Influence of adenosine on preservation of porcine pancreas in islet transplantation.

Ischemia time during transplantation has greatly restricted the quality and utilization of grafts. To improve the quality of islet transplantation, adenosine was added into the University of Wisconsin (UW) pancreas perfusate to assess its effect on islet yield and function in porcine pancreas. Ten pancreata from donation after cardiac death pigs were obtained and randomly divided into two groups: control group (N = 5) with UW perfusion solution, and experimental group (N = 5) with adenosine-enriched UW perfusion solution. The yield and purity of the islet cells were counted after they were collected, purified, and stained with dithizone. Acridine orange/propidium iodide staining was applied to determine islet cell viability. Islet function was assessed by glucose stimulated insulin secretion assays, and released insulin was quantified by enzyme-linked immunosorbent assay. The metabolic substrates of the pancreas were analyzed by trace dialysis technology. We found that the addition of adenosine in UW perfusion solution significantly increased the yield, purity and viability of islet cells, as well as enhanced their insulin release. In addition, the levels of metabolic substrates, pyruvate and lactate, were significantly reduced. The addition of adenosine could effectively increase islet cell viability during mechanical perfusions, which may improve islet transplantation. This perfusion protocol may be clinically feasible, and should be considered in the clinical setting.

Dietary supplementation with N-carbamylglutamate increases the expression of intestinal amino acid transporters in weaned Huanjiang mini-pig piglets.

Weaning is associated with reduced intestinal absorptive capacity in piglets. Our previous study indicated that dietary supplementation with N-carbamylglutamate (NCG) enhanced growth performance and improved intestinal function in weaned piglets. The present study was conducted to test the hypothesis that dietary supplementation with NCG may increase the growth performance of weaned piglets by regulating the expression of intestinal nutrient transporters, thus enhancing nutrient absorption. Twenty-four Huanjiang mini-pig piglets weaned at 21 d of age (3.17 ± 0.21 kg average BW) were randomly assigned to 2 dietary treatments consisting of a basal diet and the basal diet with 0.1% NCG supplementation for a 14-d period with 6 pens per treatment and 1 male and 1 female per pen. On d 14, 1 piglet was randomly selected from each pen for blood and tissue sampling. Dietary NCG supplementation enhanced (P < 0.05) growth rate and the efficiency of feed use in weaned Huanjiang mini-pig piglets. The NCG-supplemented diet increased (P < 0.05) mRNA expression levels of Slc6a19, Slc7a9, and Slc1a1 and the protein abundance of ASCT2, B(0)AT1, b(0,+)AT, y(+)LAT1, and EAAC1 in the jejunum. Furthermore, the contents of low density lipoprotein, ammonia, urea nitrogen, and AA as well as the activity of alkaline phosphatase in plasma were all altered (P < 0.05) by supplementation with NCG. These findings indicate that dietary supplementation with NCG may improve intestinal absorptive function in weaned piglets by increasing the expression of AA transporters in the intestine.

Prognosis of colorectal cancer with liver metastasis: value of a prognostic index

The objective of the present study was to explore the factors related to the prognosis of colorectal cancer (CRC) and to establish a prognostic model for the selection of patients who might benefit from hepatic resection for metastatic CRC. A total of 293 patients undergoing liver resection for metastatic CRC (172 males and 80 females ranging in age from 26 to 80 years) were selected and clinical, pathological and outcome data were examined in this retrospective study. The prognostic index (PI) of the patients was calculated on the basis of results of multivariate analysis. Patients were stratified into different groups, with survival curves projected according to PI. The 1-, 3-, and 5-year overall survival rates were 58.3, 26.4, and 11.3 percent, respectively. Univariate analysis indicated that degree of primary tumor differentiation, resection margin, preoperative carcinoembryonic antigen (CEA) level, number of liver metastases, and resection of liver metastases were associated with prognosis (P < 0.05). In multivariate analysis, the last three factors were found to be independent prognostic factors. The resection of liver metastases was a favorable factor. Patients were classified into three groups according to PI, which differed significantly in survival rate (P < 0.05). The individual survival rate was evaluated based on PI. Resection of hepatic colorectal metastases may produce long-term survival and cure. The proposed PI was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups.

Prognosis of colorectal cancer with liver metastasis: value of a prognostic index.

The objective of the present study was to explore the factors related to the prognosis of colorectal cancer (CRC) and to establish a prognostic model for the selection of patients who might benefit from hepatic resection for metastatic CRC. A total of 293 patients undergoing liver resection for metastatic CRC (172 males and 80 females ranging in age from 26 to 80 years) were selected and clinical, pathological and outcome data were examined in this retrospective study. The prognostic index (PI) of the patients was calculated on the basis of results of multivariate analysis. Patients were stratified into different groups, with survival curves projected according to PI. The 1-, 3-, and 5-year overall survival rates were 58.3, 26.4, and 11.3%, respectively. Univariate analysis indicated that degree of primary tumor differentiation, resection margin, preoperative carcinoembryonic antigen (CEA) level, number of liver metastases, and resection of liver metastases were associated with prognosis (P < 0.05). In multivariate analysis, the last three factors were found to be independent prognostic factors. The resection of liver metastases was a favorable factor. Patients were classified into three groups according to PI, which differed significantly in survival rate (P < 0.05). The individual survival rate was evaluated based on PI. Resection of hepatic colorectal metastases may produce long-term survival and cure. The proposed PI was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups.

Blocking the CC chemokine receptor 5 pathway by antisense peptide nucleic acid prolongs islet allograft survival.

Chemokines are important regulators in the development, differentiation, and anatomic location of leukocytes. The CC chemokine receptor 5 (CCR5) is the receptor for the proinflammatory chemokines and plays an important role in islet allograft rejection. Peptide nucleic acid (PNA) is a nucleic acid analog in which the sugar phosphate backbone of natural nucleic acid has been replaced by a synthetic peptide backbone. Studies indicate that PNA inhibits both transcription and translation of targeted genes. Fullly major histocompatibility complex (MHC)-mismatched murine islet transplant models were used to test the in vivo effect of PNA CCR5 by targeting CCR5 in acute allograft rejection. PNA CCR5-treated recipients demonstrated significant prolongation (12.0 +/- 1.75 days) of functional allograft survival compared with saline (6.5 +/- 0.58 days)- or PNA mismatch-treated recipients (6.5 +/- 0.50 days). The PNA CCR5 blocked the expression of CCR5 in spleen CD3+ T cells. Lymphocytes from PNA CCR5-treated mice exhibited a reduced degree of proliferation comparable to that of saline- and PNA mismatch-treated mice. The present study indicated that PNA CCR5 has a substantial therapeutic effect to inhibit acute allograft rejection.

Investigations on the protective action of Condonopsis pilosula (Dangshen) extract on experimentally-induced gastric ulcer in rats.

The action of Codonopsis pilosula extract in 5 animal models of gastric ulcer was investigated. It was found that the extract had higher efficacy on gastric ulcer induced by stress, acetic acid and sodium hydroxide and little significant effect on ulcers induced by pyloroligature and indomethacin. The C. pilosula extract was also capable of reducing gastric acid pepsin secretion. It is possible that inhibition of gastrointestinal movement and propulsion is one of the mechanisms underlying the antiulcer action of C. pilosula extract.