Effect of natural polyphenols on thromboxane levels in children with Crohn's disease.

OBJECTIVES: The aim of this study was to investigate the relationship between thromboxane levels and oxidative stress in children with Crohn´s disease (CD), and examine the effect of natural polyphenolic compounds on thromboxane levels. METHODS: This study involved 14 children suffering from CD and 15 healthy controls. Patients were receiving the polyphenolic extract Pycnogenol for 10 weeks. Plasma levels of the static and dynamic forms of thromboxane B2 as well as their metabolite 11-dehydro thromboxane B2 in urine were determined. RESULTS: In comparison to controls, CD patients had significantly higher levels of the static and dynamic forms of thromboxane B2. Pycnogenol decreased the level of the dynamic form of thromboxane B2 after 10 weeks of administration. CONCLUSIONS: Paediatric Crohn's disease is associated with higher thromboxane levels. Our results indicate that Pycnogenol administration reduces thromboxane levels, which may positively influence some clinical symptoms of CD such as thromboembolic episodes (Tab. 3, Ref. 49).

Natural polyphenols improve erectile function and lipid profile in patients suffering from erectile dysfunction.

OBJECTIVES: Erectile dysfunction (ED) is characterised as the inability to achieve or maintain an erection to complete sexual intercourse. ED may be considered as an early complication of diabetes mellitus (DM). The aim of this study was to assess the effect of registered food supplement, natural polyphenolic extract from the French maritime pine bark, Pycnogenol (PYC) on erectile function and lipid profile in ED patients. METHODS: 53 patients with ED were divided into two groups (32 with DM, 21 non-DM) in randomised, blinded and placebo-controlled study. During 3-month intervention with PYC or placebo and one month after the end of the intervention patients were investigated for ED with validated questionnaire International Index of Erectile Function-5 (IIEF-5); lipid profile, glycaemia was analysed in each group. RESULTS: In a randomised, blinded and placebo-controlled study, we found that natural polyphenolic extract, Pycnogenol improved erectile function in DM group by 45 % compared to the NDM group, where the improvement was also significant, but only by 22 %. Total cholesterol, LDL-cholesterol and glucose level was lowered by PYC in patients with DM. Glucose level was not affected by PYC in non-DM. Placebo showed no effect on monitored parameters in both groups. CONCLUSION: Administration of Pycnogenol leads in improvement of erectile function in patients with ED and diabetes (DM group) by 45 %, in NDM group by 22 %, in lowering of total-, LDL-cholesterol by 20 % and 21 % and glycaemia by 22 % in DM (Tab. 2, Fig. 2, Ref. 19).

Lipoprotein particle sizes in patients undergoing kidney transplantation.

Asymptomatic atherosclerotic disease is prevalent in the middle-aged group of kidney transplant recipients. In order to improve the estimation of their cardiovascular risk, dyslipidaemia pattern is very important to be evaluated. Knowledge of the lipid particle spectrum in patients undergoing kidney transplantation could help the clinicians to timely start intervention and prevention of atherosclerosis with an early hypolipidemic statin treatment (Tab. 2, Ref. 20).

Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3-10 years: randomised controlled trial.

In a double-blind, randomised, parallel-group, placebo-controlled study, healthy school children aged 3-10 years received a probiotic based supplement daily for 6 months to assess the impact on the incidence and duration of upper respiratory tract infection (URTI) symptoms. The intervention comprised Lab4 probiotic (Lactobacillus acidophilus CUL21 and CUL60, Bifidobacterium bifidum CUL20 and Bifidobacterium animalis subsp. lactis CUL34) at 12.5 billion cfu/day plus 50 mg vitamin C or a matching placebo. 171 children were included in the analysis (85 in placebo and 86 in active group). Incidence of coughing was 16% (P=0.0300) significantly lower in the children receiving the active intervention compared to the placebo. No significant differences in the incidence rate of other URTI symptoms were observed. There was significantly lower risk of experiencing five different URTI related symptoms in one day favouring the active group (Risk ratio: 0.31, 95% confidence interval: 0.12, 0.81, P=0.0163). Absenteeism from school and the use of antibiotics was also significantly reduced for those in the active group (-16%, P=0.0060 and -27%, P=0.0203, respectively). Our findings indicate that six months daily supplementation with the Lab4 probiotic and vitamin C combination reduces the incidence of coughing, absenteeism and antibiotic usage in 3 to 10 year old children.

Some current insights into oxidative stress.

Oxidative stress is a phenomenon associated with pathogenetic mechanisms of several diseases including atherosclerosis, neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, cancer, diabetes mellitus, inflammatory diseases, as well as psychological diseases or aging processes. Oxidative stress is defined as an imbalance between production of free radicals and reactive metabolites, so-called oxidants, and their elimination by protective mechanisms, referred to as antioxidative systems. This imbalance leads to damage of important biomolecules and organs with potential impact on the whole organism. Oxidative and antioxidative processes are associated with electron transfer influencing the redox state of cells and the organism. The changed redox state stimulates or inhibits activities of various signal proteins, resulting in a changed ability of signal pathways to influence the fate of cells. At present, the opinion that oxidative stress is not always harmful, has been accepted. Depending on the type of oxidants, intensity and time of redox imbalance as well as on the type of cells, oxidative stress can play a role in the regulation of other important processes through modulation of signal pathways, influencing synthesis of antioxidant enzymes, repair processes, inflammation, apoptosis and cell proliferation, and thus processes of malignity. Imprudent administration of antioxidants may therefore have a negative impact on the organism.

Hypercholesterolemia, oxidative stress and gender dependence in children.

Hypercholesterolemia (HCH) is characterized by an increase of the total- and LDL-cholesterol in serum. In hypercholesterolemia, generally recognized as a risk factor of atherogenesis, oxidative stress and oxidatively modified LDL play a crucial role. In our study, children with elevated total cholesterol (above 4.5 mmol/l) were included. Parameters of lipid profile, lipophilic vitamins and antioxidants (retinol, α-tocopherol, γ-tocopherol, xantophyll, lycophen and ß-carotene) and markers of oxidative damage to lipids (lipoperoxides and 8-isoprostanes) were evaluated. We found that children with hypercholesterolemia have significantly increased parameters of lipid profile and these are gender dependent only in HDL-cholesterol (1.27 ± 0.10 mmol/l in boys vs. 1.53 ± 0.07 mmol/l in girls; p<0.05) and TAG (1.63 ± 0.31 mmol/l in boys vs. 1.08 ± 0.09 mmol/l in girls; p<0.05). In addition, children with HCH have decreased total antioxidant capacity of serum (TEAC) (about 19.64%, p<0.05) and increased lipoperoxides (LP) (about 45.73%, p<0.001). We have revealed statistically significant correlations between parameters of lipid profile and lipophilic vitamins and antioxidants, as well as between markers of oxidative stress: positive correlation between LP and 8-iso (r=0.353, n=33, p<0.05) and negative correlations between these parameters and TEAC (r= -0.377, n=33, p<0.05 for LP and r= -0.379, n=33, p<0.05 for 8-iso). In conclusion, we confirmed relation between hypercholesterolemia and oxidative stress and effect of gender on these processes already in childhood. Since the atherosclerotic process begins in childhood before clinical symptoms, early detection of hypercholesterolemia and oxidative stress is important in later atherosclerosis prevention.

How does pycnogenol® influence oxidative damage to DNA and its repair ability in elderly people?

Our purpose in this randomized, double blind, placebo controlled study was to find out the possible effect of a polyphenolic pine bark extract, Pycnogenol® (Pyc) on the level of 8-oxo-7,8-dihydroguanine (8-oxoG) as representative of oxidative damage to DNA and on the DNA repair ability of elderly people. According to our results, three months of Pyc administration had no effect on the level of oxidative damage to DNA or on repair ability, but we found a relationship between the level of 8-oxoG and repair ability of DNA in this group. To conclude, even if the positive effect of Pyc was not confirmed in the case of elderly people it is important to highlight the necessity of further investigations about the mechanisms of Pyc acting on different age groups.

Effect of natural polyphenols, pycnogenol® on superoxide dismutase and nitric oxide synthase in diabetic rats.

The work is focused on clarifying the impact of diabetes and natural plant polyphenols contained in Pycnogenol® (PYC) on the activity and synthesis of Cu/Zn-SOD and synthesis of nNOS and eNOS in the cerebellum and cerebral cortex in rats with induced diabetes. Rats included in the study (n=38) were divided into three groups: the controls (C), (n=7), untreated diabetics (D) (n=19) and diabetic rats treated with PYC (DP) (n=12). Diabetes significantly decreased synthesis, as well as the activity of Cu/Zn-SOD in both studied parts of the brain. PYC significantly increased the synthesis of Cu/Zn-SOD but had no effect on its activity. Diabetes also reduced the synthesis of nNOS in cerebral cortex and administered PYC elevated its amount to the level of controls. In the cerebellum, diabetes does not affect the synthesis of nNOS and PYC reduces synthesis of NOS. Diabetes as well as PYC had no influence on the synthesis of eNOS in both, the cerebellum and cerebral cortex. PYC modulated level of Cu/Zn-SOD and nNOS in cerebellum and cerebral cortex of diabetic rats, but in a different way.

Fecal calprotectin as a promising marker of inflammatory diseases.

BACKGROUND: Calprotectin is a calcium binding protein present predominantly in neutrophils with antimicrobial and antiprolipherative activities. Calprotectin concentration is higher in feces than in plasma and significantly increased levels of fecal calprotectin (FC) were found in patients with bowel inflammation disease (IBD). METHODS: Nineteen out-patients with IBD, comprising 14 Crohn's disease (CD) individuals and 5 ulcerative colitis (UC) patients, and 5 healthy volunteers were investigated. Fecal calprotectin was analyzed by ELISA. RESULTS: We found that patients with IBD had significantly higher concentration of FC than in healthy children (FC median 1076.7 vs 19.5 microg/g of stool, p = 0.0053). We determined higher level of FC in patients with CD than in UC (1132.4 vs 490.98 microg/g of stool), but not statistically significant. CONCLUSION: It has been proved that FC represents a surrogate marker of neutrophils influx into the bowel lumen; hence it can be regarded as a simple and non-invasive marker of intestinal inflammation (Tab. 2, Fig. 1, Ref. 38). Full Text (Free, PDF) www.bmj.sk.

Role of oxidative stress, adiponectin and endoglin in the pathophysiology of erectile dysfunction in diabetic and non-diabetic men.

Erectile dysfunction (ED) and diabetes mellitus (DM) share common pathophysiological risk factors including endothelial dysfunction which together with hyperglycemia contribute to the increased oxidative/glycooxidative stress. A reduced NO concentration is insufficient for relaxation processes in the penis. Chronic inflammation and endoglin are involved in the regulation of endothelial function. Adiponectin from the adipose tissue has anti-inflammatory effects. Our study aimed to investigate the relation between erectile function in patients with and without DM and the oxidative stress, hormone adiponectin, and endothelial dysfunction marker endoglin. Men (n=32) with ED evaluated by the International Index of Erectile function (IIEF-5) questionnaire (17 without DM (NDM); 15 with type 2 diabetes mellitus (DM)) and 31 controls were included. Advanced glycation end products (AGEs), 8-isoprostanes (8-isoP), protein carbonyls, antioxidant capacity, adiponectin and endoglin were determined in the blood. DM patients compared to NDM patients and controls, had increased levels of glucose, C-reactive protein, triacylglycerols, 8-isoP, AGEs, endoglin and BMI. IIEF-5 score, NO and adiponectin levels were decreased. We are the first to find out that endoglin shows a negative correlation with erectile function in NDM, but not in DM patients. Endoglin can be considered as endothelial dysfunction marker in nondiabetic men suffering from ED.

Activity of paraoxonase 1 and lipid profile in healthy children.

Paraoxonase 1 (PON1) seems to have a relevant role in detoxifying processes and in atherosclerosis. The aim of this study was to determine PON1 activity, the total antioxidant capacity, as well as entire lipid profile in children for screening of possible risk of atherosclerosis development. Serum PON1 arylesterase/paraoxonase activities were determined spectrophotometrically. The total antioxidant capacity of the serum was measured by TEAC method. Parameters of lipid profile were analyzed by routine laboratory methods. It has been shown that PON1 arylesterase/ paraoxonase activities were very similar to values found in adults. In children, no significant correlation between PON1 arylesterase activity and HDL was observed. PON1 paraoxonase activity correlated only with atherogenic index. PON1 arylesterase activity was significantly higher in girls than in boys. The antioxidant capacity was inversely related to the body mass index. In this study, PON1 activity was determined in healthy children aged 11 to 12 years and we found a similarity in PON1 activities of children and adults. Moreover, the results of our study support the hypothesis that higher body weight of children may contribute to a greater risk for development of atherosclerosis in which oxidative stress plays a role.

Relationship between antioxidant potential and oxidative damage to lipids, proteins and DNA in aged rats.

Oxidative stress has been implicated to play a major role in aging and age-related diseases. In the present study, we investigated the effects of aging on the total antioxidant capacity, uric acid, lipid peroxidation, total sulfhydryl group content and damage to DNA in adult (6 months), old (15 months) and senescent (26 months) male Wistar rats. The antioxidant capacity, determined by phycoerythrin-based TRAP method (total peroxyl radical-trapping potential) was significantly decreased in the plasma and myocardium of old and senescent rats, whereas plasma level of uric acid was elevated in 26-month-old rats. Age-related decline in plasma and heart antioxidant capacity was accompanied by a significant loss in total sulfhydryl group content, increased lipid peroxidation and higher DNA damage in lymphocytes. Correlations between TRAP and oxidative damage to lipids, proteins and DNA suggest that the decline in antioxidant status may play an important role in age-related accumulation of cell damage caused by reactive oxygen species.

The redox state of glutathione in erythrocytes of individuals with Down syndrome.

BACKGROUND: The redox state of glutathione has been used as indicator for the redox environment of the cell. OBJECTIVES: To investigate relationships between the redox environments, the SOD activity, total antioxidant status and the oxidation stress markers production (MDA and lipofuscin). METHODS: Individuals with Down syndrome and age-matched healthy controls were enrolled into a study. Some parameters of oxidative stress in serum were determined: reduced glutathione, oxidized glutathione, redox potential of this couple (Eh), activity of superoxide dismutase in the red blood cells as well as malondialdehyde and lipofuscin. RESULTS: In the group of persons with DS statistically significant decrease in the GSH concentration was found, however, no differences in the GSSG concentration versus controls was observed. The redox potential values for couple GSH/GSSG are a statistically significantly increased in DS individuals compared to controls. CONCLUSION: In this study we highlighted the different ways of view at the role of GSH in metabolism of persons with DS. It is useful to look at the GSH and GSSG concentrations separately as well as at redox potential value, which influence total redox state of organism (Tab. 2, Fig. 3, Ref. 30) Full Text (Free, PDF) www.bmj.sk.

Cardiovascular diseases, depression disorders and potential effects of omega-3 fatty acids.

Cardiovascular disease (CVD) and depressive disorders (DD) are two of the most prevalent health problems in the world. Although CVD and depression have different origin, they share some common pathophysiological characteristics and risk factors, such as the increased production of proinflammatory cytokines, endothelial dysfunction, blood flow abnormalities, decreased glucose metabolism, elevated plasma homocysteine levels, oxidative stress and disorder in vitamin D metabolism. Current findings confirm the common underlying factors for both pathologies, which are related to dramatic dietary changes in the mid-19th century. By changing dietary ratio of omega-6 to omega-3 fatty acids from 1:1 to 15-20:1 some changes in metabolism were induced, such as increased pro-inflammatory mediators and modulations of different signaling pathways following pathophysiological response related to both, cardiovascular diseases and depressive disorders.

The combined effect of pycnogenol with ascorbic acid and trolox on the oxidation of lipids and proteins.

Pycnogenol (PYC), a procyanidin-rich extract of French maritime pine bark (Pinus pinaster) has strong antioxidant potential and promotes cellular health. The aim of this study was to investigate a possible cooperation of natural antioxidant PYC with synthetic antioxidants ascorbic acid and trolox in the model system of lipid peroxidation determined as conjugated dienes formation in liposomes and on the oxidation of proteins (in BSA and plasma proteins) determined as protein carbonyls. The present study shows that PYC and trolox significantly increased inhibition of lipid peroxidation initiated by copper acetate and tert-butylhydroperoxide in concentration and time dependence compared with untreated unilamellar liposomes. PYC and trolox added simultaneously to the oxidized liposomes exerted an additive preventive effect. PYC s inhibitory effect on formation of carbonyl compounds in BSA and plasma proteins, oxidized by two oxidative systems--H2O2/FeSO4 and HOCl, were studied in co-operation with other synthetic antioxidants--ascorbic acid and trolox. We found the synergistic or additive effect of PYC with mentioned antioxidants.

Betaine increases the butyrylcholinesterase activity in rat plasma.

The physiological function of butyrylcholinesterase (EC 3.1.1.8, BChE) is not clearly understood, but a role was suggested in the fat utilization process, resulting in positive correlation between plasma triglyceride (TG) levels and BChE activity. Consequently we tested the hypothesis that regular intake of betaine, a natural compound intervening in the liver TG metabolism could influence the BChE activity. The BChE activity was estimated spectrophotometrically in plasma of rats fed with betaine enriched standard (B) or high-fat diet (HFB). The results confirmed decreased TG plasma levels after betaine treatment independently on the type of diet (0.15+/-0.03 (B) vs. 0.27+/-0.08 (control) mmol/l; p=0.003 and 0.13+/-0.03 (HFB) vs. 0.27+/-0.08 (control) mmol/l; p=0.005). The BChE activity increased significantly with betaine administration, however the change was more distinct in the HFB group (0.84+/-0.34 (HFB) vs. 0.22+/-0.04 (control) O.D./min/mg; p<0.001 and 0.41+/-0.11 (B) vs. 0.22+/-0.04 (control) O.D./min/mg; p=0.001). In conclusion, betaine intake led to elevated BChE activity in plasma and this effect was potentiated by the HF diet. Since betaine is in general used as a supplement in the treatment of liver diseases accompanied by TG overload, its impact on the BChE activity in the role of the liver function marker should be taken into account.

Probiotics and vitamin C for the prevention of respiratory tract infections in children attending preschool: a randomised controlled pilot study.

BACKGROUND: This pilot study investigates the efficacy of a probiotic consortium (Lab4) in combination with vitamin C on the prevention of respiratory tract infections in children attending preschool facilities. SUBJECTS/METHODS: In a double-blind, randomised, placebo-controlled pilot study with children aged 3-6 years, 57 received 1.25 × 10(10) colony-forming units of Lactobacillus acidophilus CUL21 (NCIMB 30156), Lactobacillus acidophilus CUL60 (NCIMB 30157), Bifidobacterium bifidum CUL20 (NCIMB 30153) and Bifidobacterium animalis subsp. lactis CUL34 (NCIMB 30172) plus 50 mg vitamin C or a placebo daily for 6 months. RESULTS: Significant reductions in the incidence rate of upper respiratory tract infection (URTI; 33%, P=0.002), the number of days with URTI symptoms (mean difference: -21.0, 95% confidence interval (CI):-35.9, -6.0, P=0.006) and the incidence rate of absence from preschool (30%, P=0.007) were observed in the active group compared with the placebo. The number of days of use of antibiotics, painkillers, cough medicine or nasal sprays was lower in the active group and reached significance for use of cough medicine (mean difference: -6.6, 95% CI: -12.9, -0.3, P=0.040). No significant differences were observed in the incidence rate ratio or duration of lower respiratory tract infection or in the levels of plasma cytokines, salivary immunoglobulin A or urinary metabolites. CONCLUSIONS: Supplementation with a probiotic/vitamin C combination may be beneficial in the prevention and management of URTIs.

Influence of age on activities of antioxidant enzymes and lipid peroxidation products in erythrocytes and neutrophils of Down syndrome patients.

Thirty-seven individuals with Down syndrome (DS) were divided into four age categories: (i) 1 to < 6 years, (ii) 6 to < 13 years, (iii) 13 to < 20 years, and (iv) over 20 years. Activities of antioxidant enzymes found in individual age categories were different, but the differences between age groups were not statistically significant. We confirmed significantly higher activities of Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GPx) in blood cells of people with DS as compared to 35 controls, which consisted, for the first time, of siblings of children with DS. No significant differences were found in activities of catalase and glutathione reductase in DS vs. controls. A significant difference was observed in serum concentration of malondialdehyde (MDA) in DS vs. controls (8.39 +/- 0.34 micromol/l vs. 7.34 +/- 0.27 micromol/l; p = .021) and concentration of MDA in erythrocytes of individuals with DS between the third and fourth age group (p = .05). In DS persons, an elevated ratio of SOD to catalase plus GPx with respect to the controls in all age categories was found, suggesting oxidative imbalance, potentially contributing to accelerated aging observed in these persons.

Chemistry, physiology and pathology of free radicals.

The superoxide anion radical and other reactive oxygen species (ROS) are formed in all aerobic organisms by enzymatic and nonenzymatic reactions. ROS arise in both physiological and pathological processes, but efficient mechanisms have evolved for their detoxification. Similarly, reactive nitrogen intermediates (RNI) have physiological activity, but can also react with different types of molecules, including superoxide, to form toxic products. ROS and RNI participate in the destruction of microorganisms by phagocytes, as in the formation of a myeloperoxidase-hydrogen peroxide-chloride/iodide complex which can destroy many cells, including bacteria. It is known that the cellular production of ROS and RNI is controlled by different mechanisms. These free radicals can react with key cellular structures and molecules, thus altering their biological function. An imbalance between the systems producing and removing ROS and RNI may result in pathological consequences.

Superoxide dismutase mimetic activity of macrocyclic Cu(II)-tetraanhydroaminobenzaldehyde (TAAB) complex.

The superoxide dismutase mimetic activity of a copper(II) complex with the tetraazamacrocyclic ligand TAAB has been investigated using the xanthin-xanthine oxidase system for generation of superoxide. The complex exhibits 50% inhibition of the 3-(4-iodophenyl)-2-(4-nitrophenyl)-5-phenyltetrazolium chloride (INT) reduction at the concentration of 0.144 mumol.l-1 (pH 7.8, 25 degrees C). The activity survives in the presence of chelators including EDTA and serum albumin. The enzymatic activity of the complex represents about 3% of that of intact Cu2Zn2SOD.