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Biomedical subjects

C Cangiano

Publications and source records attributed to C Cangiano.

At least 37 records · Page 2Linked to original sources
PubMed1990

Plasma and CSF tryptophan in cancer anorexia.

Eighteen untreated cancer patients and ten sex- and age-matched healthy volunteers were studied. In all patients eating behavior was investigated by means of a specific questionnaire from which the presence of anorexia and anorexia-related symptoms was assessed. To investigate the role of tryptophan in cancer anorexia, fasting plasma and CSF levels of tryptophan and other neutral amino acids were assayed in patients and controls. Cancer patients showed abnormally high plasma free tryptophan levels. In case of patients with cancer anorexia a significant rise of the ratio in plasma between free and tryptophan/large neutral amino acids, competing with tryptophan for its brain entry, was observed. This increase was correlated to a consistent rise of CSF tryptophan levels suggesting a specific role of the serotoninergic system in the pathogenesis of cancer anorexia.

Aged↗
PubMed1989

The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects.

Nineteen obese female subjects with body mass index ranging between 30 and 40 were included in a double-blind crossover study aimed at evaluating the effects of oral 5-hydroxytryptophan administration on feeding behavior, mood state and weight loss. Either 5-hydroxytryptophan (8 mg/kg/day) or placebo was administered for five weeks during which patients were not prescribed any dietary restrictions. Feeding behavior was investigated by means of a questionnaire designed to establish the onset of anorexia and related symptoms. Food intake was evaluated using a three-day diet diary. BDI, SI, STAI-T, and STAI-S were used to assess mood state. The administration of 5-hydroxytryptophan resulted in no changes in mood state but promoted typical anorexia-related symptoms, decreased food intake and weight loss during the period of observation.

5-Hydroxytryptophan↗
PubMed1989

[Metabolico-nutritional changes in the cancer patient].

The severe impairment of the nutritional state, which usually accompanies malignant diseases, heavily contributes to the high morbidity and mortality rates observed in cancer patients. Nevertheless, the utility of an artificial energy supply to these patients is still controversial because the nutrients given to replete the host may also stimulate tumor growth. Consequently, a correct nutritional approach for cancer patients should be based upon a well-defined understanding of tumor as well as host-metabolic needs. In this regard, the most typical metabolic abnormalities observed in cancer patients and experimental animals are examined. Specific modifications of the plasma levels of different groups of amino acids--including glucogenic, aromatic, sulphur-containing and branched-chain amino acids--have been observed in cancer patients independently of the their degree of malnutrition, glucose tolerance and tumor diffusion. This may reflect a series of specific modifications induced by the neoplastic tissue on host's protein turnover. Little information is available regarding the protein metabolism in the neoplastic tissue. A number of attempts have been made to reduce tumor growth by withholding single amino acids considered essential to the tumor; nevertheless, the results obtained are still controversial. The two major abnormalities of carbohydrate metabolism observed in cancer patients are an increased glucose turnover and an impaired glucose tissue disposal. The former seems to be due to an increased glucogenesis, whereas the latter may be attributed to an insulin resistance in contrast to the high anaerobic glucose utilization observed in the neoplastic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
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↗
PubMed1986

Plasma tryptophan and anorexia in human cancer.

A correlation between anorexia and brain levels of serotonin and tryptophan (TRP) has been reported in tumor-bearing animals. In the present investigation 45 patients with various types of cancer and 13 control subjects were studied. Prior to the study the patients had received no antineoplastic therapy and were unaware of the malignancy of their disease. Feeding behavior was investigated by means of a questionnaire in which the presence of anorexia (A), aversion to meat (MA), taste (TA) or smell (SA) alterations, nausea and/or vomiting (NV) and early satiety (ES) was assessed. Plasma levels of free TRP, the other neutral amino acids (NAA), albumin and non-esterified fatty acids (NEFA) were assayed. Plasma-free TRP was significantly increased in anorectic cancer patients. The free TRP/competing NAA ratio, which might better predict brain TRP levels, was significantly higher in patients with A, MA, TA, SA, NV and ES than in controls or in non-anorectic (NA) cancer patients. These findings seem to confirm that free TRP may play an important role in human cancer anorexia.

Adult↗
PubMed1986

Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences.

The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20.5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70.6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27.6 and 31.5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma. These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure.

Amino Acids, Branched-Chain↗
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

Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study.

A controlled study was carried out in two groups of 20 patients with cirrhosis of the liver and deep coma in order to compare the efficacy of intravenous branched-chain amino acid solutions in 20% glucose (group A) vs lactulose plus glucose in isocaloric amount (group B). There were 3 drop-outs from each group. Plasma amino acids and ammonia were assayed at fixed intervals throughout the 10-day observation period. Routine tests were assayed daily. Complete mental recovery was obtained in 70% of patients in group A and in 47% in group B. The difference was not significant, likely due to the lack of placebo group. With the exception of free tryptophan/all competing amino acids ratio, the modifications in plasma amino acid levels showed no correlation with the clinical course under either treatment. Ammonia, like free tryptophan, decreased significantly upon mental recovery, paralleling the clinical course throughout the study. In conclusion, branched-chain amino acids are at least as effective as lactulose in deep hepatic coma. It is suggested that branched-chain amino acids may reverse coma either by competing with brain entry of the aromatic amino acid or by metabolically decreasing free tryptophan and ammonia.

Amino Acids↗
PubMed1982

Plasma and cerebrospinal fluid amino acid patterns in hepatic encephalopathy.

Plasma and cerebrospinal fluid amino acid levels wee measured in 12 cirrhotic patients in grade 0 hepatic encephalopathy and 17 in grade 3-4 hepatic encephalopathy. In 5 of these patients amino acid determinations were performed during the evolution of the encephalopathy. No correlation was found between the degree of hepatic encephalopathy and the plasma amino acid imbalance. In the CSF of cirrhotic patients without encephalopathy, a significant increase was found in nearly all amino acids, including those known to not easily cross the blood-brain barrier; this suggests the presence of a nonspecific modification of the blood-brain barrier permeability. In patients with severe hepatic encephalopathy, the further increase only in cerebrospinal fluid aromatic amino acids and methionine levels suggests the presence of a selective stimulation of the neutral amino acid transport system across the blood-brain barrier. Finally, the good correlation between glutamine and the sum of neutral amino acids found in the cerebrospinal fluid only in the presence of encephalopathy supports the hypothesis that brain glutamine may stimulate neutral amino acid transport across the blood-brain barrier.

Adult↗
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↗