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Methionine and 2-hydroxy-4-methylthiobutanoic acid are partially converted to nonabsorbed compounds during passage through the small intestine and heat exposure does not affect small intestinal absorption of methionine sources in broiler chicks.

Broiler chicks were fed diets supplemented with DL-methionine or DL-2-hydroxy-4-methyl-thiobutanoic acid. At 4 wk of age the chicks were subdivided into thermoneutral (22 degrees C) and heat-exposed (32 degrees C) groups and maintained under these conditions for 48 h. Highly purified 3H-L-methionine (3H-L-Met) and 3H-L-2-hydroxy-4-methyl-thiobutanoic acid (3H-L-HMB) were used to evaluate treatment effects on the small intestinal passage of sources of supplemental methionine and on the transport of methionine sources across purified small intestinal brush border vesicles. 3H-L-Met was efficiently absorbed in the upper regions of the small intestine; however, 2.5-3.5% of dietary 3H from birds fed 3H-L-Met remained unabsorbed in the distal small intestine. Dietary 3H (15%) initially associated with 3H-L-HMB was not absorbed during passage down the length of the gut. The HPLC analysis indicated that only 10% of the radiolabeled material remaining in the terminal ileum eluted at the time expected for HMB. Partial breakdown of HMB to nonabsorbed, nonmethionine products during passage down the small intestine may contribute to the difference in biopotency of the two sources of supplemental dietary methionine. Heat exposure did not affect in vivo small intestinal passage or in vitro transport of 3H-L-Met and 3H-L-HMB across small intestinal brush border membrane vesicles.

Animals↗

Segmented filamentous bacteria are indigenous intestinal bacteria that activate intraepithelial lymphocytes and induce MHC class II molecules and fucosyl asialo GM1 glycolipids on the small intestinal epithelial cells in the ex-germ-free mouse.

In ex-germ-free mice conventionalized by association with fecal microorganisms, the induction fo major histocompatibility complex class II molecules and fucosylation of asialo GM1 glycolipid occur in the small intestinal epithelial cells (IEC). The intestinal intraepithelial lymphocytes (IEL), especially alpha beta T-cell receptor-bearing ones, also remarkably expand and show cytolytic activity. In this study, we investigated the immunological and physiological characteristics of the small intestine induced by a kind of indigenous bacteria of the small intestine, segmental filamentous bacteria (SFB), among chloroform-resistant intestinal bacteria. Monoassociation of SFB with germ-free mice was confirmed by the determination of the base sequences of polymerase chain reaction products of 16S rRNA genes of the fecal bacteria of these mice and in situ hybridization using fluorescein-labeled probes based on them. SFB increased the number of alpha beta TCR-bearing IEL and induced Thy-1 expression and cytolytic activity of IEL. The induction of MHC class II molecules and fucosyl asialo GM1 glycolipids and the increases in the mitotic activity and the ratio of the number of columnar cells to those of goblet cells also occurred in the small intestinal epithelial cells on monoassociation of these bacteria. SFB are important indigenous bacteria for the development of the mucosal architecture and immune system in the small intestine, at least in mice.

Animals↗

Existence of an endogenous inhibitor of DNA synthesis in rabbit small intestine specifically effective on cell proliferation in adult mouse intestine.

Aqueous extracts from rabbit organs were prepared by homogenization and centrifugation at 105,000 g. After precipitation with ammonium sulphate, the 0-50 fraction was separated by ultrafiltration through Amicon XM 100 and XM 300 membranes yielding two filtrate fractions (U1 and U2) and one retentate fraction (U3). Only U1 and U3 inhibited thymidine incorporation into DNA. After a single injection of U1 from rabbit small intestine, the uptake of tritiated thymidine was decreased in mouse jejunal and colonic DNA. This effect, totally reversible after 7 hr, was found in neither the kidney nor the testis. The U1 fractions of colon and non-digestive organs (kidney, testis) were found not to exert a significant inhibition on thymidine incorporation into intestinal DNA in vivo. The U3 fraction from rabbit small intestine also decreased the uptake of tritiated thymidine in mouse jejunal and colonic DNA in vivo. However, this inhibition was irreversible and not tissue-specific. Slowing of cell migration was also noticed in the jejunum of mice injected with U1 or U3, as ascertained radioautographically by determining the position of the leading edge of the labelled cells in U1- or U3-injected mice compared with controls. A decrease of mitotic activity in U1- and U3-injected mice was recorded 8.5 hr after a single injection of small intestinal fractions. Our results suggest that U1 and U3 from rabbit small intestine contain one or more substances which may act on the G1-S transition of the cell cycle in the mouse intestine. However, only the effect of U1 is reversible and tissue specific. Our data suggest the existence of a factor, having a low molecular weight, which regulates intestinal cell proliferation.

Animals↗

Intestinal permeability testing in dogs with diet-responsive intestinal disease.

Fifteen dogs with signs of small and, or, large bowel disease that responded clinically to an exclusion diet were studied, using differential sugar absorption as an objective parameter of the mucosal response to the diet. Intestinal permeability and function were assessed by determining the urinary excretion ratios of lactulose/rhamnose and xylose/3-O-methylglucose, respectively, following oral administration of a mixture of these four sugars. Five dogs, all retrievers, were tentatively diagnosed as having dietary hypersensitivity, based upon resolution of clinical signs and normalisation of high intestinal permeability following an exclusion diet and recurrence of signs (in four of five dogs) upon challenge with the original diet. The fifth dog did not become symptomatic when challenged, but intestinal permeability increased. The remaining 10 dogs were diagnosed as having food intolerance, based upon clinical improvement on an exclusion diet, relapse on challenge with their original diet, but lack of improvement in intestinal permeability. These findings suggest that a differential sugar absorption test may be useful to determine the reasons for clinical response to exclusion diets. Demonstration of increased intestinal permeability with subsequent normalisation following an exclusion diet may be useful in the diagnosis of dietary hypersensitivity, while persistent abnormalities in intestinal permeability are suggestive of underlying intestinal disease and food intolerance.

Analysis of Variance↗

Pharmacokinetic modelling of the effect of activated charcoal on the intestinal secretion of theophylline, using the isolated vascularly perfused rat small intestine.

The effect of activated charcoal administration on the secretion of theophylline from the blood into the intestinal lumen has been examined by use of the rat isolated vascularly perfused small intestine. A closed two compartment model was used to analyse the vascular and luminal concentration-time curves obtained. An equation was derived to calculate the time-dependent intestinal clearance. From control experiments it was concluded that theophylline is secreted by a diffusional transport system through the intestinal wall. The intestinal clearance declined rapidly with time as a result of the concomitant increase in luminal theophylline concentration. After 120 min a steady state between the vascular and luminal perfusate was established. Administration of activated charcoal in the lumen had a profound effect on the kinetics of the drug. The vascular steady state concentration was depressed dramatically. The theophylline clearance remained nearly constant with time, because the blood to lumen concentration gradient was maximized. The maximal value for the intestinal theophylline clearance was estimated to be 0.88 mL min-1 and it equalled the value for the intestinal blood flow at the absorptive site. By use of the concept of absorptive site blood flow, the maximal effect of charcoal on systemic theophylline clearance could be adequately predicted for rats, dogs and man. Activated charcoal administration is only useful to enhance the systemic clearance of drugs or toxicants if that clearance is of the same order of magnitude as the absorptive site blood flow or lower.

Animals↗

Developmental changes in distribution of the mucous gel layer and intestinal permeability in rat small intestine.

BACKGROUND: From the developmental aspects, the distribution of fluorescein isothiocyanate dextran 70,000 (FTTC-dextran) and mucous gel across the lumen of small intestine was observed as an investigation into the role of mucous gel on intestinal permeability. Furthermore, the effect of N-acetyl cysteine (NAC), a mucolytic agent, on intestinal permeability was examined. METHODS: In suckling and weaned rats, FTTC-dextran (750 mg/kg body wt) was gavage-fed. After 3 hours, blood samples were taken by cardiac puncture to analyze plasma FTTC-dextran by fluorescence spectrometry. Samples of small intestine with luminal contents were frozen and sectioned in a cryostat for fluorescence microscopy; the same sections were placed in a 0.2% celloidin solution to preserve mucous gel and were stained by periodic acid-Schiff reaction for light microscopy. In weaned rats, intestinal permeability was examined with different concentrations of intraluminally instilled NAC. RESULTS: The plasma level of FTTC-dextran showed a significant increase (p < .01) in suckling rats compared with the weaned rats. Morphologic findings were similar in both the jejunum and ileum: The spaces between villi were not entirely filled with mucus but filled with FTTC-dextran in suckling rats, whereas the spaces were filled with mucus and not filled with FTTC-dextran in weaned rats. Intestinal permeability in groups with NAC were significantly higher (p < .01) than that in group without NAC. CONCLUSIONS: These results suggest that an increase in the mucous gel layer that coats the epithelial lining according to the maturation of the gastrointestinal tract is one of the most important factors for a restriction in intestinal permeability.

Acetylcysteine↗

Enhanced permeability of insulin across the rat intestinal membrane by various absorption enhancers: their intestinal mucosal toxicity and absorption-enhancing mechanism of n-lauryl-beta-D-maltopyranoside.

We have examined the in-vitro permeability characteristics of insulin in the presence of various absorption enhancers across rat intestinal membranes and have assessed the intestinal toxicity of the enhancers using an in-vitro Ussing chamber method. The absorption enhancing mechanism of n-lauryl-beta-D-maltopyranoside was studied also. The permeability of insulin across the intestinal membranes was low in the absence of absorption enhancers. However, the permeability was improved in the presence of enhancers such as sodium glycocholate and sodium deoxycholate in the jejunum, and sodium glycocholate, sodium deoxycholate, n-lauryl-beta-D-maltopyranoside, sodium caprate and ethylenediaminetetraacetic acid (EDTA) in the colon. Overall, the absorption enhancing effects were greater on the colonic membrane than on the jejunal membrane. The intestinal membrane toxicity of these enhancers was characterized using the release of cytosolic lactate dehydrogenase from the colonic membrane. A marked increase in the release of lactate dehydrogenase was observed in the presence of sodium deoxycholate and EDTA. The release of lactate dehydrogenase in the presence of these absorption enhancers was similar to that seen with sodium dodecyl sulphate (SDS), used as a positive control, indicating high toxicity of these enhancers to the intestinal membrane. In contrast, sodium glycocholate and sodium caprate caused minor releases of lactate dehydrogenase, similar to control levels, suggesting low toxicity. In addition, the amount of lactate dehydrogenase in the presence of n-lauryl-beta-D-maltopyranoside was much less than that seen with sodium deoxycholate, EDTA and SDS. Therefore, sodium glycocholate, sodium caprate and n-lauryl-beta-D-maltopyranoside are useful absorption enhancers due to their high absorption enhancing effects and low intestinal toxicity. To investigate the absorption enhancing mechanisms of n-lauryl-beta-D-maltopyranoside, the transepithelial electrical resistance (TEER), voltage clamp experiments and the circular dichroism spectra were studied. n-Lauryl-beta-D-maltopyranoside decreased the TEER values in a dose-dependent manner, suggesting that the enhancer may open the tight junctions of the epithelium, thereby increasing the permeability of insulin via a paracellular pathway. This speculation was supported by the findings that 20 mM n-lauryl-beta-D-maltopyranoside produced a greater increase in the paracellular flux rate than in the transcellular flux rate by the voltage clamp studies. Evaluating the circular dichroism spectra we found that insulin oligomers were not dissociated to monomers by the addition of n-lauryl-beta-D-maltopyranoside, but dissociation did occur with the addition of sodium glycocholate. Thus, the dissociation of insulin was not a major factor in the absorption enhancing effect of n-lauryl-beta-D-maltopyranoside. These findings provide basic information to select the optimal enhancer for the intestinal delivery of peptide and protein drugs including insulin.

Algorithms↗

Concentration-dependent atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts as an interface between the body and ingested compounds.

Intestinal absorption of peptides in linear form has been studied extensively, but there is little knowledge of peptides in a cyclic form. In this report, intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor of gliotoxin, was studied in isolated rat small intestine as a model cyclic dipeptide. Absorption clearance (CLabs) decreased in the presence of glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 degrees C, thus indicating that cyclo(Phe-Ser) is in part transported by PEPT1. However, the Eadie-Hofstee plot of absorption revealed an atypical profile at lower concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative experiments of absorptive and excretive transport showed that excretive transport from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the serosal side, and vice versa at a 1 mM cyclo(Phe-Ser). A kinetic model was constructed, in which cyclo(Phe-Ser) concentration for excretive transport was assumed to be at the binding site of excretive transporter, but not the unbound cytoplasmic concentration. These results as well as the results of kinetic analysis indicate that intestinal absorption consists of passive transport, carrier-mediated absorptive transport by PEPT1 and carrier-mediated excretive transport, resulting in atypical absorption. Although cyclic dipeptides have potentials as drugs, their intestinal absorption may be complex. The results of this study lead us to conclude that absorptive and excretive transport by the small intestine acts as an interface between the body and ingested compounds.

Animals↗

Evidence that neuronally released vasoactive intestinal polypeptide inhibits the release of serotonin from enterochromaffin cells of the guinea pig small intestine.

Isolated small intestinal segments of the guinea pig were arterially perfused and the release of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were intra-arterially applied. The muscarine receptor agonist oxotremorine (1 mumol/l) inhibited the release of 5-hydroxytryptamine by about 50%. In the presence of the neurotoxin tetrodotoxin, oxotremorine enhanced the release of 5-hydroxytryptamine by 145%, indicating that the inhibitory effect of oxotremorine was mediated by the release of a neurotransmitter. Exogenous vasoactive intestinal polypeptide (1-100 pmol/l) inhibited the release of 5-hydroxytryptamine by about 50%, an effect antagonized by a specific antibody to vasoactive intestinal polypeptide. This antibody to vasoactive intestinal polypeptide, on its own, had no effect on the release of 5-hydroxytryptamine. However, it prevented the inhibitory effect of oxotremorine. In the presence of the antibody to vasoactive intestinal polypeptide, unlike in the presence of tetrodotoxin, oxotremorine did not stimulate the release of 5-hydroxytryptamine. In conclusion, activation of neuronal muscarine receptors in the guinea pig small intestine enhances the release of several neurotransmitters which can inhibit the release of 5-hydroxytryptamine. The present experiments provide good evidence that vasoactive intestinal polypeptide is one of them.

Animals↗

Experimental studies on fluid pathophysiology in small intestinal obstruction in the rat. V. Effects of intraluminal hyperosmolality and simultaneous intravenous infusions on the experimentally obstructed and decompressed small intestine.

An influx of fluid into the lumen of the intestine similar to that seen in simple obstructional ileus may be provoked by introducing a hyperosmolal glucose solution into the bowel. In the otherwise intact small intestine the effect of this influx of fluid will be in accordance with a simple dilution curve. The intestinal mucosa thus functions in the manner of a semipermeable membrane permitting only hypo-osmolal fluids to enter the intestinal lumen and in amounts independent of parenteral fluid infusions, regardless of osmolality. This relationship persists even after the intestine has been totally obstructed for 3 days. The influx of fluid has the same principal characteristics, and the only limiting factor on the magnitude of this fluid shift to the intestine is the lack of fluids resulting from the marked dehydration of the organism due to ileus. Prerequisites for this are normal epithelial function and normal mucosal circulation. Thus it is clear that the organism in general and the small intestine in particular, even when exposed to prolonged obstruction, are still able to counteract intraluminal hyperosmolality by dilution with hypo-osmolal fluid.

Animals↗

Relationship between small-intestinal transit rate and intestinal absorption of (14)C-labelled mannitol and (51)Cr-labelled ethylenediaminetetraacetic acid in healthy subjects.

BACKGROUND: Although the small-intestinal transit rate is generally considered to influence the urinary excretion of markers of intestinal permeability, no study has until now formally addressed the importance of this influence in humans. METHODS: Ten healthy subjects ingested a test solution containing (99m)Tc-labelled diethylenetriaminepentaacetic acid ((99)mTc-DTPA), (14)C-labelled mannitol ((14)C-mannitol), and (51)Cr-labelled ethylenediaminetetraacetic acid ((51)Cr-EDTA). After ingestion, the small-intestinal transit rate of (99)mTc-DTPA was measured with the gamma camera technique. Urine was collected for time periods of 0-2 h, 2-4 h, and 4-6 h to measure the excretion of absorbed (14)C-mannitol and (51)Cr-EDTA. Moreover, the distribution volume and plasma clearance of (14)C-mannitol and (51)Cr-EDTA were determined in each subject. RESULTS: A positive correlation was found between mean small-intestinal transit time and 0- to 6-h urinary excretion of (14)C-mannitol. The study did not show any correlation between small-intestinal transit rate and 0- to 6-h urinary excretion of (51)Cr-EDTA. Urinary excretion of neither (14)C-mannitol nor (51)Cr-EDTA was affected by distribution volume or urine volume. A positive correlation was observed between plasma clearance and 0- to 6-h urinary excretion of (14)C-mannitol, whereas plasma clearance did not influence the urinary excretion of (51)Cr-EDTA. CONCLUSIONS: Small-intestinal transit rate seems to have a significant effect on 0- to 6-h urinary excretion of (14)C-mannitol, whereas small intestinal transit rate does not influence the timed urinary excretion of (51)Cr-EDTA.

Adult↗

Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation.

Methadone and levo-alpha-acetylmethadol (LAAM) are opioid agonists used for analgesia and preventing opiate withdrawal. Methadone is sequentially N-demethylated to the inactive metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyraline (EMDP). LAAM is essentially a prodrug that undergoes bioactivation via sequential N-demethylation to levo-alpha-acetyl-N-normethadol (nor-LAAM) and levo-alpha-acetyl-N,N-dinormethadol (dinor-LAAM). Methadone and LAAM are metabolized by CYP3A4 in human liver. Since they are administered orally, and CYP3A4 is expressed in human intestine, we tested the hypotheses that human intestine can metabolize methadone and LAAM, and evaluated the participation of CYP3A4. Intestinal microsomal methadone N-demethylation exhibited hyperbolic noncooperative kinetics and biphasic Eadie-Hofstee plots. Using a dual-enzyme Michaelis-Menten model, K(m) values were 11 and 1200 microM for EDDP and 23 and 930 microM for EMDP formation, respectively. CYP3A4 inhibitors (troleandomycin and ketoconazole) inhibited EDDP and EMDP formation by >70%. Methadone N-demethylation by CYP3A4 showed biphasic Eadie-Hofstee plots without evidence of positive cooperativity; K(m) values were 10 and 1100 microM for EDDP and 20 and 1000 microM for EMDP formation. Intestinal microsomal LAAM and nor-LAAM N-demethylation also exhibited hyperbolic kinetics and biphasic Eadie-Hofstee plots. K(m) values were 21 and 980 microM for nor-LAAM from LAAM and 18 and 1200 microM for dinor-LAAM from nor-LAAM. Troleandomycin and ketoconazole inhibited N-demethylation by >70%. LAAM and nor-LAAM metabolism by CYP3A4 showed biphasic Eadie-Hofstee plots without evidence of positive cooperativity; K(m) values were 8 and 1300 microM, 6 and 950 microM, respectively. Predicted in vivo intestinal extraction of methadone and LAAM is 21 and 33%, respectively. We conclude that methadone, LAAM, and nor-LAAM are metabolized by human intestinal microsomes; CYP3A4 is the predominant cytochrome P450 isoform; CYP3A4-catalyzed methadone, LAAM, and nor-LAAM metabolism is characterized by noncooperative, multisite kinetics; and intestinal metabolism may contribute to presystemic methadone inactivation and LAAM bioactivation.

Algorithms↗

[Transmesenteric intestinal plication for intestinal occlusion secondary to disseminated adhesions. A 12-year experience].

OBJECTIVE: To report the experience with intestinal plication in patients with adhesive intestinal obstruction that was followed up to 12 years. BACKGROUND: To diminish the high recurrence rate of adhesive intestinal obstruction, there are surgical techniques of intestinal plication. In 1977 Blanco modified a pre-existing transmesenteric technique that is the used in our institution. METHOD: We studied the medical records of 32 patients who underwent intestinal plication using the transmesenteric technique. The postoperative evaluation was based in recurrence and mortality. RESULTS: There were 32 patients, 56% women and 44% men, with a mean age of 50 years. All patients had a history of intraabdominal surgical procedures. The postoperative evaluation was satisfactory. The success rate was over 90%. The recurrence rate was 9.3% and we had no mortality. The mean follow-up was 3.5 years (median 3 [range 1-12] years). There were no significant differences between this technique and the Noble and Childs-Phillips plication techniques. CONCLUSIONS: This technique of intestinal plication is useful in the surgical management of patients with adhesive intestinal obstruction.

Adolescent↗

Mucosal lesions of the small intestine after intestinal vascular obstruction in the rat.

Small intestinal mucosal lesions, characteristically restricted to the villous tissue, have been described in shock states of different types. We have found this type of mucosal lesion in a standardized intestinal ischemia shock in rat. The pathophysiology of the mucosal lesion has been debated. In earlier work we noted a tenfold increase of platelets in the ischemic intestine. The importance of reperfusion and local platelet accumulation for the development of ischemic lesions in the intestinal mucosa was studied. Biopsy specimens taken immediately before and after reperfusion of the ischemic small intestine showed the same degree of mucosal lesion, i.e. total disintegration of the lamina propria. In thrombocytopenic rats subjected to intestinal ischemia, the severity of mucosal lesion was the same as in normothrombocytic rats. The results indirectly support the hypothesis of local villous oxygen deficit as the pathophysiologic mechanism leading to lesions of the small intestinal mucosa in shock.

Animals↗

[Application of a potential difference to evaluate the absorptive faculty in the small intestine. The changes in potential differences, uptake of sugars and amino acid and electrical transmural resistance in injured intestine].

Since there was no effective method for evaluating the absorptive capacity in the small intestine, we devised a test for evaluating the absorptive capacity with potential difference. Potential difference is provided by electrical resistance of intestine and flux of substances. Previously, we reported that the electrical resistance of the small intestine in the guinea pigs had changed very slightly throughout the entire life, and that sugars and neutral amino acids have been transported completely activity from the birth. In addition, potential difference of glycyl-glycine reflected the uptake of the intestine after the period of weanling. We experimentally studied the electrical transmural resistance and absorptive capacity of the small intestine with various damages to the small intestine by 5-Fu, ischemia and long fasting. Histologically, swelling of nucleus, intracellular edema, dilatation of capillary vein, dropping of epithelial cells, etc., were seen in these models. But the electrical resistance was slightly changed in 10% of the cases. Potential differences by sugars or neutral amino acid ingestion accurately reflected their real flux. These facts suggest that the potential differences deficiently reflect the uptake of sugars and amino acids in the small intestine under conditions with malabsorption.

Amino Acids↗

The role of intestinal intubation in obstruction of the small intestine due to carcinoma of the ovary.

A total of 165 episodes of obstruction of the small intestine associated with carcinoma of the ovary were evaluated retrospectively to define the role of intestinal intubation. Patients with prolonged tube suctioning (greater than 48 hours) had a significantly higher operative mortality than patients operated upon immediately without prior intubation or after short term intubation of no longer than 48 hours (p less than 0.05). When controlled for risk factors, such as age, tumor status, ascites and amount and type of prior therapy, the difference between the groups was no longer significant (p greater than 0.1). Another variable of importance was the response to tube suction as documented by serial plain roentgenograms of the abdomen. Prolonged tube suction did not result in increased morbidity compared with short term intestinal intubation (p greater than 0.1) if decompression of the small intestine was accomplished within 48 hours of admission. Nonoperative therapy by intestinal intubation rarely relieves small intestinal obstruction caused by carcinoma of the ovary. It may, however, relieve distension of the small intestine proximal to the obstruction, thus preventing anatomic and metabolic changes that contribute to poor outcome when surgical treatment for relief of the obstruction is delayed.

Aged↗

Compensation by the residual intestine after intestinal resection in the rat. I. Influence of amount of tissue removed.

Thirty days after resection of 10 to 80% of the midportion of the small intestine, excluding the duodenum, several cell kinetic parameters were investigated in the residual intestine. The degree of intestinal response increased in a stepwise fashion as the amount of tissue removed was increased. The response involved marked increases in: DNA synthesis per crypt expressed as disintegrations per minute of tritium (3H) reflecting (3H)thymidine incorporation, cells per crypt column, 3H-labelled cells per crypt column, cells per villus column, and thickness of all intestinal wall components. These changes occureed throughout the small intestine even at lesser resections. ""Crypt profiles'' reflected changes in cell counts, but when the labeling frequency of proliferative cells was expressed as a percentage of the total crypt height, there was no change. The total number of crypts in the duodenum remained unchanged and the total number of cyrpts in the residual jejunum plus ileum decreased proportionally to the amount of tissue removed. Intestinal compensation occurred by increasing the size of the structures present in the residual intestine, not by increasing the number of structural units.

Adaptation, Physiological↗

Increased intestinal absorption of cefixime by nifedipine in the rat intestinal perfusion model: evidence for a neural regulation.

In healthy volunteers, the simultaneous administration of nifedipine and cefixime has been shown to increase the oral absorption of the antibiotic. To investigate the pharmacological basis of this interaction, we used an in situ intestinal perfusion technique in the rat. pH 5.5 yielded optimum cefixime absorption, which was greater in segments from the duodenojejunum than in those from the jejunoileum. Cefixime absorption was similar when perfused at 0.5 and 1.0 mg/ml, suggesting transport saturation at the lower concentration. Cefixime arterial and portal blood concentrations after an intestinal perfusion of 0.5 mg/ml cefixime were significantly increased by a previous 15-min intestinal perfusion of 0.05 mg/ml nifedipine. Nifedipine did not significantly alter intestinal blood flow. At the end of the cefixime perfusion, intestinal blood flow was higher in the nifedipine group than in the control group (0.44 +/- 0.12 vs. 0.26 +/- 0.09 ml.min-1.g of intestine wt-1, respectively), although the difference did not reach statistical significance. The absorption kinetics of salicylic acid, which is strictly absorbed by passive diffusion, were unaffected by nifedipine. After 15 and 50 min of recirculation, residual salicylate levels fell from 85.1 +/- 5.6% to 57.1 +/- 2.8% with nifedipine compared with 87.4 +/- 1.4% to 52.8 +/- 1.6% without nifedipine. Thus, the improvement in cefixime absorption by nifedipine was not secondary to increased local blood flows or to induced passive diffusion mechanisms. Nifedipine did not affect intestinal motility. The action of nifedipine appears to indirect, involving a neural regulation, because any increase in cefixime absorption was prevented by tetrodotoxin and hexamethonium administration.

Animals↗