A new hypothesis on the pathogenesis of intestinal pseudo-obstruction by intestinal neuronal dysplasia (IND).
Using morphometry and image analysis, we investigated 17 patients showing intestinal pseudo-obstruction secondary to intestinal neuronal dysplasia (IND) and 20 controls. In addition to an increase in the number and size of the ganglia and the ganglionic cells, we also noted a significant increase in NO synthase-containing ganglionic cells. We found that this enzyme, responsible for the synthesis of nitrous oxide caused by oxidation of L-argynine aminoacid, is a neurotransmitter able to induce smooth muscle relaxation by activating cyclic AMP. If the increase in NO synthase-producing ganglionic cells is responsible for the increase in nitrous oxide production, one can hypothesize that an overproduction of nitrous oxide plays a role in the pathogenesis of intestinal pseudo-obstruction secondary to neuronal dysplasia. As NO synthase can be blocked, as was demonstrated by giving L-methil-arginine or N-G-nitro-L-argynine, it might be possible to treat intestinal pseudo-obstruction caused by intestinal neuronal dysplasia at the pharmacological level.
Bosman
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C
Department of Experimental Medicine and Pathology La Sapienza University Rome, Italy. cesare.bosman@uniroma1.it
Devito
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R
Fusilli
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Boldrini
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R
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D007223:Infant; D007418:Intestinal Pseudo-Obstruction / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D007422:Intestines / Q000294:innervation / Q000473:pathology* / Q000601:surgery; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D013368:Submucous Plexus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D009569:Nitric Oxide; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I