Pathogenesis of cancrum oris (noma): confounding interactions of malnutrition with infection.
This study showed that impoverished Nigerian children at risk for cancrum oris (noma) had significantly reduced plasma concentrations of zinc (< 10.8 micromol/L), retinol (< 1.05 micromol/L), ascorbate (< 11 micromol/L), and the essential amino acids, with prominently increased plasma and saliva levels of free cortisol, compared with their healthy counterparts. The nutrient deficiencies, in concert with previously reported widespread viral infections (measles, herpesviruses) in the children, would impair oral mucosal immunity. We postulate, subject to additional studies, that evolution of the oral mucosal ulcers including acute necrotizing gingivitis to noma is triggered by a consortium of microorganisms of which Fusobacterium necrophorum is a key component. Fusobacterium necrophorum elaborates several dermonecrotic toxic metabolites and is acquired by the impoverished children via fecal contamination resulting from shared residential facilities with animals and very poor environmental sanitation. (+info)
Total parenteral nutrition in the management of acute renal failure.
Malnutrition is frequently present in patients with acute renal failure and may affect morbidity and mortality in this condition. When adequate nourishment cannot be given through the gastrointestinal tract, total parental nutrition with amino acids and hypertonic glucose may have beneficial results. Total parenteral nutrition has been reported to stabilize or reduce serum urea nitrogen, potassium and phosphorus levels, improve wound healing, enhance survival from acute renal failure, and possibly increase the rate of recovery of renal function. The optimal composition of the total parenteral nutrition infusate is unknown. Preliminary results of a double-blind study are reported in which one man received hypertonic glucose alone, two received glucose with essential amino acids (21 g/day), and three received glucose with essential (21 g/day) and nonessential (21 g/day) amino acids. All infusates were isocaloric. No differences were observed in serum urea nitrogen levels, serum urea nitrogen/creatinine ratios or urea appearance rates. Nitrogen balance was negative in all patients. The ratio of essential amino acids/nonessential amino acids were higher and the tyrosine/phenylalanine ratios were lower in plasma in the two patients receiving glucose with essential amino acids. No patient survived the hospitalization. In view of the markedly negative nitrogen balance frequently observed in these and earlier studies, the use of a different composition or quantity of amino acids, a higher energy intake, and anabolic hormones deserve further investigation. (+info)
Criteria for choosing amino acid therapy in acute renal failure.
Metabolic studies were performed on 19 patients with acute renal failure. Therapy included intravenous hyperalimentation using 15 to 20 g of essential amino acids or 20 to 40 g of essential plus nonessential amino acids and hypertonic glucose (37 to 50%). The effect of this parenteral feeding appears to be primarily pharmacological. Hypertonic glucose promotes the hyperinsulinemia important to be membrane function, the operation of the sodium pump, and cell metabolism. Administration of high biological value crystalline amino acdis potentiates the effect of insulin by inhibiting protein breakdown and promoting protein synthesis, particularly in muscle. This reduces tissue catabolism and urea formation, and promotes potassium, magnesium, and phosphate homeostasis. The branched-chain ketogenic amino acids valine, leucine, and isoleucine may be of particular importance. When indicated, administration of renal failure hyperalimentation and peritoneal or hemodialysis can be expected to complement each other and accelerate recovery. This intravenous fluid therapy, in turn, must be coordinated with proper hemodynamics, usually requiring a colloidal solution to maintain intravascular volume, and cardiotrophic agents such as digitalis and dopamine. Early use of renal failure can be expected to demonstrate the most striking response in terms of survival, early recovery from acute renal failure, and the preservation of physiological homeostasis. (+info)
Postexercise net protein synthesis in human muscle from orally administered amino acids.
We examined the response of net muscle protein synthesis to ingestion of amino acids after a bout of resistance exercise. A primed, constant infusion of L-[ring-2H5]phenylalanine was used to measure net muscle protein balance in three male and three female volunteers on three occasions. Subjects consumed in random order 1 liter of 1) a mixed amino acid (40 g) solution (MAA), 2) an essential amino acid (40 g) solution (EAA), and 3) a placebo solution (PLA). Arterial amino acid concentrations increased approximately 150-640% above baseline during ingestion of MAA and EAA. Net muscle protein balance was significantly increased from negative during PLA ingestion (-50 +/- 23 nmol. min-1. 100 ml leg volume-1) to positive during MAA ingestion (17 +/- 13 nmol. min-1. 100 ml leg volume-1) and EAA (29 +/- 14 nmol. min-1. 100 ml leg volume-1; P < 0.05). Because net balance was similar for MAA and EAA, it does not appear necessary to include nonessential amino acids in a formulation designed to elicit an anabolic response from muscle after exercise. We concluded that ingestion of oral essential amino acids results in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise in humans similar to that seen when the amino acids were infused. (+info)
Effects of dorsomedial hypothalamic nuclei lesions on intake of an imbalanced amino acid diet.
Within 3 h of ingesting an imbalanced amino acid diet (Imb), rats show attenuated intake, which can be ameliorated by prior administration of the serotonin receptor antagonist tropisetron (Trop). Earlier work in which the dorsomedial hypothalamic nucleus (DMN) was electrolytically lesioned (DMNL) determined that this structure plays a role in the early detection of and subsequent adaptation to Imb. However, that study did not address whether cell bodies in the DMN, fibers of passage, or both were involved in the DMNL response to Imb. In the present investigation in experiment 1, rats were given electrolytic DMNL or a sham operation (Sham). The rats were injected with saline (Sal) or Trop just before introduction of Imb. By 3 h Sal-DMNL rats consumed more Imb than did the Sal-Sham rats; intake was normal by 12 h. Trop enhanced Imb intake, with Trop and DMNL being additive. By day 4 the DMNL rats were eating and gaining weight less than were Sham rats. In experiment 2, DMN cell bodies were destroyed by ibotenic acid (Ibo). Sal-injected Ibo-lesioned and Sham rats showed similar food intake depression on Imb; Trop similarly increased Imb intake in both groups. By day 4 both Ibo-L rats were eating and gaining weight less than were Sham rats. In experiment 3, groups of rats were given knife cuts posterior, lateral, ventral, dorsal, or anterior to the DMN. During the first 3 h of consuming Imb, all cuts except posterior enhanced the intake of Imb. Over the next 24 h the anterior cut group continued to eat more Imb than did the Sham rats. In experiment 4 DMNL rats were given novel diets; the DMNL rats did not display a neophilic response. The data suggest that fiber tracts that pass through the DMN may be involved in the early detection of Imb. DMN cell bodies, or fibers of passage, are not involved in the Trop effect. Finally, DMN cell bodies are necessary for proper long-term adaptation to Imb. (+info)
Temporal and differential effects of amino acids on bovine embryo development in culture.
The aim of the study was to determine the amino acid requirements of the in vitro-produced bovine embryo as it develops from the zygote to the blastocyst, using a two-step culture system. When added to synthetic oviduct fluid (SOF) for the first 72-h culture, Eagle's nonessential amino acids and glutamine (NeGln) significantly increased development to the 8- to 16-cell stage (Day 4 postinsemination [pi]) and subsequent blastocyst development (Day 7 pi). Glutamine alone during the first 72-h culture did not stimulate development to the 8- to 16-cell stage (p > 0.05); however, the removal of glutamine from NeGln reduced the stimulatory effects of the nonessential amino acids. Replacing glutamine with betaine (an organic osmolyte) in NeGln did not stimulate development to the 8- to 16-cell stage compared to culture in SOF, but it did improve subsequent blastocyst development, indicating an osmolytic function of glutamine during the first 72-h culture. The addition of Eagle's essential amino acids and glutamine to SOF, or to medium already containing nonessential amino acids and glutamine for the first 72-h culture, did not affect cleavage to the 8- to 16-cell stage or subsequent blastocyst development (p > 0.05). Beyond Day 4 pi, culture with 20aa (nonessential and essential amino acids and glutamine) increased blastocyst development, total cell number, and the number of cells in both the trophectoderm and inner cell mass, compared to culture with other groups of amino acids (p < 0.05). Substituting betaine for glutamine in 20aa reduced blastocyst formation, indicating a non-osmolytic function of glutamine during the second 72-h culture. Further, there was a significant negative correlation between the concentration of essential amino acids (quarter, half, or single strength) and embryo development during both the first 72-h and second 72-h culture (p < 0.01), indicating that the concentration of essential amino acids was too high during culture of the bovine embryo. This study identified the temporal and differential effects of amino acids during development of the bovine embryo from the zygote to the blastocyst. (+info)
Essential amino acids affect interstitial dopamine metabolites in the anterior piriform cortex of rats.
The anterior piriform cortex (APC) is essential for the anorectic reactions to an amino acid-imbalanced diet, and it also responds to repletion of the limiting amino acid. In the present study, we examine the dynamic changes of the interstitial dopamine metabolites in the APC following feeding of either an amino acid-corrected or -imbalanced diet. Microdialysates, collected from the APC, were analyzed using HPLC with electrochemical detection. The concentrations were 19.7 +/- 4.8 microg/L for 3, 4-dyhydroxyphenylacetic acid and 25.1 +/- 4.4 microg/L for homovanillic acid, respectively, in the baseline dialysates. After diet treatments, no significant changes occurred in 3, 4-dyhydroxyphenylacetic acid in the corrected (n = 7) or imbalanced (n = 9) groups vs. the basal group (n = 7). However, after feeding the threonine-corrected diet, the concentration of homovanillic acid was significantly less (P < 0.01) than after the basal and imbalanced diets. The homovanillic acid level in the corrected group was already significantly lower than in the basal group by 20 min (P < 0.05), and reached its lowest level at 70 min (P < 0.05). The concentrations of homovanillic acid in the corrected group remained at this low level until the end of the experiment. The present results introduce the idea that the dopaminergic system is involved in the feeding responses to essential amino acid repletion. (+info)
A tracer investigation of obligatory oxidative amino acid losses in healthy, young adults.
BACKGROUND: Estimation of the minimum requirement for indispensable amino acids (IAAs) has been attempted by assuming that obligatory oxidative losses (OOLs) of IAAs can be approximated from nitrogen losses and that the efficiency of utilization of IAAs at requirement intakes is approximately 70%. OBJECTIVE: We wished to determine the rates of OOLs in healthy adults, using L-[1-(13)C]leucine and L-[1-(13)C, methyl-(2)H(3)]methio-nine as tracers, after adjustment to a protein-free diet and how these rates compare with those when either sulfur amino acids (SAAs: methionine and cyst(e)ine) or leucine were removed from an otherwise adequate diet. DESIGN: Eleven subjects were randomly assigned to a 5-d protein-free diet or a 5-d diet providing adequate nitrogen and amino acids except for the SAAs or leucine. A 24-h constant intravenous infusion of [(15)N, (15)N]urea and L-[1-(13)C]leucine (Leu group; n = 5) or L-[1-(13)C, methyl-(2)H(3)]methionine (Met group; n = 6 ) began at 1800 on day 5 and rates of amino acid oxidation were determined. RESULTS: Mean (+/-SD) oxidation rates (mg kg(-)(1) d(-)(1)) of methionine and leucine were 6.4 +/- 1.4 and 24.7 +/- 3.6, respectively, with the protein-free diet; rates were significantly lower (3.9 +/- 2.2 and 7. 2 +/- 3.4, respectively) after the SAA- and leucine-free diets. Urea production was significantly lower (P < 0.01) with the protein-free than with the SAA- or leucine-free diet. CONCLUSIONS: Isotopically determined OOLs for methionine and leucine are consistent with losses predicted from nitrogen excretion, and consistent with our previous measurements of cysteine oxidation as an index of total SAA losses. The data further support our earlier conclusions regarding methionine sparing by cysteine and tentative recommended SAA requirements in adults. (+info)