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 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.

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.

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.

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.

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.

Genetic determinants of blood pressure responses to caffeine drinking.

BACKGROUND: The widely observed between-subject variability in cardiovascular responses to coffee may have a genetic basis. OBJECTIVE: We evaluated acute blood pressure (BP) responses to caffeine and explored whether they are influenced by candidate gene variants affecting caffeine metabolism (for cytochrome P450 1A2), adenosine metabolism (for adenosine receptor and AMP deaminase), or catecholamine receptors. METHODS: We recruited 110 healthy male habitual moderate coffee drinkers who refrained from drinking coffee on the day preceding the study. Each subject underwent ambulatory BP monitoring at 6-min intervals for 2 h. Each participant was administered, in a double-blind design, 40 mL of either a decaffeinated coffee preparation plus 3 mg caffeine/kg (caf) or the corresponding vehicle (decaf). The protocol was repeated 24 h later with the alternative preparation. Blood samples were collected for genetic and plasma caffeine and catecholamine evaluations. RESULTS: Compared with decaf, caf was associated with a mean (± SD) significant increase in systolic BP of 4 ± 12 mm Hg and in diastolic BP of 3 ± 10 mm Hg (P < 0.001 for both). Plasma caffeine and adrenaline increased after caf, but not after decaf. Of 11 gene polymorphisms analyzed, a relation was observed between the ADORA2A TT variant and the change in SBP peak and between the ADRA2B I variant and the changes in both SBP mean and peak; mean peak change in SBP; these variants were associated with increased SBP responses to caf. CONCLUSIONS: Variability in the acute BP response to coffee may be partly explained by genetic polymorphisms of the adenosine A2A receptors and α(2)-adrenergic receptors. This trial is registered at clinicaltrials.gov as NCT01330680.

High hydrophobic amino acid exposure is responsible of the neurotoxic effects induced by E200K or D202N disease-related mutations of the human prion protein.

Mutations in prion protein are thought to be causative of inherited prion diseases favoring the spontaneous conversion of the normal prion protein into the scrapie-like pathological prion protein. We previously reported that, by controlled thermal denaturation, human prion protein fragment 90-231 acquires neurotoxic properties when transformed in a ß-rich conformation, resembling the scrapie-like conformation. In this study we generated prion protein fragment 90-231 bearing mutations identified in familial prion diseases (D202N and E200K), to analyze their role in the induction of a neurotoxic conformation. Prion protein fragment 90-231(wild type) and the D202N mutant were not toxic in native conformation but induced cell death only after thermal denaturation. Conversely, prion protein fragment 90-231(E200K) was highly toxic in its native structure, suggesting that E200K mutation per se favors the acquisition of a peptide neurotoxic conformation. To identify the structural determinants of prion protein fragment 90-231 toxicity, we show that while the wild type peptide is structured in α-helix, hPrP90-231 E200K is spontaneously refolded in a ß-structured conformer characterized by increased proteinase K resistance and propensity to generate fibrils. However, the most significant difference induced by E200K mutation in prion protein fragment 90-231 structure in native conformation we observed, was an increase in the exposure of hydrophobic amino-acids on protein surface that was detected in wild type and D202N proteins only after thermal denaturation. In conclusion, we propose that increased hydrophobicity is one of the main determinants of toxicity induced by different mutations in prion protein-derived peptides.

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.

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.

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.

Glutathione transferases from Anguilla anguilla liver: identification, cloning and functional characterization.

Glutathione transferases (GSTs) constitute a class of detoxifying enzymes involved in Phase II metabolism. Using GSH-affinity chromatografy followed by HPLC analysis, two GST isoforms were isolated from the Anguilla anguilla liver cytosol. The major GST belongs to the piscine-specific rho class and accounted for about 59% of total GST affinity eluted fraction, while the remaining 41% was represented by a Pi class GST. Both isoforms were cloned, heterologously expressed in Escherichia coli and their enzyme activities were characterized with respect to a broad spectrum of well-known GST substrates. Our data indicate that only a fraction of prototypical GST substrates are conjugated by these enzymes and that Pi class GST has higher specific activity than rho class GST against 1-chloro-2,4-dinitrobenzene (CDNB), ethracrynic acid, 4-nitroquinoline-1-oxide and p-nitrophenyl acetate while trans-2-nonenal is detoxified more efficiently by rho class GST. Analysis of the kinetics parameters of the conjugation against CDNB indicated that the utilization ratio K(cat)/K(m) is slightly higher for rho class GST with respect to pi class GSTs. Finally, to determine the potential for environmental inhibition of the GST isoforms, we examined the effect of the widely used herbicide atrazine as an inhibitor of catalytic activity. The inhibition studies revealed that atrazine was an effective inhibitor of GST-CDNB catalytic activities of both isoforms at micromolar concentrations, suggesting the sensitivity of these isoforms to pesticide inhibition at environmentally relevant concentrations.

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.

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.

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.

The role of the antioxidant vitamin supplementation in the prevention of cardiovascular diseases.

Industrial and technological revolutions have resulted in dramatic shifts in the diseases that are responsible for illness and death. In particular, cardiovascular disease (CVD) has emerged as the dominant chronic disease in many parts of the world. Diet, tobacco smoking, physical inactivity, obesity, lipid levels, hypertension and diabetes mellitus have contributed to their wide diffusion. Oxidative damage and the production of free radicals in the endothelium are two of the main factors involved in the pathogenesis of the atherosclerotic process that causes CVD. One of the more important results of basic research on dietetic regimes has shown that people who consume large amounts of fruits and vegetables have a lower incidence of CVD, stroke and tumours, but the specific mechanisms of these foods (which have an apparently protective effect) are still not completely clear. Possible reasons could include a greater consumption of fruit and vegetables, and an increased consumption of dietetic fibres. Recently, it been proposed that micronourishments with an antioxidant activity could be responsible for the reduction of chronic diseases. Research supplies a hypothetical mechanism by which antioxidant substances may be reducing the risk of atherosclerosis through the inhibition of oxidative damage. Appropriate nutritional practices are of central importance in managing risk and treatment of CVD; in fact, many current guidelines for a healthy general population contain nutritional recommendations to reduce the risk of these diseases. A large number of descriptive and case-control studies suggests that the consumption of many antioxidant vitamins (A, C and E) reduces the risk of CVD. Such data raises the following problem of whether supplementation of vitamins A, C and E emerges as being useful in the primary prevention of CVD. Many important studies involving a great number of participants have not confirmed this hypothesis and the results are often contradictory. This review examines the studies published in the literature that document the effect of supplementation with antioxidant vitamins (A, C and E) in the primary and secondary prevention of CVD due to an atherosclerosis process.

Determinants of platelet activation in Alzheimer's disease.

OBJECTIVES: To investigate the rate of platelet thromboxane (TX) biosynthesis and its determinants in Alzheimer's disease. METHODS AND RESULTS: A cross-sectional comparison of urinary 11-dehydro-TXB(2) and 8-iso-prostaglandin (PG)F(2alpha) (markers of in vivo platelet activation and lipid peroxidation, respectively), plasma Vitamin E, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, was carried-out in 44 Alzheimer patients and 44 matched controls. To investigate the cyclooxygenase (COX)-isoform involved in TXA(2) biosynthesis, nine Alzheimer patients were treated with low-dose aspirin (100mg/d) or rofecoxib (25mg/d) for 4 days. Urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) were significantly higher in Alzheimer patients than in controls (Median: 1983.5 versus 517.5pg/mg creatinine and 938.5 versus 304.0pg/mg creatinine, p<0.0001, respectively), with a significant correlation between the two metabolites (rho=0.75, p<0.0001). An inverse correlation was observed between Vitamin E and both urinary metabolites (8-iso-PGF(2alpha): R(s)=-0.51, p=0.0004; 11-dehydro-TXB(2): R(s)=-0.44, p=0.0026) in Alzheimer patients. No difference was found in CRP, TNF-alpha and IL-6 levels between the two groups. Urinary 11-dehydro-TXB(2) was significantly reduced by aspirin, but not by rofecoxib, consistently with a COX-1-mediated TXA(2) biosynthesis. 8-iso-PGF(2alpha) excretion was not modified by either COX-inhibitor, consistently with its oxygen radical-catalyzed formation. CONCLUSIONS: Platelet activation is persistently enhanced in Alzheimer's disease. This is related, at least in part, to increased lipid peroxidation associated with inadequate levels of Vitamin E.

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.

Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome.

In 21 patients with chronic fatigue syndrome (CFS) versus 20 normal subjects, we investigated the oxidant/antioxidant balance and its correlation with muscle symptoms. Patients versus controls showed significantly: lower Lag Phase and Vitamin E (Vit E) concentrations in plasma and low-density lipoproteins (LDL), higher LDL thiobarbituric acid reactive substances (TBARS), higher fatigue and lower muscle pain thresholds to electrical stimulation. A significant direct linear correlation was found between fatigue and TBARS, thresholds and Lag Phase, thresholds and Vit E in plasma and LDL. A significant inverse linear correlation was found between fatigue and Lag Phase, fatigue and Vit E, thresholds and TBARS. Increased oxidative stress and decreased antioxidant defenses are related to the extent of symptomatology in CFS, suggesting that antioxidant supplementation might relieve muscle symptoms in the syndrome.