Maintaining intestinal H2 balance: credit the colonic bacteria.
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Patients with pneumatosis cystoides intestinalis have been reported to excrete excessive H2 because of a lack of H2-consuming intestinal bacteria. This study describes a patient with bacterial overgrowth and pneumatosis of the small intestine whose colonic flora avidly consumed H2 but whose small bowel flora produced but did not consume H2. There is no commonly accepted mechanism whereby excessive luminal H2 causes intramural gas. An explanation is proposed in which an initial, transitory source of intramural gas is distinguished from the mechanism that results in the persistence of the gas. Independent of the initial source of gas, rapid diffusion of H2 from the lumen into an intramural gas bubble would cause N2, O2, and CO2 to diffuse from the blood into the bubble. As a result, the bubble would expand and then persist indefinitely as long as H2 continued to diffuse from the lumen to the intramural gas collection.
Glucarate is normally present in tissues and body fluids and is in equilibrium with D-glucaro-1,4-lactone, a natural inhibitor of beta-glucuronidase activity. Dietary calcium glucarate, a sustained-release from of glucarate, elevates the blood level of D-glucaro-1,4-lactone which suppresses blood and tissue beta-glucuronidase activity. A single dose of CaG (4.5 mmole/kg body weight) inhibited beta-glucuronidase activity in serum and liver, lung, and intestinal microsomes by 57, 44, 37, and 39%, respectively. A chronic administration of calcium glucarate (4% in diet) also decreased beta-glucuronidase activity in intestinal and liver microsomes. Maximal inhibition of beta-glucuronidase activity in serum was observed from 12 noon to 2:00 PM. In contrast, maximum inhibition of beta-glucuronidase activity in intestinal and liver microsomes occurred during mornings, although a secondary depression in intestinal microsomes also occurred around 4 PM. A 4% calcium glucarate supplemented diet also inhibited beta-glucuronidase activity by 70% and 54%, of the bacterial flora obtained from proximal (small intestine) and distal (colon) segments of intestine, respectively. Due to the potential effect of dietary glucarate on net glucuronidation and on other metabolic pathways, glucaric acid levels in various foods were determined. The glucaric acid content varied from a low of 1.12-1.73 mg/100 g for broccoli and potatoes to a high of 4.53 mg/100 g for oranges.
Knowledge of the structure and catalytic function of the pancreatic proteases has increased rapidly in recent years. These advances have been less spectacular in the case of pepsin, and information concerning mucosal enzymes of the small intestine and colon has not even reached the point where one can be certain of their number, far less their nature. The role of these enzymes in disease processes is probably not significant so far as the alimentary tract is concerned, and it is not even certain that the pancreatic proteases influence the course of acute pancreatitis -- they are of more interest to the clinician as diagnostic aids. Since undesirable consequences result from their deficient output, future research should be directed towards improving replacement therapy.
BACKGROUND & AIMS: Apobec-1 is an RNA-specific cytidine deaminase whose forced overexpression in transgenic animals is associated with hepatic carcinogenesis. Apobec-1 messenger RNA (mRNA) undergoes alternative splicing, generating a catalytically inactive peptide, apobec-T. We have examined apobec-1 gene expression in human gastrointestinal tumors and in colon cancer-derived cell lines. METHODS: Levels of the full-length (apobec-1) and alternatively spliced (apobec-T) mRNAs were measured by RNase protection assay, and apobec-T distribution was determined by immunocytochemical localization. RESULTS: Apobec-1 mRNA was detectable in normal and colon cancer tissue, metastatic nodules, and certain colon cancer-derived cell lines. Apobec-T mRNA abundance was increased an average of 3.5-fold in colon cancers compared with paired control tissue (range, 0.5-14-fold). Immunocytochemical analysis showed apobec-T expression in normal fetal and adult colon and in gastric and small intestinal adenocarcinomas, colonic tubular adenomas, and both primary and metastatic colonic tumors. Overexpression of apobec-T in a tetracycline-responsive cell line decreased cellular proliferation. CONCLUSIONS: Apobec-T is expressed in normal, adenomatous, and cancerous gastrointestinal tissues, and levels of the mRNA encoding this peptide are significantly increased in colon cancer. Although its relationship to colon carcinogenesis has not been defined, the regulated overexpression of apobec-T is associated with an altered growth phenotype.
Hemolytic E. coli strain 807-13, O149:NM:K88(STb+, LT+), was isolated from the feces of a neonatal diarrheic foal. E. coli 807-13 was examined for adhesion to brush border membranes (BBM) from foals, adult horses and pigs, and its pathogenicity was assessed in neonatal foals and pigs. E. coli 807-13 did not adhere to equine BBM but adhered to pig BBM. It did not cause diarrhea nor did it colonize the intestinal epithelium of 3 colostrum-deprived and 3 suckled foals challenged at 24 h of age. Acute ulcerative gastritis and acute suppurative gastritis were observed in 2 colostrum-deprived challenged foals, and acute neutrophilic enteritis was observed in 1 colostrum-deprived and in 1 suckled challenged foal. No similar histopathologic lesions were detected in the control foals. Both gnotobiotic and suckled pigs developed diarrhea after challenge exposure to E. coli 807-13 and the intestinal epithelium of the pigs was colonized. Histopathologic evidence of gastritis and enteritis among the foals indicated some complicity of E. coli 807-13 in foal enteric disease.
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Induction of gene expression can be accomplished either by removing a restraining element (negative mode of control) or by providing a stimulatory element (positive mode of control). According to the demand theory of gene regulation, which was first presented in qualitative form in the 1970s, the negative mode will be selected for the control of a gene whose function is in low demand in the organism's natural environment, whereas the positive mode will be selected for the control of a gene whose function is in high demand. This theory has now been further developed in a quantitative form that reveals the importance of two key parameters: cycle time C, which is the average time for a gene to complete an ON/OFF cycle, and demand D, which is the fraction of the cycle time that the gene is ON. Here we estimate nominal values for the relevant mutation rates and growth rates and apply the quantitative demand theory to the lactose and maltose operons of Escherichia coli. The results define regions of the C vs. D plot within which selection for the wild-type regulatory mechanisms is realizable, and these in turn provide the first estimates for the minimum and maximum values of demand that are required for selection of the positive and negative modes of gene control found in these systems. The ratio of mutation rate to selection coefficient is the most relevant determinant of the realizable region for selection, and the most influential parameter is the selection coefficient that reflects the reduction in growth rate when there is superfluous expression of a gene. The quantitative theory predicts the rate and extent of selection for each mode of control. It also predicts three critical values for the cycle time. The predicted maximum value for the cycle time C is consistent with the lifetime of the host. The predicted minimum value for C is consistent with the time for transit through the intestinal tract without colonization. Finally, the theory predicts an optimum value of C that is in agreement with the observed frequency for E. coli colonizing the human intestinal tract.
Many methods are used for vaginoplasty, including the split-thickness skin graft, full-thickness skin graft, and inverted penile skin flap. However, these procedures are not entirely satisfactory in cases of reconstructed vaginal stenosis, inadequate vaginal length, or poor lubrication. The small intestine, ascending colon, and sigmoid colon can be used in the intestinal flap method, and the authors modified the operation first described by Baldwin in which a loop of rectosigmoid is isolated, closed at one end, and brought down on its vascular pedicle as a neovagina and then anastomosed to the perineum. Vaginoplasty using the rectosigmoid was performed in 36 patients (28 male-to-female transsexual patients, five patients with congenital vaginal atresia, and three with cervical cancer). The follow-up period ranged from 1 to 10 years. The postoperative results were analyzed through physical examination and interview regarding the patient's functional status and satisfaction during sexual intercourse. The mean depth and width of the vaginal cavity were 12.5 cm and 3.9 cm, respectively. Excessive mucosal discharge was seen in 8.3 percent, and malodor was found in 8.3 percent. All patients who had partners were able to have sexual intercourse; 2.8 percent of patients used lubricants and 5.6 percent used dilators before intercourse for more than a year postoperatively. During intercourse, 88.9 percent of the patients experienced orgasm. The cosmetic and functional results of rectosigmoid vaginoplasty were excellent. Thus, the advantages of rectosigmoid vaginoplasty are (1) rare contraction of the reconstructed vagina, (2) vaginal width and depth maintained without long-term vaginal stent, (3) spontaneous mucus production facilitating sexual intercourse, (4) avoidance of the malodor frequently accompanying skin graft, and (5) texture and appearance similar to that of the natural vagina. The authors concluded that rectosigmoid vaginoplasty is the best choice for transsexual patients who have previously undergone penectomy and orchiectomy, patients with unfavorable previous vaginoplasty, those with short vaginal length after cervical cancer surgery, and patients with congenital vaginal atresia.
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Radiotherapy plays nowadays an important role in malignancies treatment. However, collateral effects and severe complications owing to cellular damage of peritumoral tissues may occur. Different nutritional resources have been recently indicated to achieve intestinal protection during cancer irradiation. PURPOSE--The aim of this study was to set the role of glutamine and elemental diets in acute actinic enteritis prevention. METHOD--Sixty-five adult male Wistar rats with average weight of 200g were maintained in individual metabolic cages; daily body weight and food ingestion were carefully monitored. The animals were randomized into three groups and fed isocaloric and isonitrogenous diets: 1) CRt-polymeric-casein diet; 2) GRt-polymeric-casein diet supplemented with 2% glutamine and 3) ERt-elemental diet supplemented with 2% glutamine. After an adaptation period (seven days), all rats received abdominal radiation in five daily doses of 300cGy. Four days after the rats were operated on to resect the small intestine and colon for histological evaluation. RESULTS--Small intestine histological data in ERt and GRt rats were better than CRt rats, by preserving mucosal cellularity and increasing mitosis number and villi length. Simultaneously, ERt group had greater number of rats with normal villus-crypt relation than CRt or GRt groups. Large intestine histological data showed that the average crypts length in ERt and GRt rats were greater than in CRt ones. CONCLUSION--Glutamine-supplemented polymeric or elemental diets given to rats before, during and after abdominal radiotherapy showed protective effects against radiation injury, by supporting mucosal structure and recovery.
BACKGROUND: The majority of patients with Crohn's disease will eventually have colonic involvement, and more than 50% of these patients undergo resectional colonic surgery. The extent of colonic resection is discussed controversially. AIMS: We evaluated prognostic factors influencing the long-term outcome after resectional surgery including the colon. METHODS: We analyzed the postoperative course in 170 patients (mean follow-up 7.4 years) after first colonic surgery. Lifetable and multivariate factor analysis were performed to assess the influence of various factors on the postoperative long-term outcome. 85% of the patients had concomitant ileal disease, 40% had rectal disease, 48% percent of the patients had extensive colonic disease at the time of primary surgery. RESULTS: In 17% of the initial operations a colectomy was performed, the remaining 83% operations consisted in segmental colonic resections. The cumulative risks of clinical recurrence/reoperation were 63%/33% after ten years and increased by the presence of anal fistulas (relative risk 1.7/3.0) and after colocolonic type of anastomosis (relative risk 1.9/2.8). Ileal disease, rectal disease, extent of resection and pattern of colitis did not influence the recurrence rates. The risk to undergo completion colectomy was 11% ten years after segmental resection and not higher in the presence of extensive colonic disease. The risk of a definitive stoma was 11% after ten years and higher after ileorectal anastomosis (25% versus 8% after segmental resection: p < 0.003). CONCLUSION: Colocolonic type of anastomosis and the presence of anal fistulas are risk factors for recurrence after initial colonic resection. Segmental resections were not followed by increased recurrence rates or a higher stoma rate. To maintain colonic length and intestinal continuity segmental colonic resection is the treatment of choice in patients undergoing surgery for local complications, even in the presence of extensive colonic disease.
Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of gastrointestinal infections. The host's innate immune system and a complex set of Salmonella virulence factors are thought to contribute to enteric disease. The serovar Typhimurium virulence factors have been studied extensively by using tissue culture assays, and bovine infection models have been used to verify the role of these factors in enterocolitis. Streptomycin-pretreated mice provide an alternative animal model to study enteric salmonellosis. In this model, the Salmonella pathogenicity island 1 type III secretion system has a key virulence function. Nothing is known about the role of other virulence factors. We investigated the role of flagella in murine serovar Typhimurium colitis. A nonflagellated serovar Typhimurium mutant (fliGHI) efficiently colonized the intestine but caused little colitis during the early phase of infection (10 and 24 h postinfection). In competition assays with differentially labeled strains, the fliGHI mutant had a reduced capacity to get near the intestinal epithelium, as determined by fluorescence microscopy. A flagellated but nonchemotactic cheY mutant had the same virulence defects as the fliGHI mutant for causing colitis. In competitive infections, both mutants colonized the intestine of streptomycin-pretreated mice by day 1 postinfection but were outcompeted by the wild-type strain by day 3 postinfection. Together, these data demonstrate that flagella are required for efficient colonization and induction of colitis in streptomycin-pretreated mice. This effect is mostly attributable to chemotaxis. Recognition of flagellar subunits (i.e., flagellin) by innate immune receptors (i.e., Toll-like receptor 5) may be less important.
We examined the capability of 12 isolates of non-cholera toxin-producing O1 and non-O1 Vibrio cholerae to colonize the small intestine of adult rabbits and cause diarrhea. Using the removable intestinal tie-adult rabbit diarrhea model, we found that eight environmental isolates that showed no or marginal biological activity in other diarrhea models (rabbit ileal loop, infant rabbit, and suckling mouse) appeared to be incapable of attaching to and colonizing, even transiently, the small intestinal mucosa of animals with normal clearance mechanisms. In contrast, three clinical isolates attached, proliferated rapidly, and colonized mucosal surfaces of the entire small intestine within 8 h of challenge. This led to diarrhea with strikingly high rates of mortality compared with that of rabbits given similar challenges doses with strains of O1 V. cholerae that produce cholera toxin and Vibrio mimicus, which produces a toxin similar to cholera toxin. We have further demonstrated that multiple exposures to enteric infection by these strains elicited local and serum antibodies that reacted strongly with cell surface antigens of the homologous strain and showed a high degree of cross-reactivity against the cell surface antigens of the two heterologous strains. The enteric infections appeared to engender protection against subsequent infection as well, as evidenced by reduced incidence of diarrhea and duration of fecal shedding of the challenge organism upon subsequent challenges.
One rabbit pathogenic Escherichia coli strain, belonging to serogroup O103, harbors a self-transferable 117-kb plasmid (pREC-1) encoding resistance to several antibiotics. The role of this R plasmid in the colonization of the digestive tract in specific-pathogen-free (E. coli O103-free) rabbits was studied. Five-week-old rabbits were inoculated with the wild-type strain, with its variant cured of the plasmid, with an E. coli K-12 strain, or with an untypeable E. coli strain from a healthy rabbit. No symptoms and no mortality were observed in animals inoculated with strains without the plasmid pREC-1, but 87.5% of the rabbits infected by the wild strain died, generally with bloody diarrhea, between days 5 and 15 postinfection. The weight gain of animals was strongly reduced. Transfer of the plasmid to the cured strain or to nonvirulent strains led these strains to induce the same pathology but with a lower mortality. Colonization of the gut by the O103 strain and symptoms of bloody diarrhea are thus related to the presence of the pREC-1 plasmid. The GV strain, which does not produce classical heat-labile enterotoxin or heat-stable enterotoxin and is not invasive, could be considered an enteropathogenic E. coli-like strain. The presence of a conjugative plasmid such as pREC-1 encoding both antibiotic resistance and virulence determinants in O103 E. coli from rabbits could represent a prominent epidemiological hazard under selective pressure by antibiotic therapy.
OBJECTIVE: To evaluate the influence of gender on the effect of a 5-HT3 antagonist, alosetron, 1 mg b.i.d., on GI and colonic transit in D-IBS. METHODS: Thirty patients (15 male, 15 female) with D-IBS received 1 mg b.i.d. alosetron for 6 wk. Transit was measured by scintigraphy at baseline and at the end of treatment. RESULTS: Alosetron, 1 mg b.i.d., significantly retarded small bowel and, proximal and overall colonic transit in the 30 patients with D-IBS. The effect of alosetron on the primary endpoint, colonic geometric center at 24 h, was significantly greater in females than in males (p < 0.05). However, two females showed no slowing of colonic transit on treatment. Among male patients, two of 15 had a slowing of colonic transit at 24 h that was greater than the mean change in female patients, suggesting responsiveness to alosetron among a subgroup of males. CONCLUSION: A 5-HT3 antagonist, alosetron, significantly retards small intestinal and colonic transit in diarrhea-predominant IBS patients, with significantly greater female to male responsiveness. Gender partly contributes to differences in the serotonergic control of intestinal and colonic transit in patients with D-IBS.
The authors report their observations of 164 patients with cancer of the colon, complicated by an acute intestinal obstruction, operated upon on urgent indications. Radical surgery was performed in 73 patients, the postoperative mortality being 31.5%. Palliative operations were performed in 91 patients, the mortality--60%. Rather short terms of the development of acute intestinal obstruction necessitate the accomplishment of one-movement operations with the mandatory decompression of the small intestine. In patients with long term intestinal obstruction the Zeidler-Schlotter operation should be preferred.