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R Paoletti

Publications and source records attributed to R Paoletti.

At least 19 recordsLinked to original sources
PubMed2001

Direct effects of estrogen on the vessel wall.

The understanding of the biological effects of estrogen on the vessel wall has improved dramatically since the discovery of estrogen receptors (ERs). Most, but not all estrogen-mediated effects in blood vessels are thought to be mediated by ERs. Two major ER subclasses have been characterized so far: the ERalpha and the more recently described ERbeta. This review will primarily focus on a new perspective that highlights ERs as essential mediators of the vascular effects of estrogen. In view of the rising research interest in this area, it can be also expected that tissue- and ER subclass-selective agonists and antagonists will be developed over the next few years, thus providing invaluable tools for pharmacological and clinical applications.

Animals↗
PubMed2001

Acute-phase proteins before cerebral ischemia in stroke-prone rats: identification by proteomics.

BACKGROUND AND PURPOSE: A high degree of proteinuria has been reported in stroke-prone spontaneously hypertensive rats (SHRSP). We studied the effect of salt loading on the detailed protein pattern of serum and urine in 3 rat strains: Wistar-Kyoto, spontaneously hypertensive rats, and SHRSP, an inbred animal model for a complex form of cerebrovascular disorder resembling the human disease. METHODS: Rats were given a permissive diet and received 1% NaCl in drinking water. The protein pattern in body fluids was assessed over time by 2-dimensional electrophoretic analysis. Brain alterations were monitored by MRI and histology. RESULTS: Several proteins were excreted in urine after weeks of treatment and in advance of stroke: transferrin, hemopexin, albumin, alpha(2)-HS-glycoprotein, kallikrein-binding protein, alpha(1)-antitrypsin, Gc-globulin, and transthyretin. Markers of an inflammatory response, including very high levels of thiostatin, were detected in the serum of SHRSP at least 4 weeks before a stroke occurred. CONCLUSIONS: In SHRSP subjected to salt loading, an atypical inflammatory condition and widespread alterations of vascular permeability developed before the appearance of anomalous features in the brain detected by MRI. Urinary concentrations of each of the excreted serum proteins correlated positively with time before stroke occurred.

Acute-Phase Proteins↗
PubMed2001

Lacidipine [correction of Lalsoacidipine] modulates the secretion of matrix metalloproteinase-9 by human macrophages.

Activated macrophages within the arterial wall secrete matrix-degrading metalloproteinases (MMPs) that weaken the atherosclerotic plaque and contribute to its fissuration. Preclinical studies have shown that calcium antagonists may reduce atherogenesis in the arterial wall. In the present study we evaluated the effect of lacidipine on 92-kDa gelatinase B (MMP-9) expression in human macrophages in cultures. Cells were treated for 24 h with lacidipine and the conditioned media were analyzed. Lacidipine (1-20 microM) significantly reduced, in a dose-dependent manner, MMP-9 potential gelatinolytic capacity up to 50%. When MMP-9 expression was stimulated by treatment with phorbol esters or tumor necrosis factor-alpha, lacidipine was able to inhibit this enhanced gelatinolytic capacity up to 50 and 60%, respectively. Western blot analysis and enzyme-linked immunosorbent assay showed a reduction of MMP-9 protein actually released by cells. The addition of lacidipine in the incubation media determined no significant variation in Ca(2+) concentration. The drug did not affect MMP-9 mRNA levels, but it effectively reduced the amount of both active and total free MMP-9 secreted by human macrophages. Lacidipine reduced also the secretion of the tissue inhibitor of metalloproteinase-1 (TIMP-1); however we observed an overall reduction of the gelatinolytic activity of the cells. Finally, peritoneal macrophages, obtained from mice treated with lacidipine, showed a reduced secretion of MMP-9. Together, our data indicate that lacidipine may potentially exert an antiatherosclerotic activity by modulating the secretion of MMP-9 by macrophages. This, in addition to the previously demonstrated inhibition of cholesterol esterification, may contribute to increase plaque stability.

Animals↗
PubMed2000

Color Doppler sonography of uterine arteriovenous malformation.

Arteriovenous malformation of the uterus is a rare but potentially life-threatening lesion. We report a case of arteriovenous malformation of the uterus in a 19-year-old nulliparous woman. The diagnosis was made with color Doppler sonography and was confirmed histologically. Color Doppler sonography helps differentiate uterine arteriovenous malformation from other entities that have a similar appearance on gray-scale sonograms.

Adult↗
PubMed2000

Editorial

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Journal Article↗
PubMed2000

Do pleiotropic effects of statins beyond lipid alterations exist in vivo? What are they and how do they differ between statins?

The inhibition of cellular proliferation, the restoration of endothelial activity, the inhibition of platelet reactivity, and an antioxidant potential are only a few examples of pleiotropic effects of statins. This review analyzes the current knowledge on the pleiotropic properties of this class of drugs and examines the relevant data that support the presence of these effects in vivo. The favorable outcome of major trials of statins has indicated that pleiotropic factors indeed play a role in cardiovascular protection. In addition, recent data indicate that many pleiotropic effects influence mechanisms that belong to the extravascular compartment, as well. Perhaps, some of these properties may eventually justify additional indications for statins and improve the treatment of other diseases, including inflammation and cancer.

Anticholesteremic Agents↗
PubMed2000

Efficacy and safety of a combination of fluvastatin and bezafibrate in patients with mixed hyperlipidaemia (FACT study).

Preliminary data suggest that fluvastatin may be safely combined with fibrates. The Fluvastatin Alone and in Combination Treatment Study examined the effects on plasma lipids and safety of a combination of fluvastatin and bezafibrate in patients with coronary artery disease and mixed hyperlipidaemia. A total of 333 patients were randomly allocated in this multicentre double-blind trial to receive 40 mg fluvastatin alone (n=80), 400 mg bezafibrate (n=86), 20 mg fluvastatin+400 mg bezafibrate (n=85) or 40 mg fluvastatin+400 mg bezafibrate (n=82) for 24 weeks. Low-density lipoprotein (LDL)-cholesterol decreased >20% in all fluvastatin-containing regimens, with significantly greater decreases compared with bezafibrate alone (P<0.001). Bezafibrate alone and fluvastatin+bezafibrate combinations resulted in greater increases in high-density lipoprotein (HDL)-cholesterol and decreases in triglycerides compared with fluvastatin alone (P<0.001). Fluvastatin (40 mg)+bezafibrate was the most effective for all lipid parameters with a decrease from baseline at endpoint in LDL-cholesterol of 24%, a decrease in triglycerides of 38% and an increase in HDL-cholesterol of 22%. All treatments were well tolerated with no increase in adverse events for combination therapy versus monotherapy, or between combination regimens. No clinically relevant liver (aspartate aminotransferase [ASAT] or alanine aminotransferase [ALAT]) greater than three times the upper limit of normal) or muscular (creatine phosphokinase (CPK) greater than four times the upper limit of normal) laboratory abnormalities were reported. This large study shows 40 mg fluvastatin in combination with 400 mg bezafibrate to be highly effective and superior to either drug given as monotherapy in mixed hyperlipidaemia, and to be safe and well tolerated.

Adult↗
PubMed2000

Non-lipid-related effects of statins.

The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on coronary events have generally been attributed to their hypocholesterolaemic properties. However, as mevalonate and other intermediates of cholesterol synthesis (isoprenoids) are necessary for cell proliferation and other important cell functions, effects other than cholesterol reduction may explain the pharmacological properties of statins. In the present review, we discuss the current knowledge on the nonlipid-related effects of statins, with a special emphasis on their potential benefits in different diseases, such as atherosclerosis and cancer. The mechanism(s) responsible for their favourable properties are also reviewed.

Animals↗
PubMed2000

Effects of fluvastatin and bezafibrate combination on plasma fibrinogen, t-plasminogen activator inhibitor and C reactive protein levels in coronary artery disease patients with mixed hyperlipidaemia (FACT study). Fluvastatin Alone and in Combination Treatment.

AIM OF THE STUDY: We studied the effects of fluvastatin and bezafibrate in monotherapy and in combination on plasma fibrinogen, t-plasminogen activator inhibitor (PAI-1) and C reactive protein (CRP) in patients with coronary artery disease (CAD) and mixed hyperlipidaemia. DESIGN: In this randomised, double blind, multicentre trial 333 patients with stable angina pectoris or previous myocardial infarction or coronary revascularisation and mixed hyperlipidaemia (LDL-cholesterol 135-250 mg/dl and triglycerides (TG) 180-400 mg/dl) were randomised to fluvastatin 40 mg, bezafibrate 400 mg, fluvastatin 20 mg + bezafibrate 400 mg or fluvastatin 40 mg + bezafibrate 400 mg treatments for 24 weeks. RESULTS: Plasma fibrinogen significantly decreased after treatment with the combinations fluvastatin+bezafibrate (-14 and -16%) and with bezafibrate monotherapy (-9%). No significant reduction was observed after fluvastatin monotherapy (-4%). No significant changes were observed in PAI-1 and CRP plasma levels. Combination therapy significantly decreased both LDL-C and TG, and significantly increased HDL-C. CONCLUSIONS: The combined effects on fibrinogen and plasma lipids achieved by fluvastatin and bezafibrate combination treatment might be more useful than the simple reduction of cholesterol in preventing ischaemic cardiovascular disease.

Adult↗
PubMed2000

[The treatment and outlook of atherosclerosis today].

Nowadays, the success of atherosclerosis therapy and the efficacy of cardiovascular disease prevention can rely on a comprehensive strategy. New algorithms derived from large population studies have improved the risk evaluation for the single individual and, consequently, the therapeutic approach can be better adapted to the specific needs of the patient. Improvements of noninvasive techniques, such as B-mode ultrasound and magnetic resonance imaging, allow for the reproducible and precise monitoring of lesion evolution that can be easily applied to large population samples. Ongoing studies regarding the relationship between circulating markers of atherosclerosis and the occurrence of cardiovascular events will improve our assessment of impending risk. Finally, the presence of pleiotropic effects of statins in vivo (and, perhaps, of fibrates as well) underscores the added value of this class of drugs in the treatment of lipid disorders and in the prevention of cardiovascular events. Prospectively, the integration of all these approaches will have a desirable impact on the qualitative improvement of human longevity.

Arteriosclerosis↗
PubMed2000

Pleiotropic effects of statins in atherosclerosis and diabetes.

OBJECTIVE: To investigate the direct anti-atherosclerotic properties of statins. RESEARCH DESIGN AND METHODS: Using in vitro and ex vivo models, the effect of different statins on key events involved in atherogenesis has been investigated. We studied the ability of statins to modulate modified LDL-induced cholesterol esterification, metalloproteinase secretion by macrophages, and arterial myocyte migration and proliferation. The mechanisms underlying the inhibitory effect of statins have also been explored. Finally, the antiproliferative effect of sera from statin-treated patients has been confirmed in a cell culture system. RESULTS: Fluvastatin, simvastatin, lovastatin, atorvastatin, and cerivastatin, but not pravastatin, dose-dependently decrease smooth muscle cell (SMC) migration and proliferation. Moreover, statins are able to reduce cholesterol accumulation in macrophages in vitro by blocking cholesterol esterification and endocytosis of modified lipoproteins and matrix-degrading enzyme secretion. This in vitro inhibition was completely prevented by mevalonate and partially by all-trans farnesol and all-trans geranylgeraniol, confirming the specific role of isoprenoid metabolites (probably through prenylated protein[s]) in regulating these cellular events. The inhibitory effect of statins on SMC proliferation has been shown in different models of proliferating cells, such as cultured arterial myocytes and rapidly proliferating carotid and femoral intimal lesions in rabbits, independently of their ability to reduce plasma cholesterol. Finally, ex vivo studies showed that sera from fluvastatin-treated patients interfere with SMC proliferation. CONCLUSIONS: These results suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors exert a direct anti-atherosclerotic effect in the arterial wall, beyond their effects on plasma lipids that could translate into a more significant prevention of cardiovascular disease. These findings provide a basis for the beneficial effect of statins in clinical trials also involving diabetic patients--a population with a higher absolute risk of recurrent cardiovascular events.

Animals↗
PubMed2000

[Rubella vaccination in the post-partum: which is the best approach?].

BACKGROUND: Two different post partum Rubella vaccination's programs for seronegative women in puerperium are compared. METHODS: In the Borgosesia hospital (Piedmont Region) the vaccination has been proposed by gynecologists already during pregnancy to all the pregnants proved to be negative at the Rubella's test in the initial pregnancy. The little number of enlisted patients is the consequence of the availability of only one doctor to take part in the vaccination's program. In this hospital the cost of vaccination was paid by the patient that had to buy the vaccine before hospitalization. In the Vigevano's hospital (Lombardia Region) the rubella's vaccination has been instead proposed by the nursery pediatrist to all the women who has just given birth in the period between 1995-1997, seronegative for rubella's test in pregnancy or in puerperium. RESULTS: The results (88% of the seronegative women vaccinated in Borgosesia versus 72.6% in Vigevano) show that the best way is to make the pregnant women aware by the gynecologist during pregnancy, even though the vaccine wasn't free for the patients. CONCLUSIONS: The action of pediatrists combined with the availability from hospital administration to offer a free vaccine will make possible to reach an almost total success of the Rubella vaccination's program.

Female↗
PubMed1999

EDITORIAL.

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Journal Article↗
PubMed1999

Best practice--ongoing polemics.

Current treatment strategies and disease management programs for hyperlipidemia employ a range of lipid-lowering drugs. Results from early lipid-lowering trials using diet, fibrates, niacin and other classes of drug showed that lowering plasma cholesterol can significantly reduce the risk of developing ischemic cardiovascular events. The landmark statin trials have clearly demonstrated the benefits of lipid-lowering therapy in coronary heart disease (CHD) prevention and unlike early lipid-lowering studies, a reduction in mortality may become evident with statin therapy during the first year of treatment. The number of successful lipid-intervention trials continues to increase and evidence is accumulating that lipid modification can also reduce the risk of cardiovascular events among individuals with only modest degrees of blood-lipid abnormalities. With increasingly powerful drugs to modify blood lipids, the potential levels at which to initiate treatment and the appropriate target levels are rapidly changing and debate surrounds the question of where the line to initiate treatment should be drawn. The relative lack of major adverse events with statin therapy means that the level of CHD risk at which clinical benefit occurs cannot be determined by the degree of risk at which benefit exceeds adverse events. Therefore, patients with only moderately raised cholesterol levels can be treated because statin treatment is well tolerated. One of the most important aspects of the statin trials is the finding that clinical events, such as death and disability due to coronary artery disease, may be preventable or limited in a significant number of patients if they receive aggressive therapy. Current goals for cholesterol levels in patients with established CHD are rarely achieved with non-aggressive treatment; however, with aggressive lipid lowering statins can achieve these goals in a safe and effective manner.

Cardiovascular Diseases↗