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A Pezzella

Publications and source records attributed to A Pezzella.

10 recordsLinked to original sources

Iron-mediated generation of the neurotoxin 6-hydroxydopamine quinone by reaction of fatty acid hydroperoxides with dopamine: a possible contributory mechanism for neuronal degeneration in Parkinson's disease.

Exposure of dopamine to an excess of linoleic acid 13-hydroperoxide (13-hydroperoxyoctadecadienoic acid) in the presence of ferrous ions in Tris buffer, pH 7.4, resulted in a relatively fast, oxygen-independent reaction exhibiting first-order kinetics with respect to both catecholamine and metal concentrations. Product analysis in the early stages revealed the presence of significant amounts of the quinone of the neurotoxin 6-hydroxydopamine, together with some aminochrome and ill-defined melanin-like material. Quinone formation required the presence of iron, either in the ferrous or ferric form, and was unaffected by peroxidase, catalase, and hydroxyl radical scavengers, e.g. mannitol, as well as biologically relevant antioxidants, like ascorbate and glutathione. Hydrogen peroxide proved as effective as linoleic acid hydroperoxide in inducing dopamine oxidation and conversion to 6-hydroxydopamine quinone. Metal chelators, including EDTA and bipyridyl, markedly suppressed quinone formation without, however, inhibiting dopamine oxidation. These and other results are consistent with a hydroxyl radical independent hydroxylation/oxidation mechanism basically different from the Fenton reaction, which involves direct interaction of the peroxide with a dopamine-Fe(III) chelate generated during the process.

Dopamine

Generation of the neurotoxin 6-hydroxydopamine by peroxidase/H2O2 oxidation of dopamine.

At physiological pH values, oxidation of the neurotransmitter dopamine (DA) by the peroxidase/H2O2 system leads to, besides dopaminochrome and 5,6-dihydroxyindole resulting from oxidative cyclization of dopaminequinone (DQ), significant amounts of the neurotoxin 6-hydroxydopamine (6-OHDA) in the oxidized quinonoid form (topaminequinone, TQ). Formation of TQ was shown to depend critically on the presence of hydrogen peroxide in the reaction medium and was not observed when DA oxidation was carried out using the tyrosinase/O2 system or chemical agents such as periodate or ferricyanide. These and other data suggest that, under the conditions adopted, nucleophilic attack of the hydrogen peroxide anion on DQ leading to TQ significantly competes with the intramolecular cyclization path. In line with this mechanism, the reaction course was not affected by the presence of hydroxyl radical scavengers. Peroxidase/H2O2 oxidation of the model N-acetyldopamine (1) gave, as expected, the 2-hydroxy-1,4-benzoquinone 3 in yields up to 55%, depending on the catecholamine/H2O2 mole ratio. Likewise, reaction of 4-methyl-1,2-benzoquinone (4) with hydrogen peroxide afforded 2-hydroxy-5-methyl-1,4-benzoquinone (5) in good yields. Collectively, these results would point to the possibility that intraneuronal formation of 6-OHDA is associated with an increased production of hydrogen peroxide under oxidative stress conditions.

Anions

[Diltiazem in spontaneous angina: comparison with nifedipine and verapamil].

Sixteen patients with spontaneous angina were studied to assess the relative efficacy of diltiazem (D) at different doses [240 mg/day (D240) versus 360 mg/day (D360)], nifedipine (N: 120 mg/day), and verapamil (V: 480 mg/day), given according to a latin-square protocol. Of the 16 patients, 6 had ischemic attacks with ST elevation, 6 had ischemic attacks with ST depression, 4 showed ST elevation or ST depression in different ischemic attacks. All the patients underwent 24-hour Holter monitoring: at the beginning of the study; during the third day of treatment with D240, D360, N or V; after the withdrawal of each treatment. An atrioventricular block was observed in 2 patients during treatment with V, and in 1 patient during treatment with D240 and D360. In the remaining cases, D and V significantly (p less than 0,05) prolonged the PR interval (D240: + 18%; D360: + 16%; V: + 20%), and reduced the mean daily heart rate (D240: -9%; D360: -12%; V: -11%). The effects of D and V were statistically not different. All the treatments significantly reduced the frequency of the ischemic attacks (p less than 0,05) (D240: -79%; D360: -93%; N: -90%; V: -90%). In particular, D240 reduced by the same percentage (-79%) the frequency of ischemic attacks with ST elevation and ST depression, while D360 completely abolished ischemic attacks with ST elevation and reduced by 79% those with ST depression. Our results suggest that: diltiazem is highly effective in the treatment of spontaneous angina; the efficacy of 360 mg/day of diltiazem is equivalent to that of 120 mg/day of nifedipine and of 480 mg/day of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Mono-dimensional and bi-dimensional echocardiographic diagnosis of corrected transposition of the great vessels].

Three patients with corrected transposition of the great arteries (CTGA) have been studied by means of single plane (M-mode) and two-dimensional (2-D) echocardiography: the first study was performed after surgical closure of a VSD and the remaining two before cardiac catheterization. The following M-mode findings can suggest the diagnosis in CTGA: the interventricular septum (IVS) may not be visualized, there is lack of continuity between the posterior a-v valve (tricuspid) echoes and the anterior great artery (aorta), the posterior a-v valve leaflets may show some abnormalities in shape. The measurement of systolic time intervals of both semilunar valves can help in distinguishing the pulmonary artery from the aorta; further information can be obtained by means of peripheral venous contrast injection, which, in absence of right-to-left shunt, opacifies the posterior great vessel (pulmonary). The 2-D view of the heart allows the identification of the morphological type of ventricle and of the spatial great arteries relationship. The posteriorly and left located ventricle is recognized as morphologically right, because of the tricuspidal shape of its a-v valve: its attachment to IVS is lower than that of the mitral valve (4-chambers view) and three leaflets may be evident (short-axis); 3 papillary muscles and gross trabeculations can be identified (short axis and 4-chambers views, respectively). In long-axis the anterior vessel (aorta) runs parallel to the sternum; in short-axis both vessels are imaged as adjacent circles; by means of peripheral contrast injection, in conditions without right-to-left-shunt, the right and posterior vessel is recognized as a pulmonary artery. The differential diagnosis is discussed with d-transposition, Fallot's tetralogy, Taussig-Bing anomaly, common trunk, univentricular heart. According to our experience, the diagnosis of CTGA and associated defects can be made by M-mode and 2-D echocardiography.

Adult