iatrogenic vascular injury during lumbar disc surgery, although rare, should be suspected if signs of circulatory instability are noted or if lumbar pain, leg oedema or high output cardiac failure develop months to years following such surgical procedures. However, these symptoms may arise during or immediately after surgery, requiring immediate intervention.

Background/Objectives: The aim of this study was to research and draw conclusions about the effect of a parenteral nutrition (PN) fat emulsion, rich in o-3 fatty acids, on the antioxidant markers of preterm infants, when compared with a standard fat emulsion. This was a double-blind, parallel-group study conducted in Athens, Greece, using an equal randomization method. Subjects/Methods: Thirty-eight infants were selected using a double-blind method and a computer-generated randomization list. Both groups received PN, based on the same protocols. Group A received SMOFlipid fat emulsion, while group B received the standard fat emulsion (Intralipid). Serum levels of vitamin A, E and total antioxidant potential (TAP) were measured on days 0, 7 and 14 of PN support. Clinical and biochemical data were collected on days 0, 14 and on the day of discharge. Results: Serum levels of vitamin E and A were significantly increased in group A, while only vitamin A serum level was increased in group B on the fourteenth day (group A: vitamin E: P-value ¼ 0.002, vitamin A: P-value ¼ 0.000, group B: vitamin E: P-value ¼ 0.065, vitamin A: P-value ¼ 0.000). TAP was increased only in the intervention group (group A: P-value ¼ 0.000, group B: P-value ¼ 0.287). Mild anemia was developed in both groups, while no differences were detected in the infection rate, days of hospitalization, days of ventilator support and days of phototherapy. Conclusions: Oxidative stress was significantly reduced in those neonates fed with o-3 fatty acids, whereas no effect was observed in the neonates fed with standard lipids. Intervention had no effect on infants' growth and clinical outcome.

The effect of liver growth stimulation [using the rodent PXR (pregnane X receptor) activator PCN (pregnenolone-16alpha-carbonitrile)] in rats chronically treated with carbon tetrachloride to cause repeated hepatocyte necrosis and liver fibrogenesis was examined. PCN did not inhibit the hepatotoxicity of carbon tetrachloride. However, transdifferentiation of hepatic stellate cells and the extent of fibrosis caused by carbon tetrachloride treatment was significantly inhibited by PCN in vivo. In vitro, PCN directly inhibited hepatic stellate cell transdifferentiation to a profibrogenic phenotype, although the cells did not express the PXR (in contrast with hepatocytes), suggesting that PCN acts independently of the PXR. Mice with a functionally disrupted PXR gene (PXR-/-) did not respond to the antifibrogenic effects of PCN, in contrast with wild-type (PXR+/+) mice, demonstrating an antifibrogenic role for the PXR in vivo. However, PCN inhibited the transdifferentiation of PXR-/--derived mouse hepatic stellate cells in vitro, confirming that there is also a PXR-independent antifibrogenic effect of PCN through a direct interaction with hepatic stellate cells. These data suggest that the PXR is antifibrogenic in rodents in vivo and that a PXR-independent target for PXR activators exists in hepatic stellate cells that also functions to inhibit fibrosis.

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PXR activators are used to treat pruritus in chronic inflammatory liver diseases such as primary biliary cirrhosis (PBC). The aims of this study were to determine whether PXR activators could have an additional benefit of inhibiting inflammation in the liver, and determine whether cyclosporin A – which more effectively prevents PBC recurrence in transplanted patients than FK506 – is a PXR activator. In SJL/J mice (which have constitutively high levels of hepatic portal tract inflammatory cell recruitment), feeding a PXR activator inhibited inflammation, TNFα and Il-1α mRNA expression in SJL/J-PXR+/+, but not SJL/J-PXR−/−. Monocytic cells – a major source of inflammatory mediators such as TNFα – expressed the PXR and PXR activators inhibited endotoxin-induced NF-κB activation and TNFα expression. PXR activation also inhibited endotoxin-stimulated TNFα secretion from liver monocytes/macrophages isolated from PXR+/+ mice, but not from cells isolated from PXR−/− mice. To confirm that PXR activation inhibits NF-κB in vivo, 3x-κB-luc fibrotic mice (which express a luciferase gene regulated by NF-κB) were imaged after treatment with the hepatotoxin CCl4. PXR activator inhibited the induction of hepatic NF-κB activity without affecting CCl4 toxicity/hepatic damage. Using a PXR reporter gene assay, cyclosporin A – but not FK506 – was shown to be a direct PXR activator, and also to induce expression of the classic PXR-regulated CYP3A4 gene in human hepatocytes and in a cell line null for the FXR, a nuclear receptor with similar properties to the PXR. Conclusion: PXR activation is anti-inflammatory in the liver and the effects of cyclosporin A in PBC disease recurrence may be mediated in part via the PXR. Since PXR activation promotes hepatocyte growth and is also anti-fibrogenic, the PXR may be an excellent drug target for the treatment of chronic inflammatory liver disease.