Small Intestine In Response Research Articles

Mucosal Mast Cell Reconstitution and Nippostrongylus brasiliensis Rejection by W/W v Mice

The ability of congenitally mast cell-deficient W/Wv anemic mice and mast cell-reconstituted W/Wv mice to reject the intestinal parasite Nippostrongylus brasiliensis was examined. The W/Wv mice were deficient in connective tissue mast cells and mucosal mast cells and, unlike normal mice, did not accumulate intestinal mucosal mast cells in response to N. brasiliensis infection. They had higher peak egg counts than did normal littermates and were slower than littermates to reject the parasites. Reconstitution with bone marrow or spleen cells repaired both the connective tissue and mucosal mast cell defects in W/Wv mice but did not alter the time of parasite rejection or decrease the high peak egg counts. These results indicate that mucosal mast cells that accumulate in the small intestine in response to parasite infection may not be functionally involved in the rejection mechanism.

Features of small intestinal pathology (epithelial cell kinetics, intraepithelial lymphocytes, disaccharidases) in a primary Giardia muris infection.

In an attempt to correlate host and parasite-related events occurring during the course of a primary Giardia infection in the mouse we have measured epithelial cell kinetics, enzymes, and intraepithelial lymphocytes at different stages of the infection. New methods were developed for the accurate measurement of parasite numbers and distribution within the gut. In jejunum a modest decrease in villus length and intraepithelial lymphocytes at week 1 preceded a pronounced disaccharidase deficiency at week 2, the time of maximum trophozoite numbers, whereas crypt lengthening and increased cell production became maximal at week 3. As trophozoite numbers fell the intraepithelial lymphocyte count and disaccharidase values rose. With the exception of the intraepithelial lymphocyte count, which followed the same pattern as in jejunum but two weeks later, the changes seen in the ileum were the opposite of those in jejunum, suggesting rapid ileal adaptation. The results indicate that the disaccharidase deficiency associated with giardiasis is likely to represent a direct effect of the parasite on the brush border rather than enterocyte immaturity, whereas the intraepithelial lymphocyte response reflects host immunity to the parasite. Profound adaptive changes occur throughout the small intestine in response to a relatively localised insult.

Myoelectric activity in the small intestine in response to Clostridium perfringens a enterotoxin: Correlation with histologic findings in an in vivo rabbit model

Clostridium perfringens A enterotoxin, which is heat labile and cytotoxic, causes a diarrheal illness characterized by severe abdominal pain. We have previously defined two distinct myoelectric patterns: the migrating action potential complex and repetitive bursts of action potentials. In this study we characterized the effects of C. perfringens A enterotoxin on the motility of rabbit small intestine by using myoelectric recording techniques and correlated the findings with histologic changes observed in the same preparations. The model consisted of an isolated ileal loop and the adjacent proximal small intestine in New Zealand White rabbits. A 1:200 dilution of untreated or heat-treated C. perfringens A enterotoxin was infused into the isolated loop at 0.115 ml/min. Myoelectric recordings were made from monopolar silver-silver chloride electrodes spaced at 2.5 cm intervals on the isolated loop and the adjacent small intestine. After 7–8 h recording periods the animal was killed, and tissue was submitted for histologic evaluation. Untreated C. perfringens A enterotoxin induced significantly more repetitive bursts of action potentials than did heat-treated C. perfringens A enterotoxin (8.7 vs. 0.3 repetitive bursts of action potentials/h), and significantly more repetitive bursts of action potential activity than migrating action potential complex activity (8.7 repetitive bursts of action potentials/h vs. 0.9 migrating action potential complexes/h) in the isolated loops. Untreated C. perfingens A enterotoxin induced 4.2 repetitive bursts of action potentials/h in the adjacent small intestine and no migrating action potential complexes. Heat treatment of toxin not only reduced altered myoelectric activity, but prevented the leukocytic infiltration, erosion of villous tips, and edema associated with C. perfringens A enterotoxin infusion histologically. These studies suggest that alterations in motility may be responsible in part for the clinical manifestations of C. perfringens A infection.

Characteristics of the relaxant response of adenosine and its analogs in intestinal smooth muscle

Several characteristics of the relaxant response of the isolated longitudinal muscle of the rabbit small intestine in response to the administration of adenosine and related compounds are studied. Following administration of adenosine or ATP the preparation responded with a rapid initial suppression of spontaneous contractile activity followed by a secondary sustained phase of inhibition of lower magnitude. Cumulative application of relaxant doses of adenosine or ATP caused a lesser total response than that obtained by single application of the cumulative dose. Neither procaine, lidocaine or guanethidine antagonized the responses to adenosine or ATP and the responsiveness of muscles obtained from reserpinized animals appeared unchanged. A number of adenosine derivatives and analogs was tested for the ability to relax the muscle. Generally, compounds containing a primary or secondary 6-amino group acted as agonists with the exception of 8-bromoadenosine. Those nucleosides found to be inactive did not modify the responsiveness of the muscle to adenosine. Responses to adenosine and ATP were not appreciably modified by papaverine, imidazole, dipyridamole, 6-(p-nitrobenzylthio)-purine riboside. Antagonism was observed, however, with phentolamine and theophylline. Theophylline at 100 μM inhibited responses to adenosine over a wide dose range; this antagonism was surmountable by high doses of adenosine. 1-Methyl-3-isobutylxanthine did not antagonize adenosine responses. A number of 1,3-alkyl-6-thioxanthines did not modify the adenosine response at doses that did not show any direct action. The results support the concept of an extracellular receptor site of adenosine and its analogs and the absence of an indirect mechanism of action via nerve stimulation.

The response of the small intestine to vitamin D. Correlation between calcium-binding-protein production and increased calcium absorption.

1. The synthesis of calcium-binding protein, a protein produced in the small intestine in response to vitamin D, was investigated with a view to determining whether calcium-binding-protein production could be correlated with the stimulation of calcium absorption by vitamin D. 2. A radioimmunological assay, which can quantitatively estimate calcium-binding-protein concentrations as low as 1mug/g wet wt., was used to detect the synthesis of soluble calcium-binding protein. 3. When used on intestinal supernatants from chicks dosed with vitamin D, calcium-binding protein was not detectable at 8h but was present after 12h at a concentration of 8.6mug/g wet wt.; in agreement with this an increase in calcium absorption due to vitamin D was detected at 12h but not at 8h. 4. The synthesis of calcium-binding protein was also monitored directly by making use of the ability of the iodinated antiserum to bind specifically to nascent calcium-binding protein chains on intestinal polyribosomes; in this way calcium-binding-protein synthesis could be detected 8h after dosage with vitamin D. Further, the binding reaction indicated a near linear increase in the calcium-binding-protein-synthesizing capacity over a 16h period. 5. From the amount of calcium-binding protein present 12 and 24h after vitamin D administration it is calculated that calcium-binding-protein mRNA is produced at approx. 1mol/min per intestinal cell. 6. It is concluded that the high correlation between the initiation of calcium-binding-protein synthesis and the stimulation of calcium absorption by vitamin D strengthens the proposal that calcium-binding protein plays an important role in calcium transport.

Adaptive changes of the rat small intestine in response to a high fat diet

1. 1. Rats exposed to increased dietary lipid were studied for evidence of adaptive changes in the small intestine. Two experimental groups were used. One was fed regular chow supplemented to 20% lipid with additional lard. The other was fed a synthetic diet with a similar lipid but a greater carbohydrate content and devoid of fibrous filler. 2. 2. After four weeks fecal fat output was determined. Absorption of oleate was also studied by the everted sac technique and assays of one of the mucosal lipid re-esterifying enzymes were performed. 3. 3. Rats on a high fat diet excreted significantly less radioactive fat in feces. Sacs from the jejunum of these animals absorbed more oleic acid than controls. The same trend was observed in the ileum but this was of greater significance in ileal sacs from rats on the synthetic diet. Enzyme content in the jejunum was the greatest in rats on regular chow supplemented with lard while in the ileum the highest levels were found in animals on the synthetic high fat diet. 4. 4. It is concluded that the small intestine adapts to increased dietary lipid. Other components of the diet, however, can influence the site at which these adaptive changes occur.

Role of the Small Bowel and Colon in Lactose-Induced Diarrhea

The net movement of fluid in the small bowel and in the colon in response to an oral lactose load was determined by intraluminal intubation in 5 lactase-deficient and 2 normal subjects. The major net secretion of fluid in lactase-deficient individuals occurred in the stomach, duodenum, and jejunum. The test solution had been diluted approximately 5-fold when it reached midileum. The fluid response was similar to that seen with an osmotically equivalent amount of mannitol. The response to an osmotic stimulus was the same as occurred in the control subjects fed mannitol. Ileal contents were neutral or alkaline and the osmolality was 300 milliosmoles per kg after lactose feeding. In the colon there was interference with net fluid absorption when lactose was fed by mouth to lactase-deficient subjects or perfused into the ileocecal region of 4 subjects. The decrease in net absorption was demonstrable when the result was compared with that of mannitol. Net secretion did not occur in the colon. Stools were acid (mean pH 5.8) and the osmolality had risen to 379 milliosmoles per kg presumably as a result of bacterial fermentation of the undigested lactose. Lactose-induced diarrhea in lactase-deficient subjects results, in large part, from the combination of net fluid secretion by the small intestine in response to an osmotic load and interference with net fluid absorption in the small bowel and colon. The products of fermentation of lactose may play a role in the decreased colonic absorption.

Intestinal Response to the Body's Requirement for Iron

Dietary iron is absorbed by the mucosa of the small intestine in response to the body's requirement for iron. To a great extent, the amount of iron in the body is maintained at a constant level, not by excretion of excess iron but by the ability of the intestine to reject available, unneeded dietary iron.¹Excretion of iron is limited and, under normal conditions, apparently serves as a fine adjustment to the more important control provided by the intestinal mucosal block.¹When the requirement for iron increases as it does in iron deficiency states, the mucosal block is relaxed to permit the entry of more than the usual amount of dietary iron. When the iron deficiency has been satisfied, the mucosal block is restored to prevent the accumulation by the body of excessive amounts of storage iron. Ordinarily, the intestine absorbs only enough iron to replace the obligatory metabolic

Treatment of "dumping" with serotonin antagonists: preliminary report.

RECENT STUDIES in our laboratories have shown that a circulating agent of intestinal origin may be responsible for initiating the early symptomatic phase of the postgastrectomy dumping syndrome. Since serotonin and related substances have pharmacologie actions compatible with the physiologic derangements seen in dumping, and are released from the upper small intestine in response to a hyperosmolar intraluminal stimulus, we believe that serotonin or a related agent may be of etiologic importance in the syndrome. Furthermore, with certain antiserotonin drugs, it is possible to prevent the experimental "dumping" syndrome in the dog as measured by plethysmography. The present report outlines our early experience with one of these agents, cyproheptadine (Periactin), in the treatment of postgastrectomy patients with moderate to severe dumping. Ten patients, each of whom had well-documented postgastrectomy dumping, were given 12 to 24 mg. of cyproheptadine daily, in divided oral doses, taken approximately 2 hours prior to meals.