Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The CD38/cyclic ADP-ribose (cADPR) pathway plays a role in various central nervous system diseases and in morphine tolerance, but its role in local anesthetic intoxication is unknown. The aim of this study was to determine the role of the CD38/cADPR pathway in ropivacaine-induced convulsion.</p><p><b>METHODS</b>Forty male Sprague-Dawley rats were randomly divided into five groups (n = 8 per group): sham group, ropivacaine group, ropivacaine+8-Br-cADPR (5 nmol) group, ropivacaine+8-Br-cADPR (10 nmol) group, and ropivacaine+8-Br-cADPR (20 nmol) group (no rats died). Rats were intracerebroventricularly injected with normal saline or 8-Br-cADPR 30 min before receiving an intraperitoneal injection of ropivacaine. Electroencephalography and convulsion behavior scores were recorded. The hippocampus was harvested from each group and subjected to nicotinamide adenine dinucleotide and cADPR assays, Western blotting analysis, and malondialdehyde (MDA) and superoxide dismutase (SOD) assays.</p><p><b>RESULTS</b>Intraperitoneal injection of ropivacaine (33.8 mg/kg) induced convulsions in rats. CD38 and cADPR levels increased significantly following ropivacaine-induced convulsion (P = 0.031 and 0.020, respectively, compared with the sham group). Intraventricular injection of 8-Br-cADPR (5, 10, and 20 nmol) significantly prolonged convulsion latency (P = 0.037, 0.034, and 0.000, respectively), reduced convulsion duration (P = 0.005, 0.005, and 0.005, respectively), and reduced convulsion behavior scores (P = 0.015, 0.015, and 0.000, respectively). Intraventricular injection of 8-Br-cADPR (10 nmol) also increased the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein ratio (P = 0.044) and reduced cleaved Caspase 3/Caspase 3 ratio, inducible nitric oxide synthase, MDA and SOD levels (P = 0.014, 0.044, 0.001, and 0.010, respectively) compared with the ropivacaine group.</p><p><b>CONCLUSIONS</b>The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.</p>

Suppressing SNAP-25 and reversing glial glutamate transporters relieves neuropathic pain in rats by ameliorating imbalanced neurotransmission / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.</p><p><b>METHODS</b>We used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting.</p><p><b>RESULTS</b>SNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.</p><p><b>CONCLUSIONS</b>SNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1.</p>

Effect of emulsified isoflurane on apoptosis of anoxia-reoxygenation neonatal rat cardiomyocytes

OBJECTIVE@#To explore the effect of emulsified isoflurane (EI) on apoptosis of anoxia-reoxygenation neonatal rat cardiomyocytes and relevant protein expression.@*METHODS@#Cardiac muscle anoxia-reoxygenation damage model was established with culture in vitro neonatal rat cardiomyocytes. The cardiomyocytes were divided into control group, model group, fat emulsion group and EI group. The cardiomyocytes apoptosis rates and lactic dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) index standardization were detected after relevant treatment. The expression of apoptosis-related proteins Bel-2, Bax and Caspase-3 were detected with Western blot approach.@*RESULTS@#After hypoxia/reoxygenation (H/R) model was treated by EI, the cells apoptosis rate decreased and was dramatically below the fat emulsion group (P<0.05). Cardiomyocytes biochemical index detection presented that, compared with the control group that the LDH activity and MDA content dramatically increased (P<0.05), while the SOD activity notably decreased (P<0.05); compared with the H/R group, the SOD activity of the fat emulsion group and EI group increased (P<0.05); while the LDH activity and MDA content decreased (P<0.05). And the change of the EI group was more remarkable than the fat emulsion group (P<0.05). The Western blot analysis presented that, compared with the control group, the Bcl-2 protein expression of the other groups significantly decreased (P<0.05), the expressions of Bax protein and Caspase-3 protein increased significantly (P<0.05); compared with H/R group, cardiomyocytes Bcl-2 protein expression of EI group increased significantly (P<0.05), the expressions of Bax protein and Caspase-3 protein decreased significantly (P<0.05), and the change of EI group was more remarkable than the fat emulsion group (P<0.05).@*CONCLUSIONS@#EI can inhabit the apoptosis of anoxia-reoxygenation damage model cardiomyocytes, and may be related to the up-regulation of expression of Bcl-2 and down-regulation of expression of Caspase-3 protein.

Epidemiological features and risk factors of sepsis-associated encephalopathy in intensive care unit patients: 2008-2011 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Encephalopathy is a common complication of sepsis, and its onset can occur at any stage of sepsis and implies worse prognosis. However, the incidence, epidemiology, and pathogenesis of sepsis-associated encephalopathy remain controversial. The purpose of this study was to investigate the epidemiological features and risk factors for sepsis-associated encephalopathy.</p><p><b>METHODS</b>Our retrospective study included all patients with sepsis admitted to our intensive care unit from 2008 to 2011. After excluding 91 patients, 232 patients were assigned to either a sepsis-associated encephalopathy group or sepsis without encephalopathy group. Between-group differences in baseline patient data including vital signs, disease severity, pathogens, sites of infection, biochemical indicators, and time on a mechanical ventilator, intensive care unit (ICU) stay, and 28-day mortality rate were analyzed.</p><p><b>RESULTS</b>The incidence of sepsis-associated encephalopathy was 17.7%. The sepsis-associated encephalopathy group had significantly higher 28-day mortality (56.1% vs. 35.1%; P=0.013), spent a significantly longer time on a ventilator ((8.2±2.2) days vs. (2.9±0.4) days; P=0.021), and had a significantly longer ICU stay ((12.4±2.4) days vs. (7.1±0.6) days; P=0.042). Acute physiology and chronic health evaluation II score, Glasgow coma scale, heart rate, blood lactate, serum sodium, platelets, serum albumin, and pH values were related to the presence of encephalopathy. Patients with biliary tract infections and intestinal infections caused by Staphylococcus aureus, Enterococcus faecium, Acinetobacter spp, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were more prone to develop sepsis-associated encephalopathy.</p><p><b>CONCLUSIONS</b>Encephalopathy increases mortality rate in septic patients. Clinical intervention to reduce risk factors and thereby morbidity and mortality depends on a correct understanding of the differences between patients with sepsis and patients with both sepsis and encephalopathy.</p>

Intraoperative cardiac arrest during anesthesia: a retrospective study of 218,274 anesthetics undergoing non-cardiac surgery / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Patient safety has been gained much more attention in recent years. The authors reviewed patients who had cardiac arrest in the operating rooms undergoing noncardiac surgery between January 1989 and December 2001 at the University of Pittsburgh Medical Center, USA. The main objectives of the study were to determine the incidence of intraoperative cardiac arrest, to identify possible causes of cardiac arrest and to explore amenable modifications.</p><p><b>METHODS</b>With approval by the University of Pittsburgh Institutional Review Board, patients experienced cardiac arrest during surgery were retrieved from medical records, surgical operation and anesthesia records and pathological reports by searching the Medical Archival Retrieval System (MARS), a hospital electronic searching system. Cases of cardiac arrest were collected over a period of thirteen years from the Presbyterian University Hospital (PUH), USA.</p><p><b>RESULTS</b>We found 23 cases of intraoperative cardiac arrests occurred in 218 274 anesthesia cases (1.1 per 10 000). Fourteen patients (60.8%) died in the operating room, leading to a mortality rate from all causes of 0.64 per 10 000 anesthetics. Immediate overall survival rate after arrest was 39% (9/23). Half of the patients (12/23) were emergency cases with 41% survival rate (5/12). One fourth of the arrests were trauma patients (6/23). Most arrest patients (87%, 20/23) were American Society of Anesthesiologists Physical Status (ASA PS) IV and V, while only three patients were ASA PS-I, II and III, respectively. One case was attributable to an anesthesia-related cardiac arrest and recovered after successful resuscitation.</p><p><b>CONCLUSIONS</b>Most intraoperative cardiac arrests were not due to anesthesia-related causes. Anesthesia-related cardiac arrests might have a higher survival rate when compared to other possible causes of cardiac arrest in the operating room.</p>

Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies suggest that cyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats.</p><p><b>METHODS</b>Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-α (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining.</p><p><b>RESULTS</b>The rats in the I/R group had lower NDSs (P < 0.05), larger infarct volume (P < 0.05), lower HMGB1 levels (P < 0.05), and higher TNF-α levels (P < 0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P < 0.05).</p><p><b>CONCLUSIONS</b>Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.</p>

Effect of intrathecal ketamine injection on protein kinase C expression in the spinal dorsal horn of rats with formalin-induced pain / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of protein kinase C (PKC) in the spinal dorsal horn of rats with formalin-induced pain and the effect of intrathecal ketamine on PKC expression.</p><p><b>METHODS</b>Thirty-two SD rats were randomly divided into 4 equal groups, namely the control group, intrathecal saline group (NS), 50 µg ketamine group (K1) and 100 µg ketamine group (K2). The rats were anesthetized with 10% chloral hydrate, and a microspinal catheter was inserted intrathecally into the lumbar region. Five days later, the rats in groups, K1 and K2 were subjected to intrathecal administration of 50 and 100 µg ketamine (10 µl), respectively, followed by 10 µl saline, and those in NS group received 20 µl saline only. Thirty minutes later, 5% formalin (50 µl) was subcutaneously injected into the left hindpaw. The pain intensity score (PIS) was utilized to assess antinociceptive behavior within 1 h after formalin injection. Twenty-four hours later, the left hindpaw thickness was measured and the expression of PKC in the spinal dorsal horn in the L5 segment was assayed using immunohistochemistry.</p><p><b>RESULTS</b>Compared to group NS, groups K1 and K2 showed significantly decreased PIS (P<0.01) in the second phase of formalin-induced pain; 24 h later, the left hindpaw thickness of group NS increased obviously in comparison with that in the control group (P<0.01), whereas the thickness was significantly reduced in group K1 and K2 as compared to that in group NS (P<0.05). The number of immunoreactive cells and the immunohistochemical score of PKC in the spinal dorsal horn were significantly higher in group NS than in group C (P<0.01), but significantly lower in groups K1 and K2 than in group NS (P<0.05).</p><p><b>CONCLUSION</b>Intrathecal ketamine produces obvious antinociception against formalin-induced pain in rats and inhibits the enhanced PKC expression in the spinal dorsal horn in response to formalin-induced pain, suggesting the important role of PKC in nociceptive signal transmission and modulation in the spinal cord.</p>

Effects of etomidate infusion on serum cortisol in patients undergoing radical resection of lung cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of etodimate infusion on serum cortisol in patients undergoing radical resection of lung cancer operations during the perioperative period.</p><p><b>METHODS</b>Forty ASA I-II patients undergoing radical resection of lung cancer were randomly divided into etomidate group (Group E) and propofol group (Group P) (n=20). The serum cortisol was measured at 8:00 am (T(0)) before anesthesia, 4:00 pm (T(1)) on the day of operation and 24 h after the operation (T(2)) by radioimmunoassay.</p><p><b>RESULTS</b>Compared with that at T0, the serum level of cortisol significantly increased at 24 h after the operation in both groups (P<0.01); serum cortisol decreased lightly at T1, which was not statistically significant (P>0.05), and remained higher than the normal level. At each of the time points, serum cortisol levels were comparable between the two groups (P>0.05).</p><p><b>CONCLUSION</b>Etomidate infusion can not inhibit the synthesis of cortisol in patients undergoing radical resection of lung cancer.</p>

Narcotrend for monitoring the anesthetic depth during endotracheal intubation in sevoflurane anesthesia / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the feasibility of using Narcotrend (NCT) in monitoring the anesthetic depth during endotracheal intubation in sevoflurane anesthesia.</p><p><b>METHODS</b>Thirty ASA I-II patients (aged 20-49 years) undergoing gynecologic surgery under general anesthesia with tracheal intubation were randomized into sevoflurane group (n=15) and sevoflurane plus rocuronium group (n=15). In the former group, anesthesia was induced with sevoflurane at the primary concentration of 8% till the final end expiratory concentration reaching 2 MAC(minimum alveolar concentration) for 3 min, followed then by tracheal intubation and further observation of the indicators for another 3 min. The patients in sevoflurane plus rocuronium group received identical anesthesia procedures except for the administration of intravenous injection of rocuronium (0.6 mg/kg) after the loss of eyelash reflex. The NCT, BIS and hemodynamics were recorded during the process.</p><p><b>RESULTS</b>No significant differences were noted in NCT, bispectral index (BIS), MAP and heart rate before tracheal intubation between the two groups (P>0.05). The NCT and BIS increased significantly after tracheal intubation in sevoflurane group (P<0.05), but remained below 60. No significant changes in NCT and BIS occurred during intubation in sevoflurane plus rocuronium group (P>0.05). The mean arterial pressure (MAP) and heart rate were significantly increased in both groups after tracheal intubation in comparison with those before tracheal intubation (P<0.05), but the increment in sevoflurane group was significantly greater (P<0.05).</p><p><b>CONCLUSION</b>NCT may reflect the changes of the anesthetic depth resulting from the nociceptive stimulus of tracheal intubation in sevoflurane- induced anesthesia. NCT and BIS can not serve such a purpose in combined anesthesia with sevoflurane and rocuronium.</p>

Effect of cerebral state index as a measure of depth of sedation during target controlled infusion of propofol in patients of different ages / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of cerebral state index (CSI) in measuring the level of sedation during target controlled infusion (TCI) of propofol in patients of different ages.</p><p><b>METHODS</b>Forty ASA class I-II patients undergoing general anesthesia were divided into group A (65 to 79 years old, n=20) and group B (20 to 55 years, n=20). The sedation level was assessed using OAA/S scale. Anesthesia was induced with TCI of propofol. The target effect-site concentration (CE) was set initially at 0.5 µg/ml followed by increments of 0.5 µg/ml every 5 min until 5 min after the patients lost consciousness and did not respond to pain stimulation (OAA/S=0). OAA/S score was recorded every 20 s, and MAP, HR, SPO(2) and CSI were recorded. Spearman correlation coefficient between OAA/S score and CSI and their prediction probabilities (Pk) were calculated. The values of CE(05), CE(50), CE(95) and CSI(05), CSI(50), CSI(95) at loss of verbal contact (LVC) (OAA/S=2) and loss of consciousness (LOC) (OAA/s≤1) were also calculated.</p><p><b>RESULTS</b>CSI was well correlated to the sedation depth. The values of CE(50) and CSI50 were 1.3 µg/ml and 69.7 at LVC in group A, and were 1.8 µg/ml and 65.9 at LVC in group B, respectively. The values of CE(50) and CSI(50) were 1.5 µg/ml and 64.3 at LOC in group A, as compared to 2.5 µg/ml and 54.8 at LOC in group B, respectively. When the OAA/S scale was lower than 3, the CSI values in group A were significantly higher than those in group B (P<0.05).</p><p><b>CONCLUSION</b>CSI can effectively and rapidly distinguish the level of sedation in different age groups. At the same OAA/S scale, the target effect-site concentration in the elderly is obviously lower than that in the young patients, but CSI values were significantly higher in the elderly than in the young patients during TCI of propofol.</p>

Effect of human cytomegalovirus infection on the expression of hoxc4 and hoxc6 genes in the proliferation of lymphocytic progenitor cells / 中国实验血液学杂志

The objective of this study was to observe the expression of hoxc4 and hoxc6 genes in the process of differentiation of hematopoietic stem cell (HSC) to colony forming unit-T Lymphocyte (CFU-TL) in vitro. and to explore the possible mechanism of HCMV-induced maldevelopment of human cord blood CFU-TL on genetic level through effecting the differentiation progress by human cytomegalovirus (HCMV) with and/or all-trans retinoic acid (ATRA), Normal CFU-TL culture was used as blank control. After detection with MTT, mRNA expression levels in the human cord blood CFU-TL hoxc4 and hoxc6 genes following HCMV infection and ATRA treatment were detected by fluorogenic quantitative reserve transcription polymerize chain reaction (FQ-RT-PCR) method. HCMV of 10(6) plaque formation unit (PFU)/ml was diluted to 0.1 ml 10(5) PFU/ml and added into the infected group. The results showed that the expression of hoxc4 and hoxc6 genes in the differentiation process increased slightly on day 3, and were up to the most on day 7 (p < 0.05), while became lower on day 12 respectively in normal group, HCMV group and ATRA group. Compared with the expression of hoxc6, the expression of hoxc4 was obviously higher in each group (p < 0.05). Compared with the expression of hoxc4 and hoxc6 genes in normal group, the expressions of hoxc4 and hoxc6 in ATRA group were up-regulated remarkably (p < 0.05), while the expressions of hoxc4 and hoxc6 in group HCMV were down-regulated (p < 0.05). It is concluded that the regular expression of hoxc4 and hoxc6 genes mRNA appeared in each group. A positive co-relationship exits between hoxc4/hoxc6 genes and lymphocytic progenitor hematopoiesis. Compared with the expression of hoxc6 gene, the expression of hoxc4 gene is obviously higher in each group. HCMV can down-regulate the expression of hoxc4 and hoxc6 genes and lead to suppression effect on cell morphology, which confirms that the normal hematopoietic lineage determination and maturation rely on the stable and consistent expression of homeobox gene. At the same condition, ATRA (6 x 10(-8) mol/L at 60 nmol/ml) can up-regulate hoxc4 and hoxc6 genes expression. ATRA can up-regulate the expression of hoxc4 and hoxc6 genes.

Effect of controlled hypotension with different drugs combined with acute hypervolemic hemodilution on bleeding volume and gastrointestinal perfusion in nasal endoscopic surgery / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of controlled hypotension using different drugs on gastrointestinal perfusion and bleeding volume in nasal endoscopic surgery.</p><p><b>METHODS</b>Thirty ASA class I or II patients scheduled for nasal endoscopic surgery were randomized into three groups, including a routine general anesthesia group (group A) and two controlled hypotension groups (groups B and C). After anesthesia induction, anesthesia was maintained with 1%-2% isoflurane and vecuronium. ECG, mean arterial blood pressure (MAP), heart rate (HR), SpO(2) and PETCO(2) were continuously monitored. TRIP tonometry catheter 14 F was inserted into the stomach and connected to Tonocap (Datex-Ohmeda, Finland ). In groups B and C, hypotension was induced with isoflurane (1%-2%) and sodium nitroprusside (0.3-3 microg.kg(-1).min(-1)), and with isoflurane (1%-2%) and glonoine (0.5-5 microg.kg(-1).min(-1)), respectively, and the MAP was reduced to 50-55 mmHg in 10-15 min. In groups B and C, blood samples were taken for blood gas analysis after anesthesia (T(0)), after acute hypervolemic hemodilution (T(1)), at 30 and 60 min after controlled hypotension (T(2) and T(3)), and 30 min after recovery from hypotension (T(4)). In group A, blood samples were taken at different time points in the perioperative period.</p><p><b>RESULTS</b>The patients in groups B and C had smaller bleeding volume than those in group A. HR was decreased after moderate acute hypervolemic hemodilution, and increased after controlled hypotension (T(2) and T(3)) in comparison with that at T(1) to a level similar to that at T(0). No significant changes were found in pHi at T(2) and T(3) in comparison with that at T(1) in the three groups.</p><p><b>CONCLUSION</b>When appropriate measures are taken, induced hypotension at 50-55 mmHg does not necessarily produce disturbance in gastrointestinal perfusion. Induced hypotension with glonoin can decrease the bleeding volume better than sodium nitroprusside in nasal endoscopic surgery.</p>

Drug-induced fatal adverse effects in the United States from 1999 to 2004 / 中南大学学报(医学版)

OBJECTIVE@#To examine the characteristics of drug-induced fatal adverse effects in the United States from 1999 to 2004 and put forward suggestions for China's control of drug-induced adverse effects.@*METHODS@#The data came from the compressed mortality file of Centers for Disease Control and Prevention (CDC) of the United States. Drug-induced mortality was used to analyze the effects of gender, race, age, and drug on drug-induced fatal adverse effects.@*RESULTS@#During 1999-2004, 1 700 persons died of drug-induced adverse effects (mortality, 0.10/100,000). No difference was found in mortality between males and females. The drug-induced mortalities of whites, blacks and Native Americans, and other racial groups were respectively 0.10, 0.12, and 0.04 per 100,000 persons. The mortality increased quickly with the increase of age since the age group of 5-9. In this period, the 5 most common drugs that led to deaths were: (1) agents primarily affecting blood constituents; (2) analgesics, antipyretics, and anti-inflammatory drugs; (3) primarily systemic agents; (4) systemic antibiotics; and (5) hormones and their synthetic substitutes and antagonists, not elsewhere classified. At the age group of 20-84, 3 most common drugs leading to deaths for whites were: anticoagulants,opioids and related analgesics, and insulin and oral hypoglycaemic drugs. For blacks and Native Americans, they were: hydantoin derivatives, anticoagulants, and anaesthetic, unspecified. For people ages older than 84, anticoagulants, opioids and related analgesics, and drug or medicament, unspecified, were the 3 most common drugs resulting in deaths. For the rest of racial groups, the number of deaths caused by all kinds of drugs was less than 3.@*CONCLUSION@#Obvious differences on race, gender, age, and drug were found for drug-induced fatal adverse effects in the United States during 1999-2004, and these differences should be considered by the government when interventions are developed. China can learn something from the United States in controlling drug adverse effects, and improve its surveillance system of drug adverse effects as soon as possible.

Three subanaesthetic dose ketamines mixed with butorphanol in the postoperative continuous intravenous analgesia / 中南大学学报(医学版)

OBJECTIVE@#To determine an optimal clinical dose of ketamine after comparing the efficacy and security of 3 low dose ketamines mixed with butorphanol in the postoperative continuous intravenous analgesia.@*METHODS@#Eighty ASA (American Society of Anesthesiologists) I-II patients scheduled for elective gynecological surgery under general anesthesia were divided randomly into 4 groups (n=20): Group B received butorphanol 3 microg/(kg x h);Group BK1 received butorphanol 2 microg/(kg x h) mixed with ketamine 60 microg/(kg x h); Group BK2 received butorphanol 2 microg/(kg x h) mixed with ketamine 90 microg/(kg.h); and Group BK3 received butorphanol 2 microg/(kg x h) mixed with ketamine 120 microg/(kg x h). Continuous intravenous infusion pump was used when the patients had obvious pain (visual analgesia scale of five), and the bolus infusion (4 mL) was given before the operation, and continuous infusion at 2 mL/h. In the postoperative period, pain was assessed using visual analogue scale (VAS) at 2,6,12,24, and 48 h.At the same time, Ramsay scores and adverse effects were recorded.@*RESULTS@#There was no significant difference in the adverse effects and the postoperative mean arterial pressure, heart rate, respiratory rate values, and pulse oxygen among the 4 groups. Postoperative VAS values in Group BK3 was the lowest, followed by Group BK2. There was no significant difference between Group BK1 and Group B. The incidence of somnolence in Group B was higher than that in Group BK1, BK2 and BK3(P<0.05).@*CONCLUSION@#Ketamine in subanaesthetic dose added to butorphanol for postoperative continuous intravenous infusion has a better postoperative analgesic effect and sedation. It can effectively spare butorphanol consumption without increasing adverse effects. The optimal combined dose is 90-120 microg/(kg x h).

Effect of intrathecal pumping tramadol on the immune function in rats with formalin pain / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effect of intrathecal pumping tramadol on cell-mediated immunity in rats with formalin inflammatory pain.@*METHODS@#Thirty-two Sprague-Dawley adult male rats weighting 250 approximately 300 g were randomly divided into 4 groups (n=8 in each group):Saline group (NS) and 3 tramadol groups (T1,T2,and T3). The rats were anesthetized with intraperitoneal chloral hydrate (300 approximately 350)mg/kg. Microspinal catheter was inserted into the subarachnoid space at the lumber region according to modified Yaksh techniques. In the tramadol groups,after 5 days tramadol was continuously infused through the spinal catheter at 50 (T1),25 (T2), and 12.5 microg/h (T3) for 7 days. In the NS group normal saline was continuously infused instead of tramadol. On Day 7 formalin (5%, 50 microL) was injected into the plantar surface of the left hindpaw. The number of flinches, lickings and total time of licking was recorded for 60 min.Pain intensity scoring(PIS)(0 approximately 3;0= no pain, 3=severe pain) was used to assess the antinociceptive effect of intrathecal tramadol. The rats were killed after the evaluation of pain intensity. Body weight and spleen weight were measured and spleen index (spleen weight/body weight) was calculated. T-lymphocyte function was evaluated based on Concanavalin-A(ConA) induced splenocyte proliferation. A modified lactic acid dehydrogenase(LDH) release assay was done to assess the NK cell activity. Phenotypic expressions of cell surface markers of T lymphocyte subsets (CD3+, CD3+ CD4+, CD3+ CD8+, and CD4+/ CD8+) and NK cell(CD161+) in the spleen were analyzed by flow cytometry.@*RESULTS@#The PIS scores were significantly lower in the T1,T2,and T3 groups than those in the NS group. The spleen index and splenocyte proliferation induced by ConA were significantly suppressed in the T1 group,and the phenotypes of T lymphocyte subsets were significantly changed,but no significant difference was found in the T2 and T3 groups compared with the NS group. There were no differences in NK cell activity in the 3 tramadol groups from the control group.@*CONCLUSION@#Intrathecal pumping tramadol has significantly antinociceptive effect. Intrathecal pumping higher dosage tramadol (50microg/h) suppresses T lymphocyte proliferation and alteres T lymphocyte subset phenotype but does not affect NK cell activity. General analgesic dosage tramadol (25 and 12.5 microg/h) has no effect on the immune function.

Periaqueductal gray administration of HSV-I amplicon vector-mediated HPPE gene therapy of nocicepion in rats with formalin-induced pain / 中南大学学报(医学版)

OBJECTIVE@#To investigate the antinociceptive effect of periaqueductal gray (PAG) administration of herpes simplex virus type-1(HSV-I) amplicon vector-mediated human preproenkephalin gene (HPPE).@*METHODS@#Sprague-Dawley rats weighting 260 to approximately 320 g were randomly divided into pHSVIRES-HPPE-LacZ (SHPZ) group, pHSVIRES-LacZ (SHZ) group, and saline (NS) group which included 3 d,1 week,2 week,3 week,4 week,5 week, and 6 week groups (n=51). The rats were anesthetized with intraperitoneal chloral hydrate (300 to approximately 350) mg/kg. Rats were PAG delivered with recombinant HSV-I amplicon vector SHPZ, SHZ or NS. One week after PAG administration 9 rats in each group were sacrificed and lumber segment of the spinal cord was removed for determination of expression of LacZ by X-gal staining and HPPE mRNA expression by reverse transcription-polymerase chain reaction and L-enkephalin content by radioimmunoassay in PAG. Formalin 50 microL (5%) was injected into the left hindpaw, and pain intensity scoring (PIS) was used to assess the antinociceptive effect.@*RESULTS@#After in vivo transferring, neurocyte demonstrated strong positive signals with X-gal immunohistochemical staining. The expression of HPPE mRNA was detected in PAG after administration of SHPZ. PAG delivery of SHPZ showed antinociceptive effect on formalin-induced pain for 6 weeks compared with SHZ group.@*CONCLUSION@#This amplicon virus can transfer HPPE into rat PAG neural cells and make it express efficiently. PAG administration of SHPZ can produce significant analgesic effect on formalin-induced pain in rats for 5 weeks.

Alterations of myelin basic protein concentration in the plasma and ultrastructure in the spinal cord after continuous intrathecal ropivacaine injection in rats / 中南大学学报(医学版)

OBJECTIVE@#To explore the alterations of serum of myelin basic protein (MBP) concentration in the plasma and ultrastructure in the spinal cord after continuous intrathecal injection of different ropivacaine concentrations in rats.@*METHODS@#Ninety-six male Sprague-Dawley rats weighing 220 to approximately 280 g were randomly divided into a control group (Group N), Group R(1), R(2) and R(3) (24 rats in each group). Each group was subdivided into 4 subgroups (6 rats in each subgroup). According to the method of Yaksh's, a polyurethane microspinal catheter was inserted into the lumbar subarachnoid space in which 8 cm segment was left. Rats in each group were continuously received 40 microL of intrathecal injection of normal saline(Group N), 0.5%, 0.75%, and 1.0% ropivacaine (Group R(1),R(2),R(3)), 3 times every 1.5 hours. Blood (0.5 mL) was drawn from the femoral artery to determine serum concentrations of MBP at the detecting time T(0)(before inserted pipe)and T(1)(before the first intrathecal injection); for the subgroups, the examining time was at T(2), T(3), T(4) and T(5)(6, 12, 24 and 48 h respectively after the last time intrathecal administration). After blood was drawn, the rats in each subgroups were decapitated and the spinal cord of L(1-2) intumescentia lumbalis were immediately removed for electronic microscopic examination.@*RESULTS@#MBP levels were comparatively steady in Group N, R(1) and R(2), while there was statistical difference between Group R(3) and Group N, R(1),R(2),and R(3) (P<0.05). MBP level of Group R(3) was significantly higher at T(2),T(3),T(4) and T(5) than that at T(0)(P<0.01). The ultrastructural changes of the spinal cord in Group R(3) were pycnosis of most neurons, dilation of most rough endoplasmic reticulum, and vague structure of mitochondria and endocytoplasmic reticulum. A few neurons were completely de-generated losing the normal structure, with vacuole degeneration of crista mitochondriales or even partial loss.@*CONCLUSION@#The spinal cord ultrastructure is selectively vulnerable after intrathecal 1.0% ropivacaine injection, which may be one of the important pathophysiological bases for local anesthetic neurotoxicity. MBP may serve as a sensitive and specific indicator of spinal cord damage after intra-thecal administration of ropivacaine.

Investigation and analysis of the incidence of awareness during general anesthesia / 中南大学学报(医学版)

OBJECTIVE@#To investigate the incidence of awareness during general anesthesia in patients undergoing surgery.@*METHODS@#A total of 1,800 patients who underwent the selected and acute surgery with general anesthesia were enrolled. Brain function monitors were not used. Patients were interviewed twice during 24 h and 96 h postoperatively to determine intraoperative awareness.@*RESULTS@#Of all the inpatients, 13 (0.72%) reported clear awareness and never forgot anything during the operation; 145 (8.1%) reported dreaming during anesthesia with doubtful intraoperative recollection. Among the 145 patients, 108(74.5%) were females and 114(78.6%) received propofol anesthesia.@*CONCLUSION@#Intraoperative recollections are rare complication of general anesthesia, and are associated with the increased ASA physical status. Age and sex do not influence the incidence of awareness. Dreaming during anesthesia is related to younger females and propofol maintenance.

Effects of BIS and AEPindex monitoring on the depth of anesthesia in in intravenous-inhalational anesthesia anesthesia / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the effects of bispectral index(BIS) and auditory evoked potentials index(AEPindex) monitoring on the depth of anesthesia in inhalation of isoflurane and target-controlled infusion(TCI) of propofol, and to observe the changes of BIS and AEPindex.@*METHODS@#Fourty ASA physical status I - II patients undergoing selective abdominal operations were divided into 2 groups randomly: Group I1(the end-tidal isoflurane concentration was 0.6 MAC, n=20) and Group I2(the end-tidal isoflurane concentration was 1.0 MAC, n=20). Anesthesia was induced with proprofol and vecuroninm. After the tracheal intubation, the patients were ventilated with 0.6/1.0 MAC isoflurane in pure oxygen, and after 20 minutes, propofol was administered with TCI according to the different target plasma concentrations from 1.0 g/mL to 3.0 g/mL(increasing 0.5 g/mL each time). The changes of MAP, HR, BIS and AEPindex were recorded simultaneously.@*RESULTS@#There was no close correlation between MAP, HR and the end-tidal isoflurane concentration, target plasma concentration of propofol. The correlation coefficiencies between BIS, AEPindex and the end-tidal isoflurane concentration were -0.757, -0.819 and -0.832, -0.878 (P<0.001), respectively; those between BIS, AEPindex and the target plasma concentration of propofol were -0.932, -0.888 and -0.920, -0.923 (P<0.001). The correlation coefficiencies between BIS, AEPindex and the stimulation of endotracheal intubation were -0.728 and 0.544, respectively; however, there was no close correlation between BIS , AEPindex and the stimulation of skin incision, and exploration.@*CONCLUSION@#BIS and AEPindex are reliable parameters to monitor the depth of anesthesia of isoflurane and propofol combined anesthesia; and in response to the stimulation of tracheal intubation, AEPindex is better than BIS, but BIS and AEPindex can not be used to predict the cardiovascular reaction of skin incision and exploration.

Effects of intravenous anesthetics on LPS-induced production of tumour necrosis factor-alpha from primary cultures of rat glial cells in vitro / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effects of intravenous anesthetics on LPS-induced inflammatory responses of primary cultures of rat glial cells in vitro.@*METHODS@#The primary cultures of rat glial cells were stimulated with lipopolysaccharide( LPS) to produce inflammatory responses. Glial cells were divided into 8 groups (n=4): blank control (Group C), LPS(Group L), 100micromol/L ketamine with LPS(Group K1), 1000micromol/L ketamine with LPS (Group K2), 30micromol/L propofol with LPS (Group P1), 300micromol/L propofol with LPS (Group P2), 3micromol/L midazolane with LPS (Group M1), and 30micromol/L midazolane with LPS (Group M2). TNF-alpha released into the culture media was measured by radioimmunity assay.@*RESULTS@#Compared with the blank control Group C, LPS-induced TNF-alpha productions in Group L, K1, K2, P1, P2, M1 and M2 increased significantly. The levels of TNF-alpha in Group K1 and K2 were significantly lower than those in Group L (P<0.05), but TNF-alpha productions in Group P1, P2, M1 and M2 were not significantly different as compared with that in Group L.@*CONCLUSION@#Ketamine can reduce LPS-induced TNF-alpha production of glial cells, thereby inhabiting some of the inflammatory responses. Propofol and midazolam have no effect on the production of TNF-alpha from LPS-stimulated glial cells.