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Biomedical subjects

C Cangiano

Publications and source records attributed to C Cangiano.

At least 55 records · Page 3Linked to original sources

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↗

Influence of phenylethanolamine on octopamine plasma determination in hepatic encephalopathy.

Octopamine and phenylethanolamine levels were measured by a radioenzymatic procedure in 30 cirrhotic patients with and without hepatic coma and in 15 normal controls. Octopamine data were obtained either by direct extraction with 40% isoamyl alcohol in toluene according to Molinoff et al. (Molinoff, P.B., Landsberg, L. and Axelrod, J. (1969) J. Pharm. Exp. Ther. 170, 253), or after pre-extraction of phenylethanolamine with 3% isoamyl alcohol in toluene. Phenylethanolamine was statistically correlated with the grade of hepatic encephalopathy. Octopamine levels also appeared to parallel the grade of coma, although the values obtained after pre-extraction were lower and less significant than those obtained with 40% isoamyl alcohol in toluene extraction. The higher values of directly extracted octopamine are due to contamination of other beta-hydroxylated phenylethylamines, among which is phenylethanolamine.

2-Hydroxyphenethylamine↗

Plasma amino acids imbalance in patients with liver disease.

The venous plasma amino acid patterns have been determined in 12 normal individuals and in 71 shunted and nonshunted cirrhotics in various grades of hepatic encephalopathy. The free amino acids have been determined by an amino autoanalyzer; the total and free tryptophan have been measured by a spectrophotofluorimetric method. In 14 instances, arterial plasma amino acid patterns have been measured simultaneously. High levels of aromatic and sulfurated amino acids and low levels of branched-chain amino acids have been constantly found in all cirrhotics. Methionine, phenylalanine, valine, leucine, tyrosine, and free tryptophan showed a statistical difference between controls and all other groups. These altered patterns did not correlate either with the grade or the evolution of the coma or with the presence of the surgical anastomosis. No statistical differences were found between arterial and venous values. The only amino acid which statistically correlated with the grade and evolution of the hepatic encephalopathy was free tryptophan. The molar ratios between the amino acids sharing the same transport system across the blood-brain-barrier have been considered. A very good correlation with the grade of the mental disorder was found with the ratios free tryptophan/phenylalanine-tyrosine-methionine-valine-leucine-isoleucine and free tryptophan/branched-chain amino acids.

Amino Acids↗

Plasma phenylethanolamine in hepatic encephalopathy.

It has been suggested that amines other than octopamine may be involved in the pathogenesis of hepatic encephalopathy. Plasma phenylethanolamine has been determined by a radioenzymatic method in twenty-six biopsy-proven cirrhotics with or without encephalopathy and in seven normal adults. Phenylethanolamine plasma levels correlated statistically with the presence of liver cirrhosis and severe coma. These results are consistent with the false neurotransmitter hypothesis of hepatic encephalopathy.

2-Hydroxyphenethylamine↗

Octopamine and ammonia plasma levels in hepatic encephalopathy.

It has been recently proposed that hepatic encephalopathy could be due to the accumulation of octopamine acting as a false neurotransmitter, and the increase of ammonia might reflect this accumulation. The simultaneous determination of octopamine and ammonia was performed in 88 cases with or without encephalopathy. The correlation between the two substances appeared to be good (P less than 0.01; r = 0.5), except in shunted patients. All the cases with low octopamine and high ammonia were patients who had been submitted to surgical portal-systemic anastomosis. This finding does not seem to be coincidental; in this type of patients, the mechanism of hepatic encephalopathy could involve other beta-hydroxyphenylethanolamines in addition to octopamine. The presence of the inhibition of the reaction of transmethylation constantly observed during octopamine plasma assay is in favour of this hypothesis.

Ammonia↗

Octopamine plasma levels and hepatic encephalopathy: a re-appraisal of the problem.

An investigation on the blood levels of octopamine was carried out on 70 adult individuals. There was a statistically significant correlation between the levels of octopamine and hepatic encephalopathy. Normal subjects had values below 1 ng/ml, while patients with grade 3 or grade 4 encephalopathy constantly showed values above 3.2 ng/ml. In these two groups the distribution was fairly homogeneous. Through the differences between cirrhotics without neurologic involvement and those with grade 1 or 2 hepatic encephalopathy displayed statistical significance, distribution of values in these groups was rather non-homogeneous. Octopamine levels paralleled variations in mental state in 3 out 4 cases. No difference was found between venous and arterial values. The reaction of transmethylation used in the assay of octopamine was constantly found to be inhibited by the presence of plasma. This inhibition is probably due to the presence of one or more beta-hydroxyphenylethanolamines other than octopamine.

Adult↗

[Clinical use of a test for determination of coagulation factors II, X and VII].

A new clotting test, the Hepato-Quick, indicated in the study of liver insufficiency was used in 102 patients comprising 22 cases of acute hepatitis, 15 of chronic hepatitis, 21 of cirrhosis of the liver, 11 with liver conditions of various nature, 23 cases with a number of diseases without liver impairment and 10 normal subjects. Quick's test was carried out at the same time in all subjects. Results show that the Hepato-Quick test is more sensitive than Quick's test for identifying liver impairment. The greater sensitivity is statistically significant. The test presents excellent standardization and can be carried out on automatic equipment.

Blood Coagulation Disorders↗

Effect of glucose and/or branched chain amino acid infusion on plasma amino acid imbalance in chronic liver failure.

The characteristic amino acid pattern observed in chronic liver failure with high aromatic and low branched chain amino acid levels is considered to be consequent to increased muscle protein catabolism. The main catabolic stimulus has been attributed to hyperglucagonemia and to a reduced insulin/glucagon molar ratio. Intravenous administration of a solution containing branched chain amino acids and glucose to patients with chronic liver cirrhosis rapidly normalizes the plasma amino acid pattern. This effect may result from either a change in the insulin/glucagon ratio, induced by glucose, or from the anticatabolic influence of branched chain amino acids on muscle protein turnover. To discriminate between these two possibilities, a crossover study was carried out to determine the effect of a 24-hour infusion of either glucose alone, or glucose plus branched chain amino acids, in seven patients with chronic liver failure. Blood glucose, insulin, glucagon, free fatty acids, and amino acid levels were determined. Branched chain amino acids were much more effective than glucose (p less than 0.01) in decreasing the levels of aromatic amino acids. Conversely, the insulin, glucagon, and free fatty acid levels with glucose alone were not altered with the addition of branched chain amino acids. These findings suggest an anticatabolic effect of branched chain amino acids on muscle protein turnover and suggest that factors other than insulin and glucagon may be responsible for the characteristic plasma amino acid pattern present in chronic liver failure.

Adult↗

Exogenous lipid clearance in compensated liver cirrhosis.

The tolerance to exogenous fats has been evaluated in patients with liver cirrhosis. A three-stage lipid clearance test with continuous infusion (3 hr) of a triglyceride emulsion, Intralipid, was performed on 10 patients with well compensated liver cirrhosis and 10 normolipidemic volunteers. During the infusion, blood samples were collected for the measurement of particulate triglycerides (TG) by nephelometry; samples were also collected for total TG, free fatty acids (FFA) and free tryptophan (TRP) determinations. Plasma endogenous triglycerides were calculated as the total minus exogenous, particulate, TG. The fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous TG were lower in patients than in controls, though a significant difference (p less than 0.05) was found only for K1. Endogenous TG and FFA showed a comparable rise in patients and controls during Intralipid infusion. A significant increase in free TRP was noted in cirrhotics upon maximal infusion rate. It is concluded that: in patients with well compensated liver cirrhosis the maximal clearing capacity (K1) for exogenous TG is impaired. Nonetheless, moderate amounts of fat may be removed at a normal rate from the bloodstream; a normal synthesis rate of exogenous TG may be maintained even in a severely damaged liver; considering the possible role of free TRP in the pathogenesis of hepatic encephalopathy (HE), the use of large amounts of lipids should be discouraged in patients with decompensated liver cirrhosis, or even avoided in those with impending or overt HE.

Adult↗

The early cancer anorexia paradigm: changes in plasma free tryptophan and feeding indexes.

Tumor growth is accompanied by an anorexia mediated by humoral factors that appear to influence appetitive mechanisms in the brain. Because tumor resection is followed by resumption of normal food intake, the circulating anorexigenic substance(s) are produced either by the neoplastic tissue or by the host in response to the tumor. Increased levels of plasma free tryptophan and plasma ammonia have been proposed to mediate cancer anorexia. With animal models, it is often difficult to ascertain whether changes in food intake depend upon metabolic changes or the progressively increasing tumor mass per se. The feeding patterns and biochemical changes that occur during tumor growth were evaluated in 96 male Fischer rats that were inoculated with 10(6) methylcholanthrene sarcoma cells or saline (controls). Rats were placed into metabolic cages equipped with an Automated Computerized Rat Eater Meter to continuously determine meal size and meal number. Plasma free tryptophan and ammonia were evaluated 6, 10, 16, 18, 22, and 26 days after tumor inoculation. Anorexia developed by day 17-18, when food intake started to decrease via a decrease in meal size but not meal number and reached 60% of control by day 26. However, long before anorexia developed, free tryptophan was significantly higher 6 days after tumor inoculation, and the greatest increase occurred after 18 days. Ammonia did not differ from control at any time. Data confirm tumor-associated increases in plasma free tryptophan that occurred before the manifestation of anorexia and support a possible role of brain serotonin in cancer anorexia.

Ammonia↗

Increased availability of tryptophan in brain as common pathogenic mechanism for anorexia associated with different diseases.

Changes in brain serotonin and tryptophan concentrations probably represent one of the most important mechanisms in the regulation of eating behavior both in experimental animals and in humans. Anorexia, which accompanies numerous diseases, e.g., cancer, liver cirrhosis, and uremia, may recognize an increased brain availability of tryptophan as a common pathogenic mechanism. This will lead to a rise in brain serotonin synthesis, which, in turn, is responsible for a reduction in food intake. According to this hypothesis, the anorexia observed in various diseases could be improved either by a decrease in the cerebral synthesis of serotonin or by a reduction in the entry of tryptophan into the brain.

Anorexia↗

Increased plasma free tryptophan levels in human cancer: a tumor related effect?

High free tryptophan (F-TRP) plasma levels are found in cancer patients (CP). F-TRP plasma concentrations are affected by the levels of its carrier, albumin (ALB), and free fatty acids (FFA) competing with TRP for ALB binding sites. The lack of correlation between F-TRP, ALB and FFA in CP suggests a tumor-dependent effect on the rise in F-TRP. To verify this hypothesis, F-TRP, ALB and FFA levels were assayed in 12 lung and 16 breast CP susceptible to radical surgery, before and 15 days after surgical removal of the tumor. F-TRP levels significantly decreased after tumor ablation. Since no correlation was found between F-TRP, ALB and FFA variations, it is conceivable that the tumor itself may be responsible for the high F-TRP levels in CP.

Adult↗

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↗