PPAR-gamma agonist protects against intestinal injury during necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) remains a lethal condition for many premature infants. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor family, has been shown to play a protective role in cellular inflammatory responses; however, its role in NEC is not clearly defined. We sought to examine the expression of PPAR-gamma in the intestine using an ischemia-reperfusion (I/R) model of NEC, and to assess whether PPAR-gamma agonist treatment would ameliorate I/R-induced gut injury. Swiss-Webster mice were randomized to receive sham (control) or I/R injury to the gut induced by transient occlusion of superior mesenteric artery for 45 min with variable periods of reperfusion. I/R injury resulted in early induction of PPAR-gamma expression and activation of NF-kappaB in small intestine. Pretreatment with PPAR-gamma agonist, 15d-PGJ(2), attenuated intestinal NF-kappaB response and I/R-induced gut injury. Activation of PPAR-gamma demonstrated a protective effect on small bowel during I/R-induced gut injury.

Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury.

We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK)zeta, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGKzeta siRNA transfection decreased H2O2-induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGKzeta also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGKzeta rapidly translocated to the cytoplasm following H2O2 treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGKzeta, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells.

The incidence of complications associated with loop duodeno-ileostomy after single-anastomosis duodenal switch procedures among 1328 patients: a multicenter experience.

BACKGROUND: The single-anastomosis duodenal switch procedure is a type of duodenal switch that involves a loop anastomosis rather than traditional Roux-en-Y reconstruction. To date, there have been no multicenter studies looking at the complications associated with post-pyloric loop reconstruction. OBJECTIVES: The aim of the study was to report the incidence of complications associated with loop duodeno-ileostomy (DI) following single-anastomosis duodenal switch (SADS) procedures. SETTING: Mixed of private and teaching facilities. METHODS: The medical records of 1328 patients who underwent primary SADS procedure (single-anastomosis duodeno-ileal bypass with sleeve gastrectomy or stomach intestinal pylorus-sparing surgery) by 17 surgeons from 3 countries (United States, Spain, and Australia) at 9 centers over a 6-year period were retrospectively reviewed, and their results were compared with articles in the literature. RESULTS: Mean preoperative body mass index was 51.6 kg/m2. Of 1328 patients, 123 patients received a linear stapled duodeno-ileostomy (DI) and 1205 patients a hand-sewn DI. In the overall series, the anastomotic leak, ulcer, and bile reflux occurred in .6% (9/1328), .1% (2/1328), and .1% (2/1328), respectively. None of our patients experienced volvulus at the DI or an internal hernia. Overall, 5 patients (.3%) (3/123 [2.4%] with linear stapled DI versus 2/1205 [.1%] with hand-sewn DI [P<.05]) experienced stricture at the DI in this series. CONCLUSIONS: The overall incidence of complications associated with loop DI was lower than the reported incidence of anastomotic complications after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch. SADS procedures may cause much fewer anastomotic complications compared with Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch.

Bombesin induces angiogenesis and neuroblastoma growth.

Gastrin-releasing peptide (GRP), the mammalian equivalent of bombesin (BBS), is a trophic factor for highly vascular neuroblastomas; its mechanisms of action in vivo are unknown. We sought to determine the effects of BBS on the growth of neuroblastoma xenografts and on angiogenesis. BBS significantly increased the growth of SK-N-SH and BE(2)-C human neuroblastomas; tumors demonstrated increased expression of angiogenic markers, PECAM-1 and VEGF, as well as phosphorylated (p)-Akt levels. RC-3095, a BBS/GRP antagonist, attenuated BBS-stimulated tumor growth and angiogenesis in vivo. GRP or GRPR silencing significantly inhibited VEGF as well as p-Akt and p-mTOR expression in vitro. Our findings demonstrate that BBS stimulates neuroblastoma growth and the expression of angiogenic markers. Importantly, these findings suggest that novel therapeutic agents, targeting BBS-mediated angiogenesis, may be useful adjuncts in patients with advanced-stage neuroblastomas.

Complications of femoral artery catheterization in pediatric burn patients.

A retrospective analysis of all pediatric patients admitted for acute burn treatment during a 7-year period was conducted to examine patients who underwent femoral artery catheterization and discuss the associated complications and treatment options. The total number of femoral artery catheterizations performed, nature of vascular complications, treatment rendered, and patient outcome were reviewed. Of the 1800 acute burn pediatric patients treated during our study period (1996-2002), 234 patients underwent a total of 745 femoral artery catheterizations. There was a 1.9% incidence of significant complications as a result of catheterization, including problems during catheter insertion, diminished distal arterial pulses following catheter placement and catheter malfunction. Eight patients (3.4%) developed occlusion or spasm of the femoral artery evidenced by loss of distal pulses. Of these, three required thrombectomy and the other five were treated nonsurgically with immediate catheter removal and systemic heparinization. Both groups showed similar overall outcome with return of distal pulses and absence of distal limb or tissue loss. Our findings indicate that femoral artery catheterization in pediatric burn patients is associated with a low occurrence of vascular complications. The majority of patients with acute distal limb ischemic symptoms can be managed nonoperatively with immediate removal of the catheter and systemic heparinization.