Induction of precocious intestinal maturation in T-cell deficient athymic neonatal rats

AIM To investigate whether gut maturation could be induced precociously in an athymic T-cell deficient neonatal rat model.METHODS Fourteen day-old athymic(nude) rats(NIH-Foxn 1 rnu) were gavaged with either phytohaemagglutinin-a lectin from red kidney beans(PHA); trypsin-a protease(Prot); or water-vehicle(control) as a single dose on one day or once a day for 3-day. The nude rats were either nurtured by their mothers or cross-fostered by conventional foster dams of the Sprague-Dawley strain from days 3-5 after birth. At 17 d of age, 72 h after administration of the first treatment, intestinal macromolecular permeability was tested in vivo, prior to euthanasia, after which blood and gut organs were sampled.RESULTS Provocation with both, PHA and protease, resulted in increased gut growth and maturation in nude rat pupsindependent of nursing. Foetal-type enterocytes were replaced by non-vacuolated adult-type enterocytes in the distal small intestine epithelium. Decreased intestinal macromolecular permeability(gut closure) was observed, with reduced permeability markers(BIg G and BSA, P 0.001) in circulation. Increased pancreatic function, with an increased trypsin to protein ratio in pancreas homogenates, was observed independent of nursing in the nude pups. Immunostaining showed the presence of a few CD3~+-cells in the intestinal mucosa of the nude pups. The number of CD3+-cells remained unaltered by provocation and no differences were observed between the nursing sets. Growth and vitality of the nude pups were dependent on nurturing, since cross-fostering by conventional dams increased their macromolecular absorptive capacity(BSA, P 0.05), as well as their passive immunity(RIg G, P 0.05).CONCLUSION Precocious gut maturation can be induced by enteral provocation in athymic rat pups, similarly to in euthymic pups, thus showing an independence from thymusderived T-cells.     

Small intestinal bacteria overgrowth decreases small intestinal motility in the NASH rats

AIM： To explore the relationship between small intestinal motility and small intestinal bacteria overgrowth （SIBO） in Nonalcoholic steatohepatitis （NASH）, and to investigate the effect of SIBO on the pathogenesis of NASH in rats. The effect of cidomycin in alleviating severity of NASH is also studied.
METHODS： Forty eight rats were randomly divided into NASH group （n = 16）, cidomycin group （n = 16） and control group （n = 16）. Then each group were subdivided into small intestinal motility group （n = 8）, bacteria group （n = 8） respectively. A semi-solid colored marker was used for monitoring small intestinal transit. The proximal small intestine was harvested under sterile condition and processed for quantitation for aerobes （E. coli and anaerobes （Lactobacilli）. Liver pathologic score was calculated to qualify the severity of hepatitis. Serum ALT, AST levels were detected to evaluate the severity of hepatitis.
RESULTS： Small intestinal transit was inhibited in NASH group （P 〈 0.01）. Rats treated with cidomycin had higher small intestine transit rate than rats in NASH group （P 〈 0.01）. High fat diet resulted in quantitative alterations in the aerobes （E. coli） but not in the anoerobics （Lactobacill）. There was an increase in the number of E. coli in the proximal small intestinal flora in NASH group than in control group （1.70 ± 0.12 log10 （CFU/g） vs 1.28 ± 0.07 log10 （CFU/g）, P 〈 0.01）. TNF-α concentration was significantly higher in NASH group than in control group （1.13 ± 0.15 mmol/L vs 0.57 ± 0.09 mmol/L, P 〈 0.01）. TNF-α concentration was lower in cidomycin group than in NASH group （0.63 ± 0.09 mmol/L vs 1.13 ± 0.15 mmol/L, P 〈 0.01）. Treatment with cidomycin showed its effect by significantly lowering serum ALT, AST and TNF-α levels of NASH rats.
CONCLUSION： SIBO may decrease small intestinal movement in NASH rats. SIBO may be an important pathogenesis of Nash. And treatment with cidomycin by mouth can allevi     

Small doses of melatonin increase intestinal motility in rats

Since melatonin receptors are present in the intestines, the possibility that this hormone may affect intestinal motility has been studied in the rat. Sprague-Dawley male rats were given a carmine cochineal powder meal and were injected intraperitoneally with 1, 10, 100, or 1000 g/kg melatonin. Sixty minutes after treatment, intestinal transit was found to be faster in animals treated with small doses of melatonin (1 or 10 g/kg) than in saline-injected controls. This effect, however, appear to be clearly reversed with 100 or 1000 g/kg melatonin. In fact, these doses of the hormone reduced intestinal transit in rats. The nonselective melatonin receptor antagonist, luzindole (administered intraperitoneally in a dose of 0.25 mg/kg, 15 min prior to melatonin injection) totally prevented the accelerating effect of melatonin (10 g/kg) on intestinal transit. Luzindole per se failed to affect gut motility. Injection of the reversible acetylcholinesterase inhibitor and cholinergic agent, neostigmine, accelerated intestinal transit but failed to influence melatonin effect on this parameter. In contrast, intraperitoneal injection of the muscarinic receptor antagonist atropine delayed intestinal transit per se but did not reduce the stimulating effect of melatonin on this parameter. Intestinal myoelectrical recording revealed that intestinal myoelectrical activity was increased by intraperitoneal injection of melatonin (10 g/kg). Administration of luzindole totally prevented melatonin-induced increase of intestinal myoelectrical activity. These results indicate that melatonin may affect intestinal motility in rats when administered in small doses. This effect might be mediated by melatonin receptors in the intestines, although the involvement of central receptors for the hormone is also possible.     

Rat jejunal absorptive function after intestinal transplantation

Jejunal absorptive function was evaluated following small intestinal transplantation to determine the effects of extrinsic denervation. In particular, water and sodium absorption were measured following transplantation (denervated) and compared to a control group (Thiry-Vella). Water flow was initially secretory two days after transplantation (?41±27 μl/min/g dry tissue weight) but became absorptive at day 8 (25±25). Water flow in the Thiry-Vella group was not significantly different (P>0.05) from the transplant group at days 8 (17±7) and 10 (47±42). Sodium flows were also initially secretory in the transplant group and became absorptive. This study refutes previous claims that small bowel transplants have a deficiency of water absorption due to extrinsic denervation of the bowel and suggests normal absorptive function of water, electrolytes, and protein.     

Small intestinal fatty acid synthesis is increased in diabetic rats

Several studies have demonstrated that intestinal triglyceride production and secretion are increased in diabetic animals and may contribute to the hypertriglyceridemia that accompanies diabetes. There are three potential sources of fatty acids for intestinally derived triglycerides; de novo fatty acid synthesis, circulating free fatty acids, or dietarily derived fatty acids. Prior data have demonstrated that de novo cholesterol synthesis is increased in the small intestine of diabetic animals. The primary aim of the present study was to determine the effect of diabetes on small intestinal de novo fatty acid synthesis. We found that de novo fatty acid synthesis in the small intestine is increased approximately 2-fold in streptozotocin-induced diabetic rats. In contrast, hepatic fatty acid synthesis is decreased in the diabetic animals. The increase in intestinal fatty acid synthesis is observed in both the fed and fasting states. Limiting food intake by pair feeding prevents the diabetic-induced increase in small intestinal fatty acid synthesis, a finding similar to previous data on cholesterol synthesis. Thus, the increase in both small intestinal cholesterol and fatty acid synthesis is dependent on the increased food intake that accompanies poorly controlled diabetes. The present study indicates that increases in small intestinal de novo fatty acid synthesis in diabetic animals could play an important role in providing fatty acids for increased small intestinal triglyceride synthesis and secretion.     

Small intestinal crypt cell proliferation rates are increased in senescent rats

Our previous studies implied that intestinal epithelial cell replication might be increased in senescent rats. Duodenal, jejunal, and ileal crypt cell production rates (CCPR) were measured in 3-4-mo and 26-28-mo female fed control, 3-day starved and 1-day refed, and in 4-5-mo and 26-28-mo male fed Fischer rats, using the vincristine-induced metaphase arrest technique. Fed aging rats had greater proximal intestinal crypt cell numbers which fell less during starvation than those of young controls. Metaphase accumulation also was higher in aging rat duodenum and jejunum, and CCPR were 30-100% more than in young rats. Starvation reduced CCPR by more than 40% in the duodenum of young, but only by 10% in older animals. Crypt proliferative patterns demonstrated a broadened proliferative zone in aging rats. These combined results directly demonstrate that small intestinal cell production is enhanced in senescent rats and that the nutritional controls of proliferation are blunted.     

Effect of various doses of medroxyprogesterone acetate on intestinal functions in rats

The dose relationship between medroxyprogesterone acetate (MPA), a long acting contraceptive, and rat intestinal digestive and absorptive functions has been investigated. The study revealed that the activities of brush border sucrase, lactase and leucine aminopeptidase were stimulated only at high doses, viz 70 mg/kg (180 mumol/kg) body weight and above, whereas the activity of alkaline phosphate was depressed at comparatively low dose (17.5 mg/kg; 45 mumol/kg body weight). This decrease was found to be significant (p less than 0.001) at all the doses tested. The inhibition in the intestinal uptake of calcium paralleled the decrease in alkaline phosphatase activity. Relatively high amount of MPA (140 mg/kg; 360 mumol/kg) was required to augment the uptake of glucose and amino acid. The results obtained do not indicate a close relationship between the dose of the drug and the extent of alteration in the rat intestinal digestive and absorptive functions. The study appears to confirm the association between brush border enzymes activities and uptake of nutrients in rat intestine.     

Small intestinal transplantation

The purpose of this study was to determine whether small intestinal transplantation could be considered as an alternative in the treatment of patients suffering from the short-bowel syndrome. The site of absorption of oral cyclosporine A was determined as were the changes that follow small intestinal transplantation. The interactions between the lipophilic cyclosporine A molecule and fat emulsion solutions used for total parenteral nutrition were investigated. Finally, a technique for harvesting the entire small bowel in man was developed. The absorption of oral cyclosporine A in normal dogs, and in bowel-resected, autotransplanted, and allotransplanted dogs was determined. Cyclosporine A levels were monitored in all animals. This demonstrated that cyclosporine A is absorbed through the small bowel and carried through the lymphatics; that absorption is decreased to 40 percent of normal after autotransplantation or allotransplantation without rejection. Rejection further hampers cyclosporine A absorption. Administration of olive oil alone enhances absorption of cyclosporine A. We also administered cyclosporine A IV to five dogs, with and without a concomitant infusion of fat emulsion solution (Intralipid). No changes in plasma cyclosporine A levels, in the clearance of cyclosporine A, or in the in vivo distribution of cyclosporine A were noted. Finally, dissections in six cadavers and in four brain-dead organ donors were performed, and a reproducible technique for harvesting the small bowel in man was established. In selected patients with the short-bowel syndrome, small intestinal transplant may be considered as an alternative therapy to home total parenteral nutrition.     

Small intestinal neoplasms

Small intestinal neoplasms are uncommonly encountered in clinical practice. They may occur sporadically, in association with genetic diseases (e.g., familial adenomatous polyposis coli or Peutz-Jeghers syndrome), or in association with chronic intestinal inflammatory disorders (e.g., Crohn's disease or celiac sprue). Benign small intestinal tumors (e.g., leiomyoma, lipoma, hamartoma, or desmoid tumor) usually are asymptomatic but may present with intussusception. Primary malignancies of the small intestine-including adenocarcinoma, leiomyosarcoma, carcinoid, and lymphoma-may present with intestinal obstruction, jaundice, bleeding, or pain. Extraintestinal neoplasms may involve the intestine via contiguous spread or peritoneal metastasis. Hematogenous metastases to the intestine from an extraintestinal primary are unusual and are most typical of melanoma. Because the small intestine is relatively inaccessible to routine endoscopy, diagnosis of small intestinal neoplasms is often delayed for months after onset of symptoms. When the diagnosis is suspected, enteroclysis is the most useful imaging study. Small bowel endoscopy (enteroscopy) is increasingly widely available and may permit earlier, nonoperative diagnosis.     

Small intestinal bleeding

Bleeding from the small intestine may be difficult to diagnose, because of the organ's length, free intraperitoneal location, and the nature of the lesions that bleed in the small bowel. Although there are several causes of intestinal bleeding, angiodysplasias are most common. Several different tests can be used to identify a bleeding site preoperatively and intraoperatively, including enteroscopy.     

Small intestinal transplantation

The past few years have witnessed a considerable shift in the clinical status of intestinal transplantation. A great deal of experience has been gained at the most active centers, and results comparable with those reported at a similar stage in the development of other solid-organ graft programs are now being achieved by these highly proficient transplant teams. Rejection and its inevitable associate, sepsis, remain ubiquitous, and new immunosuppressant regimes are urgently needed; some may already be on the near horizon. The recent success of isolated intestinal grafts, together with the mortality and morbidity attendant upon the development of advanced liver disease related to total parenteral nutrition, has prompted the bold proposal that patients at risk for this complication should be identified and should receive isolated small bowel grafts before the onset of end-stage hepatic failure. The very fact that such a suggestion has begun to emerge reflects real progress in this challenging field.