Increased nitric oxide production in acute diarrhoea is associated with abnormal gut permeability, hypokalaemia and malnutrition in tropical Australian Aboriginal children

R Kukuruzovic, David Brewster, E Gray, Nicholas Anstey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Australian Aboriginal children hospitalized with diarrhoeal disease have severe manifestations with acidosis, hypokalaemia, osmotic diarrhoea and abnormal small bowel permeability. Nitric oxide (NO) production is increased in diarrhoeal disease, but its relationship to mucosal function and diarrhoeal complications is not known. We examined the relationship between NO production and complications of acute diarrhoea in Aboriginal and non-Aboriginal children between February 1998 and February 2000. We enrolled 318 children admitted to Royal Darwin Hospital into one of three groups: acute diarrhoea, non-diarrhoeal controls with no inflammatory illness, and non-diarrhoeal controls with inflammatory illness. Nitric oxide production was measured by urine nitrate-creatinine (NOx/Cr) excretion on a low nitrate diet. Small bowel intestinal permeability was measured by the lactulose-rhamnose (L/R) ratio on a timed blood specimen. The NOx/Cr ratios were markedly elevated in Aboriginal diarrhoeal cases (geometric mean [GM] = 1.23, 95% confidence interval [95% CI] 1.07-1.44), lowest in non-Aboriginal non-inflammatory controls (GM = 0.13, 95% CI 0.10-0.16) and intermediate in all other groups (GM = 0.35, 95% CI 0.28-0.43). Convalescent levels (day 5) in the Aboriginal diarrhoeal group (GM = 1.02, 95% CI 0.82-1.28) were slower to fall than L/R ratios. Multivariate analysis in the diarrhoeal group indicated that high NO production was associated with abnormal permeability, hypokalaemia and malnutrition, but not with the severity of diarrhoea, acidosis or osmotic diarrhoea. We concluded that increased NO production may contribute to impaired mucosal barrier function and hypokalaemia in acute gastroenteritis, which may be the cost of the known gut-protective and antimicrobial effects mediated by NO in acute intestinal inflammation.
Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalTransactions of the Royal Society of Tropical Medicine and Hygiene
Volume97
Issue number1
Publication statusPublished - 2003

Fingerprint

Hypokalemia
Malnutrition
Diarrhea
Permeability
Nitric Oxide
Confidence Intervals
Lactulose
Rhamnose
Acidosis
Nitrates
Hospitalized Child
Gastroenteritis
Creatinine
Multivariate Analysis
Urine
Diet
Inflammation
Costs and Cost Analysis

Cite this

@article{33e20885f85748c6aa449f8cb4813e41,
title = "Increased nitric oxide production in acute diarrhoea is associated with abnormal gut permeability, hypokalaemia and malnutrition in tropical Australian Aboriginal children",
abstract = "Australian Aboriginal children hospitalized with diarrhoeal disease have severe manifestations with acidosis, hypokalaemia, osmotic diarrhoea and abnormal small bowel permeability. Nitric oxide (NO) production is increased in diarrhoeal disease, but its relationship to mucosal function and diarrhoeal complications is not known. We examined the relationship between NO production and complications of acute diarrhoea in Aboriginal and non-Aboriginal children between February 1998 and February 2000. We enrolled 318 children admitted to Royal Darwin Hospital into one of three groups: acute diarrhoea, non-diarrhoeal controls with no inflammatory illness, and non-diarrhoeal controls with inflammatory illness. Nitric oxide production was measured by urine nitrate-creatinine (NOx/Cr) excretion on a low nitrate diet. Small bowel intestinal permeability was measured by the lactulose-rhamnose (L/R) ratio on a timed blood specimen. The NOx/Cr ratios were markedly elevated in Aboriginal diarrhoeal cases (geometric mean [GM] = 1.23, 95{\%} confidence interval [95{\%} CI] 1.07-1.44), lowest in non-Aboriginal non-inflammatory controls (GM = 0.13, 95{\%} CI 0.10-0.16) and intermediate in all other groups (GM = 0.35, 95{\%} CI 0.28-0.43). Convalescent levels (day 5) in the Aboriginal diarrhoeal group (GM = 1.02, 95{\%} CI 0.82-1.28) were slower to fall than L/R ratios. Multivariate analysis in the diarrhoeal group indicated that high NO production was associated with abnormal permeability, hypokalaemia and malnutrition, but not with the severity of diarrhoea, acidosis or osmotic diarrhoea. We concluded that increased NO production may contribute to impaired mucosal barrier function and hypokalaemia in acute gastroenteritis, which may be the cost of the known gut-protective and antimicrobial effects mediated by NO in acute intestinal inflammation.",
keywords = "creatinine, lactulose, nitrate, nitric oxide, rhamnose, aborigine, acidosis, acute diarrhea, acute gastroenteritis, antimicrobial activity, article, Australia, biosynthesis, blood analysis, clinical feature, confidence interval, controlled study, convalescence, correlation analysis, creatinine urine level, diet restriction, disease association, disease severity, hospital admission, human, hypokalemia, infant, inflammatory disease, intestine infection, intestine mucosa permeability, major clinical study, malnutrition, multivariate analysis, osmosis, permeability barrier, preschool child, small intestine mucosa, tropic climate, urinalysis, urinary excretion, Acute Disease, Diarrhea, Humans, Hypokalemia, Infant, Intestinal Absorption, Logistic Models, Nitrates, Nitric Oxide, Nitrites, Northern Territory, Nutrition Disorders, Nutritional Status, Oceanic Ancestry Group, Permeability, Regression Analysis",
author = "R Kukuruzovic and David Brewster and E Gray and Nicholas Anstey",
year = "2003",
language = "English",
volume = "97",
pages = "115--120",
journal = "Transactions of the Royal Society of Tropical Medicine and Hygiene",
issn = "0035-9203",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Increased nitric oxide production in acute diarrhoea is associated with abnormal gut permeability, hypokalaemia and malnutrition in tropical Australian Aboriginal children

AU - Kukuruzovic, R

AU - Brewster, David

AU - Gray, E

AU - Anstey, Nicholas

PY - 2003

Y1 - 2003

N2 - Australian Aboriginal children hospitalized with diarrhoeal disease have severe manifestations with acidosis, hypokalaemia, osmotic diarrhoea and abnormal small bowel permeability. Nitric oxide (NO) production is increased in diarrhoeal disease, but its relationship to mucosal function and diarrhoeal complications is not known. We examined the relationship between NO production and complications of acute diarrhoea in Aboriginal and non-Aboriginal children between February 1998 and February 2000. We enrolled 318 children admitted to Royal Darwin Hospital into one of three groups: acute diarrhoea, non-diarrhoeal controls with no inflammatory illness, and non-diarrhoeal controls with inflammatory illness. Nitric oxide production was measured by urine nitrate-creatinine (NOx/Cr) excretion on a low nitrate diet. Small bowel intestinal permeability was measured by the lactulose-rhamnose (L/R) ratio on a timed blood specimen. The NOx/Cr ratios were markedly elevated in Aboriginal diarrhoeal cases (geometric mean [GM] = 1.23, 95% confidence interval [95% CI] 1.07-1.44), lowest in non-Aboriginal non-inflammatory controls (GM = 0.13, 95% CI 0.10-0.16) and intermediate in all other groups (GM = 0.35, 95% CI 0.28-0.43). Convalescent levels (day 5) in the Aboriginal diarrhoeal group (GM = 1.02, 95% CI 0.82-1.28) were slower to fall than L/R ratios. Multivariate analysis in the diarrhoeal group indicated that high NO production was associated with abnormal permeability, hypokalaemia and malnutrition, but not with the severity of diarrhoea, acidosis or osmotic diarrhoea. We concluded that increased NO production may contribute to impaired mucosal barrier function and hypokalaemia in acute gastroenteritis, which may be the cost of the known gut-protective and antimicrobial effects mediated by NO in acute intestinal inflammation.

AB - Australian Aboriginal children hospitalized with diarrhoeal disease have severe manifestations with acidosis, hypokalaemia, osmotic diarrhoea and abnormal small bowel permeability. Nitric oxide (NO) production is increased in diarrhoeal disease, but its relationship to mucosal function and diarrhoeal complications is not known. We examined the relationship between NO production and complications of acute diarrhoea in Aboriginal and non-Aboriginal children between February 1998 and February 2000. We enrolled 318 children admitted to Royal Darwin Hospital into one of three groups: acute diarrhoea, non-diarrhoeal controls with no inflammatory illness, and non-diarrhoeal controls with inflammatory illness. Nitric oxide production was measured by urine nitrate-creatinine (NOx/Cr) excretion on a low nitrate diet. Small bowel intestinal permeability was measured by the lactulose-rhamnose (L/R) ratio on a timed blood specimen. The NOx/Cr ratios were markedly elevated in Aboriginal diarrhoeal cases (geometric mean [GM] = 1.23, 95% confidence interval [95% CI] 1.07-1.44), lowest in non-Aboriginal non-inflammatory controls (GM = 0.13, 95% CI 0.10-0.16) and intermediate in all other groups (GM = 0.35, 95% CI 0.28-0.43). Convalescent levels (day 5) in the Aboriginal diarrhoeal group (GM = 1.02, 95% CI 0.82-1.28) were slower to fall than L/R ratios. Multivariate analysis in the diarrhoeal group indicated that high NO production was associated with abnormal permeability, hypokalaemia and malnutrition, but not with the severity of diarrhoea, acidosis or osmotic diarrhoea. We concluded that increased NO production may contribute to impaired mucosal barrier function and hypokalaemia in acute gastroenteritis, which may be the cost of the known gut-protective and antimicrobial effects mediated by NO in acute intestinal inflammation.

KW - creatinine

KW - lactulose

KW - nitrate

KW - nitric oxide

KW - rhamnose

KW - aborigine

KW - acidosis

KW - acute diarrhea

KW - acute gastroenteritis

KW - antimicrobial activity

KW - article

KW - Australia

KW - biosynthesis

KW - blood analysis

KW - clinical feature

KW - confidence interval

KW - controlled study

KW - convalescence

KW - correlation analysis

KW - creatinine urine level

KW - diet restriction

KW - disease association

KW - disease severity

KW - hospital admission

KW - human

KW - hypokalemia

KW - infant

KW - inflammatory disease

KW - intestine infection

KW - intestine mucosa permeability

KW - major clinical study

KW - malnutrition

KW - multivariate analysis

KW - osmosis

KW - permeability barrier

KW - preschool child

KW - small intestine mucosa

KW - tropic climate

KW - urinalysis

KW - urinary excretion

KW - Acute Disease

KW - Diarrhea

KW - Humans

KW - Hypokalemia

KW - Infant

KW - Intestinal Absorption

KW - Logistic Models

KW - Nitrates

KW - Nitric Oxide

KW - Nitrites

KW - Northern Territory

KW - Nutrition Disorders

KW - Nutritional Status

KW - Oceanic Ancestry Group

KW - Permeability

KW - Regression Analysis

UR - http://www.scopus.com/inward/record.url?scp=0037622755&partnerID=8YFLogxK

M3 - Article

VL - 97

SP - 115

EP - 120

JO - Transactions of the Royal Society of Tropical Medicine and Hygiene

JF - Transactions of the Royal Society of Tropical Medicine and Hygiene

SN - 0035-9203

IS - 1

ER -