Effect of Beer Consumption on Methylation and Redox Metabolism.

To investigate the influence of beer consumption on levels of homocysteine (HCY), vitamin B6, B12, folic acid (FA), dimethylglycine (DMG), betaine (BET) and other selected markers. One hundred and sixteen male volunteers were enrolled in the study. A one-month period of alcohol abstinence was followed by a one month when participants drank 830 mL of alcoholic beer every day. After that phase, one month of alcohol abstinence followed. At the beginning and after every phase blood samples were taken and analysed. Ninety-three participants completed the study. After the phase of alcohol consumption, uric acid (UA) (p<0.0001), antioxidative capacity (AOC) (p=0.02), superoxide dismutase (SOD) (0.025), glutathione reductase (GRH) (0.0001), total cholesterol (p<0.0001), HDL-cholesterol (p<0.0001), Apolipoprotein-AI (ApoAI) (p<0.0001), LDL-cholesterol (p<0.039) and Apolipoprotein B (ApoB) (p<0.009) increased, while vitamin B12 (p=0.0001) and fibrinogen (p<0.0001) decreased. Other tested parameters (DMG, BET, vitamin B6 and FA) did not show any significant changes. UA changes and changes in AOC were statistically significantly correlated (r=0.52, p<0.0001). HCY, DMG and BET levels did not show any statistically significant changes after beer consumption, whereas some markers of redox metabolism increased (UA, AOC, SOD and GRH). A statistically significant correlation denotes the dependence of UA and AOC changes in connection with beer consumption.

Age-Related Progression of Microvascular Dysfunction in Cystic Fibrosis: New Detection Ways and Clinical Outcomes.

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

NGAL, albumin and cystatin C during cisplatin therapy.

Cisplatin is a commonly used chemotherapeutic drugs. It is known for its nephrotoxic side effects with an increased risk of acute kidney injury. Finding of clinically feasible cisplatin nephrotoxicity markers is of importance. In our study, we compared neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine, the estimated glomerular filtration rate (based on serum cystatin C) and urine albumin as markers of nephrotoxicity. The study involved 11 men and 9 women (mean ± SD age 58.2±9.5 years) with different malignancies treated with cisplatin in four cycles of chemotherapy (I - IV). Samples 0-4 were taken before, immediately after, in 3, 6 and 24 hours after administering chemotherapy. We detected significant increase of ACR in Sample 2 (p=0.03) and decrease of eGFR in Sample 4 (p=0.03) up to 24 hours after cisplatin administration in the first chemotherapy cycle only. When cumulative effect of cisplatin was assessed, significantly increased values of urine albumin (vs cycle I) were found in Sample 0 (p=0.00058), 1 (p=0.00256), 2 (p=0.00456), 3 (p=0.00006) and 4 (p=0.00319) in cycles II to IV. We found a correlation between values of urine NGAL and urine albumin (r=0.68, p<0.0001). In conclusion, urine albumin was the only measured marker that consistently and statistically significantly increased after cisplatin containing chemotherapy cycles.

Plethysmographic and biochemical markers in the diagnosis of endothelial dysfunction in pediatric acute lymphoblastic leukemia survivors - new applications.

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.

The glycation products before and after therapy for acute and chronic pain.

Pain increased the number of free radicals in the body. Previously, we studied changes mainly in oxygen and nitroxide free radicals and described these changes relative to the lipids and saccharides. In this article we focus on changes relative to proteins. Assessment of AGE products (advanced glycation end-products) was carried out by measuring fluorescence. Patients were divided into two groups: 15 patients with acute pain and 17 patients with chronic pain. Acute pain was associated with a variety of surgical procedures and patients were examined before and after surgical procedures. The group of patients with chronic pain suffered from various types of chronic pain, but mainly back pain. In patients with acute pain, total protein (TP) decreased after surgery, as did the level of AGE and the AGE/TP ratio. Nonetheless, post-operative pain increased. In patients with chronic pain, neither total protein, AGE, or AGE/TP changed, despite significant pain relief being reported after treatment. Changes in proteins, as biochemical markers, before and after pain treatment did not show any significant changes. In patients with acute pain, the recorded changes only lasted for 3-5 days after the operation. While in chronic pain, there were no significant changes at all. The assumption that changes in proteins, as biomarkers, would have the same importance as changes in lipids and saccharides was not proven.

[Distribution of lipoprotein associated phospholipase A2 in Czech population and its interaction with conventional cardiovascular risk]. / Distribuce s lipoproteiny asociované fosfolipázy A2 v ceské populaci a její interakce s konvencním kardiovaskulárním rizikem.

INTRODUCTION: Lipoprotein associated phospholipase A2 (Lp PLA2) represent new cardiovascular risk factor and potential treatment target. We aimed to analyze the epidemiological situation of this factor in Czech population. METHODS AND RESULTS: The study population consisted from 1 962 subjects, a random samples of general population (postMONICA study), and from patients with manifest coronary or cerebrovascular disease (Czech samples of EUROASPIRE III survey). Lp PLA2 activity was estimated using commercial kits by diaDexus Inc. in frozen samples. Increased activity (by definition, i.e. > 195 nmol/ min/ ml) was observed in 21.1 % of sample, no apparent difference between subject with and without manifest vascular disease was found. Males showed higher Lp PLA2 activity, than females (179.6 vs 146, resp., p < 0.0001), while no substantial increase with age was observed. Taking Lp PLA2 activity > 195 as dependent variable, following independent variables entered the multiple logistic regression: male gender [with odds ratio 4.26 (3.26- 5.58)], low HDL cholesterol (i.e. < 1.0 mmol/ l in males or < 1.2 mmol/ l in females) [3.49 (2.62- 4.64)], LDLcholesterol > 2.5 mmol/ l [6.95 (4.79- 10.07)] and lipid  lowering treatment [0.59 (0.44- 0.79)]. In subject without manifest vascular disease, 6.3 % of them showed co incidence of markedly increased Lp PLA2 activity with high conventional risk (SCORE > 10 %). Expanding this group by intermediate risk subjects (ie. with Lp PLA2 activity 152- 194 and/ or SCORE 5- 9.9 %) leads to increase of this prevalence to 28.9 % of primary prevention subjects. CONCLUSION: Increased Lp PLA2 activity is in Czech population highly prevalent and with exception of lipid parameters, generally independent from conventional cardiovascular risk. However, up to 29 % of subject in primary prevention amalgamate increased Lp PLA2 activity with high conventional cardiovascular risk.

Immediately preoperative use of biological therapy does not influence liver regeneration after large resection--porcine experimental model with monoclonal antibody against epidermal growth factor.

BACKGROUND: The aim of this work was to study the influence of isolated biological therapy administered immediately before extended liver resection on liver function and regenerative capacity of future liver remnant (FLR) in a large-animal experiment. MATERIALS AND METHODS: Nineteen piglets were included in this study (10 in the control group and 9 in the experimental group). A port-a-cath was introduced into the superior caval vein. On days 11 and 4 before liver resection, cetuximab was administered via this port at 400 mg/m2 of piglet body surface. Physiological solution was applied to the control group. Resection of the left lateral, left medial and right medial hepatic lobes was followingly performed (reduction of 50-60% of liver parenchyma). Blood samples were collected at different times before the operation and after liver resection. Serum levels of bilirubin, urea, creatinine, alkaline phosphatase, gamma glutamyltransferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase, albumin, C-reactive protein and transforming growth factor-ß1 were assessed. The ultrasonographic examinations at different time points were performed pre-operatively and after liver resection in order to assess the liver volume. The biopsies from the liver parenchyma were examined for proliferative activity, binocluated hepatocytes, size of hepatocytes, and the length of the lobuli. The comparison of distribution of the studied parameters between the groups was carried out using the Wilcoxon test. The Spearman rank correlation co-efficient was used because of the non-Gaussian distribution of the parameter values. The whole development of the studied parameters over time was compared between the groups using ANOVA. RESULTS: There were no important complications of administration of biologic therapy during the operation or throughout the peri-operative period. There was no statistically significant difference in the regeneration of FLR nor were any differences in biochemical, immunoanalytical and histological parameters detected. CONCLUSION: The achieved results of comparable liver regeneration in both the experimental and control groups confirms the use of biological treatment with cetuximab in the pre-operative period for minimizing the recovery period.

[Comparison of selective oxidative stress parameters in the follicular fluid of infertile women and healthy fertile oocyte donors]. / Srovnání vybraných parametru oxidacního stresu ve folikulární tekutine u zen s poruchou plodnosti a u zdravých fertilních dárkyn oocytu

OBJECTIVE: Follicular fluid (FF) affects oocyte development and disruption of its homeostasis has a crucial effect on egg developmental potential. The aim of this study was to compare the levels of selected oxidative stress markers in the FF of women with impaired fertility and healthy fertile oocytes donors. DESIGN: A retrospective comparative study. SETTING: Faculty of Medicine in Pilsen, Charles University in Prague; Institute of Reproductive Medicine and Endocrinology, IVF Center Prof. Zech, Pilsen. METHODS: Levels of homocysteine (Hcy), malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant capacity (AOK) and total protein (CB) were analyzed in the FF. We have analysed FF of 146 women - 74 infertile patients (mean age 31 years, SD = 4.65) and 72 healthy fertile oocyte donors (mean age 26 years, SD = 4.44). Only blood free samples were studied after pooling of all FF samples each patient. RESULTS: The study showed a statistically significantly higher Hcy levels (p < 0.0001) in the FF of healthy fertile women compared with impaired fertility group both - comparing the two groups regardless the age and in groups of the same age range (for the age group between 20 to 29 years isp = 0.0002, for the age group between 30 to 39 years is p < 0.0001). When divided into above age ranges we found statistically significantly higher levels of MDA in the control group aged 20 to 29 years compared to same age infertile patients (p = 0.0374) and statistically significantly higher AOK in infertile women between 30 to 39 years of age compared to same age control group (p = 0.0458). CONCLUSION: The presence or on the contrary the absence of prooxidant parameters in the FF has an important role in the ability of conception and subsequent embryo development.

Ischemia-reperfusion injury in kidney transplantation from non-heart-beating donor--do antioxidants or antiinflammatory drugs play any role?

BACKGROUND: Ischemia reperfusion injury (IRI) is a serious problem of transplanted kidneys from a non-heart-beating donor (NHBD). IRI is probably the main cause of primary disfunction or delayed graft function. The aim of this study was to demonstrate the reduction of IRI by intravenous application of antioxidants or immunosuppressives to the recipient before the kidney transplantation in an experimental model. METHOD: Piglets weighing between 20-25 kg were used (n=45) for the experiment. Intravenous application of multivitamins (GI) and a combination of immunosuppressives (GII) was tested one hour before the kidney transplantation from the NHBD. In control group (GIII) simple NHBD modelling was used. Plasma levels of malondiadehyde (MDA) and reduced glutathione (GSH) were assessed at intervals of 0, 20, 60 and 120 minutes after the kidney transplantation. Concentrations of both MDA and GSH were also assessed in the transplanted kidney before and 120 minutes after transplantation. RESULTS: A permanent increase in MDA plasma concentrations occurred in GIII. In GI and GII, after a transient increase in MDA plasma levels within the first 20 minutes after reperfusion, it decreased permanently (p<0.05, p<0.01). MDA plasma levels were not significantly different between GI and GII groups, but both groups differed from GIII (p<0.001). GSH plasma levels and tissue concentrations of MDA and GSH were not statistically significant in any group in the course of the experiment. CONCLUSION: Intravenous application of multivitamins or immunosuppressives before kidney transplantation could have a significant influence on the immediate function of transplanted kidneys from a NHBD (Tab. 3, Fig. 1, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

[Ischemia-reperfusion injury in kidney transplantation from non-heart beating donor--do antioxidants or antiinflammatory drugs play any role?]. / Ischemicko-reperfuzní poskození ledvin transplantovaných z nebijícího dárce (NHBD)--mají antioxidanty nebo protizánetlivé léky význam v jeho prevenci?

BACKGROUND: Ischemia reperfusion injury (IRI) represents a serious problem of transplanted kidneys from a non-heart-beating donor (NHBD). It is probably the main cause of primary a function or delayed graft function. The aim of the experimental study was to demonstrate on an experimental model the possibilities of reduction of IRI by intravenous application of antioxidants or immunosuppressives to the recipient before the kidney transplantation. METHOD: Piglets weighing between 20-25 kg were used (N = 45) for the experiment. Intravenous application of multivitamins (GI) and a combination of immunosuppressives (GII) was tested one hour before the kidney transplantation from the NHBD. As a control a group (GIII) with simple NHBD modelling was used. At intervals of 0, 20, 60 and 120 minutes after the kidney transplantation, plasma levels of malondiadehyde (MDA) and reduced glutathione (GSH) were assessed. Before and 120 minutes after transplantation tissue concentrations of both factors were assessed in the transplanted kidney. RESULTS: A permanent increase in MDA plasma concentrations occurred in GIII. In GI and GII, after a temporary increase of MDA plasma levels in the first 20 minutes after reperfusion, there was their permanent decrease then. (p < 0.05, resp. p < 0.01). The differences in the MDA plasma levels of GI and GII groups did not reach statistical significance. The both groups differed from GIII (p < 0.001). GSH plasma levels and also tissue concentrations of MDA and GSH were not statistically significant in any group in the course of the experiment. CONCLUSION: Intravenous application of multivitamins or immunosuppressives before kidney transplantation could have a significant influence on the immediate function of transplanted kidneys from a NHBD.

Asymmetric dimethylarginine and the effect of folate substitution in children with familial hypercholesterolemia and diabetes mellitus type 1.

A recently discussed cardiovascular risk factor, asymmetric dimethylarginine (ADMA), is known to act as an endogenous inhibitor of endothelial nitric oxide synthase. The aim of this study was to establish 1) the relationship between ADMA and ultrasonographically or biochemically determined endothelial dysfunction in children, and 2) the effect of folate supplementation on these parameters. The study cohort included 32 children with familial hypercholesterolemia (FH), 30 with diabetes mellitus type 1 (DM1) and 30 age-matched healthy children as the control group. Furthermore, twenty-eight randomly selected FH and DM1 children were re-examined after 3-months supplementation with folic acid. Baseline levels of ADMA and oxidized low density lipoproteins (oxLDL) were significantly higher in FH group than in DM1 and healthy children. Children in DM1 group had significantly lower concentration of homocysteine, but ADMA levels were normal. Folic acid supplementation significantly lowered homocysteine and hsCRP levels in both FH and DM1 group; however, ADMA and oxLDL concentrations remained unaltered. In conclusion, ADMA and oxLDL appear to be associated with endothelial dysfunction in children with FH. Administration of folic acid did not influence these markers in both FH and DM1 children.

Adverse effects of the high tidal volume during mechanical ventilation of normal lung in pigs.

INTRODUCTION: The "open lung concept" theory of mechanical ventilation is correct, but an unsuitable setting of the machine is not appropriate in children. TYPE OF STUDY: This experimental study is a comparative, closed, randomized, double-blind study. The aim of the study was to verify the hypothesis that even a short-term high tidal volume during the course of mechanical ventilation damages the lung parenchyma as well as extra-pulmonary organs. MATERIAL AND METHODS: The inappropriate strategy of mechanical lung ventilation was simulated on an animal model. The study was performed on 30 healthy white domestic piglets (25 kg). Using a random selection, the piglets with healthy lungs were ventilated for 120 minutes under general anaesthesia with two different strategies of mechanical ventilation, i.e. 15 animals achieving alveolar hyperinflation with a high tidal volume (14 ml.kg(-1)), and 15 animals according to the "lung protective strategy" principle. Lung tissue samples were examined morphologically using the blind test method, and the proinflammatory cytokines levels were assessed in the piglets' serum. RESULTS: The study demonstrated that a high tidal volume during mechanical lung ventilation with permanent positive pressure after 120 minutes induced very important morphological and functional lung changes that unfavourably influenced blood circulation, reduced cardiac output and induced a systemic inflammatory reaction (Fig. 9, Ref. 11).

Even mild changes in free thyroxine could influence the degree of heart failure measured by its biological surrogates.

Both, severe hypo- or hyperthyroidism may alter hemodynamic parameters. The aim of our study was to ascertain, whether also distinct changes within normal range of free thyroxine (fT4) would be associated with an impairment of left ventricle function in patients with chronic heart failure. Hundred-forty-eight patients (m121, f27, mean age 63.8 +/- 1.14 years) with chronic heart failure, fT4 levels within the normal range (9-22 pmol/l) and without thyrostatics or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP). Patients with fT4 in the range 11.9-14.6 pmol/l [optimal, second-third quintile] had significantly lower NT-proBNP (718 +/- 70.4 pg/ml), than those with fT4 < or = 11.8 [low-normal, bottom quintile](1236 +/- 223.6 pg/ml; p<0.03) and those with fT4 over 14.6 pmol/l [high-normal, top two quintiles] (1192 +/- 114.9 pg/ml; p<0.0002). These differences remain significant, also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were also found in BNP, but only when optimal and high-normal fT4 ranges were compared. In conclusion, the severity of heart failure seems to be also influenced by only mild deviations of fT4 concentrations from optimal levels.

Does the administration of antioxidants as scavengers of reactive oxygen species in kidney transplantation really have sense?

BACKGROUND: The aim of the study was to evaluate the degree of ischemia reperfusion syndrome (IRS) in serious ischemic insult of a kidney transplant and to try to mitigate the production of reactive oxygen substances (ROS) and inflammatory response. METHODS: The study was performed on 14 white pigs (20 kg). The pigs were divided in couples using a negative cross-matching and the couples were divided into the two groups. Each animal from the compatible couple was a donor/recipient of a kidney to/from the counterpart. Group II (TxII) received the intravenous antioxidants. Group I (TxI) was a control group. L-ascorbic acid 125 mg, selenium 4.4 mg, tocoferol 50 mg and N-acetyl-cysteine 200 mg were used as the antioxidants. They were applied intravenously to the TxII animals for 20 minutes before reperfusion of a kidney transplant. A serious ischemic insult was created by the left kidney hilum's cross-clamping for 30 min before donation. After the kidneys' removal, the left ones were flushed with Histidine Tryptophan Ketoglutarate (HTK) preservation solution and transplanted after the 1.5 hour (in the meantime stored in melted ice). Venous blood samples were taken for the assessment of malondialdehyde (MDA), reduced glutathione (GSH), glutathioneperoxidase (GSHPx), antioxidative capacity of plasma (AOC), interleukin 6 (IL-6), and tumor-necrosis factor alfa (TNFalfa) prior to the nefrectomy, before application of ROS scavengers (TxII), and during the 120-minute period after the transplantation (TxL+TxII). RESULTS: There wasn't a significant difference neither in production of MDA, nor in the levels of GSH, GSHPx, AOC, IL6 and TNFalfa between the TxI and TxII groups. CONCLUSIONS: Based on our results, we cannot conclude that the intravenous application of ROS scavengers in given combination and amount, administered to the recipient in the period just before transplantation, is a useful protective mechanism against kidney damage during IRS (Fig. 3, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

Effect of white wine consumption on oxidative stress markers and homocysteine levels.

The aim of this study was to assess the influence of regular daily consumption of white wine on oxidative stress and cardiovascular risk markers. Forty-two healthy male volunteers consumed 375 ml of white wine daily. Each participant provided three venous blood samples (before wine consumption, following the wine consumption period and again a month later). Levels of superoxide dismutase, glutathione peroxidase, reduced glutathione, total antioxidant capacity, total cholesterol, HDL-cholesterol, apolipoprotein A I, apolipoprotein B, triglycerides, paraoxonase 1, C-reactive protein, homocysteine, thiobarbituric acid reactive substances (TBARS) and advanced oxidation protein products (AOPP) were measured. Immediately following the month of white wine consumption there was a significant increase in HDL-cholesterol (p<0.0001), paraoxonase 1 (p<0.001), glutathione peroxidase (p<0.001) and reduced glutathione (p<0.01) levels, a decrease in superoxide dismutase activities (p<0.0001), and a decrease in oxidation protein products (p<0.001) and TBARS (p<0.05) concentrations. However, there was also a clear increase in homocysteine (p<0.0001) after a month of white wine consumption. The results of our non-placebo controlled trial suggest that regular daily white wine consumption is associated not only with both antioxidative and antiatherogenic effects but also with a potentially proatherogenic increase of homocysteine concentrations.

Folate co-administration improves the effectiveness of fenofibrate to decrease the lipoprotein oxidation and endothelial dysfunction surrogates.

Fibrate therapy results in elevation of plasma total homocysteine (tHcy), which is known to induce oxidative stress and endothelial dysfunction. We aimed to establish whether fibrate-induced elevation of tHcy has also similar consequences and whether they may be prevented by folate co-administration. Eighteen subjects with hypercholesterolemia were included in an open, prospective, cross-over study. We compared intra-individually the effect of fenofibrate on tHcy, oxidative stress and endothelial dysfunction surrogates, in monotherapy and when combined with 10 mg of folate. These effects were also compared with fluvastatin monotherapy. Fenofibrate in monotherapy significantly decreased LDL cholesterol, increased the tHcy by 39.5 %, while oxidized LDL (oxLDL), malondialdehyde (MDA), von Willebrand factors (vWf) and thrombomodulin (TMD) remained unchanged. When fibrate was co-administered with folate, the tHcy remained on the initial post-diet level, while both the total and oxLDL as well as MDA, vWf and TMD decreased. In contrast to fenofibrate monotherapy, fluvastatin (80 mg) had a similar effect as combined therapy with fenofibrate and folate, while tHcy remained uninfluenced. In conclusion, fenofibrate decreases the LDL cholesterol, but in contrast to fluvastatin, has no significant antioxidative and endothelium-protective potential, probably due to a concomitant increase of tHcy. These effects may be improved by co-administration of folate.

The influence of folate and antioxidants on homocysteine levels and oxidative stress in patients with hyperlipidemia and hyperhomocysteinemia.

The aim of this study was to observe the effect of folate and antioxidants alone on homocysteine levels and oxidative stress markers, and to evaluate whether their co-administration promotes their effects. One hundred patients with hyperhomocysteinemia were randomized into four equal groups, which were then treated with folate, antioxidants or folate plus antioxidants for 2 months; group IV was a control group. Serum homocysteine, folate and oxidative stress markers were measured before the study, at the end of folate and/or antioxidants administration and 3 months later. Folate caused a significant decrease in homocysteine concentration. Antioxidants did not influence homocysteine concentration, but they improved the antioxidative defense (plasma antioxidant capacity and intraerythrocyte glutathione were increased) and partially prevented lipid peroxidation (malondialdehyde level was slightly decreased). Supplementation with folate had a similar effect on intracellular glutathione and plasma malondialdehyde. Simultaneous administration of folate and antioxidants did not show any additive effect with the exception of a slower decrease of folate concentration after its supplementation had been discontinued. Folate may be considered as an effective antioxidant in patients with hyperhomocysteinemia; this can be a result of decreased production of free radicals due to a reduced level of homocysteine. Its antioxidative effect cannot be promoted by co-administration of antioxidants.

Markers of oxidative stress in diabetic mothers and their infants during delivery.

Oxidative stress is probably a pathophysiological process leading to disadvantageous outcomes in diabetic pregnancies. We aimed to map a complex of potential markers of oxidative stress in this condition. Diabetic mothers had significantly higher concentrations of thiobarbituric acid reactive substances in the plasma [TBARS] both before (p<0.0001) and after (p<0.001) delivery and also their newborns showed higher values of TBARS (p<0.0001) in comparison with the control group. Diabetic mothers also showed lower concentrations of reduced glutathione in erythrocytes [GSH] both before (p<0.05) and after (p<0.01) delivery and their infants also had lower levels of GSH (p<0.0001). We found a lower total antioxidative capacity of plasma [AOC] before delivery (p<0.05) in the diabetic group in comparison with the control group. Newborns of diabetic mothers had higher plasmatic concentrations of apolipoproteine B [apo B] (p<0.05), higher erythrocyte glutathione peroxidase [GPx] activity (p<0.05) and lower pH (p<0.001) in the umbilical cord blood, when compared with infants of control non-diabetic mothers. We conclude that pregestational and gestational diabetes mellitus represent increased oxidative stress for both mother and her infant. TBARS in plasma are a valuable marker of oxidative stress in this condition. Disruption of glutathione peroxidase/glutathione pattern can be involved in pathophysiology of enhanced oxidative stress in diabetic pregnancies.