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Vasoactive intestinal peptide upregulates MUC2 intestinal mucin via CREB/ATF1.

VIP exerts a spectrum of effects as a potent anti-inflammatory factor. In addition, VIP increases expression of MUC2, a major intestinal secretory mucin. We therefore investigated the effects of VIP on the promoter activity of the 5'-flanking region of the MUC2 gene. VIP activated MUC2 transcription in human colonic epithelial cells via cAMP signaling to ERK and p38. cAMP/Epac/Rap1/B-Raf signaling was not involved in MUC2 reporter activation. Furthermore, activation of MUC2 transcription was independent of many of the reported downstream effectors of G protein-coupled receptors, such as PKC, Ras, Raf, Src, calcium, and phosphoinositide 3-kinase. VIP induced cAMP response element-binding protein (CREB)/ATF1 phosphorylation, and this was prevented by treatment with inhibitors of either MEK or p38 and by PKA and MSK1 inhibitor H89. CREB/ATF1 and c-Jun were shown to bind to an oligonucleotide encompassing a distal, conserved CREB/AP1 site in the 5'-flanking region of the MUC2 gene, and this cis element was shown to mediate promoter reporter activation by VIP. This study has identified a new, functional cis element within the MUC2 promoter and also a new pathway regulating MUC2 expression, thus providing further insight into the molecular mechanism of VIP action in the colon. These findings are relevant to the normal biology of the colonic mucosa as well as to the development of VIP as a therapeutic agent for treatment of inflammatory bowel disease.

Activating Transcription Factor 1↗

Circadian rhythmicity in several small intestinal functions is independent of use of the intestine.

Fifty milliliters of a liquid diet were administered daily to rats in three different ways: 1) orally, beginning at 0000 h; 2) by continuous intravenous infusion; and 3) by discontinuous intravenous infusion from 0000 to 1400 h. Animals were killed every 6 h over a 24-h period. Activity profiles as a function of time of day were determined for the following small intestinal parameters; monosaccharide transport; five disaccharidases; alkaline phosphatase; gamma-glutamyltransferase; leucylnaphthylamide hydrolyzing activity; villus height and width; and number of columnar cells lining a villus section. Circadian rhythmicity as previously reported was observed for all parameters in rats fed orally for 7 days but was not observed in any parameters in rats fed by continuous infusion for 9 days. Rats fed by discontinuous infusion for 10 days maintained circadian rhythmicity in the following functions: monosaccharide transport; disaccharidase activities; and columnar cell number. Thus, rhythmicity in these functions can exist without nutrient delivery to the alimentary tract and presumably arises from involvement of a neuro-endocrine component. The other activities tested appear to require the alimentary tract for the existence of circadian rhythmicity.

Administration, Oral↗

Comparative studies on the evaluation of the effect of new anthelminthics on various intestinal helminthiasis in Iran. Effects of anthelminthics on intestinal helminthiasis.

The effect of pyrantel pamoate, levamisole, mebendazole, thiabendazole and bephenium hydroxynaphthoate on various intestinal helminths were evaluated among the inhabitants of four villages in the Dezful area southwest of Iran. A total number of 328 persons, all infected simultaneously with Ascaris and hookworm (Ancylostoma duodenale) and 49.2% with Trichostrongylus spp., were randomly divided into six groups. One group was kept as the control and the other five were each treated with one compound. Follow-up examinations showed that all of the drugs used were highly effective on Ascaris, and the differences in the cure rate were not statistically significant except for bephenium hydroxynaphthoate which showed a lower cure rate. For hookworm, cure rates of 100, 90, and 85% were observed with levamisole, pyrantel pamoate and bephenium hydroxynaphthoate, respectively. Cure rates observed with mebendazole and thiabendazole were 35 and 51%, respectively. For Trichostrongylus, the highest cure rate was achieved with levamisole, followed by thiabendazole and mebendazole. While the percentage of people showing side-effects was rather low for all drugs, thiabendazole and bephenium hydroxynaphthoate produced a higher, and levamisole a lower, percentage of side effects.

Adolescent↗

The effect of antibody on the intestinal absorption of macromolecules and on intestinal permeability in adult mice.

Oral immunization was shown to reduce the passage of bacterial antigen (BA) through the intestinal wall. The extent of the reduction found was dependent on the technique used for antigen assay, but with 125I-BA in an everted gut sac system, the amount of transported antigen was less than 60% of the amount in a control non-immune system. The inhibitory effect was due to coproantibodies which probably function by complexing and trapping the antigen in the mucous layer. This inhibition of antigen transport seems a prerogative of IgA antibodies since serum-derived antibodies caused concomitant adverse effects.

Aging↗

Synergistic hypotensive effect of vasoactive intestinal polypeptide and alpha-blockade with phentolamine. Evidence for vasoactive intestinal peptide alpha-adrenoceptor coupling in the cardiovascular system of newborn dogs.

Vasoactive intestinal polypeptide (VIP) is a neuropeptide with potent circulatory effects in the adult animal and human. Little is known about its effects or mechanism of action in the immature animal. These series of experiments evaluated the effects and possible mechanism of action of VIP on the developing canine cardiovascular system. In all three series, measurements of mean heart rate and blood pressure were taken in the control state, after parasympathetic denervation with bilateral cervical vagotomies, and after autonomic blockade with propranolol (1 mg/kg) and phentolamine (0.5 mg i.v.). In series 1, we characterized the role of alpha-adrenergic receptors in early newborn puppies by investigating the hemodynamic effects of phentolamine alone in five early newborn puppies. In series 2, the hemodynamic effects of intravenous VIP infusion (0.2 microgram/kg/min) were recorded and compared in six early newborn puppies and in 10 late newborn puppies. In series 3, the hemodynamic effects of phentolamine in the presence of VIP receptor binding inhibitor were studied. In early newborn puppies, VIP had essentially no effect on heart rate or blood pressure until phentolamine was given; then, blood pressure decreased by 17% (p less than 0.005). In late newborn puppies, VIP resulted in an increase in heart rate in the control state but not after parasympathetic or sympathetic denervation. In early newborn puppies, phentolamine alone resulted in a 24% decrease (p less than 0.005) in blood pressure, compared with a 54% decrease (p less than 0.005) in early newborn puppies preexposed to VIP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vitamin B12 uptake by intestinal microorganisms: mechanism and relevance to syndromes of intestinal bacterial overgrowth.

The mechanism of bacterial uptake of vitamin B(12), the spectrum of microorganisms capable of such uptake, and the factors involved were the subject of this study. Bacterial uptake of vitamin B(12) was found to be at least a two stage process. A primary uptake phase which was rapid (1 min or less), pH dependent, nontemperature dependent, did not require viable organisms and was insensitive to either the metabolic inhibitor dinitrophenol or to the sulfhydryl inhibitor N-ethyl-maleimide. Protein denaturation (formalin treatment or autoclaving) abolished all B(12) uptake. This primary uptake phase is thought to represent adsorption to binding or "receptor" sites on the cell wall. Second stage uptake was slower, pH and temperature dependent, required living bacteria, and was abolished by either dinitrophenol or N-ethyl-maleimide. This phase is dependent upon metabolic processes and may reflect transfer of B(12) from surface "receptor" sites into the bacterial cell. Although differences among organisms were observed in total 1 hr uptake, number of surface "receptor" sites, and relative avidities for B(12), all organisms except Streptococcus fecalis shared the two stage mechanism. Two Gram-positive organisms. Bacillus subtilis and Group A streptococcus, demonstrated the highest 1 hr vitamin B(12) uptake values; Gram-negative bacteria required 2,000-10,000 the number of organisms for comparable uptake. Binding constants (K(m)) varied from 5.05 +/-1.67 x 10(-10)M for B. subtilis to 6.18 +/-3.08 x 10(-9)M for Klebsiella pneumoniae which approximate the Km for human intrinsic factor (0.38 x 10(-10)M). Competition between bacteria and intrinsic factor for vitamin B(12) may be inferred from the similarity of these constants. These observations suggest that a variety of enteric and nonenteric organisms, not requiring exogenous B(12), may play a role in the pathogenesis of the vitamin B(12) malabsorption found in the intestinal bacterial overgrowth syndromes.

Bacillus subtilis↗

Diarrhoea and increased intestinal permeability in laboratory beagles associated with proximal small intestinal bacterial overgrowth.

Repeated episodes of diarrhoea were seen in 4 laboratory beagles after experimental renal surgery and feeding a modified diet. Small intestinal bacterial overgrowth (SIBO) was suspected by exclusion of other causes and measurement of plasma folate. SIBO was confirmed by quantitative duodenal bacteriology. Beagles with SIBO can show no clinical signs, experimental stress and dietary change may have been reasons why these 4 beagles exhibited clinical signs with SIBO. Despite normal gut histology an increase in gut permeability was found using sugar absorption tests. This increased permeability had the potential to cause variations in drug absorption during experimental studies.

Animals↗

Validity of serum pepsinogen I/II ratio for the diagnosis of gastric epithelial dysplasia and intestinal metaplasia during the follow-up of patients at risk for intestinal-type gastric adenocarcinoma.

A cohort of individuals (n = 136) with lesions as severe as atrophic chronic gastritis (ACG) was cross-sectionally evaluated for the validity assessment of pepsinogen I (PGI) and pepsinogen II (PGII) serum levels for the diagnosis of intestinal metaplasia (IM) and gastric dysplasia. PGI/PGII ratio [median (range)] was 4 (0.5-7.5) in patients with ACG (n = 35); 4.6 (1.9-6.8) in type I IM (n = 18); 4.2 (1.4-5.9) in type II or type III IM limited to the antrum and incisura (n = 20); 2.4 (0.4-5.6) in extensive incomplete IM (n = 38); and 1.3 (0.4-6.4) in low-grade dysplasia (n = 23) (P = .002). Using histopathologic data as a reference test, the area under the receiver operating characteristic curves (CI 95%) was 0.73 (0.64-0.82) for extensive IM, 0.72 (0.58-0.85) for the diagnosis of dysplasia, and 0.81 (0.66-0.95) for the diagnosis of high-grade dysplasia. Using a PGI/PGII ratio of < or =3 as the cutoff for dysplasia diagnosis, the sensitivity was 70% (62-78%), the specificity was 65% (57-73%), and the negative predictive value estimates were over 90%. No differences in PG levels according to age or gender were observed. Helicobacter pylori did not significantly influence validity measurement estimates. PGI/PGII serum level ratio can be used even in the management of patients with a high a priori probability for a positive test. It may be useful for the exclusion of more advanced lesions (extensive IM and neoplastic lesions).

Adenocarcinoma↗

Chronic intestinal inflammation and intestinal disease in dogs.

Normal individuals maintain tolerance to the endogenous bacterial flora residing within their alimentary tract, a phenomenon mediated by the gastrointestinal lymphoid tissue. Loss of this tolerance is a key factor in the development of chronic intestinal inflammation. Manifestations of such uncontrolled inflammation in humans include inflammatory bowel disease and celiac disease. Dogs may similarly be affected, and although the etiopathogenesis is likely similar, the lesions differ. This review includes discussion of the factors involved in breakdown of mucosal tolerance, the immunologic basis of canine enteropathies, and the use of novel immunotherapies for these diseases.

Animals↗

Effects of heat-stable Escherichia coli enterotoxin on intestinal alkaline secretion and transepithelial potential difference in the rat intestines in vivo.

The effects of the heat-stable enterotoxin of Escherichia coli (STa) on intestinal alkaline secretion and transepithelial electric potential difference (PD) were investigated in vivo in denervated segments of rat jejunum, ileum, and proximal colon. STa caused a significant increase in alkaline secretion in the jejunum but not in the ileum or colon. The jejunal effect of STa may be ascribed to a stimulation of bicarbonate secretion and/or an inhibition of Na+/H+ exchange. With regard to PD, STa caused a marked rise in colonic PD, whereas only a small response was found in the jejunum. No effect on PD was seen in the ileum. Hexamethonium (10 mg/kg intravenously) significantly diminished the effects of STa on PD, whereas only a small inhibition of the STa-induced alkaline secretion was observed. The effect of lidocaine on PD and alkaline secretion was found to be similar to that of hexamethonium. Atropine had no effect on any of the studied variables. These findings suggest that STa exerts, via nerves, a profound influence on the jejunal transport mechanisms responsible for the changes in PD, whereas the influence on alkaline secretion is to a large extent not mediated via enteric nerves. Thus, the extent of enteric nervous control of epithelial function differs for different transport functions. The findings also indicate that the bicarbonate ion is not the anion mainly responsible for the fluid secretion elicited by STa.

Animals↗

[Extended venous ischemia of the small intestine caused by portal thrombosis. Value of diagnostic celioscopy and intestinal bi-exclusion (Thiry-Vella technique)].

Mesenteric venous thrombosis is a rare disease with no specific signs. It's major risk is intestinal ischaemia and necrosis. We report the case of a young women who presented with unexplained abdominal pain and subnormal abdominal ultrasound. The diagnosis was made on laparoscopic exploration which allowed anticoagulant therapy followed by proximal and distal divertingostomies of the ischemic bowel. Small bowel continuity was re-established after 3 month of total parenteral nutrition. The patients is doing well 1 year after surgery. She is still under anticoagulant therapy. The etiology found was a hypermegacaryocytosis as seen in myeloproliferative disease.

Adult↗

Propinox in intestinal colic: multicenter randomized prospective double-blind study of three doses of propinox vs. placebo in acute intestinal colic pain.

The aim of this double-blind study was to assess the efficacy and tolerability of propinox administered i.v. and to establish a dose-response relationship according to three dose levels (10 mg, 20 mg and 30 mg), vs. placebo in patients with moderate-to-severe acute intestinal colic pain. Four hundred patients (100 per treatment group) were included and allocated to the following treatment groups: propinox 10 mg, 20 mg, 30 mg and placebo. All treatments induced significant and progressive pain reduction as from the 20 min evaluation of 20.3% in the placebo group, 45% in the group treated with propinox 10 mg; 52% in the group receiving propinox 20 mg and 56% in the propinox 30 mg group. Statistical comparison showed differences between placebo and the three active doses as well as between propinox 10 mg and the 20 mg and 30 mg doses. The 20 min evaluation revealed that 40% of patients receiving placebo had to be excluded from the study due to lack of efficacy; the percentage of which was significantly higher compared with those observed with the three doses of propinox ranging between 10% and 13%. The 120 min evaluation revealed that 47.7% of patients treated with propinox 10 mg were free from pain vs. 68.8% and 73.5% of those receiving 20 mg and 30 mg, respectively. These percentages were considerably higher than the 15% found with placebo. Statistical analysis revealed significant differences between the 10 mg vs. the 20 mg and 30 mg groups with not differences between the latter doses. No differences in blood pressure or heart rate were found among treatments. The incidence of mouth dryness was significantly more frequent with the 20 mg and 30 mg doses of propinox than with the placebo or the 10 mg dose.

Adolescent↗

[Mitotic activity of epithelium in crypts of rats' empty intestine and tissue basophils in the event of intestinal syndrome of radiation disease treated with poly-radio-modification].

In the experiment with white mongrel puberal male rats, morphological and statistical methods were used to study mitotic activity (MA) in the crypt epithelium in the empty intestine and morphofunctional state of tissue basophils (TB) in the intercrypt stroma after a single gamma-irradiation at the dose of 10 Gy and polyradiomodification including exposure to EMR in the UHF range (2.4 GHz, 10 mW/cm2, 2.5 min), normobaric oxygen (NO) or hypoxic gaseous mixture (HGM) containing 8% of O2 and 92% of N2. Polyradiomodification with the use of EMR and HGM or NO was found to be more effective as compared with the use of each of these radioprotective methods separately. A combination of EMR + HGM + II gave more apparent and earlier effect of MA recovery and TB activation as compared to EMR + NO + II.

Animals↗

Studies on intestinal adenosine triphosphatases. I. Application of a semiautomated method to the rat intestinal brush borders.

Elaboration of a semiautomated kinetic test on LKB 8600 apparatus for ATPase is described, using the PK-LDH system. As optimal ionic conditions 3 mmol-1 - minus 1 potassium chloride and 100 mmol-1 - minus 1 sodium chloride are proposed for measurement of (Na+-K+)-ATPase activities of rat intestinal brush borders. NH+4 can substitute for K+. The coefficients of variation of the method are 2.4% for Mg2+-ATPase and 4.9% for (Na+-K+)-ATPase determinations.

Adenosine Triphosphatases↗

Intestinal anisakiasis mimicking intestinal obstruction.

We report one case of acute abdomen after the ingestion of raw or undercooked fish containing nematode larvae of the genus Anisakis. Early diagnosis is very important as it could prevent unnecessary surgical procedures since the symptoms of intestinal anisakiasis may mimic other illnesses such as appendicitis, ileitis or peritonitis. We suggest that anisakiasis should be considered in the differential diagnosis of patients with acute abdomen.

Abdominal Pain↗

Intestinal herpes simplex infection presenting with intestinal perforation.

A 77-yr-old man who had received systemic steroids for more than 6 yr presented with an acute abdomen. Laparotomy revealed an ulcerative jejunitis with purulent peritonitis. The patient underwent resection of involved bowel followed by a 10-day course of aciclovir, with excellent results. Pathologic examination showed a necrotizing enteritis with intranuclear inclusions typical of Herpesvirus that reacted immunocytochemically with antibodies to herpes simplex virus types I and II. A rising herpes simplex virus serum antibody titer confirmed the diagnosis. Intestinal herpes infection with perforation should be added to the list of complications from herpes simplex in the immunocompromised patient.

Aged↗

[Intestinal ascariasis. A rare cause of obstruction of the small intestine].

Ascariasis is a benign and common disease in tropical areas. Due to its endemicity and high prevalence, serious abdominal complications requiring urgent and versatile surgical therapy do occur. An observation of intestinal obstruction by ascaris bundle, diagnosed during operation, is reported. The postoperative course was uneventful.

Adult↗