Structural relaxation in polymeric films studied by Brillouin light spectroscopy.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to L Palmieri.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The protective effect of L-carnitine, coenzyme Q10 and their combination on haemodynamic and metabolic variables has been investigated in isolated perfused working rat hearts after 10 min of global normothermic ischaemia followed by 60 min of reperfusion. In untreated rats or in rats treated only with L-carnitine or with coenzyme Q10, this experimental condition did not induce any irreversible myocardial injury as measured by leakage of cardiac enzymes; however, it decreased some haemodynamic parameters such as cardiac output and minute work, as well as the ATP concentration and the total adenine nucleotide pool. No variations in haemodynamic and metabolic parameters were observed in the rats treated with L-carnitine plus coenzyme Q10. In the perfusate of the hearts of the rats treated with both compounds, a lower purine release (a good index of myocardial energy balance) was also obtained. Although the molecular mechanisms remain to be defined, it appears that the association of L-carnitine and coenzyme Q10 is more effective than using these compounds separately. The complementary and synergic actions of L-carnitine and coenzyme Q10 on metabolism and against peroxidation by oxygen reaction species may explain the efficacy of their association.
Chondroitin sulfate is administered as a drug to man by intravenous, intramuscular or oral route. However, few data are available on the metabolic fate of exogenous chondroitin sulfate in man. After intravenous administration of 0.5 g of chondroitin sulfate to healthy volunteers, the plasma level decreases according to a two-compartmental open model. The half-lives of distribution and elimination are 25.5 +/- 6.6 and 281 +/- 32 min, respectively. The volumes of central and tissue compartments are 6.0 +/- 1.0 and 22.9 +/- 7.7 l, respectively. More than 50% of the administered chondroitin sulfate is excreted with urine during the first 24 h as high and low molecular weight derivatives. After oral administration of 3 g of chondroitin sulfate to 12 healthy volunteers, a main peak (11.4 +/- 3.7 micrograms/ml) preceded by a lower peak is observed after 190 +/- 21 min. The elimination half-life is 363 +/- 109 min. The absolute bioavailability following oral administration calculated from AUC of plasma concentration is 13.2%. A peak of oligo- and polysaccharides with a molecular weight lower than 5000 Daltons derived from partial digestion of exogenous chondroitin sulfate is also present in plasma. These observations indicate that the metabolic fate of exogenous chondroitin sulfate is similar in man and in experimental animals.
Our study has evaluated the effect of the parenteral administration of CoA on the pattern of haematic lipids and on palmitate oxidation in liver mitochondria and peroxisomes of rats made hyperlipaemic with a high fat diet with or without CoA. Lipid fractions, total cholesterol, triacylglycerols, total lipids and nonesterified fatty acids (NEFA) were determined in blood. Palmitate oxidation was determined in liver peroxisomes and mitochondria incubated in modified Krebs-Henseleit solution with 100 microM 1-14C palmitate in the presence and absence of some cofactors. Our results show that in rats fed with a high fat diet there was an increase of all lipid fractions. The increase of all lipid components was lower in animals treated with CoA. In liver peroxisomes of rats fed with high fat diet an increase in palmitate oxidation, that is higher when CoA is parenterally administered, was observed. In addition, palmitate oxidation in mitochondria of rats treated with CoA reached values higher than those of control and of rats fed with a high fat diet without CoA.
Adenine mucleotide metabolism is very active in endothelial cells. These cells are very rich in xanthine oxidase which may produce oxygen reactive species during ischaemia and reperfusion when a high amount of adenine nucleotides may be catabolized to hypoxanthine. We investigated the effect of propionyl carnitine on energy charge and nucleotide content in cultured endothelial cells during changes in oxygen partial pressure. During hypoxia the adenine nucleotide pool and the energy charge decreased more slowly in the presence of 0.5 mM propionyl carnitine than in the absence of the compound. Furthermore during reoxygenation a more rapid increase of energy charge and adenine nucleotide concentration was observed with propionyl carnitine. These observations suggest that the presence of propionyl carnitine allows the endothelial cells to maintain their functionality and regulatory role on vessel activity for a longer time and decreases the formation of oxygen reactive species due to xanthine oxidase activity on hypoxanthine formed by adenine nucleotide catabolism.
Partially depolymerized chondroitin sulfate (dCS) was tritiated and given to rats. With both the intramuscular and oral routes of administration the main route of excretion is urine. More than 40% of the radioactivity is present in tissues 24 h after administration. After intramuscular injection, radioactivity plasma levels rapidly increase with a peak at 0.6 h. The separation of the radioactive material on a Biogel P-4 column shows that the radioactivity in the first hour after injection is mainly constituted of dCS with molecular weight higher than 4000 daltons (dCS greater than 4000). The composition of the radioactive material changes with time; after 24 h the dCS greater than 4000 is a few percent of the total radioactivity. A large amount of tritiated water due to exchange and metabolization of dCS is found. Mono-, oligo- and polysaccharides resulting from the breakdown of dCS are also present. After oral administration, plasma radioactivity rapidly increases, with a shoulder and a small peak after 1 h and a large peak after 11 h. A tropism of the radioactivity towards glycosaminoglycan-rich tissues is observed. The presence of dCS greater than 4000 in plasma, synovia and cartilage after oral and intramuscular administrations of dCS may explain the chondroprotective effect of exogenous dCS. In fact, desulfated and sulfated oligo- and polysaccharides have regulatory effects on the synthesis and breakdown of hyaluronate-proteoglycan complexes of cartilage.
Explore the source record for details and available documents.
After the administration of tritiated chondroitin sulfate (CS) by oral and intramuscular route, the distribution of radioactivity was investigated in two opportunist omnivorous animals, namely the rat and the dog. More than 70% of the orally administered radioactivity was absorbed. Independently of the administration route, radioactivity was mainly excreted through the urine. Plasma levels showed a rapid increase after oral administration, followed by a large plateau with a maximum at the 14th and 28th h in the rat and in the dog, respectively. A tropism of the radioactivity was observed towards glycosaminoglycan-rich tissues, such as joint cartilage. The analysis of the molecular weight of the radioactive material showed that compounds with a molecular weight corresponding to those of CS, poly-, oligo- and monosaccharides as well as of tritiated water, were present in the plasma, urine, synovial fluid and cartilage. The level of radioactive low molecular weight material, derived from the metabolism of CS and from the exchange reaction, increased with the time after administration. The high molecular weight fraction represented at least 10% of the orally administered CS.
The effect of coenzyme Q, of L-carnitine, and of their combination, on the adenine nucleotide pool and the energy charge has been investigated in rat heart slices subjected to energy depletion and recovery. The addition of coenzyme Q or of L-carnitine alone results in a higher value of the energy charge and of the adenine nucleotide pool after hypoxia, reperfusion and rotenone inhibition of the respiratory chain, as compared to controls without additions. The protective effect is much stronger when the two compounds are given together.
Exogenous L-carnitine and coenzyme Q are used to protect the heart against anthracycline damage and to enhance energy metabolism in the heart and in the muscle. Though their metabolic function is well known and their effects on anthracycline damage have been largely studied, their combined action has not been investigated. Therefore we have used partially CoQ-depleted bovine mitochondria to evaluate the synergic action of CoQ and carnitine on palmitoylCoA oxidation, as an experimental model in which either CoQ or L-carnitine may be the limiting factor in the oxidation of activated fatty acids. The protective effect exerted by the combined use of L-carnitine and CoQ against damage by the anthracycline derivative doxorubicin has been compared to the protection exerted by each compound alone. The effect was evaluated by assessing oxygen consumption and 14C-leucine incorporation in rat heart slices. The results obtained suggest that the administration of an association of L-carnitine and CoQ exerts a stronger protection against anthracycline damage and induces a greater utilization of fatty acids as compared to the effects of each compound alone.
The assay of enzyme activity in urine seems a reliable and safe method to monitor different kidney diseases. However, its use in pregnant patients might be limited by the modifications of kidney function during pregnancy. The aim of the present study was to evaluate the trend of excretion of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG) and the brush border enzyme alanine aminopeptidase (AAP) during uncomplicated pregnancies. NAG excretion showed a significant increase (P less than 0.001) throughout pregnancy, while no significant modification of AAP levels was demonstrated. These data support the hypothesis that the two enzymes are excreted into the urine through different mechanisms and might constitute markers for different pathological events. As the increase of NAG excretion may be related to the kidney functional adaptation to pregnancy, different cut-off limits must be established in this period.
In this study the absorption and excretion of a peptide fraction from bovine Factor VIII (Vueffe) with antihaemorrhagic activity were investigated in rats and rabbits. The results obtained suggest that the peptide fraction may be absorbed from the gastrointestinal tract through an active transport or a process of nonselective pinocytosis. The radioactivity elimination was rapid and almost complete within 24 h. In addition no difference was observed between single or repeated dosing in the pharmacokinetic parameters. The evidence following routes of administration shows the good bioavailability of this peptide fraction of low molecular weight and confirms the efficacy after oral administration at very low doses.
To evaluate the humoral and hemodynamic (both systemic and renal) effects of chronic treatment with celiprolol, six out-patients with mild to moderate uncomplicated essential hypertension received placebo for 1 month and celiprolol (400 mg qid) for 6 months. At the end of placebo and of the first and sixth month of treatment, blood pressure (BP), heart rate (HR), renal plasma flow (RPF), glomerular filtration rate (GFR), plasma renin activity (PRA), aldosterone (ALD) and noradrenaline (NA), urinary enzymes (NAG: N-acetyl-beta glucosaminidase, AAP: alanine aminopeptidase) were measured. Compared to placebo, celiprolol significantly and steadily reduced BP and HR. However, although the systemic hemodynamic effect was constant during the whole period of the study, the reduction of renovascular resistance and of plasma noradrenaline, detectable at the first month of therapy, disappeared at the sixth month. However, PRA, plasma aldosterone, GFR, and urinary enzymes did not change. These findings suggest that the antihypertensive effect of celiprolol is well maintained over the 6-month period; the drug did not exert any adverse effect on the kidney, and chronic celiprolol treatment does not influence renal hemodynamics.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.