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Biomedical subjects

T Di Perri

Publications and source records attributed to T Di Perri.

At least 91 records · Page 5Linked to original sources

Ultrastructural modifications of the platelet plasma membrane in vascular diseases and the effect of a carbochromen derivative as studied by freeze-fracture and computer measurement.

A high surface density of the openings of the surface connected canalicular system (SCCS) has been observed in the freeze-fractured plasma membrane of circulating platelets in rabbits fed an atherogenic diet and in hypercholesterolemic type IIa patients. In vitro tests have revealed a correlation between the increased surface density of the SCCS openings and the initial steps of platelet activation. 8-Chlorocarbochromen, a new drug which enhances the in vivo release of prostacyclin from the arterial wall, has been found to be effective in reducing the high surface density of SCCS openings in platelets of rabbits on an atherogenic diet. The present study shows that circulating platelets from patients with peripheral vascular disease present a high surface density of SCCS openings compared to that observed in control subjects. After a single oral administration of 8-chlorocarbochromen, a reduction of the high number of these openings has been observed. Likewise, beta-thromboglobulin levels were found to be high in the patients and to be significantly reduced after oral administration of the drug. This study shows ultrastructural modifications of platelets in conditions related to atherosclerosis and includes data on the effectiveness of 8-chlorocarbochromen in reducing the platelet activation of these patients.

Administration, Oral↗

Conformation and dynamics of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine in solution.

Several conformational and dynamic features of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine in solution have been delineated by investigations of NMR and IR spectroscopic parameters. Both 1D and 2D NMR experiments have been performed for detection of scalar and dipolar proton-proton connectivities, whereas 13C and 1H relaxation parameters have been interpreted in terms of molecular dynamics. The main conformation appeared to be unfolded with the three hydrophobic side chains extending in divergent directions with respect to the backbone. The existence of relatively weak intermolecular hydrogen bonds was demonstrated, involving the formamide end group, with increase in the hydrophobicity of the external surface.

Magnetic Resonance Spectroscopy↗

Defibrotide therapy for thrombophlebitis--controlled clinical trial.

Deep venous thrombosis is a common disease with significant danger of both acute and chronic complications. Widely accepted therapies are based on anticoagulant (heparin and/or anticoagulant agents) or early fibrinolytic therapy. All these therapies frequently have severe side effects. Defibrotide is a new drug with antithrombotic and profibrinolytic activities but without anticoagulant activity and major side effects. To evaluate the efficacy of this drug against acute thrombophlebitis, we treated a group of 10 patients with 200 mg defibrotide intravenously three times a day for 15 days. Fibrinolysis parameters were monitored every other day. The indices of venous function by strain-gauge plethysmography and venous occlusion were evaluated every 7 days. The drug induced a significant improvement in plethysmographic indices and a significant profibrinolytic activity. Defibrotide-treated patients showed a fast disappearance of clinical and instrumental signs of thrombophlebitis. No side effects were reported during the study.

Aged↗

Hemorheological factors in the pathophysiology of acute and chronic cerebrovascular disease.

The hemorheologic changes in three groups of patients suffering from acute and chronic cerebrovascular diseases were studied. Firstly, a horizontal study on 57 patients with definite stroke and on 49 patients with TIA was made. Plasma viscosity, whole blood filtration rate, fibrinogen concentration and hematocrit were evaluated as markers of the rheological property of blood. Blood samples were drawn within 6 h from the onset of vascular syndrome. The findings were compared with values obtained in 112 as controls. At the same time, washed red cell filtration rate, together with lactoferrin, betaglucuronidase and beta-thromboglobulin plasma level were assayed. In both groups the onset of the vascular storm was associated with a marked increase of plasma fibrinogen and of blood and plasma viscosity and a significant decrease of whole blood filterability. Lactoferrin, betaglucuronidase and beta-thromboglobulin levels were also significantly increased. Following this, a longitudinal study was performed on 27 patients with definite stroke and 32 patients with TIA. The clinical regression of acute stroke was associated with the progressive reduction of rheological abnormalities. Finally, 81 patients with clinical diagnosis of cerebrovascular disease due to previous stroke or repeated TIA were studied together. An increase of blood viscosity, of fibrinogen concentration and of hematocrit and a decrease of blood filtration rate together with higher levels of beta-thromboglobulin were registered. These results confirm the existence of an association between CVD and hemorheological alterations and suggest more in depth research directed towards identifying the significance of these alterations in the pathogenesis of tissue ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Adenosine inhibits polymorphonuclear leukocyte in vitro activation: a possible role as an endogenous calcium entry blocker.

Adenosine is able to in vitro inhibit FMLP-dependent activation of polymorphonuclear leukocytes as evaluated by enzyme release, superoxide anion generation and chemiluminescence production. The inhibiting effect is more relevant when A23187 is employed as stimulating agent. In this case the effect is significantly reversed by increasing concentrations of extracellular calcium. Since A23187-dependent activation is strictly dependent on Ca++ influx into the cell, the hypothesis is suggested that adenosine could act by regulatory mechanisms involving membrane calcium transport.

Adenosine↗

Platelet-dependent granulocyte activation in vitro: effect of ticlopidine.

The presence of platelets or platelet release products is known to augment the injury of endothelial cells caused by stimulated neutrophils (PMN leukocytes). In our in vitro studies, platelet-rich or platelet-poor plasma (PRP or PPP) was placed in one compartment and a PMN suspension in the other of a modified Boyden chamber divided by a dialysis membrane. The addition of the aggregating substance (ADP, collagen) to PRP but not to PPP was followed by PMN activation as shown by enzyme release and O-2 generation. The in vivo treatment with ASA completely prevented the platelets from triggering PMN activation. The in vitro addition of a thromboxane synthetase inhibitor (imidazole 10(-3) M) or a lipoxygenase inhibitor (NDGA 10(-6) M) did not show any effect on platelet-dependent PMN activation, thus suggesting that neither TxA2 nor lipoxygenase by-products are involved. Finally, in vitro and in vivo treatment with ticlopidine blunted the stimulating activity of the platelets on PMN. Our data further support the hypothesis that a sequential platelet-PMN interaction may occur, and that the therapeutic effect of some antiplatelet drugs may be partly due to a protective effect against platelet-dependent PMN-mediated vascular damage.

Adenosine Diphosphate↗

[A syllectrometric method to study erythrocyte aggregation].

The authors show a new method to study erythrocyte aggregation; the results of in vitro study, obtained by modification of several parameters (hematocrit, immunoglobulins, fibrinogen concentrations), are exposed. The authors did not find in vivo correlations between MAE and hemorheological parameters in different diseases; they found low MAE values only in myelomatous subjects. Adding erythrocytes from healthy donors to myelomatous plasma and vice versa, they found low MAE values only in samples containing erythrocytes and plasma from myeloma. These results suggest that many factors, not only erythrocyte aggregability, contribute to determine MAE (Mean Aggregation Entity).

Erythrocyte Aggregation↗

Polymorphonuclear leucocytes as a model of Ca++ and Mg++-dependent cellular activation. Effect of calcium entry blockers.

Flunarizine inhibited FMLP- and A23187-induced aggregation, enzyme release and O2- generation from human PMN as a function of its concentration. A23187-dependent PMN aggregation was also studied in media devoid of Ca++ or Mg++. Flunarizine (2.4 X 10(-5)M) significantly affected not only Ca++-supported but also Mg++-sustained PMN aggregation. The inhibiting effect of the drug was reversed by increasing the level of Ca++ (1.2 mM) or Mg++ (2 mM). Nifedipine, another Ca++-entry blocker, was shown to inhibit enzyme release and O2- generation induced by FMLP and A23187 as a function of its concentration, but only slightly affected PMN aggregation at very high concentration (10(-4)M). A role for flunarizine as a specific Mg++-entry blocker is suggested.

Calcimycin↗

[Assay of erythrocyte ATP by chemoluminescence. Protective action induced by pentoxifylline on the depletion of energy from stored erythrocytes].

A new method to measure erythrocyte ATP levels is used. The authors have incubated 6 whole blood samples and 7 samples containing washed red blood cells for 6 h. They measured ATP levels and confirmed an important decrease of the values during the time. If the same samples were incubated with pentoxifylline (1.4 X 10(-4) M), the ATP decrease was less relevant.

Adenosine Triphosphate↗

Heparin inhibition of polymorphonuclear leukocyte activation in vitro. A possible pharmacological approach to granulocyte-mediated vascular damage.

The "in vitro" effects of heparin on different functions of human polymorphonuclear leukocytes were studied. Granulocyte aggregation, enzyme release induced by FMLP and zymosan-activated serum and superoxide anion and chemiluminescence generated by FMLP were assessed. Heparin (25-500 micrograms/ml) was able to inhibit in a dose-dependent way cellular aggregation and degranulation induced either by FMLP or by zymosan-activated serum. FMLP-dependent superoxide anion generation and chemiluminescence were specifically inhibited by heparin at the concentration of 25 micrograms/ml. Our results showed that heparin "in vitro" inhibits all the aspects of the functional and metabolic granulocyte activation. A possible protecting effect of the drug on leukocyte-mediated tissue injury and vascular damage is discussed.

Cell Aggregation↗

Studies of the clinical pharmacology and therapeutic efficacy of pentoxifylline in peripheral obstructive arterial disease.

Studies were carried out to investigate the effects of pentoxifylline on various hemorheological (whole blood, plasma and serum viscosity, erythrocyte filtrability, hematocrit), hemostasiological (blood coagulation and fibrinolysis: euglobulin lysis time, fibrinogen, plasminogen, alpha-2-macroglobulin, alpha-1-antitrypsin, antiplasmin; platelet function: beta-thromboglobulin), and hemodynamic factors (limb perfusion: rest and peak flow, time to peak flow; systemic blood pressure, heart rate). In addition, clinical efficacy was monitored in patients with claudication by assessing walking capacity under placebo controlled double blind cross over conditions. The investigations disclosed the positive influence of acute and chronic pentoxifylline administration on hemorheological, hemostasiological and perfusion parameters, most of the changes recorded being statistically significant. The clinical benefit of pentoxifylline (Trental 400) treatment was demonstrated by the significantly superior increase in walking capacity in comparison to placebo in the controlled study.

Alprostadil↗