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Biomedical subjects

A A Bertelli

Publications and source records attributed to A A Bertelli.

At least 37 records · Page 2Linked to original sources

Evaluation of kinetic parameters of natural phytoalexin in resveratrol orally administered in wine to rats.

In view of the increasing interest in the biological activity of resveratrol, one of the components of red wine which is considered to be one of the main ingredients responsible for the beneficial effect of wine on human health, we have studied plasma kinetics and tissue bioavailability of this compound after red wine oral administration in rats. Plasma pharmacokinetics after oral administration of resveratrol could be described by an open one- or two-compartment model. Tissue concentrations show a significant cardiac bioavailability, and a strong affinity for the liver and kidneys.

Administration, Oral↗

Plasma and tissue resveratrol concentrations and pharmacological activity.

In this study a comparison was made between results obtained from resveratrol dosages which have been shown to be pharmacologically active, in vitro and in vivo, and the results of plasma and tissue concentrations obtained after a single administration or after prolonged administration of red wine with a known resveratrol content. The dosages used by different investigators in the tests are very different and, in general, rather high in relation to the concentrations which are found in wine or grapes. The results of our tests on platelet aggregation confirm that even with modest dosages of resveratrol, a pharmacological effect can be observed, and that these dosages can be compatible with the resveratrol concentrations obtained after oral administration. The data obtained from these tests on animals can lead to the conclusion that even an average drinker of wine can, particularly in the long term, absorb a sufficient quantity of resveratrol to explain the beneficial effect of red wine on health, which has been observed in epidemiological studies carried out in populations whose daily diet includes the drinking of wine.

Animals↗

Effect of acute and chronic inflammation on plasma growth hormone levels in rats.

We investigated the effect of acute and chronic stress on growth hormone (GH) plasma levels in rats. Acute stress was provoked by intravenous administrations of IL-1 beta and TNF-alpha. Determinations were made at 10, 30, 60, 120 and 180 min following i.v. injection of these cytokines into the caudal vein. We also investigated the chronic stress induced by hind paw injections of Freund's adjuvant. Arthritis was developed by 21 days following such injection. GH levels were studied at 7, 14 and 21 days after induction of arthritis on several blood samples which were withdrawn from tail veins, and long-term hormonal profiles (3 hours' sampling) were determined at 12.00 am, 1.30 pm and 3.00 pm. Local administration of dexamethasone and the monoclonal antibody anti-ICAM-1 were also used in arthritic rats. Following acute stress, a significant reduction of plasma GH levels has been evidenced, possibly related to the stimulation of corticotropin-releasing hormone. Following chronic stress, we demonstrated a significant increase of GH levels, which were significantly reduced by dexamethasone treatment and to a lesser extent by anti-ICAM-1 administration.

Acute Disease↗

Antiplatelet activity of cis-resveratrol.

The anti-aggregating effect of cis-resveratrol (cis-3,4,5- trihydroxystilbene) has been evaluated in vitro in different concentrations on platelet-rich plasma from health volunteers. Cis-resveratrol at the concentration of 1 x 10(-5) and 1 x 10(-6) M was able to decrease collagen-induced platelet aggregation by 43.5 +/-11.4% and 26.8 +/- 14.6%, while trans-resveratrol at the same concentration showed a slightly lower activity. In view of the behaviour of these two isomers in biological fluids, the evaluation of resveratrol activity in animals and humans take into account the total amount of the two isomers.

Collagen↗

Plasma, urine and tissue levels of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after short-term or prolonged administration of red wine to rats.

The aim of the present study was to evaluate the absorption, the concentration in different organs and the excretion of natural trans- and cis-resveratrol after red wine oral administration to rats. A first group of animals was given a dose of 4 ml of red wine containing 6.5 mg/l of total resveratrol. The animals were sacrificed at different time intervals. A second group of rats was given a daily dose of 2 ml of red wine containing 6.5 mg/l of total resveratrol for fifteen days. Total resveratrol concentrations were measured in plasma, urine, heart, liver and kidney. Even though the amount of resveratrol found in these different tissues was lower than that required for pharmacological activity, it is possible that prolonged administration of red wine in the diet could lead to an increased resveratrol concentration in different tissues and this could explain its suggested beneficial role against coronary heart disease.

Animals↗

Kinetics of trans- and cis-resveratrol (3,4',5-trihydroxystilbene) after red wine oral administration in rats.

Kinetics of trans- and cis-resveratrol (3,4',5-trihydroxystilbene), a natural compound from grape products, have been evaluated in rats after oral administration of red wine. Resveratrol concentrations were measured in plasma, heart, liver and kidneys. Tissue concentrations showed a significant cardiac bioavailability and strong affinity for liver and kidneys.

Administration, Oral↗

Antiplatelet activity of synthetic and natural resveratrol in red wine.

The antiaggregating effect of the phytoalexin resveratrol (3,4,5-trihydroxystilbene), alone or associated with red wine, and polyphenol have been evaluated in vitro at different concentrations on platelet-rich plasma from healthy volunteers. Resveratrol at the concentration of 3.56 micrograms/l was able to lower platelet aggregation by 50.3% +/- 1.83. Red wine containing 1.2 mg/l of natural trans-resveratrol and 3.6 milligrams of polyphenols diluted 1000-fold (final resveratrol concentration: 1.2 micrograms/l) inhibited platelet aggregation by 41.9% +/- 2.11. By adding resveratrol to the wine up to a concentration of 1.2 micrograms/l, inhibition was raised to 78.5% +/- 4.70. These results suggest that the antiaggregating activity of resveratrol is related to its concentration in wine.

Humans↗

Acute effects of calcitonin gene related peptide on renal haemodynamics and renin and angiotensin II secretion in patients with renal disease.

The renal haemodynamic effects and renin-angiotensin II response to calcitonin gene-related peptide (CGRP) infusion were assessed in 16 patients with moderate hypertension and renal insufficiency. CGRP lowered the systemic mean blood pressure by 13% and increased the heart rate by 25%; the glomerular filtration rate rose from 56 +/- 11 ml/min to 71 +/- 8 ml/min (p < 0.005), the renal plasma flow decreased from 369 +/- 19 ml/min to 342 +/- 25 ml/min (p < 0.002) and the filtration fraction increased from 15 +/- 0.2% to 20 +/- 0.2%. Plasma renin activity rose stepwise during the CGRP infusion from 1.28 +/- 0.5 ng/ml/h to 1.66 +/- 0.4 and 1.89 +/- 0.4 ng/ml/h (p < 0.001). Angiotensin II showed a marked increase after 10 min of infusion (91.6 +/- 47.00 pg/ml) (control value 6.01 +/- 3.09 pg/ml) and at the end (28.63 +/- 16.00 pg/ml) (p < 0.001). CGRP exerts an apparently favourable effect on renal function of patients with renal insufficiency, but the observed increase of glomerular filtration rate is obtained by an increase of intraglomerular pressure secondary to angiotensin II production.

Adult↗

Evaluation of the endocrine function of the heart in humans: proposal for an integrated approach for the assessment of production, secretion, distribution and degradation of atrial natriuretic factor and related peptides.

It has become established that heart has an endocrine function because it synthesizes and secretes a family of peptide hormones, called Atrial Natriuretic Peptide (ANP), with potent diuretic, natriuretic, vascular smooth muscle-relaxing activity and complex interactions with the hormonal and nervous systems. Because ANP has important volume-regulatory characteristics, it is postulated to play a central role in volume homoeostasis under normal conditions and in several pathophysiological states, such as congestive heart failure. ANP is able to counterbalance all the detrimental effects of activation of the neuro-hormonal system in patients with heart failure may lead to new therapeutical protocols that can prevent the progression from compensation to overt heart failure. An integrated approach for the assessment of the endocrine function of the heart is proposed, consisting of four different, but complementary, steps: 1) evaluation of gene expression of ANP in the myocardial cell; 2) determination of circulating and tissue levels of ANP; 3) in-vivo assessment of the main turnover parameters of the hormone; 4) studies on localization and identification of ANP receptors. These procedures have been employed in physiological, pharmacological and/or clinical studies. The development and the standardization of new methods for the assessment of endocrine function of the heart will not only increase our understanding of the physiological regulation of production, secretion, and function, and of the pathophysiological role of ANP and its related peptides, but also may pave the way for further progress concerning our knowledge of more general physiological and pathophysiological mechanisms of the cardiovascular system itself.

Amino Acid Sequence↗

Eliminant effects of calcitonin gene related peptide on the tubular epithelial cells in an isolated and perfused rat kidney.

The effect of the infusion of calcitonin gene related peptide (CGRP) on the renal structure and enzyme release from tubular epithelial cells was studied. This study was performed in the model of an isolated perfused kidney to avoid the systemic effects and complex hormonal and neuromediated interaction following the CGRP infusion in the intact experimental animal. After infusion of CGRP, the perfused kidney, studied by semiquantitative histology and electron microscopy, did not show any alteration at the glomerular level; however, important histological lesions were apparent at the proximal tubular level: the brush border was destroyed and the epithelial cells were markedly flattened. This structural damage to epithelial cells was confirmed by electron microscopy. The alanine amino peptidase (AAP) and N-acetyl-glucosaminidase (NAG) were significantly increased in the effluent of the perfusion system, in confirmation of the histological damage. The direct toxic effect of CGRP on the tubular epithelial cells may be related to the reabsorption and tubular transport of this substance.

Acetylglucosaminidase↗

The potentiating effect of propionyl carnitine on prostacycline prevention of thrombosis induced by endothelin (ET-1) and K-carrageenin.

The aim of the present experiments was to ascertain whether prostacycline could exercise a protective effect against the formation of thrombosis in the rat tail induced by endothelin and K-carrageenin and to compare the effect of prostacycline with that of carnitine and propionyl carnitine. Both prostacycline and propionyl carnitine exhibited a similar protective effect on this experimental model. A combined protective effect of prostacycline administered with carnitine was also observed and a possible interaction between these two substances is proposed.

Animals↗

Effect of increasing doses of lisinopril on proteinuria of normotensive patients with IgA nephropathy and normal renal function.

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in patients with renal disease is well known, but the results of clinical studies appear to vary considerably from a partial decrease to a fall of 100% in urinary protein excretion. This may have been due to the use of different doses of ACE inhibitor, different renal pathology and non-standardized sodium intake. In 16 proteinuric patients with biopsy-proven IgA nephropathy, with normal renal function and blood pressure, maintained at controlled sodium intake < or = 80 mEqII, the efficacy of increasing doses of the ACE inhibitor lisinopril was studied. The lisinopril doses were 5, 10, 15 and 20 mg, administered for 4 weeks. Between each dose increment a placebo period of 3 weeks was interposed. Proteinuria stepwise decreased from the control period by 39%, 44%, 61% and 67% with lisinopril at 5, 10, 15 and 20 mg, respectively. The blood pressure decreased by 22% with lisinopril 5 mg; a similar fall was observed with the dose increment. Although the glomerular filtration rate remained unchanged, the renal plasma flow increased by 21%, 26%, 24% and 28% and the filtration fraction increased by 28% mean. The ACE plasma levels decreased by 33%, 64%, 76% and 83%. A close correlation was found between an increase in lisinopril dosage and the fall in urinary protein excretion (r = 0.88, p < 0.001). The antiproteinuric effect of lisinopril is dose-related and may be attributable to some extent to the fall in systemic (and intraglomerular) blood pressure, but it is best attributed to the modification of glomerular sieving function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Critical evaluation of endothelins assay.

Endothelin(s) is (are) generally measured by highly-sensitive RIA (radioimmunoassay) or sandwich-EIA (enzyme immunoassay) methods after preliminary extraction and chromatographic purification using Sep-Pak C18 cartridges; however, there is no general consensus about the range of endothelin circulating levels in healthy subjects and patients. We have evaluated the analytical performance of two commercial RIAs for plasma endothelin-1 assay (supplied by Peninsula Laboratories, Belmont, California, and by Biomedica Gruppe, Biomedica Gesellschaft mbH, Vienna, Austria) in order to verify whether differences in extraction procedures, antibody affinities or standard preparations can explain the different results obtained by these two RIAs. The RIA kits tested in the present study showed some differences in the analytical performance; in particular, different antibody specificities have been observed. The concentration range of endothelin(s) assayed with an imprecision better than 15%, which can be considered the working range, was wider for the Peninsula than for the Biomedica kit (i.e. from 1.6 to 50 fmol/tube vs 0.7 to 10 fmol/tube), whereas the two RIA kits showed similar sensitivity (i.e. about 0.2 fmol/tube). Taking into account the working range and sensitivity of the two RIAs to measure with an acceptable error the samples of normal subjects and the most part of patients, > or = 3-ml volumes of plasma must be extracted by Sep-Pak C18 cartridges and then measured by RIA. Owing to the central role played by the endothelin superfamily in several pathophysiological conditions, it is important to have a reliable assay for the measurement of these peptides in biological fluids and tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Protective role of propionyl carnitine in vascular disorders experimentally induced by endothelin (ET-1) serotonin and K-carrageenin.

Propionyl carnitine, a derivative of carnitine, has metabolic and cardiovascular effects similar to carnitine but with more pronounced peripheral haemodynamic activity. In these experiments we propose to prove that the administration of propionyl carnitine could prevent the experimental tail thrombosis in the rat induced by endothelin (ET-1), serotonin and K-carrageenin. In this new test of experimental thrombosis, propionyl carnitine was able to reduce the extent of tail thrombosis in a more significant manner than that of carnitine. A possible explanation of this antithrombotic effect of propionyl carnitine is its capacity to counteract the vasoconstrictor activity of endothelin modulating the release of prostanoids induced by endothelin itself.

Animals↗

Protective action of L-carnitine and coenzyme Q10 against hepatic triglyceride infiltration induced by hyperbaric oxygen and ethanol.

This investigation was conducted to ascertain whether administration of L-carnitine and coenzyme Q10 could protect from the experimentally-induced hepatic lipid infiltration and glutathione content decrease in rats exposed to hyperbaric oxygen and prolonged alcohol administration. The results indicate that administration of L-carnitine and coenzyme Q10 in association reduces damage induced by chronic alcohol poisoning and hyperbaric oxygen. This protective action is more marked when L-carnitine and coenzyme Q10 are administered together. The combined complementary biochemical activity of these two compounds is discussed.

Animals↗

Thrombosis induced by endothelin (ET-1) and carrageenin in rats treated with indomethacin and propionyl carnitine.

Propionyl carnitine can prevent endothelin and carrageenin-induced thrombosis in the rat's tail. This protective action of propionyl carnitine is probably related to its capacity to increase the synthesis of PGI2 prostaglandins and, subsequently, the amount of prostaglandins released by endothelin. Indomethacin, a well known prostanoid synthesis blocker, is unable to inhibit the protective activity of propionyl carnitine on endothelin-induced thrombosis after prolonged propionyl carnitine administration, but only a part of this protective activity after propionyl carnitine acute administration. Subsequently, other factors in addition to prostanoids seem to be involved in protective mechanisms of propionyl carnitine on endothelin-induced thrombosis.

Animals↗

Inhibition of histamine release and pressure increase induced by endothelin (ET-1) in isolated rat kidneys treated with propionyl carnitine.

Endothelin-1 (ET-1) is an amino peptide produced by endothelial cells with a potent vasoconstrictor activity; this effect is regulated by a release of other endogenous vasal factors. Recent studies have demonstrated that endothelin is capable of releasing from different tissues, and particularly from perfused organs such as spleen and kidney, many vasal factors and prostanoids. The present study investigates whether perfusion with a solution of endothelin-1 in rat isolated kidney can induce the release of histamine, another vasal factor (until now not investigated in relation with endothelin-1) and whether treatment with propionyl carnitine, a compound with vasoprotecting activity, inhibits this release. This research demonstrates that histamine released by rat kidney perfused with endothelin is lowered if previously treated with propionyl carnitine. This effect of propionyl carnitine can be considered to be another important factor in a complex mechanism involved in its vasoprotective and cardiovascular action.

Animals↗