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F Pugliese

Publications and source records attributed to F Pugliese.

At least 73 records · Page 4Linked to original sources
PubMed1989

[Short- and medium-term treatment of ventricular hyperkinetic arrhythmia with flecainide].

Our study group included 12 patients (4 males, 8 females), mean age 60 yr, with symptomatic or threatening tachyarrhythmias (Lown classes IV A, B, V); 2 patients were suffering from mitral valve prolapse syndrome, 2 from ischemic heart disease; 4 from cardiac insufficiency caused by hypertensive or ischemic heart disease; 4 had no evident clinical signs of cardiopathy. Patients suffering from: cardiac insufficiency (F.C. III e IV NYHA); II and III degree BAV; atrial flutter and fibrillation; long QT syndrome; acute ischemic heart disease were excluded from the study. During short-term treatment, patients received placebo for four days and subsequently flecainide 200 mg daily for four days. During medium-term treatment patients received flecainide 200 mg daily (for six months). Several Holter/24-hour monitorings were performed for evaluation of therapy. No significant reduction in the number of ectopic ventricular beats (B.E.V.) was found with placebo whereas reductions of B.E.V. number (97% and 95%, respectively) were found during short and medium-term treatment with flecainide. Flecainide produced: changes in Lown class: from IV A, B and V to II and I; a marked reduction of subjective symptoms (dyspnea, giddiness syncope, precordial pain); ECG changes: increases in: PR: 5-25%; QRS: 11-12%; QT: 11-22%. Flecainide produced no pro-arrhythmic effects or changes in echocardiographic ventricular function index. Flecainide can be considered one of the most effective new antiarrhythmic drugs.

Aged↗
PubMed1989

Neutralization of the anionic sites of cultured rat mesangial cells by poly-L-lysine.

Changes in eicosanoid synthesis are a feature of the functional response of rat glomerular epithelial cells to neutralization of the cell surface polyanion. In order to ascertain if this property is common to other glomerular cell types, we have investigated the effect of neutralization of the negatively charged sites of cultured rat mesangial cells by poly-L-lysine on prostaglandin E2 (PGE2) production. Addition of poly-L-lysine (10 micrograms/ml) to the cells stimulated PGE2 synthesis after an initial latency of approximately two minutes, reaching maximum levels at 60 minutes. Poly-L-lysine also progressively increased cytosolic free calcium ([Ca2+]i) in fura-2 loaded monolayers with a similar initial lag time. Poly-L-lysine-evoked PGE2 synthesis and [Ca2+]i increases were dose dependent and prevented by addition of the polyanions, heparin and albumin. Additionally, heparin was also capable of reversing the effect of poly-L-lysine on [Ca2+]i. Removal of extracellular Ca2+ prevented the increase of [Ca2+]i and PGE2 synthesis. Increased PGE2 synthesis following neutralization of mesangial cell anionic sites may play a role in the hemodynamic dysfunction and cellular derangements of glomerular inflammation.

Acid-Base Equilibrium↗
PubMed1989

Prostaglandins and hypertension.

Alterations in renal prostaglandins (PG) have been reported in hypertensive animals and in essential hypertension. Some alterations in the pattern of PG are more likely to be secondary to hypertension, whereas others may reflect a defective adaptation to the hypertensive state thus contributing to the rise in blood pressure. A major role for vasodilatory arachidonic acid (AA) metabolites is to modulate the effects of vasoconstrictor stimuli on renal vasculature and sodium excretion; thus, an alteration of this interplay may be responsible for some forms of experimental and human hypertension.

Animals↗
PubMed1988

Renal hemodynamics and urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 in newly diagnosed type I diabetic patients.

We have studied the functional importance of renal eicosanoids in renal hemodynamics of seven newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients by treatment with two structurally unrelated inhibitors of cyclooxygenase (i.e., piroxicam and sulindac). Glomerular filtration rate (GFR), renal plasma flow (RPF), daily urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of prostacyclin), and thromboxane B2 (TXB2, the stable hydrolysis product of thromboxane A2) were measured before, during, and after piroxicam (all patients) or sulindac (3 patients) treatment. Urinary excretion of 6-keto-PGF1 alpha was significantly increased (P less than .01) in diabetic patients compared with seven healthy subjects, whereas urinary excretion of TXB2 was unchanged. The baseline value of GFR was significantly (P less than .01) higher in diabetic compared with normal volunteers, whereas baseline RPF was comparable in both groups. Piroxicam (20 mg/day) reduced urinary excretion of 6-keto-PGF1 alpha and TXB2 by 65.7 +/- 26 and 64.6 +/- 33%, respectively. These biochemical changes were temporally associated with the approximately 19% decrease in GFR (P less than .01). A week after discontinuation of the drug, GFR and urinary excretion of 6-keto-PGF1 alpha were still significantly (P less than .05) reduced, whereas urinary excretion of TXB2 returned to control values. In contrast, urinary excretion of eicosanoids and renal function were not affected by sulindac (0.4 g/day) treatment. No functional changes were detected in healthy subjects despite a similar suppression of renal cyclooxygenase activity when they were treated with piroxicam.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Prostaglandins in blood pressure regulation.

Alterations in the pattern of renal PG have been reported in hypertensive animals and in human essential hypertension, reflecting a primary causative defect or changes which are secondary to hypertension. Furthermore, direct evidence for a primary role of AA metabolites in the long term control of blood pressure emerges from the interrelationship between angiotensin II, vasopressin, norepinephrine, and alfa-adrenergic stimuli. Since locally synthetized vasodilatory PG are known to modulate the effects of vasoconstrictor stimuli on renal vasculature and sodium excretion, it is suggested that an alteration of this interplay may be responsible for some forms of experimental and human hypertension.

Animals↗
PubMed1987

Effects of sulindac on renal and extrarenal eicosanoid synthesis.

We measured the renal and extrarenal synthesis of prostacyclin and thromboxane A2, as reflected by the urinary excretion of the stable hydration products 6-keto-prostaglandin F 1 alpha and thromboxane B2 and the corresponding 2,3-dinor-derivatives, during chronic administration of sulindac (200, 400, 600, and 800 mg/day, each dose given for 7 days in successive weeks) in seven healthy subjects. Urinary eicosanoids were measured by negative ion, chemical ionization-GC/MS-validated RIA techniques. Both 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F 1 alpha showed a dose-dependent reduction, ranging between 45% and 85%. In contrast, the urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 did not change significantly throughout the study. These results extend previous observations of a selective sparing of renal cyclooxygenase activity by sulindac in humans and demonstrate that this selectivity is not related to an overall weaker enzyme inhibition.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Glomerular epithelial cell, polyanion neutralization is associated with enhanced prostanoid production.

We have studied the effect of neutralizing the surface charge of rat glomerular epithelial cells (GEC) in culture on prostanoid production. Incubation of rat GEC with polycations poly-L-lysine (PL) resulted in a dose dependent increase of 6-keto-PGF1 alpha (up to 8 to 10-fold) and PGE2 (up to 7 to 8-fold) production. Other polycations such as protamine sulfate (PS) and lysozyme (LY) produced a similar effect. The stimulation of prostaglandin (PG) production by PL treated GEC was prevented by the addition of polyanions such as bovine serum albumin (BSA) and heparin (HP). The effect of PL on prostaglandin (PG) synthesis by GEC was suppressed by the cyclooxygenase inhibitor sulindac sulfide. Addition of exogenous arachidonic acid (C20:4) increased the basal production of PG and under these conditions the effect of PL was masked. We conclude that neutralization of the surface charge of rat GEC by polycations results in profound increase of prostanoid synthesis. The polycation caused increase in PG synthesis appears to be the result of increased availability of intracellular C20:4.

Animals↗
PubMed1987

Occupational asthma due to styrene: two case reports.

Two cases of occupational asthma due to styrene are described. The subjects complained of cough, breathlessness, and symptoms of asthma when coming into contact with styrene; in patient 1 the respiratory reaction was followed by a late cutaneous rash. The symptoms disappeared when the subjects were away from work on weekends or holidays. In both cases, inhalation challenge with styrene produced an immediate bronchospastic reaction which was followed by a late cutaneous rash in patient 1. Prior administration of disodium cromoglycate (40 mg from a spinhaler) prevented the respiratory reactions completely, but failed to prevent the late skin response in case 1. Styrene removal was followed by complete disappearance of the symptoms. We conclude that styrene can be a primary cause of occupational asthma.

Adult↗
PubMed1986

Effect of prostacyclin on renal kallikrein release in man.

The aim of this research was to study exogenous prostacyclin effect on urinary kallikrein excretion (UKK) in man, to define whether prostacyclin-induced renin release and/or endogenously released cyclooxygenase products were responsible for prostacyclin-induced enhancement of UKK, to determine furosemide effect on UKK. Prostacyclin was infused in eight healthy men and repeated after propranolol and indomethacin treatment. Prostacyclin caused a dose-dependent increase of UKK. Pretreatment with propranolol and indomethacin did not affect prostacyclin-induced enhancement of UKK, although it reduced absolute values of plasma renin activity. Furosemide increased UKK and simultaneously urinary 6-keto-prostaglandin F1 alpha. We conclude that prostacyclin induces an increase in UKK in a dose-dependent manner; furosemide-induced renal prostacyclin synthesis is temporally related to enhancement of UKK; partial dissociation of UKK from plasma renin activity under propranolol and indomethacin treatment and in response to furosemide might suggest a direct effect of prostacyclin on UKK.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Estimated rate of thromboxane secretion into the circulation of normal humans.

We have measured the excretion of a major urinary metabolite of thromboxane B2 (TxB2), i.e., 2,3-dinor-TxB2, during the infusion of exogenous TxB2 over a 50-fold dose range to enable estimation of the rate entry of endogenous TxB2 into the bloodstream. Four healthy male volunteers received 6-h i.v. infusions of venhicle alone and TxB2 at 0.1, 1.0, and 5.0 ng/kg X min in random order. They were pretreated with aspirin at a dose of 325 mg/d in order to suppress endogenous TxB2 production. Urinary 2,3-dinor-TxB2 was measured before, during, and up to 24 h after the infusions and in aspirin-free periods, by means of radioimmunoassay. The nature of the extracted immunoreactivity was characterized by thin-layer chromatography and confirmed by negative ion-chemical ionization gas chromatography/mass spectrometry. Aspirin treatment suppressed urinary 2,3-dinor-TxB2 excretion by 80%. The fractional elimination of 2,3-dinor-TxB2 was independent of the rate of TxB2 infusion and averaged 5.3 +/- 0.8%. Interpolation of metabolite values obtained in aspirin-free periods onto the linear relationship between the quantities of infused TxB2 and the amount of metabolite excreted in excess of control values (y = 0.0066x, r = 0.975, P less than 0.001) permitted calculation of the mean rate of entry of endogenous TxB2 into the circulation as 0.11 ng/kg X min. The rate of disappearance of immunoreactive TxB2 from the circulation was monoexponential over the first 10 min with an apparent half-life of 7 min. This corresponded to a maximal estimate of the plasma concentration of endogenous TxB2 of 2.0 pg/ml. These results suggest that ex vivo platelet activation and/or analytical problems confound estimates of endogenous thromboxane release based on plasma TxB2 and provide a rationale for seeking longer-lived enzymatic metabolites of TxB2 in plasma.

Adult↗
PubMed1985

Clinical pharmacology of platelet cyclooxygenase inhibition.

Nonsteroidal anti-inflammatory drugs and sulfinpyrazone compete dose-dependently with arachidonate for binding to platelet cyclooxygenase. Such a process closely follows systemic plasma drug concentrations and is reversible as a function of drug elimination. Peak inhibition and extent of its reversibility at 24 hr varies consistently with individual pharmacokinetic profile. Inhibition of platelet cyclooxygenase activity by these agents is associated with variable effects on prostaglandin (PG) synthesis in the gastric mucosa and the kidney. Aspirin acetylates platelet cyclooxygenase and permanently inhibits thromboxane (TX) A2 production in a dose-dependent fashion when single doses of 0.1 to 2.0 mg/kg are given. Acetylation of the enzyme by low-dose aspirin is cumulative on repeated dosing. The fractional dose of aspirin necessary to achieve a given level of acetylation by virtue of cumulative effects approximately equals the fractional daily platelet turnover. Serum TXB2 measurements obtained during long-term dosing with 0.11, 0.22, and 0.44 mg/kg aspirin in four healthy subjects could be fitted by a theoretical model assuming identical acetylation of platelet (irreversible) and megakaryocyte (reversible) cyclooxygenase. For a given dose within this range, both the rate at which cumulative acetylation occurs and its maximal extent largely depend upon the rate of platelet turnover. Continuous administration of low-dose aspirin (20 to 40 mg/day) has no statistically significant effect on urinary excretion of either 6-keto-PGF1 alpha or 2,3-dinor-6-keto-PGF1 alpha, i.e., indexes of renal and extrarenal PGI2 biosynthesis in vivo. Whether a selective sparing of extraplatelet cyclooxygenase activity by low-dose aspirin will result in increased antithrombotic efficacy, fewer toxic reactions, or both remains to be established in prospective clinical trials.

Aspirin↗
PubMed1985

Prostaglandins and other arachidonic acid metabolites in the pathogenesis of clinical and experimental glomerulonephritis.

Isolated glomeruli, glomerular epithelial cells and mesangial cells contain the cyclooxygenase enzyme that converts arachidonic acid to prostaglandin (PG)-endoperoxides. Biologically active metabolites of the latter include PGE2, PGF2 alpha, PGI2 and Thromboxane (TX) A2. These substances modulate renal cortical functions, i.e. renin release, renal blood flow (RBF) and glomerular filtration rate. Acute glomerular injury (nephrotoxic serum nephritis) augments glomerular production of PGs and TXA2. Thromboxane A2 reduces glomerular function and inhibition of TXA2 synthesis preserves GFR and RBF in this disease model. Patients with chronic glomerulonephritis have a lower urinary excretion of 6-Keto-PGF1 alpha (the stable hydrolysis product of the vasodilator PGI2). In these patients, inhibition of PGI2 synthesis by a cyclooxygenase inhibitor leads to reductions in GFR and RBF inversely related to the basal urinary excretion of 6-Keto-PGF1 alpha. These findings suggest that in both acute and chronic glomerulonephritis, arachidonate metabolites may serve as pathophysiologic mediators of changes in glomerular function.

Acute Disease↗
PubMed1984

Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin.

We investigated whether the glomerular synthesis of prostacyclin modulates the renal blood flow and glomerular filtration rate in chronic glomerular disease. The urinary excretion of 6-keto-prostaglandin F1 alpha, a stable breakdown product of prostacyclin, was significantly (P less than 0.01) reduced in 20 women with chronic glomerular disease, as compared with 19 controls, whereas excretion of urinary prostaglandin E2 was unchanged. In 10 patients randomly assigned to one week of treatment with ibuprofen, excretion of urinary 6-keto-prostaglandin F1 alpha and prostaglandin E2 was reduced by 80 per cent, the level of serum creatinine was increased by 40 per cent, and creatinine and para-aminohippurate clearances were reduced by 28 and 35 per cent, respectively. The reduction of both clearances was inversely related (P less than 0.01) to the basal urinary excretion of 6-keto-prostaglandin F1 alpha but not of prostaglandin E2. No functional changes were detected in five healthy women, despite a similar suppression of renal prostacyclin synthesis by ibuprofen. In contrast, one week of treatment with sulindac did not affect renal prostacyclin synthesis or renal function in the other 10 patients, despite a marked inhibition of extrarenal cyclooxygenase activity. We conclude that in patients with mild impairment of renal function, the renal blood flow and glomerular filtration rate are critically dependent on prostacyclin production. In such patients sulindac may be a safe substitute for other nonsteroidal antiinflammatory drugs.

6-Ketoprostaglandin F1 alpha↗