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Biomedical subjects

C Patrono

Publications and source records attributed to C Patrono.

At least 181 records · Page 10Linked to original sources
PubMed1982

Release of leukotriene C4 from human polymorphonuclear leucocytes as determined by radioimmunoassay.

Rabbits were immunized with a conjugate of leukotriene (LT) C4 and bovine serum albumin prepared by coupling the single free amino group of the hapten to the protein using gluteraldehyde. Binding of [3H]LTC4 to the antibodies obtained is inhibited by 50% with 1.5 ng LTC4. The relative cross-reaction of LTD4 is 16% and of LTC4-methyl ester 3.6%. The validity of the radioimmunoassay was demonstrated by comparison with bioassay using the isolated guinea pig ileum. Using the radioimmunoassay it could be shown that endogenous LTC4 is released in a dose-dependent manner by human polymorphonuclear leucocytes stimulated with the divalent cation ionophore A23187.

Animals↗
PubMed1982

Rheumatoid knee synovitis successfully treated with intra-articular rifamycin SV.

Thirty rheumatoid patients with persistent knee effusion were treated intra-articularly with rifamycin SV, 500 mg weekly, or with saline solution, 10 ml, in a double-blind study. A complete disappearance of effusion and an impressive clinical improvement was observed in the patients on rifamycin. The synovial fluid and membrane underwent some changes. In 2 patients the rifamycin caused a painful local reaction. After a follow-up of 5 years only one patient has experienced effusion relapse, 5 months after the termination of rifamycin SV treatment. The patients on saline showed no significant change. On the basis of the results obtained from the monoarthritis experimental model and from clinical trials it is tempting to consider that rifamycin has an antimitotic effect, impeding the synthesis of RNA and DNA polymerases in immunocompetent cells.

Arthritis, Rheumatoid↗
PubMed1982

Effects of intravenous prostacyclin in variant angina.

A lack in prostacyclin (PGI2) production due to atherosclerosis may play a role in the pathophysiology of some of the clinical manifestations of ischemic heart disease and in particular, of coronary vasospasm. We therefore evaluated the effects of i.v. PGI2 in nine patients with variant angina and six normal volunteers. In normal subjects, PGI2 (2.5, 5, 10 and 20 micrograms/kg/min) had significant antiplatelet effects, caused a dose-dependent decrease in both systolic and diastolic arterial pressure and a decrease in pulmonary resistance. Heart rate increased in a dose-dependent manner, but no consistent effects on myocardial contractility (evaluated by ultrasound) were observed. Side effects were negligible and readily reversible. Although producing obvious antiplatelet and vasodilatory effects, PGI2 did not affect the number, severity and duration of spontaneous ischemic episodes due to coronary vasospasm in five patients and ergonovine-induced spasm in three. However, the number of ischemic episodes was consistently reduced in one patient during four consecutive periods of PGI2 infusion alternated with placebo. a severe, prolonged ischemic episode with ST elevation and pain was consistently observed in this patient every time PGI2 was discontinued. In the appropriate environment, PGI2 can be administered safely to patients with ischemic heart disease. Occasionally, PGI2 may result in a complete disappearance of ischemic episodes due to coronary vasospasm, but usually it is ineffective. These conflicting results could be related to different etiologies of coronary spasm.

Adult↗
PubMed1982

Failure of thromboxane A2 blockade to prevent attacks of vasospastic angina.

Thromboxane A2 (TxA2), released by aggregating platelets, has been proposed as a potential mediator of coronary vasospasm. We studied six patients with variant angina, a clinical syndrome due to coronary vasospasm, and one patient with frequent recurrent episodes of transient ST-segment depression at rest in whom the spasm was demonstrated angiographically. All patients underwent continuous ECG monitoring for 2 days before and 2 days after a single, low, i.v. dose of aspirin (2 mg/kg), which reduced TxB2 (the stable metabolite of TxA2) to less than 3% of the control values. There were 129 transient ischemic episodes during control and 146 after aspirin, when platelet TxB2 was reduced to negligible levels. The duration, severity and incidence of symptomatic episodes were not significantly affected by TxA2 blockade. We conclude that platelet TxA2 is probably not responsible for the initiation of coronary vasospasm.

Adult↗
PubMed1982

Evidence for a direct stimulatory effect of prostacyclin on renin release in man.

THE OBJECTIVES OF THIS INVESTIGATION WERE: (a) to characterize the time and dose dependence of the effects of prostacyclin (PGI(2)) on renin release in healthy men; (b) to define whether PGI(2)-induced renin release is secondary to hemodynamic changes; (c) to determine the plasma and urine concentrations of 6-keto-PGF(1alpha) (the stable breakdown product of PGI(2)) associated with renin release induced by exogenous or pharmacologically enhanced endogenous PGI(2). Intravenous PGI(2) or 6-keto-PGF(1alpha) infusions at nominal rates of 2.5, 5.0, 10.0, and 20.0 ng/kg per min were performed in each of six normal human subjects; in three of them, PGI(2) infusion was repeated after beta-adrenergic blockade and cyclooxygenase inhibition. PGI(2), but not 6-keto-PGF(1alpha), caused a time- and dose-dependent increase of plasma renin activity, which reached statistical significance at 5.0 ng/kg per min and was still significantly elevated 30 min after discontinuing the infusion. Although combined propranolol and indomethacin treatment significantly enhanced the hypotensive effects of infused PGI(2), it did not modify the dose-related pattern of PGI(2)-induced renin release. Plasma 6-keto-PGF(1alpha) levels rose from undetectable levels (<7.5 pg/ml) in a stepwise fashion during increasingly higher infusion rates of PGI(2) or 6-keto-PGF(1alpha). The threshold concentration of plasma 6-keto-PGF(1alpha) associated with a statistically significant stimulation of renin release was approximately 200 pg/ml. Upon discontinuing PGI(2) or 6-keto-PGF(1alpha) infusion, the disappearance of 6-keto-PGF(1alpha) from blood showed an identical biphasic behavior, the initial phase having an apparent t((1/2)) of 3.2 min. The intravenous infusion of furosemide, which is known to stimulate renin release via a cyclooxygenase-dependent mechanism, caused a three-to fourfold increase of urinary 6-keto-PGF(1alpha) excretion rate, concomitant with the elevation of plasma renin activity levels, in six healthy women. 6-Keto-PGF(1alpha) remained undetectable in peripheral venous plasma throughout the study. WE CONCLUDE THAT IN HUMAN SUBJECTS: (a) PGI(2)-induced renin release occurs with a dose and time dependence similar to its reported platelet effects; (b) PGI(2)-induced renin release is not mediated by adrenergic stimuli or cyclooxygenase-dependent mechanisms secondary to hemodynamic changes; (c) furosemide-induced renin release is associated with increased renal PGI(2) formation; and (d) PGI(2) appears to act as a local modulator rather than a circulating hormone in controlling juxtaglomerular function.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects.

Acetylation of platelet cyclooxygenase by oral aspirin is dose dependent and cumulative with repeated administration. However, no single dose of aspirin has been found to be completely selective of platelet thromboxane (TX) synthesis inhibition in man. We determined the dose dependence, cumulative nature and selectivity of aspirin effects on platelet TXB(2) and renal prostaglandin (PG) and prostacyclin (PGI(2)) production. We measured, by radioimmunoassay, serum TXB(2) levels after whole blood clotting and urinary excretion of PGE(2), PGF(2alpha), and 6-keto-PGF(1alpha), before and after single or repeated oral aspirin doses given to 46 healthy subjects. Single doses of 6-100 mg aspirin resulted in a linear (r = 0.92, P < 0.01) inhibition of platelet TXB(2) production, ranging from 12 to 95% after 24 h. A daily dose of 0.45 mg/kg given for 7 d produced a cumulative and virtually complete inhibition of platelet TXB(2) production, without significantly reducing the urinary excretion of PGE(2), PGF(2alpha), and 6-keto-PGF(1alpha) in both healthy men and women. The platelet inhibitory effect of this regimen was maintained unaltered throughout 1 mo of therapy, with no evidence of cumulative inhibition of renal PG-synthesis. Moreover, furosemide-induced renal PGI(2) synthesis and renin release were unaffected by chronic low-dose aspirin. Following cessation of aspirin therapy, platelet TXB(2) production returned toward control values at a similar rate as after a single higher dose. WE CONCLUDE THAT IN HEALTHY SUBJECTS: (a) aspirin causes a dose-dependent inhibition of platelet TXA(2) production, with no obvious sex-related difference; (b) the inhibitory effect of daily low-dose aspirin is cumulative on platelet TXA(2) but not on renal PG-synthesis; (c) during chronic low-dose aspirin therapy, renal PGI(2)-producing cells are readily activable by furosemide at a time of virtually complete suppression of platelet cyclooxygenase activity.

Adolescent↗
PubMed1981

Pulmonary formation of prostacyclin in man.

The pulmonary formation of prostacyclin (PGI2), as reflected by the difference in concentration of pulmonary and systemic arterial radioimmunoassayed 6-keto-PGF1 alpha, was determined in six healthy waking subjects. The systemic arterial 6-keto-PGF1 alpha levels were low (less than or equal to 50 pg/ml), and no evidence of pulmonary formation and release of the compound was noted. In other experiments systemic arterial 6-keto-PGF1 alpha levels were determined in patients prior to and during artificial ventilation, as well as during and after occlusion of the pulmonary circulation (extra-corporeal circulation, ECC). The arterial 6-keto-PGF1 alpha concentration prior to artificial ventilation was 17 +/- 4 pg/ml, i.e. within the range observed in the healthy subjects. During artificial ventilation the arterial levels of 6-keto-PGF1 alpha increased to 191 +/- 21 pg/ml, suggesting that pulmonary formation of PGI2 was stimulated. In the patients subjected to ECC with occluded pulmonary circulation the arterial content of 6-keto-PGF1 alpha was stabilised at an elevated level (120-170 pg/ml). Following re-establishment of the pulmonary circulation the arterial concentrations of 6-keto-PGF1 alpha increased markedly, to 284 +/- 50 pg/ml. It is suggested that the basal pulmonary formation of PGI2 in man is low or non-existent, and that enhanced formation of the compound in the lungs is a consequence of intervention with normal pulmonary ventilation of perfusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Prostacyclin stimulates the adenylate cyclase system of human thyroid tissue.

Since Prostacyclin (PGI2) is a major product of arachidonic acid metabolism in the human thyroid, we have studied the effects of PGI2 on cAMP accumulation in human thyroid slices and cultured thyrocytes. In both systems, PGI2 caused a dose- and time-dependent increase of cAMP accumulation with higher potency and efficacy than PGE2. Two optically active isomers of 5,6-dihydro-PGI2, i.e. stable synthetic analogs of PGI2, had qualitatively similar effects to PGI2. The relative potency ratio between the alpha- and beta- isomer as well as their potency compared to PGI2 were substantially similar to their potency in inhibiting human platelet aggregation. In thyroid slices, PGI2 and its stable analogs had a greater effect than TSH in causing cAMP accumulation; however, in contrast to TSH, this effect was not associated with increased iodothyronine release except at maximal PGI2 concentrations. TSH had no detectable effect on thyroidal PGI2 synthesis and release. In cultured thyrocytes the effects of PGI2 and its stable analogs were considerably less than those obtained with TSH and required higher concentrations. Such a discrepancy was not found in the case of PGE2. These findings suggest the existence of a specific PGI2-responsive adenylate cyclase system in human thyroid cells other than thyrocytes, of possible physiologic significance.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Prostacyclin does not affect insulin secretion in humans.

The effects of Prostacyclin (PGI2) infusion on insulin secretion and glucose tolerance were investigated in 7 healthy subjects. PGI2 infusion caused no statistically significant changes of either glucose or insulin concentration, over the range 2.5-20 ng/Kg/min. A constant PGI2 infusion (10 ng/Kg/min) did not inhibit acute insulin responses to a glucose (20 g i.v.) pulse (response before PGI2 = 612 +/- 307%; during PGI2 = 515 +/- 468%, mean +/- SD, mean change 3-5 min insulin, % basal; P=NS). Glucose disappearance rates were similar after the first and second glucose pulse. Thus, in contrast to PGE2, PGI2 does not affect insulin secretion nor glucose disposal at doses producing platelet and vascular changes. It is hypothesized that an altered PGI2/PGE2 balance in diabetes may represent a link between vascular, platelet and metabolic changes.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs.

1 The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short-term treatment with 6alpha-methyl-prednisolone (6-MeP: 4-8 mg/day) or indoprofen (1.2 g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect.2 Measurements of prostaglandin E(2) (PGE(2)), thromboxane (TX) B(2), 6-keto-PGF(1alpha) and PGF(2alpha) were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity.3 PGE(2) and TXB(2) accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds.4 Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6-keto-PGF(1alpha) to 90% in the case of PGE(2).5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF(1alpha) concentrations were reduced by 35%, PGF(2alpha) concentrations were increased by 30%, while PGE(2) and TXB(2) were unchanged following 6-MeP.6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE(2) and TXB(2) levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti-inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side-effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1980

Plasma and synovial fluid pharmacokinetics and prostaglandin inhibitory effect of indoprofen in patients with rheumatoid arthritis.

Indoprofen was given intravenously (bolus followed by infusion) and orally to 7 patients suffering from active rheumatoid arthritis with knee joint effusion. Indoprofen readily penetrated into synovial fluid in amounts which were directly correlated with areas under curves of plasma drug levels. Synovial fluid acted as a compartment distinct from the central (plasma) compartment. Indoprofen caused a substantial decrease in E2 and F2 alpha prostaglandin concentration in synovial fluid.

Adult↗
PubMed1979

Characterization of furosemide-induced activation of the renal prostaglandin system.

A detailed time course of changes in plasma renin activity (PRA), urinary prostaglandin (PG) E2, PGF2 alpha, thromboxane (TX) B2 and sodium excretion rates following furosemide was obtained in 7 women. PRA increased within the first 15 min and remained elevated all through the experiment. PGE2, PGF2 alpha, TXB2 and sodium increased simultaneously, reached a peak between 15 and 45 min after furosemide and declined thereafter. It is concluded that furosemide induces a generalized activation of the renal PG system temporally related to the increase of renin release and natriuresis.

Adult↗