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Biomedical subjects

F Laghi Pasini

Publications and source records attributed to F Laghi Pasini.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacodynamics of salmon calcitonin in humans: new markers of pharmacological activity.

In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO2 in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU.kg-1 and 0.75 IU kg-1 IM, and 1.5 IU.kg-1 via nasal spray) were compared. sCT caused an increase in cAMP, adenosine and pO2, and a decrease in cytosolic free calcium in neutrophils, lymphocytes and platelets. The peak times of all these parameters ranged between 109 and 182 min, and 101 and 168 min after IM and nasal spray administration respectively. There was greater variability in the values after IM than nasal spray of administration of sCT. It is concluded that adenosine and pO2 in venous blood, and cytosolic free calcium in circulating cells are valuable markers of the activity of sCT and that sCT decreases the cytosolic free calcium level in neutrophils, lymphocytes and platelets. Pharmacodynamic analysis of the biological effects of the drug is highly reliable and valuable in predicting its pharmacological profile. sCT administration via a nasal spray is able to produce significant biological effects, although they are less marked than after IM dosing.

Adenosine↗
PubMed1991

Nitroprusside in vitro inhibits platelet aggregation and intracellular calcium translocation. Effect of haemoglobin.

The biologically final active compound of nitrovasodilators is now supposed to be nitric oxide (NO), a labile substance identical to EDRF. The effects of nitroprusside on platelet functions were studied in vitro. Platelet aggregation induced by several stimuli (ADP, collagen, arachidonic acid and PAF) was inhibited by increasing concentrations of the drug (1-50 uM); interestingly, the potency of nitroprusside is higher when PAF is employed as stimulating agent in comparison with the other agonists (ED50 = 2 uM for ADP, 2.5 uM for A.A., 4.5 uM for collagen and 0.3 uM for PAF-induced aggregations). The concomitant addition of haemoglobin is able to reverse the inhibitory effect of nitroprusside, according to the view that haemoglobin possesses a high affinity for NO, thus antagonizing the effect of this compound. Nitroprusside was also able to inhibit intracellular calcium translocation, as studied with the Quin 2 technique, induced by PAF and arachidonic acid. Fron these observations the hypothesis may be suggested that nitroprusside inhibits platelet functions by mimicking the endogenous NO, and that the intracellular calcium metabolism is involved in the inhibitory activity of the drug.

Adenosine Diphosphate↗
PubMed1990

Adenosine system and cell calcium translocation: interference of calcium channel blockers.

Adenosine is able to inhibit in vitro neutrophil functions induced by formyl-methionyl-leucyl-phenylalanine (FMLP) and A23187, but not phorbol 12-myristate 13-acetate (PMA). The inhibiting activity on A23187 is reversed by increasing extracellular Ca2++ concentration. The calcium entry blocker flunarizine shows an activity very similar to that of adenosine. Both adenosine and flunarizine prevent Ca++ influx into activated neutrophils as detected by the fluorescent Ca++ chelator Quin-2. Finally, flunarizine binds to the neutrophil membrane and adenosine competitively inhibits flunarizine binding as assessed by 1H-Nuclear Magnetic Resonance (1H-NMR) technique, thus indicating that the two agents share a common binding site on the cell membrane.

Adenosine↗
PubMed1989

New in vivo model to assess venous endothelial cell functions. Effect of defibrotide.

In the past few years there has been increasing interest in the role of the vascular endothelium as an active modulator of biological responses. Endothelial cells exert antithrombotic activity by the release of prostacyclin [23] and adenine nucleotides [16], the availability on the cell surface of heparin-like substances [3], and thrombomodulin-mediated activation of protein C [8]. In addition, endothelium is involved in the regulation of fibrinolysis by releasing soluble factors, such as tissue plasminogen activator (tPA; [10]) and plasminogen activator inhibitor (PAI; [22, 11]), as well as in the control of vascular responsiveness by the production of smooth muscle relaxing and contracting factors. Endothelial cells have also been shown to synthesize and to express procoagulant activities [18]. Many data on endothelial cell functions has been obtained from two experimental models, namely endothelial cell cultures and perfused segments of animal and human vessels. Both are subject to methodological criticism since they only represent in part in vivo conditions, and the necessary experimental manipulations and laboratory procedures greatly modify the naturally occurring cellular functions. In order to overcome such difficulties as far as possible, a new in vivo model has been employed to provide easily assessable and reliable data on the properties of endothelial cells in man. A venous segment was isolated functionally by cannulating a dorsal vein in the hand and a cubital vein in the same arm. Changes observed ex vivo in blood from the cubital vein following infusion into the hand vein of an active drug, can mainly be attributed to its local effect on the venous wall. At the same time, a cubital vein in the other arm was cannulated in order to provide information to distinguish systemic from regional effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Receptors on the neutrophil membrane. I. Flunarizine-adenosine antagonism as detected by 1H-nuclear magnetic resonance relaxation investigations.

Selective proton relaxation rates were measured for selected protons of flunarizine in the presence of neutrophils, yielding evidence of a binding interaction that involves different moieties of the drug. Fast exchange between bound and free environments was demonstrated as the main factor determining the selective relaxation rate enhancement, whereas viscosity effects were shown to be negligible. The relaxation effect was cancelled out by the presence of adenosine as a cosolute in a dose-dependent fashion, leading to the suggestion that the endogenous mediator adenosine affects binding of flunarizine to the neutrophil surface.

Adenosine↗
PubMed1987

Benzodiazepines inhibit in vitro free radical formation from human neutrophils induced by FMLP and A23187.

Diazepam (DZP) inhibited in vitro in a concentration-dependent manner superoxide anion generation and chemiluminescence from human neutrophils stimulated by the formylated oligopeptide FMLP and by the calcium ionophore A23187. The dose-dependent inhibitory effect of DZP on A23187-dependent superoxide generation in the presence of Ca++ 0.6 mM was highly antagonized by increasing extracellular Ca++ concentration to 1.5 mM and to 2.0 mM. Ro 5-4864, a specific ligand for peripheral type benzodiazepine (BZ) binding site, inhibited superoxide generation induced by FMLP, while clonazepam (CNZ), which is selective for brain sites, did not possess any activity. Ro 15-1788, a central type BZ receptor antagonist, did not show any antagonistic activity on DZP-dependent inhibition. A new physiological property for substances presenting an affinity for peripheral type BZ binding sites is supposed. The inhibitory effect of BZ on neutrophil functions seemed to be associated with a Ca++-involving mechanism.

Benzodiazepines↗
PubMed1987

Defibrotide in vitro inhibits neutrophil activation by a Ca++-involving mechanism.

Defibrotide, a polydeoxyribonucleotide provided with a pro-fibrinolytic and prostacyclin-like activity, was studied as an inhibitor of polymorphonuclear leucocyte activation in vitro. It was found capable of dose-dependently (1-8 X 10(-5) M) inhibiting FMLP-induced activation, as shown by a decrease of enzyme release and free-radical formation (superoxide anion generation and chemiluminescence). A similar inhibiting activity was observed on A23187-induced activation. An increase in extracellular Ca++ concentration significantly prevented the effect of defibrotide on ionophore stimulation. When PMA was employed as stimulating agent, the drug did not show any inhibiting effect. Finally the pre-treatment of cells with theophylline markedly reduced the inhibition by defibrotide of FMLP- and A23187-dependent activation. Since the stimulation of neutrophils by FMLP and A23187 depends on the increase of cytoplasmic free-calcium availability or extracellular calcium entrance respectively, whereas PMA activation is completely independent from any Ca++ change, the inhibiting effect of defibrotide could be attributed to a Ca++-involving mechanism.

Calcium↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1979

Action of levamisole on E-rosette forming cells and serum adenosine deaminase in Hodgkin's disease.

The interaction of levamisole and/or adenosine in vitro on E-rosette forming cells (RFC) of healthy subjects and on low RFC of patients affected with various diseases was investigated. Levamisole did not enhance normal RFC. The drug enhanced low RFC in some patients (responders) but not in others (non-responders). Adenosine inhibited normal and low RFC and this inhibition could be reversed by levamisole. Further, levamisole 150 mg 2 days a week was given to 12 Hodgkin's disease (HD) responders for 2 weeks, then 150 mg 1 day weekly for 2 1/2 months. After one week of treatment RFC increased and the enhancement could be maintained during the whole treatment period. Lastly levamisole in vitro and in vivo diminished serum adenosine deaminase activity in normal subjects and HD patients.

Adenosine↗
PubMed1979

Immunokinetics of a single dose of levamisole.

Ten patients with classical or definite rheumatoid arthritis and a low number of E-rosette forming lymphocytes were given single doses of 50, 100 and 150 mg of levamisole. Levamisole produced a dose-related sustained increase in E-rosette forming cells. A single dose of 150 mg restored the number of E-rosette forming cells to normal within 24 hours and this effect lasted 6 to 7 days. These immunokinetic data provide a rational basis for the once-a-week administration of levamisole.

Adult↗
PubMed1979

Inhibition of platelet aggregation by a new synthetic compound: 2-[p-(1-oxo-2-isoindolinyl)phenyl] butyric acid (K 3920).

The effect of the new synthetic compound 2-[p-(1-oxo--2-isoindolinyl)phenyl] butyric acid (K 3920) on platelet aggregation was assessed in vitro on human platelets. ADP, epinephrine and collagen at different concentrations were employed as inducing agents. From the results of the present study it appears that K 3920 inhibits human platelet aggregation in vitro, probably by acting on the release reaction.

Adenosine Diphosphate↗
PubMed1978

The effects of intravenous isoxsuprine on blood viscosity in patients with occlusive peripheral arterial disease.

1 Blood viscosity is thought to be a major factor in disorders of the peripheral circulation. 2 Ten patients with obliterative arterial disease received an infusion of isoxsuprine of 20 micrograms kg-1 for 30 min. The infusion was followed by a highly significant and prolonged fall in blood, plasma and serum viscosity, in haematocrit and in plasma fibrinogen concentration. Blood lipid levels were also studied: total lipids and total cholesterol did not alter; triglyceride level was significantly lowered at the end of, and after, drug infusion. 3 There was no change in blood, plasma or serum viscosity in the four patients receiving a control infusion 2 days before the infusion of isoxsuprine. 4 The relationships between lowered viscosity and increasing peripheral tissue perfusion are discussed.

Aged↗