Aamer Ar'Rajab

The Effect of Exogenous Administration of Lactobacillus reuteri R2LC and Oat Fiber on Acetic Acid-Induced Colitis in the Rat

The potential beneficial effect of exogenous administration of Lactobacillus on acetic acid-induced colitis was evaluated in the rat. Colitis was induced by instillation of 4% acetic acid for 15 sec in an exteriorized colonic segment. This produced uniform colitis with a threefold increase in myeloperoxidase (MPO) activity of the colonic tissue (an index of neutrophil infiltration) and a sixfold increase in plasma exudation into the lumen of the colon (mucosal permeability) as evaluated 4 days after acetic acid administration. Intracolonic administration of L. reuteri R2LC immediately after acetic acid administration, at a dose of 5 ml of 7 x 10(7) colony-forming units (CFU)/ml in two forms: either as pure bacterial suspension or as fermented oatmeal soup, prevented the development of colitis. Thus, the morphologic score, MPO activity, and mucosal permeability were almost normalized by Lactobacillus treatment. Initiating the treatment 24 h after acetic acid administration or using lower doses of 1 ml for 3 consecutive days resulted in a smaller protective effect. We conclude that exogenous administration of L. reuteri R2LC prevents the development of acetic acid-induced colitis in the rat.

Phosphatidylcholine prevents postoperative peritoneal adhesions: An experimental study in the rat

Phosphatidylcholine (PC) is the main constituent of the surface-active material coating peritoneal mesothelium. It may prevent postoperative adhesion formation through production of a lubricant film on mesothelial defects. We therefore examined the effect of its soluble form on surgically induced intraabdominal adhesions in rats. The adhesions were induced at laparotomy by any of four different operative models. PC was administered intraperitoneally (20 mg/rat) or intravenously (20 mg/rat or 50 mg/rat) at the end of the operation and on the second and third postoperative day. It was found that the degree of postoperative adhesion formation was significantly reduced by the intraperitoneal injection of PC in all 4 models. In contrast, no effect was achieved by the intravenous injection of PC, not even at a very high dose level. Our results suggest that soluble PC administered intraperitoneally might be a potent adjunct in postoperative adhesion prevention.

Presence of galanin in human pancreatic nerves and inhibition of insulin secretion from isolated human islets

SummaryIn several animal species, galanin occurs in pancreatic nerves and inhibits insulin secretion. However, the presence and action of galanin in the human pancreas have not been established. Therefore, we examined the presence and nature of human pancreatic galanin-like immunoreactive material (GLIR) and the effects of galanin on glucose-stimulated insulin secretion from isolated human islets. Immunofluorescent staining of human pancreas revealed GLIR in fine varicose fibers in both islets and exocrine parenchyma. Furthermore, acid extracts of pancreas (n=3) and isolated islets (n=3) contained 0.17±0.06 and 0.23±0.11 pmol GLIR/mg protein. Human pancreatic GLIR coeluted with synthetic porcine galanin from Sephadex G-50. Moreover, synthetic porcine galanin inhibited glucose-stimulated insulin secretion from collagenase-isolated human islets at dose rates >10-8 M. Thus, (1) human pancreas is innervated by galanin-containing nerves, (2) human pancreatic GLIR is of similar size as synthetic porcine galanin, and (3) porcine galanin inhibits glucose-stimulated insulin secretion from human islets. Therefore, galanin could be an important local regulator of insulin secretion in man.

Gastroprotective Capability of Exogenous Phosphatidylcholine in Experimentally Induced Chronic Gastric Ulcers in Rats

Phosphatidylcholine (PC) is a main component of the hydrophobic gastric mucosal barrier. Exogenously administered, it prevents acute lesions. We evaluated the gastroprotective capacity of exogenous PC in both acute (ethanol- and indomethacin-induced) and chronic (indomethacin-induced) lesions in rats. Polyunsaturated (PPC) or hydrogenated PC in different concentrations were given intragastrically, before or after the injury factor, in single or repeated doses. Mucosal lesions were significantly reduced by a single dose of PPC, given before or after the injury factor, in both acute models. In the chronic model a single dose of PPC or hydrogenated PC significantly reduced lesions evaluated 6 h after ulcer induction, whereas after 72 h no protective effect was noticed. Repeated doses of PC were ineffective. In conclusion, in acute models exogenous PC reduces lesions in a dose-dependent manner and contributes to the mucosal defense. In chronic models an incomplete and temporary protection might be due to complex pathogenesis that requires activation of all levels in the mucosal defense. Strengthening of only one level was insufficient to restrict injury.

Effects of amidated rat islet amyloid polypeptide on glucose-stimulated insulin secretion in vivo and in vitro in rats

Amidated rat islet amyloid polypeptide (IAPP) is a constituent of secretory granules in islet B-cells. We examined its influence on glucose-stimulated insulin secretion in rats. In vivo, intravenous infusion of IAPP (68 pmol/min) did not affect glucose-stimulated insulin secretion. In vitro, IAPP slightly inhibited glucose (8.3 mM)-stimulated insulin secretion from isolated rat islets at the high dose level of 10(-5) M but not at the lower dose levels. We conclude that the IAPP is not involved in the normal regulation of insulin secretion.

Green banana protection of gastric mucosa against experimentally induced injuries in rats. A multicomponent mechanism

The protective capacities of fresh green (unripe) sweet bananas and of phosphatidylcholine and pectin (banana ingredients) against acute (ethanol- or indomethacin-induced) and chronic (indomethacin-induced) gastric mucosal lesions were evaluated in rats. Banana pulp was mixed with saline and given by gavage, as a pretreatment in a single dose. The identical protocol was used for pectin and phosphatidylcholine solution, and the dosages were adjusted to equal the amount of ingredients in the banana mixture, but higher concentrations were also given. The banana suspension reduced acute lesions, as did pectin and phosphatidylcholine in higher concentrations, but in concentrations as in fresh fruit no protective effects were observed except by pectin against indomethacin injury. In the model of chronic ulcers the banana suspension provided an incomplete and temporary protective effect. We conclude that the protective capacity of fresh green sweet bananas cannot be confined to only one active component. Pectin and phosphatidylcholine may protect gastric mucosa by strengthening the mucous-phospholipid layer, but the mechanism of protection afforded by bananas has to be further elucidated.

Phospholipase-resistant phosphatidylcholine reduces intra-abdominal adhesions induced by bacterial peritonitis

The majority of intra-abdominal adhesions develop postoperatively or following peritonitis. We have previously shown thatl-phosphatidylcholine reduces postoperative peritoneal adhesions in rats. In the present study, we examined whether adhesion formation after bacterial peritonitis is also reduced byl-phosphatidylcholine or bydl-α-phosphatidylcholine, which is degraded only 50% by phospholipase A2. Peritonitis was induced in the rat by caecal ligation and double puncture; cecotomy was performed 12, 15, or 18h later. Adhesions were assessed blindly by a scoring system 7 days after cecotomy. When cecotomy was scheduled for 18h after caecal ligation and puncture, the 7-day mortality was 90% (n=20). When cecotomy was performed at 12h, no mortality was seen; however, the adhesion score was low (2.3±0.7). When cecotomy was performed 15h after caecal ligation and puncture, the mortality was 25% and the adhesion score was 4.3±0.9. This figure was reduced significantly by intraperitoneal instillation ofl-phosphatidylcholine ordl-α-phosphatidylcholine for 3 subsequent days. However, the mortality increased byl-phosphatidylcholine (P<0.01), whereas mortality afterdl-α-phosphatidylcholine remained at 30%. We conclude that administration of bothl-phosphatidylcholine anddl-α-phosphatidylcholine decrease adhesion formation after bacterial peritonitis.

Phospholipids Prevent Enteric Bacterial Translocation in the Early Stage of Experimental Acute Liver Failure in the Rat

BACKGROUND Bacterial infections and bacteremia in acute liver failure may at least partly be attributed to translocation of enteric bacteria. Attempts to prevent or treat such infections by the use of antibiotics may instead result in overgrowth of surviving microbes. METHODS In the present study, normal saline (1.5 ml/100 g body weight), phosphatidylcholine (1.5 ml/100 g body weight), and phosphatidylinositol (1.5 ml/100 g body weight) were orally administered by means of a gastric tube both 12 h and 30 min before operation. Effects of enteric administration of phospholipids on the prevention of enteric bacterial translocation, intestinal and mucosal mass, and enterocyte protein contents in acute liver failure induced by subtotal liver resection in the rat were evaluated. RESULTS The incidence of bacterial translocation increased significantly 2 and 4 h after 90% hepatectomy as compared with sham-operated animals. Enteric administration of phospholipids, however, significantly reduced the incidence of bacterial translocation after 90% hepatectomy. Phospholipid treatment prevented the postoperative decrease in intestinal mucosal mass and enterocyte protein content. CONCLUSIONS Enteral administration of phospholipids thus seems to protect against translocation of enteric bacteria and prevent against a decrease in intestinal mucosal mass and enterocyte protein content after subtotal hepatectomy in the rat.

THE EFFECT OF PANCREATIC-ISLETS ON TRANSPLANTED HEPATOCYTES IN THE TREATMENT OF ACUTE LIVER-FAILURE IN RATS

SummaryWe previously reported that co-transplantation of hepatocytes and islets of Langerhans in the spleen reduces the mortality rate after 90% hepatectomy in the rat. In the present study, we examined whether implantation of isolated hepatocytes into the pancreas is as efficient as co-transplantation of hepatocytes and islets in this respect. We found that cotransplantation of hepatocytes and islets into the renal subcapsule reduced the long-term (30-day) mortality rate after 90% hepatectomy from 100% to 36% (P<0.05) when performed the day before the hepatectomy. In contrast, there was no significant reduction of mortality when the hepatocytes were transplanted into the pancreas. The results show that a close proximity of transplanted pancreatic islets to the hepatocytes is of critical importance for the improved survival in acute liver failure.

The Influence of Surgically Induced Acute Liver Failure on the Intestine in the Rat

The influence of acute liver failure induced by 90% hepatectomy on the intestine was evaluated in the rat. Small-intestinal mucosal mass decreased 2 h after hepatectomy. Microvillous height decreased significantly from 1 h and on, and villous height and area in the distal small intestine from 2 h after operation. Ninety per cent hepatectomy resulted in a decrease in systemic arterial blood pressure and an increase in portal venous pressure. Subserosal microcirculation and small-arterial circulation in the proximal and distal small intestine and colon decreased significantly after 90% hepatectomy. Overgrowth and colonization of Escherichia coli occurred in the distal small intestine from 1 h and on after hepatectomy. Protein content in enterocytes and bile secretion from the liver remnant were markedly reduced in hepatectomized rats. Thus, the present study shows evidence of alterations in intestinal morphology and function that can contribute to explain the enteric bacterial translocation after surgically induced acute liver failure.