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[Preparation of the large intestine for the surgical treatment of intestinal obstruction].

Obstruction of the large intestine of tumorous origin was treated by the traditional methods in 191 patients: an emergency operation in peritonitis or nonoperative management of the obstruction by cleansing enema, purgatives, and infusion-transfusion therapy. In another group of 341 patients emergency colonoscopy and ultrasonic diagnosis were resorted to and the "obstruction index" (Deltz et al. 1989) was used for objectification of the indications for an emergency operation. The method of fractional oral treatment with 30% solution of polyethelyne oxide-400 and 1% chloramphenicol was applied in this group. Traditional treatment caused resolution of the obstruction in 22.8% of patients in the control and in 28.3% of patients in the experimental group. Postoperative mortality was 24.1% and 16.4%, respectively. The obstruction index allowed correct evaluation of the indications for operation in 97% of cases, the number of forced operation reduced from 52.2% to 14.1%.

Combined Modality Therapy↗

Effect of the addition of Peptostreptococcus productus ATCC35244 on the gastro-intestinal microbiota and its activity, as simulated in an in vitro simulator of the human gastro-intestinal tract.

Peptostreptococcus productus ATCC35244, a reductive acetogenic strain, was added daily over 9 successive days to the fourth vessel (ascending colon) of the SHIME, a six-stage reactor system simulating the in vivo continuous culture conditions of the human gastro-intestinal tract. Final numbers of organisms (cfu)/ml reactor contents (c) were attained such that log10c = 6.9 +/- 0.1. The addition caused the CH4 production to decrease below the detection limit while total gas and CO2 production in the fifth (transverse colon) and sixth reactor (descending colon) were lowered and the acetic acid concentration was augmented. Ending the supplementation caused CH4 production to re-establish within 4 days, while CO2 production increased much more slowly. The concentration of acetic acid only started to decrease after 7 days. The results indicate that P. productus, upon regular administration, is able to compete with methanogens for H2 in the gastro-intestinal microbial ecosystem because of its reductive acetogenic character.

Acetic Acid↗

Involvement of cholinergic neurons in intestinal contraction caused by vasoactive intestinal contractor.

The mechanism of the contractile response to vasoactive intestinal contractor (VIC) was examined in the isolated guinea-pig small intestine. VIC at 10(-9) to 10(-7) M produced a transient relaxation followed by a contraction, and this contraction was partially inhibited, to the same degree, by either atropine or tetrodotoxin. VIC (10(-8) M) induced an increase in the release of [3H]acetylcholine from the ileum preloaded with [3H]choline. The VIC-induced acetylcholine release was dependent on external Ca2+. Thus, the VIC-induced contractions may relate to stimulation of cholinergic neurons and smooth muscle cells.

Acetylcholine↗

Use of enzyme linked immunosorbent assay in intestinal and extra-intestinal amoebiasis (amoebic liver abscess).

The sera of patients with amoebic liver abscess, intestinal amoebiasis and non-specific hepatomegaly were examined for the presence of antibodies to Entamoeba histolytica antigen by enzyme linked immunosorbent assay (ELISA). All the amoebic liver abscess sera were strongly positive. The test was also positive in all the proved cases of intestinal amoebiasis but the ELISA values were relatively slightly lower. Nine of 10 cases of non-specific hepatomegaly with stools negative for E. histolytica gave positive results with ELISA. The IHA titre in all but one of the non-specific hepatomegaly cases was within normal value.

Antibodies↗

Age-related changes in substance P and vasoactive intestinal polypeptide immunoreactivity in the rat stomach and small intestine.

Immunoreactivity for substance P (SP-LI) and vasoactive intestinal polypeptide (VIP-LI) in the stomach, duodenum, jejunum and ileum of young (3-month-old), adult (12-month-old) and old (28-month-old) male Wistar rats were determined by radioimmunoassay. SP-LI and VIP-LI did not show changes in the stomach or in the small intestine portions investigated in adult in comparison with young rats. In old rats SP-LI levels were unchanged in the stomach and in the duodenum, reduced in the jejunum and increased in the ileum. VIP-LI concentrations were unchanged in the stomach, and remarkably reduced in the duodenum, jejunum and ileum of old rats. Since the two neuropeptides investigated are localized primarily within different intrinsic gastrointestinal neurons, the present findings suggest that the various populations of gastrointestinal neurons are affected in a different manner during aging.

Journal Article↗

Ketamine may modify intestinal motility by acting at GABAA-receptor complex; an in vitro study on the guinea pig intestine.

In the present study the effect of ketamine, a dissociative anaesthetic, on the GABA- and on the specific GABAA-agonist muscimol-induced responses of the isolated guinea pig ileum was investigated. GABA as well as muscimol produce a concentration-dependent contractile effect on the duodenum, jejunum and ileum. The sensitivity of the intestinal parts to both the above substances increases from the duodenum to the ileum. Ketamine produces a non-competitive inhibition of the GABA- and muscimol-induced contractions of the ileum, while it does not influence the ileal cholinergic contractions induced by exogenous acetylcholine. These results suggest that ketamine may modify intestinal motility through its antagonistic action at the GABAA-receptor complex.

Acetylcholine↗

Transport of leuprolide across rat intestine, rabbit intestine and Caco-2 cell monolayer.

The purpose of this study was to investigate the transport mechanisms and causes of low bioavailability of leuprolide. The everted gut sac technique and Caco-2 cell monolayer were used to examine: (1) transport properties, enzyme degradation and apparent permeation coefficient (Papp); (2) the influence of trypsin inhibitor, EDTA, chitosan and alginate on drug transport; and (3) the effect of animal species on the intestinal transport. Results showed flux increased with increasing concentration of drug, showing a passive diffusion pathway. The enzyme degradation in rabbit gut was the highest. The Papp of (4.19 +/- 1.33) x 10(-5) cm/s in rat gut was the largest and the Papp of (5.20 +/- 0.20) x 10(-7) cm/s in Caco-2 cell the smallest. At a low concentration of drug, trypsin inhibitor had strong enhancement effect on the Papp by protecting enough drug for permeation. Chitosan had no effect on the activity of alpha-chymotrypsin. The increase in Papp was due to opening of the tight junctions and interaction with cells. In conclusion, both inhibition of proteolytic enzymes and opening the tight junctions to allow for paracellular transport improved the intestinal absorption. At low drug concentration, reduction of enzyme degradation is the most important factor.

Alginates↗

Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity for and transport via hPepT1 in the human intestinal Caco-2 cell line.

The human intestinal di/tri-peptide carrier, hPepT1, has been suggested as a drug delivery target via increasing the intestinal transport of low permeability compounds by designing peptidomimetic prodrugs. Model ester prodrugs using the stabilized dipeptides D-Glu-Ala and D-Asp-Ala as pro-moieties for benzyl alcohol have been shown to maintain affinity for hPepT1. The primary aim of the present study was to investigate if modifications of the benzyl alcohol model drug influence the corresponding D-Glu-Ala and D-Asp-Ala model prodrugs' affinity for hPepT1 in Caco-2 cells. A second aim was to investigate the transepithelial transport and hydrolysis parameters for D-Asp(BnO)-Ala and D-Glu(BnO)-Ala across Caco-2 cell monolayers. In the present study, all investigated D-Asp-Ala and D-Glu-Ala model prodrugs retained various degrees of affinity for hPepT1 in Caco-2 cells. These affinities are used to establish a QSAR of our benzyl alcohol modified model prodrugs, aided at elucidating the observed differences in model prodrug affinity for hPepT1; additionally, these data suggest that the hydrophobicity of the side-chain model drug is the major determinant in the compounds affinity for hPepT1. Transepithelial transport studies performed using Caco-2 cells of D-Asp(BnO)-Ala and D-Glu(BnO)-Ala showed that the K(m) for transepithelial transport was not significantly different for the two compounds. The maximal transport rate of the carrier-mediated flux component does not differ between the two model prodrugs either. The transepithelial transport of D-Asp(BnO)-Ala and D-Glu(BnO)-Ala follows simple kinetics, and the release of benzyl alcohol is pH-dependent, but unaffected by 1 mM of the esterase inhibitor Paraoxon in 80% human plasma and Caco-2 cell homogenate.

Caco-2 Cells↗

Molecular cloning of the rat intestinal trefoil factor gene. Characterization of an intestinal goblet cell-associated promoter.

Intestinal trefoil factor (ITF) is a small peptide bearing the unique motif of intrachain disulfide bonds characteristic of the trefoil family. Previous work had localized expression of ITF primarily within goblet cells in the small and large bowel, making it a candidate gene for the study of the molecular basis of intestinal and goblet cell-specific gene expression. In order to study the regulation of ITF expression, we have cloned the rat ITF gene and sequenced 1.7 kilobases of the 5'-flanking region. RNase protection analysis demonstrated a single transcriptional start site. Various lengths of the 5'-flanking region were linked to the reporter gene luciferase and transfected into the colon cancer cell lines LS174T and Caco-2, representing, respectively, cells with and without goblet cell-like phenotype. Expression in the goblet cell-like LS174T colon cancer cell line was nearly 10-fold greater than expression in Caco-2 cells which exhibit columnar enterocyte-like phenotype. The pattern of goblet cell-associated selective transcription required only 153 base pairs of the rat ITF 5'-flanking sequence. Transfection of a construct of human growth hormone under the control of the rat ITF promoter in the N2 subclone of HT-29 cells demonstrated expression of the reporter gene only in those cells exhibiting a goblet cell phenotype as assessed by expression of immunoreactive mucin. These initial studies of the 5'-flanking region of the ITF gene demonstrate the presence of cis-regulatory elements capable of directing goblet cell specific expression.

Amino Acid Sequence↗

Manometric study on the intestinal motility in a case of megacystis-microcolon-intestinal hypoperistalsis syndrome.

We report on the intestinal motility in a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) based on a total registered time of 9.5 h by means of a manometric method we recently developed for neonates. The characteristics of this case are as follows: (a) the frequency of the contractions in the stomach and duodenum was significantly lower than that of healthy infants; and (b) bands of rhythmic contractions, resembling phase III activity of the interdigestive migrating contractions in adults, were recorded in the duodenum, but their occurrence was less frequent and the amplitude was significantly lower than that of healthy infants. The present study indicates that "hypoperistalsis" in MMIHS means not only the low frequency, but also the low amplitude, of the contractions in the alimentary tract.

Colon↗

Tumor necrosis factor alpha is a key mediator of gut inflammation seen in amebic colitis in human intestine in the SCID mouse-human intestinal xenograft model of disease.

We used Entamoeba histolytica infection in human intestinal xenografts to study the roles interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) in the pathogenesis of amebic colitis. We found that blockade of TNF-alpha reduced inflammation and intestinal damage in amebic infection, while inhibition of IL-1 reduced cytokine production but had less marked effects on inflammation and disease.

Animals↗

[Value of indirect immunofluorescence test in the diagnosis and prognosis of intestinal and extra-intestinal amoebiasis in endemic areas (author's transl)].

A comparative study of 108 patients with patient amoebiasis and a reference group of 85 free of the disease but living in endemic area. The positivity of the test has been more frequent and has given higher titers in the extra-intestinal forms than in the intestinal ones. The positivity rate in the reference group has been 15 per 100.

Amebiasis↗

[The laboratory diagnosis of the intestinal malabsorption syndrome of intestinal origin].

Normal absorption and digestion occurs in sequential stages. In the lumen of the proximal intestine pancreatic enzymes and bile salts transform complex substances in simple products which can be absorbed by the enterocyte and transported by lymphatics or portal veins. Malabsorption syndromes can be secondary to alterations in both digestion and/or absorption process. We herein review the tests used to establish the diagnosis of intestinal malabsorption syndromes with special reference to those available in our country. Finally we propose an algorithm taking into account the frequency of diseases causing malabsorption in Mexico.

Breath Tests↗

[Inflammatory intestinal diseases and their extra-intestinal manifestations observed at Liban].

101 cases classified as inflammatory bowel disease at the Hôtel-Dieu de France Hospital between 1982 and 1994 were investigated. Files containing a sure diagnosis and complete clinical and biological investigations were included. 65 files were retained for the study: 48 cases had ulcerative colitis (UC), 17 had Crohn's disease (CD). UC averaged 4.7 admissions per 10,000 admissions to the hospital, while CD averaged 1.54 per 10,000. The UC/CD ratio was 2.8 and the Female/Male ratio was 1.4 for UC and 0.9 for CD. Medium follow-up was 6.4 years. 30% of our group was followed for more than 10 years. Overall frequency of extra-intestinal manifestations was similar to that reported worldwide. This is especially true for UC. However, no cases of ankylosing spondylitis, sclerosing cholangitis or erythema nodosum were found. One case of pyoderma gangrenosum was found in the series of CD. Extra-intestinal manifestations were found in 54% of UC patients and 94% of CD patients, probably because milder cases of this disease were misclassified as infectious diarrhea.

Adult↗

Intestinal absorption kinetics of amiodarone in rat small intestine.

Amiodarone is a widely used antiarrhythmic agent with highly variable therapeutic effects. These seem to be related, at least in part, to the pharmacokinetics of the drug and particularly to some features of its gastrointestinal absorption process. The drug exhibits physico-chemical properties highly suitable for diffusion across lipophilic absorbing membranes, but its low aqueous solubility can act as the rate limiting step for absorption, making the process erratic and variable. In order to gain an insight into the intestinal absorption mechanism of the drug and detect possible non-linearities, a series of experiments using a classical rat gut in situ preparation were carried out with three amiodarone hydrochloride solutions (10, 75, and 200 micrograms mL-1). A synthetic non-ionic surfactant, polysorbate 80, at supramicellar concentration (2 mM) was used as the drug solubilizer. Amiodarone was assayed in biological samples by HPLC using a rapid, sensitive technique that was validated. The amiodarone first-order absorption rate constants obtained in these conditions were similar. No significant differences between ka values were found. Amiodarone absorption was clearly identified as a passive diffusion process.

Administration, Oral↗

The stem-cell zone of the small intestinal epithelium. IV. Effects of resecting 30% of the small intestine.

In the mouse jejunum, as in the rat, a new steady state was established 3 weeks after resection of 30% of the small intestine. The mean height of a villus, crypt, and proliferative zone increased. We studied the effects of this new steady state on the distribution of the four main epithelial cell types and on the stem-cell zone. Beginning 2 cm distal to the ligament of Treitz, 10 cm of jejunum were resected. In control animals the jejunum was transected 12 cm distal to the ligament of Treitz and then rejoined. The mice were killed 1 and 3 weeks after surgery and a piece of jejunum 4 cm distal to the anastomosis collected. One hour before death the animals were given an injection of 1 mu Ci/gm 3H-thymidine. The tissue was embedded in Epon and then serial 1 micron sections were prepared and radioautographed. One week after resection there was a transient increase in the proportion of enteroendocrine cells in the crypts. This returned to control levels 3 weeks after resection. Thus, there appeared to be a feedback from the enteroendocrine population onto enteroendocrine cell production. After resection, amplification of mucous cell numbers by mucous cell division was reduced and yet normal proportions of mucous cells were observed in the epithelium. Therefore, an increased proportion of stem-cell output must have been committed to the mucous and enteroendocrine cell lines. The increased height of the proliferative zone that followed 30% resection was not due to an increase in the number of transit divisions through the proliferative zone. Instead it was due to an increased output from the stem-cell zone into the proliferative zone. Evidence was presented which indicates that the increased output from the stem-cell zone was due to an increased number of stem cells in the zone, at the expense of non-stem cells. The height of the stem-cell zone, as indicated by the Paneth cell distribution, the mucous cell distribution, and the distribution of labeled mucous cells, did not change after 30% resection.

Animals↗

The effect of raising the concentration of potassium in the blood or intestinal lumen on the transport of potassium in the dog intestine.

The rates of transport of potassium, sodium and water across the intestinal mucosa of Thiry-Vella fistulas of colon and ileum, were studied in dogs in two experimental situations; (1) following intravenous infusion of potassium (15 mEg) over 30 minutes and (2) during variations in the intraluminal concentration of potassium in the range 0.8-16.0 mEg/l. Following intravenous infusion of potassium the rates of potassium secretion into the colon were usually increased; the rates of sodium and water absorption were either unchanged or decreased. The unidirectional rate of movement of potassium into the lumen increased as the concentration difference across the mucosa increased; the movement of potassium in the opposite direction remained relatively constant. The undirectional movement of sodium and water into the lumen of the colon also increased but to a lesser extent. The effect on potassium transport in the ileum was not so marked. With increase in the intraluminal concentration of potassium there was a decrease in the rate of net potassium secretion in both colon and ileum. The rates of net absorption of sodium and water were not significantly altered. Unidirectional potassium movement into the body increased in all the ileal fistulas.

Animals↗

Intestinal absorption of drugs. I: The influence of taurocholate on the absorption of dantrolene in the small intestine of the rat.

The influence of sodium taurocholate (1) on the intestinal absorption of the lipophilic drug dantrolene (2) was studied in vivo in a chronically isolated internal loop in the rat. Concentrations of 2 were kept below the saturation concentration in saline. Absorption kinetics of 2 were evaluated on the basis of steady-state blood levels, which develop during single-pass perfusions, and on the basis of the rate of disappearance of the drug from the perfusate during recirculating perfusions. Compound 1 at a concentration of 10 mM in the perfusate induced a twofold reduction of the absorption rate compared with the same concentration of 2 in saline. Pretreatment of the absorptive surface with a 10 mM solution of 1 had no detectable effect on the absorption rate of 2 in saline. After perfusions with 10 mM solutions of 1, the perfusate concentration of proteins, phosphorus, and hexoses in the effluent was increased. The reduction of the absorption rate can be ascribed mainly to a reduction of the thermodynamically active concentration of 2 as calculated from the phase-separation model. In addition, 10 mM 1 seems to temporarily increase the barrier function of the mucous layer.

Animals↗