1,720,985 research outputs found
Oxygen-mediated myocardial damage during ischameia and reperfusion: Role of the cellular defences against oxygen toxicity
No full textThe possibility that myocardial ischaemia alters the defence mechanisms against oxygen toxicity has been investigated. Ischaemia was induced in isolated, perfused rabbit hearts by reducing coronary flow from 25 ml/min to 1 ml/min for 90 min. Two different degrees of ischaemic damage have been achieved using either spontaneously beating or electrically stimulated hearts. The effects of post-ischaemic reperfusion were also followed for 30 min. Tissue activity of superoxide dismutase (SOD), glutathione peroxidase and reductase (GPD and GRD) have been determined together with tissue content of reduced and oxidized glutathione (GSH and GSSG) and of protein SH groups. The changes in myocardial ATP and CP content and release of CPK and of GSH and GSSG were also determined. Systolic and diastolic pressures were continuously monitored. In the spontaneously beating hearts ischaemia induced a reduction of tissue GSH and protein SH groups. On reperfusion there was a recovery of mechanical function, a transient release of GSH into the coronary effluent and an increase of tissue GSH. In the paced hearts, ischaemia resulted in 50\% reduction of mitochondrial SOD activity together with a reduction of tissue GSH and protein SH groups. Reperfusion induced a massive release of CPK and of GSH and GSSG, a further reduction of tissue GSH concomitant with an increase of GSSG and no recovery of mechanical function. GPD and GRD activity were not affected by ischaemia and reperfusion. These data indicate that severe ischaemia induces a reduction of the protective mechanisms against oxygen toxicity
Effect of superoxide generation on rat heart mitochondrial pyruvate utilization
No full textPrevious research has shown that heart mitochondria are able to produce reactive species of oxygen such as superoxide radicals, hydrogen peroxide and hydroxyl radicals [10, 11]. When these compounds are formed beyond a certain level they are not completely removed by the enzymatic and metabolic processes which neutralize their toxicity, and as a result they are able to produce structural and functional damages that impair mitochondrial function [5, 10]. In order to study the molecular mechanism/s by which the oxygen radicals may function as mediators of cellular injury a flow of these radicals by chemical, enzymatic or photochemical methods has been generated in vitro in the presence of cellular preparations. For example, the exposure of isolated subcellular particles to the enzymatic flow of oxygen radicals produced by the reaction of xanthine oxidase upon xanthine reduced both calcium uptake velocity and Ca2+-ATPase activity in sarcoplasmic reticulum [7], while it reduced Ca2+-stimulated ATPase activity in myofibrillar preparations [4]. In addition, incubation with the xanthine oxidase reaction produced an impairment of the respiratory functions associated with an increased lipid peroxidation in the isolated mitochondria [5, 10]. These negative effects were augmented in alpha-tocopherol-deficient mitochondria [3], but were opposed by the exogenous addition of superoxide dismutase [10]. This report shows that the superoxide radicals generated by the xanthine oxidase reaction reduced rat heart mitochondrial respiration induced by pyruvate. This negative effect was partially prevented by superoxide dismutase and catalase and by thiol protecting agents. Moreover, the generation of free radicals caused a significant reduction in the rate of (1-14C) -pyruvate decarboxylation, while it did not change the transport of pyruvate into mitochondria
Effect of oxygen radicals and hyperoxia on rat heart ornithine decarboxylase activity
No full textRat heart ornithine decarboxylate activity from isoproterenol-treated rats was inactivated in vitro by reactive species of oxygen generated by the reaction xanthine/xanthine oxidase. Reduced glutathione, dithiothreitol and superoxide dismutase has a protective effect in homogenates and in partially purified ornithine decarboxylase exposed to the xanthine/xanthine oxidase reaction, while diethyldithiocarbamate, which is an inhibitor of superoxide dismutase, potentiated the damage induced by O2- on enzyme activity. Dithiothreitol at concentrations above 1.25 mM had an inhibitory effect upon supernatant ornithine decarboxylase activity, while at 2.5 mM it was most effective in the recovery of ornithine decarboxylase activity, after the purification of the enzyme by the ammonium sulphate precipitation procedure. The ornithine decarboxylase inactivated by the xanthine/xanthine oxidase reaction showed a higher value of Km and a reduction of Vmax with respect to control activity. The exposure of rats to 100% oxygen for 3 h reduced significantly the isoproterenol-induced heart ornithine decarboxylase activity. The injection with diethyldithiocarbamate 1 h before hyperoxic exposure further reduced heart ornithine decarboxylase activit
Phosphatidylinositol 3-kinase is required for the induction of ornithine decarboxylase in leukemia cells stimulated to growth.
No full textThe involvement of phosphatidylinositol 3-kinase (PI3K) in the induction of ornithine decarboxylase (ODC) was investigated by using specific PI3K inhibitors. In difluoromethylornithine-resistant L1210 cells stimulated to growth from quiescence, treatment with LY294002 inhibited cell growth and provoked a complete block of the induction of ODC activity (IC50 approximately 2 microM) and ODC protein. Some reduction in the accumulation of ODC mRNA was also observed, whereas ODC turnover was not affected significantly. Wortmannin, another specific inhibitor of PI3K, structurally unrelated to LY294002, also inhibited ODC induction with an IC50 of about 10 nM. These results indicate that PI3K activity is required for the induction of ODC, possibly affecting both ODC mRNA level and translation. Since p70 S6 kinase (p70S6K) is considered an important mediator of PI3K action in several experimental systems, the effect of rapamycin, which can lead to selective inhibition of p70S6K, was also investigated. Rapamycin inhibited p70S6K activity and produced ODC inhibiting effects similar to those elicited by LY294002. However, LY294002 and wortmannin at concentrations which inhibited almost completely PI3K activity did not decrease p70S6K activity, suggesting that p70S6K does not mediate the PI3K effects on ODC, but may lie on a separate pathway in this experimental model
Studio delle delezioni del DNA mitocondriale durante l'invecchiamento in relazione al danno ossidativo del DNA
No full textDottorato di ricerca in biochimica e fisiopatologia dell'invecchiamento. 7. ciclo. Coordinatore C. M. Caldarera. Docente guida P. PudduConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Cardiac resynchronization therapy: could a numerical simulator be a useful tool in order to predict the response of the biventricular pacemaker synchronization?
No full textBackground and Objectives: Cardiac resynchronization therapy (CRT) can be considered as an established therapy for patients with moderate or severe heart failure (HF), depressed systolic function and a wide QRS complex. Biventricular stimulation through the CRT is applied at patients with an intra and/or inter-ventricular conduction delay. The goal of this technique is to resynchronize contraction between and within ventricles. A numerical model of the cardiovascular system, together with the numerical model of the biventricular pacemaker (BPM), can be an useful tool to study the better synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay. Subjects and Methods: Within a group of patients which were representative of the most common disease etiologies of heart failure, seven patients, affected by dilated cardiomyopathy undergoing CRT with BPM, were studied and simulated using the numerical model of the cardiovascular system CARDIOSIM (c). The patients were submitted to echocardiographic evaluation (with pulsate Doppler and tissue Doppler imaging) and electrocardiography evaluation in order to evaluate intra-ventricular and/or inter-ventricular dyssynchrony. These evaluations were made three times: the first one before BPM implantation, the second and the third one respectively within seven days and six months after BPM implantation. Also haemodynamic parameters were measured. Using the software simulator, the pathological conditions before CRT, within seven days and within six months since CRT were reproduced for each patients in order to evaluate the following haemodynamic parameters: the end-systolic and end-diastolic left ventricular volume, the systolic pulmonary arterial pressure, the systolic, diastolic and mean aortic blood pressure and the ejection fraction. Also the trend of the left ventricular elastance was studied for each patient in order to evaluate the benefits produced by the CRT. Results: The results obtained by means the numerical simulator were in good agreement with clinical data measured on the patients. For each patient also the evolution of the left ventricular elastance was in accordance with the literature data. Conclusion: The cardiovascular numerical model seems to be a useful tool to study the synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay and to reproduce the condition of a patient
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