Biomedical subjects

A Bertelli

Publications and source records attributed to A Bertelli.

At least 55 records · Page 3Linked to original sources

PubMed1995

Effect of L-propionyl carnitine on some properties of erythrocytes and leukocytes of alcohol abusers.

The effect of L-propionyl carnitine, the carnitine derivative utilized as a more effective drug for membrane protection, on Na-K ATPase activity of erythrocyte ghosts of alcohol-dependent patients and blood donors has been investigated. The effect of L-propionyl carnitine on leukocyte chemotaxis and cytochrome c reduction, a measure of superoxide ion production was also studied. It has been in fact observed that alcohol is immunotoxic on both the non-specific and the specific immune response. In alcohol-dependent erythrocytes, a significant higher value of the 1H-NMR spin lattice relaxation time (T1) was observed as compared to blood-donor erythrocytes. The in-vitro addition of ethanol increases the T1 values of blood donor erythrocytes, whereas it is without effect on the T1 value of alcohol-dependent erythrocytes. The Na-K ATPase activity is higher in alcohol-dependent erythrocyte ghosts as compared to blood-donor ghosts. A non-significant increase of the Na-K ATPase activity of blood-donor ghosts was observed with the increasing of L-propionyl carnitine concentrations (from 0.2 to 5.0 mM), whereas the Na-K ATPase activity of alcohol-dependent ghosts decreases. From these combined effects the differences of Na-K ATPase activity progressively decrease with the increasing of L-propionyl carnitine concentration, and no significant differences are observed between the two groups at L-propionyl carnitine concentrations higher than 0.5 mM. The in-vitro addition of ethanol increases the enzyme activity to a greater extent in blood-donor ghosts as compared to alcohol-dependent ghosts. This in-vitro activation by ethanol is decreased by the addition of L-propionyl carnitine. The chemotaxis induced by N-formyl-methionyl-leucylphenylalanine and the superoxide anion production stimulated by zymosan is significantly lower in alcohol-dependent neutrophils. L-Propionyl carnitine increases, in a dose-dependent way, both chemotaxis and superoxide anion production of alcohol-dependent neutrophils, and no significant difference was observed between the two groups at 5 mM L-propionyl carnitine. These experimental results suggest that L-propionyl carnitine administration may be useful for reducing some acute and chronic damages due to alcohol ingestion. The protective and modulatory actions of L-propionyl carnitine may be even more evident in cells and tissues different from those investigated in this study and in which ethanol determines several biochemical damages.

Alcoholism↗

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

Protective effect of L-propionylcarnitine on cyclosporine-induced nephrotoxicity.

Nephrotoxicity has represented the major limitation in the use of cyclosporine A (CyA). The structural abnormalities at the level of the proximal tubular cells are necrosis, vacuolisation and lipid droplets, as well as CyA-induced glomerular afferent arteriole constriction and granular juxtaglomerular cell hyperplasia. The mode of action of vasoconstriction is not well known, but there appears to be substantial impairment of endothelial cell function leading to enhanced release of vasoconstrictors such as endothelin and thromboxane. L-propionylcarnitine (PC), one of the most potent analogues of carnitine, is able to correct and to prevent alterations in endothelial membrane permeability and it has been identified in the kidney of various animal species. To investigate a possible reduction of CyA-induced nephrotoxocity, we examined the effects of a pretreatment with PC before administering several doses of CyA in an isolated and perfused rat kidney. The histological findings showed that the perfusion with PC reduces the vasoconstrictive effect of CyA on the glomerular capillaries and preserves the tubular epithelium. The ratio of the diameter between the glomerular capillary tuft and Bowman's capsule was higher, while at the tubular level the ratio internal-diameter/diameter evaluated at the level of the basal membrane was lower in PC + CyA perfused kidneys than in only CyA perfused ones. The final value of perfusion pressure was lower in PC + CyA perfused kidneys than in only CyA perfused ones, confirming the histological findings. The release induced by CyA of alanine aminopeptidase (AAP) and N-acetyl-glucosaminidase (NAG), markers of tubular damage, was significantly reduced by pretreatment with PC. These data suggest that the pretreatment with PC reduces the CyA-induced nephrotoxicity in an isolated and perfused rat kidney.

Analysis of Variance↗

PubMed1994

Effect of L-propionyl carnitine on in-vitro membrane alteration of sickle-cell anaemia erythrocytes.

Sickle-cell anaemia erythrocytes are under oxidative stress which contributes to some of the reversible and irreversible modifications observed in these cells. L-Propionyl carnitine, which protects myocardium, endothelium and erythrocytes from peroxidative damages and is able to stabilize damaged cell membranes, is also able to decrease the formation of thiobarbituric acid reactive substances which are produced by incubating erythrocytes with hydrogen peroxide in the presence of atmospheric oxygen or 95% N2-5% CO2 mixture. In these experimental conditions the increase of thiobarbituric-acid-reactive substances is significantly lower at 5 mM and 10 mM L-propionyl-carnitine concentrations. The formation of irreversibly sickled cells induced by 24-h incubation of sickle-cell anaemia erythrocytes under 95% N2-5% CO2 mixture is significantly decreased in the presence of 1 mM or higher L-propionyl-carnitine concentrations. The percent filtration of sickle red blood cells through micropore filters is significantly decreased at oxygen tensions between 20 and 40 mmHg. These in-vitro observations suggest that L-propionyl carnitine may be beneficial in maintaining the normal shape of sickle-cell anaemia erythrocytes at low oxygen tension and in decreasing the peroxidative damages which accumulate during the life of red blood cells.

Anemia, Sickle Cell↗

PubMed1994

Protection of beta-thalassaemic erythrocytes from oxidative stress by propionyl carnitine.

Susceptibility to oxidative stress is increased in erythrocytes of patients with beta-thalassaemia due to the free alpha-chain pool and to the excess of iron. We have investigated the effect of L-propionylcarnitine concentrations on oxidative stress determined by lactoperoxidase-hydrogen peroxide-iodide and by xanthine oxidase-acetaldehyde on erythrocytes of patients with beta-thalassaemia (major and intermedia). L-propionyl carnitine protects the erythrocytes from oxidative stress as measured by cell lysis. The protection is concentration-dependent. L-propionyl carnitine also stabilizes the cell membranes in which a latent peroxidative damage has been produced. These data suggest that L-propionyl carnitine may prove beneficial in protecting in vivo patients in which peroxidative damage of cell structure is increased as in the case of beta-thalassaemic patients.

Adult↗

PubMed1994

Evaluation of calcitonin-gene related peptide on haemodynamics of isolated perfused rat kidney.

Outside the central nervous system, calcitonin-gene-related peptide (CGRP) plays an important role in the control of regional blood flow. The present authors studied the renal haemodynamic effects of CGRP in the model of isolated perfused rat kidney (IPRK). This experimental model avoids the complex feed-back mechanisms activated by any modification of renal perfusion pressure. It was found that the infusion of CGRP in the IPRK induced a marked decrease of perfusion pressure; this vasoactive effect is well measured by the glomerular morphometric analysis that shows a striking increase in the glomerular diameter and volume.

Animals↗

PubMed1994

L-propionyl carnitine protects erythrocytes and low density lipoproteins against peroxidation.

The effects of peroxidation on the erythrocytes of rats orally treated with L-propionyl carnitine for 15 days (50 mg/kg/day) were investigated. Peroxidation was produced by incubating the cells in the presence of the cytotoxic system: lactoperoxidase-hydrogen peroxide and iodide ions. Lysis of erythrocytes was evaluated by measuring the turbidity following the decrease in absorbance at 600 nm. The 50% of erythrocyte lysis of untreated animals was observed after 16 min and in about 30 min all the cells were lysed. With L-propionyl carnitine-treated rat erythrocytes the time at which 50% of lysis was observed increased to 23 min. L-propionyl carnitine also exerted its protective effect in vitro when incubated with untreated rat erythrocytes or human erythrocytes in the presence of the cytolytic system. The presence of L-propionyl carnitine in the incubation mixture markedly decreased the malonaldehyde formation. The protection was concentration-dependent. To establish if L-propionyl carnitine protects from oxygen reactive species or is able to stabilize the damaged membranes, a latent damage was produced by incubating the erythrocytes with the cytolytic system for a few minutes. The cells were then removed and suspended in buffered saline in the absence or in the presence of different L-propionyl carnitine concentrations. L-propionyl carnitine decreased the velocity of lysis of damaged erythrocytes. These data suggest that L-propionyl carnitine protects erythrocytes from oxygen reactive species and also stabilizes the damaged membrane probably by specific binding with protein and/or phospholipid domains. Low density lipoproteins (LDLs) from human blood were peroxidized by exposure to Cu2+ ions in the presence of various L-propionyl carnitine concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

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↗

PubMed1994

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↗

PubMed1993

Perinatal morphine treatment inhibits pruning effect and regeneration of serotoninergic pathways following neonatal 5,7-HT lesions.

Lesion of the serotoninergic system in neonate rats is an ideal model for assessing the activity of chemical substances capable of affecting neuronal plasticity and regeneration (Jonsson et al., Dev Brain Res 16: 171-180, 1984). Treatment of newborn rats within 6 hr from birth with the selective neurotoxin 5,7-dihydroxytryptamine causes degeneration of the most distal serotoninergic axons. In our experimental conditions we have observed that after such neurotoxic treatment there is spinal cord denervation, which is particularly remarkable in the lumbar segment. This degenerative event is followed by gradual regeneration of the lesioned axons, with good reinnervation of the entire cord within 8 weeks. The degeneration-regeneration process is correlated with a transient hyperinnervation of the pons-medulla and hypothalamus by the short collaterals (pruning effect), as evidenced by increased serotonin content. Perinatal morphine exposure markedly impairs serotonin regeneration in the spinal cord. In addition, opiate treated rats are more susceptible to lesions, as shown by the neurotoxin induced denervation of the cortex, pons-medulla, and hypothalamus, which does not occur in lesioned controls. Therefore, our observations suggest that perinatal exposure to morphine affects the plasticity and regeneration of the developing serotoninergic system by increasing its susceptibility to neurotoxic lesions and reducing its regenerative capacity.

5,7-Dihydroxytryptamine↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1992

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↗

PubMed1992

Early neurochemical changes in the autonomic neuropathy of the gut in experimental diabetes.

Some neurochemical changes in the gut of rats after five weeks of alloxan-induced diabetes were investigated. It was found that at this stage of diabetes the changes were restricted mainly to the small intestine with a special selectivity for the duodenum. No changes were found in the most part of the large intestine and rectum. The methionine-enkephalin content was markedly reduced throughout the small intestine, while vasoactive intestinal polypeptide was increased in duodenum, ileum and caecum. Substance P content was unaffected, while at later stages of the disease it was significantly reduced in the entire small intestine. Sympathetic noradrenaline and intrinsic serotonin contents were significantly increased in the duodenum and unchanged throughout the rest of the intestine. These data suggest that the small intestine and caecum might be the early target of diabetic autonomic neuropathy, that might involve progressively the rest of the large intestine at later stages as recent results have suggested. It is likely that the gastrointestinal dysfunctions, often present in diabetic patients, might also be due to the combined pre-synaptic alterations, and to the functional imbalance between Gs and Gi/Go transduction proteins recently reported. Insulin therapy, begun seven days after alloxan treatment, reduced drastically the hyperglycaemia, restored normal body growth and prevented all the gut neurochemical changes associated with alloxan-induced diabetes.

Animals↗

PubMed1992

Peptide alterations in autonomic diabetic neuropathy prevented by acetyl-L-carnitine.

Autonomic neuropathy and gastrointestinal problems are among the most common complications of diabetes. In this report it is shown that a possible correlation between the two disorders might exist, since diabetes causes a profound alteration of the peptidergic innervation of the gut. It is reported that 14 weeks after diabetes induction with alloxan the levels of substance P and methionine-enkephalin are markedly reduced throughout the intestine, while vasoactive intestinal polypeptide content is dramatically increased. Therefore the enteric innervation of diabetic animals is completely disorganized, with some systems undergoing atrophy and others undergoing hypertrophy. Treatment of diabetic animals with acetyl-L-carnitine prevents the onset of the marked peptide changes described above. The results suggest a potential for acetyl-L-carnitine in the treatment of autonomic neuropathies.

Acetylcarnitine↗

PubMed1992

Acetyl-L-carnitine prevents substance P loss in the sciatic nerve and lumbar spinal cord of diabetic animals.

Diabetic neuropathy is a disease of peripheral nerves, characterized by axonal atrophy and degeneration that might be preceded by a marked impairment of axonal transport and by a reduced conduction velocity. Sensory nerves are particularly susceptible to diabetes. In the present report it is shown that experimental diabetes in rats causes a significant reduction of the content of the pain-related neuropeptide substance P in sciatic nerve and lumbar spinal cord. Such a loss of substance P is fully prevented by acetyl-L-carnitine treatment. The neuroprotective pharmacological effect is selective and takes place without significant changes of hyperglycaemia and without modifications of the reduced rate of body growth typical of diabetic animals.

Acetylcarnitine↗