Daniel Rajdl

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 μg 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.

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 ≤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.

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.

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

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.

Asymmetric dimethylarginine and progression of chronic kidney disease: a one-year follow-up study.

Background/Aims: Asymmetric dimethylarginine (ADMA) is a prognostic factor in patients with chronic kidney disease (CKD). However, the relationships among factors influencing the metabolism of ADMA and the CKD progression are not fully understood. Methods: Serum ADMA, and variables related to the metabolism of ADMA were measured in 181 non-dialysis patients (CKD stages 3-5) and in 46 controls. Patients were assessed at baseline, and 6 and 12 months after the initiation of the study. Results: Patients had increased baseline ADMA, advanced glycation end products (AGE), and advanced oxidation protein products (AOPP) compared with controls (P<0.001). In a total of 164 patients who completed a one-year study, the estimated GFR (eGFR) declined from 23.5 (17.7-36) mL/min/1.73m2 to 21 (14.7-31.5) (P=0.018), AGE rose from 1.58 (1.38-1.90) μmol/L to 1.76 (1.52-2.21) (P<0.001), while ADMA, AOPP, tubular function, and proteinuria remained stable. In a multiple regression model (adjusted R2 = 0.49, P<0.0001), the interaction of relatively higher baseline eGFR, i.e. > 25 mL/min/1.73m2, with higher ADMA (P=0.02) and higher AOPP (P=0.04) predicted the severest decrease in eGFR per year. Other predictors of progression were higher baseline AGE (P<0.001), proteinuria (P=0.003), hypertension (P=0.01), and higher baseline eGFR (P=0.03). Conclusion: Elevated ADMA and markers of oxidative stress were strong predictors of progression in patients with eGFR between 25-40 mL/min/1.73m2 , i.e. at the borderline of CKD stages 3-4.

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/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) μmol/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.

Parasympathetic regulation of heart rate in rats after 5/6 nephrectomy is impaired despite functionally intact cardiac vagal innervation

BACKGROUND Chronic renal failure is frequently associated with a high risk of sudden cardiac death due to dysfunction of the autonomic nervous system. The pathogenic mechanisms underlying the parasympathetic cardiac dysautonomia are not fully elucidated yet. METHODS Chronic renal failure was induced in rats by 5/6 nephrectomy. Blood pressure, resting heart rate and plasma levels of creatinine, urea and asymmetric dimethylarginine (ADMA) were measured. To characterize the parasympathetic innervation of the heart, chronotropic responses to atropine, metipranolol and to vagal stimulation in the absence or presence of ADMA were investigated in vivo. In vitro, chronotropic and inotropic effects of carbachol and ADMA and mRNA expression of muscarinic M2 receptors, high affinity choline transporter (CHT1), vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) were assessed in the isolated cardiac tissues. RESULTS In 5/6 nephrectomy rats, the resting heart rate was significantly higher and the parasympathetic tone, measured as the effect of atropine after administration of metipranolol was significantly lower than in control animals. Plasma ADMA levels were significantly elevated in the uraemic rats and significantly inversely correlated with the effect of atropine on the heart rate. No differences were revealed in the plasma norepinephrine concentrations, negative chronotropic responses to stimulation of the vagus nerves, chronotropic and inotropic responses to carbachol and the relative expression of M2 receptors, CHT1, VAChT and ChAT. CONCLUSION The data suggest that cardioacceleration in chronic renal failure is caused by a diminished cardiac parasympathetic tone in the presence of a functionally intact intrinsic cardiac cholinergic signalling system.

Cardiac remodeling in rats with renal failure shows interventricular differences

Chronic renal failure (CRF) is associated with an increased incidence of cardiovascular diseases. Intensive research revealed a number of alterations in the heart during CRF; however, possible interventricular differences in CRF-induced cardiac remodeling have so far not been addressed. CRF was induced by two-stage surgical 5/6 nephrectomy (NX) in male Wistar rats. Cellular hypertrophy was quantified using immunohistological morphometric analysis. Contraction force and membrane potential were recorded in left and right ventricle papillary muscles with an isometric force transducer and high-resistance glass microelectrodes. Hypertrophy was present in the left ventricle (LV) of NX animals, but not in the right ventricle (RV) of NX animals, as documented by both ventricle/body weight ratios and cellular morphometric analysis of the cross-sectional area of myocytes. The contraction force was reduced in the LV of NX animals but increased in the RV of NX animals compared with sham-operated rats. Rest potentiation of contraction force was relatively more pronounced in the LV of NX rats. Fifty percent substitution of extracellular sodium with lithium significantly increased the contraction force only in the LV of NX animals. Action potential durations were shortened in both ventricles of CRF animals. Cardiac structural and contractile remodeling in CRF shows significant interventricular differences. CRF induces hypertrophy of the LV but not of the RV. LV hypertrophy was associated with a reduction of contraction force, whereas in the RV, the contraction force was enhanced. Partial recovery of contractile function of the LV by rest potentiation or lithium substitution indicates a role of the Na+/Ca2+ exchanger in this phenomenon.

Prolonged Corrected QT Interval as a Predictor of Clinical Outcome in Acute Ischemic Stroke

BACKGROUND This study aimed to investigate changes of corrected QT (QTc) interval during acute ischemic stroke and its correlation with high-sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP), neurological outcome, and 1-year mortality. METHODS We registered electrocardiogram in 69 patients immediately after admission to the intensive care unit and then after 24 and 48 hours. Computed tomography was performed on admission to determine brain infarct size and localization. Neurological outcome was assessed by modified Rankin scale (mRS) at discharge. RESULTS Forty-five (65.2%) patients had prolonged QTc at baseline; only 18 (26.1%) patients had prolonged QTc after 48 hours. Baseline QTc was not associated with neurological outcome (P = .27). However, prolonged QTc after 48 hours was associated with worse mRS at discharge (4.5 [4.0-6.0] versus 2.0 [1.0-3.0]; P < .0001). Patients who deceased during hospitalization (n = 7 [10.1%]) as compared with survivors had more frequently prolonged QTc after 48 hours (38.9 versus 0%; P < .0001), higher level of hsTnI (48.4 [36.1-75.0] versus 8.6 [3.4-26.5]; P = .003), and BNP (334 [224-866] versus 109 [30-190]; P = .014). In univariate analysis, 1-year mortality was associated with prolonged QTc after 48 hours, hsTnI, and BNP. In multivariate analysis, only BNP remained to be associated with 1-year mortality (odds ratio 3.41, 95% confidence interval 1.06-11.03). CONCLUSIONS QTc interval in patients with acute ischemic stroke is a dynamic parameter. Prolonged QTc after 48 hours, but not baseline QTc, correlated with neurological outcome and 1-year mortality. Patients with prolonged QTc had higher level of hsTnI.

High-Sensitivity Troponins after a Standardized 2-Hour Treadmill Run

Summary 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. 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. 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. 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.