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Biomedical subjects

M Cristina Polidori

Publications and source records attributed to M Cristina Polidori.

At least 19 recordsLinked to original sources
PubMed2006

Congestive heart failure and Alzheimer's disease.

The increase in average life expectancy is resulting in an increasing prevalence of major invalidating illnesses, such as cardiovascular disease and dementia. Congestive heart failure (CHF) is a chronic, progressive disease representing the advanced stage of cardiac illnesses. Cognitive impairment is known to be a frequent feature of CHF patients. The epidemiologic pictures of mild cognitive impairment (MCI), Alzheimer's disease (AD) and CHF are predicted to worsen with the demographic expansion of the elderly population. Nevertheless, there has been little structured research on cognitive impairment in patients with CHF. This is unfortunate not only because CHF is the leading cause of hospitalization in the elderly and a leading cause of disability and death, but also for important clinical and socioeconomic implications including those related to comorbidity in advanced age and the need to early detect factors which may precipitate the conversion of MCI to AD. In this review, several aspects of the role of CHF in cognitive impairment are evaluated. Owing to the lack of studies focusing on CHF in AD, the pathophysiology of cardiac failure in cognitive impairment is addressed in light of possible preventive strategies against the onset of AD. These include prevention of oxygen radical and peroxynitrite production, supplementation of nitric oxide (NO) donors, as well as the achievement of an adequate antioxidant supply, better if obtained with a targeted and individualized nutritional approach. A systematic neuropsychologic testing of older patients with heart failure is to identify those with early cognitive impairment and promptly establish traditional therapies such as angiotensin converting enzyme (ACE) inhibitors, digoxin or beta-blockers. The neuropsychologic assessment in CHF patients is also fundamental to disclose conditions potentially favoring the onset of cognitive impairment such as depression. Finally, management schemes should include exercise training programs as well as patient and caregiver education.

Alzheimer Disease↗
PubMed2005

Potential markers of oxidative stress in stroke.

Free radical production is increased in ischemic and hemorrhagic stroke, leading to oxidative stress that contributes to brain damage. The measurement of oxidative stress in stroke would be extremely important for a better understanding of its pathophysiology and for identifying subgroups of patients that might receive targeted therapeutic intervention. Since direct measurement of free radicals and oxidized molecules in the brain is difficult in humans, several biological substances have been investigated as potential peripheral markers. Among lipid peroxidation products, malondialdehyde, despite its relevant methodological limitations, is correlated with the size of ischemic stroke and clinical outcome, while F2-isoprostanes appear to be promising, but they have not been adequately evaluated. 8-Hydroxy-2-deoxyguanosine has been extensively investigated as markers of oxidative DNA damage but no study has been done in stroke patients. Also enzymatic and nonenzymatic antioxidants have been proposed as indirect markers. Among them ascorbic acid, alpha-tocopherol, uric acid, and superoxide dismutase are related to brain damage and clinical outcome. After a critical evaluation of the literature, we conclude that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

Aldehydes↗
PubMed2005

Low levels of carotenoids and retinol in involutional osteoporosis.

Previous epidemiological studies conducted in retinol-supplemented subjects showed an association between high serum levels or dietary intake of retinol and risk of hip fracture. On the other side, observational studies revealed that non-supplemented subjects with higher dietary intake of retinol lose less bone with age than subjects with lower intake. This discrepancy, currently unexplained, suggests that nutrition plays a major role in conditioning the effects of retinol on bone. Since retinol is derived from both retinoids--contained in animal food--and carotenoids--contained in vegetables and fruits--we evaluated a possible role of carotenoids in involutional osteoporosis. Therefore, plasma levels of beta-carotene and other carotenoids, in addition to those of retinol, were measured in free-living, non-supplemented, elderly women with or without severe osteoporosis. Plasma levels of retinol and of all carotenoids tested, with the exception of lutein, were consistently lower in osteoporotic than in control women. A weak association was found only between retinol and femoral neck bone mineral density in osteoporotic women. Our study suggests a bone sparing effect of retinol, to which the provitamin A activity of some carotenoids might have contributed.

Aged↗
PubMed2005

Effects of vitamin C and aspirin in ischemic stroke-related lipid peroxidation: results of the AVASAS (Aspirin Versus Ascorbic acid plus Aspirin in Stroke) Study.

A condition of oxidative stress is known to occur in ischemic stroke, the current therapeutic intervention of which is largely limited to thrombolysis. To assess the effect of vitamin C - in conjunction to aspirin - in ischemic stroke-related lipid peroxidation, we measured plasma levels of ascorbate, of 8,12-isoprostanes F2alpha-VI (8,12-iPF2alpha-VI) and activities and levels of a broad spectrum of antioxidant enzymes and micronutrients in stroke patients randomized to receive, from stroke onset and up to three months, either vitamin C (200 mg/day) plus aspirin (300 mg/day) or only aspirin (300 mg/day). By the end of the first week, patients treated with vitamin C plus aspirin had higher vitamin C levels (p = 0.02) and lower 8,12-iPF2alpha-VI levels (p = 0.01) than patients treated with aspirin alone. The significance was maintained for the increase of vitamin C after three months of therapy (p < 0.01). The clinical functional outcome for both groups of patients similarly ameliorated after three months of treatment. We conclude that vitamin C, at the dose of 200 mg/day and in conjunction with aspirin, significantly decreases ischemic stroke-related lipid peroxidation in humans. Further studies are warranted to clarify whether the use of vitamin C may add clinical long-term beneficial effects in patients with stroke.

Ascorbic Acid↗
PubMed2005

Dietary habits are major determinants of the plasma antioxidant status in healthy elderly subjects.

Previous studies indicate that regular consumption of a diet rich in fruits and vegetables is associated with a lower risk for age-related diseases. The aim of the present study was to evaluate whether the often-reported age-related decrease of plasma antioxidants in man depends on differences in dietary intake or on other age- and gender-related factors. In this observational case-control study, thirty-nine community-dwelling healthy subjects aged 65 years and older consuming high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma levels of retinol, tocopherols and carotenoids were significantly higher in group HI than in group LI subjects independent of age and gender. MDA levels were inversely correlated with vitamin A and alpha-carotene. Protein carbonyls were inversely correlated with gamma-tocopherol. In the elderly, a higher daily intake of fruits and vegetables is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables. Modification of nutritional habits among other lifestyle changes should be encouraged to lower prevalence of disease risk factors in later life.

Age Factors↗
PubMed2004

Plasma antioxidant status, immunoglobulin g oxidation and lipid peroxidation in demented patients: relevance to Alzheimer disease and vascular dementia.

A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. A vascular component might be critical in the pathophysiology of AD, but there is a substantial lack of data regarding the simultaneous behavior of peripheral antioxidants and biomarkers of oxidative stress in AD and vascular dementia (VaD). Sixty-three AD patients, 23 VaD patients and 55 controls were included in the study. We measured plasma levels of water-soluble (vitamin C and uric acid) and lipophilic (vitamin E, vitamin A, carotenoids including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) antioxidant micronutrients as well as levels of biomarkers of lipid peroxidation [malondialdehyde (MDA)] and of protein oxidation [immunoglobulin G (IgG) levels of protein carbonyls and dityrosine] in patients and controls. With the exception of beta-carotene, all antioxidants were lower in demented patients as compared to controls. Furthermore, AD patients showed a significantly higher IgG dityrosine content as compared to controls. AD and VaD patients showed similar plasma levels of plasma antioxidants and MDA as well as a similar IgG content of protein carbonyls and dityrosine. We conclude that, independent of its nature-vascular or degenerative-dementia is associated with the depletion of a large spectrum of antioxidant micronutrients and with increased protein oxidative modification. This might be relevant to the pathophysiology of dementing disorders, particularly in light of the recently suggested importance of the vascular component in AD development.

Aged↗
PubMed2004

Short-term and long-term vitamin C supplementation in humans dose-dependently increases the resistance of plasma to ex vivo lipid peroxidation.

To assess the effects of short-term and long-term vitamin C supplementation in humans on plasma antioxidant status and resistance to oxidative stress, plasma was obtained from 20 individuals before and 2h after oral administration of 2g of vitamin C, or from eight subjects enrolled in a vitamin C depletion-repletion study using increasing daily doses of vitamin C from 30 to 2500 mg. Plasma concentrations of ascorbate, but not other physiological antioxidants, increased significantly after short-term supplementation, and increased progressively in the long-term study with increasing vitamin C doses of up to 1000 mg/day. Upon incubation of plasma with a free radical initiator, ascorbate concentrations were positively correlated with the lag phase preceding detectable lipid peroxidation. We conclude that vitamin C supplementation in humans dose-dependently increases plasma ascorbate concentrations and, thus, the resistance of plasma to lipid peroxidation ex vivo. Plasma and body saturation with vitamin C in humans appears desirable to maximize antioxidant protection and lower risk of oxidative damage.

Adult↗
PubMed2004

Increased F2 isoprostane plasma levels in patients with congestive heart failure are correlated with antioxidant status and disease severity.

BACKGROUND: A growing body of evidence supports the pathophysiologic role of oxidative stress and the protective role of naturally occurring antioxidants in congestive heart failure (CHF). Circulating levels of a sensitive and specific marker of lipid peroxidation and levels and activities of a broad spectrum of essential antioxidant micronutrients, vitamins, and enzymes, however, have been never simultaneously evaluated in well-characterized CHF patients. METHODS AND RESULTS: Plasma levels of 8,12-isoprostane F(2alpha)-VI; vitamins A, C, and E; uric acid; and five carotenoids as well as activities of plasma superoxide dismutase and glutathione peroxidase were measured in 30 patients with class II and III New York Heart Association (NYHA) CHF and in 30 controls. Ejection fraction was measured in all patients. Significantly higher 8,12-isoprostane F(2alpha)-VI levels and lower antioxidant levels and activities were found in CHF patients in comparison to controls. Levels of 8,12-isoprostane F(2alpha)-VI were higher in class III than in class II NYHA CHF patients (P=.0012), and inversely correlated with ejection fraction; vitamins A, C, and E; uric acid; carotenoid levels; and superoxide dismutase activity. CONCLUSION: There is an association between increased lipid peroxidation and both antioxidant status and disease severity in CHF in humans. These findings support the rationale for intervention trials aiming at exploring beneficial effects of antioxidant micronutrients in this disease.

Aged↗
PubMed2004

Oxidative stress and risk factors for Alzheimer's disease: clues to prevention and therapy.

The protective role of antioxidants against the development of several diseases and conditions recognized as risk factors for Alzheimer's disease (AD) is discussed in the present work. A variety of health behaviors, including an adequate supply of antioxidant micronutrients with the diet might help preventing AD directly, or indirectly through the mitigation of pathologic conditions associated with AD, such as vascular disease and diabetes.

Aging↗
PubMed2003

Cigarette smoking cessation increases plasma levels of several antioxidant micronutrients and improves resistance towards oxidative challenge.

Cigarette smoking is associated epidemiologically with increased risk of cardiovascular diseases, but the pathophysiological mechanisms are still not fully understood. There is evidence that smoking is related to increased free radical production and antioxidant depletion, but the effects of smoking cessation on plasma concentrations of antioxidants and susceptibility to oxidative stress are largely unknown. Plasma levels of vitamins A, C, E, uric acid, total thiols, carotenoids (including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) and malondialdehyde (MDA, a biomarker of lipid peroxidation) were measured in fifteen healthy, normolipidaemic subjects (seven males, eight females, 35.2 (sd 2.3) years) before and 4 weeks after smoking cessation. To determine plasma resistance towards oxidative challenge, plasma was incubated for up to 5 h with the peroxyl radical-generator 2,2'-azobis(2-amidinopropane) (AAPH); MDA and ascorbate levels were measured at various time points. The concentrations of all plasma antioxidants were lower before smoking cessation than afterwards; MDA levels were higher before than after termination of smoking. Upon AAPH exposure, the consumption of plasma ascorbate and the production of MDA occurred at a significantly faster rate before smoking cessation as compared with afterwards. Cigarette smoking cessation is followed by a marked increase in plasma antioxidant concentrations and substantially improves plasma resistance towards oxidative challenge. Given the importance of cigarette smoking as a risk factor for cardiovascular diseases and the pathophysiological role played by oxidative stress in these illnesses, quitting smoking represents an irreplaceable preventive strategy against tobacco-induced oxidative stress and vascular damage.

Antioxidants↗
PubMed2003

Cathepsin D polymorphism in Italian elderly subjects with sporadic late-onset Alzheimer's disease.

Alzheimer's disease (AD) is the most frequent cause of dementia in elderly people. Different pathological pathways have been involved in the development of late-onset AD. Among them, numerous genes have been proposed as pathogenetic factors acting independently or interactively. It has been suggested that the cathepsin D gene (CTSD) is associated with late-onset AD. We analyzed an exonic polymorphism of the CTSD gene [C-->T (Ala-->Val) transition at position 224] in 142 AD patients and 120 controls. Our data indicate no significant association between this polymorphism and the risk of AD. Likewise there was no association between CTSD polymorphism and the apolipoprotein E genotype in the risk of developing AD.

Age of Onset↗
PubMed2003

Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study.

Although recent epidemiological studies found a positive correlation between dietary vitamin C intake and bone mineral density, data on plasma levels of vitamin C or other antioxidants in osteoporotic subjects are scanty. The aim of this study was to evaluate whether antioxidant defenses are decreased in elderly osteoporotic women and, if this is the case, to understand whether osteoporosis is a condition characterized by increased oxidative stress. To answer these questions, plasma vitamins C, E, and A; uric acid; and the enzymatic activities of superoxide dismutase in plasma and erythrocytes and of glutathione peroxidase in plasma were measured in 75 subjects with osteoporosis and 75 controls. Dietary and endogenous antioxidants were consistently lower in osteoporotic than in control subjects. On the other hand, plasma levels of malondialdehyde, a byproduct of lipid peroxidation, did not differ between groups. Our results reveal that antioxidant defenses are markedly decreased in osteoporotic women. The mechanisms underlying antioxidant depletion and its relevance to the pathogenesis of osteoporosis deserve further investigation.

Activities of Daily Living↗
PubMed2002

Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease.

CONTEXT: A large body of experimental evidence suggests that in Alzheimer disease (AD) pathogenesis an important role is played by oxidative stress, but there is still a lack of data on in vivo markers of free radical-induced damage. OBJECTIVES: To evaluate levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage to DNA, in peripheral lymphocytes; to measure plasma concentrations of several nonenzymatic antioxidants; and to assess the relationships between any observed changes in lymphocyte DNA 8-OHdG content and plasma antioxidant levels in patients with AD and healthy aged control subjects. SUBJECTS: Forty elderly outpatients with AD and 39 healthy age- and sex-matched controls were studied. MAIN OUTCOME MEASURES: The level of 8-OHdG was determined in DNA extracted from lymphocytes and plasma levels of vitamin C, vitamin A, vitamin E, and carotenoids (zeaxanthin, beta-cryptoxanthin, lycopene, lutein, and alpha- and beta-carotene) were measured by high-performance liquid chromatography. RESULTS: Lymphocyte DNA 8-OHdG content was significantly higher and plasma levels of antioxidants (with the exception of lutein) were significantly lower in patients with AD compared with controls. In patients with AD, a significant inverse relationship between lymphocyte DNA 8-OHdG content and plasma levels of lycopene, lutein, alpha-carotene, and beta-carotene, respectively, was observed. CONCLUSIONS: Markers of oxidative damage are increased in AD and correlate with decreased levels of plasma antioxidants. These findings suggest that lymphocyte DNA 8-OHdG content in patients with AD reflects a condition of increased oxidative stress related to a poor antioxidant status.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Tocopherol metabolites 2, 5, 7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2, 7, 8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC) in human serum after a single dose of natural vitamin E.

BACKGROUND: alpha- and gamma-Tocopherol are vitamin E compounds in human blood and tissues. alpha-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman) and gamma-CEHC (2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman) have been identified as water-soluble metabolites which are excreted with the urine in humans. AIM OF THE STUDY: To assess over-time changes of serum levels of alpha- and gamma-CEHC in humans after a single dose of vitamin E from a natural source. METHODS: Twenty-one healthy subjects ingested a single dose of vitamin E (306 mg of RRR-alpha-tocopherol and 1.77 mg of gamma-tocopherol). Blood was collected before (baseline) and 2, 6, 12, 24, 35, 50, and 74 h after ingestion. Serum was separated and levels of alpha- and gamma-tocopherol and alpha- and gamma-CEHC were determined by HPLC. RESULTS: After vitamin E ingestion, a statistically significant increase was observed for alpha-tocopherol and alpha-CEHC. Maximum serum levels for both compounds were measured 12 h after application (33.3 +/- 11.1 micromol alpha-toco-pherol /L and 42.4 +/- 18.3 nmol alpha-CEHC /L); baseline values were reached again after 72 h. While gamma-tocopherol levels decreased during the study period, an increase in the metabolite gamma-CEHC was observed. The optical isomer formed in the metabolism of RRR-alpha-tocopherol was assigned as S-alpha-CEHC. CONCLUSIONS: alpha-CEHC levels increase after administration of a single dose of natural vitamin E in humans. The appearance of the metabolite in blood parallels that of the parent compound. The gamma-tocopherol analog appears to be metabolized more efficiently than alpha-tocopherol.

Adult↗
PubMed2002

In vitro antioxidant activity of 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC), a vitamin E metabolite.

2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) has been identified as a major water-soluble metabolite of vitamin E, which circulates in the blood and is excreted with the urine. The aim of this study was to assess the antioxidant activity of alpha-CEHC using several methods with different prooxidant challenges. In the Oxygen Radical Absorbance Capacity assay, a fluorescent protein acts as a marker for oxidative damage induced by peroxyl radicals. In the Trolox Equivalent Antioxidant Capacity (TEAC) assay, a stable free radical, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS.+) is reduced directly by antioxidants. Scavenging properties vs. reactive nitrogen species were studied measuring the effects on tyrosine nitration after reaction with peroxynitrite. Trolox, alpha-tocopherol, ascorbic acid, and (-)-epicatechin were simultaneously tested in order to compare their antioxidant activities. In all mentioned systems, alpha-CEHC exhibited antioxidant properties similar to those of Trolox. We conclude that alpha-CEHC is a molecule with good antioxidant activity, having the advantage over Trolox of being a naturally occurring compound. These properties might be useful for research or industrial purposes.

Antioxidants↗
PubMed2002

Plasma carotenoid and malondialdehyde levels in ischemic stroke patients: relationship to early outcome.

An association between ischemic stroke and increased oxidative stress has been suggested from animal studies. However, there is a lack of evidence with respect to this association in humans. Here, the time course of plasma levels of six carotenoids, which are lipophilic micronutrients with antioxidant properties, as well as of malondialdehyde (MDA), a marker of lipid peroxidation, was followed in ischemic stroke patients. Plasma levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, as well as MDA were measured by high-performance liquid chromatography in 28 subjects (19 men and nine women aged 76.9+/-8.7 years) with an acute ischemic stroke of recent onset (<24h) on admission, after 6 and 24 h, and on days 3, 5, and 7. Carotenoid and MDA levels in patients on admission were compared with those of age- and sex-matched controls. Plasma levels of lutein, lycopene, alpha- and beta-carotene were significantly lower and levels of MDA were significantly higher in patients in comparison with controls. Significantly higher levels of MDA and lower levels of lutein were found in patients with a poor early-outcome (functional decline) after ischemic stroke as compared to patients who remained functionally stable. These findings suggest that the majority of plasma carotenoids are lowered immediately after an ischemic stroke, perhaps as a result of increased oxidative stress, as indicated by a concomitant rise in MDA concentrations. Among the carotenoids, only lutein plasma changes are associated with a poor early-outcome.

Aged↗
PubMed2002

Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease.

Oxidative stress is believed to play a major role in the pathogenesis of Alzheimer disease (AD). Plasma concentrations of vitamins C, A and E, of uric acid, thiols and carotenoids were lower and of malondialdehyde (MDA) higher in 35 AD patients (85.9 +/- 5.5 y) compared to 40 controls 85.5 +/- 4.4 y). Differences were significant for vitamin C, vitamin E, lutein, lycopene, alpha-carotene and MDA (p < 0.001). Plasma exposed to peroxyl radicals showed a rate of antioxidant consumption and of MDA production higher in AD patients than in controls. AD in advanced age is accompanied by a poor plasma antioxidant status and increased plasma lipid peroxidation, as well as by a low resistance to peroxyl radical exposure.

Aged↗