The effects of tumour necrosis factor-alpha on circulating amino acids in the pregnant rat.

The administration of an acute dose (6 nmol) of tumour necrosis factor-alpha (TNF-alpha) to 20-day pregnant rats resulted in important changes in the circulating concentration of maternal blood amino acids. The main changes concern increases in the concentration of neutral (alanine, glycine, threonine, proline), branched-chain (valine, leucine, isoleucine), basic (lysine, histidine), aromatic (phenylalanine) and acidic (aspartate and glutamate) amino acids. The cytokine treatment also increased the total concentration of circulating amino acids. In contrast, the cytokine did not promote any changes in the concentration of amino acids in the fetal circulation. The results suggested support that TNF-alpha may be responsible for impaired fetal growth as a consequence of a decrease in the transplacental passage of amino acids.

Gas chromatographic determination of oxo- and hydroxycarboxylic acids in serum and urine of diabetic and normal subjects.

Oxo- and hydroxycarboxylic acids in serum and urine are metabolites of valine, leucine and isoleucine and products of ketogenesis. They are simultaneously determined in the form of their methyl esters and methyl esters-O-methyloximes by gas chromatography, using internal and external standards. Normal values for the urinary excretion of these amino acid metabolites are between 3 +/- 2 mumole per 24 h (mean +/- standard deviation) for 2-oxoisocaproic acid and 122 +/- 58 mumole per 24 h for 3-hydroxyisobutyric acid. In diabetic ketoacidosis the values are increased by a factor of 2-10. In the urine of diabetic patients under fasting conditions all metabolites are elevated and reach a maximum on about the seventh day of fasting. In the serum only 2-oxoisocaproic acid, 3-oxobutyric acid and 3-hydroxybutyric acid reach elevated levels under fasting conditions.

Correlation of aspartate dose, plasma dicarboxylic amino acid concentration, and neuronal necrosis in infant mice.

Eight-day-old mice were administered aspartate at 0, 1.88, 3.76, 4.89, 5.64 and 7.52 mmol/kg body wt and the degree and extent of neuronal necrosis determined. In addition, plasma aspartate and glutamate concentrations were determined at each aspartate dose. Animals administered aspartate at 0, 1.88 and 3.76 mmol/kg body wt did not develop neuronal necrosis. Hypothalamic neuronal necrosis (7.33 +/- 1.52 necrotic neurons/section of maximal damage) was found in 3 of 10 animals administered aspartate at 4.89 mmol/kg body wt. The extent of neuronal necrosis was proportional to dose once a neurotoxic dose of aspartate was reached. All 12 animals administered aspartate at 5.64 mmol/kg body wt developed lesions (49.5 +/- 7.2 necrotic neurons/section of maximal damage). Similarly, all 18 mice administered aspartate at 7.52 mmol/kg developed hypothalamic lesions (80.8 +/- 17.8 necrotic neurons/section of maximal damage). Infant mice administered the highest dose of aspartate not producing neuronal necrosis (3.76 mmol/kg) had a mean (+/- S.D.) peak plasma aspartate concentration of 87 +/- 23 mumol/dl and a mean peak plasma glutamate concentration of 64 +/- 22 mumol/dl. Thus, the toxic threshold for these amino acids must be greater than those values.

Arterial blood levels of energy substrates and evidence for renal glucose production in the baboon infant.

The age-related changes in fasting arterial levels of energy substrates and insulin were studied at birth and/or 6 wk in eleven baboon infants. In addition, the renal contribution to glucose release in the primate infant was estimated. Arterial blood glucose levels were similar in six fasted newborns and in nine fasted 6-wk-old infants. Arterial blood lactate, alanine, pyruvate, glutamate, and glutamine levels were significantly higher (P < 0.01) in the new born animals, and beta-hydroxybutyrate was significantly higher in the older animals (P < 0.001). Arterial plasma insulin levels were low in both groups. Levels of blood glucose in the inferior vena cava below the renal vein were significantly lower than levels in the aorta (P < 0.01). In contrast, levels of blood glucose in the inferior vena cava above the renal vein were significantly higher than in the aorta (P < 0.05). Computed renal vein glucose levels were higher than those in the aorta (P < 0.01). In the newborn infants, there was significant renal uptake of lactate, pyruvate, glycerol, and glutamine (P < 0.01), and release of beta-hydroxybutyrate (P < 0.05). In the older animals, there was renal uptake of alanine, lactate, pyruvate, and glycerol (P 0.01). Mean cardiac output per kg body weight did not differ significantly in the newborn and 6-wk-old infants. Lactate uptake was potentially responsible for 59% of mean renal glucose output in the newborn and 76% of mean renal glucose output in the older infant. Net renal glucose release in eight 6-wk-old infants was estimated to be 3.5 +/- 1.1 microM/min . kg (95% confidence limits, 0.7 < 3.5 < 6.2). Net renal glucose release in three newborn infants was 4.7, 5.4, and 19.8 microM/min . kg. There was a significant linear relationship between arterial lactate levels and renal glucose production in the older infants (P < 0.05). Extremely low arterial pH was associated with increased renal glucose release in the newborn, and high arterial pH with decreased or absent glucose release in the 6-wk-old animals.

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.

[Spontaneous deamidation of gamma-globulin]. / Spontanooe dezamidirovanie gamma-globulina.

gamma-Globulin from human blood serum was incubated in thermostat at 37 degrees within 15, 30, 45, 60 and 72 days. Amount of readily and poorly hydrolyzed amide groups as well as an increase in amino acid content were estimated in the protein at zero time and at these periods. The sterility of the preparation was examined in each case. Spontaneous deamidation of gamma-globulin, observed during incubation, caused an increase in negative charge and altered electrophoretic mobility of the protein molecule. gamma-Globulin was attacked by prothelin more effectively as amount of amide groups was decreased in the protein. Spontaneous deamidation appears to be one of reasons of the protein molecules ageing.

Protein and amino acid pattern in juvinile diabetes.

A number of 21 diabetic juveniles and 20 controls comprised the material of this study. Serum total proteins and their electrophoretic separated fractions were estimated. Serum free amino acids were also investigated. Results showed that serum proteins were within normal range. An average increase of 49.5% in total free amino acids was reported. In general, the data for all the detected amino acids showed an average increase when compared with normal values. The significance of these findings in relation to the normal values were discussed.

Changes in free and bound amino acids in experimental silicosis.

The amino acid composition of lung, serum and liver in silicotic rats was studied in order to assess the availability of precursors in lung for fibrogenesis. It was observed that the pool of ornithine, arginine, alanine, leucine, valine, glutamic acid, lysine, proline and glycine underwent marked alterations. Free arginine, proline and leucine were only detectable in silicotic lung, while free glycine, glutamic acid and glutamine pools decreased significantly in liver. Changes in amino acid metabolism as a result of silicosis are discussed.