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C Basso

Publications and source records attributed to C Basso.

80 records · Page 5Linked to original sources
PubMed1985

Prominent role of DT-diaphorase as a cellular mechanism reducing chromium(VI) and reverting its mutagenicity.

Rat liver postmitochondrial (S-12) fractions accounted for the bulk of the activity of whole cell homogenates in reducing chromium(VI) and accordingly in decreasing its mutagenicity. Both cytosolic (S-105) and microsomal fractions concurred to this process, which in all subcellular preparations tested was selectively induced by phenobarbital and especially by Aroclor 1254, but not by 3-methylcholanthrene. Cytosolic fractions were markedly more efficient in reducing chromium(VI) than microsomal fractions recovered from the same amount of tissue (liver or lung), although the latter preparations had a higher specific activity. The microsomal activity was exclusively NADPH dependent. A minor part of the cytosolic reduction was determined by nonenzymatic components, notably by some electron donors and chiefly by reduced glutathione, which proved to reduce chromium(VI) at physiological concentrations. However, also in cytosolic fractions, the most important contribution to chromium reduction was enzyme catalyzed, as shown by the following properties: thermolability; requirement for exogenous NADH or NADPH [supplied as such or in the form of a NADPH-generating system (S-9 mix)]; and saturation by chromium(VI). The likely involvement of DT-diaphorase in this metabolic process is supported by several findings, including its sharp pH dependence and its partial suppression by known inhibitors of this enzyme protein, such as p-chloromercuribenzoate, L-thyroxine, and dicumarol (which conversely did not counteract the metabolic deactivation of the other direct-acting mutagens 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine 2HCl and epichlorohydrin). Similarly, cytosolic reduction of chromium(VI) was partially inhibited by selective metabolic depletors of both coenzymes of DT-diaphorase, i.e., NADPH and NADH. Pretreatment of rats with enzyme inducers (phenobarbital and 3-methylcholanthrene) stimulated the activity of DT-diaphorase in liver cytosolic fractions. A dramatic stimulation (35 to 40 times over untreated controls) was produced by Aroclor 1254, which also coinduced the liver cytosolic activity of enzymes involved in the glucose 6-phosphate-dependent pathway of both nicotinamide-adenine-dinucleotide phosphate and glutathione reduction (glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase). In the lung cytosol, a slight yet significant stimulation of some of these enzyme activities was determined by the daily intratracheal instillations of high doses of chromium(VI) itself for 4 weeks, a condition which has been found to enhance the pulmonary metabolism of this metal ion.

Animals↗
PubMedDate not supplied

Genotoxicity assay of oil dispersants in bacteria (mutation, differential lethality, SOS DNA-repair) and yeast (mitotic crossing-over).

5 oil dispersants and a sample of paraffin were devoid of mutagenic activity in the Ames reversion test, with and without S9 mix, using 7 his- S. typhimurium strains (TA1535, TA1537, TA1538, TA97, TA98, TA100, TA102). However, 3 dispersants produced direct DNA damage in E. coli WP2, which was not repairable in repair-deficient strains (WP2uvrA, CM871, TM1080), as shown by two different DNA-repair test procedures. The uvrA excision-repair system was in all cases the most important mechanism involved in repairing the DNA damage produced by oil dispersants, while the combination of uvrA with other genetic defects (polA, recA, lexA) decreased the efficiency of the system. The observed genotoxic effects were considerably lowered in the presence of S9 mix containing liver S9 fractions from Aroclor-treated rats. The sample of oil dispersant yielding the most pronounced DNA damage in repair-deficient E. coli failed to induce gene sfiA in E. coli (strain PQ37), using the SOS chromotest, or mitotic crossing-over in Saccharomyces cerevisiae (strain D5). The direct toxicity of the oil dispersant to both bacterial and yeast cells was markedly decreased in the presence of rat-liver preparations. These two short-term tests were effective in detecting the genotoxicity of both direct-acting compounds (such as 4-nitroquinoline N-oxide and methyl methanesulfonate) and procarcinogens (such as cyclophosphamide, 2-aminoanthracene and 2-aminofluorene). Moreover, the SOS chromotest was successfully applied to discriminate the activity of chromium compounds as related to their valence (i.e. Cr(VI) genotoxic and Cr(III) inactive). Combination of oil dispersants with Cr(VI) compounds did not affect the direct mutagenicity to S. typhimurium (TA102) of a soluble salt (sodium dichromate) nor did it result in any release of a water-soluble salt (lead chromate), as also confirmed by analytical methods. On the other hand, exposure to sunlight tended to decrease, to a slow rate, the direct genotoxicity of an oil dispersant in the bacterial DNA-repair test.

Chromates↗
PubMedDate not supplied

Cardiovascular causes of sudden death in young individuals including athletes.

From 1978 to 1993 in the Veneto region, we collected 200 cases of sudden death in the young (</=35 years). Sudden death was cerebral in 15 cases (7.5%), respiratory in 10 (5%), and cardiovascular in 163 (81.5%), whereas it remained unexplained in 12 cases (6%). Among cardiovascular sudden death, obstructive coronary atherosclerosis accounted for 23% of cases, arrhythmogenic right ventricular cardiomyopathy for 12.5%, mitral valve prolapse for 10%, conduction system abnormalities for 10%, congenital coronary artery anomalies for 8.5%, myocarditis for 7.5%, hypertrophic cardiomyopathy for 5.5%, aortic rupture for 5.5%, dilated cardiomyopathy for 5%, nonatherosclerotic-acquired coronary artery disease for 3.5%, postoperative congenital heart disease for 3%, aortic stenosis for 2%, pulmonary embolism for 2%, and other causes for 2%. Cardiac arrest remained unexplained in 6% of the cases. Specific pathology and pathogenetic mechanisms of each disease were investigated and correlated with clinical signs and symptoms in detail. A large spectrum of cardiovascular disorders, both congenital and acquired, may represent the organic substrate of sudden death in the young. The underlying abnormality is frequently concealed and discovered only at postmortem examination. Most of the diseases, although asymptomatic, are potentially detectable during life with proper imaging tests.

Adolescent↗
PubMedDate not supplied

What is the Brugada syndrome?

In 1992, Brugada and Brugada reported a distinct subgroup of patients with episodes of "idiopathic"polymorphic ventricular tachycardia or ventricular fibrillation characterized by a unique electrocardiographic (ECG) pattern, which consisted of right bundle branch block and ST-segment elevation from V1 to V2-V3. As in patients with long QT syndrome, the ECG changes and the ventricular electrical instability could not be explained by structural heart disease, myocardial ischemia, or electrolyte disturbances. The syndrome can be inherited and predominantly affects males. Clinical presentation includes cardiac arrest or syncope caused by rapid ventricular tachycardia or fibrillation characteristically occurring at rest or during sleep. The clinical outcome of affected patients is poor unless they receive an implantable cardioverter defibrillator. The ECG pattern and the electrical ventricular instability have been explained by the dispersion of repolarization between the right ventricular epicardium and endocardium, which predisposes to local reexcitation of myocytes with different action potential durations. A disease-causing missense mutation in the cardiac sodium channel gene SCN5A has been recently reported in patients with Brugada syndrome. It is mandatory for the clinician to carefully rule out any organic heart disease before suggesting a diagnosis of Brugada syndrome, because the typical ECG pattern with the risk of sudden arrhythmic death is also observed in patients with structural heart diseases in the setting of arrhythmogenic right ventricular cardiomyopathy.

Adult↗
PubMedDate not supplied

Arrhythmogenic right ventricular cardiomyopathy: current diagnostic and management strategies.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease of unknown etiology characterized by the peculiar right ventricular (RV) involvement. Distinctive pathologic features are myocardial atrophy and fibro-fatty replacement of the RV free wall, and clinical presentation is usually related to ventricular tachycardias with a left bundle branch block pattern or ventricular fibrillation leading to cardiac arrest, mostly in young people and athletes. Later in the disease evolution, progression and extension of RV muscle disease and left ventricular involvement may result in right or biventricular heart failure. The diagnosis of ARVC may be difficult because of several problems with specificity of ECG abnormalities, different potential etiologies of ventricular arrhythmias with a left bundle branch morphology, assessment of RV structure and function, and interpretation of endomyocardial biopsy findings. Therefore, standardized diagnostic criteria have been proposed by the Study Group on ARVC of the European Society of Cardiology. According to these guidelines, the diagnosis of ARVC is based on the presence of major and minor criteria encompassing electrocardiographic, arrhythmic, morphofunctional, histopathologic, and genetic factors. Since the assessment of sudden death risk in patients with ARVC is still not well established, there are no precise guidelines to determine which patients need to be treated and what is the best management approach. The therapeutic options include beta-blockers, antiarrhythmic drugs, catheter ablation, and implantable cardioverter defibrillator (ICD). The ICD is the most effective safeguard against arrhythmic sudden death. However, its precise role in changing the natural history of ARVC by preventing sudden and nonsudden death needs to be evaluated by a prospective study of a large series of patients. In patients in whom ARVC has progressed to severe RV or biventricular systolic dysfunction with risk of thromboembolic complications, treatment consists of current therapy for heart failure including anticoagulant therapy. In cases of refractory congestive heart failure, patients may become candidates for heart transplantation.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Congenital coronary artery anomalies as an important cause of sudden death in the young.

Unlike sudden cardiac death in adults and elderly people, sudden cardiac death in young people (< or =35 years) is often triggered by nonatherosclerotic coronary artery disease, either acquired (arteritis, spontaneous dissection) or congenital in origin. In particular, congenital coronary artery malformations were reported as the cause of 5%-35% of sudden death in the young, and a wide range of abnormalities including anomalous origin, course, or both were described.

Adolescent↗
PubMedDate not supplied

Detoxifying activities in alveolar macrophages of rats treated with acetylcysteine, diethyl maleate and/or aroclor.

Single or sequential treatment of rats with the thiol N-acetyl-L-cysteine (NAC), the glutathione depletor diethyl maleate (DEM) and the enzyme inducer Aroclor 1254 (AR) produced several significant variations on metabolic activities of pulmonary alveolar macrophages (PAM). Specifically, all three compounds elicited an increase in some oxidoreductase activities, including the two dehydrogenases involved in the hexose monophosphate shunt (G6PD and 6PGD) and NADH- or NADPH-dependent diaphorases. Diaphorase activities were especially increased by sequential treatments with AR and DEM or with DEM and NAC. Both NAC and AR also stimulated other detoxifying mechanisms, such as those related to GSH S-transferase activity and to the NADPH-dependent reduction of hexavalent chromium. Therefore, all the monitored parameters were significantly enhanced not only by the enzyme inducer, but also by the thiol, demonstrating its protective role in the biotransformation of mutagenic/carcinogenic compounds.

Acetylcysteine↗