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Lorenzo Ghiadoni

Publications and source records attributed to Lorenzo Ghiadoni.

At least 19 recordsLinked to original sources
PubMed2007

Ramipril dose-dependently increases nitric oxide availability in the radial artery of essential hypertension patients.

DESIGN AND PARTICIPANTS: A double-blind, crossover, randomized study was designed to evaluate the effect of 3-month treatment with a lower versus a higher antihypertensive dosage of ramipril (5 or 10 mg/day) on nitric oxide (NO)-dependent vasodilation in 46 untreated patients with essential hypertension. Radial artery flow-mediated dilation (FMD), before and after the intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA), to block NO synthase, and the response to sublingual glyceril trinitrate (GTN, 25 microg) were measured at baseline and after the two treatment periods as a change in artery diameter (computerized system from ultrasound scans). Plasma angiotensin II and oxidative stress markers were also assessed. RESULTS: FMD was significantly (P < 0.01) lower in hypertensive patients (4.6 +/- 1.8%) than in normotensive subjects (7.1 +/- 2.6%), whereas the response to GTN was similar. L-NMMA significantly (P < 0.001) inhibited FMD in normotensive but not in hypertensive subjects. Mean 24-h ambulatory blood pressure, plasma angiotensin II and oxidative stress marker levels were similarly reduced at the end of the two treatment periods. Both dosages of ramipril significantly (P < 0.001) increased FMD (5 mg: 5.9 +/- 2.1%; 10 mg: 6.3 +/- 2.4%) without modifying the response to GTN. However, compared with baseline (11 +/- 19%), the inhibiting effect of L-NMMA on FMD (NO-dependent FMD) was significantly (P < 0.01) greater with ramipril 10 mg (49 +/- 12%) than 5 mg per day (38 +/- 15%). The improvement in FMD and NO-dependent FMD was not related to changes in plasma levels of angiotensin II or markers of oxidative stress. CONCLUSION: Treatment with ramipril at a higher dosage induced a greater improvement in NO-dependent vasodilation compared with the lower antihypertensive dosage in hypertensive patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Soy protein diet improves endothelial dysfunction in renal transplant patients.

BACKGROUND: Since it has been demonstrated that soy diet can improve endothelial function, in the present study we evaluated the effect of dietary substitution of 25 g of animal proteins with soy proteins on endothelial dysfunction in renal transplant patients. METHODS: In 20 renal transplant patients (55 +/- 11 years, serum creatinine 1.7 +/- 0.6 mg/dl), brachial artery flow mediated dilation (FMD) and endothelium-independent vasodilation (sublingual nitroglycerine, 25 microg) were measured at baseline, after 5 weeks of a soy diet and finally after 5 weeks of soy wash-out. Changes in plasma lipids, markers of oxidative stress (lipid peroxides, LOOH) and inflammation (C-reactive protein), isoflavones (genistein and daidzein), asymmetric dimethyl arginine (ADMA) and L-arginine were also evaluated. RESULTS: At baseline, patients showed a significantly lower FMD as compared with age-matched healthy subjects (3.2 +/- 1.8 vs 6.3 +/- 1.9, respectively; P < 0.001), while response to nitroglycerine was similar. After soy diet, actual protein intake was not changed, cholesterol and lipid peroxides were significantly reduced, and isoflavones were detectable in plasma. Soy diet was associated with a significant improvement in FMD (4.4 +/- 2.0; P = 0.003 vs baseline), while response to nitroglycerine was unchanged. Improvement in FMD was related to L-arginine/ADMA ratio changes, but no significant relation was found to changes in cholesterol, lipid peroxides or genistein and daidzein plasma concentrations. After 5 weeks of soy diet discontinuation, FMD (3.3 +/- 1.7%) returned to baseline values and isoflavones were no longer detectable in plasma. CONCLUSIONS: A soy protein diet for 5 weeks improves endothelial function in renal transplant patients. This effect seems to be strictly dependent on soy intake as it disappears after soy withdrawal and is mediated by an increase in the L-arginine/ADMA ratio, independently of change in lipid profile, oxidative stress or isoflavones.

Adult↗
PubMed2006

Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto's thyroiditis.

OBJECTIVE: The objective of this study was to assess whether low-grade systemic inflammation might contribute to the pathogenesis of endothelial dysfunction in patients with subclinical hypothyroidism (sHT) and autoimmune thyroiditis. BACKGROUND: sHT patients are characterized by peripheral endothelial dysfunction and low-grade inflammation. METHODS: In 53 sHT and 45 healthy subjects, we studied the forearm blood flow (strain-gauge plethysmography) response to intrabrachial acetylcholine (Ach) (0.15-15 microg/min.dl) with and without local vascular COX inhibition by intrabrachial indomethacin (50 microg/min.dl) or nitric oxide synthase blockade by N-mono methyl arginine (L-NMMA) (100 microg/min.dl) or the antioxidant vitamin C (8 mg/min.dl). The protocol was repeated 2 h after systemic nonselective COX inhibition (100 mg indomethacin) or selective COX-2 blockade (200 mg celecoxib) oral administrations. RESULTS: sHT patients showed higher C-reactive protein and IL-6 values. In controls, vasodilation to Ach was blunted by L-NMMA and unchanged by vitamin C. In contrast, in sHT, the response to Ach, reduced in comparison with controls, was resistant to L-NMMA and normalized by vitamin C. In these patients, systemic but not local indomethacin normalized vasodilation to Ach and the inhibition of L-NMMA on Ach. Similar results were obtained with celecoxib. When retested after indomethacin administration, vitamin C no longer succeeded in improving vasodilation to Ach in sHT patients. Response to sodium nitroprusside was unchanged by indomethacin or celecoxib. CONCLUSIONS: In sHT patients, low-grade chronic inflammation causes endothelial dysfunction and impaired nitric oxide availability by a COX-2-dependent pathway leading to increased production of oxidative stress.

Acetylcholine↗
PubMed2006

Recombinant human thyrotropin reduces endothelium-dependent vasodilation in patients monitored for differentiated thyroid carcinoma.

AIM: We evaluated endothelial-dependent vasodilation after administration of recombinant human TSH (rhTSH) in patients monitored for differentiated thyroid carcinoma. The role of inflammation and oxidative stress was also assessed. PROTOCOL: Twenty-four patients (21 women, mean age 40.5 +/- 9.2 yr) received rhTSH (0.9 mg daily) on 2 consecutive days. At baseline and the day after the second rhTSH injection, endothelium-dependent vasodilation as flow-mediated dilation (FMD, induced by 5 min of forearm ischemia) and endothelium-independent vasodilation (glyceril trinitrate 25 microg, sublingual) were evaluated by high-resolution ultrasound in the brachial artery. At each experimental time, blood was drawn for the evaluation of thyroglobulin, TSH, free T(3), free T(4), as well as IL-6, C reactive protein, TNFalpha, lipoperoxides, and ferric reducing antioxidant power levels as markers of inflammation and oxidative stress. RESULTS: At baseline, patients' serum TSH values were below the normal range [0.12 mIU/liter (range 0.01-0.30)] in the face of normal free T(4) and free T(3) levels; FMD (8.9 +/- 3.4 vs. 9.2 +/- 3.1%, respectively) and response to glyceril trinitrate (11.0 +/- 4.3 vs. 10.8 +/- 4.7%, respectively) were similar in patients and controls. All the patients had serum thyroglobulin value less than 1 ng/ml, suggesting the absence of cancer recurrences. Besides the expected elevation of serum TSH, rhTSH induced a significant impairment of FMD (7.4 +/- 3.0 vs. 8.9 +/- 3.4%; P < 0.01) along with a significant elevation of blood IL-6 (P = 0.01), TNFalpha (P < 0.001), and lipoperoxide levels (P = 0.01), as well as a reduction of ferric reducing antioxidant power (P = 0.01). CONCLUSIONS: rhTSH administration acutely impaired endothelium-dependent vasodilation, possibly through the induction of low-grade inflammation and reduced nitric oxide availability by oxidative stress.

Adult↗
PubMed2006

Identification of a cytochrome P450 2C9-derived endothelium-derived hyperpolarizing factor in essential hypertensive patients.

OBJECTIVES: We assessed the role of cytochrome P450 2C9 (CYP 2C9)-derived endothelium-derived hyperpolarizing factor (EDHF) in the forearm microcirculation of essential hypertensive patients (EH) by utilizing sulfaphenazole (SUL), a selective CYP 2C9 inhibitor. BACKGROUND: In EH patients, EDHF acts as a compensatory pathway when nitric oxide (NO) availability is reduced. Cytochrome P450 2C9 is a possible source of EDHF. METHODS: In 36 healthy subjects (normotensive [NT]) and 32 hypertensive patients (HT), we studied forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (ACH) and bradykinin (BDK), repeated during N(G)-monomethyl-L-arginine (L-NMMA) (100 mug/100 ml/min) or SUL (0.03 mg/100 ml/min). In HT, the effect of SUL on ACH and BDK was repeated during vitamin C (8 mg/100 ml/min). Sodium nitroprusside (SNP) was utilized as control. RESULTS: In NT, vasodilation to ACH and BDK was blunted by L-NMMA and not changed by SUL. In contrast, in HT responses to ACH and BDK, reduced compared with NT, were resistant to L-NMMA. In these patients, SUL blunted vasodilation to ACH and to a greater extent the response to BDK. When retested with vitamin C, SUL was no longer effective on both endothelial agonists. In 2 final groups of normotensive control subjects, vasodilation to ACH or BDK residual to cyclooxygenase and L-NMMA blockade was further inhibited by simultaneous SUL infusion. Response to SNP, similar between NT and HT, was unaffected by SUL. CONCLUSIONS: Cytochrome P450 epoxygenase-derived EDHF acts as a partial compensatory mechanism to sustain endothelium-dependent vasodilation in HT, particularly the BDK-mediated response, when NO activity is impaired because of oxidative stress.

Acetylcholine↗
PubMed2006

Vascular reactivity in congenital hypogonadal men before and after testosterone replacement therapy.

CONTEXT: The contribution of endogenous testosterone (TS) in the functional integrity of peripheral circulation in men was studied. OBJECTIVE: The objective of this study was to observe vascular reactivity in male congenital hypogonadal patients before and after prolonged exposure to normal TS levels. DESIGN: This was a longitudinal study in which, basically and after 6-month (range, 6-8 months) androgen treatment, we investigated forearm blood flow (strain-gauge plethysmography) changes induced by intraarterial acetylcholine (Ach), alone or in the presence of N(G)-monomethyl-l-arginine infusion, and by sodium nitroprusside. We also evaluated, by Doppler ultrasound, flow-mediated dilation of the brachial artery (BA) in response to reactive hyperemia (RH) and glyceryl trinitrate (GTN). SETTING: The studies were conducted at university referral centers for andrologic and blood pressure diseases. PATIENTS: Eight adult male Caucasian hypogonadal patients and nine healthy matched control subjects were studied. INTERVENTION: Intervention was TS enanthate (250 mg in 1 ml oily solution) by im injection every 3 wk. RESULTS: At baseline, BA diameter and RH, flow-mediated dilation, and GTN responses showed no difference between the two groups. TS therapy increased plasma total TS (P < 0.02) and reduced high-density lipoprotein (P < 0.01) and total cholesterol (P < 0.04). It did not affect vasodilation to sodium nitroprusside (355 +/- 47%), but it further reduced the vascular response to Ach (187 +/- 29%, P < 0.01 vs. baseline) and abolished the inhibition by N(G)-monomethyl-l-arginine on Ach (inhibition, 3.2%). Moreover, TS therapy decreased (P < 0.01) flow-mediated dilation, whereas it did not modify BA diameter and responses to RH and GTN. CONCLUSIONS: Hypogonadal patients show impaired vascular reactivity, including endothelial-dependent vasodilation due to reduced nitric oxide availability. TS administration further impairs nitric oxide availability in these patients.

Adult↗
PubMed2006

Carotid vascular remodeling in patients with pheochromocytoma.

CONTEXT: The influence of catecholamines on vascular remodeling in humans was investigated. OBJECTIVE: The objective was to study the carotid vascular wall in patients with pheochromocytoma (PHEO). DESIGN AND SETTING: An observational study was conducted in a university referral center for blood pressure diseases. PATIENTS: Fourteen patients with PHEO, 15 matched high-normal essential hypertensives, 15 mild essential hypertensives, and 15 controls underwent two-dimensional conventional ultrasonography and ultrasonic tissue characterization of the carotid wall. MAIN OUTCOME MEASURES: Intimal media thickness (IMT), diameter, and corrected ultrasonic integrated backscatter signal (C-IBS) of carotid arteries were evaluated. RESULTS: IMT in PHEOs (0.844 +/- 0.18 mm, mean +/- sd) was greater than not only controls (0.596 +/- 0.09 mm, P < 0.0002) but also high-normal (0.710 +/- 0.17 mm, P < 0.03), and even mild (0.727 +/- 0.20 mm, P = 0.06) hypertensives. IMT in the latter was higher than in controls (P < 0.03), without difference in comparison with high-normal hypertensives. C-IBS values in PHEOs (-21.71 +/- 2.0 dB, mean +/- sd) were greater than in controls (-26.20 +/- 1.73 dB, P < 0.0001) but also than in high-normal (-23.84 +/- 1.16 dB, P < 0.002) and mild (-23.37 +/- 1.99 dB, P < 0.01) hypertensives. C-IBS values in controls were lower than in high-normal (P < 0.0005) and mild (P < 0.0001) hypertensives. Carotid diameter was not significantly different in the four groups. In PHEOs, C-IBS was associated with urinary noradrenaline (r = 0.640, P < 0.01) and normethanephrine (r = 0.737, P < 0.009). CONCLUSIONS: Carotid IMT of PHEOs is higher than in controls and matched groups of hypertensives with comparable or even higher blood pressure. This vascular rearrangement is characterized by increased IBS values due to collagen deposition and vascular fibrosis. Therefore, our data show that abnormal catecholamine levels take part per se in carotid wall remodeling of patients with PHEO.

Adrenal Gland Neoplasms↗
PubMed2006

Endothelium, aging, and hypertension.

Endothelium plays a primary role in modulating vascular tone and structure through production of the relaxing factor nitric oxide (NO), which also protects the vessel wall against the pathogenesis of atherosclerosis and thrombosis. A dysfunctioning endothelium due to reduced NO availability and increased production of oxidative stress is considered an early indicator of atherothrombotic damage and of cardiovascular events. Aging is associated with the development of cardiovascular structural and functional alterations, which can explain the age-related increase in cardiovascular risk. Advancing age is associated with endothelial dysfunction in both normotensive subjects and essential hypertensive patients, an alteration caused by a progressive impairment of the NO pathway and production of oxidative stress. Once oxidative stress production becomes detectable, NO availability is totally compromised. Essential hypertension represents a mere acceleration of the changes induced by aging on endothelial function. Currently, dynamic physical activity represents the only effective intervention in preventing age-related impaired endothelium-dependent vasodilation in aged healthy individuals.

Aging↗
PubMed2006

Tissue kallikrein gene polymorphisms induce no change in endothelium-dependent or independent vasodilation in hypertensive and normotensive subjects.

BACKGROUND: Tissue kallikrein (TK) generates Lys-bradykinin, which is then converted to bradykinin and releases nitric oxide (NO) from endothelial cells via B2 receptors. TK gene inactivation in mice causes severe endothelial dysfunction, which is also a hallmark of human primary hypertension (PH). Healthy carriers of a loss-of-function Arg to His substitution at position 53 (R53H) of the TK gene exhibit paradoxical arterial eutrophic remodeling. We therefore investigated the impact of this and other TK gene single nucleotide polymorphisms (SNPs) on endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIV) in PH patients and normotensive (NT) subjects. METHODS: The TK gene SNPs were genotyped blind to the phenotype by sequencing. We compared EDV and EIV vasodilatation across TK genotypes in 131 uncomplicated PH patients and 51 healthy NT subjects. EDV and EIV were assessed as the forearm blood flow response to a graded infusion of acetylcholine and sodium nitroprusside, respectively. We also evaluated the impact of the SNPs on NO-mediated EDV and on reactive oxygen species (ROS)-induced NO breakdown with the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine or vitamin C, respectively. RESULTS: Genotypes and allele frequencies were in Hardy-Weinberg equilibrium and similar in PH and NT. EDV was lower in PH patients than in NT subjects. No TK genotype affected either EDV or EIV per se, or via interaction with gender and age. NO inhibition and scavenging of ROS showed no TK genotype effect on EDV. Similar conclusions were obtained with haplotype analysis. CONCLUSIONS: These results do not support the contention that TK gene SNPs have a major impact in determining NO-mediated responses to acetylcholine.

Adult↗
PubMed2006

Which endothelium-derived factors are really important in humans?

The endothelium plays a primary role in the local control of vascular function and structure, mainly by the production and release of NO, a potent vasodilator that also inhibits all the mechanisms involved in the pathogenesis of atherosclerosis, thus protecting the vessel wall against the development of atherosclerosis and thrombosis. Cardiovascular risk factors are associated with endothelial dysfunction, which involves enhanced production of oxygen free radicals that reduce NO availability and the release of contracting factors, including prostanoids and endothelin-1. In humans, endothelium-dependent relaxation can be assessed by tests that explore vascular reactivity. Besides the degree of vasodilation, which represents a crude estimate of endothelial function, the utilization of a complex experimental design, requiring the administration of specific agonists and antagonists, allows detailed exploration of the mediators and mechanisms involved in endothelium-dependent vasodilation. At present, the degree of endothelium-dependent vasodilation (evoked by receptor-operated agonists or the application of mechanical forces) is considered an independent predictor of cardiovascular events. In contrast, scant information is available concerning the clinical relevance of different mediators involved in endothelial function. Further studies are needed in the future to assess the specific impact of different endothelial responses on the clinical outcome in patients with cardiovascular risk factors and disease.

Biological Factors↗
PubMed2006

Thiazide diuretics in the treatment of hypertension: an update.

Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients, the following considerations should be taken into account. Although there are some indications that chlorthalidone can offer additional advantages as compared with other compounds, a recent meta-analysis of placebo-controlled trials suggested that the beneficial effects of thiazide diuretics could be a class effect. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes, in whom thiazide diuretics should be used at the lowest active dose and possibly in combination with drugs that block the renin-angiotensin system. Finally, the current debate on whether thiazide diuretics are the first-choice drug for most patients with uncomplicated hypertension, as stated in the Seventh Joint National Committee Report, or are included in the major classes of antihypertensive agents that are suitable for initiation and maintenance of therapy, as reported in the European Society of Hypertension-European Society of Cardiology Guidelines, derives from different interpretations of controlled clinical trial data on drug class comparison and of cost-benefit analyses. However, considering that the benefit of antihypertensive drugs seems to be due principally to BP lowering per se without definitive evidence of the superiority of a particular drug class and that there is no cost-benefit analysis showing the superiority of thiazide diuretics, it is believed that these drugs should not be considered as the only first-choice drug but included among first-choice drugs.

Antihypertensive Agents↗
PubMed2006

[Obesity and endothelial dysfunction].

The endothelium plays a crucial role in modulating vascular function and structure. In healthy conditions, nitric oxide produced by endothelial cells exerts not only vasodilating properties, but also several other protective actions toward the vessel wall against the development of atherosclerosis and thrombosis. Traditional cardiovascular risk factors are characterized by endothelial dysfunction caused by an enhanced production of oxidative stress leading to destroy nitric oxide, thus reducing its availability. Abdominal obesity is associated with endothelial dysfunction, through direct mechanisms, such as insulin resistance and the association with risk factors (including diabetes mellitus, hypertension and dyslipidemia), and direct, by the production of adipokines and pro-inflammatory cytokines, which in turn induce oxidative stress leading to a reduced nitric oxide availability. A reduced endothelium-dependent relaxation is a predictor of cardiovascular events in high-risk patients and represents a putative clinical parameter to stratify the cardiovascular risk and a useful marker for therapy efficacy. Weight loss and a modification of lifestyle ameliorate endothelial function in obese patients, an effect due not only to a better glycemic profile, but also secondary to reduced plasma levels of inflammatory markers and adipokines. At present, whether an improvement of endothelial dysfunction secondary to weight loss is significantly associated with a better cardiovascular prognosis is still unknown. (G Ital Cardiol 2006; 7 (11): 715-723)

Cytokines↗
PubMed2005

Interleukin-8 is a powerful prognostic predictor of all-cause and cardiovascular mortality in dialytic patients.

BACKGROUND: Cohort studies have demonstrated an association between C-reactive protein (CRP) and interleukin-6 (IL-6) and all-cause and cardiovascular mortality in end-stage renal disease (ESRD) patients. Interleukin-8 (IL-8) appears to be not only the plasma expression of the acute-phase response but also a direct pathogenetic mediator of the atherosclerotic process. METHODS: To evaluate the role of IL-8 in predicting outcome, 76 chronic dialytic patients were prospectively followed for 18 months. At baseline, blood samples were taken for analysis of high-sensitivity CRP, IL-6, IL-8 and other standard laboratory analyses. RESULTS: Median IL-8 was 5.2 mg/l, therefore near half of the patients had IL-8 values within the range of 'normal limits'. IL-6 and CRP were significantly correlated (r = 0.45, p < 0.001) and a positive correlation was also found between IL-6 and IL-8 (r = 0.39, p < 0.001). The correlation coefficient between IL-6 and CRP was 0.43 (p < 0.001) and 0.50 (p < 0.001) in patients without and with history and/or clinical signs of cardiovascular disease, respectively. After a follow-up of 1.5 years, 8 patients had died from cardiovascular causes and another 7 patients for other reasons; furthermore 9 major nonfatal cardiovascular events were recorded. Stepwise regression analysis showed IL-8 as the strongest independent predictor of all-cause and cardiovascular events (p = 0.0025) even after adjustment for age and dialytic age, followed by IL-6 and CRP (p < 0.01). CONCLUSION: Despite a small population and a relatively short follow-up period, this study firstly demonstrated that IL-8 is a powerful independent predictive factor for cardiovascular and overall mortality cause in ESRD patients.

Aged↗
PubMed2005

Endothelium-dependent vasodilation and carotid artery wall remodeling in athletes and sedentary subjects.

In this study, the relationship between age, carotid artery remodeling, and endothelium-dependent vasodilation is investigated in sedentary subjects and athletes. Thirty-two young and old healthy sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring intima-media thickness (IMT) and corrected integrated backscatter (C-IBS), two early indicators of the atherosclerosis process. Endothelium-dependent vasodilation was assessed by intra-brachial acetylcholine (strain-gauge plethysmography), at baseline and during NO sythase inhibitor NG-monomethyl-L-arginine (L-NMMA), and the antioxidant Vitamin C. Response to sodium nitroprusside (SNP) was also evaluated. Independently of trained status, IMT and C-IBS were higher in older than in young individuals (p<0.0001), while response to acetylcholine, but not to SNP, was lower (p<0.0001). Older athletes showed lower IMT, lower C-IBS (p<0.0001), greater response to acetylcholine (p<0.0001), and greater inhibition of acetylcholine by L-NMMA (p<0.001) than older controls. Only in older sedentary individuals, Vitamin C increased response to acetylcholine (p<0.001) and restored the inhibiting effect of L-NMMA (p<0.01). In the whole population maximal acetylcholine-induced vasodilation was inversely related to IMT (r=-0.60, p<0.0001) and to C-IBS (r=-0.56, p<0.0001). In conclusion, regular physical training can attenuate the age-related impairment of endothelium-dependent vasodilation, which is related to an attenuation of the age-induced remodeling of the carotid wall.

Acetylcholine↗
PubMed2005

Characterization and quantification of soy isoflavone metabolites in serum of renal transplanted patients by high-performance liquid chromatography/electrospray ionization mass spectrometry.

During a dietary intervention study on 16 renal transplanted patients, in which 25 g/day of animal proteins were replaced with 25 g of soy proteins, the metabolic profile of soy isoflavones in serum was characterized. This paper describes a reliable and fast liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) method, in negative ion mode, allowing the characterization and simultaneous quantification of several soy isoflavone metabolites. Six metabolites were identified and quantified: daidzein ([M-H](-) at m/z 252.8), dihydrodaidzein (DHD, [M-H](-) at m/z 254.8), equol ([M-H](-) at m/z 240.9), O-desmethylangolensin (O-DMA, [M-H](-) at m/z 256.8), genistein ([M-H](-) at m/z 268.8), and dihydrogenistein (DHG, ([M-H(+)](-) at m/z 270.8). Quantification was assessed using two deuterated internal standards, D(3)-daidzein and D(4)-genistein. This method permitted a limit of quantification (LOQ, S/N = 10) and a limit of detection (LOD, S/N = 3) of 0.05 microM and 0.005 microM for all analytes, except for genistein, where the LOQ and LOD were 0.005 microM and 0.001 microM, respectively. The linearity ranges were from 0.005 to 1.5 microM for genistein, from 0.05 to 1.5 microM for DHG, and from 0.05 to 0.7 microM for the other metabolites. The relative standard deviations (RSDs) were between 0.19% and 13.9% at the LOQ concentration for all metabolites, and between 0.6% and 4.8% at the maximum concentration. On the basis of the results obtained in the dietary intervention study, it was possible to split the patients into five groups characterized by different metabolic pathways.

Adult↗
PubMed2005

Physical activity, plasma antioxidant capacity, and endothelium-dependent vasodilation in young and older men.

BACKGROUND: Sedentary aging is associated with oxidative stress and endothelial dysfunction. The aim of this study was to evaluate the relationship between long-term physical activity, plasma antioxidant status, and conduit artery endothelial function in young and older healthy men. METHODS: In young (n = 16) and older athletes (n = 16) and in matched healthy sedentary subjects, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent response to glyceryl trinitrate (GTN), 400 microg, were measured in the brachial artery from high-resolution ultrasonography. Plasma malondialdehyde (MDA) and antioxidant capacity as total oxyradical scavenging capacity (TOSC) were also evaluated. RESULTS: We found that FMD was lower (< or =0.01) in sedentary older subjects (2.3% +/- 1.0%) as compared with older athletes (5.3% +/- 3.2%) and both sedentary (5.4% +/- 2.0%) and athletically trained (6.1% +/- 3.2%) young subjects. Sedentary older subjects showed higher (P < or = .05) MDA levels and lower (P < .0001) plasma antioxidant capacity as compared with the other subgroups, whereas in older athletes MDA levels and antioxidant capacity were similar to those observed in the young subgroups. In the whole group, FMD, but not GTN, was negatively related to age (r = -0.31, P < .05) and directly related (P < or = .01) to VO2max (r = 0.49) and TOSC against peroxyl (r = 0.69) and hydroxyl radicals (r = 0.53). In the multivariate analysis, TOSC against peroxyl radicals resulted as the most significant predictor of FMD (R2 = 0.60; P = .003). CONCLUSIONS: These results suggest that regular physical activity is associated with preserved antioxidant defenses and endothelial function in older individuals.

Adult↗