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P Cardelli-Cangiano

Publications and source records attributed to P Cardelli-Cangiano.

12 recordsLinked to original sources
PubMed1988

Uptake of amino acids by brain microvessels isolated from rats with experimental chronic renal failure.

The neurological disorders seen in patients with chronic renal failure and liver cirrhosis are analogous. Previous in vivo studies have shown that the impaired blood-brain amino acid transport seen in rats with chronic renal failure is similar to that of rats with portocaval anastomosis. To elucidate whether a comparable underlying pathogenic mechanism plays a role in both pathological conditions, blood and brain amino acid levels together with amino acid transport by isolated brain microvessels have been studied in rats with chronic renal failure and in sham-operated rats. Brain microvessels isolated from rats with experimental chronic renal failure showed that the uptake of labeled large neutral amino acid, i.e., leucine or phenylalanine, but not of lysine or alpha-methylaminoisobutyric acid, was significantly increased with respect to sham-operated rats; conversely, the uptake of glutamic acid in rats with chronic renal failure was significantly lower compared with values in controls. Kinetic analysis indicated that this was mainly due to increased exchange transport activity (Vmax) of the L-system, rather than to changes in the affinity (Km) of the carrier system for the relative substrate. These data, together with the significant rise of brain glutamine levels and an increased brain-to-plasma ratio of the sum of large neutral amino acids, are analogous to what was previously observed in rats with portocaval anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Amino acids and hepatic encephalopathy.

The consideration of HE and its etiology has undergone a radical turn within the past decade. At present HE is seen in the context of severe metabolic derangements, which failure of the liver, the central biochemical powerhouse of the body, must bring with it. The increased awarenesses on the biochemical mechanisms involved in the pathogenesis of HE have found, step by step, their own place in a complex but consequential mosaic of events, in which amino acid and HE are tightly linked. Clinical and experimental studies are needed to further improve the knowledge in this field, nontheless a certain number of corner-stones can be identified: A profound alteration of the central nervous system neurotransmission is responsible for most, if not all, of the symptoms characterizing HE. The plasma amino acid imbalance observed in cirrhotic patients represents a 'condicio sine qua non' HE may develop. A functional impairment of the amino acid transport systems at the level of the blood-brain barrier seems to play a crucial role in causing deleterious modifications of the synaptic neurotransmission in the central nervous system. The reduction of the brain entry of the "toxic" aromatic amino acids usually obtained by parenteral administration of especially tailored amino acid mixtures is most frequently followed by awakening from HE. In conclusion, most of the results obtained have demonstrated that HE represents a research field in which progresses in the knowledge of some of the pathogenic mechanisms have brought the investigators to new therapeutic approaches which have clearly improved the prognosis of patients suffering from this severe neuropsychiatric syndrome.

Amino Acids↗
PubMed1987

Isolated brain microvessels as in vitro equivalents of the blood-brain barrier: selective removal by collagenase of the A-system of neutral amino acid transport.

On treatment with collagenase, brain microvessels, together with several protein components, lose some enzymatic activities such as alkaline phosphatase and gamma-glutamyltranspeptidase, whereas no change occurs in the activities of 5'-nucleotidase and glutamine synthetase. The energy-requiring "A-system" of polar neutral amino acid transport is also severely inactivated, whereas the L-system for the facilitated exchange of branched chain and aromatic amino acids is preserved. In the collagenase-digested microvessels, this leads to loss of the transtimulation effect of glutamine on the transport of large neutral amino acids, because such transtimulation is due to a cooperation between the A- and L-systems. By contrast, NH4+ maintains (and even enhances) its ability to stimulate the L-system of amino acid transport, presumably through glutamine synthesis within the endothelial cells.

5'-Nucleotidase↗
PubMed1984

Effect of ammonia on amino acid uptake by brain microvessels.

NH+4 ions, at a concentration (0.25 mM) similar to that found in the plasma of patients with hepatic encephalopathy, cause, in vitro, a significant stimulation of the uptake by brain microvessels of large neutral amino acids, without any effect on the uptake of alpha-methylaminoisobutyric acid, glutamic acid, or lysine. Such a stimulation occurs essentially through an increase of the maximal transport capacity (Vmax) of the saturable component. It is apparently mediated by the intracellular formation of glutamine, which is then exchanged, through the L-system of transport, for large neutral amino acids such as leucine, phenylalanine, or tyrosine. At higher concentrations (greater than or equal to 0.5 mM), NH+4 ions cause also a decrease of carrier affinity for neutral amino acids, which counteracts the stimulatory effect on their uptake.

2,4-Dinitrophenol↗
PubMed1983

Brain microvessels take up large neutral amino acids in exchange for glutamine. Cooperative role of Na+-dependent and Na+-independent systems.

Some regulatory aspects of neutral amino acid transport were investigated in isolated brain microvessels, an in vitro model of the blood-brain barrier. Preloading of the microvessels with glutamine stimulated the subsequent uptake of other neutral amino acids by way of the Na+-independent L system, but had no effect on the uptake of either basic or acidic amino acids. Moreover, this stimulation was abolished when the loading step was carried out in the absence of Na+ ions or in the presence of a high concentration of alpha-methylaminoisobutyric acid, indicating that the microvessels were able to concentrate glutamine via the A system of amino acid transport. Since the presence of the A system of neutral amino acid transport has not been detected in studies of blood-brain transport performed in vivo, the A system is probably associated with the antiluminal side of brain microvessels. Our results indicate, therefore, that the concentrative Na+-dependent A system and the exchanging Na+-independent L system can cooperate in the uptake of the large neutral hydrophobic amino acids. Such a cooperation may be relevant in the pathogenesis of some neurological disturbances such as hepatic encephalopathy, in which brain glutamine concentration is unusually high.

Amino Acids↗
PubMed1983

Plasma aminoacid levels across the brain in patients with respiratory failure.

Animal studies and theoretical considerations have suggested that in hypercapnic respiratory failure there is interconversion of glutamic acid to glutamine within the brain, perhaps as part of a local buffering mechanism to minimize hypercapnia-induced cerebral acidosis. Detection of transcerebral arteriovenous differences, positive for glutamic acid and negative for glutamine, would lend support to this hypothesis. We measured arterial and internal jugular venous levels of twenty-three aminoacids in four patients with hypercapnic respiratory failure and in four suitable controls. In patients, arterial as well as venous glutamine levels were elevated proportionally, and there was no demonstrable A-V difference across the brain; arterial and venous glutamic acid levels were the same as controls. All other aminoacid levels, arterial and venous, were normal. These findings confirm the previous observations that in hypercapnic respiratory failure glutamine metabolism is altered, but provide no support for the proposed glutamic acid-glutamine interconversions within the brain.

Amino Acids↗
PubMed1983

On the stimulation by insulin of tryptophan transport across the blood-brain barrier.

Following previous studies showing that in vivo insulin administration increases brain tryptophan levels, we have tested the effect of insulin on tryptophan uptake by isolated bovine brain capillaries, which represent the in vitro equivalent of the blood-brain barrier. In the presence of insulin and Na+ ions, the uptake of 14C-labelled tryptophan was significantly increased with respect to controls, this increase being essentially due to a higher affinity of the transport system for the amino acid, while the Vmax was not affected. Insulin increased also, to a similar extent, the uptake of alpha-methylaminoisobutyrate in the presence of Na+ ions, while the uptake of beta-aminobicyclo(2.2.1)heptane carboxylic acid was not affected. Addition of phloretine, or of anti-insulin antibodies, as well as omission of Na+ ions from the buffer abolished the effect of insulin. Insulin appears therefore to increase specifically the substrate affinity of the A-system for neutral amino acid transport, without exerting any influence on the L-system. The absence of the A-system from the luminal side of the microvessels, and the high insulin concentrations needed, raise however some problems as to the physiological significance of this effect.

Animals↗
PubMed1982

Plasma levels of false neurotransmitters across the brain in portal-systemic encephalopathy.

Arterial and internal jugular venous levels of false neurotransmitters (FNTs: octopamine, OCT, and phenylethanolamine, PEA), aromatic and branched-chain amino acids, glutamine, ammonia, and pH were measured in patients with portal-systemic encephalopathy (PSE) and in appropriate controls to define the role of these parameters in the pathogenesis of hepatic coma. The typical plasma patterns reported in the literature were observed: hyperammonaemia (59 +/- 8 mumol/l v. controls 30 +/- 4, P less than 0.005), elevated OCT (19 +/- 3 nmol/l v. 6 +/- 1, P less than 0.001) and PEA (64 +/- 8 nmol/l v. 27 +/-3, P less than 0.001), high ratio of aromatic to branched-chain amino acids (0.92 +/- 0.12 v. 0.32 +/- 0.04, P less than 0.005), and variable glutamine levels 216-734 mumol/l). No consistent net flux into or out of the brain could be demonstrated for any of these substances. The degree of encephalopathy correlated with the level of respiratory alkalosis (r=0.325, P less than 0.05) which, in turn, correlated with the degree of elevation of plasma OCT (r=0.439, P less than 0.05) and PEA (r=0.489, P less than 0.05) as well as with the excess of glutamine efflux from the brain (r=0.927, P less than 0.05). These findings support current views that hyperammonaemia, plasma amino acid imbalance, and elevated production of FNTs are interrelated disturbances which contribute to the pathogenesis of PSE. In addition, the data suggest that alkalosis accentuates the altered metabolism of these substances within the brain.

2-Hydroxyphenethylamine↗
PubMed1981

Simultaneous radioenzymatic determination of phenylethylamine, phenylethanolamine, tyramine and octopamine in plasma of patients with hepatic encephalopathy.

A sensitive radioenzymatic assay for the simultaneous determination of phenylethylamine, phenylethanolamine, tyramine and octopamine in plasma samples is reported. After extraction with ethanol, the amines are subjected to enzymatic N-methylation with labelled S-adenosylmethionine, preceded in the case of phenylethylamine and of tyramine, by an enzyme-catalyzed beta-hydroxylation step. The procedure is completed by extraction with toluene containing different amounts of isoamylalcohol, followed by controlled evaporation of the solvent. A generalized and highly significant increase in the concentration of all the four amines was found in plasma samples from patients suffering from hepatic encephalopathy.

Ethanolamines↗
PubMed1981

Uptake of amino acids by brain microvessels isolated from rats after portacaval anastomosis.

The uptake of amino acids by microvessels isolated from brains of rats was studied. Previous studies have demonstrated alterations in blood-brain amino acid transport after portacaval shunt in rats. In order to elucidate whether such changes in the blood-brain barrier were located in the microvessels, brain microvessels were isolated from both rats with portacaval shunt and controls. Brain microvessels from rats 2 weeks after shunt operations took up significantly greater amounts of 14C-labeled neutral amino acids, but not of glutamic acid, lysine, or alpha-methylaminoisobutyric acid than microvessels from sham-operated controls. Measurement of uptake kinetics showed a higher Vmax for phenylalanine and leucine uptake and a lower Vmax for lysine uptake in microvessels from shunted rats compared with control, whereas the respective Km's of uptake were similar in both preparations. The results suggest that changes in brain microvessel transport activity account for altered brain neutral amino acid concentrations after portacaval shunt and that such changes can be studied in vitro in isolated microvessels.

Amino Acids↗
PubMedDate not supplied

Plasma clearance of exogenous lipids in patients with malignant disease.

Abnormalities in lipid metabolism have been widely described in cancer-bearing patients and animals. In particular, the presence of the tumor seems to profoundly affect triglyceride (TG) utilization by interfering with lipoprotein lipase (LPL) activity. Exogenous TG plasma clearance was evaluated in 10 nonmalnourished patients with cancers of various origin and 10 normolipidemic volunteers by means of a three-stage intravenous lipid clearance test. This technique allows precise determination of both the fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous lipids. Mean K2 values (min-1) were found to be significantly reduced in cancer patients compared with control subjects (0.07 +/- 0.006 vs 0.13 +/- 0.013 SEM, p less than 0.005). K1 values (mumol/L/min) were also found to be significantly lower in cancer patients than in the control group (109.43 +/- 6.3 vs 143 +/- 6.3 SEM, p less than 0.01). The data obtained indicate that the capacity to eliminate exogenous lipids from the bloodstream is reduced in cancer-bearing patients. This may be the consequence of a tumor-related impairment of LPL system activity.

Adult↗