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Rodolfo Paoletti

Publications and source records attributed to Rodolfo Paoletti.

At least 19 recordsLinked to original sources
PubMed2006

Levels of the n-3 fatty acid eicosapentaenoic acid in addition to those of alpha linolenic acid are significantly raised in blood lipids by the intake of four walnuts a day in humans.

BACKGROUND AND AIMS: Ingestion of alpha linolenic acid (ALA), with the richest source among dry fruits such as walnuts, is associated with cardiovascular prevention. The aim of this study was to selectively evaluate the effects of moderate walnut consumption on the levels of ALA and its metabolic derivatives in human blood. METHODS AND RESULTS: After a 2-week run-in period, 10 volunteers consumed 4 walnuts per day (in addition to their habitual diet) for 3 weeks. Fatty acid profiles, with special attention to levels of ALA and long chain polyunsaturated fatty acids (LC-PUFA), were assessed in blood drops collected from fingertips. The data indicate that the administration of a few walnuts a day for 3 weeks significantly increases blood levels, not only of ALA (from 0.23+/-0.07 SD to 0.47+/-0.13 SD), but also of its longer chain derivative eicosapentaenoic acids (EPA) (from 0.23+/-0.37 to 0.82+/-0.41) with levels remaining elevated over basal values after washout. CONCLUSION: The findings of this pilot study indicate that plant ALA in appropriate food items favourably affects the n-3 LC-PUFA status.

Adult↗
PubMed2006

Activation of NF-kB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment.

We investigated the effects of simvastatin treatment on the expression of IL-1beta and MCP-1, the activity of NF-kB, and the signaling pathways related to NF-kB activation in a rat model of permanent middle cerebral artery occlusion (pMCAO). IL-1beta and MCP-1 expression, determined using RT-PCR, was enhanced by pMCAO; this effect was inhibited by the administration of simvastatin before ischemia. Pre-treatment with simvastatin abolished the ischemia-induced activation of NF-kB observed in vehicle-treated animals. The evaluation of signal transduction pathways, including extracellular signal-regulated kinase (ERK1/2), SAPK/JNK 46/54 and p38, indicated that only ERK1/2 phosphorylation was enhanced by ischemia, and this activation was prevented by simvastatin. ERK1/2-inhibitor, U0126, reduced brain ischemia but not cytokine induction. These results provide evidence that the HMG-CoA reductase inhibitor induces its effect in the protection of ischemic brain damage with a more complex mechanism which also involve anti-inflammatory properties rather than simple inhibition of ERK1/2 signaling pathway.

Animals↗
PubMed2006

Recombinant apolipoprotein A-IMilano for the treatment of cardiovascular diseases.

Apolipoprotein A-I(Milano) (apoA-I(M)) is a natural variant of apoA-I characterized by a cysteine for arginine substitution at position 173 of the primary sequence. ApoA-I(M) carriers have much less atherosclerosis than expected from their very low plasma high-density lipoprotein (HDL) cholesterol levels, suggesting that the variant might be protective. Synthetic HDL (sHDL) made with a recombinant form of the dimeric A-I(M) (A-I(M)/A-I(M)) and phospholipids given in single or multiple injections is effective in inducing the regression of atherosclerotic plaques, preventing arterial restenosis, and limiting cardiac dysfunction after ischemia/reperfusion injury. In a phase II trial in patients with acute coronary syndromes, a short-term treatment with A-I(M)/A-I(M) sHDL caused a remarkable reduction of atheroma burden. Although at early stages of drug development, A-I(M)/A-I(M) sHDL holds vast promise for the treatment of a variety of cardiovascular diseases in humans.

Animals↗
PubMed2006

Biomarkers for atherosclerosis: pathophysiological role and pharmacological modulation.

PURPOSE OF REVIEW: The aim of this article is to discuss the potential value of biomarkers for atherosclerosis in the assessment of risk for cardiovascular disease, in the pathogenesis of atherosclerosis, and in the monitoring of pharmacological treatment. RECENT FINDINGS: In an attempt to improve global cardiovascular risk prediction, considerable effort has been made in the discovery and characterization of soluble biomarkers which can go beyond the measure of total and LDL cholesterol levels. In particular, circulating molecules related to chronic inflammation have emerged as potential biomarkers for atherosclerosis. Evidence, obtained from in-vitro and in-vivo experimental models, has also documented that the majority of biomarkers play a pathological role in atherogenesis. Multiple screening of different biomarkers may therefore improve the assessment of risk, diagnosis, and prognosis for cardiovascular disease. In addition, soluble biomarkers have been shown to be modulated by hypolipidemic drugs and to be potentially useful in determining the clinical benefits of pharmacological therapies that do not alter serum lipid levels. SUMMARY: Altered levels of soluble biomarkers are associated with cardiovascular disease, and profiling of multiple biomarkers for atherosclerosis will be a useful indicator for better risk assessment, diagnosis, and prognosis, as well as monitoring pharmacological treatments for atherosclerosis.

Atherosclerosis↗
PubMed2006

The emerging link between nutrition, inflammation and atherosclerosis.

A number of dietary components modulate the inflammatory response in humans, thereby affecting cardiovascular risk. As basic research provides a better understanding of the molecular mechanisms of vascular function regulation by nutrients, clinical investigation and outcome studies demonstrate the relevance of dietary factors to the prevention and treatment of vascular disease. Benefits of dietary interventions may be attributable to weight loss or to more specialized mechanisms in which inflammation is targeted directly. Available evidence indicates that dietary intervention should be an integral part of therapeutic approaches for treating conditions such as the metabolic syndrome and, ultimately, for the prevention of cardiovascular disease.

Alcohol Drinking↗
PubMed2005

Rosuvastatin, but not simvastatin, provides end-organ protection in stroke-prone rats by antiinflammatory effects.

OBJECTIVE: Brain abnormalities, preceded by a systemic inflammation, develop in spontaneously hypertensive stroke-prone rats (SHRSP). In this model, we investigated whether the hydrophilic statin, rosuvastatin, influences the development of inflammation associated with brain abnormalities. Because differences in hydrophilicity/hydrophobicity contribute to the differences in statin pharmacology, we also evaluated the effects of simvastatin, a lipophilic molecule METHODS AND RESULTS: SHRSP, fed a high-salt diet, were treated long-term with vehicle or rosuvastatin (1 and 10 mg/kg per day). Brain abnormalities developed after 40+/-5 days and after 60+/-5 days of salt loading, in vehicle-treated and in rosuvastatin-treated (1 mg/kg per day) SHRSP, respectively. After 100 days of treatment, no damage was detectable in 30% of the rats treated with the highest dose of the drug. In comparison with vehicle-treated SHRSP, rosuvastatin treatment attenuated the transcription of monocyte chemoattractant protein-1, transforming growth factor-beta1, IL-1beta, and tumor necrosis factor-alpha in the kidney, and of P-selectin in brain vessels and increased the transcription of endothelial nitric oxide synthase mRNA in the aorta. Urinary excretion of acute-phase proteins increased with time in vehicle-treated animals but remained negligible in drug-treated animals. These effects are independent of changes in physiological parameters. Treatment of SHRSP with simvastatin (2 to 20 mg/kg per day) did not exert any protective effect. CONCLUSIONS: Rosuvastatin attenuates inflammatory processes associated with cerebrovascular disease.

Acute-Phase Proteins↗
PubMed2005

Implications of emerging risk factors for therapeutic intervention.

Recently, the National Cholesterol Education Panel (NCEP) of the United States of America commented on the implications of new clinical trials for the Adult Treatment Panel III (ATP III) guidelines. In this commentary, new categories of "moderately high" and "very high" coronary risk were proposed with new "therapeutic options" for low-density lipoprotein (LDL) cholesterol of < or = 100 mg/dL and < or = 70 mg/dL respectively. In ATP III, these "moderately high" risk patients had been classified as moderate risk with an LDL treatment goal of < or = 130 mg/dL, while the "very high" risk patients had been classified as high risk with a treatment goal of < or = 100 mg/dL. Risk classification in the new NCEP publication is based essentially on the combination of the Framingham risk score plus counting of classical risk factors. In the present document, the International Task Force for Prevention of Coronary Heart Disease responds to this NCEP commentary and supports the suggestion of more intensive LDL cholesterol lowering in particular cases. However, the Task Force feels that a classification based on a combination of a risk score plus a count of emerging risk factors is a more logical way to identify such patients requiring lower LDL cholesterol levels than a scheme in which classical risk factors are taken into account twice, once in a count and once in a risk score.

Advisory Committees↗
PubMed2004

Analysis of pathological events at the onset of brain damage in stroke-prone rats: a proteomics and magnetic resonance imaging approach.

Spontaneously hypertensive stroke-prone rats (SHRSP) develop brain abnormalities invariably preceded by the accumulation of acute-phase proteins in body fluids. This study describes the sequence of pathological events, and in particular the involvement of inflammation, at the onset of brain injury in this animal model. In SHRSP subjected to permissive dietary treatment, the appearance of brain damage and of altered permeability of the blood-brain barrier (BBB) was monitored over time by magnetic resonance imaging (MRI) after intravenous injection of gadolinium. The protein content in cerebrospinal fluid and brain extracts was analyzed by two-dimensional electrophoresis. Gadolinium diffusion showed impairment of the BBB after 42 +/- 3 days from the start of salt loading, simultaneously with the detection of brain abnormalities by MRI. Tissue lesions were initially localized at one or more small foci and then spread throughout the brain in the form of fibrinoid necrosis. This type of lesion is characterized by fibrin deposition, in particular around the vessels; loss of tissue texture; and infiltration of macrophages and lymphocytes. High levels of plasma-derived proteins of molecular mass up to >130 kDa were detected in the cerebrospinal fluid after MRI had revealed brain abnormalities. Plasma proteins extravasated from brain vessels were immunodetected in tissue homogenates from affected areas. The results obtained in this study provide new insights into the pathogenesis of the spontaneous brain damage in SHRSP and in particular on the involvement of the inflammatory cascade. These studies may be useful in evaluating new pharmacological strategies aimed at preventing/treating brain diseases.

Animals↗
PubMed2004

Inflammation in atherosclerosis and implications for therapy.

Atherosclerosis is now understood to be a disease characterized by inflammation that results in a host of complications, including ischemia, acute coronary syndromes (unstable angina pectoris and myocardial infarction), and stroke. Inflammation may be caused by a response to oxidized low-density lipoproteins, chronic infection, or other factors; and markers of this process, such as C-reactive protein, may be useful to predict an increased risk of coronary heart disease. Thus, we believe that inflammatory processes may be potential targets of therapy in preventing or treating atherosclerosis and its complications.

Acute-Phase Reaction↗
PubMed2004

Safety of statins: focus on clinical pharmacokinetics and drug interactions.

Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, however, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions.

Binding, Competitive↗
PubMed2004

Statins effect on smooth muscle cell proliferation.

Clinical trials have firmly established that 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors (statins) can induce regression of vascular atherosclerosis as well as reduction of cardiovascular-related morbidity and death in patients with and without coronary artery disease. These beneficial effects of statins are usually assumed to result from their ability to reduce cholesterol synthesis. However, because mevalonic acid is the precursor not only of cholesterol but also of many nonsteroidal isoprenoid compounds, inhibition of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase may result in pleiotropic effects. Indeed, statins can interfere with major events involved in the formation and the evolution of atherosclerotic lesions, such as arterial myocyte migration and proliferation and cholesterol accumulation, independent of their hypolipidemic properties. The aim of this article is to focus on clinical and experimental data that show that statins possess effects beyond cholesterol lowering, particularly on arterial smooth muscle cell proliferation. The contribution of these direct vascular effects to the reduction of cardiovascular events observed in clinical trials with statins represents one of the major challenges for future studies to understand the antiatherosclerotic benefits of these agents.

Animals↗
PubMed2003

Efficacy of rosuvastatin 10 mg in patients with the metabolic syndrome.

The constellation of risk factors known as the metabolic syndrome increases the risk of coronary artery disease at any low-density lipoprotein (LDL) cholesterol level. We performed an exploratory analysis of data from 5 trials to study the effects of rosuvastatin 10 mg on lipid levels and ratios in hypercholesterolemic patients (LDL cholesterol > or =160 mg/dL and <250 mg/dL) who met a modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition of the metabolic syndrome. Of 580 patients completing 12 weeks of treatment with rosuvastatin 10 mg, 194 (33%) met the definition of the metabolic syndrome by exhibiting > or =3 of the following: body mass index >30; triglycerides > or =150 mg/dL; high-density lipoprotein (HDL) cholesterol <40 mg/dL in men and <50 mg/dL in women; blood pressure > or =130/> or =85 mm Hg or receiving current medication for hypertension; and fasting blood glucose > or =110 mg/dL. Patients with the metabolic syndrome had higher triglyceride, non-HDL cholesterol, apolipoprotein B, and lipid ratios, and lower HDL cholesterol and apolipoprotein A-I levels, at baseline compared with patients without the metabolic syndrome. In patients with the metabolic syndrome, rosuvastatin 10 mg improved LDL cholesterol (-47%), non-HDL cholesterol (-43%), non-HDL cholesterol/HDL cholesterol ratio (-47%), apolipoprotein B (-37%), apolipoprotein B/apolipoprotein A-I ratio (-40%), triglycerides (-23%), apolipoprotein A-I (+7%), and HDL cholesterol (+10%)-in a manner similar to that in hypercholesterolemic patients who did not meet these criteria. Among patients who met the metabolic syndrome criteria and who had triglycerides > or =200 mg/dL, 64% met their ATP III non-HDL goals.

Adult↗
PubMed2003

Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage.

OBJECTIVE: In the present study, MRI has been used to investigate therapeutic intervention with statins in a model of permanent focal cerebral ischemia in rat. METHODS AND RESULTS: Brain ischemia was induced in rats by the permanent occlusion of middle cerebral artery (MCAO) and the brain infarct size followed up in alive animals 2, 24, and 48 hours after MCAO, using the trace of apparent diffusion coefficient [Tr(D)] maps and T2-weighted images. In vehicle-treated rats, the infarct volumes increased by 38.5% and 89% after 24 and 48 hours, respectively, compared with the damage detected at 2 hours after MCAO. Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours. This effect was similar to that observed when simvastatin was administered before the induction of focal ischemia. T2W-MRI images confirmed these findings. The neuroprotective effects of simvastatin were paralleled by an increase in endothelial NO synthase immunoreactivity, detectable in the brain of simvastatin-treated rats. CONCLUSIONS: Statins, in addition to their preventive effect on cerebral ischemia, exert a neuroprotective role in the attenuation of brain damage after acute stroke.

Animals↗
PubMed2003

Plasma low-density lipoprotein cholesterol and bone mass densitometry in postmenopausal women.

OBJECTIVE: The prevalence and the clinical and social importance of osteopenia and osteoporosis are increasing in western societies. To improve knowledge of the risk factors associated with these conditions, we assessed the relationship between bone mass density and plasma lipid profile in a cohort of postmenopausal women. METHODS: We studied 1303 postmenopausal women who attended a menopause outpatient clinic. All women underwent bone mineral density determination at the level of the lumbar spine. Plasma lipids and lipoproteins and bone metabolic markers were assessed on a blood sample obtained after a 12-hour fast. RESULTS: Statistically significant associations were found by univariate analysis between prevalence of osteopenia and age, time since menopause, body mass index, and low-density lipoprotein (LDL) cholesterol. Specifically, women with plasma LDL cholesterol levels of at least 160 mg/dL had a more than doubled probability of being osteopenic compared with women with lower LDL cholesterol (47.9% versus 21.2%, respectively). Time since menopause, body mass index, and LDL cholesterol were the only variables significantly associated with the prevalence of osteopenia, by multivariable analysis. CONCLUSION: Postmenopausal women with increased plasma LDL cholesterol levels had a greater probability of being classified as osteopenic than women with normal plasma LDL cholesterol levels. Our data, if confirmed, suggest that elevated levels of plasma LDL cholesterol should be regarded as an additional risk factor for reduced bone mineral density.

Aged↗