Parenteral Nutrition Administration Leads to Specific Alterations in the Expression of Adipocytokines and Peroxisome Proliferator‐Activated Receptors in a Rat Model

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141876/1/jpen0329-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141876/2/jpen0329.pd

Interleukin-6 changes tight junction permeability and intracellular phospholipid content in a human enterocyte cell culture model

Proinflammatory cytokines and secretory phospholipase A 2 (sPLA 2 ) are elevated in patients with inflammatory bowel disease (IBD). We previously reported that the proinflammatory cytokine IL-6 increased the expression of sPLA 2 (a hydrolyzer of phosphatidylcholine) and decreased membrane integrity in an intestinal epithelial cell culture model. To determine the physiological effects of the IL-6 mediated increase in sPLA 2 on decreased epithelial layer integrity, we investigated alterations of intracellular/secretory phospholipid (PL) composition in a cell culture model. In addition, since other PLs may also mediate epithelial membrane activity, we investigated the effect of IL-6 on PL activity in a Caco-2 enterocyte culture model. Caco-2 cells were incubated for 72 h with IL-6 or media alone (control). Both media and cell lysate were analyzed for PL composition using thin-layer chromatography. The PL composition in the media did not show any differences between the two groups ( p >0.1). Total intracellular PL contents were also unchanged; however, IL-6 led to significant changes in PL composition including an increase in phosphatidylethanolamine (PE) and sphingomyelin (SM) and a decrease in phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) ( p <0.05). Both PE and SM are known as inflammatory signaling factors involved in human IBD. Our study suggests that the decreased membrane integrity seen with IL-6 application may occur via intracellular PL alterations, rather than through the direct effects of sPLA 2 .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47156/1/383_2003_Article_1003.pd

The effect of hypoxia on permeability and bacterial translocation in Caco-2 adult and I-407 fetal enterocyte cell culture models

Hypoxia has been implicated in the breakdown of the intestinal epithelial barrier in animals, leading to bacterial translocation (BT); however, the mechanism of this hypoxic insult is unknown. To determine the effects of hypoxic injury in vitro on epithelial membrane integrity, transepithelial electrical resistance (TEER), mannitol permeability (Ma-Pm), and BT were measured in both an adult (Caco-2) and fetal (I-407) intestinal epithelial cell culture model. Caco-2 adult and I-407 fetal epithelial cell monolayers were treated with or without bacteria (1×10 7 Escherichia coli. C-25), and then incubated under either normoxic (5% CO 2 in room air) or hypoxic (5% CO 2 and 95% N 2 ) conditions at 37°C for 6 h. Hypoxia caused a 10% increase in Ma-Pm in the I-407 fetal cell model independent of the bacterial challenge. In contrast, a bacterial challenge in the Caco-2 adult model caused a 485% increase in Ma-Pm independent of hypoxia. Neither hypoxia, nor C-25 bacteria, for 6 h caused BT in either cell culture model. In the adult cell culture model, bacteria appear to mediate changes in epithelial barrier function, with hypoxia having no effect. On the other hand, hypoxia is the major factor in the loss of epithelial barrier function in fetal epithelium, but has no effect on adult epithelium. The data suggest that the breakdown of barrier function caused by a hypoxic insult is the primary stimulus for subsequent BT in neonates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47155/1/383_2003_Article_1002.pd

Effects of lipid administration on liver apoptotic signals in a mouse model of total parenteral nutrition (TPN)

Lipids are an important component of total parenteral nutrition (TPN), contributing the largest caloric load per volume of solution and providing essential fatty acids necessary for survival. However, lipids are known to be causative factors in oxidative stress, which are expressed via the Bcl-2 family of proteins and/or Fas-mediated apoptosis in several tissues. Interestingly, we have recently observed an increase in hepatocyte apoptosis with administration of TPN. To address the mechanism of this apoptosis, we investigated the effects of parenteral lipid administration on apoptotic signaling in a mouse model. C57BL/6J male mice received physiologic saline and standard chow (control) or standard TPN solution with (TPN+L) or without lipid (TPN-L) emulsion. After 7 days of infusion, apoptosis increased in the TPN+L at a significantly higher rate compared with control and TPN-L groups ( p <0.05). Both TPN, with and without lipids, suppressed the pro-apoptotic signals Bid and Bcl-xs ( p <0.05). In contrast, TPN with lipid increased the expression of Fas and both the pro-apoptotic factor Bad and the anti-apoptotic factor Bcl-xl ( p <0.05). These changes may contribute to TPN-induced hepatocyte injury (apoptosis) or suppress the ability of liver hepatocytes to regenerate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47162/1/383_2003_Article_1115.pd

Successful recording perioperarive hemodynamic changes with the severe right diaphragmatic hernia

We experienced a case of severe congenital diaphragmatic hernia (CDH) with severe deleterious hypoxemia after birth in which we succeeded in saving the patient with radical surgery. Observation of the patient's detailed hemodynamics was possible for the entire perioperative period. The central venous pressure (CVP) was high according to the pressure in the liver. The CVP subsequently decreased after the operation, and the oxygen saturation increased. Therefore, the cardiac diastolic disorder improved. This case suggests that the diastolic dysfunction in severe CDH patients is worsen by compression from herniated visceral organs

Clinical implications of serum autotoxin in regular follow up after pediatric living donor liver transplantation for biliary atresia

Background: : Pediatric patients sometimes develop graft fibrosis after living donor liver transplant (LDLT). Autotaxin is a recently developed serum marker for hepatic fibrosis. We studied the relationship between serum autotaxin levels and histological findings in patients after LDLT for biliary atresia (BA). Methods: Information on patients aged <19 years who received LDLT for BA and were followed for at least 1 year after LDLT was gathered. Autotaxin levels were compared with pathological fibrosis scores. Results: The study included 52 patients, of whom 4 patients had no fibrosis (F0), 36 patients had F1 fibrosis, and 12 patients had F2. The median serum autotaxin level was 0.89 mg/L. In patients with portal vein (PV) complications such as stenosis or thrombosis (n = 7), the mean autotoxin level was 1.25 mg/L compared with 0.95 mg/L in patients without PV complications (p = 0.004). Among patients without PV complications, the mean autotaxin level was 0.90, 0.88, and 1.18 mg/L in F0, F1, and F2 fibrosis, respectively. The mean autotaxin was higher in F2 fibrosis than in F0 or F1 fibrosis (p<0.05). Autotoxin had a high area under the curve (0.86) with the cut-off level of 0.897 mg/L. Conclusion: Serum autotaxin is a novel marker for liver fibrosis in patients after pediatric LDLT for BA. Type of study: : Study of Diagnostic Test. Level of evidence: : Level II