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E Grandone

Publications and source records attributed to E Grandone.

66 records · Page 4Linked to original sources
PubMed1995

Cu/Zn superoxide dismutase in patients with non-familial Alzheimer's disease.

Chromosome 21 contains genes whose altered expression has long been associated with Down's syndrome and whose altered structure with some cases of Alzheimer's disease (AD). The gene for the Cu/Zn superoxide dismutase enzyme (SOD-1), a key enzyme in the metabolism of oxygen free radicals, is located on the distal portion of chromosome 21. Due to the triplication of the SOD-1 gene, patients with Down's syndrome have an almost 50% increase in their SOD activity. On the other hand, almost 25% of the patients with Down's syndrome over 40 years of age develop progressive dementia, with clinical symptoms of AD. Therefore, we decided to evaluate whether abnormalities in the production of free radicals could be detected in blood cells from AD patients, and whether they correlated with molecular variations in the Cu/Zn SOD-1 gene. Superoxide anion production was evaluated spectrophotometrically in suspensions of monocytes from 9 sporadic AD patients, and from 9 aged-matched apparently normal controls. After stimulation with increasing concentrations of n-formyl-methionyl-leucyl-phenylalanine (fMLP) or Ca ionophore A23187, monocyte free radical generation was quantitatively and qualitatively normal. Furthermore, restriction fragment length polymorphism (RFLP) analysis of leukocyte DNA digested with a variety of enzymes, gave comparable results in patients and controls. Our data support the possibility that in addition to the generation of free radicals, other directions should be explored to elucidate the mechanisms of dementia in AD.

Aged↗
PubMed1995

Raised plasma fibrinogen concentrations in subjects attending a metabolic ward--relation to family history and vascular risk factors.

We have evaluated plasma fibrinogen levels in 171 subjects attending a metabolic ward. As in the general population, a significant difference in plasma fibrinogen concentrations (p < 0.05) was found between subjects with diabetes mellitus or hypertension and those without. However, fibrinogen was also abnormally high (p < 0.05) when evaluated according to the presence of a family history of ischemic complications of atherosclerosis (p < 0.05). In this setting, fibrinogen correlated with diabetes mellitus or hypertension as well as with familial risk, and the latter interacted with hypertension (p < 0.05) in accounting for plasma fibrinogen. The relationships between certain fibrinogen genotypes and familial risk have then been evaluated. Analysis of a locus (1.3 kb, HAE III digestion) of the promoter region of the B beta fibrinogen gene, identified a polymorphic cutting site. The allele with the alternative restriction site (H1) was associated with mean fibrinogen levels which were 0.1-0.3 g/l lower than those associated with the other allele (H2). This difference was not statistically significant. No obvious association was found between the familial risk and the presence of the H2 allele. We conclude that in a group of subjects from a metabolic ward, a positive family history for ischemic complications of atherosclerosis is consistently associated with high plasma fibrinogen levels. Interaction with hypertension significantly strengthens the association.

Adult↗
PubMed1994

Abnormally high circulation levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with a history of ischemic stroke.

We evaluated 106 subjects with and 109 subjects without a history of ischemic stroke. All were attending a metabolic ward. The two groups were compared for major risk factors for ischemic events. A positive family history for ischemic complications of atherosclerosis was more common in subjects with a history of stroke than in those without; moreover, plasma levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (TPA) were higher in patients with documented previous events. A strong positive significant correlation was found between TPA and PAI-1 levels, and an interaction between age and TPA was observed when the sample was stratified according to ages being above or below 70 years. When the patient population was analyzed according to the number of ischemic events, it was found that 62 of the 106 subjects with a history of stroke had experienced more than one ischemic event. Under these conditions, the levels of TPA and PAI-1 still correlated with the occurrence of previous ischemic episodes. As in the whole patient sample, TPA was the strongest discriminator. We conclude that in subjects attending a metabolic ward, TPA and PAI-1 levels consistently help identify subjects with a history of cerebral ischemic episodes and that TPA is the strongest discriminator.

Adult↗
PubMed1993

Plasma predictors of ischemic complications of atherosclerosis: open issues.

In western countries, acute myocardial infarction is the commonest cause of morbidity and mortality [19]. An occlusive coronary thrombus on an ulcerated atherosclerotic plaque in the coronary arteries is the etiological event in more than 90% of patients with Q-wave myocardial infarction [38]. The underlying abnormality in non-Q-wave myocardial infarction is often a ruptured atherosclerotic plaque, which acts as a nidus for the deposition and activation of platelets. In this case, thrombosis occurs, but may not be totally occlusive, or an early spontaneous recanalization may occur. On the other hand, some clinical trials showed that a prolonged treatment with antiplatelet drugs significantly reduces the recurrence of coronary ischemia. Thus, atherosclerosis is a necessary condition for myocardial infarction, but it is not sufficient in that it usually needs the occurrence of thrombosis. However, only 25-30% of these thrombotic events are prevented by the administration of antiplatelets drugs. In recent years, epidemiological studies identified some hemostatic parameters whose abnormalities may help predict the risk of ischemic events: fibrinogen [14], plasminogen activator inhibitor-1 (PAI-1) [3], lipoprotein(a) [46], anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) [10], leukocyte count [34], blood viscosity [34]. Some of these, such as fibronogen and PAI-1 are acute-phase proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anticardiolipin↗
PubMed1993

Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism.

Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, P < 0.001). The administration to four patients of low-dose aspirin (50 mg/d for 1 wk) reduced metabolite excretion by > 80%. The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity. Prolonged partial reduction in the abnormally high excretion of both 11-dehydro-TXB2 and 2,3-dinor-TXB2, was also observed in seven patients who ingested 500 mg daily for 3 wk of the antioxidant drug probucol. These results provide evidence for enhanced thromboxane biosynthesis in homocystinuria and for its partial dependence on probucol-sensitive mechanisms. Furthermore, the elevated TXA2 formation in homocystinuria is likely to reflect, at least in part, in vivo platelet activation.

Adolescent↗
PubMed1992

Fibrinogen and mechanisms of thrombosis. A difficult link.

Epidemiological observations indicate that high plasma fibrinogen levels are strongly correlated to the frequency of two major thrombotic complications of atherosclerosis: stroke and myocardial infarction. Thrombosis is increasingly recognized as a central mechanism in stroke and myocardial infarction, and fibrinogen is involved in events thought to play a major role in thrombosis. Therefore, elucidation of the relationship between fibrinogen and thrombosis may strengthen the predictive value of this protein and define new interventions against stroke and myocardial infarction. In addition, advances in the understanding of the atherogenic potential of several risk factors of coronary heart disease took advantage of information emerging from the measurement of the factor in population-based studies. Thus, it is conceivable that measuring plasma fibrinogen to predict stroke and myocardial infarction is a major direction to be followed to gain insight into the thrombogenic potential on this protein and inspire new strategies against thrombotic complications of atherosclerosis.

Blood Viscosity↗
PubMed1991

In vitro inhibition by defibrotide of monocyte superoxide anion generation: a possible mechanism for the antithrombotic effect of a polydeoxyribonucleotide-derived drug.

In an attempt to elucidate the antithrombotic potential of defibrotide (D) we have evaluated several functions of monocytes from 7 healthy subjects before and after in vitro incubation of the cells with increasing concentrations of this drug. At concentrations as high as 40 micrograms/ml, D hardly affected the expression of both the procoagulant activity of monocytes and the formation of superoxide anion in response to 1 mg/ml zymosan (STZ). In contrast, at concentrations that may be achieved in vivo following the administration of the drug (5-20 micrograms/ml), D impaired in a dose-dependent manner (p less than 0.05) the generation of O-2 in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP, 1 microM) or calcium ionophore A23187 (10 microM). Regardless of the agonist employed, at concentrations between 1 and 5 mM, extracellular Ca2+ had little effect on the impairment of superoxide anion generation by D. In contrast, the inhibitory effect was time-dependent, the maximum impairment (greater than 30%) being observed when the cells were preincubated with the drug for 20 h. These data support the concept that the antithrombotic potential of D involves the ability of the drug to affect the generation of free radicals by leukocytes and suggest that future in vivo studies for the evaluation of the activity of D should take into account the role of monocytes in hemostasis and thrombosis.

Adult↗
PubMedDate not supplied

[Acute biocompatibility of hemodiafiltration with endogenous reinfusion (HFR)].

PURPOSE: In order to reduce the hemodialysis (HD)-induced pro-inflammatory activity we need to use a biocompatible dialysis membrane, avoid backfiltration and possibly use adsorbents. Hemodiafiltration reinfusion (HFR) is a new on-line hemodiafiltration (HDF) technique combining these aspects. This study aimed to evaluate the biocompatibility of the single dialysis session comparing standard HD and HFR. METHODS: Eighteen patients on chronic HD were enrolled in five Centers. Patients underwent one standard and two HFR study sessions; in each session we evaluated leukocyte activation at 0, 5, 15, 60 and 240 min; and interleukin-6 (IL-6), C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1Ra) levels at 0, 60 and 240 min. RESULTS: Leukocyte activation was similar in HD and HFR, while the post-dialysis IL-6 increase was lower with HFR; CRP levels were stable during HFR, but increased after HD, and IL-1Ra did not demonstrate any difference. CONCLUSIONS: These preliminary data show that HFR still has a better biocompatibility in the single dialysis session.

Hemodiafiltration↗