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Biomedical subjects

F Pugliese

Publications and source records attributed to F Pugliese.

At least 91 records · Page 5Linked to original sources
PubMed1984

Differential effects of dazoxiben, a selective thromboxane-synthase inhibitor, on platelet and renal prostaglandin-endoperoxide metabolism.

Pharmacologic inhibition of thromboxane (TX) synthase can result in redirection of prostaglandin (PG) endoperoxide metabolism, possibly affecting platelet, vascular and renal function. This study explores the in vitro, ex vivo and in vivo effects of dazoxiben, an orally active TX-synthase inhibitor, on platelet and renal TXB2 production and associated changes in PG-endoperoxide metabolism. Dazoxiben inhibits TXB2 production in clotting human whole blood with an IC50 of 0.3 micrograms/ml and causes parallel enhancement of PGE2 greater than PGF2 alpha greater than 6-keto-PGF1 alpha production. Similar redirection of PG-endoperoxide metabolism is observed ex vivo, after the oral administration of 1.5 and 3.0 mg/kg to six healthy volunteers. Plasma 6-keto-PGF1 alpha ranges between less than 4 and 8 pg/ml during the first 3 h. Urinary TXB2 excretion, a reflection of renal TXA2 production, is significantly reduced by 30% with no evidence of redirection of renal PG-endoperoxide metabolism. In vitro inhibition of TXB2 production in rat kidney glomeruli requires significantly higher dazoxiben concentration (IC50 = 1.60 micrograms/ml) than in rat whole blood (IC50 = 0.32 micrograms/ml) and is not associated with changes in PGE2, PGF2 alpha and 6-keto-PGF1 alpha production. These results demonstrate quantitatively and qualitatively diverse effects of dazoxiben in different TXA2-producing cells and suggest the possibility of developing tissue-selective TX-synthase inhibitors.

Adult↗
PubMed1983

[Various psychological parameters in subjects occupationally exposed to radiofrequencies].

Because of increasing interest for electromagnetic fields biological effects we examined possible effects on behaviour produced by prolonged exposition to radiofrequencies on some wood industry workers. The results of psychological tests seem to prove a significant difference between exposed and control groups in the answers concerning social relations and anxiety. However these results have to be confirmed by other and more complete studies.

Adult↗
PubMed1983

[Proposal for evaluating the psychological effects of exposure to non-ionizing radiation in the work environment].

Because of the growing national and international spreading of devices producing non-ionizing radiations, the AA consider the possibility of a deep study on some of the most precious and interesting effects, though controversial at the same time, described in occupationally exposed subjects: the psychological ones. Such a study, however, presents considerable difficulties because of the great deal of personal, domestic and social factors responsible for the arising of such a symptomatology. Therefore the AA suggest the use of a set of tests particularly aiming at leaving out such factors in the genesis of the psychological troubles; this set must be previously administered to a carefully selected sample in order to verify its accuracy, reliability, sensitivity and specificity, so that it will be possible to extend afterwards the research to larger samples of population.

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↗
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↗
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↗
PubMed1979

Evidence for an extra-renal origin of urinary prostaglandin E2 in healthy men.

In order to verify the validity of the assumption that male urinary Prostaglandin (PG) E2 reflects its renal production, PGE2 and PGF2 alpha concentrations were measured by radioimmunoassay in the renal venous plasma (RVP) and urine (U) of 12 male and 4 female healthy volunteers. While women had a similar PGE2/PFG2 alpha ratio in RVP (0.59 +/- 0.18) and U (0.41 + 0.06), men and a significantly (P less than 0.05) higher ratio in U (1.43 +/- 1.72) as compared to RVP (0.54 +/- 0.16). This was largely due to considerably higher and more variable U-PGE1 concentrations (roughly 6 times higher than female values), despite almost identical RVP levels. The possibility of an increased U excretion of a cross-reacting member of the PG-system, as a cause of such apparently high PGE2-like immunoreactivity (LI), was ruled out by TLC characterization of PGE2-LI with three different anti-PGE1 sera. Thus, male U-PGE2 may variably reflect an extra-renal source, such as contamination with trace amounts of seminal fluid. It is concluded that, unless such a contamination can be monitored and corrected for, measurement of male U-PGE1 should be considered of questionable relevance to renal PG-synthesis.

Chromatography, Thin Layer↗
PubMed1978

Aspirin intolerance: unaltered susceptibility of platelet cyclo-oxygenase to inhibition by aspirin in vitro.

Inhibition of prostaglandin (PG) biosynthesis has been proposed as a mechanism of aspirin-induced asthma. In order to verify the existence of a generalized abnormal sensitivity of the PG cyclo-oxygenase in intolerant patients, we have compared the inhibitory effects of aspirin on platelet PGE2 and PGF2alpha spontaneous formation in vitro, in 10 healthy subjects, 10 aspirin-sensitive asthmatics, and 10 nonasthmatic aspirin-sensitive patients. No statistically significant differences were found in the pattern nor in the absolute concentrations of both PGs in the control platelet superfusates. Moreover, the synthesis and release of both PGs were inhibited by aspirin with the same potency in the three groups studied.

Adult↗