AIM:To evaluate the effects of bowel rehabilitation and combined trophic therapy on intestinal adaptation in short bowel patients.METHODS:Thirty-eight patients with severe short-bowel syndrome (SBS) were employed in the present study, whose average length of jejunum-ileum was 35.8+/-21.2 cm. The TPN treatment was initiated early to attain positive nitrogen balance and prevent severe weight loss. The TPN composition was designated to be individualized and altered when necessary. Enteral feeding was given as soon as possible after resection and increased gradually. Meals were distributed throughout the day. Eight patients received treatment of growth hormone (0.14 mg/kg.day) and glutamine (0.3 g/kg.day) for 3 weeks. D-xylose test, 15N-Gly trace test and 13C-palmitic acid breath test were done to determine the patients' absorption capability.RESULTS:Thirty-three patients maintained well body weight and serum albumin concentration. The average time of follow-up for 33 survival patients was 5.9+/-4.3 years. Twenty-two patients weaned from TPN with an average TPN time of 9.5+/-6.6 months. Two patients, whose whole small bowel, ascending and transverse colon were resected received home TPN. An other 9 patients received parenteral or enteral nutritional support partly as well as oral diet. Three week rhGH+GLN therapy increased nutrients absorption but the effects were transient.CONCLUSION:By rehabilitation therapy, most short bowel patients could wean from parenteral nutrition. Dietary manipulation is an integral part of the treatment of SBS. Treatment with growth hormone and glutamine may increase nutrients absorption but the effects are not sustained beyond the treatment period.

BACKGROUND:Studies have proven the validity of interleukin-10 (IL-10) in the treatment of experimental pancreatitis. Prophylactic human IL-10 (hIL-10) gene treatment attenuated the severity in cerulein models. Our research aims to study whether the therapeutic hIL-10 gene could decrease both severity and mortality in a lethal pancreatic model.METHODS:Severe acute pancreatitis (SAP) was induced by sodium taurocholate. A plasmid-hIL-10 construct (pcDNA3-hIL-10) complexed with cationic liposomes was administered to SAP rats by a single intraperitoneal injection. Levels of hIL-10 in the pancreas, liver, and lungs were determined by ELISA kits. The severity of pancreatitis was assessed in terms of serum amylase, histology, and tissue tumor necrosis factor alpha (TNF-alpha). Mortality, observed for 7 days, was evaluated for gene therapy or control groups.RESULTS:After hIL-10 gene therapy, hIL-10 levels in the pancreas, liver, and lungs increased significantly and the serum amylase, tissue TNF-alpha, and histological changes in pancreas, liver, and lungs decreased markedly. Therefore, mortality was significantly reduced in the hIL-10 gene therapy group, in which 70% of rats survived in the 7-day observation, while only 10% survived in untreated groups (P < 0.05).CONCLUSION:We found that liposome/hIL-10 gene therapy decreased severity and mortality in SAP, even carried out after SAP establishment, predicting a more convenient shift to clinical applications.

OBJECTIVE: To study the effects and the underlying mechanism of recombinant human growth hormone (rhGH) and glutamine (Gln) on the adaptation of the remnant small intestine in parenterally nourished, short bowel syndrome (SBS) rats. METHOD: Four parenteral nutrition (PN) treatment groups of SBS rats were randomly arranged in a 2 × 2 factorial design as follows: (i) STD (standard PN) group (–rhGH, –Gln); (ii) Gln group (–rhGH, +Gln); (iii) rhGH group (+rhGH, –Gln); and (iv) rhGH + Gln group (+rhGH, +Gln). Morphological changes of the intestinal mucosa were investigated and the expression of proliferating cell nuclear antigen (PCNA) and the occurrence of apoptosis were observed by immunohistochemical staining and terminal deoxynucleotidyl transfer‐mediated dUTP‐biotin nick end‐labeling (TUNEL) methods. The level of intestinal insulin‐like growth factor‐1 (IGF‐1) mRNA was determined by northern blotting. RESULTS: The mucosal thickness, villous height, crypt depth and villous surface area of the remnant small intestine in the rhGH + Gln group were increased significantly as compared with the other three experimental groups, and there were synergistic effects between rhGH and Gln (P < 0.01). The expression of PCNA was higher in the rhGH + Gln group than in the rhGH, Gln and STD groups (24.95 ± 3.93 vs 19.28 ± 3.25, 17.27 ± 3.38, and 8.37 ± 2.23 positive cells per crypt of Lieberkuhn, respectively; P < 0.01) but the rate of apoptosis was lower in the rhGH + Gln group than in the rhGH, Gln and STD groups (5.68 ± 2.07 vs 8.06 ± 2.33, 10.00 ± 2.24 and 22.32 ± 3.84 positive cells per 100 cells, respectively; P < 0.01). The intestinal IGF‐1 mRNA was also expressed at a higher level in the rhGH + Gln group than in the rhGH, Gln and STD groups (0.73 ± 0.05 vs 0.62 ± 0.04 vs 0.51 ± 0.04 and 0.41 ± 0.22, respectively; P < 0.05). CONCLUSION: The synergistic combination of rhGH and Gln can significantly improve the adaptation of the remnant small intestine in parenterally fed SBS rats. An increase in cell proliferation and a decrease in cell apoptosis are both responsible for the intestinal adaptation. An increase in local IGF‐1 plays an important role in this process.

Objective To understand the effect of insulin- like growthfactorⅠ (IGFⅠ) on the adaptation of the small intestine in growth hormone (GH)-treated rats. Method 20 SD rats were randomized into GH group and STD group. Parenterally fed, short bowel rat models were established. The morphological changes of the intestinal mucosal epithelia were examined, serum GH, IGFⅠ concentrations were determined by RIA method. The local intestinal IGFⅠ mRNA was evaluated by Northern blot m ethod. Result At the end of the st udy, mucosal thickness, villous height, crypt depth in GH group (471±16, 299±1 7, 161±20 μm respectively) increased significantly compared to that in STD gr oup (374±13, 212±19, 96±9 μm respectively, all P＜0.01). Rats in GH g roup showed higher serum GH and IGFⅠ concentrations (5.2±0.8, 425±19 ng/ml respectively) than that in STD group (3.3±1.7, 326±30 ng/ml respectively, al l P＜0.05). The relative abundance of IGFⅠ mRNA in local small intestine was higher in GH group than in STD group (0.62±0.04 vs. 0.41±0.02 respecti vely, P＜0.05). Conclusion I GFⅠ plays an important role in growth-promoting effects of GH in the adaptatio n of the remnant small intestine, the increase of the systemic IGFⅠ and the loc al IGFⅠ may both be responsible for this process.