Cri-du-chat disease: plasma and urinary amino acids

Ten cases of cri du chat disease due to a del(5)(p14p15) were observed. A highly significant excess of the plasmatic and urinary relative amount of asparagine + aspartate was detected. A highly significant excess of the relative amount of histidine was also noted in the urine but not in the plasma. Excess of asparagine + aspartate could be related to a disorder of purine metabolism. The urinary excess of histidine could be related to a disorder of the aminoacid catabolism.     

Effects of branched-chain amino acids on plasma amino acids in amyotrophic lateral sclerosis

Summary Although the cause of amyotrophic lateral sclerosis (ALS) remains unknown, biological findings suggest that the excitatory amino acid glutamate contributes to the pathogenesis of ALS. In previous studies of ALS, the therapeutic effect of the branched-chain amino acids (BCAAs) leucine, valine and isoleucine has been evaluated. The present study aimed at investigating the acute effect of BCAAs on plasma glutamate levels in ALS patients. Following two oral doses of BCAAs, significantly increased plasma levels were seen for valine (500%), isoleucine (1,377%) and leucine (927%), however the plasma level of glutamate was not affected. The plasma level of several other amino acids (tryptophan, tyrosine, phenylalanine and methionine) were found decreased after oral BCAAs, which may indicate a diminution in the rate of degradation of muscle protein and/or an increase in tissue disposal of amino acids.     

Effects of hypoxia on plasma amino acids of fetal sheep

Summary. Secondary amino acid disturbances from circulatory responses during hypoxia may cause problems in interpreting plasma amino acid profiles of sick babies investigated for possible inherited defects. Systematic studies to characterise them are difficult in man. We investigated the effects of hypoxia on plasma amino acids by studying 9 late gestation fetal sheep in utero during 11 one hour episodes of moderately severe isocapnic hypoxia. In 6 experiments, maternal plasma amino acids were also monitored. Fourteen fetal plasma amino acids increased significantly, with the largest proportionate changes in alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, ornithine and lysine. Maternal amino acids did not increase. Probable explanations were reflex peripheral vasoconstriction in skeletal muscle beds and decreased hepatic blood flow. The findings extend our knowledge of the fetal response to hypoxic stress, demonstrate the importance of skeletal muscle in branched-chain amino acid metabolism, and should help with interpretation of postnatal plasma amino acid disturbances. Received January 29, 1999, Accepted February 22, 1999     

Simultaneous determination of triamcinolone acetonide and hydrocortisone in human plasma by high-performance liquid chromatography

A validated HPLC method for the simultaneous determination of triamcinolone acetonide and hydrocortisone has been established to monitor the plasma levels of the compounds in healthy volunteers following intramuscular (i.m.) administration of triamcinolone acetonide. Plasma (1.0 ml) was extracted with dichloromethane after addition of the internal standard, fluocortolone. The compounds were separated using a LiChrospher RP 18 column and detected by UV absorbance. Specificity, linearity, as well as the repeatability, intermediate precision and accuracy of the method were established. The limit of quantification was 0.6 ng/ml for triamcinolone acetonide (C.V.=8.7%, R.E.=2.6%, n=6) and 2.0 ng/ml for hydrocortisone (C.V.=8.3%, R.E.=2.8%, n=6). Data on the stability of triamcinolone acetonide in human plasma are presented. Recovery of the compounds and the internal standard have been studied. The results of quality control samples (n=126) determined during routine analysis of volunteer samples are described. Plasma levels of triamcinolone acetonide after i.m. administration of 40 mg of triamcinolone acetonide are presented.     

Molecular approach of gossypol-induced reproductive toxicity in male rabbits. Changes in seminal plasma amino acids and fatty acids

This study was done to evaluate the effects of two sublethal doses of gossypol (4 and 20 mg/kg of BW, every other day) on some amino and fatty acid concentrations in male rabbit seminal plasma. Rabbits were chosen as an experimental animal owing to the fact that they are excellent model for reproductive toxicological effects. The experiment lasted 16 weeks and included two periods: a treatment period (first 8 weeks) where the animals were given the tested product, and a recovery period (second 8 weeks) where all drugs were withdrawn. Results showed that total amino acids (TAA), total essential amino acids (EAA), total non-essential amino acids (non-EAA) and EAA/non-EAA ratio were decreased in a dose-dependent manner during gossypol treatment. The deleterious effect on TAA concentrations was mainly due to the reduction in total EAA. However, these concentrations regained their normal values after gossypol cessation. Basic, acidic, neutral amino acids and basic/acidic amino acids ratio decreased in a dose-dependent manner by gossypol treatment. Additionally, gossypol administration caused decreases in total unsaturated fatty acids (USFA) and increases in total saturated fatty acids (SFA) and the SFA/USFA ratio in a dose-dependent manner. During the recovery period, total SFA and USFA showed significant reduction and significant increase, respectively, after gossypol withdrawal. In conclusion, gossypol administration affected rabbit seminal plasma concentrations of amino and fatty acids in a dose-dependant manner. Gossypol reduced TAA, total EAA and total non-EAA. Additionally, gossypol caused decreases in total USFA and increases in total SFA. These deleterious effects were associated with poor-quality semen observed in our previous studies.     

Changes of plasma insulin, urea, amino acids and rumen metabolites in somatotropin treated dairy cows

Summary An experiment was performed to evaluate the effects of somatotropin on plasma free amino acid, urea and insulin concentrations and rumen fermentation pattern and to assess their relationships. Four Italian Friesian dairy cows fitted with rumen cannulae were used in a switch-back design. Slow releasing recombinant bovine somatotropin (640 mg/cow) was injected every 28 days for two consecutive periods. Rumen fluid and blood samples were collected before and after feeding at 0, 7 and 21 days after rbST injection. Exogenous rbST increased plasma insulin concentration and the insulin response to feeding, and decreased plasma urea and free essential and branched chain amino acid concentrations. rbST did not affect rumen fermentation pattern. No correlation was found between rumen and plasma parameters measured after feeding. Our results are consistent with the notion that the main effect of somatotropin is post-absorptive.     

Abnormal concentrations of B vitamins and amino acids in plasma and B vitamins in bile of rabbits with aflatoxicosis

The dosages of aflatoxin B1 (AFB1) required to produce significant changes in concentrations of B vitamins in plasma and bile and of amino acids in plasma of rabbits were determined. Folate increased by 98% in plasma, whereas concentration of thiamine, vitamin B6, and biotin decreased by more than 50%. In bile, choline and biotin increased 14- and 18-fold, respectively, whereas folate and niacin decreased by more than 50%. All amino acids in plasma increased between 76 and 155%. The dosages of AFB1 required to induce these changes were usually between 12.5 and 37.5 microgram/kg of body weight per day. Except for changes in biliary concentrations of pantothenic acid, folic acid, and biotin, lower threshold dosages of aflatoxin were required to produce weight loss and anorexia (5.0 and 8.5 microgram of AFB1/kg per day, respectively) than for changes in vitamins and amino acids (approximately 25 to 50 microgram of AFB1/kg per day). The data indicated that AFB1 interfered with the metabolism of B vitamins and amino acids in rabbits.     

Changes in plasma and urinary taurine and amino acids in runners immediately and 24 h after a marathon

Summary. Changes in urinary and plasma taurine and amino acids have been evaluated in trained runners competing in the Rotterdam Marathon, 1998, both immediately after completing the event and 24 h after recovery. There were significant changes in the urinary amino acids excretion, the majority showing a significant decrease both immediately at the completion of the Marathon and after 24 h recovery. In contrast urinary taurine excretion increased immediately post Marathon, although not significantly as the range of results was wide. Such changes in urinary taurine correlated with percentage changes in plasma creatine kinase both immediately post race, (r = 0.972, P < 0.001), and 24 h later (r = 0.872, P < 0.001), possibly indicating that the source of the taurine was muscle. Significant correlations between the individual values for urinary and plasma amino acids in all of the athletes were calculated for taurine (r = 0.528), glycine (r = 0.853), threonine (r = 0.749), alanine (r = 0.747), serine (r = 0.620), glutamine (0.614), arginine (r = 0.507), histidine (r = 0.470) and valine (r = 0.486). Changes in the mean plasma concentrations of amino acids were comparable to our previously published data (Ward et al., 1999) the majority showing significant decreases immediately and 24 h post Marathon, such an adaptation being due primarily to their utilisation for gluconeogenesis. However, in contrast, the mean taurine concentrations were significantly elevated both post race, P < 0.01 and after 24 h, P < 0.05. The physiological response by the muscle to exhaustive exercise, particularly with regard to changes in plasma and urinary taurine concentrations remain to be elucidated, but is probably related to muscle function impairment. The increase in taurine urinary excretion could be used as an indicator of muscle damage occurring during exhaustive exercise. Whether taurine supplementation would minimise such changes is an interesting scientific question and merits investigation. Received January 6, 2000 / Accepted February 1, 2000     

The metabolic fate of triamcinolone acetonide in laboratory animals

The metabolic fate of 9-fluoro-11β,16α,17,21-tetrahydroxy-l, 4-pregnadiene-3,20-dione cyclic 16,17-acetal with 2-¹⁴C-acetone, triaacinolone acetonide (TA) was studied in rabbits, dogs, monkeys and rats and found to be qualitatively similar in all species. In the dog, rat and monkey the major excretory route was the feces irrespective of the mode of administration. In the rabbit the excreted radioactivity was equally distributed between urine and feces. The metabolites were isolated by preparative thin layer chroma tography, located by autoradiography, eluted and analyzed by MS, IR, UV and NMR. The major metabolites of triamcinolone acetonide (TA) were identified as the C-21 carboxylic acids of TA and of the 6β hydroxy-TA,(6β-OH-TA) and the previously identified (1,2) 6β-OH-TA. In addition MS and UV data indicate the presence of 9-fluoro-11β,16α, 17-trihydroxy-3,20-dioxo-1,4,6-pregnatrien-21-oic acid cyclic 16,17 acetal with 2-¹⁴C-acetone.     

Diurnal rhythms in rat plasma amino acids

To obtain detailed data on the diurnal rhythm in rat plasma amino acids, groups of rats were killed every two hours during 24 hours and the amino acids in plasma were measured. By using such a short interval between the blood samples, it was possible to reveal differences in rhythmicity between the various amino acids, more detailed than those previously described. Furthermore, it was found that those large neutral amino acids (LNAA) which compete with each other for the carrier mediated transport from plasma into the brain demonstrated different rhythms, whereby also the relation between these competing amino acids varied during the day. This finding might have implications for the transport of the various LNAAs into the brain, and secondarily also for the synthesis of the monoaminergic neurotransmitters in the neurons, for which the LNAAs tyrosine and tryptophan serve as precursors.     

Some biochemical effects of triamcinolone acetonide on rat liver and muscle

1. The powerful anti-inflammatory glucocorticoid triamcinolone acetonide, administered to rats at 20 and 2.5mg/kg, leads to a decrease in the incorporation in vivo of [(3)H]uridine and [(32)P]orthophosphate into hind-limb skeletal muscle. 2. At the higher dose, this decrease in the rate of incorporation of precursors into RNA precedes a decrease in the incorporating ability of muscle ribosomes, which commences about 4-5h after drug administration, but is unaccompanied by any changes in the concentration of tissue ATP or free amino acids. 3. The ribosomal dysfunction extends to polyribosomes, which can only be successfully isolated from the muscle of triamcinolone-treated animals after the addition of alpha-amylase to the tissue homogenate to remove glycogen. 4. The specific radioactivity of muscle protein labelled in vivo with (14)C-labelled amino acids does not decrease progressively after triamcinolone administration. After 2h there is an apparent stimulation of incorporation which leads to an overall discrepancy between measurements of protein-synthetic activity made in vivo and in vitro. 5. There is a significant increase in muscle-glycogen concentration between 8 and 12h after the administration of triamcinolone acetonide (20mg/kg), although a significant decrease occurs after 4h. The fall in glycogen concentration may be due to a decrease in the rate of synthesis of protein essential for glucose uptake into the tissues. 6. As judged by (a) incorporation of (14)C-labelled amino acids into protein, (b) [(3)H]uridine and [(32)P]-orthophosphate incorporation into RNA, (c) the rate of induction of tryptophan pyrrolase and (d) changes in the pool sizes of taurine and tryptophan, the responses in liver followed the same time-course as those in muscle after administration of the drug.     

Effect of urea and amino acids of the ornithine cycle on the biomass accumulation and amino acids synthesis by Candida guilliermondii]

When assimilating urea, arginine, ornithine and citrulline as the sole source of nitrogen, C. guilliermondii shows a higher economic coefficient of biomass accumulation (54.2, 59.7, 40.6% respectively) as compared with ammonium sulphate whose coefficient is 35.6%. Nitrogen sources exert a significant influence on the content of essential amino acids in the alcohol soluble fraction of cell biomass. For instance, urea and arginine are responsible for the accumulation of ornithine (220 and 480 mug/100 mg abs. dry weight), arginine (470 and 587 mug), aspartic acid (220 mug), glutamic acid (520 and 444 mug), alanine (460 and 500 mug), whereas ammonium sulphate provides an accumulation of serine--52 mug, glycine--57 mug, gamma-aminobutyric acid--480 mug, phenyl alanine--96 mug and leucine--96 mug.     

Effects of carbohydrate feedings on plasma free tryptophan and branched-chain amino acids during prolonged cycling

Brain serotonin (5-hydroxytryptamine, 5-HT) has been suggested to be involved in central fatigue during prolonged exercise. Changes in the ratio of plasma free tryptophan (free Trp) to branched-chain amino acids (BCAA) are associated with altered brain 5-HT synthesis. The purposes of this study were to describe systematically the effects of prolonged exercise on changes in plasma free Trp and BCAA and to examine the effects of carbohydrate (CHO) feedings on these same variables. Eight well-trained men [VO2max = 57.8 (SE 4.1) ml kg-1 min-1] cycled for up to 255 min at a power output corresponding to VO2 at lactate threshold (approximately 68% VO2max) on three occasions separated by at least 1 week. Subjects drank 5 ml kg-1 body wt-1 of either a water placebo, or a liquid beverage containing a moderate (6% CHO) or high (12% CHO) concentration of carbohydrate beginning at min 14 of exercise and every 30 min thereafter. Exercise time to fatigue was shorter in subjects receiving placebo [190 (SE 4) min] as compared to 6% CHO [235 (SE 10) min] and 12% CHO [234 (SE 9) min] (P < 0.05). Glucose and insulin decreased in the placebo group, and free Trp, free-Trp/BCAA, and free fatty acids increased approximately five- to sevenfold (P < 0.05). These changes were attenuated in a dose-related manner by the carbohydrate drinks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Administration of branched-chain amino acids during sustained exercise--effects on performance and on plasma concentration of some amino acids.

Previous studies have shown that sustained exercise in human subjects causes an increase in the plasma concentration ratio of free tryptophan: other large neutral amino acids [including the branched-chain amino acids (BCAA)]. This should favour the transport of tryptophan into the brain and also the synthesis of 5-hydroxytryptamine, which is thought to contribute to fatigue during prolonged exercise. A mixture of the three BCAA was given to subjects during a 30-km cross-country race or a marathon (42.2 km) and the effects on mental and physical performances were measured. The mental performance, measured as the performance in the Stroop Colour and Word Test (CWT), was improved after, as compared to before the 30-km cross-country race when a BCAA supplement was given during the race, whereas the CWT scores were similar before and after in the placebo group. The running performance in the marathon was improved for the "slower" runners (3.05 h-3.30 h) when BCAA was taken during the race; however, there was no significant effect on the performance in the "faster" runners (less than 3.05 h). The results showed that both mental and physical performance was improved by an intake of BCAA during exercise. In addition, the effects of exercise on the plasma concentration of the aromatic amino acids were altered when a BCAA supplement was given during the marathon.