Several observed clinical and immunological similarities between lipopolysaccharide (LPS), an integral component of the outer cell membranes of gram-negative bacteria, and peptidoglycan (PGN), a component of the cell walls of gram-positive bacteria, suggest that the two bacterial components initiate analogous signaling pathways after being recognized by monocytes/macrophages (8,12,15,33,49). These signaling pathways are thought to be cascades for NF-B activation. Activated NF-B controls the transcription of numerous genes including those involved in cell proliferation, transformation, inflammation, and survival (2, 3, 32). Besides activating NF-B, LPS and PGN similarly activate other transcription factors, such as CREB/ATF and AP-1, in a membrane CD14 (mCD14)-dependent or -independent manner (13, 14, 18). The real dissimilarity between their signal pathways was revealed recently, and their initial discrimination by different Drosophila melanogaster Toll proteins, evolutionarily conserved from fruit flies to humans, is under way (4, 21). To date, six human Toll-like receptors (TLRs) have been cloned (40,44). Of these, TLR2 and TLR4 have been extensively investigated and are thought to be signal transducers of PGN and LPS, respectively (7,24,32,35,50).TLR2, predominantly distributed in monocytes/macrophages and polymorphonuclear cells (PMNs) (34), had been thought to be a signal transducer of LPS. Conclusive evidence mainly came from the following data. First, the overexpression of TLR2 in human embryonic 293 cells conferred LPS responsiveness on the cells, resulting in NF-B activation and interleukin-8 (IL-8) mRNA expression. Second, the cotransfection of TLR2 with mCD14 synergistically enhanced LPS signaling (24, 50). Third, the putative complex of mCD14-TLR2 after LPS exposure to the cotransfected cells was found to initiate an IL-1 receptor-like NF-B signaling cascade (51). Fourth, the LPS-elevated expression of the TLR2 gene, as measured by reverse transcription-PCR (RT-PCR), was observed in human monocytes and in mouse peritoneal macrophages (31,50). Like the transcriptional expression of TLR2, the transcriptional expression of mCD14 in human monocytes is upregulated by LPS (30). The elevated expression of the TLR2 and mCD14 genes undoubtedly contributes to the resensitization of macrophages to invasive pathogens. However, the finding that TLR4 but not TLR2 senses LPS has challenged the above conclusions.TLR4 is predominantly present in monocytes/macrophages, PMNs, dermal microvessel and umbilical vein endothelial cells, and intestinal epithelial cells (6,9,34). Several studies have shown that a TLR4 transfectant initiates a series of events for NF-B activation, as does TLR2 (7,32). Moreover, the macrophages and B cells from mice (C3H/HeJ) that have a TLR4 mutation in the intracellular domain consisting of the replacement of a conserved proline residue by histone are hyporesponsive to LPS in vitro and in vivo (22,36,38). Further evidence from TLR2 and TLR4 knockout mice has confirmed

Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

Our data suggest that the redox behavior of cyt. ox. during an operation is a good (though not perfect) predictor of postoperative cerebral outcome, and that overall tissue oxygen sufficiency can be confirmed by near-infrared measurement of cyt. ox.

† Sugammadex is increasingly used for the reversal of rocuronium neuromuscular block. † Report of three cases showing evidence of an allergic response immediately after sugammadex. † Two patients had a subsequent positive skin test to sugammadex, the third declined testing. Summary. Neuromuscular blocking agents have been implicated in 60-70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.

Endotoxin is a causative factor in peripheral vascular failure, resulting in a hemodynamic depression that includes a reduction in liver blood flow. The administration of olprinone (phosphodiesterase III inhibitor) improves the liver blood flow circulation in a porcine model of endotoxemia.