Use of smaller-sized ETT combined with i.v. lidocaine decreases the incidence and severity of POST in women undergoing thyroid surgery.

Purpose: Flurbiprofen axetil (FA) is a potent non-steroidal antiinflammatory drug (NSAID). We examined the effects that perioperative intravenous administration of FA, combined with thoracic epidural anesthesia and postoperative patient-controlled epidural analgesia (PCEA), have on bowel function, postoperative pain, and cytokine release, after open colorectal surgery. Methods:This was a prospective, randomized, double-blind, placebo-controlled study. Forty patients were randomly assigned to one of two groups (n = 20 in each group). The FA group patients received FA 1 mg·kg -1 iv, 30 min before and six hours after skin incision; whereas the control group patients received an equal volume of intralipid. Blood cytokine levels were measured before FA administration, at the end of surgery, and six hours and 24 hr postoperatively. All patients received postoperative PCEA for pain control. Analgesic efficacy was evaluated for 72 hr postoperatively using visual analogue scale (VAS) pain scores both at rest and during coughing. Gastrointestinal motility was recorded. Temperature and leukocyte count were measured preoperatively, and 24 hr postoperatively. Results:The times to first bowel movement (87 ± 23 vs 105 ± 19 hr, P = 0.008) and first flatus (63 ± 16 vs 75 ± 11 hr, P = 0.01) were earlier in the FA group compared to the control group. For the first 24 hr, the pain scores in the FA group were also lower during coughing (P < 0.001 compared to control). The plasma concentrations of interleukin (IL)-6 and IL-8 in the FA group were lower, postoperatively (P < 0.01 and P < 0.05, respectively, compared to control). In contrast, the IL-10 levels were significantly increased at six hours, postoperatively, in the FA group (P = 0.009). The total leukocyte count and the incidence of pyrexia were also lower in patients of the FA group (P = 0.001 and P = 0.006, respectively, compared to control). Conclusion:Flurbiprofen axetil may have an anti-inflammatory effect in major abdominal surgery. The combination of perioperative intravenous FA, intraoperative thoracic epidural anesthesia, and postoperative PCEA facilitated recovery of bowel function, enhanced analgesia, and attenuated the cytokine response.

Propofol has been reported to protect vascular endothelial cells against oxidative stress and dysfunction, but the underlying mechanisms are not clear. In this study, we studied hydrogen peroxide (H(2)O(2))-induced oxidative stress and cell dysfunction in human umbilical vein endothelial cells (HUVECs) and especially, their modulation by propofol. HUVECs were treated with different concentrations (0.1 and 0.5 mM) of H(2)O(2) for different times (1, 3, and 6 h). Then HUVECs were pretreated with different concentrations of propofol (10, 25, and 50 microM), followed by H(2)O(2) treatment (0.5 mM, 3 h). In another set of experiments, we pretreated cells with p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580, followed by H(2)O(2) treatment (0.5 mM, 3 h). After treatment, oxidative stress, p38 MAPK phosphorylation, transcription factor NF-kappaB activation, nitric oxide synthase (NOS) expression, nitric oxide (NO) production, and monocyte adhesion were measured. We observed H(2)O(2) treatment significantly induced oxidative stress, which could be attenuated by 25 microM propofol pretreatment. In addition, H(2)O(2) treatment significantly induced p38 MAPK phosphorylation, NF-kappaB activation, NOS expression, and NO production. More importantly, our study showed these H(2)O(2)-induced changes were attenuated by propofol or SB203580 pretreatment. Further, we measured monocyte adhesion as a marker of endothelial cell dysfunction. H(2)O(2) increased the adhesion of monocytes to HUVECs, and propofol pretreatment reduced the adhesion in a fashion similar to SB203580. We concluded that propofol, by inhibiting p38 MAPK and NF-kappaB activity, decreasing NOS expression, reducing NO production, could protect HUVECs which are exposed to oxidative stress and becoming dysfunctional.

In response to dibutyryl cyclic AMP (dbcAMP) and all-trans retinoic acid, human promyelocytic leukemic HL60 cells differentiate into granulocyte-like cells. In cell lysate and in vitro reconstitution system, phospholipase D (PLD) activity in response to guanosine 5-O-(3-thiotriphosphate) (GTP␥S) was up-regulated by dbcAMP or all-trans retinoic acid treatment. In the present study, the mechanism(s) for increased PLD activity during differentiation was examined. Western blot analysis revealed that the contents of ADP-ribosylation factor, Rac2, and Cdc42Hs but not RhoA and Rac1 in the cytosolic fraction were elevated during differentiation. However, the cytosolic fraction from undifferentiated cells was almost equally potent as the cytosolic fraction from differentiated cells in the ability to stimulate membrane PLD activity. It was shown that the GTP␥S-dependent PLD activity in membranes from differentiated cells was much higher than that in membranes from undifferentiated cells, suggesting that the increased PLD activity during differentiation was due to alterations in some membrane component(s). Clostridium botulinum ADP-ribosyltransferase C3 and C. difficile toxin B, which are known as inhibitors of RhoA and Rho family proteins, respectively, effectively suppressed PLD activity in membranes from differentiated cells. In fact, the amount of membrane-associated RhoA was increased during differentiation. Furthermore, the extent of GTP␥S-dependent PLD activity partially purified from membranes from differentiated cells was greater than that from membranes from undifferentiated cells in the presence of recombinant ADP-ribosylation factor 1. The PLD (hPLD1) mRNA level was observed to be up-regulated during differentiation, as inferred by reverse transcription-polymerase chain reaction. Our results suggest the possibility that the increased Rho proteins in membranes and the changed level of PLD itself may be, at least in part, responsible for the increase in GTP␥S-dependent PLD activity during granulocytic differentiation of HL60 cells. Increasing evidence has indicated that phospholipase D (PLD)1 plays an important role in signal transduction in many types of cells (1). PLD hydrolyzes membrane phospholipids, especially phosphatidylcholine (PC), and produces phosphatidic acid, which can be further metabolized to diacylglycerol by phosphatidic acid phosphohydrolase (2). PLD is activated by many extracellular signal molecules, and several factors are involved in its activation. In reconstitution experiments, activation of membrane-associated PLD by nonhydrolyzable guanine nucleotide, guanosine 5Ј-O-(3-thiotriphosphate) (GTP␥S), was observed only when cytosol was present in the reaction mixture (3). Similar findings were obtained in permeabilized cells in which the loss of cytosolic components resulted in the reduction of GTP␥S-dependent PLD activity (4). These results imply that cytosolic factors for PLD activation are presumed to be GTP-binding proteins. Indeed, two small GTP-binding proteins have been identified as re...

Tetracaine induces apoptosis of PC12 cells via the MAPK family. ERK activation protects cells from death, but JNK plays the opposite role. Toxic Ca2+ influx caused by tetracaine seems to be responsible for the cell death, but blocking of Na+ channels or L-type Ca2+ channels is unlikely involved in the tetracaine's action for apoptosis.

Cancer stem cells (CSCs) can form new tumors and contribute to post-operative recurrence and metastasis. We showed that CD133CD13 hepatocytes isolated from HuH7 cells and primary HCC cells display biochemical and functional characteristics typical of CSCs, suggesting that CD133CD13 hepatocytes in primary HCC tumors function as CSCs. We also found that arsenite treatment reduced the viability and stemness of CD133CD13 hepatocytes, enhanced the sensitivity of HuH7 cells to pirarubicin, and reduced the tumorigenicity of CD133CD13 hepatocytes xenografts in mice. The effects of sodium arsenite treatment in CD133CD13 hepatocytes were mediated by the post-transcriptional suppression of PML expression and the inhibition of Oct4, Sox2, and Klf4 expression at the transcriptional level. Incomplete rescue of Oct4 expression in arsenic-treated cells ectopically expressing an siRNA-resistant PML transcript suggested that OCT4 regulation in liver CSCs involves other factors in addition to PML. Our findings provide evidence of a specific role for PML in regulating Oct4 levels in liver CSCs and highlight the clinical importance of arsenic for improving the efficacy of other chemotherapeutic agents and the prevention of post-operative HCC recurrence and metastasis.

Propofol protected HCAECs from Ang II-induced apoptosis by interfering with the generation of oxidative stress and redox-sensitive apoptotic pathways.

The current results indicate that local anesthetics inhibit the activity of the signal-transducing molecule(s) leading to M3 muscarinic acetylcholine receptor-mediated ERK activation in PC12 cells. Such action is unlikely to be a result of the drug's action on Na+ channels or on the electrochemical gradients of the neuronal cell membrane.