UHPLC-UV/Vis Quantitative Analysis of Hydroxylated and O-prenylated Coumarins in Pomegranate Seed Extracts.

A simple and rapid analytical UHPLC methodology with spectrophotometric (UV/Vis) detection, coupled with different extraction procedures, has been perfected to investigate the presence of biologically active O-prenylated umbelliferone derivatives, such as auraptene and umbelliprenin, in pomegranate (Punica granatum L.) seed extracts. Absolute ethanol was the most efficient extraction solvent in terms of yields, after a short ultrasound-assisted. The highest concentration values recorded under these experimental conditions were 1.99 µg/g of dry extract and 6.53 µg/g for auraptene and umbelliprenin, respectively. The parent metabolite umbelliferone was also detected (0.67 µg/g). The extraction and UHPLC analytical methodology set up in the present study proved to be an efficient, powerful, and versatile technique for the simultaneous qualitative analysis and quantification of oxyprenylated coumarins in pomegranate seed extracts. The characterization of such secondary metabolites in the mentioned phytopreparation represents, to the best of our knowledge, the first example in the literature.

Dilated cardiomyopathy following use of xenadrine EFX.

We describe a case of a 35-year-old man presented at the emergency room of our institution with acute onset of dyspnea and dizziness. He was a body builder and had been using Xenadrine EFX for weight loss reduction. The laboratory analyses were normal. A chest radiograph showed an enlarged cardiac silhouette with clear lung fields. Transtoracic two-dimensional color Doppler echocardiography revealed a diffuse hypokinesia with a marked decreased in systolic function and a high teledyastolic diameter. This case document the possible relation to use of Xenadrine EFX for weight loss and the recurrence of dilated cardiomyopathy.

ADMA/SDMA in elderly subjects with asymptomatic carotid atherosclerosis: values and site-specific association.

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor known as a mediator of endothelial dysfunction and atherosclerosis. Circulating ADMA levels are correlated with cardiovascular risk factors such as hypercholesterolemia, arterial hypertension, diabetes mellitus, hyperhomocysteinemia, age and smoking. We assessed the relationship between ADMA values and site-specific association of asymptomatic carotid atherosclerosis (intima-media thickness (CIMT) and plaque) in elderly subjects. One hundred and eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). All subjects had no acute or chronic symptoms of carotid atherosclerosis. Statistical analyses showed that high plasma levels of ADMA/SDMA were positively correlated to carotid atherosclerosis (CIMT and plaque) (p<0.001), with significant site-specific association. Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p<0.001). High serum concentrations of ADMA and SDMA were associated with carotid atherosclerotic lesions as measured by CIMT ad plaque and may represent a new marker of asymptomatic carotid atherosclerosis in elderly subjects.

Iron deficiency in myocardial ischaemia: molecular mechanisms and therapeutic perspectives.

Systemic iron deficiency (SID), even in the absence of anaemia, worsens the prognosis and increases mortality in heart failure (HF). Recent clinical-epidemiological studies, however, have shown that a myocardial iron deficiency (MID) is frequently present in cases of severe HF, even in the absence of SID and without anaemia. In addition, experimental studies have shown a poor correlation between the state of systemic and myocardial iron. MID in animal models leads to severe mitochondrial dysfunction, alterations of mitophagy, and mitochondrial biogenesis, with profound alterations in cardiac mechanics and the occurrence of a fatal cardiomyopathy, all effects prevented by intravenous administration of iron. This shifts the focus to the myocardial state of iron, in the absence of anaemia, as an important factor in prognostic worsening and mortality in HF. There is now epidemiological evidence that SID worsens prognosis and mortality also in patients with acute and chronic coronary heart disease and experimental evidence that MID aggravates acute myocardial ischaemia as well as post-ischaemic remodelling. Intravenous administration of ferric carboxymaltose (FCM) or ferric dextrane improves post-ischaemic adverse remodelling. We here review such evidence, propose that MID worsens ischaemia/reperfusion injury, and discuss possible molecular mechanisms, such as chronic hyperactivation of HIF1-α, exacerbation of cytosolic and mitochondrial calcium overload, amplified increase of mitochondrial [NADH]/[NAD+] ratio, and depletion of energy status and NAD+ content with inhibition of sirtuin 1-3 activity. Such evidence now portrays iron metabolism as a core factor not only in HF but also in myocardial ischaemia.

The biological effect of pharmacological treatment on dimethylaminohydrolases (DDAH-1) and cationic amino acid transporter-1 (CAT-1) expression in patients with acute congestive heart failure.

AIM: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) which plays an important role in controlling vascular tone and regulates the contractile properties of cardiac myocytes. The aim of this study was to investigate the effect of pharmacological treatment on symmetric dimethylarginine (SDMA), ADMA and arginine plasma concentrations in patients with acute congestive heart failure (ACHF) through the evaluation of type-1 system cationic amino acid transporter-1/type 1 dimethylarginine dimethylaminohydrolases-1 (CAT-1/DDAH-1). METHODS AND RESULTS: 25 hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction<35%) were included in the study. ADMA, SDMA, and arginine plasma concentrations were assessed before and after pharmacological treatment by high performance liquid chromatography. All patients received an adequate pharmacological treatment for ACHF. ADMA and SDMA plasma levels were significantly higher after pharmacological treatment respect to baseline values (pre-treatment) (0.75 vs 0.48; 1.31 vs 1.03; p<0.01). Arginine plasma concentration was significantly lower after therapy respect to baseline values (0.78 vs 0.99; p<0.01). This is associated more with the modulation of DDAH-1 protein than with of CAT-1 system transport. CONCLUSIONS: In patients with ACHF, acute renal impairment function and the modulation of metabolism and extracellular transport by the DDAH-1/CAT-1 system determine high ADMA and SDMA levels after therapy for acute congestive heart failure.

The membrane depolarization and increase intracellular calcium level produced by silver nanoclusters are responsible for bacterial death.

This work highlights how our silver ultra nanoclusters (ARGIRIUM-SUNc) hand-made synthesized, are very useful as a bactericide and anti-biofilm agent. The Argirium-SUNc effective antibacterial concentrations are very low (< 1 ppm) as compared to the corresponding values reported in the literature. Different bacterial defense mechanisms are observed dependent on ARGIRIUM-SUNc concentrations. Biochemical investigations (volatilome) have been performed to understand the pathways involved in cell death. By using fluorescence techniques and cell viability measurements we show, for the first time, that membrane depolarization and calcium intracellular level are both primary events in bacteria death. The ARGIRIUM-SUNc determined eradication of different biofilm at a concentration as low as 0.6 ppm. This suggests that the effect of the nanoparticles follows a common mechanism in different bacteria. It is highly probable that the chemical constitution of the crosslinks could be a key target in the disrupting mechanism of our nanoparticles. Since the biofilms and their constituents are essential for bacterial survival in contact with humans, the silver nanoparticles represent a logical target for new antibacterial treatments.

Oxidation of Cys278 of ADH I isozyme from Kluyveromyces lactis by naturally occurring disulfides causes its reversible inactivation.

The inactivation of the homotetrameric cytosolic alcohol dehydrogenase I from Kluyveromyces lactis (KlADH I) by naturally occurring disulfides, oxidized glutathione, cystine and cystamine, was studied. The inactivation was fully reversed by dithiothreitol. The nicotinamide coenzyme, but not the substrate ethanol, protected KlADH I from inactivation. Gel filtration experiments and SDS-PAGE analysis, also, revealed that enzyme inactivation coincides with inter-subunits disulfide bond formation which are noticeably enhanced after prolonged oxidation with GSSG. Moreover, oxidized KlADH I, as its reduced state, retained the tetrameric stucture and appears mainly as a dimer under non-reducing SDS-PAGE. Conversely, KlADH I Cys278Ile mutant is unaffected by disulfides treatment. Therefore, in vitro, KlADH I wild-type could exist in two reversible forms: reduced (active) and oxidized (inactive), in which the Cys278 residues of each tetramer are linked by disulfide bonds. The redox state of KlADH I could represent the path for modulating its activity and then a regulatory step of glycolysis under hypoxic conditions. It might be hypothesized that KlADH I could represent an important target in redox signaling of Kluyveromyces lactis cell by inhibiting, under oxidative stress, the glycolytic pathway in favor of the pentose-phosphate shunt to restore its reducing potential.

A novel and efficient subcritical butane extraction method and UHPLC analysis of oxyprenylated phenylpropanoids from grapefruits peels.

Biologically active prenyoxyphenylpropanoids are well known to be biosynthesized by Citrus species, for which they have been found most abundantly in fruit peels. Although several extraction methodologies have been described, the development of novel and alternative extraction processes is a field of research of current interest. In this preliminary communication, we studied the performance of the subcritical butane promoted extraction of selected oxyprenylated phenylpropanoids from grapefruit peels under a counter-current mode using a handmade extraction apparatus coupled to UHPLC analysis. The application of such a method yielded 7-isopentenyloxycoumarin, auraptene, and boropinic acid in quantities higher than those recorded for other extraction methodologies like the ultrasound- and microwave-assisted macerations (0.234, 1.035, and 0.211 mg/g of dry extract respectively). The use of subcritical butane as the extraction solvent for oxyprenylated phenylpropanoids is reported herein for the first time and can be easily adopted for several other food matrices.

Relationship between plasma antioxidant concentrations and carotid intima-media thickness: the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study.

BACKGROUND: Few studies have examined the relationship among carotid atherosclerosis, vascular risk factors, and antioxidant plasma concentrations, and those that have reported conflicting results. The aim of this study was to assess the relationship between asymptomatic carotid atherosclerosis, as defined by carotid intima-media thickness (CIMT), and inflammatory markers, plasma lipids and serum antioxidant vitamins. METHODS AND RESULTS: We examined baseline characteristics of the 640 participants in the Asymptomatic Carotid Atherosclerotic Disease In Manfredonia Study. All participants were asymptomatic with respect to carotid artery disease in 2006-2007 and underwent physical examination with carotid ultrasound investigation, the collection of medical history and laboratory data. Analysis of variance methods were used to examine differences between participants by category of CIMT. Of the 640 participants, 291 did not have evidence of carotid atherosclerosis (CIMT<0.8 mm), 232 were found to have some atherosclerosis (0.8 mm< or =CIMT<1.2 mm), and 117 were found to have extensive atherosclerosis (CIMT>1.2 mm). Among participants with CIMT> or =0.8 mm, body mass index, blood pressures, total cholesterol, LDL cholesterol, triglycerides, uric acid, C-reactive protein, and fibrinogen were significantly higher, whereas concentrations of vitamin A, vitamin E, lycopene, and beta-carotene were all significantly lower when compared with participants who did not show evidence of carotid atherosclerosis (P<0.001). CONCLUSION: The optimal control of hypertension, diabetes, and dyslipidemia, in addition to smoking cessation and an adequate intake of antioxidant micronutrients from foods represent a key for the prevention of atherosclerotic disease.

Leukotriene modifiers in the treatment of cardiovascular diseases.

Cysteinyl-leukotrienes (Cys-LTs) and LTB4 are potent proinflammatory mediators derived from arachidonic acid through the 5-lipoxygenase (5-LO) pathway, which exerts important pharmacological effects through their interaction with specific receptors: Cys-LT receptors (CysLT1 and CysLT2) and LTB4 receptors (BLT1 and BLT2). Published evidence justifies a broader role for LT receptor antagonists (LTRAs), in particular, montelukast, in the treatment of bronchial asthma, allergic rhinitis, and recently, in cardiocerebrovascular disease. The actions of Cys-LTs on the cardiovascular (CV) system are well-documented and include a broad array of activities with promising therapeutic targets in animal models exploring the use of selective 5-LO (or 5-LO-activating protein) inhibitors or dual LO-cycloxygenase-blocking agents in experimentally induced acute myocardial infarction. The picture that emerges from studies with LTRAs is more controversial at the moment, and some findings suggest a role for Cys-LTs in the extension of ischemic damage and in cardiac dysfunction during reperfusion; others do not. The aim of this short review is to summarize the state of present research about LT modifier treatment in CV disease.

Novel biologically active principles from spinach, goji and quinoa.

Spinach leaves, goji berries and quinoa seeds are claimed to have a great nutraceutical potential due to their high content of compounds providing benefits for human health, such as amino acids, polyunsaturated fatty acids, carotenoids, betaine, vitamins, fibre, minerals and polyphenols. Samples of these plants were extracted with different solvent mixtures (e.g. EtOH, H2O/EtOH 3:7 and H2O/EtOH 7:3) and extractions were accomplished using a microwave apparatus. Subsequent UHPLC analysis and photodiode array detection were employed for the quantification of biologically active compounds like 7-isopentenyloxycoumarin, auraptene, umbelliprenin, boropinic acid and 4'-geranyloxyferulic acid. EtOH was found to be the best solvent in terms of extractive yields and the above-mentioned phytochemicals were recorded in the concentration range 2.01-49.22 µg/g dry extract. The findings depicted herein revealed that spinach, goji and quinoa are good sources of oxyprenylated umbelliferone and ferulic acid derivatives.

Plasma antioxidants and asymptomatic carotid atherosclerotic disease.

BACKGROUND: Atherosclerosis remains clinically mute for a long time and frequently manifests itself with an acute cardiovascular event. The possibility of detecting this disease in a subclinical phase and reducing or reversing its progression is an issue of relevance. Published studies on the association between antioxidant vitamins and carotenoids and carotid intima-media thickness (CIMT) have been inconclusive. METHODS: We enrolled 220 consecutive, asymptomatic participants. After carotid ultrasound investigation, a medical history was taken, a physical examination was performed and venous blood samples were collected. Venous blood samples were analyzed for concentrations of antioxidant vitamins and carotenoids. RESULTS: Low concentrations of vitamin A (p < 0.01), vitamin E (p < 0.001), lycopene (p < 0.01) and beta-carotene (p < 0.001) were significantly associated with carotid atherosclerosis (CIMT > or = 0.8 mm). In addition, marginally higher body mass index, plasma haemoglobin and high-density lipoprotein cholesterol were also associated with carotid atherosclerosis, while other laboratory parameters considered in this study (total cholesterol, low-density lipoprotein cholesterol, triglycerides and C-reactive protein) were not significantly associated with carotid atherosclerosis. CONCLUSIONS: Low plasma concentrations of antioxidant vitamins (A, E, beta-carotene) and lycopene were associated with early carotid atherosclerotic lesions as measured by CIMT. Regular intake of foods rich in lycopene and antioxidant vitamins may slow the progression of atherosclerosis.

Analysis of biologically active oxyprenylated phenylpropanoids in Tea tree oil using selective solid-phase extraction with UHPLC-PDA detection.

An efficient analytical strategy based on different extraction methods of biologically active naturally occurring oxyprenylated umbelliferone and ferulic acid derivatives 7-isopentenyloxycoumarin, auraptene, umbelliprenin, boropinic acid, and 4'-geranyloxyferulic acid and quantification by UHPLC with spectrophotometric (UV/Vis) detection from Tea tree oil is reported. Absorption of the pure oil on Al2O3 (Brockmann activity II) prior washing the resulting solid with MeOH and treatment of this latter with CH2Cl2 resulted the best extraction methodology in terms of yields of oxyprenylated secondary metabolites. Among the five O-prenylphenylpropanoids herein under investigation auraptene and umbelliprenin were never detected while 4'-geranyloxyferulic acid was the most abundant compound resulting from all the three extraction methods employed. The UHPLC analytical methodology set up in the present study resulted to be an effective and versatile technique for the simultaneous characterization and quantification of prenyloxyphenylpropanoids in Tea tree oil and applicable to other complex matrices from the plant kingdom.

Electrochemically Synthesized Silver Nanoparticles Are Active Against Planktonic and Biofilm Cells of Pseudomonas aeruginosa and Other Cystic Fibrosis-Associated Bacterial Pathogens.

A novel, electrochemically synthesized, silver nanoparticles (AgNPs) formulation was evaluated in vitro against Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, and Staphylococcus aureus strains from cystic fibrosis (CF) patients. AgNPs were particularly active against P. aeruginosa and B. cepacia planktonic cells (median MIC: 1.06 and 2.12 µg/ml, respectively) by a rapid, bactericidal and concentration-dependent effect. AgNPs showed to be particularly effective against P. aeruginosa and S. aureus biofilm causing a viability reduction ranging from 50% (1×MIC) to >99.9% (4×MIC). Electron microscopy showed that AgNPs deconstruct extracellular matrix of P. aeruginosa biofilm, and accumulate at the cell surface causing cell death secondary to membrane damage. Compared to Tobramycin, AgNPs showed comparable, or even better, activity against planktonic and biofilm P. aeruginosa cells. AgNPs at concentrations effective against B. cepacia and P. aeruginosa were not toxic to G. mellonella larvae. Our silver-based formulation might be an alternative to antibiotics in CF patients. Further in vitro and in vivo studies are warranted to confirm this therapeutic potential.

Increased oxidative stress in prepubertal children born small for gestational age.

CONTEXT: Low birth weight is associated with an increased risk of metabolic and cardiovascular diseases in adulthood. The development of insulin resistance (IR) seems to play a pivotal role; no data on the oxidant-antioxidant status are available in this risk group. OBJECTIVE: This study is an assessment of oxidant-antioxidant status in prepubertal children born small for gestational age (SGA) in comparison to healthy controls and the relationship to IR. DESIGN: This cross-sectional study compares indexes of IR and oxidant-antioxidant status in three different groups (SGA+, SGA-, controls), with analysis by post hoc and Pearson correlation. SETTING: The study was conducted in the Academic Department of Pediatrics. PARTICIPANTS: A total of 19 SGA+ and 16 SGA- children were compared with 13 controls. INTERVENTION: No intervention was used. MAIN OUTCOME MEASURES: Indexes of IR (glucose to insulin ratio, homeostasis model assessment of IR) were evaluated, and markers of oxidative stress (lag phase, malonildialdehyde, vitamin E) were measured. RESULTS: Homeostasis model assessment of IR was significantly higher in SGA+ than SGA- children (1.32+/-0.9 vs. 0.69+/-0.47; P=0.03) and controls (0.71+/-0.37; P=0.04). Glucose to insulin ratio was significantly lower in SGA+ than SGA- children (12.41+/-5.01 vs. 26.54+/-17.18; P=0.02) and controls (26.96+/-20.70; P=0.04). Lag phase was significantly shorter in SGA+ than SGA- children (24.3+/-4.38 vs. 35.59+/-11.29 min; P=0.003) and controls (45.28+/-7.69 min; P=0.0001) and in SGA- than controls (P=0.01). Malonildialdehyde was significantly higher in SGA+ than SGA- children (0.79+/-0.3 vs. 0.6+/-0.1 nmol/mg; P=0.03) and controls (0.36+/-0.04 nmol/mg; P=0.0001) and in SGA- children than controls (P=0.02). Vitamin E was significantly reduced in SGA+ children than controls (27.54+/-7.9 vs. 43.23+/-11.32 micromol/liter; P=0.002). CONCLUSION: Oxidative stress is present in both SGA+ and SGA- children, with a continuous alteration in relation to IR. Therefore, catch-up growth might exert the greatest influence in the development of future diseases.

Antioxidant vitamin supplementation in asthma.

The influence of nutrition on chronic bronchial asthma has an important place in the management of this disease. Evidence suggests that specific inflammatory abnormalities exist in the airways of subjects suffering from mild-to-moderate persistent asthma, in whom an inflammatory state is often associated with increased generation of reactive oxygen species and the damaging effects of free radicals. For this reason oxidant stress may be an important pathogenic factor in the progress of the disease. The role of nutrition in bronchial asthma is related to antioxidant vitamins A, C, and E. By counteracting oxidants and reducing external attacks (bacteria, virus, toxins, xenobiotics) in the lung, antioxidant vitamins modulate the development of asthma and the impairment of pulmonary function. Dietary studies suggest relations between oxidative stress, bronchial inflammation, development of asthmatic symptoms, and reduction of cellular functions. Dietary interventions may reduce oxidant stress and prevent or minimize asthmatic symptoms. Such interventions may provide a cost-effective approach to asthma management that may supplement current pharmacological strategies, although this conclusion is not supported by many randomized, placebo-controlled studies. The aim of this short review is to summarize current knowledge regarding the relations between antioxidant vitamins and the treatment of bronchial asthma.

Antioxidant vitamin supplementation in cardiovascular diseases.

Cardiovascular disease is the most important adult health problem in wealthy countries, where biological factors such as obesity, hypertension, dyslipidemia, diabetes, inappropriate diet, cigarette smoking, and sedentary life-style have contributed to its dissemination. Research concerning nutritional regimens has shown that persons who consume large amounts of fruit and vegetables have lower incidences of cardiovascular diseases, stroke, and tumors, although the precise mechanisms for this protective effect are elusive. Possible explanations include (a) increased consumption of dietary fiber, (b) reduced consumption of dietary cholesterol and other lipids, and (c) increased intake of the antioxidant vitamins (A, C, and E). Numerous studies have raised the question whether vitamin supplements help to prevent cardiovascular diseases. Results of randomized controlled trials of antioxidant vitamin supplements in large numbers of participants has been ambiguous or contradictory. This minireview examines the relevant clinical reports on dietary supplements of vitamins A, C, and E to determine whether they support the premise that patients at risk of cardiovascular disease may be candidates for this therapeutic option.

Is nasal polyposis a determinant of bronchial hyperresponsiveness and altered quality of life in asthmatic subjects? A case-control study.

Asthmatic patients with nasal polyposis (NP) have been reported to have a high prevalence of bronchial hyperresponsiveness (BHR) and a worsening of quality of life (QoL). The aim of this case-control study was to evaluate if NP is a determinant of BHR and is responsible for modifying the QoL in asthmatic subjects. Eighty-nine asthmatic subjects, including 24 patients with NP and 65 patients without NP (controls), underwent spirometry, methacholine challenge test (MCHt), skin prick tests, and were evaluated with the Asthma Quality of Life Questionnaire (AQLQ). Results of the MCHt test are expressed as the provocative concentration of methacholine that causes 20% (PC20) fall of forced expiratory volume at 1 sec (FEV1). The PC20 (mean +/- SD) in NP cases was 1149 +/- 668 microg/ml vs 894 +/- 691 microg/ml in controls (p <0.001). This demonstrates that BHR was not enhanced by the presence of NP in asthmatic subjects. No significant differences were found between the NP cases and controls for overall QoL or for single QoL domains. This study shows that the presence of NP did not impair the QoL of asthmatic patients, as indicated by the items included in the AQLQ questionnaire.

Low-density lipoprotein level reduction by the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitor simvastatin is accompanied by a related reduction of F2-isoprostane formation in hypercholesterolemic subjects: no further effect of vitamin E.

BACKGROUND: Both statins and vitamin E, by reducing the rate of lipid peroxidation, may interfere with oxidative stress, but the impact of their combination is unknown. METHODS AND RESULTS: We randomized 43 hypercholesterolemic patients (21 men, 22 women, age 63+/-11 years) to either simvastatin, to achieve >20% reduction of total cholesterol, or simvastatin plus 600 mg/d vitamin E for 2 months. Patients were then crossed over to the alternative treatment. Lipid parameters documented patients' compliance to simvastatin, whereas plasma levels of vitamin E documented compliance and absorption of vitamin E. We assessed urinary excretion of the isoprostane 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) as an in vivo index of oxidative stress at baseline and after each month of therapy. 8-Iso-PGF(2alpha) was significantly reduced by simvastatin, from 361+/-148 pg/mg creatinine (mean+/-SD) at baseline to 239+/-124 pg/mg creatinine after 1 month. The addition of vitamin E did not reduce such levels any further (256+/-125 after 1 month). Linear regression analysis showed a weak inverse relationship of 8-iso-PGF(2alpha) with vitamin E levels but a much stronger relationship with LDL cholesterol (R(2)=0.162; P<0.001). CONCLUSIONS: In hypercholesterolemic patients, LDL cholesterol is a major correlate of oxidative stress. Concomitant with LDL cholesterol reduction, simvastatin causes a drastic reduction of oxidative stress to a level that is not further reduced by the addition of vitamin E. Results of clinical trials with vitamin E may have been hampered by inadequate knowledge of the background level of lipid peroxidation, which is a major determinant of vitamin E bioactivity.

Physical exercise reduces synthesis of ADMA, SDMA, and L-Arg.

Increased levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and low plasma level of L-arginine (L-ARG) are all conditions likely to decrease nitric oxide (NO) production. Aim of this study is to evaluate ADMA, SDMA, and L-ARG plasmatic levels before and after physical exercise in patients with coronary artery disease (CAD). We studied 30 patient with mean age 52 + 4.5 years. After inclusion in the study, before the execution of physical exercise, heparinized blood sample was drawn from an indwelling arterial line for determination of ADMA, L-ARG and SDMA (baseline values). Subsequently a blood sample was drawn after the physical exercise. The mean plasma concentrations of ADMA (0.68 + 0.06 vs 0.48 + 0.05 µmol/L) and SDMA (0.45 + 0.03 vs 0.30 + 0.03 µmol/L) were significantly lower after physical exercise in comparison to baseline value, while L-ARG mean levels were increased (44.20 + 10.5 vs 74.13 + 11.2 µmol/L). Physical exercise has a beneficial effect by reducing plasmatic ADMA and SDMA levels, and increasing L-ARG substrate for endothelial NO.