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Biomedical subjects

A Ghiselli

Publications and source records attributed to A Ghiselli.

At least 37 records · Page 2Linked to original sources
PubMed1992

Mechanism of reaction of a suggested superoxide-dismutase mimic, Fe(II)-N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine.

The interaction of a recently developed intracellular superoxide dismutase analogue, Fe(II)-N,N,N',N'-tetrakis(2- pyridylmethyl)ethylenediamine (Fe(II)-TPEN), with reactive oxygen species was investigated under in vitro conditions. The complex catalyzed the dismutation of enzyme- or radiolysis-generated superoxide with the production of H2O2; under steady-state conditions the equilibrium was strongly shifted toward Fe(III)-TPEN. Fe(II)-TPEN reacted with H2O2 to generate hydroxyl radicals in a Fenton reaction. The oxidized Fe(III)-TPEN was readily reduced by ascorbate or glutathione. Given the capacity to produce hydroxyl radicals and the reaction with cellular reductants it seems unlikely that Fe-TPEN may find widespread use as an intracellular superoxide dismutase substitute.

Ascorbic Acid↗
PubMed1992

Reaction of dipyridamole with the hydroxyl radical.

Dipyridamole [2,6-bis-diethanolamino-4,8-dipiperidinopyrimido-(5,4-d)pyri midine], a well known platelet aggregation inhibitor, shows powerful hydroxyl radical scavenging activity by inhibiting OH.-dependent salicylate and deoxyribose degradation. Steady-state competition kinetics experiments with deoxyribose were carried out to evaluate the second-order rate constant for the reaction between hydroxyl radical and dipyridamole. OH. radicals were generated either by a Fenton-type reaction or by X-ray irradiation of water solutions. A second-order rate constant k(Dipyridamole + OH.) of 1.72 +/- 0.11 X 10(10) M-1 s-1 and of 1.54 +/- 0.15 X 10(10) M-1 s-1 was measured by Fenton chemistry and by radiation chemistry, respectively. Mannitol was used as an internal standard for hydroxyl radicals in steady-state competition experiments with deoxyribose. A rate constant K(Mannitol + OH.) of 1.58 +/- 0.13 X 10(9) M-1 s-1 and 1.88 +/- 0.14 X 10(9) M-1 s-1 was measured in the Fenton model and in the water radiolysis system, respectively. Both these rate constants are in good agreement with the published data obtained by the "deoxyribose assay" and by pulse radiolysis.

Deoxyribose↗
PubMed1992

Salicylate hydroxylation as an early marker of in vivo oxidative stress in diabetic patients.

In vivo metabolism of salicylic acid produces two main hydroxylated derivatives (2,5- and 2,3-dihydroxybenzoic acid). The former can be produced by enzymatic pathways through the cytochrome P-450 system, while the latter is reported to be solely formed by direct hydroxyl radical attack. Therefore, measurement of 2,3-dihydroxybenzoate, following oral administration of salicylate in its acetylated form (aspirin), has been proposed for assessment of oxidative stress. In this article we report plasma levels of 2,3- and 2,5-dihydroxybenzoates following the administration of 1 g aspirin and plasma levels of thiobarbituric acid-reactive material (TBARM) in well-controlled diabetic patients and in healthy subjects. 2,3-Dihydroxybenzoate levels were significantly higher (23%) in diabetic patients than in controls (63.4 +/- 20.1 versus 49.0 +/- 6.8 nM; p < .05). On the other hand, TBARM values were not significantly different between groups. These results suggest that the method is useful to reveal in vivo oxidative stress independently from the peroxidation of lipids, and they support the hypothesis that oxygen radicals are involved in the pathogenesis of chronic complications of diabetes.

Adult↗
PubMed1991

Superoxide dismutase triggers activation of "primed" platelets.

Superoxide dismutase (SOD) triggers activation of human platelets exposed to subthreshold concentrations of arachidonic acid and collagen. The subthreshold concentrations used are not able to activate platelets but "prime" platelets to be activated by SOD. The addition of SOD to arachidonic acid-or collagen-primed platelets induced aggregation, thromboxane A2 production, and release of [3H]serotonin. Superoxide dismutase does not have any effect on resting platelets and ADP-, thrombin-, calcium ionophore A23187-, PAF-, or U46619-stimulated platelets. Furthermore, superoxide dismutase-dependent platelet activation is fully prevented by catalase and/or aspirin, suggesting a role for H2O2 and the involvement of the cyclooxygenase pathway of arachidonic acid in such activation.

Adult↗
PubMed1991

Plasma thiobarbituric acid reactive substances a predictive marker of cerebral ischemia in patients at high risk?

The clinical meaning of high values of blood lipid peroxides, assessed as thiobarbituric acid reactive substances (TBA-RS), was investigated in 19 selected high risk patients with transient ischemic attacks (TIA). Patients were checked every 3-6 months and followed-up for 3 years. 8 patients experienced further vascular episodes, 4 having minor stroke and 4 TIA; one of the latter died from myocardial infarction. Unlike blood cholesterol and glucose. TBA-RS values discriminated patients with vascular episodes: they, indeed, showed significant higher values of TBA-RS. Discriminant analysis further indicated that TBA-RS levels differentiate patients with and without vascular accidents, suggesting that high blood values of lipid peroxides could represent a predictive sign of vascular ischemia.

Aged↗
PubMed1991

Hydrogen peroxide as trigger of platelet aggregation.

In order to verify if H2O2 affects platelet function, platelet-rich plasma and human washed platelets were incubated with subthreshold concentrations (STC) of collagen or arachidonic acid or ADP and/or with 75-150 microM H2O2. While H2O2 alone did not affect platelet aggregation, it amplified platelet aggregation response in samples stimulated with STC of arachidonic acid and collagen but not in samples stimulated with STC of ADP. When platelets were preventively treated with aspirin, a cyclooxygenase inhibitor, the platelet activation by H2O2 was not observed. Thromboxane A2 (TxA2) was not produced by human washed platelets stimulated with STC of arachidonic acid, collagen or by H2O2 alone. On the contrary, when STC of agonists were tested on platelets supplemented with H2O2 an evident TxA2 production was seen. This effect was prevented by aspirin pretreatment or by the addition of catalase, an enzyme which destroys H2O2. This study suggests that H2O2 triggers the activation of platelets exposed to STC of collagen and arachidonic acid, via the cyclooxygenase pathway.

Adult↗
PubMed1990

Tubular supravalvar aortic stenosis: replacement of ascending aorta in a young patient.

The diffuse form of supravalvar aortic stenosis represents a surgical challenge when ascending aorta and proximal aortic arch are involved. We describe a technique performed on a 14-year-old patient with normal aortic annulus and severe diffuse supravalvar aortic stenosis in which the replacement of ascending aorta and proximal aortic arch with a tubular prosthetic graft completely relieved the obstruction as confirmed by cardiac catheterization.

Adolescent↗
PubMed1990

Inhibition of cyclooxygenase-independent platelet aggregation by low vitamin E concentration.

Platelet aggregation induced by threshold concentrations of agonists such as collagen, PAF or epinephrine was inhibited in vitro by 100 microM aspirin but was restored by stimulating platelets with high concentrations of collagen, PAF or by a combination of epinephrine and PAF. Incubating aspirin-treated platelets with 50-100 microM vitamin E or vitamin E acetate inhibited platelet aggregation by high concentrations of collagen and PAF and by the combination of epinephrine and PAF; platelet thromboxane A2 formation was less than 10% in samples incubated with 100 microM aspirin. Apyrase, added to aspirin-treated platelet, did not influence platelet aggregation induced by epinephrine and PAF. The present study suggests that concentrations of vitamin E as low as 50-100 microM inhibit cyclooxygenase-independent platelet aggregation when combined with an inhibitor of the arachidonate pathway.

Apyrase↗
PubMed1989

Inhibition of cyclooxygenase-independent platelet aggregation by sodium salicylate.

The effect of acetylsalicylic acid (ASA) on platelet aggregation (PA) and thromboxane A2 (TxA2) formation was investigated in vitro and ex vivo after 1 g or 300 mg ASA administration to healthy subjects. 50-100 microM ASA inhibited PA by single aggregating agent such as platelet aggregating factor (PAF) or epinephrine and reduced to less than or equal to 5% of control platelet TxB2 formation, but did not influence PA by epinephrine plus PAF. The latter was inhibited by increasing ASA concentration. In samples incubated with 100 microM ASA and stimulated with epinephrine plus PAF, PA could be inhibited by the addition of 100-300 microM sodium salicylate. After 300 mg-1 g ASA administration to healthy subjects, the inhibition of PA by epinephrine plus PAF was more marked by highest doses of ASA. This study suggests that aspirin inhibits PA with a cyclooxygenase-independent mechanism; this effect is mediated, at least in vitro, by salicylic acid.

Adult↗
PubMed1989

Blood lipid peroxides in TIA: relation to platelet function and metabolic profile.

Patients with transient ischemic attacks (TIA) were previously shown to have high plasma values of thiobarbituric acid-reactive substances (TBA-RS). To study whether these changes could be related to platelet activability, TBA-RS was investigated in 24 TIA patients before and 24 h after 1 g aspirin, an inhibitor of platelet cyclooxygenase pathway. Baseline TBA-RS values were significantly higher in TIA than in controls. Conversely, TIA patients had TBA-RS values after aspirin similar to controls, suggesting that the increase of plasma TBA-RS was not attributable to platelet hyperfunction. The evaluation of metabolic profile showed that patients with highest TBA-RS had hypercholesterolemia, hypertriglyceridemia, and/or diabetes mellitus. This study suggests that the increase of plasma TBA-RS in TIA could be an epiphenomenon of altered metabolic pathway.

Administration, Oral↗
PubMed1988

Inhibition by picotamide of thromboxane production in vitro and ex vivo.

The effect of picotamide on platelet function has been studied in vitro and ex vivo. Picotamide at micromolar concentrations inhibited platelet aggregation induced by ADP, arachidonic acid and collagen, and it also inhibited the production of thromboxane A2 (TxA2). Unlike aspirin, picotamide did not affect the synthesis of prostacyclin by blood vessels. In eight healthy subjects who took picotamide 1200 mg/d platelet aggregation and TxA2 production were inhibited. Picotamide appears to be an antiplatelet drug that reduces TxA2 synthesis without affecting cyclo-oxygenase activity.

Adult↗
PubMed1988

Influence of hydroxyl radical scavengers on platelet function.

The influence of four hydroxil radical (OH.) scavengers on platelet function was investigated. OH. scavengers inhibited ADP, collagen, arachidonic acid, PAF-induced platelet aggregation, and platelet cyclooxygenase pathway activation, which was studied by evaluating platelet malondialdehyde and serum thromboxane A2 formation. The latter was not affected by superoxide dismutase, catalase, or metal ion chelants such as desferioxamine or DETAPAC. The detection of deoxyribose degradation by stimulated platelets suggested that platelets produce OH.. This study shows that activated platelets produce free radicals and that antioxidant agents such as OH. scavengers inhibit platelet function.

Adult↗