Effects of age and parasitemia on nitric oxide production/leukocyte nitric oxide synthase type 2 expression in asymptomatic, malaria-exposed children.

Anstey, Nicholas M.; Weinberg, J. Brice; Wang, Zhiqiang; Mwaikambo, Esther D.; Duffy, Patrick E.; Granger, Donald L.

doi:10.4269/ajtmh.1999.61.253

Cited by 26 publications

(24 citation statements)

References 35 publications

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“…However, multiple regression analysis showed age as the only predictor variable of whole-body NO synthesis, suggesting that normal aging modulates NO homeostasis in children. This finding agrees with other independent research groups who reported high levels of urinary nitrate excretion (index of NO synthesis) in infancy that declined with age (35)(36)(37). A similar age-related decrease was also observed in plasma (6,37) and cerebrospinal fluid nitrate concentrations (38).…”

Section: Subjectssupporting

confidence: 82%

A Noninvasive, Sensitive, Specific, and Reliable Approach to Assess Whole-Body Nitric Oxide Synthesis in Children

2006

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Determination of nitric oxide (NO) synthesis in vivo is essential to understand the pathophysiologic role and therapeutic implications of the L-arginine/NO pathway in pediatric diseases. The aim of this study was to establish a noninvasive, sensitive, specific, and reliable approach to determine whole-body NO synthesis in healthy children. Seventeen healthy children (eight boys/nine girls, 4 -16 y) were studied twice, and six of them on three occasions. Fasting children received a single oral dose of nonradioactive T he L-arginine/NO pathway has been an exciting research area for the past two decades. NO is endogenously synthesized from the amino acid L-arginine by NO synthase (NOS) in numerous cells, including platelets, neurons, macrophages, and endothelial cells (1). Three isoforms of human NOS have been cloned: neuronal, endothelial, and inducible (2). Both the neuronal NOS and endothelial NOS are constitutively expressed in cells and produce picomolar amounts of NO. By contrast, the inducible isoform produces high and sustained levels of NO and is usually expressed in macrophages and vascular smooth muscle cells following the exposure to cytokines and lipopolysaccharide (3). The physiologic importance of the L-arginine/NO pathway has been extensively studied in humans. It is known to play a major role in controlling vascular tone, platelet function, neurotransmission, and bronchial airway reactivity (1,4).Basic research on NO derived from in vitro and in vivo experimental models has started to have an impact on pediatrics. Accumulating evidence suggest that the NO signaling pathway is abnormal in a number of pediatric conditions including primary pulmonary hypertension (5), childhood essential hypertension (6), and cerebral malaria (7) and markedly increased in others such as septic shock (8), gastroenteritis (9,10), bronchial asthma (11), type 1 diabetes mellitus (12), and autoimmune and inflammatory diseases (13). Accurate and reliable determination of NO synthesis in vivo is essential to understand the pathophysiologic and therapeutic roles of this biologic pathway. Direct measurement of exhaled NO is a noninvasive and practical approach for assessing airway inflammation in children (14). Indeed, exhaled NO has been proposed as a tool for screening and monitoring airway inflammation and titration of anti-inflammatory therapy in asthmatic children (15). On the other hand, determination of systemic NO synthesis has been proved difficult because of NO's short plasma half-life (3-5 s) (16). This limitation has led to the development of functional and chemical markers to determine NO bioactivity. Biomarkers such as cyclic guanosine monophosphate, L-citrulline, and nitrate concentrations in plasma and urine have been used in clinical studies to assess systemic NO synthesis. However, these metabolites are not specific for the L-arginine/NO pathway (17). An approach to assess whole-body NO synthesis in critically ill children (i.e. septic shock) consists of a primed, 5-8-h constant i.

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Section: Subjectssupporting

confidence: 82%

A Noninvasive, Sensitive, Specific, and Reliable Approach to Assess Whole-Body Nitric Oxide Synthesis in Children

2006

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“…Thus RNI could possibly contribute to the epidemiological patterns of severe anemia and cerebral malaria. 13 The role of the spleen in anemia in the patient populations studied here remain unclear. Previously, we have observed indirect signs of decreased clearance in helminth-infected malaria patients.…”

Section: Discussionmentioning

confidence: 99%

Association of helminth infection with decreased reticulocyte counts and hemoglobin concentration in Thai falciparum malaria.

Nacher

Singhasivanon²,

Phumratanaprapin³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Following a study showing an association between Ascaris and protection from cerebral malaria, we conducted a cross-sectional study comparing admission hemoglobin concentrations in relation to exposure to helminth infection in 2 separate groups of patients: 111 cerebral malaria cases and 180 mild Plasmodium falciparum malaria cases. Hookworm infections were excluded. Mean hemoglobin concentrations were significantly lower in helminthinfected patients compared to those without helminths, both in the cerebral malaria group (10.1 Ϯ 3 [n ϭ 47] versus 11.2 Ϯ 2.4 g/dl [n ϭ 64], P ϭ 0.04) and the mild malaria group (11 Ϯ 2.5 [n ϭ 89] vs 12.2 Ϯ 2.7 g/dl [n ϭ 91], P ϭ 0.004). Median reticulocyte counts, only available in the cerebral malaria group, were lower in helminth-infected patients compared to those without helminths (15,340/23,760 per l, P ϭ 0.03). Adjustments for confounders such as body mass index did not alter these associations. These data are consistent with a mechanism causing anemia linked to differences in the immune response of helminth-infected patients during malaria.

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“…Up-regulated iNOS genes were also present in the mucosa throughout the disease course in pediatric and adult patients as well as in healthy controls. Thus, depressed NO 2 Ϫ /NO 3 Ϫ levels in urine of pediatric patients may be due to reduced production of NO ⅐ within the renal compartment. This finding is in agreement with our previous reports of increased local production of cytokines in stool and rectum at the site of inflammation compared to decreased systemic production in plasma during acute shigellosis (28).…”

Section: Discussionmentioning

confidence: 99%

“…The minimum detection limit of the assay for urine was 2.5 M. The creatinine content of urine was measured (24a). Finally, the concentration of the total nitrate plus nitrite was expressed in millimoles per liter/millimoles per liter of creatinine in urine and was referred to as NO 2 Ϫ / NO 3 Ϫ . SOD assay.…”

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confidence: 99%

Innate Immune Responses in Children and Adults with Shigellosis

Raqib¹,

MIa²,

Qadri³

et al. 2000

Infect Immun

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An array of pro-and anti-inflammatory mediators of the innate immune system was analyzed in stool, urine, and rectal mucosa samples from adults and children with shigellosis to better understand their role in recovery from and in the immunopathogenesis of the disease. Increased concentrations of lactoferrin (Lf), myeloperoxidase (MPO), prostaglandin E 2 , and leukotriene B 4 (LTB 4 ) in stool during acute shigellosis in both children and adults indicated that activated cells of the innate defense system at the mucosal site were secreting the mediators. Increased concentration of MPO and 8-iso-prostaglandin F 2␣ and lower levels of superoxide dismutase (SOD) activity in stool during acute Shigella infection suggested increased formation of reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In children, lower expression of SOD in tissue with severe inflammation and lower levels of SOD activity in stool for longer periods compared to adults may further worsen the tissue damage and predispose the children to a lowered defense. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflammation, compared to that seen with mild inflammation, accompanied by persistently up-regulated iNOS mRNA, reflecting increased production of nitric oxide at the local site. However, in contrast to adults, reduced urinary nitrate levels in pediatric patients during acute shigellosis suggested lower production of nitric oxide in the renal compartment.

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Effects of age and parasitemia on nitric oxide production/leukocyte nitric oxide synthase type 2 expression in asymptomatic, malaria-exposed children.

Cited by 26 publications

References 35 publications

A Noninvasive, Sensitive, Specific, and Reliable Approach to Assess Whole-Body Nitric Oxide Synthesis in Children

A Noninvasive, Sensitive, Specific, and Reliable Approach to Assess Whole-Body Nitric Oxide Synthesis in Children

Association of helminth infection with decreased reticulocyte counts and hemoglobin concentration in Thai falciparum malaria.

Innate Immune Responses in Children and Adults with Shigellosis

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