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Background Anastomotic leakage is one of the most serious postoperative complications of esophageal carcinoma. A new method of anastomosis has been adopted to reduce the incidence of anastomotic leakage. The aim of this study was to verify the safety and effectiveness of this new anastomosis method by comparing with the traditional anastomosis method. Methods A total of 121 patients with esophageal cancer from January 2020 to January 2022 in our department were included. They were divided into two groups according to the different methods of esophagogastrostomy: Side-to-side, end-to-end, embedded anastomosis group (SEE group, n=68) and traditional end-to-side anastomosis group (TE group, n=69). On the 7th day after operation, esophagography was performed to confirm the existence of anastomotic leakage, dysphagia, anastomotic stenosis, and gastroesophageal reflux. Results The incidence of anastomotic leakage in TE group and SEE group were 14.5% and 3.4%, respectively, with statistical significance(p＜0.05). The incidence of anastomotic stenosis in TE group was 21%, while in SEE group it was 3.4%. These differences were statistically significant(p＜0.01). The incidence of reflux in the TE group and the SEE group was 24.2% and 8.5%, respectively, with statistical significance(p＜0.05). The first esophagography after operation showed that the incidence of swallowing disorder was 27.4% in TE group and 57.6% in SEE group. These differences were statistically significant(p＜0.01). However, the incidence of swallowing disorder in TE group and SEE group was 9.7% and 15.3%, respectively, with no significant difference after 3 months (p＞0.05). Conclusion SEE anastomosis is a safe and effective surgical method, which is worthy of clinical application.

Long non-coding RNA (lncRNA) TSPEAR-AS2 (TSPEAR Antisense RNA 2) participates in many human diseases, while its roles in rheumatoid arthritis (RA) are unknown. Plasma expression levels of TSPEAR-AS2 and microRNA (miR)-212-3p in both RA patients and healthy controls were measured by RT-qPCR. Diagnostic potentials of plasma TSPEAR-AS2 and miR-212-3p were assessed by ROC curve analysis. Normalized expression levels of TSPEAR-AS2 and miR-212-3p were subjected to Pearson's correlation coefficient to evaluate their corrections. TSPEAR-AS2 was significantly downregulated in RA patients, while plasma expression levels of miR-212-3p were significantly increased in RA patients. The expression of TSPEAR-AS2 and miR-212-3p showed promising diagnostic value for RA. Plasma expression levels of TSPEAR-AS2 and miR-212-3p were significantly and inversely correlated in RA patients but not in healthy controls. Besides, overexpression of TSPEAR-AS2 decreased the apoptosis of RA HFLSs, while miR-212-3p increased cell apoptosis. In addition, miR-212-3p attenuated the effects of overexpression of TSPEAR-AS2. Overexpression of TSPEAR-AS2 decreased the expression levels of miR-212-3p in HFLS, while overexpression of miR-212-3p did not affect the expression of TSPEAR-AS2. In conclusion, TSPEAR-AS2 is downregulated in RA and its overexpression can decrease the apoptosis of RA HFLSs by downregulating miR-212-3p.

The present study investigated the problem of a large slab on a Winkler-type foundation subjected to a circular load. The slab is modeled as a ductile Kirchhoff plate and obeys Rankine’s yield criterion with associative flow rule. A circular uniform load is applied onto the top of the plate. As the load increases, the radial cracks occur and spread out at the bottom of the slab. The slab’s load-carrying capacity is defined by the onset of a negative yield line, namely a circumferential crack at the upper side of the slab. Depending on whether the circumferential bending curvature of the plate reaches its elastic limit, the slab was divided into two regions: the inner rigid-plastic region and the outer elastic region. A closed-form solution of the governing equations for each region is found. The influence of the material and geometrical parameters, size of the loaded area, and temperature gradient on the plate’s load-carrying capacity is then investigated. The load-carrying capacities found in previous investigations are compared with the predictions of the present analysis. Based on the analytical results, a regression formula for calculating the plate’s ultimate bearing capacity resting on a Winkler foundation is proposed.

The unconfined compression test is widely used because of convenient specimen formation, simple experimental process, and low requirement for equipment. In view of the experimental characteristics, the axisymmetric mechanical model of a cylinder with horizontal friction was constructed and its elastic analytic solution was also deduced. The stress and the strain of the cylinder under unconfined compression with different boundary conditions were analyzed by using the analytical solution, and the failure characteristics of the cylinder under unconfined compression were studied and verified by laboratory testing. The results showed that the end restraint effect of the cylinder increased with the decrease of the height-to-diameter ratio and the increase of the Poisson ratio. When the end surface of the cylinder was constrained, the maximum tensile strain appeared in the middle of the cylindrical side; its value increased with the constraint effect, and greater loads were needed to make the same vertical displacement. The compressive strength derived from the current method would be too weak, and the compressive modulus of elasticity would be too great. If the end constraint was large, a small network crack first formed in the middle of the outer side of the cylinder, forming the double-tapered destruction. If the end face was weakly restrained, the cracks descended from the top to the bottom, and the specimens split.

Currently, hepatocellular carcinoma (HCC) patients still have poor survival outcomes mainly due to the powerful mobility of HCC cells. Increasing evidences hint that abnormally expressed miRNAs are capable to modulate HCC cells invasion and migration. MiR-1202 has been proposed as a ponderable molecular tumor marker in a variety of tumors. Here, results from real-time PCR indicated the decreased expression of miR-1202 in HCC. Clinically, statistical analysis showed that miR-1202 under-expression was closely associated with metastasis-related clinicopathologic characteristics. In addition, 5-year overall survival (OS) and disease-free survival (DFS) rates of HCC patients with high miR-1202 expression were much better than that in low miR-1202 group. Functionally, gain- and loss-of -function studies were performed to investigate the roles of miR-1202. Intriguingly, Would healing assay and Transwell assays indicated that elevated miR-1202 weakened HCC cells migration and invasion abilities, while miR-1202 knockdown presented the contrary effects. Furthermore, cyclin dependent kinase 14 (CDK14) was identified as a downstream target of miR-1202 by bioinformatics analysis, Dual luciferase reporter assay, detection of CDK14 expression and Pearson correlation analysis. More importantly, rescue experiments demonstrated that CDK14 mediated miR-1202 to exert its anti-tumor effects, which further confirmed the above finding. Taken together, miR-1202 may act as a new biomarker and potential therapeutic target for HCC.

Cancer stem cells (CSCs) can form new tumors and contribute to post-operative recurrence and metastasis. We showed that CD133+CD13+ hepatocytes isolated from HuH7 cells and primary HCC cells display biochemical and functional characteristics typical of CSCs, suggesting that CD133+CD13+ hepatocytes in primary HCC tumors function as CSCs. We also found that arsenite treatment reduced the viability and stemness of CD133+CD13+ hepatocytes, enhanced the sensitivity of HuH7 cells to pirarubicin, and reduced the tumorigenicity of CD133+CD13+ hepatocytes xenografts in mice. The effects of sodium arsenite treatment in CD133+CD13+ 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.

Two-dimensional locality preserving projections (2DLPP) was recently proposed to extract features directly from image matrices based on locality preserving criterion. A significant drawback of 2DLPP is that it only works on one direction (left or right) to reduce the dimensionality of the image matrices and thus too many coefficients are needed for image representation in low-dimensional subspace. In this paper, we propose a novel method called two-dimensional bilinear preserving projections (2DBPP) for image feature extraction. We generalized the image-based (2D-based) feature extraction techniques into bilinear cases, in which 2DLPP is a special case of our proposed method. In order to obtain the bilinear projections, we proposed an iteration method by solving the corresponding generalized eigen-equations. Moreover, analyses show that 2DBPP has stronger locality preserving abilities than 2DLPP. By using the label information and defining different local neighborhood graphs, the proposed framework is further extended to supervised case. Experiments on three databases show that 2DBPP and its supervised extension are superior to some other image-based state-of-the-art techniques.

Summary Intra-operative awareness can lead to serious adverse psychological consequences. We conducted a prospective, randomised, double-blinded trial in 920 patients undergoing breast cancer surgery under bispectral index-guided total intravenous anaesthesia to evaluate the effect of penehyclidine hydrochloride on intra-operative awareness. Patients were randomly divided to receive 0.01 mg.kg−1 penehyclidine hydrochloride or saline intravenously 30 min before surgery. The pre-administration, pre-operative anxiety levels were assessed using a 100-mm visual analogue scale. Intra-operative awareness was defined as recall of intra-operative events using a modified Brice interview administered 2–6 h postoperatively, and in the next 24–48 h. A committee of three experts, blinded to the study conditions, independently scrutinised all reported recollections. We found no differences in depth of anaesthesia and patients' pre-operative anxiety levels between the two groups. The incidence of awareness with penehyclidine hydrochloride (0/456 patients; 0%) was significantly lower than with saline (5/452; 1.1%), p = 0.030. We conclude that penehyclidine hydrochloride reduced the incidence of intra-operative awareness in patients undergoing breast cancer surgery during general anaesthesia.

Cancer stem cells (CSCs) can form new tumors and contribute to post-operative recurrence and metastasis. We showed that CD133

Angiotensin II (Ang II) induces oxidative stress and apoptosis in vascular endothelial cells. We hypothesized that propofol may attenuate Ang II-induced apoptosis in human coronary artery endothelial cells (HCAECs) and aimed to identify the underlying mechanisms.Endothelial cells were pre-treated with propofol and then stimulated with Ang II. Apoptosis was examined by TUNEL, DNA laddering, and caspase-3 activity assays. The effect of propofol on Ang II-modulated NADPH oxidase expression and activity, nitric oxide synthase III (NOSIII) expression and phosphorylation and activity, lipid peroxidation, superoxide anion generation, nitric oxide production, caspase activity, and protein expression of cytochrome c, Bcl-2, and C-IAP-1 were measured.Ang II induced apoptosis, which was attenuated by 50 µM propofol (P0.05). Propofol ameliorated Ang II-induced NADPH oxidase expression and activation (P0.01), lipid peroxidation (P0.05), and superoxide anion generation (P0.05), whereas restoring NOSIII phosphorylation and activity (P0.01) were down-regulated by Ang II. Propofol attenuated Ang II-modulated cytochrome c release, and the expression of Bcl-2 and C-IAP-1. In addition, propofol inhibited Ang II-induced caspase-9 (P0.01) and caspase-3 activity (P0.01).Propofol protected HCAECs from Ang II-induced apoptosis by interfering with the generation of oxidative stress and redox-sensitive apoptotic pathways.

Amnesia is a fundamental component of a proper general anesthetic. The mechanism of anesthetic-induced amnesia remains poorly understood. Nowadays, intraoperative awareness and postoperative cognitive dysfunction are two distressing problems receiving increased attention by clinicians, patients and the general public. Extensive evidence indicates that general anesthetics cause amnesia by working on hippocampus and basolateral amygdala (BLA). Recently, evidence from studies in experimental animals has shown that either intra-hippocampus or intra-BLA injection of endogenous cannabinoid receptor 1 (CB1) drugs result in significant changes of cognitive function. In addition, several general anesthetics (i.e. propofol, etomidate and isoflurane) have been reported to interact with the endocannabinoid system. However, there are few studies about whether the CB1 receptor system is involved in anesthetic-induced amnesia. We hypothesize that the CB1 receptor activity in hippocampus and BLA might be regulated by general anesthetics. Once the involvement of the endocannabinoid system in anesthetic-induced amnesia is proved, it will provide a new way to prevent and treat post-traumatic stress disorder caused by intraoperative awareness and postoperative cognitive dysfunction in the future.

In prior studies, Eph/ephrin system was demonstrated to be involved in inflammatory and neuropathic pain modulation. The present study was to investigate whether the spinal Eph/ephrin signaling was involved in modulation of spinal inflammatory cytokines in bone cancer pain (BCP) of rats. BCP was induced by intra-tibial inoculation of Walker 256 mammary gland carcinoma cells. The expressions of EphB1/ephrinB1 in spinal cord (SC) and dorsal root ganglia (DRG) were determined. At 16 days post inoculation, the pain relieving effect and the mRNA levels of inflammatory cytokines were detected after intrathecal administration of EphB1-Fc (blocker of EphB1 receptor, 10μg). The results showed that the EphB1/ephrinB1 expression was significantly increased in SC, but ephrinB1 was decreased in DRG after Walker 256 inoculation. The mechanical allodynia induced by bone cancer was significantly alleviated by intrathecal administration of EphB1-Fc. Furthermore, the RT-PCR analysis showed that the mRNA levels of IL-1β, IL-6 and TNF-α were significantly increased at 16 days post Walker 256 inoculation and were significantly suppressed by intrathecal administration of EphB1-Fc in SC. We concluded that Eph/ephrin might be involved in the maintenance of mechanical allodynia, via modulating the expression of spinal inflammatory cytokines, in the present rat model of BCP. This study suggested that Eph/ephrin signaling would be a potential target for the treatment of BCP.

This paper reports the reactive ion etching (RIE) characteristics of benzocyclobutene (BCB) in sulfur hexafluoride/oxygen (SF"6/O"2) plasmas. The dependence of etching rate and etch anisotropy on the processing parameters, including RF power, chamber pressure, and SF"6 concentration, are investigated comprehensively ranging from 50 to 200W, 22.5 to 270mTorr, and 0% to 80%, respectively. The BCB etching rate increases with chamber pressure and RF power in spite of nonlinearity, but decreases with the increase in SF"6 concentration. Anisotropic etching can be achieved using low chamber pressure, large RF power, and high SF"6 concentration. To avoid grass-like residue that happens at low pressure and large power fluorine-poor conditions, processing parameters with respect to residue-free etching are recommended. The etching mechanisms of the dependence of the etching characteristics on the processing parameters are discussed. Optimal processing parameters are presented as a guideline for isotropic etching of BCB as sacrificial layers to release structures and for anisotropic etching of BCB to precisely control etching dimensions and profiles.

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.

Objective In this study, we evaluated the effect of preemptive analgesia of flurbiprofen axetil (FA) and tramadol on immune response in patients undergoing radical mastectomy.

Background To explore whether cytotoxicity of local anesthetics is related to apoptosis, the authors examined how local anesthetics affect mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs)-stress-activated protein kinases, and p38 kinase, which are known to play important roles in apoptosis. Methods Cell death was evaluated using PC12 cells. Morphologic changes of cells, cellular membrane, and nuclei were observed. DNA fragmentation was electrophoretically assayed. Western blot analysis was performed to analyze phosphorylation of the MAPK family, cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase. Intracellular Ca2+ concentration was measured using a calcium indicator dye. Results Tetracaine-induced cell death was shown in a time- and concentration-dependent manner and characterized by nuclear condensation or fragmentation, membrane blebbing, and internucleosomal DNA fragmentation. Caspase-3 activation and phosphorylation of ERK, JNK, and p38 occurred in the cell death. PD98059, an inhibitor of ERK, enhanced tetracaine-induced cell death and JNK phosphorylation, whereas ERK phosphorylation was inhibited. Curcumin, an inhibitor of JNK pathway, attenuated the cell death. Increase of intracellular Ca2+ concentration was detected. In addition to the increase of ERK phosphorylation and the decrease of JNK phosphorylation, two Ca2+ chelators protected cells from death. Neither cell death nor phosphorylation of the MAPK family was caused by tetrodotoxin. Nifedipine did not affect tetracaine-induced apoptosis. Conclusions 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.

To solve the worldwide problem of structural analysis for port interlocking concrete block pavements, a three dimensional mechanistic model is developed. In particular, the layout pattern of interlocking concrete blocks and its size are carefully considered. A dual spring with uniaxial compression and lateral shearing functions is employed to simulate the interlock effects among concrete blocks. The influences of concrete block sizes, sub-grade reaction modulus and the interlock intensity on the structural responses of port interlocking concrete block pavements are discussed. The deflections and the flexural stresses on base are summarized, by comparison of results based on the model hereof and obtained with a multi-layered elastic system model. The validity of the model is logically verified. The study showed that with increase of the lateral shearing stiffness of dual spring, the elections and the flexural stresses on base decrease slightly, and the size of concrete block has somewhat influence on the structural responses of port interlocking concrete block pavements, whereas the effect of sub-grade reaction modulus on the structural responses is substantial. Therefore, the research can be used as a basis for design of port interlocking concrete block pavements.

This paper presents a study of risk control on transportation finance, based on real cases of default from a commercial bank in China in 2012, and analyzes the features of investment risks of transportation projects during recessionary period. The identified risk factors are divided into several categories and specific preventing measures are proposed. Transportation industry is commonly thought of as capital intensive and bank credit has always been one of main financing sources for the transportation industry in China. When conducting evaluation of transportation projects, commercial banks need to comprehensively consider returns and risks, under the premise of the risks are controllable, maximizing returns through optimizing capital allocation. After the financial crisis, commercial banks are urged to improve their risk-control procedures. When commercial bank makes strategic decision on transportation projects, the feasibility study reports provided by consulting engineers are often used as references. However, the feasibility study reports usually focus on demonstrating the pending projects' potential for success, which are of comparatively great distance to commercial bank's actual needs. Based on above facts, the paper plans, through studying real cases of non-performing loans to transportation projects occurring in year 2012 by one commercial bank, to classify and analyze the investment risks for transportation projects in the economic recession period. By classifying the risks factors as well as presenting corresponding prevention measures, the paper provides references for investment and financing of transportation projects in economic recession period.

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) (GTPgammaS) 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 GTPgammaS-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 GTPgammaS-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 GTPgammaS-dependent PLD activity during granulocytic differentiation of HL60 cells.

A simplified three-dimensional model is established to analyze the responses in asphalt overlay (AC) paved on existing concrete pavements (PCC) slabs under vehicle loads, by using the finite element method, through some examples, the convergence of loading stresses in AC nearby the joint of PCC slabs and interface forces are discussed, the expressions of the nominal maximum tensile stress σ1max in AC are then formulated, and the influences of load position x, structural parameters (E1, h1, h2, k0, δ), interlayer stiffness and void underneath PCC slabs on the stresses σ1max, τ1max in AC and the internal forces q2max, τ2max are analyzed, in the end, the damage modes of AC on PCC structure are issued based on the strength theory. The study indicated that the sectional internal forces (axial force N and momentM) can be taken as convergence criteria to reasonably determine the model meshing density. The stress σ1max can be calculated upon corresponding sectional internal forces N, M and a stress concentration factor ξp; the stresses σ1max, τ1max may reach peak values when the load position x not exceeding ±0.2m; the influences of structural parameters E1, h1 on the stresses σ1max, τ1max and the interface forces q2max, τ2max are much significant; eliminating the void underneath PCC slabs will have a disadvantageous effect on the stress σ1max but an active effect on the interface forces q2max, τ2max; a higher joint spring stiffness Cw will considerably reduce the stresses σ1max, τ1max and the interface forces q2max, τ2max; the placing width of soft interlayer over the joint should be 0.3∼0.4m; the soft interlayer with higher stiffness will reduce the stress σ1max, but raise the interface force q2max, therefore increase the risk of interface damage.

Background Thoracic epidural anesthesia can contribute to facilitate the fast-track approach in lung surgery. However, data regarding the effects of thoracic epidural anesthesia on oxygenation during one-lung ventilation (OLV) are scarce and contradictory. Therefore, the authors conducted a prospective, randomized, double-blinded trial in patients undergoing lung surgery under spectral entropy-guided intravenous anesthesia to evaluate the effects of thoracic epidural anesthesia with different concentrations of ropivacaine on oxygenation, shunt fraction (Qs/Qt) during OLV, and maintenance doses of propofol. Methods One hundred twenty patients scheduled for lung surgery were randomly divided into four groups to epidurally receive saline (Group S), 0.25% (Group R0.25), 0.50% (Group R0.50), and 0.75% (Group R0.75) ropivacaine. Ropivacaine was administered intraoperatively (6-8 ml of first bolus + 5 ml/h infusion). Arterial oxygen tension (Pao2) and Qs/Qt were measured before, during, and after OLV. Results Pao2 was significantly lower in Group R0.75 compared with that in Group S and Group R0.25 10 min (170 +/- 61 vs. 229 +/- 68 mmHg, P = 0.01; 170 +/- 61 vs. 223 +/- 70 mmHg, P = 0.03) and 20 min after OLV (146 +/- 52 vs. 199 +/- 68 mmHg, P = 0.009; 146 +/- 52 vs. 192 +/- 67 mmHg, P = 0.03). During OLV, Qs/Qt was significantly higher in Group R0.75 compared with that in Group S and Group R0.25 (P < 0.05). Maintenance doses of propofol were significantly lower in Group R0.75. Vasopressor requirements were higher in Group R0.75. Conclusion A decrease in oxygenation during OLV occurred only at the highest dose of epidural local anesthetic and not at lower doses. Higher doses of epidural medication required less propofol and more vasopressors.

Local anesthetics possess a wide range of anti-inflammatory properties through their effects on neutrophils. However, limited information is available on the effects of ropivacaine (a new local anesthetic) on neutrophil function. The aim of this study was to investigate anti-inflammatory properties of ropivacaine with regard to its effects on the expression and function of CD11b in human neutrophils. CD11b expression was examined by flow cytometry and its function was determined by measuring adhesion of neutrophils to human umbilical vein endothelial cells (HUVECs). Ropivacaine inhibited CD11b expression in formyl-methionyl-leucyl-phenylalanine (fMLP)-activated neutrophils in a concentration-dependent manner, but not in a time-dependent manner. The inhibitory potency of ropivacaine was similar to that of bupivacaine and levobupivacaine, but was more potent than that of lidocaine. The up-regulation of CD11b induced by platelet-activating factor (PAF) priming was also inhibited by ropivacaine. fMLP increased adhesion of neutrophils to HUVECs, which was inhibited by ropivacaine. In addition, ropivacaine more potently inhibited the fMLP-induced CD11b expression in the presence of ethylene glycol-bis(2-aminoethylether)-N,N,N´,N´-tetraacetic acid (EGTA), a chelator of extracellular Ca 2+ . However, ropivacaine showed no effect on the fMLP-induced CD11b expression in the presence of butan-1-ol, a blocker of phospholipase D (PLD) pathway, which completely inhibited the fMLP-induced CD11b expression in neutrophils. Our results suggest that ropivacaine exerts anti-inflammatory activity, and this appears to be mediated through inhibiting the expression and function of adhesion molecule CD11b in neutrophils.

Bradykinin induces activation of phospholipase D (PLD) via B(2) receptors in neuronal cells. To demonstrate molecular mechanism(s) of local anesthetics, we examined whether and how local anesthetics affect bradykinin-induced PLD activation in PC12 cells. Using [(3)H]Palmitic acid-labeled PC12 cells stimulated with bradykinin, formation of [(3)H]phosphatidylbutanol was measured as a variable of PLD activity. Bradykinin-stimulated PLD activity seemed to peak at 2 min. Procaine, lidocaine, ropivacaine, bupivacaine, and tetracaine suppressed the bradykinin-induced PLD activation. We chose tetracaine, the most potent drug among the local anesthetics tested, to examine how local anesthetics affect phospholipase C, protein tyrosine kinase, and extracellular signal-regulated kinase, which are the molecules upstream of PLD. Tetracaine at clinically relevant concentrations (1 approximately 10 x 10(-4) M) inhibited the bradykinin-induced PLD activation in a dose- and time-dependent manner, but neither tetrodotoxin nor nifedipine affected the PLD activation. Tetracaine (5 x 10(-4) M) slightly potentiated brady-kinin-induced phospholipase C activation. Bradykinin-stimulated protein tyrosine-phosphorylation and extracellular signal-regulated kinase activation were not affected by tetracaine. Tetracaine significantly decreased PLD activity of membrane fraction in PC12 cells. These results indicate that local anesthetics depress bradykinin-induced lipid signaling pathway(s) and may provide some clues to understanding the molecular mechanisms of these drugs for anesthesia or analgesia.Local anesthetics depressed the bradykinin-induced activation of phospholipase D (PLD) in PC12 cells. The effects of tetracaine, the most potent among the anesthetics tested, on the bradykinin-induced intracellular signaling molecules were examined. The bradykinin-induced PLD activation could be one of the potential intracellular signaling molecular sites of local anesthetic action.

Local anesthetics impair certain functions of neutrophils, and phospholipase D (PLD) is considered to play an important role in the regulation of these functions. To understand the mechanisms by which local anesthetics suppress the functions of neutrophils, we examined the effects of local anesthetics on PLD in neutrophil-like differentiated human promyelocytic leukemic HL60 cells. Tetracaine, a local anesthetic, inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)- and 4β-phorbol 12-myristate 13-acetate (PMA)-induced PLD activation, but potentiated fMLP-stimulated phospholipase C activity. All four local anesthetics tested suppressed PMA-induced PLD activation to different extents, and the order of their potency was tetracaine > bupivacaine > lidocaine > procaine. In a cell-free system, tetracaine suppressed guanosine 5′- O- (3-thiotriphosphate) (GTPγS)-induced PLD activation as well as PMA-induced PLD activation. Western blot analysis revealed that tetracaine prevented the membrane translocation of PLD-activating factors, ADP-ribosylation factor, RhoA, and protein kinase Cα. Tetracaine also inhibited the activity of recombinant hPLD1a in vitro . These results suggest that local anesthetics suppress PLD activation in differentiated HL60 cells by preventing the membrane translocation of PLD-activating factors, and/or by directly inhibiting the enzyme per se . Therefore, it could be assumed that local anesthetics would suppress the functions of neutrophils by inhibition of PLD activation.