[Ketamine inhalation before one-lung ventilation for perioperative lung protection in thoracic surgery patients].

OBJECTIVE: To explore the effects of ketamine inhalation before one-lung ventilation (OLV) in patients undergoing transthoracic esophagectomy for esophageal cancer. METHODS: Upon the approval of hospital ethic committee, 90 American Society of Anesthesiologists grade I-II patients scheduled for elective trans-left-thoracic esophagectomy for esophageal cancer were randomly and single-blindly divided into 3 groups. After intravenous anesthesia with double-lumen endobronchial intubation, the patients in each group received different therapies before OLV, i.e. inhaling ketamine 1 mg/kg in Group Ki, intravenous infusion of ketamine 1 mg/kg in Group Kv and inhaling normal saline 10 ml in Group C. Arterial blood gas analysis was performed. And (oxygen saturation) SpO2, (partial pressure of end-tidal carbon dioxide) PETCO2, (airway pressure) Paw and hemodynamic indicators were recorded at these points:before OLV (T1), OLV for 30 min (T2), OLV for 1 h (T3), OLV for 2 h (T4), OLV ended 5 min (T5) and end of surgery (T6). Central venous blood was sampled at T1, T2 and 2 h after surgery (T7) for the determination of interleukin-6 (IL-6), interleukin-8 (IL-8) and soluble intercellular adhesion molecule-1 (sICAM-1) concentrations by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of IL-6, IL-8 and sICAM-1 in all groups increased significantly than those at previous timepoints. Serum levels of IL-6, IL-8 and sICAM-1 in Groups Ki and Kv were significantly lower than those in Group C at T7. PaO2 in Groups Ki and Kv was significantly higher than that in Group C at T4. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Group Kv were significantly higher than that in Groups Ki and C at T2-T4; HR in Group Kv was significantly higher than that in Group C at T2-T3. Paw in Group Kv was significantly higher than that in Group C at T2-T6. CONCLUSION: Inhalation and intravenous infusion of ketamine before OLV are equally effective in lowering the serum levels of IL-6, IL-8 and sICAM-1. And ultrasonic atomizing inhalation of ketamine can avoid adverse effects on airway pressure and circulatory system caused by an intravenous infusion of ketamine.

[Ridge regression analysis of pulmonary infection rate after transthoracic esophagectomy for esophageal cancer].

OBJECTIVE: To identify the influencing factors of pulmonary infections after transthoracic esophagectomy for esophageal cancer. METHODS: A retrospective review of 349 patients undergoing transthoracic esophagectomy at our hospital for esophageal cancer was performed between January and December 2009. The postoperative pneumonia rate was examined and 26 perioperative factors possibly affecting the postoperative respiratory complications were collected. Ridge regression modeling was performed to determine if a significant association existed between perioperative factors and postoperative pneumonia. RESULTS: The postoperative pneumonia rate of all patients was 27.8%. Eight perioperative factors were found to have affected significantly the postoperative respiratory complications. The influencing factors included (according to contribution): patient control epidural analgesia (PCEA), diabetes, general anesthesia plus epidural analgesia, other postoperative complications, one lung ventilation (OLV), transfusion volume of red blood cells (RBC), body mass index (BMI) and age. CONCLUSION: The major influencing factors of pulmonary infection after transthoracic esophagectomy for esophageal cancer are PCEA, diabetes, general anesthesia plus epidural analgesia, other postoperative complications, OLV, transfusion volume of RBC, BMI and age.

Activation of platelet membrane glycoprotein induced by parenteral nutrition: a preliminary report.

BACKGROUND: Long-term parenteral nutrition (PN) is a standardized treatment in many patients who are unable to use their gastrointestinal tract to absorb nutrients and water. Catheter-related thrombosis (CRT) is one of the most common complications of PN. Several factors predispose patients to CRT. The main objective of this study was to assess the platelet membrane glycoprotein (GP) activation and coagulopathy induced by PN. METHODS: Fifteen patients with intestinal failure were given PN for 47.9 days (range, 30-92 days) and 15 oral-fed healthy volunteers served as controls. Complete blood counts and coagulation and biochemical parameters were determined. The platelet surface GPs, P-selectin and GPIIb/IIIa were measured by flow cytometry. RESULTS: There was no significant difference between the control group and PN group in coagulation and biochemical parameters. Platelet P-selectin expression of the PN group was significantly higher than that of the control group (3.43% ± 1.22% and 1.99% ± 0.58%, respectively; P < .01). There was no significant difference in GPIIb/IIIa expression between the 2 groups. CONCLUSIONS: Long-term PN (>30 days) induced the activation of platelet membrane GPs, which may be a significant risk factor for the development of CRT in patients with intestinal failure who require PN.

Eicosapentaenoic acid inhibits TNF-alpha-induced Lnk expression in human umbilical vein endothelial cells: involvement of the PI3K/Akt pathway.

n-3 Polyunsaturated fatty acids (PUFAs) exert anti-inflammatory properties by influencing inflammatory cell activation processes. Lnk is an adaptor protein involving endothelial cell (EC) activation because it is induced by tumor necrosis factor-alpha (TNF-alpha). This study was conducted to evaluate the role of eicosapentaenoic acid (EPA), an n-3 PUFA, in the regulation of Lnk expression in human umbilical vein endothelial cells (HUVECs). Primary HUVECs were pretreated with EPA for 12 h at various concentrations (0-40 muM) and then exposed for another 12 h in the presence or absence of TNF-alpha (10 ng/ml). Lnk mRNA and protein were detected using reverse transcriptase polymerase chain reaction, immunoprecipitation and Western blot analysis. Results showed that pretreatment of HUVEC with EPA inhibited TNF-alpha-induced expression of Lnk in a dose-dependent manner. TNF-alpha-induced Lnk was also inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. Thus, we investigated the role of PI3K/Akt signaling pathway in this process. Phosphorylation of Akt was assessed by Western blot analysis. We found that EPA treatment decreased the amount of activated Akt. These results showed that EPA inhibited TNF-alpha-induced Lnk expression in HUVECs through the PI3K/Akt pathway. This may be a potential mechanism by which EPA protects ECs under inflammatory conditions.

TNF-alpha induces Lnk expression through PI3K-dependent signaling pathway in human umbilical vein endothelial cells.

BACKGROUND: A better understanding of activation process of endothelial cells (ECs) might reveal new ways of controlling inflammation. Adaptor proteins play crucial roles in ECs activation. Lnk is a newly discovered adaptor protein that has been proposed as a negative regulator of cytokine signaling. While limited information is available about Lnk in human ECs. This study was conducted to investigate the effect of TNF-alpha on Lnk expression in ECs and to identify the signal transduction pathway that is associated with Lnk regulation. MATERIALS AND METHODS: Primary human umbilical vein endothelial cells (HUVECs) were cultured with designated doses of TNF-alpha and harvested at designated time points. Then Lnk mRNA and protein were detected using real-time polymerase chain reaction, immunoprecipitation and Western blot analysis, respectively. RESULTS: The data demonstrated that Lnk mRNA and protein expression are induced significantly (P < 0.05) by TNF-alpha in a dose- and time-dependent manner. This inductive effect was abolished while phosphatidylinositol 3-kinase (PI3K) pathway was blocked by the PI3K inhibitor LY294002 and Wortmannin. CONCLUSION: These results suggest that TNF-alpha induces Lnk expression through PI3K-dependent signaling pathway in HUVEC. This may indicate a role for this new adaptor protein in the regulation of TNF-alpha-induced ECs activation.

Eicosapentaenoic acid and docosahexaenoic acid modulate mitogen-activated protein kinase activity in endothelium.

Omega-3 polyunsaturated fatty acids (PUFA) regulate inflammation and immunoreaction partially via affecting endothelial functions. However, the intracellular signaling mechanisms for inhibiting endothelial activation by omega-3 PUFA remain unclear. We investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mitogen-activated protein kinases (MAPK) of endothelium. We analyzed the expression of extracellular signal-related kinases (ERK1/2), Jun amino-terminal kinases (JNK), and p38 mRNA by real-time RT-PCR and the kinases activity by western blotting in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVEC). We observed that EPA or DHA alone significantly reduced the TNF-alpha-induced activation of p38 and JNK kinases at a concentration of 20 microM, but EPA is a more potent inhibitor than DHA. In contrast, both EPA and DHA significantly counteracted the TNF-alpha-mediated deactivation of ERK1/2 kinases. Meanwhile, both EPA and DHA significantly attenuated the TNF-alpha-induced expression of p38 and ERK1/2 mRNA, and DHA but not EPA also reduced the TNF-alpha-induced JNK mRNA expression. We present data show that both EPA and DHA alone diminish activation of p38 and JNK kinases, while maintaining the activation of ERK1/2 kinases of TNF-alpha-stimulated HUVEC. This may contribute to the inhibiting effects of omega-3 PUFA on endothelial activation by proinflammatory stimuli.

Growth hormone receptor overexpression predicts response of rectal cancers to pre-operative radiotherapy.

In this study, we evaluated the possible role of Growth Hormone Receptor (GHR) expression pattern in determining rectal cancer radiosensitivity. We examined GHR expression in pre-treatment biopsy materials and post-operative specimens from 98 patients by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). GHR expression was evaluated for association with tumour radiosensitivity, which was defined according to Rectal Cancer Regression Grade (RCRG). IHC results demonstrated that GHR overexpression was significantly associated with a poor response to radiotherapy (P < 0.001, r(s) = 0.399); RT-PCR detection of GHR expression on pre-radiation biopsy specimens also showed that GHR mRNA negative group had a higher radiation sensitivity (P < 0.001, r(s) = 0.398). Compared with the pre-radiation biopsy specimens, the paired post-operative specimens showed a significantly up-regulated GHR expression in the reliquus cancer cells (P < 0.001). In conclusion, GHR expression levels may be an indicator for rectal cancer radiosensitivity before pre-operative irradiation. The administration of GHR antagonist may have the potential to increase rectal cancer radiosensitivity.