Effect of extensive small bowel resection on the enzyme secretory function of the stomach

Summary In 9 dogs with stomachs isolated after Pavlov and Heidenhain and with stomach fistulas, a study was made on the secretion of pepsin with gastric juice in response to meat, hematogen, histamine and alcohol sham feeding with meat as well as on the pepsinogen content of the blood serum and secretion of uropepsin with 24 h urine before and after an extensive resection of the small intestine (50–70%). Following excision of the proximal portion of the small intestine in 5 dogs, the secretion of pepsin with gastric juice, the pepsinogen and uropepsin levels increased, while in 4 dogs, which had undergone resection of the distal portion of the small intestine, no substantial change in these responses was noted with regard to most of the stimulating agents. The possibility is discussed of using the determination of the pepsinogen and uropepsin content for conclusion on the enzyme-secretory function of the stomach.(Presented by Academician V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 59, No. 5, pp. 42–47, May, 1965     

Role of gastrin in gastrointestinal adaptation after small bowel resection

Gastrin is a trophic hormone for the mucosa of the oxyntic gland area of the stomach, the proximal small intestine, and the colon. It also has trophic effects on the pancreas. All these tissues undergo hyperplasia to some extent following distal small bowel resection. This study evaluates the role of gastrin in postresectional hyperplasia by examining the growth of these tissues in antrectomized rats following intestinal resection. Antrectomy itself caused atrophy of the oxyntic gland mucosa, colonic mucosa, and the pancreas but had no effect on ileal mucosa. Resection by itself stimulated growth of all tissues and significantly increased serum gastrin levels. After resection in antrectomized animals, all tissues underwent an adaptational response. The increase in total DNA content after resection in antrectomized rats was as great in all tissues, except the colon, as it was in animals with intact antrums and normal gastrin levels. These results indicate that gastrin plays no role in the postresectional hyperplasia observed in the various tissues of the gastrointestinal tract.     

Glutamine on the luminal microbial environment after massive small bowel resection

To evaluate the oral glutamine (GLN) on the luminal microbes and bacterial translocation (BT) in short bowel, 45 Wistar rats were utilized in three groups; A (control), and B and C (short bowel, 85% of small bowel resected). The group A was fed with elemental diet (EmD), B with EmD+2% glycine, and C with EmD+2% GLN. The groups B and C were isocaloric and isonitrogenous. Wet weight, DNA, protein, and histomorphometry of the mucosa and parallel microbial culture from cecal contents, caval blood, and tissue blocks of the liver, spleen, and mesenteric lymph nodes were performed on the 5th, 10th, and 15th day. Mucosal growth was higher in group C than B. Colony forming units (CFU) from cecal contents increased more in group B than in C. BTs in A, B, and C were 7/15, 8/15, and 2/15, respectively. Total CFUs in blood and tissues were 5.8 X 10(4)/g, 5.5 X 10(6)/g, and 1.8 X 10(4)/g, respectively. As for BT, the most frequent organism was Klebsiella in A (79.3%), but E. coli in B and C (94.2% and 55.6%). GLN seems to suppress luminal microbes, and reduces BT in short bowel due to enforced barrier function and proliferation of the mucosa.     

Effects of trimebutine on intestinal motility after massive small bowel resection.

Effects of trimebutine maleate (TM) on intestinal motility in short bowel syndrome (SBS) were studied in conscious canines in both acute and chronic phases following 80% massive distal small bowel resection (MSBR). TM was administered orally to beagles with MSBR or as controls in the postprandial and fasting states, and given simultaneously with meals. Intestinal motility was measured using bipolar electrodes for approximately 1 month after the electrodes were implanted in each beagle and the data compared between treatment groups. When TM was given with meals, the postprandial period without duodenal migrating myoelectric (or motor) complexes (MMCs) was shorter than in those given meals only. When TM was given in the postprandial state in short bowel beagles, the initial duodenal MMCs occurred earlier, i.e. the postprandial period was shorter. Diarrhea did not occur in these beagles. When TM was given in the fasting state, duodenal MMCs occurred and propagated to the distal intestine. In conclusion, oral TM administration can produce a more appropriate intestinal condition for the next food intake and make enteral nutrition possible even in the acute phase after MSBR. Such feeding can be carried out without overloading gut function as a result of the modulation of gastrointestinal motility by TM.     

Separation of adaptive mucosal growth and transport after small bowel resection

In rats 70% of the small bowel was resected with preservation of duodenum and terminal ileum. Two and four weeks later transport of sodium, chloride, water, and galactose was studied in duodenum and ileum. Controls were sham-operated and unoperated rats. There was significant mucosal growth 2 and 4 wk after resection. By 2 wk postresection transport specific activities (transport per gram mucosa) were generally decreased. Mucosal growth compensated only sufficiently so that transport capacities (transport per centimeter segment length) remained unaltered from controls. By 4 wk postresection transport specific activities had either increased or were unchanged from controls. Therefore, in association with mucosal growth, transport capacities increased. The major adaptive increases for electrolytes and water occurred in duodenum; ileum was the site of increased galactose transport. The data indicate that 1) mucosal growth and functional transport changes occur as separate adaptive phenomena and 2) adaptive transport mechanisms are selectively localized to particular regions of the intestine.     

Effect of some new H2-receptor antagonists on gastrointestinal motility

Inflammation Research - Some new histamine H2-receptor antagonists were tested for their effects on gastrointestinal motility. Ranitidine was found to possess definite stimulatory effects which...     

Evaluation of combined H1- and H2-receptor blocking agents in the treatment of seasonal allergic rhinitis

During an 8 wk period (September 23 to July 30) 23 patients with histories of late-summer allergic rhinitis received, on a random basis, alternating 2 wk courses of either chlorpheniramine (anti-H1), 12 to 48 mg/day, plus placebo, or anti-H1 in the same dose plus cimetidine (anti-H2), 300 mg t.i.d. Symptom (SX) and medication (MED) scores were recorded twice daily. After the season the immediate (ICR) and late (LCR) reactions to allergens and histamine were measured in six of these patients while on: (1) no drugs, (2) anti-H1 plus placebo, or (3) anti-H1 plus anti-H2 in the doses employed during the season. Mean weekly SX scores were significantly lower on anti-H1 plus anti-H2 compared with anti-H1 plus placebo during the sixth week of the study (p less than 0.001). MED scores were lower on the anti-H1 and anti-H2 combination than on anti-H1 alone during weeks four and five (p less than 0.02). In the six patients studied after the season, the ICRs were consistently smaller with the anti-H1 and anti-H2 combination, but the differences were only significant for the histamine-induced wheal (p less than 0.01). In this study of allergic rhinitis there appeared to be a small but statistically significant additive effect of anti-H2 to the clinical response to anti-H1. No additional side effects were noted.     

Histamine H2-receptor blocking activity of ranitidine and lamtidine analogues containing aminomethyl-substituted aliphatic systems

The possibility that the aromatic component in the classical H₂-antagonists might not be essential for histamine H₂-receptor blockade has been investigated. In the ranitidine series the removal of the furan ring is accompanied by a drastic decrease in H₂-blocking activity, but not by its disappearance (compound HB5: K_B on guinea pig isolated atria 31.6 M) whereas in the lamtidine analogues the substitution of the phenyl moiety with the more reduced -bonded CH₃-C=N-area generates a compound whose activity is comparable to that of cimetidine (K_B on atria 1.12M; ID₅₀ in the lumen-perfused stomach of the anaesthetized rat 3.61 mol/kg i.v.). The results also indicate that the diaminofurazan group confers high affinity at the histamine H₂-receptor.It is concluded that the aromatic portion of H₂-antagonists related to ranitidine and lamtidine is not a minimal requisite for activity when an appropriate polar group is used as an urea equivalent moiety.     

Haemodynamic effects of roxatidine,an H2-receptor antagonist

Summary The haemodynamic effects of roxatidine were investigated in 12 patients with congestive heart failure (New York Heart Association class II) in a placebo-controlled, double-blind, randomized, cross-over study. Impedance and mechanocardiography were determined following successive 7-day treatment periods with placebo and roxatidine 150 mg once daily. Comparison with placebo values showed roxatidine to significantly increase the preejection period (109.7 ± 2.7 ms versus 117.3 ± 2.7 ms, 1.5 h after administration). Heart rate and blood pressure remained the same. In contrast to other, newer H₂-receptor antagonists, which decrease stroke volume and/or cardiac output, roxatidine did not reduce these parameters but increased the preejection period and the ratio of the preejection period to the left ventricular ejection time, indicating a slight negative influence on cardiac performance.Abbreviations CO cardiac output - CPT carotid pulse tracing - ECG electrocardiogram - LVET left ventricular ejection time - PCG phonocardiogram - PEP preejection period - STI systolic time intervals     

New ranitidine analogues containing the 2-aminobenzimidazole moiety:in vivo andin vitro histamine H2-receptor blocking activity

The paper reports the pharmacological profile of a new series of ranitidine analogues in which the diaminonitroethene group is replaced by the 2-amino-5(6)-substituted and unsubstituted benzimidazole moieties. These derivatives show a histamine H₂-receptor blocking activity comparable to that of the model bothin vitro (K _B on atria 0.16–1.15 M) andin vivo (ID₅₀ on the perfused stomach of the anaesthetized rat from 0.34 to 4.10 mol kg^–1 i.v.). The results are consistent with the hypothesis that, at least in the ranitidine analogues, the urea equivalent moiety may be replaced by a polar group partially ionized at physiological pH without loss of H₂-blocking activity.     

Characterization and heterogeneity of monoclonal antibodies directed to intestinal mucin derived from Crohn's disease small bowel

A panel of 12 monoclonal antibodies were produced by immunization of Balb/c mice with small bowel epithelial cells obtained from a patient with active well-documented Crohn's disease. The clones were derived by screening with immunofluorescence microscopy; those with staining patterns suggestive of mucin directed epitopes were chosen for study. Several distinct patterns of staining reactivity were noted, including reagents with homogeneous, luminal, heterogeneous and peripheral goblet cell activity. In addition, SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis revealed reactivity to high molecular weight mucin. The reactive antigen was resistant to proteinase digestion. No endoneuraminidase activity was detected; however, one neuraminidase sensitive sialic acid epitope was demonstrated. Confirmation of glycoprotein epitopes was accomplished by testing purified mucins from several areas of the gastrointestinal tract by ELISA. Finally, individual small bowel goblet cell heterogeneity was demonstrated by immunofluorescence, Western blotting, and antibody affinity chromatography. These data demonstrate both by morphology and specific binding of antibody affinity chromatography a significant degree of small bowel goblet cell mucin heterogeneity.     

Pseudopolyps of the small intestine in Crohn's disease

The morphologic features of two types of pseudopolyps of the terminal ileum in a patient with Crohn's disease are described. One form of pseudopolyp is indistinguishable from that observed in the large intestine in Crohn's colitis, while the second, nodular lymphangiectasia, seems to be unique to the small bowel.     

The electrophoretic analysis of low molecular weight nucleic acids from Crohn's disease tissues in the search for an unconventional small infections agent

Summary A small unconventional, viroid-like aetiological agent might initiate Crohn's disease (CD). Electrophoresis of radiolabelled low molecular weight nucleic acids from mesenteric lymph nodes and leucocytes did not distinguish CD-specific sequences compatible with a viroid-like agent.With 2 Figures