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Rectal electrogenic secretion--is it a putative indicator of intestinal secretory status induced by nutritional deprivation in the rat?

Intestinal secretion is enhanced by starvation in rats. The rectum from fed and 3-day-starved rats generates a basal electrogenic ion transfer (short-circuit current) in vitro which is mainly electrogenic Na+ absorption (amiloride-sensitive, 66-71%) with a small component of electrogenic chloride secretion (furosemide-sensitive, 14-22%). Bethanechol, a muscarinic agonist, caused an increase in the short-circuit current (mainly furosemide-sensitive chloride secretion) and potential difference in rectums from both fed and starved rats but the respective values for the starved animals were 100% and 64% greater. In starvation, the rat rectum is an indicator of intestinal secretory status. The result warrants investigation of human rectal electrogenic secretion in nutritional deprivation.

Absorption↗

Effects of bile and pancreatic secretions on intestinal mucosa after proximal small bowel resection in rats.

After proximal small bowel resection the remaining small intestine undergoes adaptive hyperplasia. In the present study, the relative contributions of bile and (or) pancreatic juice to adaptive intestinal hyperplasia following proximal resection was studied. Using male Sprague-Dawley rats a 50% proximal intestinal resection was done starting 10 cm distal to the beginning of the jejunum. The animals were also subjected to diversion of bile and (or) pancreatic secretions to the distal ileum at 18 cm proximal to the ileocecal junction. After 8 days gut and mucosal weights, mucosal proteins, and DNA were measured in the duodenojejunum (gut segment proximal to the resection anastomosis) and in the ileum (first half of the small bowel segment distal to the diversion site). The results indicate that (1) in rats fed either chow (Purina rat chow) or a chemically defined diet diversion of pancreaticobiliary secretions to the ileum significantly stimulated ileal mucosa growth whereas no changes were observed in the duodenojejunum, (2) in rats fed a chemically defined diet neither bile nor pancreatic juice affected ileal mucosa when separately diverted to the ileum, and (3) pancreatic juice draining into the duodenum while bile was diverted to the ileum induced hypoplastic changes in the duodenojejunum. The present study suggests that following jejunectomy the regulation of mucosal growth by pancreatic and bile secretions is different in the proximal and distal small intestine. Pancreaticobiliary secretions are trophic for the ileum. However, in the proximal gut bile offers protection against a direct or indirect catabolic action of pancreatic juice.

Animals↗

Selective transport of serum-derived IgA into mucosal secretions.

The relative contribution of serum-derived and locally produced IgA has been estimated in sheep mammary secretion at various stages of lactation by comparing the transport of radiolabeled IgA and IgG2 from serum to secretions. During early and mid-lactation, but not during involution, serum IgA was selectively transported to mammary secretion on a large scale; in comparison, there was no transport of serum IgA into intestinal secretion. Estimates of local production indicated that the bulk of the IgA in mammary involution secretion and intestinal secretion was locally produced, whereas there was no evidence for local production of IgA in early or mid-lactation secretion. Our studies reveal an inverse relationship between the extent of local production of IgA by plasma cells underlying secretory epithelia and the selective transport of IgA from serum. This finding suggests that selective transport of serum IgA occurs at a number of mucosal sites, but is dependent on secretory component availability, because where local production is predominant, there are fewer secretory component molecules available for serum IgA transport. For this reason, bile transport of IgA does not represent a unique mechanism for the removal of IgA from serum.

Animals↗

Quantitation of the immunoglobulins in reproductive tract secretions of the mare.

IgG, IgA, IgM and albumin concentrations were measured in serum, follicular fluid and oviductal, uterine and intestinal secretions of the horse. Follicular protein concentrations were found to be dependent on serum concentration and molecular size. Of the immunoglobulins only IgG was detectable in oviductal secretions, but IgG:albumin ratios did not differ significantly from those in serum. IgG, IgA and IgM were measured in uterine secretions, with IgG predominant. Serum transudation into uterine secretions was minimal. In intestinal secretions, IgA levels were slightly higher than IgG, with albumin and IgM at low levels. In five mares with histories of chronic metritis, IgG, IgA and albumin concentrations were significantly elevated in uterine secretions.

Albumins↗

Watery diarrhoea and a vasoactive intestinal peptide secreting ganglioneuroma.

A case of a 12-month-old child with chronic water diarrhoea, weight loss, abdominal distension, hypokalaemia and hypochlorhydria, which were associated with a vasoactive intestinal peptide secreting ganglioneuroma, is reported. Removal of the tumour led to complete clinical and biochemical recovery. Measurement of vasoactive intestinal peptide levels should be included in the evaluation of chronic diarrhoea after the more common causes have been ruled out.

Adenoma, Islet Cell↗

Interleukin-4 and interleukin-13 differentially regulate epithelial chloride secretion.

Intestinal epithelia are in intimate contact with subepithelial and intraepithelial lymphocytes. When stimulated, mucosal lymphocytes generate cytokines that act locally and influence functional aspects of many cell types. We have previously defined functional epithelial receptors for interferon-gamma, interleukin (IL)-4, and a recently described IL-4-like cytokine IL-13. In this study, we examine the ion transport properties of T84 cells, a crypt-like epithelial cell line, following exposure to IL-4 and IL-13. Basolateral exposure of epithelial monolayers to both IL-4 and IL-13 attenuated epithelial barrier function and increased paracellular flux of a dextran marker by greater than 65% in a dose- and time-dependent fashion. Stimulated Cl- secretion, as measured by epithelial short circuit current, however, was diminished only by IL-4 and not IL-13, demonstrating cytokine specificity in this epithelial function. Decreased Cl- secretion following IL-4 exposure was associated with diminished Cl- channel activity and IL-4 pretreatment of epithelia decreased expression of the cystic fibrosis transmembrane regulator. Finally, stimulated fluid transport across cultured epithelia was diminished following exposure to IL-4, but not IL-13. These results indicate that while post-receptor signaling events induced by IL-13 and IL-4 may be similar, end point function is cytokine-specific.

1-Methyl-3-isobutylxanthine↗

Watery diarrhea syndrome due to an adrenal pheochromocytoma secreting vasoactive intestinal polypeptide.

A 55-year-old woman presented with several protracted episodes of diarrhea; it was found to be secretory in origin. In the course of evaluating the diarrhea, an ultrasound of the abdomen was performed which disclosed a large right adrenal mass. Endocrinologic studies revealed elevated serum levels of gastrin, vasoactive intestinal polypeptide (VIP), catecholamines, and its metabolites. Surgery was performed successfully without any intraoperative complications, and postoperatively the patient was asymptomatic without further episodes of diarrhea. Histologically the tumor was a pheochromocytoma with neuroendocrine granules of vasoactive intestinal polypeptide and norepinephrine. To our knowledge, there have been six previously reported cases of pheochromocytoma secreting vasoactive intestinal polypeptide. In a patient with secretory diarrhea of unknown etiology, the adrenal glands as well as the pancreas should be examined by ultrasound and/or computerized tomography for the presence of a mass. Should an adrenal mass be discovered, it is necessary to evaluate the tumor for catecholamine production, despite the absence of clinical symptoms of a pheochromocytoma.

Adrenal Gland Neoplasms↗

Secretory antibodies against turkey coronaviral enteritis.

Studies on local immunity to transmissible coronaviral enteritis of turkeys (bluecomb) was made. Intestinal secretions and bile from affected birds contained secretory immunoglobulins against coronaviral antigen throughout the 6 months' duration of the experiment. Attempts to purify and to characterize the globulins in intestinal secretions and bile of the affected birds were made, using the techniques of gel filtration, DEAE chromatography, and immunoelectrophoresis. Class-specific anti-turkey IgA antiserum in the agar gel precipitin test further established the presence of IgA in the intestinal secretions and bile.

Animals↗

[Duodenal stimulation of insulin secretion. Role of intestinal villi].

Insulin secretion is partially regulated by hormonal and nervous signals arising from the duodenum. To ascertain the role of absorption through the villi on insulin secretion, the blood levels of immunoreactive insulin (IRI) in 13 normal children (T) were compared with those in 13 with flat jejunal mucosae (MJP). The bowel was stimulated by the infusion of Nutramigen direct into the duodenum at 4 ml/mn m2. In the control group (T) IRI increased from the 10th minute of the perfusion to reach a plateau after the first hour (256 +/- 107 pmol/l). In the MJP group the rise of IRI was delayed and the plateau lower (169 +/- 25 pmol/1) but the difference in the two groups was not statistically significant. During the first 10 minutes when there is no significant change in blood glucose levels IRI levels increased in the T group (p less than 0.01) but there was no significant change in the MJP group. These results suggest that when villi are intact stimulation of the duodenum causes insulin secretion; but when there are no villi, there is a delay in the secretion.

Blood Glucose↗

Appraisal of gut lavage in the study of intestinal humoral immunity.

Direct investigation of intestinal humoral immunity requires collection of intestinal secretions or mucosal biopsy specimens, or both. A non-invasive technique of gut lavage, with a polyethyleneglycol electrolyte lavage solution as a means of collecting intestinal secretions for immunoglobulin and antibody studies, was evaluated. Fifty patients were studied--25 immunologically normal patients or volunteers, 15 patients with untreated coeliac disease, and 10 patients with active Crohn's disease. Protease inhibitors were added promptly to samples to prevent proteolysis of immunoglobulin content. Treated lavage samples were assayed by enzyme linked immunosorbent assay for immunoglobulin and antibody content. Studies of serial lavage specimens showed that early, faecally contaminated specimens contained negligible quantities of immunoglobulin, but once the specimens became clear a steady state was reached, with little variation in immunoglobulin content between serial specimens and with a uniform dilution (around 20%) of the ingested polyethyleneglycol. Gut lavage fluid IgA was predominantly secretory, comprising 92%, 81.6%, and 76.7% respectively of the total IgA gut lavage fluid content in the control, coeliac, and Crohn's groups. High values of total IgM and IgA and IgM antigliadin antibodies were detected in the coeliac group, and high values of IgG in the Crohn's disease group. This method of gut lavage is not only an effective bowel cleanser, but also a noninvasive means of obtaining intestinal secretions for the study of humoral immunity in gastrointestinal disease.

Adolescent↗

Vasoactive intestinal polypeptide secreting islet cell tumors: a 15-year experience and review of the literature.

BACKGROUND: Vasoactive intestinal polypeptide (VIP)-secreting tumors of the pancreas represent a rare subtype of pancreatic islet cell tumors with an estimated incidence of 0.2 to 0.5 per million per year. We provide data on a relatively large series of patients with VIP-secreting tumors and review current literature regarding this specific entity. METHODS: A retrospective review was performed of all patients with VIP-secreting tumors of the pancreas treated from 1977 to 1992 at our institution. Presenting signs, symptoms, mode of diagnosis, extent of disease, surgical resectability, tumor size, treatments, hormone levels, and survival were assessed. RESULTS: Eighteen patients were identified, 9 male and 9 female. Ages ranged from 23 to 74 years (mean 51 years). Secretory diarrhea was the most common symptom, occurring in 16 of 18 patients (89%). The most common tumor location was the tail of the pancreas (9 patients). Fourteen patients (78%) had liver metastasis at diagnosis. Curative resections were attempted in only 5 patients (28%). The mean survival was 3.6 years with the longest disease-free survival being 15 years and longest overall survival 15 years. CONCLUSIONS: VIP-secreting tumors are extremely rare entities and usually metastatic at the time of diagnosis. Despite advanced disease, these patients can have extended survival.

Adenoma, Islet Cell↗

The intestinal phase of gastric secretion.

The intestinal phase hormone, elaborated by the jejunum in response to an intestinal meal or simple distension, produces profound gastric hypersecretion when it escapes hepatic degradation through a portacaval anastomosis. The hormone is released within 30 min of the application of the stimulus and rapidly reaches peak concentration in the portal blood. Intravenous infusion into a donor dog of active portal plasma from a shunted, intestinally fed dog stimulates gastric acid secretion after a delay of approximately 1 h, and requires a mean 1 1/2 h to stimulate peak secretion, which suggests that intermediate steps may be necessary before the hormone can effectively stimulate the parietal cell mass. The pig develops portacaval-shunt-related gastric acid hypersecretion in response to food comparable to that observed in the dog and in man. Porcine jejunal mucosa is thus an appropriate source for isolation of the intestinal phase hormone. Pig intestinal mucosal extract contains a heat-stable acidic peptide which is a potent stimulator of gastric acid secretion. Administration of crude intestinal mucosal extract elicits gastric acid secretion after a brief delay, again indicating that some intermediate reactions occur before the target organ--the parietal cell mass--is stimulated.

Animals↗

CFTR pharmacology and its role in intestinal fluid secretion.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated Cl(-) channel expressed in epithelial cells in the airways, pancreas, intestine and other fluid-transporting tissues. Cystic fibrosis is caused by mutations in the CFTR, resulting in impaired Cl(-) transport and plasma membrane targeting. CFTR is expressed in the lumenal membrane of enterocytes, where it functions as the principal pathway for secretion of Cl(-) and fluid in enterotoxin-induced secretory diarrheas such as cholera. Small-molecule CFTR inhibitors reduce enterotoxin-induced intestinal fluid secretion in animal models. CFTR inhibition might also reduce intestinal fluid losses in cholera and possibly in other infectious and non-infectious diarrheas.

Animals↗

Small bowel fistulas treated with somatostatin: preliminary results.

Small bowel cutaneous fistula appearing after laparotomy was treated with the tetradecapeptide somatostatin in six patients to reduce the volume and enzyme content of the intestinal secretion. Continuous intravenous infusion of somatostatin diminished output from the fistula in all cases. Spontaneous fistula closure occurred after 11 to 33 days of treatment in four patients. There were no complications such as sepsis, peritonitis, or wound or skin problems from the contact with intestinal secretion. The hospital stay ranged from 19 to 50 days and bowel function was restored to normal. These preliminary results indicated that somatostatin can promote healing of small bowel fistula by inhibiting intestinal secretions.

Adult↗

Secretion of sparfloxacin from the human intestinal Caco-2 cell line is altered by P-glycoprotein inhibitors.

The mechanism of intestinal secretion of the difluorinated quinolone sparfloxacin was investigated with the epithelial cell line Caco-2 and was compared to that of the P-glycoprotein (P-gp) substrate vinblastine. The P-gp inhibitors verapamil and progesterone significantly increased the epithelial cell accumulation of both vinblastine and sparfloxacin. This increase is likely to result from an inhibition of drug secretion since both vinblastine uptake and sparfloxacin uptake are known to proceed through a passive transmembrane diffusion. The unidirectional fluxes across cell monlayers grown on permeable filters indicated that a net secretion of sparfloxacin and vinblastine occurred across Caco-2 cells. These secretions were significantly inhibited by the MDR-reversing agent verapamil. We conclude that the P-gp is likely to be involved in the intestinal elimination of the difluorinated quinolone sparfloxacin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗