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Biomedical subjects

M Attanasio

Publications and source records attributed to M Attanasio.

31 records · Page 2Linked to original sources
PubMed1995

Defibrotide reduces monocyte PAI-2 and procoagulant activity.

Defibrotide is a polydeoxyribonucleotide-derived anti-ischemic drug with multiple sites of action involving both plasmatic and cellular targets. This agent has been demonstrated to produce profibrinolytic, cytoprotective, and vaso-facilatory actions. Since monocytes are increased in the mediation of some of the pathophysiologic responses seen in ischemic disorders, the functional properties of these cells were investigated in experimental conditions to evaluate their behavior during resting and stimulated states. Defibrotide was supplemented in these systems to determine its modulatory action. In this investigation Defibrotide was found to decrease the PAI-1 levels and may indicate that this may be the mechanism for its profibrinolytic actions. Defibrotide was also found to reduce the procoagulant activity of monocytes in these experimental settings. Both PAI and procoagulant factors play an important role in the pathophysiology of inflammation, DIC, and ischemia. Defibrotide induced reduction of these two factors represents the mechanism whereby this agent produces its therapeutic action.

Blood Coagulation Factors↗
PubMed1993

Interleukin-1 beta and interleukin-6 release by peripheral blood monocytes in head and neck cancer.

In patients with advanced head and neck squamous cell carcinoma (HNSC), evidence of cell-mediated immunity and monocyte functional abnormalities has been reported. We studied the production of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by peripheral blood monocytes from 22 patients with HNSC (12 larynx and ten oral cavity cancers) in comparison with monocyte cytokine production of age-matched healthy subjects. Pure monocytes were incubated with and without lipopolysaccharides (LPS) (10 micrograms ml-1) for 4 h at 37 degrees C and IL-1 beta and IL-6 concentrations were determined in supernatants by specific ELISA. There was no significant difference in IL-1 beta levels in monocyte supernatants from cancer in comparison to control subjects; conversely, a higher IL-6 production by unstimulated and LPS-activated cells from HNSC patients than from controls was found. No relationship was observed between cytokine production and cancer stage. The regression analysis evidenced a significant correlation between IL-1 beta and IL-6 monocyte-release in HNSC patients and in controls, so suggesting a possible autocrine control of IL-6 production by other cytokines.

Aged↗
PubMed1993

Lupus anticoagulant and monocyte procoagulant activity in polyabortive women.

Monocyte stimulation may be induced by various agents. Monocytes generate procoagulant activity (PCA) in response to stimulation; they widely interact with the hemostatic system and participate in thrombin formation. Extensive placental thrombotic infarction has been implicated in fetal death in polyabortive patients with lupus anticoagulant (LA). We investigated 38 polyabortive women: 17 LA negative (LA-) and 18 LA positive (LA+). We compared the results with 25 clinically normal women. After four hours of incubation, the mean value of monocyte PCA in the LA+ women was significantly higher than in either the LA- or the control group (p < 0.0001). The monocyte PCA was out of the range of the controls in 9 of the 18 LA+ women. No correlation was observed between the levels of LA and monocyte PCA (r = 0.02; p = 0.94). No differences were found in monocyte PCA increase when induced by LA-, LA+ or control plasma; in all cases the increase was about five-six fold. Our results indicate that an increased monocyte PCA is present in some LA+ polyabortive women, thus suggesting that monocyte activation might be involved in the formation of thrombotic placental infarction and the consequent fetal loss in some patients. It might also suggest that these patients, in particular, could benefit from corticosteroid treatment, which is known to inhibit the formation of monocyte PCA.

Abortion, Habitual↗
PubMed1992

Transient intermittent lymphocyte activation is responsible for the instability of angina.

BACKGROUND: Blood clotting activation is an important component of the inflammatory response; the outbursts of unstable angina are usually associated with increased thrombin formation and coronary mural thrombosis. METHODS AND RESULTS: To investigate 1) whether monocyte activation is responsible for the enhanced thrombin formation during bursts of unstable angina and 2) what mechanism(s) might be responsible for monocyte activation, we studied patients with unstable angina (n = 31), stable effort angina (n = 23), left endoventricular thrombosis (n = 8), and control subjects (n = 44), measuring plasma fibrinopeptide A (FPA) levels and the capacity of monocytes to express procoagulant activity (PCA) and of lymphocytes to modulate this expression. Patients with unstable angina and patients with endoventricular thrombosis had significantly (p less than 0.0001) higher FPA plasma levels than patients with effort angina and control subjects. However, only monocytes from unstable angina patients expressed significantly increased PCA characterized as tissue factor-like activity (units/10(5) monocytes, median and range; 120, 1.1-463.2 versus 10.8, 0.8-39.1 in control subjects; p less than 0.0001 versus the other groups). When 14 patients with unstable angina were restudied 8-12 weeks later, they showed neither elevated plasma FPA levels nor monocyte PCA. In unstable angina patients, there was a correlation between FPA and PCA (r = 0.56, p less than 0.001). For expression of PCA by monocytes, both an incubation of at least 2 hours with lymphocytes and direct monocyte-lymphocyte contact were needed. In reconstitution and cross-mixing experiments, only lymphocytes from patients with active unstable angina induced the expression of PCA by monocytes from both control and patient groups. CONCLUSIONS: The results demonstrate that the increased thrombin formation in unstable angina patients is due to the expression of tissue factor-like activity by activated monocytes. The monocyte activation appears to be a part of a lymphocytic cell-instructed response intermittently triggered by unknown factors.

Aged↗
PubMed1992

Monocyte tumor necrosis factor production in head and neck squamous cell carcinoma.

Changes in monocyte and macrophage function have been demonstrated in patients with head and neck squamous cell carcinoma. The purpose of this study was to evaluate tumor necrosis factor (TNF) production by activated monocytes from patients with head and neck squamous cell carcinoma and to evaluate its relation to cancer stage, weight loss, and performance status. Monocytes from patients (n = 10) and controls (n = 10) were isolated from peripheral blood mononuclear cells by plastic adherence and incubated with lipopolysaccharide (10 micrograms/mL). The TNF concentration of supernatants was assayed by TNF alpha-specific immunoassay. The TNF production by monocytes from head and neck squamous cell carcinoma patients was significantly higher (P less than .001) than those of controls. No significant relationship was found to cancer stage, weight loss, and performance status. These findings indicate that, in head and neck squamous cell carcinoma patients, an increased TNF production by activated monocytes takes place which does not correlate with cancer stage, cancer-related weight loss, and performance status.

Activities of Daily Living↗
PubMed1990

Cyclooxygenase and lipoxygenase metabolite synthesis by polymorphonuclear neutrophils: in vitro effect of dipyrone.

Functional activity of polymorphonuclear neutrophils (PMN) is associated with the metabolism of Arachidonic Acid (AA) released from membrane phospholipids. In this study the in vitro effect of dipyrone, a non steroidal anti-inflammatory drug, on the production of AA metabolites through cyclooxygenase (CO) and lipoxygenase (LO) pathways by stimulated PMN has been investigated. PMN isolated by counterflow centrifuge elutriator were greater than 98% pure and viable. Metabolite production was evaluated by RIA of Thromboxane A2 (TxA2), Prostaglandin E2 (PGE2), Leukotriene B2 (LTB4) and Leukotriene C4 (LTC4) after PMN stimulation with calcium ionophore A 23187 (20 microM). The levels of beta-thromboglobulin (RIA) lower than 5 ng/ml allowed us to rule out activation of residual contaminant platelets. In these experimental conditions, in the absence of dipyrone the products (ng/10(6) cells) of AA metabolism were LTB4 (3.51 +/- 0.22), LTC4 (0.81 +/- 0.08), TxB2 (0.144 +/- 0.025) and PGE2 (0.150 +/- 0.017). Incubation with dipyrone induced changes of PGE2 and TXB2 production in a dose dependent fashion (r = 0.83 and r = 0.87, p less than 0.001), obtaining already at the lowest drug concentration (5 micrograms/ml) a significant inhibition (33 and 40% for TxB2 and PGE2 p less than 0.005). No significant changes of LTB4 and LTC4 production have been observed. The results of this study indicate that dipyrone relevantly affects CO metabolite synthesis by stimulated PMN at concentrations comparable to those reached in therapeutic use. The inhibition of PGE2 synthesis which is present in inflamed tissues and actively participates in inflammatory reactions, could contribute to the therapeutic anti-inflammatory action of dipyrone.

Arachidonic Acids↗
PubMed1990

Sex related differences in platelet TxA2 generation.

Platelet lipid composition, c arachidonic acid (AA) metabolism by platelets (stimulated with thrombin), serum thromboxane (Tx)B2 production and plasma lipid composition were investigated in 53 healthy females (18-45 years) and 65 males (19-45 years) with similar dietary habits. In males, serum TxB2 production and cholesterol platelet membrane levels were found significantly higher (p less than 0.001 and p less than 0.05) than in females. No differences were observed between the two groups in the AA conversion through cyclo-oxygenase and lipoxygenase pathways or in the platelet phospholipid fatty acid composition. These findings indicate that in males the platelet proaggregatory capacity is greater than in females and the higher platelet TxB2 production does not depend on a larger AA availability or on enzyme activation for its conversion. The increased TxB2 production may be, at least in part, induced by functional differences such as a different membrane cholesterol content inducing, in its turn, an increased microviscosity and/or higher number of platelet receptors for thrombin.

8,11,14-Eicosatrienoic Acid↗
PubMed1990

Heparin, monocytes, and procoagulant activity.

Monocytes are able to specifically bind heparin rapidly, reversibly, and saturably with 5.5 +/- 2.6 x 10(6) binding sites per monocyte and a dissociation constant of 330 +/- 221 nmol/l. Moreover, at least 40-50% of the cell-bound heparin can be internalized. Heparin binding by monocytes is affected by cell stimulation with an increase of the availability of binding sites after challenge with calcium ionophore, lipopolysaccharide, and interleukin 2. The interaction of heparin with monocytes reversibly decreases the expression of tissue factor on the cellular surface, so hampering the cellular procoagulant potential.

Blood Coagulation↗
PubMed1990

Low-dose heparin as an antithrombotic agent.

Heparin, after subcutaneous administration, has been found to be able to bind to endothelial receptors both in rabbits and in humans. N-sulphonate 35S-heparin remains bound in rabbits for at least 24 h and is able to enhance the inactivation process of thrombin and factor Xa. Heparin subcutaneously (200 U/kg) injected for 2 weeks resulted in an enhanced inactivation of thrombin and factor Xa by the endothelium. The antithrombin-enhancing activity persists longer than the anti-Xa activity. In man, daily subcutaneous administration of heparin (12,500 U/day) for 2 weeks significantly reduces the increased fibrinopeptide A plasma levels and normalizes the increased 125I-fibrinogen turnover. The present work indicates that heparin administration at a low dose represents a treatment able to remarkably enhance the antithrombotic properties of the vessel wall, independently of the presence of detectable heparin levels in the circulating blood.

Animals↗
PubMed1989

Polyamines in the small intestine of rats after whole-body irradiation.

The behaviour of polyamines (putrescine, spermidine and spermine) in the small intestine was studied in rats exposed to a single whole-body dose of 3 Gy administered at four different times of the day. Polyamine content decreased a few hours after irradiation but quickly returned to normal values. Putrescine levels reached the lowest values and returned to the control levels later than spermidine and spermine. A temporary increase in spermidine and spermine content was observed from 5 to 20 days. The postirradiation behaviour of the animals exposed at different times of the day showed no important differences. Polyamine modifications were studied in relation to [3H]thymidine uptake and other morphological and biochemical parameters. The results indicate that polyamine content can be used to monitor the damage and recovery phases of radiation injury in the small intestine.

Animals↗