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Biomedical subjects

G Emanuelli

Publications and source records attributed to G Emanuelli.

At least 91 records · Page 5Linked to original sources
PubMed1987

Heparin neutralizes serum antiplasmin inhibition of peripheral blood leukocyte fibrinolytic activity.

Serum inhibition of peripheral blood fibrinolytic activity has been evaluated with the 125I-fibrin coated well method. The inhibitory activity was found in a 140,000 d serum fraction that contained alpha 2-antiplasmin. Addition of heparin to cell cultures at concentrations in the range of values obtained during anticoagulant therapy has been demonstrated to counteract such inhibitory activity. The phenomenon has been shown to be linked with plasminogen activation in the presence of fibrin, to lead to a weakening of antiplasmin activity. By clarifying an important aspect of the mechanism of heparin action, our findings support the view that heparin can be usefully employed in treating thrombotic syndromes, not only as an anticoagulant, but also as a "profibrinolytic" agent.

Fibrin↗
PubMed1987

The pattern of cardiovascular alterations induced by infusion of platelet-activating factor in rabbit is modified by pretreatment with H1-H2 receptor antagonists but not by cyclooxygenase inhibition.

The intravenous infusion of platelet activating factor (PAF) (0.8 micrograms/kg b.w.) induced ECG and hemodynamic alterations characterized by the following sequential three phases. Phase I (15 sec) consisted of a transient bradycardia with reduction in left ventricular pressure (LVPs), mean arterial pressure (MAP) and cardiac output (CO). Phase II developed within 30 sec and consisted of a rise in cardiac frequency, increase in LVPs, MAP and total peripheral resistances (TPR), which were associated with a decrease in CO. Finally, phase III, that occurred about 90 sec after PAF infusion, was characterized by marked ECG changes (ST segment depression and conduction arrhythmias), a decrease in LVPs and MAP, as well as a rise in TPR and in right atrial pressure (RAP). All these alterations were reversible within 30-60 min. Pretreatment with promethazine and cimetidine, as H1 and H2 histamine receptor antagonists, markedly prevented the development of phase II, namely the rise in cardiac frequency, LVPs, MAP and TPR, but did not significantly modify phase I and III. In contrast, pretreatment with indomethacin, an inhibitor of cyclooxygenase, moderatively attenuated, but did not abolish, the three phases of cardiovascular changes induced by PAF infusion.

Animals↗
PubMed1987

Increased incidence of cancer in chronic pancreatitis.

Patients affected by chronic pancreatitis were followed between 1970 and 1984 in a study set up to evaluate the natural history of the disease. The study population included 172 consecutive patients diagnosed as having chronic pancreatitis in the Gastroenterology Unit of the S. Giovanni Battista Hospital in Torino, Italy. Of them, 23 were found to be affected by cancer during the 14-year follow-up period. The incidence calculated using the person-year method was compared with data from the General Population Cancer Registry of Piemonte Region. The age-specific relative risks of cancer were increased manifold. Sex- and age-specific relative risks were markedly increased for liver, tongue, lip, and rectum tumors in males, and for liver, bone, and breast tumors in females. Selection bias did not seem to be an adequate explanation of this association. Survival curves were plotted by the estimation methods of Cutler-Ederer with year intervals for the complete study population and for the different type of cancer. Known risk factors and indicators for the expected tumors were evaluated by the Cox Proportional Hazard Regression Model. The incidence of cancer increases significantly with age but not with smoking, alcohol use, and diabetes. Our epidemiological study suggests an increased risk of pancreatic as well as extrapancreatic cancer in patients with chronic pancreatitis compared with the general population. Cancer seems to be a main determinant in the natural history of the disease.

Adult↗
PubMed1987

Protective effect of verapamil on the cardiac and circulatory alterations induced by platelet-activating factor.

The role of calcium channels in the mediation of the cardiovascular effects of synthetic (1-O-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) platelet-activating factor (PAF) was studied in vivo in the rabbit and in vitro in the coronary-perfused isolated heart and papillary muscle of the guinea pig following pretreatment with verapamil, a calcium antagonist. In the rabbit, verapamil (0.3 mg/kg) abrogated the ECG changes, and reduced all the hemodynamic alterations caused by PAF (0.8 microgram/kg). Verapamil (20 nmol) reduced both the electrical and mechanical alterations observed in the isolated heart and papillary muscle after the infusion of PAF (0.2 nmol). These results suggest that the transmembranal calcium channels play a crucial role in the mechanism by which PAF acts on the cardiovascular tissues.

Animals↗
PubMed1987

[Lymphocyte subpopulations in idiopathic dilatational cardiomyopathy].

Lymphocyte subsets have been examined in 23 patients affected by idiopathic dilated cardiomyopathy (IDCM). Patients were divided according to their functional class showing that compromised subjects exhibited high T-lymphocyte helper/suppressor ratio whereas the contrary was observed in the other patients. It has therefore suggested that IDCM is characterized by 2 distinct phases, each of them with different helper/suppressor ratio.

Adult↗
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

Influence of age on polymorphonuclear leukocytes in vitro: phagocytic activity in healthy human subjects.

Polymorphonuclear leukocytes (PMNs) represent an important defensive mechanism against infectious agents. Some of their functions are impaired in old people, with a decreased effectiveness of nonspecific immunity. In vitro PMN phagocytic activity was studied with different techniques on 74 healthy subjects (20-82.5 years; 40 males, 34 females). Serum-mediated ingestion resulted to be impaired with age with a lower ratio of active PMNs and a lower activity of phagocytosing cells. The behavior of these parameters was age-related, without significant difference between males and females; the decline was found to be a continuous phenomenon with no threshold age. Serum-independent ingestion had very low values and was not impaired with aging. The present data can represent a further explanation for the finding of a higher incidence and mortality of bacterial diseases in elderly population.

Adult↗
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

Studies on mechanisms involved in hypoglycemia-induced platelet activation.

The aim of our study was to investigate the mechanisms involved in hypoglycemia-induced platelet activation. Sixteen healthy male subjects received a 60-min intravenous infusion of human regular insulin at the rate of 64 mU . m-2 . min-1: throughout 150 min, we serially measured plasma concentrations of glucose, insulin, and counterregulatory hormones; platelet sensitivity to ADP, thrombin and platelet-activating factor; plasma concentrations of platelet markers for specific proteins of in vivo release reaction (beta-thromboglobulin and platelet factor 4). Our study showed that insulin-induced hypoglycemia causes a significant increase in platelet sensitivity to aggregating agents in vitro and a platelet release reaction in vivo. Hypoglycemia-induced platelet activation was not correlated with plasma glucose concentrations at nadir and occurred before the increase of plasma growth hormone and cortisol. To further elucidate the mechanisms of hypoglycemia-induced platelet activation, we incubated in vitro platelet-rich plasma (PRP) of seven fasting healthy subjects with the same concentrations of insulin, epinephrine, glucagon, growth hormone, and cortisol measured in vivo during insulin-induced hypoglycemia. Only epinephrine was able to increase platelet sensitivity to aggregating agents. To investigate the role of alpha-adrenergic receptors in this phenomenon, we also studied four healthy subjects on another occasion, repeating the above-described insulin infusion together with intravenous infusion of phentolamine (-15 to +150 min), 5 mg over 2 min followed by 500 micrograms/min. alpha-Blockade was able to suppress hypoglycemia-induced increase of platelet sensitivity to aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗