Glucagonlike peptide-2 analogue enhances intestinal mucosal mass and absorptive function after ischemia-reperfusion injury

BACKGROUND/PURPOSE: This study was designed to explore the efficacy of a synthetic analogue of glucagonlike peptide-2 (GLP-2a) in enhancing mucosal mass and absorptive function in a rat model of intestinal ischemia-reperfusion (I-R) injury. METHODS: Each of 20 Sprague-Dawley rats underwent placement of a jugular venous catheter connected to a subcutaneous osmotic pump designed to deliver its contents over 3 days. Rats were divided into 4 groups (n = 5 per group): (1) normal intestine/saline infusion; (2) 30-minute superior mesenteric artery occlusion/saline infusion, (3) normal intestine/ GLP-2alpha infusion, and (4) 30-minute superior mesenteric artery occlusion/GLP-2alpha infusion. Subsequently, mean mucosal 14C-galactose and 14C-glycine absorption and DNA content were determined for each group. RESULTS: In saline-treated rats, 30 minutes of mesenteric ischemia decreased mean mucosal galactose absorption by 29% (P < .05), glycine absorption by 22% (P = .12), and DNA content by 28% (P < .01) when compared with rats with uninjured intestine. In rats subjected to 30 minutes of intestinal ischemia, GLP-2alpha significantly improved galactose absorption by 46% (P < .05), glycine absorption by 84% (P < .01), and DNA content by 63% (P < .01) when compared with saline-treated control rats. In rats with mesenteric I-R injury treated with GLP-2a, galactose absorption was returned to normal. Glycine absorption and DNA content were increased significantly by 44% (P < .01) and 18% (P < .05), respectively, beyond the baseline for normal intestine. CONCLUSIONS: Thirty minutes of intestinal ischemia followed by immediate reperfusion significantly decreased mucosal mass and absorptive function, validating this rat model of I-R injury. After mesenteric I-R, GLP-2a significantly increased mucosal DNA content and absorption of 14C-galactose and 14C-glycine when compared with untreated control rats. After I-R injury, GLP-2a restored mucosal mass and absorptive function to normal or above-normal levels.     

Patient-controlled thoracic epidural infusion with ropivacaine 0.375% provides comparable pain relief as bupivacaine 0.125% plus sufentanil after major abdominal gynecologic tumor surgery

BACKGROUND AND OBJECTIVES: We tested the hypothesis that an opioid-free local anesthetic alone is able to provide comparable analgesia to the opioid supplemented epidural application of local anesthetics using thoracic epidural catheters after major abdominal surgery. METHODS: In a prospective, randomized, and double-blind study, we have compared the analgesic efficacy and side effects of ropivacaine 0.375% (group R) versus bupivacaine 0.125% in combination with sufentanil 0.5 microg/mL(-1) (group B/S) via a thoracic epidural catheter for a duration of 96 hours after major abdominal surgery in 30 gynecologic tumor patients. Piritramide was given for breakthrough pain. Assessments were performed every 12 hours after start of the epidural infusion using continuous (first 24 hours) and patient-controlled epidural analgesia (PCEA) (24 to 96 hours). RESULTS: No differences were seen in demographic and perioperative data. Dynamic pain scores (visual analog scale [VAS] values) were comparable between groups during mobilization (group R v group B/S: 24 hours: 40 +/- 30 v 36 +/- 14, P =.9; 48 hours: 46 +/- 33 v 42 +/- 25, P =.93; 72 hours: 42 +/- 24 v 48 +/- 26, P =.78; 96 hours: 42 +/- 25 v 29 +/- 28, P =.49) and on coughing during the whole study period. Hemodynamics, intensity of motor block (Bromage scale), and side effects like nausea, vomiting, pruritus, and bladder disfunction also did not differ between groups. CONCLUSION: The present study shows that thoracic epidural infusion of ropivacaine 0.375% provides comparable pain relief and incidence of side effects after major abdominal gynecologic surgery as bupivacaine 0.125% in combination with 0.5 microg/mL(-1) sufentanil and may therefore represent an alternative in epidural pain management.     

Enhancement of small intestine function by gastrin

Frequently, congenital or acquired small intestine (SI) abnormalities in infants lead to inadequate absorption. Gastrin has been suggested as a trophic hormone for SI epithelial cells. We chose to evaluate the effect of gastrin on the function and maturation of developing SI using a rat fetal intestine transplant model. Jejunoileal segments (7-8 cm) obtained from 19 to 20 days gestation fetal rats were implanted subcutaneously in syngeneic adult rats. Two weeks following transplantation the control group (N = 10) was continuously infused with saline and the study group (N = 9) was continuously infused with gastrin-17 (13.5 nM/kg/day) for 14 days. Following the infusion, intestinal maturation and function were evaluated by mucosal DNA concentration, disaccharidase activity, and absorption of [14C]galactose and [14C]glycine. Absorption (microM/cm2 SI) by the control and study groups for galactose was 1.10 +/- 0.18 vs 2.73 +/- 0.25, and for glycine was 1.68 +/- 0.23 vs 2.22 +/- 0.26, respectively. DNA concentration (microgram/mg SI) of the control and study groups was 410 +/- 43 vs 1031 +/- 158, respectively. Lactase and sucrase activity were similar in both groups. Although maltase (microM substrate hydrolyzed/min/g SI) was 13.5 +/- 2.7 for the gastrin group vs 7.9 +/- .9 for the control group, statistical significance was not achieved. Thus, gastrin produced a statistically significant increase in DNA concentration (cell mass) (P less than 0.01). More importantly, to our knowledge, this is the first demonstration that exogenously administered gastrin can increase absorption of carbohydrate (galactose; P less than 0.01) and protein (glycine; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion

BACKGROUND/PURPOSE: Glucagonlike peptide-2 (GLP-2), a product of the posttranslational processing of proglucagon, has been shown to enhance mucosal mass and function in both normal intestine and in the residual intestine after massive small bowel resection. This study was designed to determine if a synthetic, protease-resistant analogue of GLP-2 (GLP-2alpha) can enhance mucosal mass in small intestine after ischemia and reperfusion (I/R) injury. METHODS: Ten young adult male Sprague-Dawley rats underwent laparotomy and superior mesenteric artery occlusion for a period of 40 minutes. During this period of ischemia, each rat underwent placement of a jugular venous catheter that was connected to a subcutaneously placed osmotic pump designed to deliver its contents over 3 days. The rats were divided into 2 groups based on the contents of the pumps: group 1, saline at 1 microL/h (n = 6) and group 2, GLP-2alpha at 100 microg/kg/d (n = 4). Three days after insertion of the pumps the small intestine was harvested from the surviving rats for determination of mucosal DNA and protein content. Statistical analysis was performed using unpaired Student's t test. RESULTS: After I/R injury to the small intestine, a 3-day systemic infusion of GLP-2alpha significantly increased mucosal DNA content 41% (P<.05) and mucosal protein content 60% (P<.05) when compared with saline-treated controls. In addition, infusion of GLP-2alpha reduced mortality from 50% to 25%. CONCLUSIONS: These data show for the first time that GLP-2alpha enhances mucosal mass following I/R injury to the small intestine. GLP-2alpha may be of benefit to patients with intestinal ischemia syndromes such as necrotizing enterocolitis and midgut volvulus.     

Interleukin-11 enhances small intestine absorptive function and mucosal mass after intestinal adaptation

BACKGROUND/PURPOSE: Interleukin-11 (IL-11) recently has been shown to enhance mucosal mass after massive small bowel resection (MSBR). However, enhanced mucosal mass may not correlate with increased substrate absorption. This study was designed to examine the effect of systemic administration of increasing doses of IL-11 on small intestine absorptive function and mucosal mass after MSBR. METHODS: Twenty-five Sprague-Dawley rats underwent an 80% small bowel resection and end-to-end jejunoileal anastomosis. Seven days after resection, all rats had placement of a jugular venous catheter connected to a subcutaneously placed osmotic pump. The rats were divided into 5 groups based on the content of the pump: group 1 (control, n = 5) received 0.1% bovine serum albumin (BSA) and groups 2 through 5 (n = 5 each) received IL-11 at 250, 500, 750, and 1,000 microg/kg/d, respectively. After a 14-day infusion period, [14C] galactose and [14C] glycine absorption was measured using an in vivo closed-recirculation technique. Mucosal DNA content also was determined for each group. Statistical analysis was performed by analysis of variance and expressed as mean +/-SEM. RESULTS: IL-11 administered at 250 microg/kg/d, a dose used in previous studies, did not significantly affect substrate absorption. However, compared with the control group, administration of higher doses of IL-11 produced a significant increase in substrate absorption and mucosal mass. The dose of IL-11 producing the overall optimal response based on the parameters measured (galactose absorption, 72% increase over control; glycine absorption, 112% increase over control; and DNA content, 98% increase over control) was 750 microg/kg/d. CONCLUSIONS: In addition to an increase in mucosal mass, these data show for the first time that IL-11 enhances absorptive function beyond the normal adaptive response after MSBR. Furthermore, the maximum effect of IL-11 on absorptive function was shown at 750 microg/kg/d, which is 3 times the dose used in previously reported studies. This study suggests that IL-11 may be useful clinically in patients with inadequate intestinal function.     

Enhancement of small intestine absorption by intraluminal gastrin

Several studies have suggested that gastrointestinal peptides can produce trophic changes in the small intestine epithelium. In a previous study utilizing a rat fetal intestine transplant model, we reported that chronic, continuous, systemic administration of gastrin-17 increased carbohydrate absorption 2.5-fold and protein absorption 1.3-fold. The present study was designed to evaluate the effect of chronic luminal perfusion of gastrin on substrate absorption in rat mature small intestine. A 10-cm segment of mid small intestine was isolated with both ends brought out as abdominal wall stomas (creating a Thiry-Vella loop) and bowel continuity was established by end-to-end anastomosis. After a 1-week recovery, the tips of two catheters were positioned at approximately 3 and 6 cm from the proximal end of the isolated small intestine segment. A 14-day continuous luminal perfusion was accomplished by connecting the other ends of the catheters to subcutaneously placed osmotic pumps filled to deliver saline (control; N = 10) or gastrin-17 (13.5 nM/kg/day; N = 7). At the completion of the luminal perfusion, intestinal absorption was determined with labeled substrates [14C]galactose and [14C]glycine) using a closed, recirculation technique. Absorption (microM/cm2 small intestine) of galactose in the control animals was 1.44 +/- 0.18 and for the gastrin infused rats, it was 6.56 +/- 0.46. Glycine absorption was 1.63 +/- 0.31 for the control group and 7.83 +/- 0.62 for the gastrin infused group. Thus, in this rat model, intraluminal gastrin infusion was capable of increasing carbohydrate (galactose) absorption 456% (P less than 0.01) and protein (glycine) absorption 480% (P less than 0.01). These data represent the first demonstration that intraluminal gastrin can influence small intestine mucosal function by enhancing substrate absorption.(ABSTRACT TRUNCATED AT 250 WORDS)     

卡巴胆碱对烧创伤后肠道功能障碍影响的研究

目的观察肠道内给予卡巴胆碱对兔肠部分缺血再灌注(I/R)损伤及重度烧伤患者肠道功能障碍的影响。方法将50只大白兔制成肠部分I/R损伤模型后,随机分为肠部分I/R损伤组(25只)、卡巴胆碱组[25只,于肠系膜上动脉(SMA)阻断后1h肠内注入3g/L卡巴胆碱(3μg/kg)]；另取25只设为假手术组,仅分离SMA,不阻断；取5只作为正常对照组,不致伤,处死后留取标本待测。检测兔SMA阻断前后及肠道内给予卡巴胆碱后肠黏膜的血流量。各致伤组均在处理后2、4、6、8、24、48、72h留取静脉血测定其血浆二胺氧化酶(DAO)活性及D-乳酸和D-木糖含量。并行葡聚糖蓝排出实验,以检测胃肠道吸收功能。同时选择大面积烧伤[烧伤总面积(84±12)%TBSA]患者8例,在患者肠呜音＜2次/min或腹胀明显时,口服1g/L卡巴胆碱(15μg/kg),观察给药后每分钟肠鸣音次数及腹胀情况。结果SMA阻断后肠部分I/R损伤组肠黏膜血流量为(48±6)PU,较正常对照组[(102±5)PU]明显减少,而肠道内注入卡巴胆碱后1h血流量增至(77±3)PU。肠缺血后肠部分I/R损伤组血浆DAO活性及D-乳酸含量开始升高,处理后24h达峰值[(4．63±0．27)U/ml、(7．9±2．4)mg/L],以后逐渐下降,但仍高于正常对照组[(0．89±0．14)U/ml、(2．0±1．1)mg/L,P＜0．05]。卡巴胆碱组的变化基本同肠部分I/R损伤组,但变化幅度较小；而假手术组则无明显变化(P＞0．05)。在给予D-木糖后2h,肠部分I/R损伤组血浆D-木糖含量显著降低,但处理后6h肠部分I/R损伤组及卡巴胆碱组明显升高,以后逐渐下降；假手术组略有波动。SMA处理后2h肠部分I/R损伤组葡聚糖蓝未见排出,处理后6h其运动距离逐渐增加,但处理后24h其运动距离仍明显短于正常值(P＜0．05),48～72h基本恢复正常；卡巴胆碱组注入葡聚糖蓝后即可见其排出,其运动距离明显增加,处理后6h达峰值(43±6)cm,以后逐渐缩短接近正常(28±3)cm。给药前患者肠呜音较弱(1．6±1．1)次/min,给药后10 min明显增强为(6．9±1．7)次/min,30 min时为(8．3±2．4)次/min,给药后1h患者肠鸣音仍较活跃,为(6．1±1．3)次/min。给药后2h患者腹胀明显减轻,其中有6例患者开始排便。结论肠内给予卡巴胆碱可增加兔肠黏膜血流量,改善其肠道运动、吸收、屏障功能；大面积烧伤患者口服卡巴胆碱,可改善其肠道功能障碍。     

Influence of epidermal growth factor on intestinal function in the rat: comparison of systemic infusion versus luminal perfusion

Epidermal growth factor may be a trophic substance for the small intestine. Previous studies had not evaluated intestinal absorption after long-term continuous administration of epidermal growth factor or compared luminal perfusion with systemic infusion. Epidermal growth factor (150 micrograms/kg/day) was continuously infused either systemically or luminally for 14 days into young adult Fisher strain rats. Luminal studies were performed by creating 10 cm Thiry-Vella loops. At the conclusion of the 14 day infusions, mucosal DNA concentration and absorption of carbon-14 galactose and carbon-14 glycine were determined. The increase in DNA concentration after systemic or luminal infusion of epidermal growth factor was not statistically significant. However, galactose absorption increased 1.9-fold (p less than 0.05) after systemic epidermal growth factor infusion and glycine absorption increased 4.4-fold (p less than 0.01). Luminal epidermal growth factor perfusion increased galactose absorption 2.4-fold (p less than 0.05) and glycine absorption 4.1-fold (p less than 0.01). Thus, both systemic and luminal administration of epidermal growth factor can significantly increase substrate absorption. Additional studies on the physiologic implications and clinical usefulness of these data are warranted.     

No difference in intestinal strontium absorption after oral or IV calcitriol in children with secondary hyperparathyroidism. The European Study Group on Vitamin D in Children with Renal Failure

BACKGROUND: Oral and intravenous calcitriol bolus therapy are both recommended for the treatment of secondary hyperparathyroidism, but it has been claimed that the latter is less likely to induce absorptive hypercalcemia. The present study was undertaken to verify whether intravenous calcitriol actually stimulates intestinal calcium absorption less than oral calcitriol and whether it is superior in suppressing parathyroid hormone (PTH) secretion. METHODS: Twenty children (16 males, age range of 5.1 to 16.9 years, mean creatinine clearance 21.9 +/- 11.5 mL/min/1.73 m2, range of 7.4 to 52.7) with chronic renal failure (CRF) and secondary hyperparathyroidism [median intact PTH (iPTH), 327 pg/mL; range 143 to 1323] received two single calcitriol boli (1.5 mg/m2 body surface area) orally and intravenously using a randomized crossover design. iPTH and 1,25(OH)2D3 levels were measured over 72 hours, and intestinal calcium absorption was measured 24 hours after the calcitriol bolus using stable strontium (Sr) as a surrogate marker. Baseline control values for Sr absorption were obtained in a separate group of children with CRF of similar severity. RESULTS: The peak serum level of 1,25(OH)2D3 and area under the curve baseline to 72 hours (AUC0-72h) were significantly higher after intravenous (IV) calcitriol (AUC0-72h oral, 1399 +/- 979 pg/mL. hour vs. IV 2793 +/- 1102 pg/mL. hour, P < 0.01), but the mean intestinal Sr absorption was not different [SrAUC0-240min during the 4 hours after Sr administration 2867 +/- 1101 FAD% (fraction of the absorbed dose) vs. 3117 +/- 1581 FAD% with oral and IV calcitriol, respectively]. The calcitriol-stimulated Sr absorption was more then 30% higher compared with control values (2165 +/- 176 FAD%). A significant decrease in plasma iPTH was noted 12 hours after the administration of the calcitriol bolus, which was maintained for up to 72 hours without any differences regarding the two routes of administration. CONCLUSIONS: These results demonstrate that under acute conditions, intravenous and oral calcitriol boli equally stimulate calcium absorption and had a similar efficacy in suppressing PTH secretion.     

The influence of gastrin on gastrointestinal function

To improve intestinal function in children with short bowel syndrome, our laboratory has focused on identifying substances, which may enhance the function of small intestine epithelium. Previous studies have demonstrated that gastrin appeared to exert a trophic effect on the gastrointestinal tract. We chose to evaluate the influence of chronic, systemic, and luminal administration of gastrin-17 on substrate absorption in both fetal and mature rat small intestine. Transplanted fetal small intestine, mature small intestine in situ, and isolated mature small intestine segments were the surgical preparations used. Saline (control) or gastrin-17 (13.5 nmol/kg/d) was administered continuously for 14 days either systemically or luminally using osmotic pumps. The response to the saline or gastrin-17 infusions was determined by measuring absorption of radiolabeled substrates (14-C-galactose and 14-C-glycine). Following transplantation of fetal small intestine to a syngeneic host, galactose absorption rose 250% (P less than .01) and glycine absorption rose 130% (P less than .05) when compared with controls (N = 10). The response of mature jejunum and ileum following systemic gastrin infusion was a mild to moderate rise in galactose and glycine absorption, although statistical significance was not achieved. However, following luminal gastrin infusion into mature small intestine segments, there was a 4.54 fold rise in galactose absorption (P less than .01) and a 4.79 fold rise in glycine absorption (P less than .01) when compared with controls. These data suggest that gastrin can enhance substrate absorption in rat fetal and mature small intestine and that luminal perfusion appears to induce the greatest response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertonic saline infusion for pulmonary injury due to ischemia-reperfusion

HYPOTHESIS: Inhibition of neutrophil-endothelial cell interactions by hypertonic saline (HTS) may confer protection against organ injury in states of immunologic disarray. This study tested the hypothesis that infusion of HTS modulates the development of end-organ injury in a model of lower-torso ischemia-reperfusion injury. DESIGN: Ischemia-reperfusion injury was induced in 30 male Sprague-Dawley rats by infrarenal aortic cross-clamp for 30 minutes, followed by reperfusion for 2 hours. At 0 and 60 minutes of reperfusion, intravenous HTS (7.5% sodium chloride, 4 mL/kg) was administered to 6 rats each, and another 12 received either 4 or 30 mL/kg of isotonic sodium chloride solution. Six rats received HTS, 4 mL/kg, before ischemia. At 2 hours, we assessed liver function, pulmonary injury, neutrophil infiltration (myeloperoxidase activity), endothelial permeability (bronchoalveolar lavage and wet-dry weight ratios), and proinflammatory cytokine levels (tumor necrosis factor alpha and interleukin 6). RESULTS: Infusion with HTS before or after ischemia significantly reduced end-organ injury. Histopathologic pulmonary injury scores were markedly attenuated in the HTS group (5.82 +/- 1.3) and the HTS pretreated group (4.91 +/- 1.6) compared with the isotonic sodium chloride solution groups (8.54 +/- 1.1) (P =.04). Pulmonary neutrophil sequestration (2.07 +/- 0.23) and increased endothelial permeability (4.68 +/- 0.44) were manifest in animals resuscitated with isotonic sodium chloride solution compared with HTS treatment (1.54 +/- 0.19 [P =.04] and 2.06 +/- 0.26 [P =.02]) and pretreatment (1.18 +/- 0.12 [P =.04] and 1.25 +/- 0.07 [P =.002]). In addition, a significant reduction in serum tumor necrosis factor alpha (P =.04) and interleukin 6 (P =.048) levels was observed, whereas HTS resuscitation attenuated the upsurge in aspartate transaminase (P =.03) and alanine transaminase levels (P =.047). CONCLUSIONS: Resuscitation with HTS attenuates the pulmonary edema and tissue injury due to lower-torso ischemia-reperfusion and maintains a more benign immunologic profile.     

Systemic GLP-2 levels do not limit adaptation after distal intestinal resection

BACKGROUND/PURPOSE: Glucagonlike peptide 2 (GLP-2) is trophic for the small bowel; it is produced by L cells in the distal intestine in response to luminal nutrients. This study tests the hypothesis that distal small bowel and cecal resection would decrease GLP-2 levels and reduce adaptation. METHODS: Male Sprague-Dawley rats (200 to 300 g) underwent either ileal transection (controls) or resection of the ileum and cecum, leaving 10 or 20 cm jejunal remnant anastomosed to the ascending colon. Animals were followed up for up to 21 days. Endpoints were daily weights, intestinal histology, in vivo absorption of 3-0 methylglucose (a measurement of active nutrient absorptive capacity), and serum GLP-2 levels. RESULTS: The control group had a maximum 6% weight loss around day 2, and then recovered with a steady weight gain. The 10-cm jejunal remnant group lost weight continuously and never recovered postsurgery. The 20-cm jejunal remnant group of animals had a maximum of 12% weight loss by day 4 and then slowly gained weight. The average villus height increased significantly (P <.01) in the 10-cm and 20-cm jejunal remnant groups compared with controls. Absorption of 3-0 methylglucose was significantly decreased (P <.01) in both resected groups. Serum GLP-2 levels were increased significantly (P <.05) when compared with controls in both resection groups. CONCLUSIONS: Increased serum GLP-2 levels were found in the ileocecal resection rat model, and these levels correlated with morphologic adaptation. However, this morphologic adaptation was not sufficient to restore nutrient absorption as shown by weight changes and 3-0 methylglucose absorption. Thus, the original hypothesis of this study is incorrect: systemic GLP-2 levels do not limit adaptation following distal ileocecal resection.     

Interleukin-11 enhances intestinal absorptive function after ischemia-reperfusion injury

Background/Purpose: Interleukin-11 (IL-11) is a multifunctional cytokine that has been shown to improve small bowel adaptation and enhance cellular recovery after bowel ischemia. This study was designed to examine the effects of systemic IL-11 on small bowel absorptive function in a rat model of intestinal ischemia and reperfusion (IR) injury. Methods: Sprague-Dawley rats underwent placement of a venous catheter connected to an osmotic pump, which delivered its contents over 3 days. Rats were divided into 3 groups: sham operation/systemic saline; 30-minute superior mesenteric artery occlusion/systemic saline; superior mesenteric artery occlusion/systemic IL-11, 750 [mu ]g/kg/d. After the infusion, ¹⁴C-galactose or ¹⁴C-glycine absorption was measured using an in vivo, recirculation technique. Statistical significance was determined using analysis of variance. Results: In control rats, 30 minutes of IR decreased absorption of galactose from 2.62 to 2.02 [mu ]moles/cm² (P [lt ] .01), and glycine from 2.79 to 1.72 [mu ]moles/cm² (P [lt ] .01). Rats treated with systemic IL-11 showed improved absorption of galactose of 2.39 [mu ]moles/cm² (P [lt ] .05), and glycine at 2.21 [mu ]moles/cm² (P [lt ] .05). Mucosal DNA content was reduced significantly from 7.37 to 5.61 [mu ]g DNA/mg by IR (P [lt ] .01). IL-11 treatment did not significantly alter DNA content during this period. Conclusions: These data show that 30 minutes of intestinal IR significantly decreases intestinal absorptive function in this animal model. When compared with untreated control animals, administration of systemic IL-11 significantly increased the absorption of carbohydrate and amino acid in rats recovering from mesenteric IR.     

Protective effects of glucagon-like peptide 2 on intestinal ischemia-reperfusion rats

Our objective was to evaluate the protective effects of glucagon-like peptide 2 (GLP-2) on intestinal ischemia/reperfusion (I/R) rats. Thirty-two rats were randomly assigned to four experimental groups, each of 8: Group A, sham rats underwent laparotomy only, without superior mesenteric artery (SMA) occlusion; Group B, I/R animals underwent laparotomy and occlusion of the SMA for 60 minutes followed by 120 minutes of reperfusion; Group C, I/R animals underwent intestinal I/R, and received pretreatment with GLP-2 for 3 days preoperatively; and Group D, I/R animals underwent intestinal I/R, received pretreatment with GLP-2 as above, and during the reperfusion phase were injected intravenously with GLP-2. After the reperfusion of intestinal ischemia, samples of intestinal mucosa, mesenteric lymph nodes (MLN) and blood were prepared for determination. In the pretreatment rats with GLP-2 (group C), Chiu's scores, bacterial colony counts, serum D-lactate, intestinal mucosal MDA and ET-1, and serum endotoxin, TNF-alpha and IL-6 were significantly reduced compared with intestinal I/R rats (group B). Administration of GLP-2 during the reperfusion phase following pretreatment (group D) showed further protective effects in comparison with the pretreatment rats (group C). We conclude that treatment with GLP-2 attenuates intestinal I/R injury, reduces bacterial translocation, inhibits the release of oxygen free radicals and ET-1, and may well inhibit the production of proinflammatory cytokines.     

重组胰高血糖素样多肽2对烧伤大鼠肠黏膜的保护作用

目的验证重组胰高血糖素样多肽2（GLP-2）对严重烧伤大鼠的肠道保护作用。方法将SD大鼠随机分为正常对照组；烧伤对照组；重组GLP-2治疗组（重组治疗组），烧伤后4h皮下注射重组GLP-2，100nmol·kg^-1·d^-1；化学合成GLP-2治疗组（合成治疗组），烧伤4h后皮下注射合成GLP-2，剂量同上。每组6只大鼠。伤后第7天检测各致伤组大鼠肠黏膜通透性、肠黏膜湿质量与肠段及躯壳质量比、肠黏膜蛋白含量以及观察肠道组织病理学变化，正常对照组观察指标相同。结果重组治疗组及合成治疗组与烧伤对照组[（0．350±0．040）mg／m1]比较，大鼠肠黏膜通透性明显降低（P〈0．01），分别为（0．250±0．026）、（0．243±O．008）mg／ml；肠黏膜湿质量与躯壳质量比及肠黏膜蛋白含量明显增加，重组治疗组大鼠肠黏膜蛋白含量为（57．9±2．8）mg／g，高于合成治疗组（48．9±4．1）mg／g。与正常对照组比较，各致伤组大鼠伤后第7天肠黏膜绒毛明显变短脱落、排列紊乱、基底层变薄。重组治疗组损伤较烧伤对照组有所减轻，与合成治疗组大鼠无明显区别。结论重组GLp02与合成GLP-2，能减轻烧伤大鼠肠道损伤，具有明显的肠道保护作用。     

Does tranexamic acid reduce desmopressin-induced hyperfibrinolysis?

OBJECTIVE: Desmopressin releases tissue-type plasminogen activator, which augments cardiopulmonary bypass--associated hyperfibrinolysis, causing excessive bleeding. Combined use of desmopressin with prior administration of the antifibrinolytic drug tranexamic acid may decrease fibrinolytic activity and might improve postoperative hemostasis. METHODS: This prospective randomized study was carried out with 100 patients undergoing coronary artery bypass operations between April 1999 and November 2000 in Gülhane Military Medical Academy. Patients were divided into 2 groups. Desmopressin (0.3 microg/kg) was administrated just after cardiopulmonary bypass and after protamine infusion in group 1 (n = 50). Both desmopressin and tranexamic acid (before the skin incision at a loading dose of 10 mg/kg over 30 minutes and followed by 12 hours of 1 mg.kg(-1).h(-1)) were administrated in group 2 (n = 50). RESULTS: Significantly less drainage was noted in group 2 (1010 +/- 49.9 mL vs 623 +/- 41.3 mL, P =.0001). Packed red blood cells were transfused at 2.1 +/- 0.5 units per patient in group 1 versus 0.9 +/- 0.3 units in group 2 (P =.0001). Fresh frozen plasma was transfused at 1.84 +/- 0.17 units per patient in group 1 versus 0.76 +/- 0.14 units in group 2 (P =.0001). Only 24% of patients in group 2 required donor blood or blood products compared with 74% of those in the isolated desmopressin group (group 1, P =.00001). Group 1 and group 2 findings were as follows: postoperative fibrinogen, 113 +/- 56.3 mg/dL versus 167 +/- 45.8 mg/dL (P =.0001); fibrin split product, 21.2 +/- 2.3 ng/mL versus 13.5 +/- 3.4 ng/mL (P =.0001); and postoperative hemoglobin level, 7.6 plus minus 1.2 g/dL versus 9.1 plus minus 1.2 g/dL (P =.0001). CONCLUSION: Tranexamic acid administration significantly reduces desmopressin and bypass-induced hyperfibrinolysis. Combined use of tranexamic acid and desmopressin decreases both postoperative blood loss and transfusion requirement.     

The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis

BACKGROUND: Acute pancreatitis (AP) initiates a generalized inflammatory response that increases intestinal permeability and promotes bacterial translocation (BT). Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon-like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the intestinal mucosa by stimulating epithelial growth. The purpose of this study was to determine whether GLP-2 decreases intestinal permeability and BT in AP. METHODS: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied. AP was induced in group I and group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II rats received a similar volume of normal saline as a placebo postoperatively for 3 days. Group III and group IV received GLP-2 analog and placebo, respectively. At 72 hours postoperatively, blood was drawn for culture of gram-negative organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum were harvested for culture of gram-negative bacteria. Intestinal resistance as defined by Ohm's law was determined using a modified Ussing chamber to measure transepithelial current at a fixed voltage. A point scoring system for five histologic features that include intestinal edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and ileum were taken for pathology. RESULTS: All group I and group II rats had AP. The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas, and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%, 30%, and 20% translocation in group II. CONCLUSION: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis.     

Comparisons of the effects of calcium carbonate and calcium acetate on zinc tolerance test in hemodialysis patients.

Because aluminum hydroxide, as a phosphate binder, lowered intestinal zinc absorption, we studied the effects of calcium carbonate (CaCO3) and calcium acetate (CaAc), two other phosphate binders, on intestinal Zn absorption in nine patients on hemodialysis and in 11 controls by measuring 1- and 2-hour serum Zn levels after oral administration of 50 mg of elemental Zn as Zn gluconate with or without concomitant administration of 2 g CaCO3 (800 mg elemental Ca) or 3 g CaAc (750 mg elemental Ca). Fasting serum Zn levels were not different between patients and controls (14.0 +/- 2.3 v 14.1 +/- 1.2 mumol/L [91.8 +/- 14.9 v 92.3 +/- 8.0 micrograms/dL]), but the area under the curve of serum Zn increment (AUC) 2 hours after an oral Zn challenge without or with either of two of phosphate binders used was significantly smaller in patients than in controls (P less than 0.05). The AUC after concomitant administration of Zn with CaCO3 did not differ from that of Zn alone in either patients or controls, but it was significantly less in Zn with CaAc than in Zn alone or in Zn with CaCO3 in both groups. The results demonstrate that intestinal Zn absorption after an oral Zn challenge decreased in patients on hemodialysis and concomitant administration of CaAc, but CaCO3 did not decrease intestinal Zn absorption in either group.