Abstract:
BACKGROUND:Ketamine is widely used as an i.v. anaesthetic agent and as a drug of abuse. Hepatocytes contribute to the metabolism of endogenous and exogenous substances. This study evaluated the toxic effects of S-(+)-ketamine and possible mechanisms using human hepatoma HepG2 cells as the experimental model. METHODS:HepG2 cells were exposed to S-(+)-ketamine. Cell viability and the release of lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GPT) were measured to determine the toxicity of S-(+)-ketamine to HepG2 cells. Cell morphology, DNA fragmentation, and apoptotic cells were analysed to evaluate the mechanism of S-(+)-ketamine-induced cell death. Amounts of Bax, an apoptotic protein, and cytochrome c in the cytoplasm or mitochondria were quantified by immunoblotting. Cellular adenosine triphosphate levels were analysed using a bioluminescence assay. Caspases-3, -9, and -6 were measured fluorometrically. RESULTS:Exposure of HepG2 cells to S-(+)-ketamine increased the release of LDH and GPT, but decreased cell viability (all P<0.01). S-(+)-Ketamine time-dependently caused shrinkage of HepG2 cells. Exposure to S-(+)-ketamine led to significant DNA fragmentation and cell apoptosis (P=0.003 and 0.002). S-(+)-Ketamine increased translocation of Bax from the cytoplasm to mitochondria, but decreased the mitochondrial membrane potential and cellular adenosine triphosphate levels (all P<0.01). Sequentially, cytosolic cytochrome c levels and activities of caspases-9, -3, and -6 were augmented after S-(+)-ketamine administration (all P<0.001). Z-VEID-FMK, an inhibitor of caspase-6, alleviated the S-(+)-ketamine-induced augmentation of caspase-6 activity, DNA fragmentation, and cell apoptosis (all P<0.001). CONCLUSIONS:This study shows that S-(+)-ketamine can induce apoptotic insults to human HepG2 cells via a Bax-mitochondria-caspase protease pathway. Thus, we suggest that S-(+)-ketamine at a clinically relevant or an abused concentration may induce liver dysfunction possibly due to its toxicity to hepatocytes.
journal_name
Br J Anaesthjournal_title
British journal of anaesthesiaauthors
Lee ST,Wu TT,Yu PY,Chen RMdoi
10.1093/bja/aen322subject
Has Abstractpub_date
2009-01-01 00:00:00pages
80-9issue
1eissn
0007-0912issn
1471-6771pii
S0007-0912(17)34074-6journal_volume
102pub_type
杂志文章abstract::We have investigated the effect of interpleural morphine on postoperative pain and pulmonary function after thoracotomy. At the end of surgery, an interpleural catheter was inserted in 17 patients and, in a double-blind and randomized manner, either a bolus of morphine 2.5 mg interpleurally (i.p.) and normal saline i....
journal_title:British journal of anaesthesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/bja/69.6.637
更新日期:1992-12-01 00:00:00
abstract::In 10 dogs, one carotid sinus was isolated from the systemic circulation without disturbing its sympathetic innervation. The isolated sinus was connected to a servo-controlled pressure generator which kept mean intrasinus pressure, pulse pressure, and frequency of pulsation constant. The carotid sinus baroreceptor ner...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/59.4.489
更新日期:1987-04-01 00:00:00
abstract::Six patients with airway stenosis were submitted to bronchoscopy under general anaesthesia. Each was ventilated with a gas mixture of 50% oxygen and nitrogen using successively manual jet insufflation (JV) using the Sanders technique at 20 b.p.m., and high frequency jet ventilation (HFJV) at rates of 150, 300 and 500 ...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/55.10.969
更新日期:1983-10-01 00:00:00
abstract:BACKGROUND:Paradoxical excitement response during sedation consists of loss of affective control and abnormal movements. Chronic alcohol abuse has been proposed as a predisposing factor despite lack of supporting evidence. Because alcohol and propofol have a common site of action, we postulated that paradoxical excitem...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/aer275
更新日期:2011-12-01 00:00:00
abstract::Following antagonism of tubocurarine block with a mixture of atropine 20 microgram/kg and neostigmine 50 microgram/kg in 20 children, heart rate decreased from a control value of 110.4 beat/min to 90.1 at 5 min and 89.2 at 6 min (P less than 0.02). Stroke volume index did not change during the first 5 min from a contr...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/49.9.901
更新日期:1977-09-01 00:00:00
abstract::Although well established in clinical practice, both propofol and midazolam have limitations. New hypnotics with different and potentially superior pharmacokinetics and pharmacodynamics are under development. These include the benzodiazepine receptor agonists CNS7056 and JM-1232 (-), the etomidate-based methoxycarbony...
journal_title:British journal of anaesthesia
pub_type: 杂志文章,评审
doi:10.1093/bja/aeq190
更新日期:2010-09-01 00:00:00
abstract::We describe the anaesthetic management of a patient who underwent transthoracic endoscopic vagotomy. One-lung ventilation was necessary to provide adequate surgical access. Potential intraoperative problems involved arterial oxygen saturation during one-lung ventilation, unequal intrathoracic pressures causing mediast...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/68.3.318
更新日期:1992-03-01 00:00:00
abstract::We report two patients who developed skin necrosis following an intramuscular injection of non-steroidal anti-inflammatory drug into the anteriolateral area of their thigh. Both patients required further multiple operations and one developed life threatening septicaemia. They were left with disfiguring scars. Skin nec...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/88.1.139
更新日期:2002-01-01 00:00:00
abstract::We studied 52 adults undergoing elective craniotomy, allocated randomly to one of three opioid treatments: alfentanil 50 micrograms kg-1 followed by 0.833 microgram kg-1 min-1 until dural closure (group Alf.); alfentanil 50 micrograms kg-1 followed by 0.833 microgram kg-1 min-1 for 2 h, then remifentanil 0.25 microgra...
journal_title:British journal of anaesthesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/bja/81.3.361
更新日期:1998-09-01 00:00:00
abstract::We have determined the influence of 0.1 minimum alveolar concentration (MAC) of sevoflurane on ventilation, the acute ventilatory response to a step change in end-tidal carbon dioxide and the ventilatory response to sustained hypercapnia in 10 healthy adult volunteers. Subjects undertook a preliminary 10-min period of...
journal_title:British journal of anaesthesia
pub_type: 临床试验,杂志文章
doi:10.1093/bja/83.2.204
更新日期:1999-08-01 00:00:00
abstract::Recent research has shown that high-frequency, gamma-band electroencephalographic (EEG) oscillations (40-60 Hz) may be an important marker of the conscious state. We compared the ability of the bispectral index (BIS) to distinguish the awake and anaesthetized states during the induction of general anaesthesia with: (i...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/86.1.50
更新日期:2001-01-01 00:00:00
abstract::Blood concentrations of nitrous oxide were measured in anaesthetists, surgeons and theatre nurses. Comparison of anaesthetists and surgeons working in the same theatre showed that in ENT surgeons concentrations were greater (P < 0.01), while in general surgeons they were smaller (P < 0.003). Blood concentrations of ni...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/52.11.1143
更新日期:1980-11-01 00:00:00
abstract:Background.:Perioperative administration of cefazolin reduces the incidence of perioperative infections. Intraoperative re-dosing of cefazolin is commonly given between 2 and 5 h after the initial dose. This study was undertaken to determine whether intraoperative continuous infusions of cefazolin achieve better probab...
journal_title:British journal of anaesthesia
pub_type: 杂志文章,随机对照试验
doi:10.1093/bja/aex026
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Arterial cannulation is a common anaesthetic procedure that can be challenging and time-consuming in small children. By visualizing the position of the radial artery, near-infrared vascular imaging systems (NIRVISs) might be of assistance in arterial cannulation. The present study evaluates the effectiveness...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/aes193
更新日期:2012-09-01 00:00:00
abstract::We have investigated the effects of propofol on beat-to-beat fluctuations in heart rate, arterial pressure (continuous arterial tonometry) and infrared finger plethysmography in 10 healthy male patients undergoing elective surgery. Administration of Diprivan (propofol 10 mg ml-1) 0.2 ml kg-1, followed by an infusion o...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/73.2.167
更新日期:1994-08-01 00:00:00
abstract::We have examined the role of benzodiazepine receptors in nitrous oxide-induced neuronal depression in rats. The changes in neuronal excitability induced by nitrous oxide and the benzodiazepine inverse agonist, Ro15-4513, were monitored by measurement of visual evoked potentials (VEP). Administration of Ro15-4513 10 mg...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/77.4.522
更新日期:1996-10-01 00:00:00
abstract::We have undertaken a prospective, randomized study to determine the incidence of postoperative nausea and vomiting during intensive care stay after cardiac surgery, and to study the effect of addition of droperidol to an infusion of morphine used for postoperative analgesia. Data from 398 patients were examined. The u...
journal_title:British journal of anaesthesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/bja/77.3.356
更新日期:1996-09-01 00:00:00
abstract::The effect of prostaglandin E1 (PGE1) on local cerebral blood flow (LCBF) and carbon dioxide reactivity (CO2R) was studied during cerebral aneurysm surgery for subarachnoid haemorrhage in 24 patients under neuroleptanaesthesia. Eleven patients had good neurological status (Hunt and Kosnik grade I: group A) and 13 pati...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/68.3.268
更新日期:1992-03-01 00:00:00
abstract:BACKGROUND:We describe a practical method of training anaesthetists in the technique of awake fibreoptic intubation. This is performed on a training course using the delegates as subjects. METHODS:The first 15 subjects underwent cardiovascular monitoring during airway fibreoptic endoscopy performed by other course mem...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/aef226
更新日期:2002-10-01 00:00:00
abstract::Using in vivo microdialysis, we have investigated the effects of propofol on acetylcholine (ACh) release from various regions of the rat brain. Propofol 25 and 50 mg kg-1 i.p. decreased basal ACh release from the frontal cortex by 70% and 85%, respectively. Propofol 25 and 50 mg kg-1 i.p. decreased basal ACh release f...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/80.5.644
更新日期:1998-05-01 00:00:00
abstract::A 72-yr-old patient was to undergo a left lumbar plexus block by the posterior approach to achieve postoperative analgesia after hip replacement. The block failed after three unsuccessful attempts to identify nerve structures and a fascia iliaca compartment block was performed. Postoperatively the patient received eno...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/aeh242
更新日期:2004-10-01 00:00:00
abstract::This is the report of a 55-yr-old female who developed severe myotonia and dystonia after general anaesthesia. Before starting on gabapentin therapy for a neuropathic pain condition, she had undergone numerous uneventful general anaesthetics. Since receiving treatment with gabapentin, she has experienced severe moveme...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/aem130
更新日期:2007-08-01 00:00:00
abstract:Background:The influence of different head and neck positions on the effectiveness of ventilation with the air-Q® self-pressurizing airway remains unevaluated. This study aimed to evaluate the influence of different head and neck positions on ventilation with the air-Q® SP airway. Methods:In this prospective, randomiz...
journal_title:British journal of anaesthesia
pub_type: 杂志文章,随机对照试验
doi:10.1093/bja/aew448
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:We explored whether a previously successful initiative to improve first-case on-time starts succeeded because (i) preoperative steps started earlier (but the process did not necessarily improve) or (ii) the process was brought into better control. METHODS:We analysed 35 months of data comprising 28 882 firs...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1016/j.bja.2018.05.043
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:With the increasing prevalence of children who are overweight and with obesity, anaesthesiologists must determine the optimal dosing of medications given the altered pharmacokinetics and pharmacodynamics in this population. We therefore determined the single dose of dexmedetomidine that provided sufficient s...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1016/j.bja.2020.11.037
更新日期:2021-01-22 00:00:00
abstract:BACKGROUND:Transtracheal jet ventilation (TTJV) is recommended in several airway guidelines as a potentially life-saving procedure during the 'Can't Intubate Can't Oxygenate' (CICO) emergency. Some studies have questioned its effectiveness. METHODS:Our goal was to determine the complication rates of TTJV in the CICO e...
journal_title:British journal of anaesthesia
pub_type: 杂志文章,评审
doi:10.1093/bja/aew192
更新日期:2016-09-01 00:00:00
abstract::The respiratory effects of a new strong analgesic, meptazinol, were compared with a placebo and with equianalgesic doses of morphine and pentazocine in a double-blind crossover trial in seven healthy volunteers. No significant change in the ventilatory response to rebreathing carbon dioxide was observed after meptazin...
journal_title:British journal of anaesthesia
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/bja/51.6.497
更新日期:1979-06-01 00:00:00
abstract::The face-grafting techniques are innovative and highly complex, requiring well-defined organization of all the teams involved. Subsequent to the first report in France in 2005, there have been 17 facial allograft transplantations performed worldwide. We describe anaesthesia and postoperative management, and the proble...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/aet159
更新日期:2013-10-01 00:00:00
abstract::We have studied the relationship between gas exchange and mechanical frequency response during high frequency jet ventilation (HFJV) at 0.5-5.0 Hz in anaesthetized pigs. The mechanical gain curve showed a minimal "anti-resonant" response at 0.8 Hz (f1) and a maximal "resonant" response at 5.0 Hz (f2). This finding may...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/64.4.453
更新日期:1990-04-01 00:00:00
abstract::We describe a 25 mg intrathecal morphine overdose during a combined spinal-epidural block for a Caesarean delivery. Naloxone infusion (5.24 mg over 24 h) was started prior to the patient becoming symptomatic and almost immediately after the overdose. Invasive therapeutics such as mechanical ventilation were avoided. ...
journal_title:British journal of anaesthesia
pub_type: 杂志文章
doi:10.1093/bja/aef286
更新日期:2002-12-01 00:00:00