Increase of beta-amyloid and C-reactive protein in liver transplant recipients with postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is an adverse condition characterized by declined cognitive functions following surgeries and anesthesia. POCD has been associated with increased hospital stay and mortality. There are histological similarities to Alzheimer's disease. Most early studies were conducted in patients receiving cardiac surgery. Since there is no information about POCD in liver transplant recipients, we measured the incidence of POCD in patients after liver transplantation and examined the correlation between neurological dysfunction and biological markers of dementia-based diseases. METHODS: We studied 25 patients who had a liver transplan-tation between July 2008 and February 2009. Patients with prior encephalopathy or risk factors associated with the development of POCD were excluded from the study. Five validated neuropsychiatric tests were used for diagnosis. The diagnosis was based on one standard deviation decline in two of the five neuropsychiatric tests. The correlation between patient variables and the development of POCD was examined. Serum levels of beta-amyloid and C-reactive protein were measured by standard ELISA and compared between patients with and without POCD. RESULTS: POCD was present in 11 (44%) of the 25 patients. Patients with POCD had significantly higher MELD scores, were more often Child-Pugh class C and received more blood transfusion during surgery. The serum beta-amyloid protein and C-reactive protein concentrations were significantly increased at 24 hours after surgery in the POCD group. CONCLUSIONS: The incidence of POCD in our group of liver transplant patients was greater than that reported in other surgical patients. The increase in the serum biomarkers of dementia in the POCD patients supports the hypothesis that chronic cognitive defects are due to a process similar to that seen in Alzheimer's disease.

Glutamate-induced c-Jun expression in neuronal PC12 cells: the effects of ketamine and propofol.

Transcription factor c-Jun affects neuronal cell death and survival in mammalian brain. As general anesthetics, such as ketamine and propofol, are thought to provide some degree of neuroprotection, this study was intended to test whether the protection of injured neuronal PC12 cells by ketamine and propofol is related to the inhibition of phospho-c-Jun. Using neuronal PC12 cells from rat pheochromocytoma cells differentiated with nerve growth factor, we found that 24 hours of exposure to glutamate (1 to 100 mM) induced concentration-dependent cell death as determined by an ability to reduce the tetrazolium derivative, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) into a blue formazan salt. Neuronal PC12 cells were exposed to ketamine (0.1, 1.0 mM) or propofol (0.5, 5.0 microM) and glutamate (0, 20 mM) for 24 hours. Cell injury was assessed using MTT, in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, and c-Jun activity assay. Glutamate, 20 mM, induced about 70% of cell death as determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining. Glutamate-induced cell death was related to an increase in expression of phospho-c-Jun. Glutamate-induced cell death was reduced by ketamine (0.1, 1.0 mM) in a dose-dependent manner and also by propofol (0.5, 5.0 microM). In addition, the expression of phospho-c-Jun was substantially reduced by ketamine (0.1, 1.0 mM) and propofol (0.5, 5.0 microM), respectively, as determined by Western blot assay. These results suggest that inhibition of c-Jun activity is involved in the neuroprotective effects of ketamine and propofol on glutamate-induced injury in neuronal PC12 cells.

[Clinical evaluation of execution of early goal directed therapy in septic shock].

OBJECTIVE: To evaluate the efficacy of early goal directed therapy (EGDT) in septic shock. METHODS: Two hundred and three patients with septic shock were assigned into treatment group (n=98) and control group (n=105). According to the state of organ function at the beginning of treatment and multiple organ dysfunction syndrome (MODS) evaluation scores, each group was categorized into three strata: stratum A (mild organ dysfunction), stratum B (medium organ dysfunction) and stratum C (severe organ dysfunction). Mortality and incidence of organ dysfunction in each group were analyzed. RESULTS: At stratum A, the mortality and incidence of organ dysfunction in treatment group were significantly lower than those of control group [27.78% (15/54 cases) vs. 37.50% (18/48 cases), 31.48% (17/54 cases) vs. 43.75% (21/48 cases), both P<0.05]. There was no significant difference between treatment group and control group in patients of stratum B [75.86% (22/29 cases) vs. 76.92% (20/26 cases), 55.17% (16/29 cases) vs. 57.69% (15/26 cases)] and stratum C [93.33% (14/15 cases) vs. 96.77% (30/31 cases), 40.00 % (6/15 cases) vs. 41.93% (13/31 cases), all P>0.05]. CONCLUSION: In the earlier period of septic shock, EGDT can remarkably decrease the patients'mortality and incidence of organ dysfunction, but can not improve survival rate and prognosis in patients in advanced stage of septic shock.

[Changes of IFN-gamma, IL-2, IL-6 and IL-10 in the patient with cardiac surgery under combined acupuncture anesthesia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on cytokines in the cardiac surgical patient and to evaluate the application of combined acupuncture anesthesia to cardiac surgery. METHODS: Thirty patients with atrial septal defect were divided into 3 groups, general anesthesia group (A), acupuncture anesthesia group (B) and combined general anesthesia and EA group (C). Peripheral blood samples were collected before anesthesia, before cardiopulmonary bypass (CPB), 30 min after CPB and 24 h after operation to determine the levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-6 and IL-10. RESULTS: The levels of IFN-gamma and IL-2 decreased in the 3 groups after CPB and further decreased 24 h after operation, and in the group C were higher than those in the group B. The levels of IL-6 and IL-10 significantly increased 24 h after operation in the 3 groups with no significant difference among the 3 groups. CONCLUSION: The general anesthesia combined with EA can not completely improve the decrease of IFN-gamma and IL-2 induced by CPB, indicating that the good response of the general anesthesia combined with EA to stress can partially improve the immunosupression induced by CPB. Acupuncture does not have significant effect on inflammatory cytokine reaction induced by cardiac surgery.

Hippocampus bcl-2 and bax expression and neuronal apoptosis after moderate hypothermic cardiopulmonary bypass in rats.

Using a rat model of moderate hypothermic (26 degrees C-28 degrees C) cardiopulmonary bypass (CPB) with hemodilution, we investigated hippocampal apoptotic gene expression and neuronal apoptosis up to 6 h after CPB. The CPB was performed on male rats (380-400 g) under general anesthesia with isoflurane and fentanyl. The right atrium and tail artery were cannulated, and a peristaltic pump and membrane oxygenator were used for CPB. Two groups were studied: Group 1 consisted of fasted rats (n = 15) subjected to 60 min of moderate hypothermic nonpulsatile CPB; Group 2 consisted of sham-operated rats (n = 15). At 1 h after CPB, in 6 rats per group, hippocampus was processed for the apoptotic gene (bcl-2 and bax) messenger RNAs detection by reverse transcriptase polymerase chain reaction, and messenger RNA expression was determined by the ratio of the polymerase chain reaction product of bcl-2 or bax to the beta-actin gene. At 6 h after CPB, in 6 rats per group, hippocampus expression of Bcl-2 and bax protein was determined by immunohistochemistry, and neuronal apoptosis was detected by TUNEL. At 6 h after CPB, in three rats per group, changes in hippocampal CA1 neuronal ultra structure were determined with electron microscopy. Group 1 had increased ratios of bcl-2/beta-actin, bax/beta-actin, and bax/bcl-2 mRNA at 1 h after CPB (bcl-2/beta-actin, 0.82 +/- 0.14 versus 0.63 +/- 0.07; P = 0.03; bax/beta-actin, 1.04 +/- 0.14 versus 0.56 +/- 0.03; P = 0.00; bax/bcl-2, 1.31 +/- 0.12 versus 0.84 +/- 0.09; P = 0.02; Group 1 versus Group 2, respectively). Group 1 had increased bcl-2 and bax protein expression in hippocampal CA1 region at 6 h after CPB (bcl-2, 0.18 +/- 0.05 versus 0.09 +/- 0.01; P = 0.02; bax, 0.20 +/- 0.06 versus 0.04 +/- 0.02; P = 0.01; Group 1 versus Group 2, respectively). Group 1 had increased TUNEL staining in hippocampus CA1 at 6 h after CPB (0.14 +/- 0.02 versus 0.03 +/- 0.01; P = 0.00; Group 1 versus Group 2, respectively). In Group 1 CA1 hippocampus neurons, ultra-structural changes consistent with apoptosis occurred. In rats, moderate hypothermic CPB with hemodilution is associated with CA1 hippocampus bax and bcl-2 gene expression and neuronal apoptosis during the early post-CPB recovery period.

[Effects of moderate hypothermia on expression of nuclear factor-KappaB in rats with acute pancreatitis].

OBJECTIVE: To observe the dynamic changes in the DNA binding activity of nuclear factor-KappaB (NF-KappaB) in rat pancreatic and lung tissues in acute hemorrhagic necrotizing pancreatitis (AHNP), and investigate the effects of moderate hypothermia on AHNP-induced NF-KappaB binding activity in a time-dependent fashion. METHODS: A group of 24 rats was randomly divided into control group, 2, 5 or 12 hours groups after reproduction of AHNP. NF-KappaB binding activity in pancreas and lung tissues was determined using electrophoretic mobility shift assay (EMSA). In another group of 36 rats were randomized into three groups with equal number: sham-operated rats which were kept under 37-37.5 degrees C after laparotomy; AHNP rats with normothermia (37-37.5 degrees C); AHNP rats with moderate hypothermia (32-33 degrees C). Activity of NF-KappaB was assessed at 2 or 5 hours after reproduction of pancreatitis. RESULTS: DNA binding activity of NF-KappaB in pancreas and lung tissue of AHNP rats gradually increased after the development of pancreatitis, and NF-KappaB binding activity was more prominent in pancreas than that in lung tissue at each time point (all P<0.01). NF-KappaB binding activity was inhibited at 2 and 5 hours of moderate hypothermia in lung tissue (P<0.01), but there was no difference in pancreatic tissue between normothermic and hypothermic rats at each time point. CONCLUSION: These data suggest that the expression of NF-KappaB is significantly increased after the development of AHNP. Moderate hypothermia could inhibit the expression of NF-KappaB in lung tissue in acute pancreatitis.

[Effects of moderate hypothermia on pancreatic injury and survival in rats with acute hemorrhagic necrotizing pancreatitis].

OBJECTIVE: To investigate the effect of moderate hypothermia on pancreatic injury and survival of rats with acute hemorrhagic necrotizing pancreatitis (AHNP). METHODS: A set of 112 rats were randomly divided into three equal groups: (1)sham-operated rats (n=24) which were kept at 37.0-37.5 centigrade after laparotomy; (2)AHNP rats (n=44) treated with normothermia (37.0-37.5 centigrade); (3)AHNP rats (n=44) treated with moderate hypothermia (32.0-33.0 centigrade). AHNP was induced by the infusion of 5% sodium taurocholate. Hypothermia was induced immediately after induction of pancreatitis by surface cooling until their rectal temperature reached 32.0-33.0 centigrade. Samples were obtained at 2 or 5 hours after pancreatitis induction in 24 rats of each group. Changes in serum amylase, lipase, wet/dry weight ratio and vascular permeability index, as well as pathology were observed. Another 40 rats of normothermic or hypothermic groups with AHNP were kept at scheduled temperature for 12 hours after pancreatitis induction. Survival was monitored for 72 hours. RESULTS: Serum amylase and lipase levels, vascular permeability index were significantly reduced at 2 or 5 hours, and pancreatic edema significantly reduced at 5 hours after pancreatitis induction in hypothermic group compared with normothermic group (all P<0.05). Mean survival time, which was 7.5 hours (3.0-18.0 hours) in normothermic group, was prolonged with hypothermia to 25.5 hour (13.0-72.0 hours). The survival of hypothermic animals was higher than normothermic ones after pancreatitis induction ( P=0.000 1). CONCLUSION: Moderate hypothermia applied after pancreatitis induction can provide protection against pancreatic injury, and increase survival in rats with AHNP. While the mechanism underlying this protection remains to be clarified, the findings of present study have implications for the possibility that hypothermia may be helpful as an adjunctive clinical therapy in acute pancreatitis.

[Effect of acupuncture-drug compound anesthesia on alteration of immune function in patients undergoing open-heart surgery].

OBJECTIVE: To observe the effect of electro-acupuncture (EA) on alteration of immune function of patients undergoing open-heart surgery with cardiopulmonary bypass (CPB), and to appraise the value of acupuncture-drug compound anesthesia in the operation. METHODS: Thirty patients undergoing atrial septal defect repairing operation were selected and divided into three groups, Group A was the general anesthesia group; Group B, the acupuncture anesthesia group and Group C, the general anesthesia plus EA group. Peripheral venous blood of patients was collected at different time points, i.e. before anesthesia, before CPB, 30 min and 24 hrs after CPB, to determine natural killer cells activity (NKCA), and the levels of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in supernatant of cell culture were also tested. RESULTS: NKCA was significantly lowered in Group A before CPB but increased in Group B, while no evident change was found in Group C, so the level of NKCA in Group B was significantly higher than in the other two groups. It lowered in all the three groups after CPB, especially evidently in Group B, so as to cause the NKCA level in Group B lower than that in Group A. The lowering further progressed, 24 hrs after CPB, NKCA in Group B was more reduced than that in Group C. Levels of IFN-gamma and IL-2 lowered in all the three groups after CPB, and further lowered at time point of 24 hrs after CPB, but the parameters in Group C were significantly higher than those in Group B. CONCLUSION: EA could enhance NKCA, but acupuncture anesthesia couldn't inhibit the suppressive effect of CPB on NKCA, IL-2 and IFN-gamma, suggesting that the immunosuppression induced by stress has a prior effect. General anesthesia plus EA yielded better effect than general anesthesia and acupuncture anesthesia, but it could't improve the immunosuppression completely, indicating that the compound anesthesia could partially improve the immunosuppression induced by CPB.