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Disease-specific amino acid infusion (F080) in hepatic encephalopathy: a prospective, randomized, double-blind, controlled trial.

Seventy-five patients with acute hepatic decompensation superimposed on chronic alcoholic cirrhosis were prospectively randomized for a blinded trial of the treatment of hepatic encephalopathy. The control group received 4 g of enteral neomycin daily along with 25% dextrose by a central venous catheter. The experimental group received a placebo resembling neomycin and isocaloric dextrose plus a modified amino acid mixture enriched with branched-chain amino acids to 36% and deficient in aromatic amino acids and methionine. Thirty patients in the F080 group and 29 in the control group completed the trial. The group receiving the modified amino acid mixture demonstrated a statistically significant improvement in encephalopathy as compared to the neomycin group, while maintaining nitrogen equilibrium. Survival and discharge from the hospital were statistically greater in the group treated with the modified amino acid solution and hypertonic dextrose. Treatment of hepatic encephalopathy in the presence of hepatic decompensation with an amino acid solution formulated for its treatment seems to produce faster, more complete recovery with improved capacity for nutritional support.

Adolescent↗

Electro-olfactogram and multiunit olfactory receptor responses to complex mixtures of amino acids in the channel catfish, Ictalurus punctatus.

In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that both electro-olfactogram and integrated neural responses of olfactory receptor cells to complex mixtures consisting of up to 10 different amino acids were predictable with knowledge of (a) the responses to the individual components in the mixture and (b) the relative independence of the respective receptor sites for the component stimuli. All amino acid stimuli used to form the various mixtures were initially adjusted in concentration to provide approximately equal response magnitudes. Olfactory receptor responses to both multimixtures and binary mixtures were recorded. Multimixtures were formed by mixing equal aliquots of 3-10 different amino acids. Binary mixtures were formed by mixing equal aliquots of two equally stimulatory solutions. Solution 1 contained either one to nine different neutral amino acids with long side-chains (LCNs) or one to five different neutral amino acids with short side-chains (SCNs). Solution 2, comprising the binary mixture, consisted of only a single stimulus, either a LCN, SCN, basic, or acidic amino acid. The increasing magnitude of the olfactory receptor responses to mixtures consisting of an increasing number of neutral amino acids indicated that multiple receptor site types with highly overlapping specificities exist to these compounds. For both binary mixtures and multimixtures composed of neutral and basic or neutral and acidic amino acids, the receptor responses were significantly enhanced compared with those mixtures consisting of an equal number of only neutral amino acids. These results demonstrate that receptor sites for the basic and acidic amino acids, respectively, are highly independent of those for the neutral amino acids, and suggest that a mechanism for synergism is the simultaneous activation of relatively independent receptor sites by the components in the mixture. In contrast, there was no evidence for the occurrence of mixture suppression.

Amino Acids↗

Electro-olfactogram and multiunit olfactory receptor responses to binary and trinary mixtures of amino acids in the channel catfish, Ictalurus punctatus.

In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that responses to binary and trinary mixtures of amino acids were predictable with knowledge obtained from previous cross-adaptation studies of the relative independence of the respective binding sites of the component stimuli. All component stimuli, from which equal aliquots were drawn to form the mixtures, were adjusted in concentration to provide for approximately equal response magnitudes. The magnitude of the response to a mixture whose component amino acids showed significant cross-reactivity was equivalent to the response to any single component used to form that mixture. A mixture whose component amino acids showed minimal cross-adaptation produced a significantly larger relative response than a mixture whose components exhibited considerable cross-reactivity. This larger response approached the sum of the responses to the individual component amino acids tested at the resulting concentrations in the mixture, even though olfactory receptor dose-response functions for amino acids in this species are characterized by extreme sensory compression (i.e., successive concentration increments produce progressively smaller physiological responses). Thus, the present study indicates that the response to sensory stimulation of olfactory receptor sites is more enhanced by the activation of different receptor site types than by stimulus interaction at a single site type.

Amino Acids↗

The effect of acute tryptophan depletion and fenfluramine on quantitative EEG and mood in healthy male subjects.

BACKGROUND: Efforts to model putative serotonergic deficits associated with affective disorders have frequently involved acute tryptophan depletion (ATD) as a manipulation strategy aimed at lowering brain serotonin synthesis. In an attempt to widen the scope of the measurement probes used in these investigations, the central actions of ATD and a subsequent dose of fenfluramine were examined via utilization of quantitative electroencephalography (EEG) and mood ratings. METHODS: Electroencephalograms (EEG) and subjective mood ratings were assessed in 28 healthy men before and after double-blind ingestion of a tryptophan-depleting (T-) amino acid mixture, or a nutritionally balanced (B) amino acid mixture containing tryptophan, and again after a single-blind oral dose of D,L-fenfluramine hydrochloride (60 mg). RESULTS: Compared to the B mixture, the T- mixture reduced total plasma tryptophan by more than 75% 5 hours after ingestion. Tryptophan depletion was associated with a modest lowering of mood and a slowing of EEG as indicated by increases in delta amplitude. Fenfluramine caused no change in mood but increased fast wave (beta) activity in anterior recordings when administered after the T-, but not after the B mixture. CONCLUSIONS: Quantitative EEG measurements may be a promising method for studying the central mechanisms underlying serotonin-mediated changes in mood and behavior.

Adolescent↗

Influence of L-methionine-deprived total parenteral nutrition on the tumor tissue and plasma amino acids fraction and the host metabolism: experimental study with Sato lung carcinoma-bearing rats.

Creation of an amino acid imbalance, particularly curtailment of L-methionine, at the tumor cell level is thought to have a favorable effect on the inhibition of tumor growth. In the present study, we examined the influence of a specially-formulated amino acid mixture, avoid of sulfur-containing amino acids (L-methionine and L-cysteine), on the growth and amino acid fraction of Sato lung carcinoma (SLC) and the host metabolism in SLC-bearing rats. The rats were treated by total parenteral nutrition containing the above amino acid mixture, plus other nutrients (methionine-deprived TPN) for 10 days. Tumor growth began to decrease 4 days after the start of this treatment and the size was significantly less at the end of the treatment than in rats receiving conventional TPN with general purpose Vuj-N type amino acid solution as a protein source. The tumor-to-carcass weight ratio also showed a similar trend. In biochemistry, the albumin level and albumin-to-globulin ratio were significantly lower than in the rats receiving conventional TPN but other parameters such as total protein, glucose, GOT and GPT were not affected by the treatment. In the amino acid fraction of the tumor tissue extraction, both L-methionine and L-tyrosine were decreased and L-serine was increased significantly compared with the control group.

Amino Acids↗

Glossopharyngeal taste responses of the channel catfish to binary mixtures of amino acids.

This study examines the neural processing of binary mixtures in the glossopharyngeal (IX) taste system of the channel catfish, Ictalurus punctatus, and finds that the nature of the components of a mixture determines the intensity of the neural response to it. Taste buds in fish innervated by IX are located along the gill rakers of the first gill arch and rostral floor of the oral cavity, and function primarily in the consummatory phase of feeding behavior; however, few studies of IX taste responses have been reported in any species of teleost. Here, we report IX taste responses to eight different binary mixtures of amino acids whose components were adjusted to be approximately equipotent in electrophysiological recordings. Four binary (group I) mixtures whose components were indicated from prior electrophysiological cross-adaptation experiments to bind to independent receptor sites resulted in significantly larger (22% average increase) integrated IX taste activity than four other (group II) binary mixtures whose components were indicated to bind to the same or highly cross-reactive receptor sites. These results are similar to those observed previously from facial nerve recordings in channel catfish, and to olfactory and taste responses in other vertebrate and invertebrate species. The group I results help to explain behavioral observations that chemical mixtures of chemosensory stimuli are often more stimulatory than their individual components.

Amino Acids↗

Changes in hematological parameters of athletes after receiving daily dose of a mixture of 12 amino acids for one month during the middle- and long-distance running training.

Previous studies have shown that a mixture of amino acids, consisting of 9 essential amino acids and 3 non-essential amino acids was effective in facilitating muscle recovery from athletic activities. In this study, the objective was to determine whether this amino acid mixture improved the physical condition and associated blood parameters of athletes in training when administered for a prolonged period. Thirteen college middle- and long-distance runners were placed in a 6-month experiment and received the amino acid mixture at the dose of 2.2 g/day for one month, 4.4 g/day for one month, and 6.6 g/day for one month with washout periods between test periods. The physical condition was scored and blood samples were collected before and after each test period. When the subjects received 2.2 g of the amino acid mixture three times a day, the physical condition was significantly improved along with increases in red blood cell count, hemoglobin, hematocrit, serum albumin, and fasting glucose, and a decrease in creatine phophokinase (p<0.05), suggesting increased hematopoiesis and glycogenesis, and rapid alleviation of muscle inflammation by the amino acid mixture.

Adult↗

Threonine imbalance, deficiency and neurologic dysfunction in the kitten.

The effect of feeding threonine-imbalanced and threonine-deficient purified diets (containing L-amino acids as the only source of dietary nitrogen on food intake, weight gain and blood plasma amino acid pattern has been examined in growing kittens. The imbalance was created by adding 17.5% of amino acid mixture lacking threonine to a low amino acid basal diet comtaining 17.5% amino acid mixture including 0.4% threonine. A depression in food intake and weight gain occurred while feeding the imbalanced diet which was corrected by adding an additional 0.2% threonine to the imbalanced diet. There was no adaptation with time in the form of increased food intake or weight gain while feeding the imbalanced diet. Plasma threonine was consistently and similarly depressed (10 to 35% of normal) while feeding the basal, imbalanced and corrected diets and increased to normal when the standard diet with 1.4% threonine was fed. Plasma threonine and total amino acid concentrations of kittens fed the imbalanced diet did not differ from those observed in kittens fed the basal diet. Signs of neurologic dysfunction and/or lameness developed in 14 of the 17 kittens fed threonine-imbalanced or deficient diets, which resolved as dietary threonine was increased.

Amino Acids↗

Nitrogen source primarily supplied by amino acids and the efficacy for maximal growth of rats.

The effect of osmotic pressure of diets on be food intake of young rats was investigated by comparing the nutritional effect of casein with the corresponding amino acid mixture at 3.2% nitrogen level. Changes in the osmolarity of diets due to the type of dietary carbohydrate had a little effect on food intake, whereas partial substitution of casein for amino acids resulted in significant increase in food intake. Weight gain and food intake of rats fed the 25% replaced amino acid diet were compared with those of rats fed the casein diet. Food intake was lower at 12.5% replacement than at 25% replacement. These observation suggest that a well-balanced amino acid mixture supported maximal growth of rats when 25% of the amino acid mixture was replace with casein. This suggestion could be experimentally confirmed by using an amino acid mixture based on the amino acid composition of whole-egg protein.

Amino Acids↗

Kinetic method for the simultaneous chiral analysis of different amino acids in mixtures.

The kinetic method has been extended to enantiomeric excess (ee) determinations on amino acids present in mixtures. Singly charged trimeric clusters [Cu(II)(ref*)(2)(A(m)) - H](+) are readily generated by electrospraying solutions containing Cu(II), a chiral reference ligand (ref*), and the amino acids (analytes A(m), m = 1-3). A trimeric cluster ion for each amino acid is individually mass-selected and then collisionally activated to cause dissociation by competitive loss of either the reference ligand or the analyte. For each analyte in the mixture, as shown from separate experiments, the logarithm of the ratio of the fragment abundances for the complex containing one enantiomer of this analyte expressed relative to that for the fragments of the corresponding complex containing the other enantiomer is linearly related to the enantiomeric composition of the amino acid. Formation and dissociation of each trimeric complex ion are shown to occur independently of the presence of other analytes. Chiral selectivity appears to be an intrinsic property and the chiral selectivity R(chiral(m)) measured from the mixture of analytes is equal to R(chiral) measured for the pure analyte. The sensitive nature of the methodology and the linear relationship between the logarithm of the fragment ion abundance ratio and the optical purity, characteristic of the kinetic method, allow the determination of chiral impurities of less than 2% ee in individual compounds present in mixtures by simply recording the ratios of fragment ion abundances in a tandem mass spectrum.

Amino Acids↗

A chemically defined diet for maximal growth of pigs.

Three growth assays and one balance experiment were conducted to determine the optimal mixture of dietary amino acids for 10-kg pigs fed a chemically defined diet. Pigs were meal fed at 0700 and 1700 h in all experiments. Increasing all indispensable amino acids by 20% from their original levels improved weight gain and gain:feed ratio to levels equivalent to those of pigs fed a 20% protein corn-soybean meal-dried whey positive control diet. Replacing the glutamate-glycine-proline dispensable amino acid mixture with a complete mixture of dispensable amino acids (i.e., glutamate, glycine, proline, glutamine, serine, alanine, aspartate and asparagine) did not improve growth rate. A balance study showed that retention of nitrogen and energy (percentage of intake) from the final purified diet was superior to that of pigs fed the corn-soybean meal-dried whey diet. Metabolizable energy and metabolizable energy corrected for nitrogen retention of the final purified amino acid diet were determined to be 14.43 and 13.96 MJ/kg diet, respectively. The chemically defined diet developed here for young pigs provides a means of studying nutrient utilization in the pig under conditions in which all nutrients are essentially 100% bioavailable.

Amino Acids↗

[Pharmacological studies on small peptide fraction derived from soybean. The effects of small peptide fraction derived from soybean on fatigue, obesity and glycemia in mice].

The present research was an attempt to determine the pharmacological actions as for anti-fatigue, anti-obesity and hypoglycemia of small peptide isolated from soybean in mice. Small peptide administration prevented the decrease in sporting movement induced by concussion stress for 3 h in mice. In addition, it should be noted that the recovery rate of fatigue in 60 min after small peptide administration was over one hundred percentage in comparison with that after pretreatment, while the equivalent dose administration of amino acid mixture with the same small peptide amino acid composition did not prevent the decrease in sporting movement. In gold-thioglucose (500 mg/kg (i.p.))-induced obese mouse body weight gain, liver weight and body lipid level around uterine were significantly reduced by the chronic oral administration of small peptide (200, 1000 mg/kg). Administration in 1000 mg per kg of small peptide significantly lowered hyperglycemia in 30 and 120 min after glucose (3 g/kg (p.o.)) administration, whereas the equivalent amino acid mixture showed no effect. In conclusion, it suggested that small peptide isolated from soybean might have some pharmacological effects of anti-fatigue, anti-obesity, and hypoglycemia.

Animals↗

Uptake of a mixture of amino acids by mouse blastocysts.

Preimplantation mouse embryos exhibit growth at the blastocyst stage when there is a dramatic increase in protein content between days 4 and 5 after hCG treatment. This increse in protein synthesis requires the uptake of amino acids from the surrounding medium, but the consumption of individual amino acids present as a mixture has not been examined. We therefore measured the simultaneous depletion of 18 amino acids by mouse blastocysts in culture on days 4 and 5 after hCG treatment. Two culture media were used: one with amino acids present at concentrations largely based on those reported to give optimal rates of embryo development (M16/mix AA), and a second with the amino acids each at 0.1 mmol l-1 (M16/0.1 AA). After derivatization with o-phthaldialdehyde to yield highly fluorescent products, amino acid concentrations in the media were measured by HPLC. On day 4, seven amino acids were depleted from M16/mix AA at rates significantly greater than zero: aspartate, arginine, glycine, alanine, isoleucine, leucine and lysine; on day 5, nine amino acids were depleted at significant rates: aspartate, glutamate, asparagine, tyrosine, methionine, valine, phenylalanine, isoleucine and leucine. Average amino acid depletion from M16/mix AA was 32% greater on day 5 than on day 4. Aspartate, glutamate, arginine, isoleucine and leucine appeared to be the key amino acids sought by embryos on both days tested. Embryos grown in amino-acid-containing media appeared morphologically normal and their volume increased compared with embryos cultured in the absence of amino acids.

Amino Acids↗

Mutagenicity of Maillard browning reaction products from various nitrosated amino acid-glucose mixtures.

Ten different amino acid-glucose Maillard browning products before and after reaction with nitrite were evaluated by the Ames mutagenicity assay. No mutagenic response was observed in the methylene chloride extracts of any browning products tested before nitrosation. However, mutagenicity was showed in most of the browning mixtures, e.g., glycine-glucose, lysine-glucose (I), arginine-glucose, phenylalanine-glucose (II), and methionine-glucose after nitrosation when examined by Salmonella typhimurium strains TA98 and TA100 either with or without S-9 metabolic activation. Among the browning mixtures, (I) and (II) showed the greatest mutagenic activity after reaction with nitrite. The mutagenicity of lysine-glucose with nitrite was dependent on browning intensity, nitrosation pH, nitrosation time, nitrite level and blocking agents.

Amino Acids↗

Intravenous glutamine does not stimulate mixed muscle protein synthesis in healthy young men and women.

We investigated the effects of a glutamine-supplemented amino acid mixture on vastus lateralis muscle protein synthesis rate in healthy young men and women. Three men and 3 women (27.8 +/- 2.0 yr, 22.2 +/- 1.0 body mass index [BMI], 56.1 +/- 4.5 kg lean body mass [LBM]) received a 14-hour primed, constant intravenous infusion of L[1-13C]leucine to evaluate the fractional rate of mixed muscle protein synthesis. In addition to tracer administration, a clinically relevant amino acid mixture supplemented with either glutamine or glycine in amounts isonitrogenous to glutamine, was infused. Amino acid mixtures were infused on separate occasions in random order at a rate of 0.04 g/kg/h (glutamine at approximately 0.01 g/kg/h) with at least 2 weeks between treatment. For 2 days before and on the day of an infusion, dietary intake was controlled so that each subject received 1.5 g protein/kg/d. Compared with our previous report in the postabsorptive state, amino acid infusion increased the fractional rate of mixed muscle protein synthesis by 48% (P < .05); however, the addition of glutamine to the amino acid mixture did not further elevate muscle protein synthesis rate (ie, 0.071% +/- 0.008%/h for amino acids + glutamine v 0.060% +/- 0.008%/h for amino acids + glycine; P = .316). Plasma glutamine concentrations were higher (P < .05) during the glutamine-supplemented infusion, but free intramuscular glutamine levels were not increased (P = .363). Both plasma and free intramuscular glycine levels were increased when extra glycine was included in the infused amino acid mixture (both P < .0001). We conclude that intravenous infusion of amino acids increases the fractional rate of mixed muscle protein synthesis, but addition of glutamine to the amino acid mixture does not further stimulate muscle protein synthesis rate in healthy young men and women.

Adult↗

[Clinical application and therapeutic effects of elementalin].

Elementalin, similar to Vivonex NH in composition. consisted of an amino acid mixture and many other essential nutrients. The amino acid mixture was extracted from swine blood and supplemented with some crystal L-amino acids. Animal experiment suggested that it have a better therapeutic effects than a domestic elemental diet. 86 malnourished patients with digestive tract diseases were selected to carry out its clinic evaluation. The results showed that it could maintain or increase body weight, improve nitrogen balance and elevate the level of plasma proteins postoperatively. The total effective rate was 94.2%. No obvious side effect was found.

Adult↗

13C CP/MAS of LDLL mixtures of amino acids.

A unit cell in which three isomers are in an L configuration and one is in a D configuration is inherently asymmetrical. For LDLL mixtures of amino acids with identical chemical structures (apart from chirality), the inter- and intramolecular interactions observed from the 13C CP/MAS NMR spectra are even larger than those which have been observed with mixtures of diastereoisomers in the solid state. This occurs even though the chemical composition of these molecular clusters consists only of nearest neighbor enantiomers. Because D and L isomers have identical chemical shifts, changes in chemical shift and peak intensities of these asymmetrical solid mixtures cannot be unambiguously assigned to either the D or one of the L isomers. In LLDL mixtures of amino acids in which half is L isomers and the other half is DL isomers, the NMR spectra clearly depend upon which amino acid contains the D isomer. Any further structural interpretation of these molecular clusters is equivocal without assigning chemical shifts to the D isomer (or alternatively designated the R, [-] or [+] isomer). Both more rigorous mathematical analysis and new NMR experiments are required which link interactions at chiral centers with NMR spectra of LLDL mixtures in the solid state.

Amino Acids↗

Relative role of the glutaminase, glutamate dehydrogenase, and AMP-deaminase pathways in hepatic ureagenesis: studies with 15N.

We have studied the relative roles of the glutaminase versus glutamate dehydrogenase (GLDH) and purine nucleotide cycle (PNC) pathways in furnishing ammonia for urea synthesis. Isolated rat hepatocytes were incubated at pH 7.4 and 37 degrees C in Krebs buffer supplemented with 0.1 mM L-ornithine and 1 mM [2-15N]glutamine, [5-15N]glutamine, [15N]aspartate, or [15N]glutamate as the sole labeled nitrogen source in the presence and absence of 1 mM amino-oxyacetate (AOA). A separate series of incubations was carried out in a medium containing either 15N-labeled precursor together with an additional 19 unlabeled amino acids at concentrations similar to those of rat plasma. GC-MS was utilized to determine the precursor product relationship and the flux of 15N-labeled substrate toward 15NH3, the 6-amino group of adenine nucleotides ([6-15NH2]adenine), 15N-amino acids, and [15N]urea. Following 40 min incubation with [15N]aspartate the isotopic enrichment of singly and doubly labeled urea was 70 and 20 atom % excess, respectively; with [15N]glutamate these values were approximately 65 and approximately 30 atom % excess for singly and doubly labeled urea, respectively. In experiments with [15N]aspartate as a sole substrate 15NH3 enrichment exceeded that in [6-NH2]adenine, indicating that [6-15NH2]adenine could not be a major precursor to 15NH3. Addition of AOA inhibited the formation of [15N]glutamate, 15NH3 and doubly labeled urea from [15N]aspartate. However, AOA had little effect on [6-15NH2]adenine production. In experiments with [15N]glutamate, AOA inhibited the formation of [15N]aspartate and doubly labeled urea, whereas 15NH3 formation was increased. In the presence of a physiologic amino acid mixture, [15N]glutamate contributed less than 5% to urea-N. In contrast, the amide and the amino nitrogen of glutamine contributed approximately 65% of total urea-N regardless of the incubation medium. The current data indicate that when glutamate is a sole substrate the flux through GLDH is more prominent in furnishing NH3 for urea synthesis than the flux through the PNC. However, in experiments with medium containing a mixture of amino acids utilized by the rat liver in vivo, the fraction of NH3 derived via GLDH or PNC was negligible compared with the amount of ammonia derived via the glutaminase pathway. Therefore, the current data suggest that ammonia derived from 5-N of glutamine via glutaminase is the major source of nitrogen for hepatic urea-genesis.

AMP Deaminase↗