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Biomedical subjects

G Del Re

Publications and source records attributed to G Del Re.

9 recordsLinked to original sources

Liquid chromatographic method for the analysis of tocopherols in malt sprouts with supercritical fluid extraction.

A simple, specific and sensitive high-performance liquid chromatographic method has been developed for the determination of tocopherols in malt sprouts. A supercritical fluid extraction (SFE) procedure was used to isolate tocopherols from the vegetal matrix before quantitative analysis. The analytes were separated on a Zorbax reversed-phase column using methanol-water as mobile phase and quantified by measuring its fluorescence at lambda(em)=328 nm after excitation of the analytes at lambda(exc)=303 nm. The limits of detection for alpha-, gamma- and delta-tocopherols were 0.04, 0.05, and 0.05 microg/ml, respectively. The calibration graphs of the method were linear from 0.1 to 1.5, 0.2 to 2.5, and 0.2 to 2.0 microg/ml, for alpha-, gamma- and delta-tocopherols, respectively. This SFE and HPLC procedure is simple, precise and accurate for the determination of tocopherols in malt sprouts.

Calibration↗

Clinical and hormonal effects of the new angiotensin II receptor antagonist LRB081.

The renin-angiotensin system is a major contributor to the pathophysiology of cardiovascular diseases such as congestive heart failure and hypertension. Antagonizing angiotensin (Ang) II at the receptor site may produce fewer side effects than inhibition of the promiscuous converting enzyme. The present study was designed to assess in healthy human subjects the effect of LRB081, a new orally active AT1-receptor antagonist, on the pressor action of exogenous Ang II. At the same time, plasma hormones and drug levels were monitored. At 1-week intervals and in a double-blind randomized fashion, 8 male volunteers received three doses of LRB081 (10, 40, and 80 mg) and placebo. Blood pressure (BP) was measured at a finger by photoplethysmograph. The peak BP response to intravenous injection of a standard dose of Ang II was determined before and for < or = 24 h after administration of an oral dose of LRB081 or placebo. After drug administration, the blood BP response to Ang II was expressed in percent of the response before drug administration. At the same time, plasma renin activity (PRA), Ang II, aldosterone, catecholamine (radioassays), and drug levels (by high-performance liquid chromatography) were monitored. After LRB081 administration, a dose dependent inhibition of the BP response to Ang II was observed. Maximal inhibition of the systolic BP response was 54 +/- 3 (mean +/- SEM), 63 +/- 2, and 93 +/- 1% with 10, 40, and 80 mg LRB081, respectively. The time to peak was 3 h for 6 subjects and 4 and 6 h for 2 others. Preliminary plasma half-life (t1/2) was calculated at 2 h. With the highest dose, the inhibition remained significant for 24 h (31 +/- 5%, p < 0.05). Maximal BP-blocking effect and maximal plasma drug level coincided, suggesting that the unmetabolized LRB081 is responsible for the antagonistic effect. PRA and Ang II increased dose dependently after LRB081 intake. Aldosterone, epinephrine, and norepinephrine concentrations remained unchanged. No clinically significant adverse reaction was observed during the study. LRB081 is a well-tolerated, orally active, potent, and long-acting Ang II receptor antagonist. Unlike in the case of losartan, no active metabolite of LRB081 has been shown to be responsible for the main effects.

Adult↗

Pharmacokinetics and biochemical efficacy of idrapril calcium, a novel ACE inhibitor, after multiple oral administration in humans.

The pharmacokinetic profile and biochemical efficacy of idrapril calcium, a novel angiotensin converting enzyme (ACE) inhibitor, were evaluated in healthy volunteers after multiple dosing for 5 days at the doses of 100, 200 and 400 mg twice daily. The study was conducted as a double-blind, cross-over comparison of idrapril calcium against placebo. Plasma concentrations of idrapril were determined by an indirect enzymatic method. Urinary concentrations were measured by reverse phase high performance liquid chromatography (h.p.l.c.). Plasma samples were also analysed for ACE activity. The pharmacokinetics of idrapril calcium did not change significantly between day 1 and day 5. The values of Cmax and AUC were dose-related over the range of doses tested; tmax was 3-4 h and apparent elimination half-life was 1.4-1.6 h. Plasma ACE activity was maximally inhibited (94-96%) at all dose levels and remained more than 80% depressed from 2 to at least 6 h after idrapril calcium. Although the maximum effect was not dose-related, the duration of inhibition showed some dose-dependency, ACE activity returning to 56, 45 and 29% of the basal value 12 h after the 100, 200 and 400 mg doses, respectively. There were no clinically significant adverse events experienced by the volunteers. No dose-related effects on blood pressure or heart rate were observed. There were no changes in clinical pathology tests, urine analyses or electrocardiograms after dosing with idrapril calcium. Idrapril calcium, the prototype of a new class of ACE inhibitors, appears to be well-tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Reversal of left ventricular hypertrophy after one-year treatment with clonidine: relationship between echocardiographic findings, blood pressure, and urinary catecholamines.

Previous studies have shown that some antihypertensive drugs, beside controlling arterial pressure (AP), reverse left ventricular hypertrophy (LVH) by reducing adrenosympathetic activity. The aim of our study was to evaluate the relationship between AP levels, echocardiographic LVH and 24-h urinary excretion of epinephrine (UE) and norepinephrine (UNE) in 23 previously untreated stable hypertensive individuals with LVH and in 18 healthy normotensive control subjects before and after 1-year treatment with oral clonidine. Intraventricular septal (IVS) and posterior wall (PW) thickness and left ventricular mass index (LVMI) were related to systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP), as well as to UE and UNE by multivariate regression analysis. Before clonidine treatment increased values for IVS and PW thickness correlated with DAP (r = 0.54; p less than 0.05), and MAP (r = 0.50; p less than 0.05), a positive relation between IVS thickness and LVMI and UNE was found. After clonidine treatment, in addition to a statistically significant reduction in SAP, DAP, MAP, and in NE and UNE (all p less than 0.01), a decrease in IVS (12.5 to 9.5 mm; p less than 0.01) and in PW (11.2 to 9.3 mm; p less than 0.01) thickness as well as in LVMI (152.3 to 108.6 g/m2; p less than 0.01) was observed in hypertensive patients. LVMI weakly correlated with UNE change (r = 0.50; p less than 0.05). These data support a possible influence of catecholamines in modulating the development of LVH. They also confirm the parallel action of clonidine in controlling AP, in reducing UE and UNE, and in reversing LVH in hypertensive patients.

Adult↗

Net-charge models in the analysis of ion and electron transfer in enzyme reactions.

A number of key questions arising in the study of proton-relay chains and of the driving forces causing them to operate are discussed with main emphasis on the net-charge distribution of relevant model systems. Special reference is made to the role of water, histidine imidazole, and peptide bonds and to the description of hydride transfer in ADH-NAD+ complexes. Suggestions are given for treating H-bonds by the so-called Del Re method.

Electron Transport↗