syndromes. We aimed to establish the association between NT-proBNP and all-cause mortality in patients with stable chronic coronary heart disease. Three-hundred-eighty-five patients, 6-24 months after acute coronary syndrome or coronary revascularisation, but without history or symptoms of chronic heart failure, were included into the cohort study. The NT-proBNP was measured at baseline and all-cause mortality was ascertained after more than 6 years of follow-up. Patients with NT-proBNP above 862 pmol/l (i.e. in top quintile) showed significantly higher mortality rates, than patients with lower NT-proBNP; the adjusted odds ratio (and 95% confidence intervals) for all-cause death was in patients with NT-proBNP >862 pmol/l 3.26 (1.40-7.62). In conclusion, the asymptomatic elevation of NT-proBNP provides prognostic information also in stable coronary patients not yet manifesting any symptoms of heart failure.

Assessment of biochemical markers in patients with pain of vascular origin.

The aim of this study was to analyse blood plasma biochemical parameters in patients with pain of vascular origin. Blood samples were taken from 62 patients (38-86 years of age) with critical limb ischaemia, claudication or lower limb embolism, and from a control group. The samples were taken at the time of hospital admission, 1 h after surgery, 24 h after surgery, and before discharge. Pain intensity was assessed as mild, moderate or intense. The following biochemical parameters were measured: C reactive protein, total protein, albumin, total cholesterol, HDL and LDL cholesterol, glucose, triglycerides, reduced glutathione, malondialdehyde (MDA), and total antioxidative capacity. In the control subjects, MDA increased postoperatively, whereas albumin, total protein, HDL and total cholesterol decreased. In patients with claudication triglycerides and LDL cholesterol also decreased postoperatively. In patients with critical limb ischaemia, reduced glutathione and antioxidative capacity decreased postoperatively and MDA increased. Except in patients with embolism, MDA and C reactive protein increased following surgery. Patients with critical limb ischaemia and embolism reported the worst preoperative pain. In patients with ischaemia, intense pain persisted during the whole postoperative period while in patients with embolism pain continuously decreased. At different time intervals, pain intensity was related to different biochemical markers. We suggest that the described blood plasma changes might play an important role in pain assessment and pain management.

High-sensitivity Troponins after a Standardized 2-hour Treadmill Run.

BACKGROUND: The aim of this study was to examine high-sensitivity troponin T and I (hsTnT and hsTnI) after a treadmill run under laboratory conditions and to find a possible connection with echocardiographic, laboratory and other assessed parameters. METHODS: Nineteen trained men underwent a standardized 2-hour-long treadmill run. Concentrations of hsTnT and hsTnI were assessed before the run, 60, 120 and 180 minutes after the start and 24 hours after the run. Changes in troponins were tested using non-parametric analysis of variance (ANOVA). The multiple linear regression model was used to find the explanatory variables for hsTnT and hsTnI changes. Values of troponins were evaluated using the 0h/1h algorithm. RESULTS: Changes in hsTnT and hsTnI levels were statistically significant (p<0.0001 and p<0.0001, respectively). In a multiple regression model (adjusted R2: 0.60, p=0.005 for hsTnT and adjusted R2: 0.60, p=0.005 for hsTnI), changes in both troponins can be explained by relative left wall thickness (LV), training volume, body temperature after the run and creatinine changes. According to the 0h/1h algorithm, none of the runners was evaluated as negative. CONCLUSIONS: Relative LV wall thickness, creatinine changes, training volume and body temperature after the run can predict changes in hsTnT and hsTnI levels. When medical attention is needed after physical exercise, hsTn levels should be tested only when clinical suspicion and the patient's history indicate a high probability of myocardial damage.

Brain natriuretic peptide and N-terminal proBNP in chronic haemodialysis patients.

BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are released into circulation as a result of congestive heart failure (HF). As HF and water overload are frequent complications in haemodialysis (HD) patients, we decided to study the levels of BNP and NT-proBNP and their changes during HD. METHODS: BNP and NT-proBNP levels were determined in 94 HD patients before and after a regular 4-h HD. We followed changes in these peptides during HD depending on age, sex, HF (NYHA classification and left ventricular ejection fraction [LVEF]), duration on HD, presence of hypertension, coronary artery disease, type of membrane used for HD [low-flux (LFx) or high-flux (HFx)] and body mass change during HD. Furthermore, patients basic medication and creatinine levels and presence of diabetes mellitus were monitored. RESULTS: Respectively,94% and 100% of the patients had pre-dialysis concentrations of BNP and NT-proBNP above the cut-off values for HF. The marker levels correlated significantly both before and after HD (r = 0.903 and 0.888, respectively, p < 0.001). BNP levels significantly decreased (p < 0.0001), whereas NT-proBNP significantly increased (p < 0.0001) during HD on LFx membranes. HD on HFx membranes caused greater decrease of BNP (compared to LFx membranes, p < 0.001), but also a decrease of NT-proBNP (p < 0.001).We did not find any significant differences in marker levels for HF and non-HF patients (NYHA classification). However, both peptides reached higher levels in the group with LVEF < or = 50% (p < 0.001 for both peptides). Body mass change during HD negatively correlated only with the change of NT-proBNP (r = -0.27, p < 0.05). In the multiple regression model, the change of both peptides during HD was significantly influenced by membrane type (p = 0.003 for BNP and p = 0.001 for NT-proBNP). NT-proBNP change during HD was further significantly influenced by LVEF (p = 0.012), sex (p = 0.002) and duration on HD (p = 0.006). CONCLUSIONS: Both BNP and NT-proBNP levels were significantly increased in HD patients prior to dialysis. The change in concentrations of both peptides during HD is influenced by membrane type. HD probably triggers increased production of both peptides and this increase is emphasized by impaired LVEF. This fact can be clinically observed only on NT-proBNP levels, because BNP levels are biased by significant removal of this protein during HD.

Influence of chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes mellitus.

The aim of this study was to determine the effect of chromium (Cr)- enriched yeast on blood glucose and insulin variables, blood lipids, and blood markers of oxidative stress in persons with type 2 diabetes mellitus (median duration: 3.0 yr). Thirty-six subjects (9 men, 27 women; mean age: 61.3 yr; mean body mass index: 34.33 kg/m2) were supplemented with 400 microg Cr/d as Cr-enriched yeast (n = 19) or placebo (n = 17) for 12 wk in a randomized, double-blind study. The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group. The Cr group showed a significantly greater increase in serum Cr compared to the placebo group (p < 0.05). Supplementation with Cr-enriched yeast was associated with a significant decrease in fasting serum glucose compared to placebo (p < 0.01). Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk, but decreased significantly in the placebo group (p < 0.05, p < 0.01, respectively). Serum HbA1c and glycated protein (fructosamine) were essentially unchanged in the Cr group, whereas HbA1c tended to increase in the placebo group (from 6.94% to 7.11%). Fasting serum insulin decreased in both groups, with a greater tendency in the Cr group (-16.5% vs -9.5%). These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress.

Ischemic training and immunosuppressive agents reduce the intensity of ischemic reperfusion injury after kidney transplantation.

OBJECTIVES: Ischemia-reperfusion injury affects posttransplant renal function, directly increases the probability of acute rejection, and is associated with chronic rejection and impaired long-term function. Animal studies suggest that ischemic preconditioning enhances resistance to ischemia and may be augmented by treating donors using immunosuppressant agents. This study sought to confirm the hypothesis that a combination of ischemic training and immunosuppression prior to renal harvest would maximize a transplanted kidney's resistance to ischemia-reperfusion injury. MATERIALS AND METHODS: Landrace pigs underwent either preharvest immunosuppression plus left kidney ischemic training (group 1, n=6) or ischemic training alone (group 2, n=6). Immunosuppression was composed of mycophenolate mofetil (20 mg/kg) and tacrolimus (0.1 mg/kg) administered intravenously 30 minutes before training. Training comprised 2 cycles of left renal pedicle occlusion for 5 minutes followed by release (reperfusion) for 10 minutes. Warm renal ischemia was then induced by clamping the left renal pedicle for 30 minutes, followed by heterotopic left kidney transplantation. Blood from the transplanted kidney renal vein was sampled directly at 0, 10, 20, 40, and 60 minutes posttransplantation for malondialdehyde (a reactive oxygen species marker), tumor necrosis factor-alpha (TNF-alpha), interleukins 6 and 8 (inflammatory cytokines), and erythrocyte-reduced glutathione (an antioxidant). Renal histology was graded on a 3-point scale. RESULTS: Reperfusion levels of malondialdehyde, TNF-alpha, and interleukin 6 were significantly lower in group 1 at both 40 and 60 minutes. None of the animals in group 1 (0/6) that received preharvest immunosuppression showed severe interstitial inflammation, compared with 4 of 6 animals in group 2 that did (P<.03). CONCLUSIONS: Preharvest immunosuppression with mycophenolate mofetil and tacrolimus significantly decreases immediate posttransplant reactive oxygen species and inflammatory cytokine production, enhances the protective effect of ischemic training, and should not only reduce ischemiareperfusion injury in transplanted kidneys but also should enhance immediate and long-term graft function while preventing acute rejection.

Effect of Folic Acid, Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine.

UNLABELLED: Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. METHODS: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration.