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Biomedical subjects

F Violi

Publications and source records attributed to F Violi.

At least 199 records · Page 11Linked to original sources

Nitric oxide and its role in lipid peroxidation.

Nitric oxide (NO) is a free radical with an unpaired electron in the highest orbital. This is why it behaves as a potential antioxidant agent by virtue of its ability to reduce other molecules. In vitro experiments support this concept inasmuch as NO is able to inhibit lipid peroxidation. However, NO is rapidly inactivated by the superoxide anion (O(*2) to form peroxynitrite (ONOO-), which is a potent oxidant. Therefore, in the presence of O(*2), NO behaves as a potent pro-oxidant. This is the mechanism that accounts for the low density lipoprotein (LDL) oxidation that occurs when NO and O(*2) are simultaneously present in the medium. As NO and O(*2) are simultaneously released by cells such as endothelial cells, the balance between these two radicals is crucial in understanding the net effect of NO on lipid peroxidation. Thus an excess of NO will favour lipid peroxidation inhibition, while an excess of O(*2) or equimolar concentration of NO and O(*2) will induce lipid peroxidation. Modulation of this balance may have important clinical implications, particularly in the atherosclerotic process in which oxidant stress seems to play a pivotal role in the onset and progression of vascular lesions.

Antioxidants↗

Metformin decreases platelet superoxide anion production in diabetic patients.

BACKGROUND: Patients with type 2 diabetes mellitus are usually treated with oral antidiabetic agents but it is still not known whether these drugs have antioxidant effects in humans. METHODS: We studied 60 patients with type 2 diabetes mellitus, divided into three groups on the basis of hypoglycaemic treatment (Group A: metformin, Group B: glibenclamide, Group C: diet). All patients were followed for at least 1 year. The three subgroups had similar clinical characteristics. Twenty healthy subjects, of comparable sex and age, were enrolled as controls. In each subject, platelet production of superoxide anion (O(2)(-)) elicited by collagen, was determined by lucigenin assay. RESULTS: Patients with diabetes had higher platelet O(2)(-) production than controls; no correlation was observed between blood glucose and platelet O(2)(-) production. Group A patients had platelet O(2)(-) production similar to that of healthy subjects but lower than Group B and Group C patients. CONCLUSION: The present findings suggest an in vivo antioxidant activity of metformin and warrant prospective studies to further explore this hypothesis.

Antioxidants↗

Daily hemofiltration in severe heart failure.

Heart failure of class IV NYHA has a very severe prognosis. Its most frequent electrolytic alterations are hyponatremia, hypokalemia, and hypomagnesemia which can cause serious arrhythmias and sudden death. The regulation of the electrolytic equilibrium by means of pharmacological therapy becomes impossible in patients with severe heart failure resistant to strong doses of diuretics in the oligo-anuric phase. This study focused on the use of daily hemofiltration in a group of patients suffering from cardiac insufficiency of class IV NYHA. The results have been evaluated over 1 year.

Aged↗

Early dialysis in heart insufficiency of patients with chronic renal failure.

In patients with severe heart failure life expectancy is short, the quality of life is affected, and the service costs are very high. Drug therapies remain restricted despite continuous clinical research. Therefore new therapeutic approaches have been attempted to improve the signs and symptoms of the disorder. In our study we followed patients suffering from class-IV cardiac failure concomitant with chronic renal failure. The patients were initially treated by means of hemofiltration, and subsequently they underwent a personalized dialysis program. The survival rate after 2 years was 62.5%. In 7 of the 8 patients the results revealed a drop to a class-III condition. The hospitalization period was limited to a few days. Early dialytic therapy represents a reality for such patients.

Aged↗

[The future prospects of antithrombotic therapy in peripheral vasculopathy].

Peripheral vascular disease is characterized by progressive atherosclerotic deterioration of peripheral arteries and coronary and cerebral vascular complications. Antiplatelet treatment retards the progression of peripheral atherosclerosis but it is still unclear if this is associated with a reduced risk of amputation. Vasodilator prostaglandins have been administered in critical ischemia but the results have been disappointing. An alternative approach to enhance peripheral vasodilation is to increase nitric oxide production, which is reduced in peripheral vascular disease, particularly in the case of severe ischemia. Critical ischemia secondary to thromboembolism has been treated with thrombolysis within 7 days of the acute episode, but this approach is no more effective than vascular surgery in reducing amputation; earlier treatment should be planned to further investigate its clinical efficacy. The effect of antiplatelet treatment in preventing cardiovascular events was investigated in three randomized trials with negative results. A post-hoc analysis of the CAPRIE study demonstrated that clopidogrel is superior to aspirin in preventing cardiovascular disease. This suggests that antiplatelet treatment may be efficacious in this setting; future study should assess if its combination with other drugs, such as statins, that retard coronary atherosclerotic progression, could further reduce cardiovascular complications in peripheral vascular disease.

Disease Progression↗

Association between prolonged bleeding time and gastrointestinal hemorrhage in 102 patients with liver cirrhosis: results of a retrospective study.

BACKGROUND: Gastrointestinal bleeding is a frequent complication of liver cirrhosis (LC) and represents an important warning sign of imminent death. Platelet dysfunction is an abnormality occurring prevalently in severe liver failure, and could well predispose to bleeding. METHODS: One hundred and two patients with liver cirrhosis diagnosed by needle liver biopsy were studied. According to the Child-Pugh classification, 23 were A class, 42 B class and 37 C class cases. Prothrombin activity, aPTT, fibrinogen, FDPs, XDP and platelet count were measured in each patient; bleeding time was measured in all but 17 of them. Forty (39%) had experienced gastrointestinal bleeding during the last 3 years (2 A class, 12 B class, 26 C class). RESULTS: Patients with a history of previous gastrointestinal bleeding showed lower values for prothrombin activity and fibrinogen, and higher percentage of elevated FDP and XDP levels; moreover, they presented lower platelet counts and more prolonged bleeding times than patients without gastrointestinal blood loss. CONCLUSIONS: While our findings confirm the relationship between hyperfibrinolysis and bleeding, the association between bleeding time prolongation and gastrointestinal blood loss suggests studying platelet function prospectively in LC in order to analyze its role, if any, in favoring hemorrhage activity.

Adult↗

[Dialytic treatment in patients with renal insufficiency and heart failure refractory to combined drug therapy].

The incidence and prevalence of heart failure are continuously on the increase. Pharmacological therapy is not sufficient in the advanced stages of the illness to control the signs and symptoms, especially when stressing factors intervene and complicate the illness course. Dialytic treatments are always indicated more than necessary in the severe forms of heart failure, but the optimal treatment has not yet been established. In our division, 24 patients with heart failure (III-IV NYHA) and renal failure (III-IV NKF-DOQI) were treated with low flux bicarbonate dialysis, variable dialysate and limited ultra-filtration. Arrhythmia, pericarditis, ischemic cardiopathy and hyponatremia were the stressing factors that determined acute heart failure. Fifteen patients presented with diastolic failure, whereas nine patients had systolic heart failure. The first group of patients had higher arterial pressure, better ejection fraction and better prognosis regarding renal function and survival rate. The results obtained with this treatment in prevalently diastolic heart failure are satisfactory in terms of survival, as well as in renal function recovery, whereas they are not adequate in systolic failure where other approaches are being studied. Therefore, we believe that the therapeutic choice must always be determined in relation to the type of heart failure.

Aged↗

[Sustained low-efficiency dialysis (SLED) in patients with prevalent systolic heart failure refractory to medical treatment and with chronic renal failure].

Systolic heart failure refractory to conventional medical therapy is the principal cause of the high hospitalization rates and of high mortality risks. When this condition is associated with chronic renal failure it is necessary to treat the body liquid composition alterations, and the alterations in the hemodynamic state without creating low flow conditions, trying to achieve an electrolytic and an acid-base balance to reduce the plasmatic volume and permit refilling between the interstitium and plasm. Sustained low-efficiency dialysis (SLED) is a dialysis technique allowing the maintenance of hemodynamic stability through a reduced ultrafiltration rate, it allows an adequate clearance of small solutes, and with sustained treatment it maximizes the dialysis dose and determines a clinical improvement through the removal of the hydric overload. Our experience suggests that SLED is a substitutive treatment for acute dialysis in patients with systolic heart failure refractory to conventional medical treatment.

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[Quality of life in patients with combined treatments for heart failure].

The low quality of life in patients with end-stage heart failure is correlated, above all, to frequent hospitalization and to the awareness of having an illness that limits survival. The quality of life in these patients with heart failure using treatment with sustained low efficiency dialysis (SLED) is determined through the Minnesota Living with Heart Failure (MLHF) Questionnaire. The reliability of this evaluation system has been examined through consultation with international trials. After 1 yr of this treatment, we observed an improvement in quality of life.

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Dipyridamole potentiates the inhibition of platelet aggregation by aspirin (in human platelet rich plasma and whole blood).

This study investigates the influence of dipyridamole on platelet aggregation as evaluated by a single agonist or a pair of agonists in human platelet rich plasma and whole blood. Dipyridamole up to 30 microM was not found to influence the platelet aggregation of platelet rich plasma or whole blood; aspirin (100 microM), on the contrary, did inhibit platelet aggregation. The inhibition of platelet aggregation by aspirin could be reversed by using high concentrations of agonists or pairs of agonists. In this model dipyridamole inhibited platelet aggregation in both platelet rich plasma and whole blood in a dose-dependent fashion. Thromboxane A2 was less than 10% of controls in aspirin-treated PRP stimulated with low or high concentrations of collagen or with a pair of agonists. This study suggests that dipyridamole has direct antiplatelet activity in platelet rich plasma and whole blood when the cyclooxygenase pathway is blocked by aspirin.

Adult↗

Clinical use of antiplatelet therapy.

The authors report the principal clinical models in which inhibitors of platelet aggregation were used to prevent the clinical complications of atherosclerosis. The models at risk which were considered include unstable angina, TIAs, myocardial infarction and atherosclerotic vascular disease of the lower limbs. Overall, the studies suggest the value of this therapy for the prevention of cardiovascular accidents. TIAs, unstable angina and myocardial infarction are the models which provide the best evidence for this; however, the effectiveness of this therapy in peripheral vascular disease, while showing positive results, needs to confirmed by further clinical studies. Lastly, therapy with inhibitors of platelet aggregation has been shown to be useful in the prevention of aortocoronary bypass occlusion; however, its efficacy has been shown only when therapy is initiated early.

Animals↗

Anticardiolipin antibodies possess anticoagulant activity which is blocked by a monoclonal antibody against a cross reacting idiotype of antiphospholipid antibodies.

Anticardiolipin (aCL) antibodies were isolated from systemic lupus erythematosus serum using cardiolipin liposomes. In a sensitized activated partial thromboplastin time (aPTT) system, low concentrations of aCL were found to significantly prolong aPTT in a dose-dependent fashion. This effect was abolished by adding phosphatidylserine/phosphatidylcholine liposomes to the aPTT system, and could be significantly reduced by a monoclonal antibody against a cross-reacting idiotype of antiphospholipid antibodies (MoAb 5.2) previously incubated with aCL. These results suggest that the anticoagulant properties of aCL are mediated by an interaction with phospholipid components of the coagulation system. The functional block of this activity using monoclonal MoAb 5.2 antibody could be useful for investigating the mechanisms by which aCL is associated with clinical thrombosis.

Antibodies, Anti-Idiotypic↗

Blood lipid abnormalities in patients suffering from peripheral vascular disease.

Blood lipid profile was investigated in 40 patients suffering from peripheral vascular disease (PVD). The most frequent abnormality was the increase of cholesterol and triglycerides. HDL-cholesterol and the subfractions HDL2 and HDL3 were decreased but not significantly. Cholesterol/HDL-cholesterol ratio was significantly increased suggesting an abnormal cholesterol distribution on lipoprotein fractions. Apolipoproteins AI and AII were within normal range while apolipoproteins B, CII, CIII, and E were significantly increased. This study provide further findings on the blood lipid abnormalities in patients affected by PVD.

Aged↗