Metabolic effects of acute measles in chronically malnourished Nigerian children

Phillips, Reshma S.; Enwonwu, Cyril O.; Okolo, SN; Hassan, Alaa Ali

doi:10.1016/j.jnutbio.2003.11.006

Cited by 30 publications

(36 citation statements)

References 48 publications

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“…The increase in plasma leucine is accompanied by an increase in muscle protein synthesis in neonatal pigs. Contrary to reports in children and adults with sepsis and infection (7,30,49), we did not find alterations in aromatic amino acids (i.e., phenylalanine tyrosine, and tryptophan).…”

Section: Discussioncontrasting

confidence: 99%

“…In an attempt to establish homeostasis, amino acids are released from peripheral tissues and shifted to the liver for promotion of hepatic protein synthesis, gluconeogenesis, and urea synthesis (24, 25). Plasma amino acid concentrations in patients with sepsis or disease are lower than in persons without sepsis (17,30,49), and attempts have been made to use the extent of this difference as a marker of the severity and prognosis of the disease process (16, 58). The uptake of amino acids by the liver is elevated, despite the reduced plasma amino acid concentration; thus, hepatic extraction of serum amino acids is increased (25).…”

mentioning

confidence: 99%

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Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

Orellana¹,

Jeyapalan²,

Escobar³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis. growth; sepsis; mammalian target of rapamycin; eukaryotic initiation factor 4G; ribosomal protein S6 kinase THE SYSTEMIC INFLAMMATORY RESPONSE and sepsis syndromes elicited in the host in response to a bacterial pathogen or its products (35) are associated with hypermetabolism, increased oxygen consumption and energy expenditure, activation of peripheral protein catabolism, and alteration in the flux of metabolic substrates between skeletal muscle and liver (4, 39). Derangements in skeletal muscle glucose and amino acid metabolism evoked by sepsis result from the body's attempt to maintain the balance between peripheral substrate stores and the increased metabolic demands required to activate the immune system and the stress response (4, 37). These adaptative responses are different from those in the normal fasting person in that the immune response is the drive for the metabolic enhancement (11,59). In an attempt to establish homeostasis, amino acids are released from peripheral tissues and shifted to the liver for promotion of hepatic protein synthesis, gluconeogenesis, and urea synthesis (24, 25). Plasma amino acid concentrations in patients with sepsis or disease are lower than in persons without sepsis (17,30,49), and attempts have been made to use the extent of this difference as a marker of the severity and prognosis of the ...

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Section: Discussioncontrasting

confidence: 99%

mentioning

confidence: 99%

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

Orellana¹,

Jeyapalan²,

Escobar³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Measles promotes a T H 1 to T H 2 cytokine shift, with depletion of plasma IL-12, a key cytokine in the development of cell-mediated immunity. 51 The effects of primary malnutrition are reversible by refeeding. Renutrition studies in children show that innate immune functions, such as phagocytic function and microbicidal killing, and adaptive lymphocyte proliferative response improve in parallel with growth.…”

Section: Primary Malnutritionmentioning

confidence: 99%

Mechanisms of nutrient modulation of the immune response

Cunningham‐Rundles

McNeeley

Moon

2005

Journal of Allergy and Clinical Immunology

444

330

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“…25 During infections, otherwise healthy as well as malnourished individuals may experience high ACTH-induced plasma cortisol levels. [26][27][28][29][30][31] During severe infection, these levels may be equivalent to prednisolone concentrations following a single dose of 20 mg/m 2 in children with ALL. Here, the median peak level is 221 ng/ml, which corresponds to 613 nM prednisolone or 2453 nM cortisol, given an equipotency of 1:4.…”

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confidence: 99%

Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

et al. 2008

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The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations -the adrenal hypothesis -that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets that dominate in the first 5-7 years of life and may furthermore suppress the Th1-dominated proinflammatory response to infections, and thus lower the proliferative stress on preexisting preleukemic cells.

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Metabolic effects of acute measles in chronically malnourished Nigerian children

Cited by 30 publications

References 48 publications

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation

Mechanisms of nutrient modulation of the immune response

Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

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