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B Lettieri

Publications and source records attributed to B Lettieri.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial genome involvement in ischemia/reperfusion-induced adaptive changes in human myocardial cells.

AIM: Following previous studies on the ischemia-induced adaptive changes in human cardiac mitochondria, we examined in the present paper the interaction between nitric oxide-induced (NO) partial inhibition of Cyt. c oxidase (Cyt.OX) and mitochondrial encoded subunit 2 expression. Aim of the study was to investigate specific stages of the biochemical and molecular cascade which takes place in cytoprotective mechanisms of ischemic and reperfused cardiac cell. METHODS: We examined human left ventricle samples obtained from 20 patients undergoing elective valve surgery before aortic cross-clamping, 20+/-2 min (prolonged ischemia), 58+/-5 min after cross-clamping (intermittent ischemia) and 21+/-4 min after reconstitution of coronary blood flow (reperfusion). Cyt.OX activity was determined by spectrophotometric method and adenosine triphosphate (ATP) content using bioluminescent assay. Malondialdehyde (MDA) assumed as reactive oxygen species (ROS) generation marker was determined by high-performance liquid chromatography method. On the same cardiac samples mitochondrial encoded Cyt.OX subunit 2 expression was examined by immunoblot analysis and blu native gel electrophoresis method. Statistical study of obtained data was performed using repeated measures analysis of variance (ANOVA). RESULTS: Prolonged as well intermittent ischemia caused reduction of Cyt.OX activity and ATP, a moderate accumulation of ROS and down-regulation of Cyt.OX subunit 2. When reperfused the cardiomyocytes showed a progressive increase of Cyt.OX activity, ATP pools and Cyt.OX subunit 2 expression. ROS generation was significantly increased by the rapid oxygen re-immission in the cardiac cell. CONCLUSIONS: These data confirm the suggestion that prolonged as well as intermittent ischemia induces activation of cytoprotective mechanisms crucial for cardiac cell survival. Indeed, co-ordinated down-regulation of Cyt.OX activities, ATP pools and mitochondrial encoded Cyt.OX subunit 2 are in favour of an ischemia-activated adaptive mechanism leading to transient and reversible oxidative injury. This observation is confirmed by reduction of apoptosis molecular markers and by complete recovery of mitochondrial oxidative activities in reperfused cardiac tissue.

Adaptation, Physiological↗
PubMed2005

Mechanisms of cell protection by adaptation to chronic and acute hypoxia: molecular biology and clinical practice.

Several experimental and clinical studies have shown that specific biochemical and molecular pathways are involved in the myocardial and skeletal muscle cell tolerance to acute and/or chronic hypoxic injury. A number of different factors were proposed to play a role in the preservation of tissue viability, but to a few of them a pivotal role in the adaptive mechanisms to hypoxic stimuli could be ascribed. Starting from the observation that mitochondrial electron transport chain (ETC) enzymic complexes are the targets of oxygen reduced availability, most of data are compatible with a mechanism of enzymic adaptation in which the nitric oxide (NO) generation plays the major role. If the partial and reversible NO-induced inhibition of ETC enzymic complexes represents the most rapid and prominent adaptive mechanism in counteracting the damaging effects of hypoxia, the sarcolemmal and mitochondrial K+(ATP) channels activation results to be closely involved in cytoprotection. This process is depending on protein kinase C (PKC) isoform activation triggered by reactive oxygen species (ROS) generation, adenosine triphosphate (ATP) depletion and Ca++ overload. It is well known that all these factors are present in hypoxia-induced oxidative damage and mitochondrial Ca++ altered pools represent powerful stimuli in the damaging processes. The activation of mitochondrial K+(ATP) channels leads to a significant reduction of Ca++ influx and attenuation of mitochondrial Ca++ overload. Closely linked to these adaptive changes signal transduction pathways are involved in the nuclear DNA damage and repair mechanisms. On this context, an essential role is played by the hypoxia-induced factor-1alpha (HIF-1alpha) in terms of key transcription factor involved in oxygen-dependent gene regulation. The knowledge of the biochemical and molecular sequences involved in these adaptive processes call for a re-evaluation of the therapeutic approach to hypoxia-induced pathologies. On this light, some specific aspects of the therapeutic management of critically ill patients are taken into consideration and discussed in relation to the cellular biodynamics.

Acute Disease↗
PubMed2005

The aged patient who has undergone an operation in the intensive care unit.

The reaching of 13% within the Italian population of those who are older than 70 has caused a significant rise in the number of the elder people who undergo major surgery operations; this is due also to the availability of mini-invasive endo-laparoscopic techniques, to the availability of new very manageable anaesthetics and new anaesthesia plans, suitable for the elder, to a more effective control of post-operative pain, and mostly to a comfortable access to I.C.U. in the post-operative phase.

Aged↗
PubMed2002

Ozonized autohaemotransfusion and fibrinolytic balance in peripheral arterial occlusive disease.

The acute effects of a major ozonized autohaemotransfusion on blood fibrinolytic capacity were evaluated in 20 subjects affected by peripheral arterial occlusive disease (PAOD). The parameters examined were tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). In subjects not previously submitted to autohaemotransfusion ('unaccustomed' subjects), whether they were PAOD patients or healthy volunteers, the PAI-1/t-PA ratio in the blood samples taken 15 min before the autohaemotransfusion was higher (P < or = 0.05) than at baseline. These changes were independent of the presence of ozone in the autohaemotransfusion blood. Values in both healthy and PAOD-affected individuals were again at baseline 120 min after the end of autohaemotransfusion. In PAOD patients and in healthy subjects previously submitted to several autohaemotransfusions ('accustomed' subjects), the PAI-1/t-PA ratio did not significantly change before, during and after an additional autohaemotransfusion. The results (the increased heart rate and epinephrine and norepinephrine urinary excretion only in non-accustomed subjects) suggest that the acute fibrinolytic imbalance is caused by the apprehensive state produced by the procedure in unaccustomed subjects. Autohaemotransfusion with ozonized blood per se does not significantly influence the fibrinolytic balance.

Adult↗
PubMed2001

[The nitric oxide metabolism in the hypoxic, ischemic and reperfused human skeletal muscle cell: clinical and therapeutical observations].

BACKGROUND: The biochemical and metabolic role played by nitric oxide (NO) in course of oxidative stress due to cell hypoxia, ischemia and reperfusion has a determinant relevance in the mitochondrial adaptive changes which antagonize the irreversible morpho-functional damage. In particular conditions, such as in prolonged ischemia and/or exogenous NO supplementation, this element is present in the radical form (NOO*) concurring to peroxidative cell injury. Aim of this study was to investigate these opposite NO aspects in hypoxic, ischemic and reperfused human skeletal muscle tissue. METHODS: Skeletal muscle samples were taken during elective knee orthopedic surgery in 10 consecutive patients. The biopsies were obtained before, after 5+/-1 min and 58+/-2 min from tourniquet application and then after 18+/-3 min following muscle reperfusion. The samples, immediately frozen in liquid nitrogen, were assayed for endocellular free NO following the gas-amperometric method described by Palmerini C. RESULTS: When compared with normoxic tissues, a significant decrease in free NO content was observed in hypoxic samples. After about 60 min of prolonged ischemia the NO levels show an evident increase, while the tissue reperfusion leads to a progressive restoration of physiological content in the cellular free nitric oxide. CONCLUSIONS: The obtained data in hypoxic muscle cell seem to underline the pivotal role played by NO in adapting the cytochrome c oxidase oxidative activity to lower O2 bio-availability. On the other hand the prolonged ischemia leads to a consistent NOO* generation triggered by oxyradical generation and Ca2+ intracellular over load. Even if the tissue reoxygenation restores the normal NO levels it is arguable that the pre-treatment of ischemic cell with antioxidants, Ca-antagonist and Dexamethasone supplementation could represent a crucial and specific therapeutic approach to critically ill patient.

Adult↗
PubMed2001

Biomolecular and biochemical response of myocardial cell to ischemia and reperfusion in the course of heart surgery.

BACKGROUND: Previous studies have shown that biomolecular and biochemical adaptive changes antagonize oxidative damage due to hypoxia and ischemia in myocardial cells. The aim of our study was to verify in human ischemic and reperfused cardiac tissue the relationship between mitochondrial enzyme activities and the activation of HSP70 and c-fos syntheses in the context of a cytoprotective mechanism. Nitric oxide (NO) modulating effects on mitochondrial respiratory chain enzyme activities in ischemic and reperfused tissue were investigated (preliminary report). METHODS: During elective coronary artery bypass grafting, in 30 consecutive patients ventricle samples were taken one before aortic clamping the second after 55+/-8 min ischemic period and the third 34+/-5 after final reperfusion. Coronary sinus blood samples were taken in parallel to assess free radical release measured by malonaldehyde (MDA) levels. In a small number of patients (N=5) nitric oxide tissue levels were analyzed. RESULTS: When compared with normoxic tissue, a significant decrease in cytochrome Coxidase (COX) and succinate Cyt-c reductase (SCR) activities in ischemic and reperfused samples were observed. The activation of HSP70-72 and c-fos transcription factor was evident in courses of ischemia and reperfusion. Blood MDA levels underline the concept that oxyradical generation characterize the peroxidative damage in reoxygenated myocardial tissue while adaptive changes which occur in ischemic cells seem to antagonize the oxyradical injury. CONCLUSIONS: In the course of heart surgery the myocardial cell seems to prevent ischemic damage by activating some peculiar biomolecular and biochemical adaptive changes which permit the reversibility of the oxidative injury. In contrast it appears evident that massive and rapid reoxygenation of the cardiac tissue leads to peroxidative damage due to oxyradical generation. Nitric oxide seems to play a crucial role in cellular adaptation to ischemia even if further studies will be needed to elucidate these findings. From the data obtained in this work we cannot draw certain conclusions in terms of human cardiac cell adaptation to ischemia whereas it seems convincible that reoxygenation, as actually employed in clinical practice, compromises the integrity of the cells.

Blotting, Northern↗
PubMed2001

Signal transduction mechanisms and nitric oxide in hypoxic and ischemic human cardiac ventricular cell.

BACKGROUND: Nitric oxide (NO) plays a well-known role in regulating endocellular adaptive changes to acute hypoxia and ischemia. The reversible inhibition of complex IV of the mitochondrial respiratory chain fulfils a cytoprotective function, whereas the progressive inhibition of complex I and II reveals the onset of irreversible oxidative damage due to persistent NO production in response to prolonged hypoxia and/or ischemia. In hypoxic or ischemic human myocardial cells, death may be caused by apoptosis or necrosis following the activation of the biomolecular signal transduction mechanisms. The activation of MAPK (mitogen-activated protein kinase) followed by ERK (extracellular regulated kinase) and p21waf is necessary in this respect. The myocardial cell is well known for its postmitotic nature and through their activation these kinases aim to repair DNA damaged by oxidative stress in order to guarantee the survival of the cell itself. A direct correlation has been found between the activation of these kinases and NO production. It was decided to carry out this study in hypoxic and ischemic human heart ventricular tissue in order to confirm this connection. METHODS: In 10 patients undergoing cardiac valvular replacement, ventricular samples were collected before aortic clamping, after 15 min of ischemia and after 60 minutes during which the patients received doses of hematic cardioplegic solution at regular intervals. RESULTS: The results show a rapid increase in NO production in response to ischemia followed by a tendency for levels of this element to fall. MAPK, ERK and p21waf activation was parallel to No production, irrespective of the repeated administration of hematic cardioplegic solution. The heart tissue examined 60 minutes after aortic clamping came from a ventricular area subject to preconditioning mechanisms. In view of this, the data obtained must be seen in terms of the close correlation between the mitochondrial action played by NO and the contemporary and consequent activation of unique signal transduction mechanisms. CONCLUSIONS: This may prove important to our understanding of preconditioning mechanisms involving the myocardial and confirms the role played by the said kinases with regard to the survival of hypoxic and ischemic human heart tissue. Although not final, these deductions may be important in clinical and therapeutic terms for the management of critical patients.

Heart Ventricles↗
PubMed2000

[Biochemical and metabolic aspects of oxyradical pathology in the hypoxic-ischemic reperfused human skeletal muscle tissue. Clinical markers and therapeutic approach].

BACKGROUND: Following our previous studies on the biomolecular and biochemical aspects of the human tissue oxidative damage due to hypoxia, ischemia and reperfusion, aim of the present work is to evaluate the role played by oxyradical generation in the morphofunctional cellular injury. We evaluated the tissue levels of some metabolic markers (MDA, Catalase, Uric Acid) to obtain a pathogenic picture and then a therapeutic approach closely related to the cellular biodynamics. METHODS: A skeletal muscle samples were taken during elective knee orthopedic surgery in 20 consecutive patients. The biopsies were taken in normoxic conditions and after 5 +/- 1 and 62 +/- 3 min form tourniquet application and finally 21 +/- 2 min following muscle reperfusion. The samples were assayed for tissue Malondialdeyade (MDA), uric acid and catalase (CAT) contents with HPLC and fluorimetric procedures. All data were evaluated in terms of computerized statistical analysis. RESULTS: When compared to normoxic tissue (1.24 +/- 0.26 nmoli.mg-1 protein), the MDA levels show a moderate increase in hypoxic (1.66 +/- 0.12) and ischemic tissue (1.78 +/- 0.13), while highly significant is the rise in reperfused muscle MDA content (5.94 +/- 0.15). The uric acid as far as CAT shows no appreciable alterations in hypoxia and ischemia. Following reoxygenation an increase in uric acid contents with a concomitant CAT tissue consumption appear evident. CONCLUSIONS: The obtained data seem to underline the cytoprotective role played by adaptive changes in the hypoxic and ischemic human cells. On the contrary, the rapid reoxygenation of the ischemic tissue appears to start oxyradical neo-generation. In clinical and therapeutic terms these observations underline a peculiar and different approach to the critically ill patient.

Adult↗
PubMed1991

Cardiogenic shock and L-carnitine: clinical data and therapeutic perspectives.

Research experiences on the use of L-carnitine in conditions of acute hypoxia underline the protective role of this molecule on the cellular enzymic complex. To obtain unconfutable clinical data at this regard, the survival rate in two groups of patients affected by cardiogeic shock was evaluated. The first group (80 patients) was treated with L-carnitine while the second group (36 patients) received sodium bicarbonate. The results showed a significant response to L-carnitine treatment, indicating the role of this molecule on the metabolic acidosis due to shock. The sum of these data confirmed the role of L-carnitine in the reversible phase of cardiogenic shock in terms of enzymic protection in the course of cellular oxidative damage.

Adult↗