Plasma Amino Acid Imbalance Research Articles

Correction of imbalance of essentialaminoacids of blood plasma in Patients with stableangina

Introduction. Ischemic heart disease is the leading nosology calunit in the structure of cardiovascular diseases interms of disability and mortality among the population of Ukraine. The purpose. To improve the treatment of patients with stable angina by studying the effect of L-arginine on the balance of essential amino acids in blood plasma. Material and methods. It was examined 85 patients with stable angina. They were divided into two groups: group Ipatients received antianginal basic therapy, group II patients received basic antianginal therapy and L-arginine. The amino acid spectrum of patients' blood plasma was studied by ion-exchange liquid column chromatography, using an automatic amino acid analyzer T-339 Microtechna (Czech Republic, Prague). Results and discussion. In patients with stable angina who received basic therapy and L-arginine, in contrast to patients who received only basic therapy, plasma levels of arginine became normalized, which probably contributes to the synthesis of NO. The level of valine, leucine and isoleucine, which provide the synthesis of acyl-CoA and succinyl-CoA, became also normalized.Conclusion. Administration of L-arginine to patients with stable angina together with antianginal therapy helps to correct plasma amino acid imbalances, which is likely to effectively affect the course of the disease and prognosis.

Significance of serum branched-chain amino acid to tyrosine ratio measurement in athletes with high skeletal muscle mass

BackgroundFew nutritional markers reflect the hypermetabolic state of athletes with high levels of skeletal muscle. Although branched-chain amino acids (BCAA) play crucial roles in protein metabolism in skeletal muscle, the relationship between skeletal muscle mass and amino acid imbalances caused by the metabolism of BCAA and aromatic amino acids remains unclear. The aim of this study is to test the hypothesis that athletes with high levels of skeletal muscle mass have plasma amino acid imbalances, assessed by serum BCAA to tyrosine ratio (BTR) which can be measured conveniently.MethodsThe study enrolled 111 young Japanese men: 70 wrestling athletes and 41 controls. None of them were under any medications, extreme dietary restrictions or intense exercise regimens. Each participant’s body composition, serum concentrations of albumin and rapid turnover proteins including transthyretin and transferrin, BTR, and thyroid function were assessed.ResultsCompared to the controls, the athletes had significantly higher skeletal muscle index (SMI) (p < 0.001), and lower serum albumin concentration (p < 0.001) and BTR (p < 0.001). Kruskal–Wallis tests showed that serum albumin concentration and BTR were significantly lower in the participants with higher SMI. Serum albumin concentration and BTR were inversely correlated with SMI by multiple regression analysis (logarithmic albumin, β = − 0.358, p < 0.001; BTR, β = − 0.299, p = 0.001). SMI was inversely and transthyretin was positively correlated with serum albumin (SMI, β = − 0.554, p < 0.001; transthyretin, β = 0.379, p < 0.001). Serum concentration of free 3,5,3′-triiodothyronine (FT3) was inversely correlated with BTR, and, along with SMI and albumin, was independent predictor of BTR (SMI, β = − 0.321, p < 0.001; FT3, β = − 0.253, p = 0.001; logarithmic albumin, β = 0.261, p = 0.003). However, FT3 was not correlated with SMI or serum albumin. Serum concentrations of rapid turnover proteins were not correlated with BTR.ConclusionsIncreased skeletal muscle mass enhances the circulating amino acid imbalances, and is independently facilitated by thyroid hormones. Serum BTR may be a useful biomarker to assess the hypermetabolic state of wrestling athletes with high levels of skeletal muscle.

The effect of L-arginine on the balance of essential amino acids in plasma of the patients with stable angina

Background. Despite the significant achievements of clinical medicine in the prevention, diagnosis and treatment of coronary heart disease, the levels of morbidity, disability and mortality among the population of Ukraine from this pathology remain consistently high. The purpose. To improve the treatment of patients with stable angina by studying the effect of L-arginine on the balance of essential amino acids in blood plasma. Material and methods. It was examined 67 patients with stable angina. They were divided into two groups: group Ipatients received antianginal basic therapy, group II patients received basic antianginal therapy and L-arginine. The amino acid spectrum of patients' blood plasma was studied by ion-exchange liquid column chromatography, using an automatic amino acid analyzer T-339 Microtechna (Czech Republic, Prague). Results and discussion. In patients with stable angina who received basic therapy and L-arginine, in contrast to patients who received only basic therapy, plasma levels of arginine became normalized, which probably contributes to the synthesis of NO. The level of valine, leucine and isoleucine, which provide the synthesis of acyl-CoA and succinyl-CoA, became also normalized. Conclusion. Administration of L-arginine to patients with stable angina together with antianginal therapy helps to correct plasma amino acid imbalances, which is likely to effectively affect the course of the disease and prognosis.

Effect of a High Fat and High Protein Diet on Exercise-Induced Skeletal Muscle Hypertrophy in Rats

The skeletal muscle mass varies by race. Dietary habits over generations are a factor that influences the skeletal muscle mass, as well as genetic factors. Therefore, we investigated the effects of diets with different macronutrient contents on exercise-induced muscle hypertrophy in rats. Male 4-week-old Sprague–Dawley rats were randomly divided into three groups: a normal-diet (N), high-protein diet (HP) and high-fat diet (HF) group. The food intake was manipulated to gain comparable body weight across the three groups. All rats were performed a climbing training exercise for 8 weeks. The final body weight and weight of the liver, kidneys and adipose tissues did not significantly differ among the groups. The flexor hullucis lingus was significantly higher in the HF group than in the HP group. The total lipid content in the muscle was significantly higher in the HF group than in the N group, while it did not differ significant between the HF and HP groups. There were no marked differences in the water or protein content in the muscle among the groups. The plasma amino acid concentration was significantly or tended to be lower in the HP group than in the HF or N group, except for the branched-chain amino acid concentration, which tended to be higher after ingesting the HP diet than other diets. These findings suggest that consuming an HP diet is not likely to facilitate exercise-induced muscle hypertrophy, partly due to the plasma amino acid imbalance induced by habitual HP diet consumption.

Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI)

BackgroundLysinuric protein intolerance (LPI [MIM 222700]) is an aminoaciduria with defective transport of cationic amino acids in epithelial cells in the small intestine and proximal kidney tubules due to mutations in the SLC7A7 gene. LPI is characterized by protein malnutrition, failure to thrive and hyperammonemia. Many patients also suffer from combined hyperlipidemia and chronic kidney disease (CKD) with an unknown etiology. MethodsHere, we studied the plasma metabolomes of the Finnish LPI patients (n=26) and healthy control individuals (n=19) using a targeted platform for analysis of amino acids as well as two analytical platforms with comprehensive coverage of molecular lipids and polar metabolites. ResultsOur results demonstrated that LPI patients have a dichotomy of amino acid profiles, with both decreased essential and increased non-essential amino acids. Altered levels of metabolites participating in pathways such as sugar, energy, amino acid and lipid metabolism were observed. Furthermore, of these metabolites, myo-inositol, threonic acid, 2,5-furandicarboxylic acid, galactaric acid, 4-hydroxyphenylacetic acid, indole-3-acetic acid and beta-aminoisobutyric acid associated significantly (P<0.001) with the CKD status. Lipid analysis showed reduced levels of phosphatidylcholines and elevated levels of triacylglycerols, of which long-chain triacylglycerols associated (P<0.01) with CKD. ConclusionsThis study revealed an amino acid imbalance affecting the basic cellular metabolism, disturbances in plasma lipid composition suggesting hepatic steatosis and fibrosis and novel metabolites correlating with CKD in LPI. In addition, the CKD-associated metabolite profile along with increased nitrite plasma levels suggests that LPI may be characterized by increased oxidative stress and apoptosis, altered microbial metabolism in the intestine and uremic toxicity.

Skin Lesions Associated with Dietary Management of Maple Syrup Urine Disease: a Case Report

Abstract Leucinosis (maple syrup urine disease - MSUD) is an inherited aminoacidopathy and organic aciduria caused by severe enzyme defect in the metabolic pathway of amino acids: leucine, isoleucine, and valine. The classical variant of the disease is characterized by accumulation of both amino and α-keto acids, particulary the most toxic rapid elevation of circulating leucine and its ketoacid, α-ketoisocaproate, which cause encephalopathy and life-threatening brain swelling. However, patients with the most severe form, classical maple syrup urine disease, may appear normal at birth, but develop acute metabolic decompensation within the first weeks of life with typical symptoms: poor feeding, vomiting, poor weight gain, somnolence and burnt sugar-smelling urine, reminiscent of maple syrup. Early diagnosis and dietary intervention improve the patient’s condition, prevent severe complications, and may allow normal intellectual development. We present a 4-month old infant with leucinosis dignosed 3 months earlier, due to elevated levels of amino acids: leucine, isoleucine and valine. The patient was full-term neonate with an uncomplecated delivery, without any family history of metabolic disorder or consanguinity. The infant was referred to a dermatologist, because of maculopapular exanthema on the scalp, trunk, upper and lower extremities, and exfoliative dermatitis of the perioral, particularly anogenital regions, associated with diarrhea. Skin involvement was associated with poor general condition of the infant exhibiting severe hypotension, anemic syndrome, dyspepsia and neurological symptoms. Exanthema developed a few days after the initiation of nutritional therapy for MSUD: isoleucine-, leucine-, and valine-free powdered medical food (MSUD-2) supplemented with iron. Zink levels were within normal ranges. Rapid skin improvement occurred after adequate branched-chain amino acids supplementation was commenced under regular laboratory control (normal zinc serum level with deficiencies of leucine and valine), skin hygiene with antiseptics, emollients and low potent topical corticosteroids. Treatment of acute metabolic decompensation and dietary restriction of branched-chain amino acids are the main aspects in the management of maple syrup urine disease. Common findings in patients with MSUD include: plasma amino acid imbalance, particularly of essential amino acids, failure to thrive attributed to restriction of particular precursor amino acids and natural proteins, micronutrient deficiencies or higher energy requirement due to chronic illness or inflammation. Due to low intake of branched-chain amino acids, some patients develop skin lesions known as acrodermatitis enteropathica-like syndrome. Here we report a case of an infant who developed acrodermatitis enteropathica-like skin eruptions due to branched-chain amino acid deficiency during treatment of maple syrup urine disease. According to available world literature, this is the first report of acrodermatitis enteropathica-like syndrome in an infant with maple syrup urine disease (leucinosis) in the Republic of Bulgaria.

Plasma amino acids imbalance in cirrhotic patients disturbs the tricarboxylic acid cycle of dendritic cell

An imbalance of plasma amino acids (AA) is observed cirrhotic patients. Here we report that the imbalance suppresses the maturation of dendritic cells (DCs) by reducing the intracellular ATP due to interference with the mitochondrial tricarboxylic acid (TCA) cycle. We used serum-free culture medium consistent with the average concentration of the plasma AA from a healthy volunteer (HCM) and that from patients with advanced cirrhosis (ACM). We compared the function of DCs and the metabolism of glucose-amino acids under each medium. The maturation and intracellular ATP of immature DCs were lower under ACM in spite of the enhancement of mitochondrial respiratory chain complex genes. Metabolomics revealed that the TCA cycle metabolite, fumarate and 2-oxoglutarate were increased in DCs generated under ACM. Consistent with in vitro, In CD1c+ or CD14+ cells from cirrhotic patients, the gene expression of 2-oxoglutarate-succinate-fumarate transition enzymes were significantly different from the cells of healthy controls.

The Relationship between Renal Dysfunction and Abnormalities of the Immune System in Patients with Decompensated Cirrhosis

In patients with advanced cirrhosis, not only hepatocellular carcinoma but also bacterial infections, such as spontaneous bacterial peritonitis (SBP) or pneumonia, are frequent clinical complications in such immune-compromised patients. These pathologies often progress to renal dysfunction, especially hepatorenal syndrome (HRS). The central pathology of HRS is splanchnic arterial vasodilation and hyperpermeability followed by bacterial translocation (BT). BT induces a severe inflammatory response in the peritoneal lymphoid tissue, with the activation of the immune systems and the long-lasting production of vasoactive mediators that can impair the circulatory function and cause renal failure. Recent studies report that the plasma amino acid imbalance appeared to be related to an abnormality of the immune system in patients with decompensated cirrhosis. This paper can provide a new approach for future studies of the pathology in cirrhotic patients with renal dysfunction.

Relationship between nutritional depletion and cell-mediated immune function in active pulmonary tuberculosis

A survey on the nutritional status and cell-mediated immune function of 47 hospitalized patients with active pulmonary tuberculosis and healthy controls was conducted. In the patients group: 1) Anthropometric measurements, such as %ideal body weight (%IBW), %arm circumference (%AC), %arm muscle circumference (%AMC) and %triceps skin fold (%TSF), were significantly reduced. 2) Visceral proteins including serum albumin (Alb), transferrin (Tf), prealbumin (PA) and retinol binding protein (RBP) were significantly reduced. 3) The imbalance of plasma amino acids, which was characterized by the depression of Fischer ratio, a molar ratio of branched chain amino acids (BCAA) to aromatic amino acids (AAA), was observed. Fischer ratio was significantly correlated with anthropometric measurements (%IBW, %AC and %AMC). Delayed-type hypersensitivity to DNCB (2,4-dinitrochlorobenzene) and lymphocyte transformation to phytohemagglutinin (PHA) and concanavalin A (Con A) were significantly impaired in the patients group, whereas NK cell activity was higher than that of controls. Alb, PA, RBP and Fischer ratio were significantly lower in the patients with reduced DNCB reaction than in those with normal responses. Lymphocyte transformation was significantly correlated with Fischer ratio, and NK cell activity was significantly correlated with Alb, PA, RBP. These data may suggest that the imbalance of plasma amino acids represented by the reduction of Fischer ratio and the depletion of visceral proteins are closely related to the impairment of lymphocyte function in the patients with active pulmonary tuberculosis.

Plasma amino acid imbalance: dangerous in chronic diseases?

In various diseases amino acid imbalances occur which have been described especially in the 1980s of the last century. It was noted that some of these imbalances may exert specific negative physiological effects. However, mainly because of economic reasons, no real attempts have been made to develop special amino acid solutions for disease processed associated with amino acid imbalances to restore normal amino acid concentrations. A recent study performed in the fruit-fly Drosophila indicated that modifying the amino acid supply may influence both lifespan and fecundity. It was shown that adding amino acids but not carbohydrates or fat to a restricted diet decreases lifespan. In contrast, administration of certain amino acids especially of methionine increased fecundity without decreasing lifespan. It is known that dietary restriction can decrease fecundity at the cost of a prolonged lifespan. Recent investigations revealed that amino acids are powerful molecules in mediating cell signalling. Therefore, it can be hypothesized that the severe amino acid imbalances as observed in uraemia or liver failure may exert a relevant impact on various physiologic processes and on organ function. The recent results described in Drosophila should stimulate a new research area on the effect of amino acid supply in various disease processes.

Branched chain amino acids enhance the maturation and function of myeloid dendritic cells ex vivo in patients with advanced cirrhosis†

An imbalance of plasma amino acids is observed in patients with advanced cirrhosis. The aim of this study was to investigate the influence of the extracellular amino acid imbalance on the function of myeloid dendritic cells (DCs) in patients with advanced cirrhosis. We made a serum-free culture medium consistent with the average concentration of plasma amino acids from healthy controls (HC, n = 25) or patients with advanced cirrhosis (LC, n = 43) to reflect more closely the actual environment of the living body. We compared the phenotypical and biological functions of blood dendritic cells antigen-positive dendritic cells (BDCA+ DCs) and monocyte-derived dendritic cells (MoDCs) from LC and HC with these media. After adding stimulants, the CD83 and CD86 expressions of DCs from LC were lower than those from HC. In both HC and LC, both CD83 and CD86 expressions of DCs stimulated under the cirrhotic medium were lower than under the control medium. This phenomenon was accompanied by a suppression of the mammalian target of rapamycin (mTOR)/S6K-signaling pathways. The interleukin 12 (IL-12) production in the cirrhotic medium was significantly lower than in the control medium and increased when valine or leucine was added to the medium. In patients with advanced cirrhosis, peripheral blood mononuclear cells stimulated in the autologous plasma after oral administration of branched-chain amino acid (BCAA) granules had significantly increased interferon gamma production. In advanced cirrhosis, there is impairment of the function and maturation of DCs, which has been shown to be related to an imbalance in the extracellular amino acid profile. Elevating the extracellular concentration of BCAAs ex vivo in patients with advanced cirrhosis improved the function of DCs.

Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosis

Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation.

Nutritional and Clinical Evaluation of a Modified Soy Protein with Covalently Bound Branched-Chain Amino Acids in Cirrhotic Sprague-Dawley Rats

Several studies suggested that branched-chain amino acids (BCAA) improve plasma amino acid imbalance as well as protein metabolism in patients with cirrhosis. However, commercial formulas supplemented with free BCAA have their limitations. We evaluated a modified soy protein diet with covalently bound BCAA (diet M) by comparing it with diets based on casein (diet C) or Hepatic Aid II (diet H; commercial formula) as protein sources. After 3 weeks of bile duct obstruction, 24 Sprague-Dawley rats divided into three groups received diets with 9% (w/w) protein/amino acids for 7 days. Nutritional and clinical parameters were determined. Nitrogen balance and weight gain (g)/protein intake (g) with diet M (0.19 ± 0.31 and 1.33 ± 1.43 g, respectively) were significantly higher (p < 0.05) than with diet H (–0.34 ± 0.20 and –0.34 ± 1.11 g), but comparable to those with diet C (0.04 ± 0.38 and 0.20 ± 0.93 g). Animals on diet M had a significantly (p < 0.05) increased plasma BCAA:aromatic amino acid ratio (1.8 ± 0.3) as compared with those on diets H (1.3 ± 0.1) and C (0.8 ± 0.0). There were no significant differences in organ weight or liver function among the groups. We conclude that the BCAA-modified protein is an attractive option in the nutritional support of patients having cirrhosis.

Large-animal models of fulminant hepatic failure.

For the development of an artificial liver support system, a clinically relevant large-animal model of fulminant hepatic failure (FHF) is indispensable. Although several large-animal models have been reported so far, they have not been entirely satisfactory. Recently, we have developed a new porcine model of FHF by means of intraportal administration of 0.1 mg/kg of alpha-amanitin and 1 microg/kg of lipopolysaccharide (LPS). This model has the following superior features: 100% mortality within 5 days along with a marked elevation of aspartate transaminase (AST) levels to around 10,000 IU/l, and severe metabolic disorders such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia; an onset of hepatic encephalopathy and a significant increase in intracranial pressure immediately before death; a reversal of FHF by orthotopic liver transplantation, proving that the toxicity is liver-specific and that the graft liver is unaffected; and the capability of the damaged liver to recover and achieve both morphological and functional regeneration in 1 week if supported by an efficient auxiliary graft. Because this porcine model satisfies many of the required criteria of an optimal FHF model, it is expected to provide a useful tool for the study of FHF and the development of new therapies.

RETRACTED: Nitrogen utilization and bone mineralization in very low birth weight infants fed partially hydrolyzed preterm formula

Partialy hydrolyzed formulas have been proposed for term and preterm infants, but decreased nitrogen and calcium intestinal absorption rates, together with plasma amino acid imbalances have been reported in preterm infants. We evaluated a new formula with modified nitrogen and calcium sources (glycerophosphate). During their second week of life, 16 preterm infants were randomly assigned to 1 of 2 groups: 9 were fed the new partially hydrolyzed formula and 7 a conventional formula. A nutrient balance was performed at the end of the first month of life. Amino acid concentrations and whole-body mineralization were measured at the end of study period (theoretical term). Birth weight and gestational age (mean +/- SD) were similar in the 2 groups (28.9 +/- 7.0 wks and 1,183 +/- 242 g v 27.7 +/- 1.0 wks and 1,139 +/- 162 g). Median nitrogen absorption rate (85% v 89%; P = .03) was lower in infants fed the new formula than in those fed the conventional one. After correction for difference in nitrogen intake, there was no significant difference in N retained between the 2 groups (P = .11). Plasma amino acid concentrations were also similar in the 2 groups. At theoretical term, median bone mineral content was not significantly different between the 2 groups (50 g/kg v 55 g/kg; P = .17) and it was close to the reference values obtained in term neonates just after birth. As long as nitrogen content is 10% higher in protein hydrolyzed formula than in entire protein formula, appropriate nitrogen retention, plasma amino acid profile can be achieved with the new partially hydrolyzed formula. In both groups, bone mineralization at theoretical term was close to the mineralization observed term neonates just after birth.

Mechanisms of hyperammonemia.

Hyperammonemia is mainly found in hepatic encephalopathy and in genetic defects of the urea cycle or other pathways of the intermediary metabolism. Clinically a difference has to be made between chronic moderate hyperammonemia and acutely increased concentrations. Pathogenetic mechanisms of ammonia toxicity to the brain are partly unraveled. In some animal models confounding variables, such as the reduced intake of food and amino acid imbalance due to liver insufficiency, do not allow to establish unequivocal causal relationships between the ammonia concentration and measured effects. In chronic moderate hyperammonemia an increased flux through the serotonin pathway is a key factor. It is caused by an increased transport of large neutral amino acids (including tryptophan) through the blood-brain barrier, accentuated by the imbalance of plasma amino acids in hepatic insufficiency. It is stimulated by D- or L-glutamine. Evidence is presented showing that a functioning gamma-glutamyl cycle (glutathione formation) is a prerequisite. In acute hyperammonemia involvement of NMDA receptors, glutamate, NO and cGMP plays an additional role. In hyperammonemic crises the increased cerebral blood flow leads to brain edema; factors discussed here are increased osmolytes in astrocytes and serotoninergic activity. Recent data indicate that axonal development is affected by ammonia and can be normalized in vitro by creatine supplementation in developing mixed brain cell aggregate cultures, thus reviving the old hypothesis of the impact of hyperammonemia on energy metabolism in the developing brain that could cause mental retardation.

Increased intracranial pressure in a porcine model of fulminant hepatic failure using amatoxin and endotoxin

Background / Aims : The purpose of this study was to develop a clinically relevant porcine model of fulminant hepatic failure (FHF) by means of administration of amatoxin and endotoxin. Methods : Pigs were intraportally administered only saline in group 1 ( n =3), 1 μg/kg of lipopolysaccharide (LPS) in group 2 ( n =4), 0.1 mg/kg of α-amanitin in group 3 ( n =5), and amanitin plus LPS in group 4 ( n =9). Results : All the pigs in groups 1 and 2 survived with minimal changes in liver function tests. In contrast to the 60% mortality in group 3, all the pigs in group 4 died within 96 h, with a significant increase in aspartate transaminase at 24 h (9757±2167 IU/l). In addition, they demonstrated severe metabolic disorders, such as serum lactate accumulation, hypoglycemia, coagulopathy, plasma amino acid imbalance, and hyperammonemia. The intracranial pressure significantly increased to 17.8±2.5 mmHg immediately before death. Reversal of FHF in these pigs following orthotopic liver transplantation confirmed that the toxicity is liver-specific and that the graft liver is unaffected. Conclusions : This porcine model of FHF induced by a combination of amanitin and LPS will be of much use in the development of new therapies for human FHF.

Nutritional Efficacy of Preterm Formula With a Partially Hydrolyzed Protein Source: A Randomized Pilot Study

ABSTRACTBackgroundDecreased nitrogen levels, calcium intestinal absorption rates, and plasma amino acid imbalances were reported for preterm infants who were fed partially hydrolyzed preterm formulas. In this pilot study, we evaluated a new formula with modified nitrogen and calcium sources.MethodsDuring their second week of life, 16 preterm infants were randomly assigned to one of two groups: 9 were fed the new partially hydrolyzed formula and 7 were fed a conventional formula. Nutrient balance was performed at the end of the first month of life. Amino acid concentrations and anthropometric parameters were measured at theoretical term.ResultsBirth weight and gestational age (mean ± SD) were similar in the two groups (28.9 ± 7.0 weeks and 1183 ± 242 g vs. 27.7 ± 1.0 weeks and 1139 ± 162 g). Median nitrogen absorption rates (85% vs. 89%;P = 0.03) and biological values (59% vs. 69%;P = 0.13) were lower for infants who were fed the new formula than for those fed the conventional formula. After correction for difference in nitrogen intake, there was no significant difference in nitrogen retained between the two groups (P = 0.11). Plasma amino acid concentrations were also similar in the two groups. Median calcium absorption tended to be higher in the new‐formula group than in the conventional‐formula group (54% vs. 45%, P = 0.19). At theoretical term, infants fed the conventional formula were heavier than infants fed the new formula (3559 ± 362 g vs. 3193 ± 384 g, P = 0.04).ConclusionsBecause nitrogen content is 10% higher in hydrolyzed‐protein formula than in entire‐protein formula, appropriate nitrogen retention, plasma amino acid profile, and mineral use can be achieved with the new partially hydrolyzed formula. Further studies with larger groups are needed to evaluate the effect on growth.

ARGININE ASPARTATE SUPPLEMENTATION IN MARATHON RUNNERS REDUCES TOTAL PLASMA AMINO ACID LEVEL

706 The metabolic influence of a 14 day long supplementation to the habitual diet with L-arginine-L-aspartate (15 g daily) was investigated in 14 endurance-trained athletes during a non-competitive marathon run. In this double-blind crossover field study, specific blood parameters and the respiratory exchange ratio were analyzed before the run, after 31 km, at the end of the run, and after a recovery period of two hours. The supplementation caused no significant change in the plasma level of carbohydrate (glucose, lactate, pyruvate) and fat metabolites (fatty acids, glycerol, β-hydroxybutyrate). However, the plasma level of urea and arginine was significantly increased, and the level of most of the remaining plasma amino acids was significantly reduced. The plasma level of ammonia, lactate dehydrogenase, and creatine kinase as well as the respiratory exchange ratio was unaffected by the treatment. The plasma level of cortisol and insulin did not change either, but somatotropic hormone and glucagon were significantly higher during the exercise bout with the arginine aspartate treatment. The metabolic impact of the supplementation had no influence on the running time. Since in humans the metabolic effects of a plasma amino acid imbalance (increased arginine, decreased total amino acid level) are not known, the practice of using single amino acid supplements as potential ergogenics should be critically reevaluated.

四塩化炭素による肝障害進展過程における病理組織学的変化と血しょうアミノ酸濃度の変動

The relationship between changes in plasma amino acid and histological findings in the process of carbon tetrachloride (CCl4)-induced liver injury was studied in rats intraperitoneally injected with CCl4 at 0.2 ml/kg twice a week for 5 weeks. The degree of CCl4-induced liver injury was evaluated by measuring serum GPT activity, and the correlation between serum GPT activity and histological changes was investigated. In the histopathological study, diffuse centrilobular necrosis, coagulation necrosis, acidophilic, ballooning and fatty degeneration, fibrosis, and the formation of pseudolobule of hepatocytes were observed in the liver after CCl4 administration. Serum GPT activity was elevated after CCl4 administration and well-correlated with the histologic score of liver injury (r=0.887, p< 0.01). The coagulation necrosis changes and the pseudolobule formation caused by fibrosis proliferation were marked in the rats showing serum GPT activity of more than 500 unit.The plasma amino acid concentrations increased in the development process of CCl4-induced liver injury except for that of branched chain amino acids, which decreased with an increase severity of liver damage. The molar ratio of Val+Ile+Leu/Tyr+Phe (Fischer ratio) decreased in parallel to the increase in severity of liver parenchymal damage. The decrease in the Fischer ratio was correlated with serum GPT (r=-0.800), serum GOT (r=-0.711) and histologic scores (r=-0.851). These results suggest that plasma amino acid imbalance occurs prior to liver cirrhosis induced by severe liver damage, and that serum GPT and GOT activities and the Fischer ratio are closely correlated to the histological findings in the development process of CCl4-induced liver injury.