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.

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.

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.

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.

Can ischemia-reperfusion syndrome in transplanted kidneys procured from non-heart-beating donors be influenced by adding selenium into the reperfusion solution? An experimental study.

Ischemia-reperfusion syndrome significantly influences the function of a kidney transplanted from a non-heart-beating donor (NHBD). An animal model of NHBD was used to monitor the influence of the exogenous addition of selenium in the perfusion solution (HTK, Custodiol) on the generation of free oxygen radicals between 0 and 120 minutes after transplantation of the NHBD organ. During this interval, the malondialdehyde concentration, an indicator of free oxygen radicals in the venous blood of the transplanted kidney, significantly decreased. The augmentation of the anti-oxidant capacity of the preservation solution might represent a possible improvement in the function of kidneys transplanted from NHBDs.

Can the ischemia-reperfusion syndrome in transplanted kidneys procured from non-heart-beating donors be influenced by adding selenium into the reperfusion solution? An experimental study.

The ischemic-reperfusion syndrome significantly influences the function of a kidney transplanted from a non-heart-beating donor (NHBD). The animal model of a NHBD was used to monitor the influence of exogenous addition of selenium into the reperfusion solution (HTK, Custodiol) with respect to the formation of free oxygen radicals at 0 to 120 minutes after the NHBD transplantation. This maneuvers produced a statistically significant decrease in malondialdehyde concentration, an indicator of free oxygen radicals in the venous blood of the transplanted kidney. The augmentation of the antioxidative capacity of the preservation solution might be a possible route to improve the function of kidneys transplanted from NHBDs.

Hyperinsulinemia and oxidative stress.

The aim of the study was to compare the effect of short-term hyperglycemia and short-term hyperinsulinemia on parameters of oxidative stress in Wistar rats. Twenty male rats (aged 3 months, average weight 325 g) were tested by hyperinsulinemic clamp (100 IU/l) at two different glycemia levels (6 and 12 mmol/l). Further 20 rats were used as a control group infused with normal saline (instead of insulin) and 30 % glucose simultaneously. Measured parameters of oxidative stress were malondialdehyd (MDA), reduced glutathion (GSH) and total antioxidant capacity (AOC). AOC remained unchanged during hyperglycemia and hyperinsulinemia. Malondialdehyde (as a marker of lipid peroxidation) decreased significantly (p<0.05) during the euglycemic hyperinsulinemic clamp, and increased significantly during isolated hyperglycemia without hyperinsulinemia. Reduced glutathion decreased significantly (p<0.05) during hyperglycemia without hyperinsulinemia. These results suggest that the short-term exogenous hyperinsulinemia reduced the production of reactive oxygen species (ROS) during hyperglycemia in an animal model compared with the control group.

[Antioxidant effects of melatonin]. / Antioxidacní úcinek melatoninu.

Increase in knowledge about reactive oxygen species action mechanisms and oxidative stress effects in living organisms led to intensive seeking for new, more effective substances, which prevent extreme development of oxidative stress or are able to decrease its negative influence, damaging cell structures and many cell functions. These substances are called antioxidants, scavengers, trappers or quenchers. In nineties, melatonin became the centre of the interest in the filed of investigation of antioxidative properties of different chemical substances. This is in living organisms ubiquitous substance with relatively simple chemical structure, good physical properties and wide physiological effects. The main role of endogenous melatonin comprises receptor-mediated biological rhythms synchronisation. Among other functions mentioned later belong anti-gonadotropic, immunotropic and non-receptor-mediated antioxidative effects. Melatonin is said to have also antineoplastic properties. Its anti-aging effect is discutable.

[Antioxidative properties of ascorbic acid]. / Antioxidacní vlastnosti kyseliny askorbové.

Vitamin C (ascorbic acid) is an important hydrophilic compound with antioxidative effect. In the introduction the authors describe possible consequences of loss of vitamin C synthetic ability in an evolutionary ancestor of Anthropoidea. Metabolism of this vitamin is described briefly along with possibilities of its supplementation and determination in biological fluids. Highest attention is paid to metabolic effects of vitamin C, respectively to changes which can be observed after its deprivation, or after the supplementation with this vitamin. Protective effect of vitamin C against lipoperoxidation, its role in modulation of immunity and tumorigenesis are described. Many effects of vitamin C can be explained by its antioxidative activity. The authors show that under concrete conditions, administration of vitamin C can be accompanied by a prooxidative effect. Since vitamin C works in cooperation with other antioxidants, its administration in diseases which are followed by oxidative stress is move effective when used in combined preparations.

Suppression of adjuvant arthritis in rats with chronic bromocriptine treatment does not prevent associated oxidative stress.

We studied the effect of prolactin (PRL) inhibition by bromocriptine (BRC) in the first phase of adjuvant induced arthritis (AA), up to day 11(BRCl-AA), and in the whole time course of AA, up to day 23 (BRC-AA), on the development of the disease in male Lewis rats. On day 24, arthritic rats showed inhibition of PRL secretion, but not PRL mRNA expression in adenopituitaries. BRC treatment suppressed PRL serum levels and PRL mRNA expression in adenopituitaries. In BRC/-AA group PRL levels and PRLmRNA were at the level of rats with AA. Serum corticosterone (CORT) was stimulated by AA from 16.9+/-5.8 to 59.1+/-8.7 ngml(-1), p<0.05, to the same level in BRC-control (BRC-C) and BRC-AA group and further potentiated in BRCI-AA group (148.2+/-33.1 ngml(-1), p<0.05 vs. group with AA). Hind paw swelling was reduced but not completely inhibited in BRC1-AA group and totally prevented in BRC-AA rats as was the core temperature (36.5+/-0.1 degrees C vs. 37.4+/-.0.1 degrees C in AA rats on day 23, p<0.01). Serum concentration of NO-ZNO-3 rose in rats with AA to 28.7+/-2.5 &mgr;mo1L-1 against. 13.9+/-1.9 &mgr;molL(-1) in controls (p<0.01), remained elevated in BRC-AA group and was potentiated in BRC1-AA group (48.2+/-3.5 &mgr;mol(-1), p<0.01 vs. AA or BRC1-AA group) Thiobarbituric acid reactive substances (TBARS) and antioxidant capacity in the spleen were enhanced in rats with AA and to the same extent in BRC-AA or BRC1-AA groups. These results show a discrepancy between the suppression of clinical symptoms and persisting oxidative stress in AA rats after the BRC induced PRL inhibition. The potentiation of nintric oxide (NO-) production after the sudden cessation of PRL inhibition during the disease may promote further joint damage.