title: Gut motility in the expulsion of parasites
Creators: name: Farmer, Stephen George
Publisher: name: University of Glasgow
Year: 1980
Subjects: subject: Parasitology.

description: The aim of this project was to investigate the intestinal motility during infection with Nippostrongylus brasiliensis in the rat, and the possible role of motility in the expulsion of this parasite from the gut. 1. Intestinal propulsive motility was measured in rats infected with 4,000 brasiliensis larvae by following the transit of radioactive chromium (51Cr), a non-absorbable marker, through the gut. On days 6, 8, 10, 12 and 14 post-infection, 51Cr was injected through an indwelling catheter into the duodenum. 15 minutes later the animals were killed and the distribution of radioactivity in the small intestine measured. A group of uninfected, catheterised rats served as controls. Intestinal propulsive activity was increased only on day 8 of infection. On day 6, although the overall motility appeared unchanged, propulsion in the upper small intestine may have been reduced. The possible causes of these observations, and their role during infection and/or expulsion is discussed. 2. To examine the effect of artificially stimulating intestinal motility upon an established worm population, a dose of carbachol which caused diarrhoea, but no other marked physical symptoms, was employed. Rats were injected regularly with carbachol on days 5 and 6 post-infection, killed on day 7 and their worm burdens determined. Similarly, another group was treated on days 7 and 8 and killed on day 9. However, increased gut motility, as influenced by carbachol, had no apparent effect upon the worm population size, either before or after the worms had probably sustained some immunological damage. 3. The responses and sensitivity of isolated rat intestinal segments to field stimulation and a number of agonists were examined on days 6-20 post-infection with 5,000 N. brasiliensis larvae. In addition, the spontaneous contractile activity of the preparations was recorded. Infection with a dramatic increase in the maximum contractile responses of intestinal smooth muscle to both electrical stimulation and drugs, which reached a peak around day 14 of infection. The amplitude of spontaneous contractions also increased markedly on days 10, 12 and 14, but this activity was either very erratic or non-existent on days 6 and 8. These changes were not associated with any shift of the dose-response curves for acetylcholine or carbachol. The dose-response curve for 5-hydroxytryptamine (5-HT) however, was displaced to the right. This was probably due to desensitization of the preparations, due to the high intestinal levels of 5-HT known to occur daring infection. It is not known how these changes in gut sensitivity were produced, and at present it is not possible to assess their relevance to worm expulsion. Their possible causes and significance a.re discussed. 4. Because of its inhibitory effect upon worm expulsion, one wondered whether the drug betamethasone would also prevent the onset of hypersensitivity of isolated gut preparations from infected rats. This was indeed the case, though betamethasone did not completely abolish the effect. Neither did pretreatment with the drug have any effect upon the sensitivity of the gut smooth muscle from uninfected control rats. It is suggested therefore, that the increased reactivity of the intestine was due to some aspect of the immune response, rather than to a direct action of the worms themselves. However, it is still not known whether supersensitivity plays a role in worm expulsion, or whether it is simply an ineffectual consequence of infection. 5. supersensitivity similar to that occurring in the rat small intestine during nippostrongylosis has been reported in other tissues following various treatments, and alterations in the blood levels of various hormones have been implicated as a possible cause. It was therfore decided to measure the serum levels of thyroxine and corticosterone during infection in order to determine if any charges occurred. However, no change in the blood level of corticosterone was apparent, and although the thyroxine levels appeared to be lower during infection, difficulty in the interpretation of this result was encountered since the serum thyroxine levels were also reduced in uninfected, control rats which had received a single saline injection,