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Biomedical subjects

F Galletti

Publications and source records attributed to F Galletti.

At least 73 records · Page 4Linked to original sources

Kinetics of caffeine metabolism in control and 3-methylcholanthrene induced rat liver microsomes.

The kinetics of formation of primary metabolites of caffeine (paraxanthine, theophylline, theobromine and 1,3,7-trimethyluric acid) was studied in control (CO) and 3-methylcholanthrene-induced (MC) rat liver microsomes. Vmax was similar but Km was 16 times lower for total caffeine metabolism in CO and MC microsomes, respectively. Similar behavior was observed in the formation of each metabolite. Single metabolites showed different degrees of induction at non-saturating concentrations of caffeine. Kinetics was non-linear in CO microsomes.

Animals↗

Side effects during therapy with low dosage amiodarone.

Amiodarone is a very active antiarrhythmic agent, but true incidence of Amiodarone-related side effects is still questionable. In a prospective trial of 400 or 200 mg of Amiodarone day for 56 days in 58 patients, we monitored thyroid and liver function, blood count, chest x-ray, ecg. In addiction we took regularly notice of subjective disturbances and physical signs. Side effects were: conduction disturbances 6%, bradycardia less than 50/min. 2%, gastrointestinal 12%, sleep disorders 12%, hyperthyroidism 4,15% and hypothyroidism 6.25%. Blood levels of Amiodarone and desethylamiodarone were not predictive of side effects. Noteworthy was the absence of cutaneous and pulmonary side effects. On the other hand, thyroid function should be monitored carefully because disfunction is not rare (10.4%) and in the case of hyperthyroidism could be related to worsening of arrhythmias.

Adolescent↗

Altered kinetics of an intravenous calcium load in hypertensive patients.

Essential hypertensive (EH) patients have a higher rate of urinary calcium excretion and, according to some reports, somewhat lower levels of serum ionized calcium. The aim of this study was to investigate the kinetics of an i.v. calcium load in EH patients and in normotensive controls. Fifteen EH patients and twelve sex-and weight-matched controls received a constant ionized rate i.v. calcium infusion (0.1 mmol Ca2+/kg body weight/h) for 2 h. Serum ionized calcium and urinary calcium excretion were determined at regular intervals during the infusion and, in two subgroups of seven hypertensives and seven controls, for up to 4 hours later. EH patients had significantly higher excretion rates (P less than (P less than 0.001) and slightly, but not significantly, lower serum ionized calcium compared to controls. The serum ionized calcium concentration attained at 60 and 120 min of the Ca2+ infusion was significantly lower in EH (P less than 0.01) and it remained appreciably lower for up to 220 min from the beginning of the test. The area under the curve of serum ionized calcium calculated at different time points was significantly reduced in the hypertensives. The mean renal calcium clearance of the patients during the infusion and the elimination phase was somewhat higher, but the difference from controls did not reach statistical significance. These data indicate an abnormal handling of a calcium load by patients with EH and raise the possibility that such abnormality may not be due simply to a renal defect but perhaps to an altered calcium distribution among different compartments in the body.

Adult↗

Plasma levels of salicylate and aspirin in healthy volunteers: relevance to drug interaction on platelet function.

Salicylate can prevent the inhibitory effect of aspirin on platelet cyclooxygenase activity. We investigated whether salicylate and aspirin interact in platelets in humans at doses and plasma levels of clinical relevance. In our first experiment in healthy volunteers, the lowest dose of intravenously administered aspirin that suppressed arachidonate-induced platelet aggregation and serum immunoreactive thromboxane B2 generation was 40 mg. In our second experiment, volunteers given oral doses of sodium salicylate (250 or 1000 mg) had peak plasma salicylate levels averaging 20 and 76 micrograms/ml, respectively. Neither platelet aggregation or thromboxane B2 formation was modified by either salicylate treatment. Forty minutes later, all six volunteers received 40 mg of aspirin intravenously. Aspirin levels were not affected by previous salicylate ingestion, but inhibition by aspirin of both platelet aggregation and thromboxane B2 generation was significantly prevented by the higher salicylate dose. In our last experiment, peak plasma levels of aspirin and salicylate were measured in healthy volunteers after ingestion of either 320 mg of compressed or 800 mg of enteric-coated aspirin. Salicylate levels averaged 19 and 51 micrograms/ml, respectively, after the lower and higher doses of aspirin, whereas aspirin averaged 3 micrograms/ml after either dose. Serum thromboxane B2 generation was almost completely inhibited 1 hour after either aspirin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long term treatment with tienilic acid or thiazides: comparison of antihypertensive and metabolic effects.

A comparison has been made of arterial pressure and major metabolic parameters during long term treatment with tienilic acid and a hydrochlorothiazide-amiloride combination, using a randomized single-blind study without cross-over. A significant fall in systolic and diastolic blood pressure and no change in most biochemical parameters was observed with both drugs. Serum uric acid concentration was decreased during tienilic acid and was slightly increased whilst subjects took the hydrochlorothiazide-amiloride combination; serum potassium was slightly decreased on tienilic acid. No sign of hepatotoxicity was detected.

Adult↗

Acute overdosage of amiodarone in a suicide attempt.

Clinical and biochemical variables and blood levels of amiodarone and its metabolite are reported after acute self-intoxication in a young woman. Despite the huge amount of drug ingested no clinical side effects were documented over the monitored period of 3 months.

Adult↗

Caffeine disposition after oral doses.

Caffeine (TMX) disposition was studied in mean after 1, 5, and 10 mg/kg in water, as mocha coffee (1.54 mg/kg) and as a soft drink (0.22 mg/kg). TMX and its metabolites were analyzed in plasma and urine by high-pressure liquid chromatography. The design permitted confirmation of most of the partial results in various experimental settings and contributed new data on the metabolic disposition of TMX, with specific reference to main dimethylxanthine metabolite found in plasma, paraxanthine (1,7-dimethylxanthine). Different analysis methods were compared for the calculated parameters (absorption and elimination rate constants and renal clearance)to assess the consistency of results. The kinetics of TMX and of its dimethylated metabolites in plasma were described with a model that used an analogdigital hybrid computing system. In addition to providing a comprehensive profile of TMS disposition in the healthy adult, the results indicate tha TMX exhibits dose-independent kinetics at the levels at which man normally takes TMX.

Administration, Oral↗

Salicylate-aspirin interaction in the rat. Evidence that salicylate accumulating during aspirin administration may protect vascular prostacyclin from aspirin-induced inhibition.

Aspirin inhibits cyclooxygenase, thus preventing thromboxane A2 production in blood platelets and prostacyclin in vascular cells. Aspirin is rapidly hydrolyzed to salicylate in the circulation. The objectives of this study were (a) to evaluate whether administration of salicylate, though ineffective by itself, prevents the inhibitory effect of aspirin on platelet and/or vascular cyclooxygenase activity; (b) to verify whether salicylate accumulating in blood after aspirin administration interferes with the pharmacological activity of further doses of aspirin. Pretreatment of rats with sodium salicylate (25-100 mg/kg i.p.) resulted in dose-related prevention of the effect of a subsequent dose of aspirin (2.5-10 mg/kg i.v.) on both platelet and vascular cells. Sodium salicylate appeared to amplify the greater response of platelets to aspirin compared with vessel wall. Pretreatment of rats with repeated high doses of aspirin (200 mg/kg) resulted after 24 h in blood salicylate levels (150-200 microgram/ml) that significantly prevented the inhibitory effect of a subsequent dose of aspirin on newly synthesized vascular prostacyclin. Blood salicylate levels obtained after 36 or 48 h (less than 50 microgram/ml) were too low to blunt aspirin's effect. The interference with aspirin of its major endogenous metabolite should be borne in mind when interpreting results obtained with high dose aspirin or during repeated administration of this drug.

Animals↗