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Biomedical subjects

G Emanuelli

Publications and source records attributed to G Emanuelli.

At least 73 records · Page 4Linked to original sources
PubMed1990

Sodium taurocholate affects prostacyclin constitutive production by cultured human vascular endothelial cells.

The prostaglandin system is impaired in cholestasis; bile salts, which are a specific biochemical feature of this condition, have been shown to affect functional properties of cells and tissues, and, in some cases, their action is mediated through an alteration of prostaglandin pathway. Endothelium is a privileged site for the production and the action of arachidonate metabolites-prostacyclin in particular. To determine the effects of bile salts on the properties of vascular endothelium, cultured human endothelial cells were studied. Cholic acid sodium salt was seen to induce a direct injury on endothelial cells, as was demonstrated by a massive dismission of the intracellular radiolabel chromium 51. In the absence of detectable toxic effect, sodium taurocholate caused a significant depression of prostacyclin constitutive production from human endothelial cells. The action of sodium taurocholate was related to its concentration and to the time of exposure, and the alteration of prostacyclin production was found to be reversible. Conversely, the generation of thromboxane A2 was not influenced by this bile salt, which may suggest a specific action of sodium taurocholate on arachidonic acid metabolism. These findings indicate that bile salts may directly alter some functional properties of cultured human endothelial cells and may provide a basis for explaining some generalized manifestations that are observed in pathologic conditions characterized by cholemia.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Role of platelet-activating factor in the reperfusion injury of rabbit ischemic heart.

This study shows that the administration of the PAF receptor antagonist SDZ 63.675 (5 mg/kg body weight) before reperfusion significantly reduced the hematologic and hemodynamic alterations, as well as the size of necrotic area in rabbits subjected to 40 minutes of coronary occlusion and reperfusion. Pretreatment with SDZ 63.675 prevented the reduction of platelet counts in the blood obtained from the right ventricle (86.6 +/- 2.8% of the control preischemia value) and the transient bradycardia (85.0 +/- 2.8%), the systemic hypotension (58.0 +/- 2.8%), and the increase in right ventricular pressure (125.0 +/- 3.6%) that were evident in the first minutes of reperfusion in untreated control rabbits. Two as well as 24 hours after reperfusion, the infarct size, judged by staining with tetrazolium, was significantly reduced in rabbits treated with SDZ 63.675 (infarct size in control animals, 66.0 +/- 2.9% and 63.46 +/- 2.09% of the risk region at 2 or 24 hours, respectively, compared with 38.9 +/- 5.2% and 37.11 +/- 2.44% of the risk region at 2 and 24 hours in rabbits treated with SDZ 63.675). This result was confirmed by histologic examination of cardiac tissue 24 hours after reperfusion. In addition, SDZ 63.675 markedly reduced the accumulation of 111In-oxine-labeled platelets that occurs 15 minutes after reperfusion in the central ischemic area of the heart and in the lungs. These results suggest that PAF plays a role in the evolution of myocardial injury observed during reperfusion.

Animals↗
PubMed1989

Insulin influences the renin-angiotensin-aldosterone system in humans.

This study investigates whether insulin influences the renin-angiotensin-aldosterone system in humans. Six healthy male volunteers were placed on a 30-minute euglycemic insulin clamp at 160 microU/mL; euglycemia was maintained also in the following 60 minutes by means of appropriate dextrose infusion. Throughout the study, plasma renin activity, angiotensin II, aldosterone, and factors involved in the regulation of the renin-angiotensin-aldosterone system were measured: catecholamines, angiotensin-converting enzyme, sodium, and potassium. A significant increase of plasma renin activity and angiotensin II was observed, and a decrease of aldosterone was also detected. These changes can be ascribed to the effects of the rapid insulin-induced plasma potassium decrease on plasma renin activity and aldosterone secretion because they did not occur in a control clamp study with a potassium infusion.

Adult↗
PubMed1989

Influence of propranolol on platelet aggregation and thromboxane B2 production from platelet-rich plasma and whole blood.

The beta-adrenoceptor antagonist propranolol is used in the therapy of hypertension and ischemic heart disease. The aim of our study was to evaluate the effects of this drug on platelet aggregation and on synthesis of thromboxane B2 (the stable metabolite of Thromboxane A2) from platelet rich plasma (PRP), whole blood samples and during spontaneous clotting. The results indicate that propranolol at concentrations near the therapeutic range, significantly inhibit collagen and thrombin-induced platelet aggregation and TxB2 synthesis from PRP. Furthermore the drug demonstrates inhibitory activity on B-TG release and TxB2 production from whole blood samples and on spontaneous clotting. The results suggest that some benefits of propranolol in the treatment of patients with coronary artery disease or cardiovascular conditions associated with platelet hyperaggregability may also be related to interference with platelet activation "in vivo" and with TxA2 generation.

Adult↗
PubMed1989

Platelet activating factor is produced during infectious peritonitis in CAPD patients.

Peritonitis, a frequent complication of continuous ambulatory peritoneal dialysis (CAPD), is a model of inflammation which provides the opportunity to recover the exudate fluid. To date, various endogenous mediators (histamine, bradykinin, activated complement factors, prostanoids) have been implicated in the mediation of peritoneal inflammation and increased peritoneal permeability. In the present study, a lipid compound with physicochemical and biological characteristics similar to platelet activating factor (PAF) (1-0-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) was extracted in significant amounts from the dialysate of eight out of nine peritonitis episodes in seven CAPD patients (Group A; 6771.4 +/- 3025.9 pM, mean +/- SEM at the first exchange during peritonitis). The amounts of PAF recovered in the first exchange dialysate from patients of Group A were linearly correlated with the loss of albumin (y = -3157.64 + 91.4x; r = 0.7394; N = 9; P less than 0.03) and number of leukocytes (y = 902.45 + 1.52x; r = 0.7576 N = 9; P less than 0.02). PAF was not detectable in the dialysate fluid from patients of Group A after recovery. Twelve patients on CAPD who had no past or present history of peritonitis (Group B) were used as controls; no PAF (9 patients) or only minimal amounts (3 patients: 7.0 pM; 23.0 pM; 70.0 pM) of this mediator were detected. This is the first direct demonstration of the local generation of PAF in a septic inflammatory reaction involving the peritoneal serosa in man. PAF produced by various cell types (neutrophils, peritoneal macrophages, endothelial cells) during peritoneal inflammation may contribute to the increased permeability of the peritoneal vascular bed.

Adult↗
PubMed1989

Release of platelet-activating factor from ischemic-reperfused rabbit heart.

This study shows that platelet-activating factor (PAF) is released in significant amounts (10.9 +/- 12.8 ng/min) during the initial reperfusion of the ischemic-isolated rabbit heart. When reperfusion was performed in the presence of autologous rabbit platelets, the electrical and mechanical alterations characteristic of this phase were significantly worsened. These alterations were antagonized by pretreatment of rabbit platelets with a PAF receptor antagonist (SDZ 63-675), suggesting a contribution of PAF released during reperfusion in the cardiac dysfunction. To discriminate whether the effect of PAF was platelet dependent, infusion of PAF (10-40 ng) was performed in nonischemic rabbit hearts perfused with or without autologous platelets. Although the effect of PAF per se was minimal, in the presence of platelets PAF induced a biphasic effect characterized by a transient positive inotropism followed by a dose-dependent decrease in coronary flow, negative inotropism, reduction of action potential duration, and conduction arrhythmias. These effects were abolished by pretreatment of platelets with SDZ 63-675, suggesting a PAF receptor-mediated platelet activation. In addition, a relative contribution of histamine, thromboxanes, and leukotrienes released from activated platelets was inferred by experiments performed with pyrilamine and cimetidine, imidazole, and FPL 55712, respectively.

Animals↗
PubMed1989

Antitissue antibodies in chronic pancreatitis.

Organ- and nonorgan-specific autoantibodies (AA) have been investigated in 49 patients affected by alcoholic or idiopathic chronic pancreatitis (CP) to evaluate their prevalence and correlation with the clinical features of the disease. AA have been found in about 50% of CP and their recurrence rate was similar to that of alcoholic or cryptogenic liver cirrhosis (LC); age- and sex-matched healthy subjects (C) showed only about 8% positive sera (C vs. CP, p less than 0.001). Quite different IFL patterns between CP and LC have been detected. Antibrush border, antireticulin and antigastric parietal cell antibodies alone or combined prevailed in CP, while antinuclear and antismooth muscle AA prevailed in LC. No correlation with sex, age, etiology, presence of pancreatic stones, diabetes, symptoms and years of CP was found for one or more AA. In conclusion, the detection of AA in CP is a quite common finding of still unclear clinical significance.

Alcoholism↗
PubMed1989

Experimental acute pancreatitis induced by platelet activating factor in rabbits.

This study indicates that a single injection of platelet activating factor (PAF, 50-500 ng) into the superior pancreaticoduodenal artery of rabbits induces dose-dependent morphologic alterations of pancreatic tissue and increases serum amylase levels, both consistent with the development of an acute pancreatitis. The main histologic findings observed by light microscopy 24-72 hours after the injection of PAF were edema, polymorphonuclear neutrophil infiltration, cell vacuolization, and acinar cell necrosis. Fat cell necrosis was present in 30% of animals. By electron microscopy an increase of the number of zymogen granules in the apical region of acinar cells was observed 3 hours after PAF challenge. At 24-72 hours, many acinar cells showed vacuoles containing myelinlike figures, zymogen granules, and cellular debris. Pancreatic lesions developed in the area supplied by the artery injected with PAF and they were completely antagonized by the pretreatment of rabbits with CV 3988, a specific antagonist of PAF. In addition, the significant protective effect of atropine suggests a potential role for cholinergic mechanisms in the pancreatic alterations induced by PAF.

Acute Disease↗
PubMed1988

Insulin-induced hypoglycaemia increases plasma concentrations of angiotensin II and does not modify atrial natriuretic polypeptide secretion in man.

Insulin-induced hypoglycaemia causes profound haemodynamic changes, commonly ascribed to catecholamine increase. The aim of the present study was to investigate the influence of insulin-induced hypoglycaemia on non-adrenergic factors potentially involved in haemodynamic regulation: angiotensin II and alpha-human atrial natriuretic polypeptide. Fourteen healthy male subjects, aged 25.5 +/- 0.74 years, body mass index 23.81 +/- 0.68 kg/m2, received (after an overnight fast and at least 60 min rest in a supine position) an i.v. bolus injection of human regular insulin (Actrapid HM, Novo, Bagsvaerd, Denmark: 3.84 U/m2). Serial venous blood samples were drawn in the following 150 min, to measure plasma glucose, angiotensin II, alpha-human natriuretic polypeptide, and factors potentially involved in the regulation of the renin-angiotensin-aldosterone system. During the study, we observed a plasma glucose fall, reaching a nadir of 1.95 +/- 0.11 mmol/l between 25 and 30 min, and an increase of angiotensin II (from 7.6 +/- 0.8 to 13.5 +/- 1.1 pg/ml, p = 0.01, quadratic model evaluated by an analysis of the variance for repeated measures), whereas atrial natriuretic polypeptide remained unchanged. As far as the regulation of the renin-angiotensin-aldosterone system is concerned, the increase of angiotensin II is attributable to the increased plasma renin activity, whereas angiotensin converting enzyme was not modified. The increase of plasma renin activity, in turn, is attributable both to the increased catecholamine concentrations and to the decreased potassium levels. Both adrenocorticotropic hormone and angiotensin II are potentially involved in the hypoglycaemia-induced increase of aldosterone concentrations.

Adrenocorticotropic Hormone↗
PubMed1988

Influence of urapidil on in vitro platelet response to adrenaline and other aggregating agents.

The effects of hypotensive drug urapidil on human platelet functions were investigated. Urapidil failed to evidence direct aggregating properties or potentiating effects. Furthermore, drug high concentrations inhibited the platelet response to ADP, PAF, collagen, adrenaline and bovine thrombin, and influenced the platelet release reaction induced by ADP and PAF. Data indicate that urapidil possesses negligible agonistic effects on human platelet alpha 2-adrenoceptors and interferes at high concentrations with the platelet activation, as evidenced for other anti-aggregating compounds.

Adenosine Diphosphate↗
PubMed1988

Effect of labetalol on human platelet function.

1. The effects of the alpha-beta-adrenergic antagonist labetalol on the activation of human platelets by adrenaline and other aggregating stimuli have been investigated. 2. Labetalol inhibited platelet aggregation and secretion induced by collagen and the second phase of aggregation caused by ADP, platelet activating factor, adrenaline and ionophore A23187. Adrenaline-induced platelet activation was inhibited by the lowest labetalol concentration. The response to Na arachidonate was minimally affected and the arachidonate-induced thromboxane B2 generation was only partially prevented. 3. The pre-incubation with low concentration of ionophore A23187 overcame labetalol's inhibition of collagen-induced platelet aggregation. 4. Labetalol did not influence intraplatelet cyclic AMP levels. 5. The present investigation provided evidences that the modulation of human platelet function by labetalol could be related also to a decreased Ca2+ availability.

Adult↗
PubMed1988

Insulin directly reduces platelet sensitivity to aggregating agents. Studies in vitro and in vivo.

The aim of this study was to investigate the influence of insulin on platelet function, both in vitro and in vivo. For the in vitro investigation, we evaluated whether insulin affects platelet function at a physiological hormone concentration by incubating the platelet-rich plasma (PRP) of fasting subjects with human regular insulin at the final concentration of 40 microU/ml for 30 min; we observed a significant reduction of platelet sensitivity to all the aggregating agents employed, i.e., ADP, platelet-activating factor (PAF), epinephrine, collagen, and Na+ arachidonate. To investigate whether the insulin effect on platelets is dose dependent, we incubated the PRP of fasting subjects with different concentrations of human regular insulin (40, 80, 120, and 160 microU/ml) for 5 min, and we observed that the insulin-induced reduction of platelet sensitivity to aggregating agents is a dose-dependent phenomenon. Furthermore, the comparison between the platelet responses after 5 and 30 min of incubation with insulin showed that the insulin effect on platelet aggregation is time dependent. The lack of specificity of its inhibiting activity suggests that insulin does not interfere with the initial binding of each aggregating agent at specific sites but does influence a common step of platelet aggregation. Our study rules out the possibility that insulin reduces platelet-function-modifying intraplatelet cAMP levels or thromboxane A2 production, because this hormone decreases the platelet concentrations of cAMP--a phenomenon that, per se, promotes platelet aggregation--and does not modify collagen or Na+ arachidonate--induced platelet production of thromboxane A2, measured by radioimmunoassay of its stable-metabolite thromboxane B2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1988

Postprandial exercise in type I diabetic patients on multiple daily insulin injection regimen.

This study shows the influence on plasma glucose concentrations of 45 min of mild exercise (48 +/- 4% of maximum aerobic capacity) performed 180 min after breakfast and 195 min after a subcutaneous injection of regular insulin by six type I (insulin-dependent) diabetic patients on a three-daily insulin injection regimen (regular insulin before breakfast and lunch, regular + intermediate insulin before supper). It has been observed that such exercise does not induce a large plasma glucose decrease. Actually, plasma glucose concentrations were 99 +/- 18 mg/dl before exercise, reached a nadir of 78 +/- 17 mg/dl at 35 min, and were 81 +/- 15 mg/dl at the end of exercise. During the control study at rest, in the same 45-min time interval, plasma glucose decreased from 146 +/- 31 to 128 +/- 31 mg/dl. In the exercise study, one patient began exercising while hypoglycemic, and another patient developed asymptomatic hypoglycemia during exercise. In the control study at rest, one patient showed hypoglycemic glucose concentrations. Throughout the exercise study, plasma free-insulin concentrations decreased (from 32 +/- 5 to 20 +/- 4 microU/ml) as a result of the pharmacokinetics of subcutaneously injected insulin.

Adult↗
PubMed1988

Urinary enzyme release following aminoglycoside administration in single low dose.

Urinary enzyme excretion was investigated in healthy volunteers before and after infusion of single low doses of aminoglycoside (gentamicin, tobramycin and amikacin) in the same subjects. Significant increases were detected in urinary leucine aminopeptidase, lactate dehydrogenase and alkaline phosphatase following gentamicin infusion; after amikacin administration only urinary release of leucine aminopeptidase was found to be increased. No difference was detected compared to basal values in enzyme excretion after tobramycin infusion. Urinary enzyme release in our conditions suggests low tubular damage after single doses of gentamicin and amikacin.

Adult↗