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Biomedical subjects

G Montrucchio

Publications and source records attributed to G Montrucchio.

66 records · Page 4Linked to original sources
PubMed1986

In vitro contractile effect of platelet-activating factor on guinea-pig myometrium.

Platelet-activating factor (PAF) evoked myometrial contractions in two different patterns, depending on whether spontaneous activity was present. In spontaneously active myometrial strips (58%), both PAF and oxytocin enhanced the amplitude of myometrial contractions. In quiescent myometrial strips, PAF induced contractions characterized by a prompt development of tension, a plateau, and a final, rapid relaxation. In 54% of these strips, PAF-induced contraction was followed by rhythmic activity. PAF contractile response was dependent upon the concentration (0.1-100 nM); the minimal effective concentration of PAF was 0.1 nM and the EC50 was 1 nM. The response to oxytocin (0.01-10 mU/ml), assumed as reference stimulus, was characterized by a prompt development of tension, which was followed by a sustained, slow contraction and relaxation. PAF response was almost completely dependent on cyclooxygenase and partially on lipoxygenase pathways, as inferred from studies with indomethacin and FPL 55712, respectively. A receptor mediated mechanism of PAF action was suggested by specific desensitization of the myometrium to a second challenge with an equimolar concentration of PAF (but not with oxytocin) and the blocking effect of CV 3988, a specific PAF receptor antagonist.

Animals↗
PubMed1986

Effect of platelet-activating factor (PAF) on human cardiac muscle.

The effect of platelet activating factor (PAF) on three mechanical [maximal mechanical tension (Pmax); time to peak tension; maximal rate of rise of tension (+dP/dt)] and four electrical [action potential duration (APD); resting membrane potential; overshoot; maximum rate of depolarization] parameters of cardiac function was studied on fragments of isolated human cardiac papillary muscle. 20 specimens of small tissue fragments excised from the left ventricle by open heart surgery were challenged with various doses of synthetic PAF (10(-10)-10(-6) M). PAF, but not its biologically inactive 2-lyso-derivative (lyso-PAF), induced a biphasic dose-dependent effect, characterized by a transient positive effect on inotropism (increased Pmax, +dP/dt) and of APD, followed by a marked, prolonged negative effect on both inotropism (decreased Pmax, time to peak tension, +dP/dt) and APD. No changes in resting membrane potential, overshoot and maximum rate of depolarization were detected after PAF challenge. Propranolol (2 X 10(-7) M) completely prevented the positive inotropic effect suggesting a stimulation of beta-receptors, possibly exerted by endogenous catecholamines. Indomethacin (1 X 10(-4) M) did not modify the initial positive effect, but markedly reduced the subsequent negative effect induced by PAF on inotropism. These findings are consistent with the interpretation that the effect of PAF on the inotropism is related to liberation of cyclooxygenase-derived metabolites.

Action Potentials↗
PubMed1986

Platelet-activating factor contracts human myometrium in vitro.

The myometrial contractile responses to synthetic 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor, PAF) and to oxytocin were evaluated in vitro on uterine (lower segment) strips obtained from pregnant women at term (39th week), undergoing elective cesarean section. Contractility was measured isometrically in an isolated organ bath using a superfusion technique. PAF in a concentration range between 5 and 100 nM as well as oxytocin (0.1-10 mU/ml) induced a dose-dependent contraction which could be categorized in two patterns, depending on whether spontaneous activity was present. In resting strips, oxytocin induced a prompt (0.5-1 min) development of active tension, followed by a prolonged (6-18 min), slow contraction and a final relaxation. However, at variance with oxytocin, PAF-induced contractions were rhythmic (3-8/hr), and characterized by a prompt (0.5-2 min) development of tension, followed by a brief (0.5-2 min) plateau, and a final, rapid relaxation. In spontaneously active strips, both stimuli induced a marked potentiation of the contractile activity. PAF response was dependent on both cyclooxygenase- and lipoxygenase-derived products as inferred from the abrogating effects of indomethacin and FPL 55712. A receptor-mediated mechanism of action was inferred from the occurrence of specific desensitization to PAF (but not to oxytocin), and from the blocking effect of CV 3988, a specific PAF receptor antagonist. The present study indicates that PAF stimulates the contraction of human myometrium in vitro and suggests that this mediator may have a role in labor.

Adult↗
PubMed1986

Cardiovascular alterations in the rabbit infused with platelet activating factor (PAF): effect of kadsurenone, a PAF-receptor antagonist.

The ECG and haemodynamic alterations caused by the i.v. infusion of platelet-activating factor (PAF) in the rabbit were studied after pretreatment with Kadsurenone, a specific PAF-receptor antagonist. Infusion of PAF at 0.8 microgram/kg in the rabbit caused important ECG changes, such as ST-segment depression and conduction arrhythmias, concomitantly with a marked reduction in left ventricular systolic pressure, mean arterial pressure and cardiac output, with a rise in total peripheral resistances and mean right atrial pressure. These physiological parameters became maximal at 75-120 seconds after PAF challenge, and returned to near prechallenge values within 25-60 minutes. Pretreatment with Kadsurenone, administered either intravenously (0.014 M, 1 ml/kg) or intraperitoneally (0.14 M, 1 ml/kg), exerted a quite complete protective effect in regard to the ECG changes and caused a significant reduction in the magnitude of all the haemodynamic alterations observed after intravenous infusion of PAF (0.8 microgram/kg). These results suggest that Kadsurenone is an effective inhibitor of PAF-induced cardiovascular changes in the rabbit, probably due to its competitive antagonism against PAF binding to specific receptors.

Animals↗
PubMed1985

The role of platelet-activating factor in experimental immune complex pathology.

Tissue localization of immune complexes (IC) after infusion of synthetic platelet-activating factor (PAF) in rabbits was studied. Bovine serum albumin (BSA) was injected intravenously either before or after the infusion of synthetic PAF, later followed by the administration of anti-BSA antibodies over a 30-min period. Control rabbits received both BSA and anti-BSA antibodies, followed by lyso-PAF or saline-BSA instead of PAF. The infusion of PAF induced structural alterations in the heart, lung and kidney which were consistent with an increased vascular permeability. Deposits of BSA, IgG, and C3 were found in the heart, lung, and kidney of rabbits infused with PAF but not in control rabbits. In the liver of PAF-infused rabbits, immune deposits were only infrequently observed, whereas they were constantly present in the cardiac valves, thoracic aorta and at the bifurcation of the renal artery as they were in the control rabbits. These results suggest that PAF favors the localization of IC in the heart, lung and kidney vessels but does not influence the formation of immune deposits at the sites of turbulence of the blood flow.

Animals↗
PubMed1984

Effect of platelet activating factor on guinea-pig papillary muscle.

Platelet activating factor (PAF) induces a biphasic effect on guinea-pig papillary muscle: 1. a transient positive inotropic effect preceded by an increase in action potential duration (APD); 2. a marked negative effect on inotropism and on APD. Since Ca++ slow action potentials were initially enhanced by PAF and then markedly depressed, it is suggested that PAF specifically interferes with the Ca++ slow channel.

Action Potentials↗
PubMed1983

[Hypotensive effect of sotalol under basic conditions and during exercise. Clinical cases].

An assessment was made of the efficacy of Sotalol, a beta1 selective beta blocker, in the management of essential arterial hypertension. A single 160 mg dose per diem was administered per os to 34 patients over a period of 14 weeks. Arterial pressure and heart rate were checked periodically. In addition, SAP, DAP and heart rate were evaluated before and during the third week of treatment in 8 subjects under maximum ergometric test conditions. Excellent tolerance was observed. Under basal conditions, all subjects displayed good reduction of SAP and DAP. This was highly significant. During exercise, it was less evident, and the results were only significant for low work loads. It is nevertheless felt that the simple dose protocol of the drug, its good tolerance and its effectiveness under basal conditions suggest that more extensive ergometric studies should be conducted.

Female↗
PubMed1983

Platelet-activating factor-mediated contraction of rabbit lung strips: pharmacologic modulation.

Synthetic platelet-activating factor (PAF) (1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, AGEPC) has been shown to induce a slowly developing contraction of rabbit lung parenchymal strips in an isolated organ bath. The spasmogenic effect of AGEPC appeared to be mediated by specific receptors distinct from H1, H2, cholinergic and C5a anaphylatoxin receptors. Prior exposure to AGEPC induced specific desensitization of lung parenchymal strips. Experiments with several pharmacological agents indicated that AGEPC-induced contraction was independent from cyclooxygenase, but was blocked when phospholipase A2 and lipoxygenase were inhibited and when the Ca++ channels were antagonized. Corticosteroids exhibited an inhibitory effect specific for AGEPC. Intracellular levels of cyclic AMP or cyclic GMP seemed to have a modulatory role in AGEPC-induced contraction of rabbit lung parenchymal strips.

Acetylcholine↗
PubMedDate not supplied

[The humoral and cellular factors of glomerular damage].

The present review summarizes current concepts on glomerular non-inflammatory and inflammatory immune injury. Non-inflammatory glomerular injury can be ascribed to mechanisms involving antibody alone, terminal component of complement (C5b-9) or cytokines having as primary target the glomerular epithelial cells. These mechanisms induce changes in cell cytoskeleton and in surface distribution of adhesion molecules leading to functional alterations which may account for loss of glomerular permselectivity. Inflammatory glomerular injury is mediated by neutrophils, macrophages, platelets and lymphocytes as well as by resident glomerular cells. Cell derived mediators include proteases, reactive oxygen species, cationic proteins, cytokines and growth factors that may variably affect recruitment of inflammatory cells, proliferation of resident glomerular cells and production of extracellular matrix. These alterations may determine proteinuria, impairment of renal function and eventually progression of glomerular injury to sclerosis. The inflammatory type of glomerular injury is mainly initiated by subendothelial-mesangial immune deposits and/or activation of cell mediated immunity. The role of factors such as the nature, intensity and persistence of initiating mechanisms, the types of inflammatory cells involved and the response of intrinsic glomerular cells, in expression and progression of glomerular injury are discussed.

Antibody Formation↗
PubMedDate not supplied

[Functional changes of the endothelium and atherosclerotic process].

The aim of this review is to summarize the current concepts concerning the active role of the endothelium in the pathogenesis of atherosclerosis. Activated endothelium may promote the adhesion of monocytes and their transmigration into the intima. The coordinated expression of adhesion molecules of the selectin, integrin or immunoglobulin superfamily on the surface of endothelial cells and of monocytes modulates these events. The role of lipoproteins and their oxidative derivatives as well as that of selected cytokines and platelet activated factor in initiating changes on the endothelial cell surface has been investigated: these events are associated with an increased endothelial permeability to lipids and lipoproteins with their accumulation in the subendothelium. Once migrated into the intima, monocytes undergo morphological and functional modifications leading to the generation of a polypeptide mediator network which is instrumental in the migration, differentiation and proliferation of smooth muscle cells. Mediators produced by macrophages infiltrating the atherosclerotic plaque and by the endothelium may render the surface of the endothelial cells thrombogenic thus favoring thrombotic occlusion. In conclusion, the most recent studies suggest that the endothelium plays an active role in the pathogenesis of atherosclerosis.

Arteriosclerosis↗