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Biomedical subjects

D Giannessi

Publications and source records attributed to D Giannessi.

At least 73 records · Page 4Linked to original sources
PubMed1983

Antiplatelet effects of isosorbide dinitrate in man.

Variable antiplatelet effects have been described for various antianginal drugs, including beta-blockers, verapamil, and nifedipine. To assess and characterize a possible similar effect of nitrates, platelet-rich plasma (PRP) from 22 healthy donors was incubated with scalar concentrations (1.25, 12.5, 125 micrograms/ml) of isosorbide dinitrate (ISDN) and with the vehicle alone for periods of 5 and 10 min. Platelet aggregation was successively induced by ADP (0.4-1.2 microM), adrenaline (0.8-8 microM), collagen (16.7 micrograms/ml), arachidonic acid (AA; 1 mM) and thrombin (0.5-2 U/ml). At the end of aggregation thromboxane (TX) B2 levels in PRP were assessed by RIA. A dose-dependent decrease in both platelet aggregation and TXB2 levels by all the inducers tested was demonstrated with both incubation times. Maximum inhibition of platelet aggregation was observed with ADP and adrenaline (72.0% and 55.6% respectively with 10-min incubation and the highest ISDN concentration. P less than 0.01 and P less than 0.05 respectively). A reduction in TXB2 levels in PRP was also observed, but reached statistical significance (P less than 0.01) only for AA-induced TXB2 generation. For an in vivo study ISDN was infused for periods of 30 min at 4 mg/h in 11 angina patients, and for periods of 20 min at 30 mg/h in an other eight, under ECG and arterial blood pressure monitoring. ADP- and adrenaline-induced aggregation and TXB2 production, and determination of circulating platelet aggregates (CPA) were performed in basal conditions and at 5, 15, 30 and 90 min from infusion start in the first group, at 5, 15, and 80 min in the second group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1980

Labeled metabolites appearing in human serum after 125I-triiodothyronine (T3) administration: a quantitative reappraisal.

The appearance in human serum of labeled iodothyronines arising from 3,5,3'-triiodothyronine (T3) catabolism was measured after bolus administration of 125I-T3. The use of column chromatography made it possible to separate in the plasma samples iodoproteins, iodide, T3 and a fourth peak ("pre-T3") eluting just before T3. The radioactivity associated with this pre-T3 peak was found to be 0.5% of T3 activity 30 min after injection, and reached a plateau value of 5.6% +/- 1.2 (mean +/- SD) from the 10th hr onward. From these data, we calculated that a maximal 5% underestimation in T3 metabolic clearance rate is inherent in those analytical methods that do not completely separate pre-T3 from T3 radioactivity. The MCR of 3,3'-diiodothyronine (T2) was also measured from the plasma disappearance curve after single injection of 125I-3,3'-T2. From these data and the mean disappearance curve of T3, the appearance curve of 3,3'-T2 in plasma was reconstructed by convolution under the assumption of a 100% conversion of T3 to 3,3'-T2. A plateau value of 4.6% of T3 activity was computed, very comparable to the experimentally determined 5.6%. This suggest that, if labeled 3,3'-T2 is the main component of the pre-T3 peak, the conversion into 3,3'-T2 represents a major pathway of T3 metabolism in man.

Chromatography, Gel↗
PubMed1979

Triiodothyronine turnover studies in euthyroid patients with autonomous thyroid nodules.

Triiodothyronine (T3) kinetic studies were carried out using 126I-T3 and the single injection technique in eight clinically euthyroid patients with autonomous thyroid nodules and the metabolic results were compared to those obtained in a group of 12 healthy control subjects. Plasma labeled T3 concentration was measured by a chromatographic method based on the extraction of the hormone on Sephadex G-25 columns, followed by its elution with a specific anti-T3 antiserum. The analysis of the experimental plasma disappearance curves of the labeled hormone was performed using the noncompartmental method. The results obtained showed a significantly increased metabolic clearance rate of T3 in the patients with autonomous thyroid nodules, as compared to the control group. On the average, the T3 production rates were increased more significantly than the corresponding circulating levels of the hormone, therefore, suggesting that the significant TSH inhibition observed in the euthyroid patients with autonomous thyroid nodules could be related with an increased peripheral utilization of triiodothyronine.

Adolescent↗
PubMed1979

Radioimmunoassay of unconjugated and total serum estetrol using a 125I-iodinated tracer.

A radioimmunossay (RIA) for the measurement of both unconjugated and total serum estetrol has been developed, using an antiserum to an E4-3-conjugate and a 125I-radioiodinated E4 tracer. Assay of dried ethyl ether extracts was used for the determination of unconjugated E4, while a direct measurement of unextracted hydrolyzed serum in the presence of 0.3% 8-anilino-1-naphthalene sulphonic acid (ANS) proved adequate for total E4. Assay reliability was evaluated and the procedure standardized through a series of tests aimed at assessing accuracy, sensitivity and precision. No steroidal interference was found to practically affect the assay (0.3% estriol cross-reactivity), nor were solvent and sample blanks observed in the case of unconjugated E4. For total E4 assay, the sample blank effects were acceptably overcome by using hydrolyzed male serum and 0.3% ANS, as a standard diluent. An interassay variability amounting to approximately 10 and 6% resulted for unconjugated E4 and total E4 RIA, respectively. A number of serum samples (285 for unconjugated E4, 147 for total E4) randomly collected throughout normal pregnancy were assayed. The unconjugated E4 levels at 15th week and at term were 62.7 +/- 22.6 and 766.5 +/- 208.2 (SD) pg/ml, respectively. Total E4 was about 6--7 times higher than the levels of free E4 and increased 7 times from the 15th week to term.

Circadian Rhythm↗
PubMed1979

Effect of endogenous thyroid stimulating hormone levels on the secretion of thyroid hormones in man.

The effect of endogenous thyroid stimulating hormone (TSH) on the thyroid secretion of triiodothyronine (T3) and thyroxine (T4) was evaluated by serial determinations of serum T3. T4 and TSH concentrations in the following groups of patients: a) three patients submitted to surgical removal of a solitary, autonomous thyroid nodule which had completely inhibited the extranodular tissue; b) five subjects, with the same disease, in whom functional recovery of the extranodular tissue was induced by increased circulating TSH levels, produced by treatment with methimazole; c) one patient submitted to hemithyroidectomy for multinodular goitre; d) two hyperthyroid patients who had been treated with methimazole. In all these patients serum T3 and T4 levels progressively decreased, with a consequent progressive increase in serum TSH concentrations, leading to stimulation of the thyroid gland. During this TSH-induced stimulation of thyroid tissue, a significant positive correlation was found between the serum TSH concentrations and the corresponding ratio between the serum levels of T3 and T4 (T3/T4), both within each patient group (P less than 0.001) and among all patients (P less than 0.001). The same correlation also governs the relationship between the TSH and the T3/T4 values of 34 euthyroid control subjects and one patient with incipient hypothyroidism. These data strongly suggest that endogenous TSH can induce a preferential secretion of T3 over T4 by the human thyroid.

Goiter↗
PubMed1978

Evaluation of triiodothyronine (T3) kinetics in normal subjects, in hypothyroid, and hyperthyroid patients using specific antiserum for the determination of labeled T3 in plasma.

Triiodothyronine (T3) kinetics was evaluated using [125I]T3 and the single injection technique; 5 hypothyroid, 6 hyperthyroid patients, and 10 euthyroid control subjects were studied. Plasma-labeled T3 concentration was measured by means of a new method based on extraction of the hormone on Sephadex G-25 columns followed by elution with the specific antiserum. This technique allows a far better separation of the hormonal radioactivity from the labeled iodide produced from T3 catabolism in comparison with the TCA-precipitation-butanol extraction method. The analysis of the experimental data has been performed using non-compartmental treatment (integral approach); results of mono-compartmental analysis of the same data are also reported for comparison. Average metabolic clearance was 15.3 +/- 0.6 (mean + SEM) liters/day/m2 body surface in normal subjects; it was significantly decreased in hypothyroid patients (11.4 +/- 1.1) and significantly increased (33.4 +/- 4.0) in hyperthyroidism. The total plasma equivalent distribution volume was found significantly enlarged in hyperthyroid patients (22.6 +/- 0.9 liters/m2) in respect to that measured in the control group (15.6 +/- 0.4), whereas it was not different from normal value in hypothyroid patients (17 +/- 1.7). Using plasma concentration of native T3, absolute turnover rate and extrathyroidal pool were also estimated; their values were 6.5, 23.7, and 131.7 micrograms/day/m2 and 10.1, 24.2, and 90.6 micrograms/m2, respectively, in hypothyroid, normal, and hyperthyroid groups.

Adolescent↗
PubMed1977

Direct radioimmunoassay of estradiol in serum extracts.

The feasibility of direct radioimmunoassay of unconjugated estradiol in dried serum extracts in the assessment of ovarian function in the regulation of the menstrual cycle has been investigated. Using an antiserum to an estradiol-6-conjugate, assay reliability was evaluated and the procedure standardized through a series of tests aimed at assessing accuracy, sensitivity, and precision. These included multiple titration with competing steroids, the definition of blank effects from solvent and sample, the assay both of samples to which known amounts of estradiol had been added and of serially diluted samples, and clinical validation using as a reference samples related to well-defined physiological situations. The variability of replicate estimates and the repeatability of the calibration curve were evaluated to obtain information on assay precision and sensitivity. The analytical performances proved to be perfectly adequate for the clinical purposes for which the assay was intended, in terms both of reliability of results and of methodologic practicability.

Animals↗
PubMedDate not supplied

Effects of nabumetone, a new non-steroidal anti-inflammatory drug, on urinary prostaglandin excretion in man.

Nabumetone is a non-acidic pro-drug which, after absorption, is transformed by the liver into 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite responsible for its anti-inflammatory activity. The urinary concentrations of 6-MNA are very low and its urinary metabolites are weak inhibitors of cyclo-oxygenase. For these reasons we hypothesized that nabumetone could spare renal cyclo-oxygenase products and, consequently, better preserve renal function unlike most other non-steroidal anti-inflammatory drugs (NSAIDs) which are known to cause an impairment of renal function, mostly related to inhibition of renal prostaglandin synthesis. We measured serum creatinine, creatinine clearance and the urinary excretion of stable prostaglandins (PG)E2 and 6-keto-PGF1 alpha, as a reflection of the renal production of PGE2 and PGI2, respectively, in 12 arthritic patients (5 males, 7 females) with normal creatinine clearance. Measurements were performed before and after a 2-week treatment with nabumetone (1 g day-1). 6-keto-PGF1 alpha and PGE2 were measured by specific radioimmunoassays (RIA) after organic solvent extraction and silicic acid column chromatography. The assay sensitivity to detect renal cyclo-oxygenase inhibition was independently verified by measuring urinary 6-keto-PGF1 alpha in normal subjects before and after aspirin and ibuprofen, known inhibitors of renal prostaglandins. At the end of treatment, serum levels of 6-MNA ranged between 24.5 and 122.4 mg 1-1, within the described therapeutic range for the drug. After nabumetone, no significant differences in the urinary excretion of the two prostaglandins with respect to baseline values were observed (for 6-keto-PGF1 alpha from 12.3 +/- 6.0 to 12.1 +/- 8.7 ng h-1, mean +/- S.D.; for PGE2 from 12.3 +/- 13.6 to 11.3 +/- 15.3 ng h-1). Also no changes in serum creatinine or creatinine clearance were observed. These results suggest that nabumetone does not significantly impair renal prostaglandin synthesis in patients with osteoarthritis.

Adult↗