Intestinal Permeability in Small Children during and after Rotavirus Diarrhoea Assessed with Different‐Size Polyethyleneglycols (PEG 400 and PEG 1000)

Stintzing, G; Johansen, Kari; Magnusson, Karl‐Eric; Svensson, Lennart; Sundqvist, Tommy

doi:10.1111/j.1651-2227.1986.tb10331.x

Cited by 39 publications

(24 citation statements)

References 14 publications

(14 reference statements)

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“…Regarding RV, only a few human studies have been done (15)(16)(17); all of these studies were conducted on children already infected with RV, and the time course for conceivable permeability changes was not studied.…”

Section: Discussionmentioning

confidence: 99%

“…Previous human studies investigating intestinal barrier functions (15,17) all were conducted at a time point at which subjects already had diarrhea. Thus, it remains unclear whether permeability changes are a late host response following diarrhea and/or the result of extensive lesions of the epithelia rather than the actual cause of diarrhea onset.…”

Section: The Intestinal Permeability To 4-and 10-kda Dextran Probes Imentioning

confidence: 99%

“…Intestinal permeability has only rarely been investigated in humans infected with RV (14). In the early 1980s, Stintzing and coworkers (15) assessed the intestinal permeability in young children with RV infection using polyethylene glycols (PEG) of different molecular weights, and a significantly low urinary recovery of PEG was noted. A similar observation was made in adults by Serrander and coworkers (16).…”

mentioning

confidence: 99%

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Rotavirus Infection Increases Intestinal Motility but Not Permeability at the Onset of Diarrhea

Istrate

Hagbom

Vikström

et al. 2014

J Virol

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The disease mechanisms associated with onset and secondary effects of rotavirus (RV) diarrhea remain to be determined and may not be identical. In this study, we investigated whether onset of RV diarrhea is associated with increased intestinal permeability and/or motility. To study the transit time, fluorescent fluorescein isothiocyanate (FITC)-dextran was given to RV-infected adult and infant mice. Intestinal motility was also studied with an opioid receptor agonist (loperamide) and a muscarinic receptor antagonist (atropine). To investigate whether RV increases permeability at the onset of diarrhea, fluorescent 4-and 10-kDa dextran doses were given to infected and noninfected mice, and fluorescence intensity was measured subsequently in serum. RV increased transit time in infant mice. Increased motility was detected at 24 h postinfection (h p.i.) and persisted up to 72 h p.i in pups. Both loperamide and atropine decreased intestinal motility and attenuated diarrhea. Analysis of passage of fluorescent dextran from the intestine into serum indicated unaffected intestinal permeability at the onset of diarrhea (24 to 48 h p.i.). We show that RV-induced diarrhea is associated with increased intestinal motility via an activation of the myenteric nerve plexus, which in turn stimulates muscarinic receptors on intestinal smooth muscles. IMPORTANCEWe show that RV-infected mice have increased intestinal motility at the onset of diarrhea, and that this is not associated with increased intestinal permeability. These new observations will contribute to a better understanding of the mechanisms involved in RV diarrhea.

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Section: Discussionmentioning

confidence: 99%

Section: The Intestinal Permeability To 4-and 10-kda Dextran Probes Imentioning

confidence: 99%

mentioning

confidence: 99%

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Rotavirus Infection Increases Intestinal Motility but Not Permeability at the Onset of Diarrhea

Istrate

Hagbom

Vikström

et al. 2014

J Virol

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“…The effect of paracellular leakage might be induced by NSP4 97 . In vivo studies of intestinal permeability in rotavirus--infected children has been done, showing the opposite results with less permeability of polyethylene glycol molecules in urine of rotavirus infected children compared to their uninfected state 98 . The same observation, no increase in permeability, has been found in animal studies 99 .…”

Section: Paracellular Permeabilitymentioning

confidence: 99%

“…Stintzing et al investigated intestinal permeability in young children with rotavirus infection using polyethylene glycols (PEG) of different molecular weight 98 . PEG was given orally to 9 children having acute rotavirus diarrhoea and 6 h urine was collected and PEG concentrations were determined.…”

Section: Paper II Rotavirus Infection Increases Intestinal Motility Bmentioning

confidence: 99%

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Hagbom¹

2015

Linköping University Medical Dissertations

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Rotavirus infections cause diarrhea and vomiting that can lead to severe dehydration. Despite extensive tissue damage and cell death, the inflammatory response is very limited. The focus of this thesis was to study pathophysiological mechanisms behind diarrhea and vomiting during rotavirus infection and also to investigate the mechanism behind the limited inflammatory response. An important discovery in this thesis was that rotavirus infection and the rotavirus toxin NSP4 stimulate release of the neurotransmitter serotonin from intestinal sensory enterochromaffin cells, in vitro and ex vivo. Interestingly, serotonin is known to be a mediator of both diarrhea and vomiting. Moreover, mice pups infected with rotavirus responded with central nervous system (CNS) activation in brain structures associated with vomiting, thus indicating a cross-talk between the gut and brain in rotavirus disease. Our finding that rotavirus infection activates the CNS led us to address the hypothesis that rotavirus infection not only activates the vagus nerve to stimulate vomiting, but also suppresses the inflammatory response via the cholinergic anti-inflammatory pathway, both of which are mediated by activated vagal afferent nerve signals into the brain stem. We found that mice lacking an intact vagus nerve, and mice lacking the α7 nicotine acetylcholine receptor (nAChR), being involved in cytokine suppression from macrophages, responded with a higher inflammatory response. Moreover, stimulated cytokine release from macrophages, by the rotavirus toxin NSP4, could be attenuated by nicotine, an agonist of the α7 nAChR. Thus, it seems most reasonable that the cholinergic anti-inflammatory pathway contributes to the limited inflammatory response during rotavirus infection. Moreover, rotavirus-infected mice displayed increased intestinal motility at the onset of diarrhea, which was not associated with increased intestinal permeability. The increased motility and diarrhea in infant mice could be attenuated by drugs acting on the enteric nervous system, indicating the importance and contribution of nerves in the rotavirus mediated disease. In conclusion, this thesis provides further insight into the pathophysiology of diarrhea and describe for the first time how rotavirus and host cross-talk to induce the vomiting reflex and limit inflammation. Results from these studies strongly support our hypothesis that serotonin and activation of the enteric nervous system and CNS contributes to diarrhea, vomiting and suppression of the inflammatory response in rotavirus disease

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Low‐Dose Methotrexate‐Induced Changes in Intestinal Permeability Determined by Polyethylene Glycol Polymers

Lifschitz,

Mahoney

1989

J. pediatr. gastroenterol. nutr.

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The impact of chemotherapeutic agents on small bowel mucosa has not been investigated adequately in children. To determine the effect of low‐dose methotrexate (MTX) on the permeability and mucosal integrity of the small bowel, we administered low molecular weight polyethylene glycol (PEG) to 19 children who were in the maintenance phase of treatment of acute lymphocytic leukemia. PEG was administered before and after the children received their weekly oral or intramuscular doses of MTX. PEG recoveries from a 6‐h urine collection were calculated by a mathematical formula to determine the polymer with maximal recovery (PCD0) and the polymer whose recovery was 50% of PCDo (N1/2). Compared with pre‐MTX levels, a significant increase was observed in the polymer with maximal recovery (PCDo) in 15/19 children after MTX administration (p < 0.015) which indicated increased transmucosal passage of PEG. A decrease in the PEG parameter (N1/2) was observed in 11/38 studies, and may have indicated diminished enterocyte cell mass. These changes indicate that treatment with MTX results in an increase in intestinal permeability by the paracellular pathway, which may affect the absorption of other molecules.

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Intestinal Permeability in Small Children during and after Rotavirus Diarrhoea Assessed with Different‐Size Polyethyleneglycols (PEG 400 and PEG 1000)

Cited by 39 publications

References 14 publications

Rotavirus Infection Increases Intestinal Motility but Not Permeability at the Onset of Diarrhea

Rotavirus Infection Increases Intestinal Motility but Not Permeability at the Onset of Diarrhea

Rotavirus Disease Mechanisms Diarrhea, Vomiting and Inflammation : How and Why

Low‐Dose Methotrexate‐Induced Changes in Intestinal Permeability Determined by Polyethylene Glycol Polymers

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