Intrathecal betamethasone for cancer pain: A study of its analgesic efficacy and safety.

BACKGROUND: A preliminary study has shown effective cancer pain relief by intrathecal betamethasone (ITB). However, further evidence is needed to support this new approach. METHODS: Cancer patients with opioid-resistant pain received lumbar intrathecal administration of betamethasone 2 or 3 mg once a week for 28 days. Immediate and short-term analgesia (using a percentage pain reduction scale and a numerical rating scale, NRS) and long-term analgesia (using NRS) were assessed. Patients were classified into two groups according to the most painful site of metastasis: vertebral column and/or surrounding nerve plexus metastases (group A) and other metastases distal from the vertebral column (group B). RESULTS: A total of 104 patients received ITB. Pain relief was observed not only in the lower half but also in the upper half of the body. The proportion of group A patients who experienced immediate analgesia was 81% (47/58), which was significantly greater than that of group B (P < 0.001). A decrease in NRS scores 1 day after ITB administration was observed in significantly more patients in group A than in group B (P < 0.001). Long-term analgesia was also recorded in a greater proportion of patients in group A than in group B in the 7-day (59%, 38/64 vs 6%, 2/33) and 28-day periods (71%, 40/56 vs 31%, 8/26) (P < 0.001). No adverse effects related to neurotoxicity were recorded. CONCLUSION: Intrathecal injection of betamethasone produced analgesia for opioid-resistant cancer pain, and may be a potent therapeutic option for intolerable pain from vertebral column and/or surrounding nerve plexus metastases.

Mitigation of inflammation using the intravenous anesthetic dexmedetomidine in the mouse air pouch model.

Dexmedetomidine, an α2-adrenergic/imidazoline receptor agonist, is a widely used intravenous anesthetic. Its primary current usage is for sedation of patients in the intensive care unit. The mouse air pouch model is versatile in studying the anti-inflammatory effect of a drug on a local inflammation, which is induced by a variety of substances. In the present study, using the carrageenan-induced air pouch inflammation model, we tested whether dexmedetomidine mitigates inflammation occurring locally in the mouse air pouch. We found that dexmedetomidine dose-dependently inhibited the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the pouch and decreased the number of white blood cells (WBC) recruited into the pouch. Dexmedetomidine also dose-dependently inhibited the production of neutrophil chemokines, cxcl1 and cxcl2. Furthermore, the dexmedetomidine-induced decreased recruitment of WBC into the pouch was successfully reversed with intra-pouch administration of cxcl1/cxcl2, but not TNF-α or IL-6. Lastly, the inhibition of the production of the cytokines and chemokines with dexmedetomidine was reversed by the treatment of yohimbine, suggesting that dexmedetomidine's anti-inflammatory effect is primarily via the stimulation of the α2-adrenergic receptor. We conclude that dexmedetomidine has an anti-inflammatory property in the carrageenan-induced mouse air pouch inflammation model, and that the dexmedetomidine-induced inhibition of production of the neutrophil chemokines, cxcl1 and cxcl2, may be related, at least in part, to the inhibition of WBC intra-pouch recruitment.

Use of Sugammadex in a Patient with Myotonic Dystrophy Undergoing Laparoscopic Cholecystectomy.

A 37-year-old female patient with myotonic dystrophy was scheduled for laparoscopic cholecystectomy for gall stone under general anesthesia with continuous propofol infusion. Rocuronium was administered with careful monitoring using TOF- Watch®, measuring train-of-four count (Tc), TOF ratio (Tr), and posttetanic count The total amount of rocuronium was 70 mg ; 0.6 mg .kg⁻1 for anesthetic induction and 0.3 mg .kg⁻1 when Tc exceeded 1. When the operation was completed, Tc was 4, Tr was uncountable and she showed reaction to calling her name. Then sugammadex 2 mg .kg⁻1, rapidly antagonized the neuromuscular block, such that the Tr recovered to 100% but tidal volume was 250 ml in 3 minutes. Additional dorsage of sugammadex, 2 mg .kg⁻1, was required for tidal volume to recover to 530 ml. After 20 minutes of first administration of sugammadex, we extubated the tracheal tube without respiratory depression. To avoid respiratory depression, we did not use postoperative opioids. Intraoperative transversus abdominis plane block and postoperative thoracic epidural block with ropivacaine were successful for postoperative pain relief.

The antioxidant N-acetyl cysteine suppresses lidocaine-induced intracellular reactive oxygen species production and cell death in neuronal SH-SY5Y cells.

BACKGROUND: The local anesthetic lidocaine can affect intra- and extra-cellular signaling pathways in both neuronal and non-neuronal cells, resulting in long-term modulation of biological functions, including cell growth and death. Indeed, lidocaine was shown to induce necrosis and apoptosis in vitro. While several studies have suggested that lidocaine-induced apoptosis is mitochondrial pathway-dependent, it remains unclear whether reactive oxygen species (ROS) are involved in this process and whether the observed cell death can be prevented by antioxidant treatment. METHODS: The effects of lidocaine and antioxidants on cell viability and death were evaluated using SH-SY5Y cells, HeLa cells, and HeLa cell derivatives. Cell viability was examined via MTS/PES ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt]/phenazine ethosulfate) assay. Meanwhile, cell apoptosis and necrosis were evaluated using a cell death detection assay with Annexin V-FITC and PI staining, as well as by assaying for caspase-3/7 and caspase-9 activity, and by measuring the release of lactate dehydrogenase, respectively. Mitochondrial transmembrane potential (ΔΨm) was assessed using the fluorescent probe tetramethylrhodamine ethyl ester. RESULTS: Lidocaine treatment resulted in suppression of the mitochondrial electron transport chain and subsequent attenuation of mitochondrial membrane potential, as well as enhanced ROS production, activation of caspase-3/7 and caspase-9, and induction of apoptosis and necrosis in SH-SY5Y cells in a dose- and time-dependent manner. Likewise, the anesthetics mepivacaine and bupivacaine also induced apoptosis in SH-SY5Y cells. Notably, the antioxidants N-acetyl cysteine (NAC) and Trolox successfully scavenged the mitochondria-derived ROS and suppressed local lidocaine-induced cell death. CONCLUSIONS: Our findings demonstrate that the local anesthetics lidocaine, mepivacaine, and bupivacaine inhibited the activity of mitochondria and induced apoptosis and necrosis in a dose-dependent manner. Furthermore, they demonstrate that treatment with the antioxidants NAC, Trolox, and GGA resulted in preservation of mitochondrial voltage and inhibition of apoptosis via suppression of caspase activation.

[Anesthetic Management for a Patient with Stiff-person Syndrome].

The stiff-person syndrome (SPS) is a rare autoimmune neurologic disorder that affects the gamma-aminobutyric acid (GABA) mediated inhibitory network in the central nervous system with anti-glutamic acid decarboxylase (GAD) antibodies. SPS is characterized by muscle rigidity and painful episodic spasms in axial and lower limb muscles. This case report describes successful peri-operative management of a 61-year-old female (height, 158 cm; weight, 60 kg, ASA-PS 2) with her right upper arm fracture who was scheduled for open reduction and internal fixation. This patient had bulbar paralysis, dysphagia and muscle rigidity associated with a high titer of anti-GAD auto antibodies (2,800 U x ml(-1)). She was diagnosed as SPS and has been treated with predonisolone (30 mg x day(-1)) and diazepam (20 mg x day(-1)) for 1 year. Predonisolone (15 mg) and diazepam (30 mg) was given orally before induction of general anesthesia with propofol, remifentanil and rocuronium bromide. Posture change from supine to beach-chair position led to sudden drop in blood pressure to 38/25 mmHg, which recovered promptly by injecting intravenous ephedrine hydrochloride (28 mg) and hydrocortisone (100 mg). Postanesthetic course was uneventful without postoperative neurologic abnormalities.

Impact of steroid medication before hospital admission on barotrauma in mechanically ventilated patients with acute respiratory distress syndrome in intensive care units.

PURPOSE: To investigate the association between steroid medication before hospital admission and barotrauma in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). METHODS: An observational single-center retrospective study was conducted using patients admitted to the general intensive care unit (ICU) of a university hospital in Japan. We analyzed 149 mechanically ventilated patients with ARDS hospitalized between March 2008 and March 2011. ARDS was identified according to criteria from the Berlin Definition. Barotrauma was defined as pneumothorax, subcutaneous emphysema, or mediastinal emphysema occurring during mechanical ventilation in the ICU. The influence of steroid medication before hospital admission on barotrauma was studied using multiple logistic regression analysis. RESULTS: There were no differences in baseline patient characteristics except for congestive heart failure, peak pressure during mechanical ventilation, and steroid pulse therapy between the barotrauma and non-barotrauma groups. Logistic regression analysis showed that peak pressure ≥35 cmH2O was associated with barotrauma in patients with ARDS [odds ratio (OR), 17.34; P < 0.01], whereas steroid medication before hospital admission was not a significant factor for barotrauma (OR, 1.63; P = 0.51). CONCLUSIONS: Barotrauma in ARDS patients was associated with higher pressure during mechanical ventilation but not with steroid medication before hospital admission.

[Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

Suppression of phagosome proteolysis and Matrigel migration with the α2-adrenergic receptor agonist dexmedetomidine in murine dendritic cells.

Dexmedetomidine is a highly-selective α2-adrenergic receptor agonist used for sedation of critically ill patients in an intensive care setting. Dendritic cells (DCs) in peripheral tissues sense certain foreign antigens and ingest and process them, while migrating to the regional lymph node. Then, DCs present the processed antigen on their surface to stimulate the clonal proliferation of cognitive lymphocytes, leading to the establishment of adaptive immunity. In murine bone marrow-derived DCs, dexmedetomidine significantly delayed the intracellular proteolytic degradation of ovalbumin, while it did not affect phagocytosis, decreased the expression of the surface molecules I-A(b) and CD86, and suppressed cognitive helper T-cell proliferation. Furthermore, dexmedetomidine significantly suppressed DC migration both in vitro, using a Matrigel migration assay, and in vivo, using a foot pad-popliteal lymph node migration assay, which may be ascribed to the inhibition of type IV collagenase/gelatinase activity. Finally, vaccination with dexmedetomidine-treated DCs significantly suppressed the contact hypersensitivity reaction in vivo. These results indicate that dexmedetomidine may suppress immunity by inhibiting DC antigen processing/presentation and migration.

[A case of Rh incompatible transfusion after use of anti-D immunoglobulin for unexpected intraoperative massive hemorrhage].

A 69-year-old woman with Rh-negative blood type was scheduled for total pelvic exenteration. Despite having prepared suspected amount of blood, we were forced to transfuse Rh-positive blood after use of anti-D immunoglobulin (0.25 mg) for unexpected massive hemorrhage. Although some strategies (blood-withdrawal system, vascular embolization, discontinuation of operation, et al.) for reduction of incompatible transfusion were considered, we fortunately could acquire additional matched blood after transfusion of Rh-positive blood (4 units), and the operation was completed. On postoperative days 1-2, we administered anti-D immunoglobulin (each 0.25 mg) prophylactically. It is reported that 0.02 mg immunoglobulin prevents sensitization against 1 ml transfused red cells. In this case, total dose of immunoglobulin was not enough, but antiD antibody was not detected over 6 months nonetheless. Two reasons were speculated for lack of anti-D anti body; this patient was immune-suppressed for chemoradiation against rectal cancer, and remaining Rh-positive red cells in her body were of small amount because of massive hemorrhage. Anyway, anti-D globulin administration with the aim of complete neutralization against incompatible transfusion is considered impossible, as there are few Rh-negative people in Japan. It is necessary to prepare sufficient matched blood for major surgery of Rh-negative patients, and to consider above-described strategies. Unavoidable Rh incompatible transfusion needs long-term (about 6 months) follow-up based on erythrocyte life-span and time of antibody production.

[A case of the transversus abdominis plane block in a super obese patient using a convex probe].

We report that the transversus abdominis plane block (TAP block) can be performed under ultrasound guidance using not a linear probe but a convex probe in a markedly obese patient undergoing laparoscopy-assisted distal gastrectomy. The TAP block is effective for providing perioperative analgesia. The common probe for the TAP block is a high-frequency linear probe, which can not depict the deeper tissues. We used a low-frequency convex probe for TAP block, which clearly showed the spread of local anesthetics in TAP block in a markedly obese patient. A convex probe is preferable for TAP block in markedly obese patients.

[Case of successful management with mirtazapine for prolonged pain after esophagectomy].

This case report describes a successful outcome of mirtazapine treatment in a patient with difficult post-thoracotomy pain. A 63-year-old man received thoracotomy for the resection of esophageal tumor. The pain continued 2 years after the operation. Allodynia was present in the region of the intercostal nerves from the surgical wound. Remedies such as clonazepam, amitriptyline, gabapentin, and acetaminophen were not effective, and epidural block effect was only temporal. The patient experienced a reduction in shooting pain after taking pregabalin; however, he still suffered from persistent pain and, mirtazapine was additionally administrated. One month after this, shooting and persistent pain was reduced, and the patient's appetite was improved, which had been present since the thoracotomy. Since then, his weight slightly increased and the administration of mirtazapine was stopped in accordance with the patient's request. The pain became worse again. Therefore, mirtazapine, commonly used as an antidepressant agent, was considered to be beneficial for neuropathic pain as an analgesic adjuvant.

Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol.

The intravenous anesthetic propofol has a number of well-known nonanesthetic effects, including anti-oxidation and anti-emesis. Another interesting nonanesthetic effect of propofol may be its cyclooxygenase (COX)-inhibiting activity. This activity may have important clinical implications, as propofol could have antitumor properties through COX inhibition. Propofol could counteract the activity of COX, which elicits, via its major product prostaglandin E(2), (1) tumor growth stimulation, (2) increased tumor survival, (3) enhanced tumor invasiveness, (4) stimulation of new vessel formation, and (5) tumor evasion of host immune surveillance through suppression of immune cell functions. Indeed, accumulated evidence indicates that propofol suppresses the proliferation, motility, and invasiveness of tumors in vitro and in vivo. Therefore, propofol could be a particularly suitable anesthetic for use during the perioperative period for cancer surgery. However, whether the COX-inhibiting activity of propofol is related to the reported antitumor properties of propofol is not known. Definitive evidence remains to be provided.

[Use of sugammadex in a patient with narrow angle glaucoma].

An 86-year-old woman was scheduled to receive fourth reconstructive surgery for femoral bone fracture under general anesthesia. She had been suspected with narrow angle glaucoma due to headache and bloodshot eyes during gastroscopy. During transfer to our hospital, she fell down and suffered from the right femoral neck fracture. The patient underwent femoral head replacement under spinal anesthesia. Later, she received surgeries twice uneventfully under spinal anesthesia; removal and re-implantation of the femoral bone head due to infection of the implanted head. Six months later, she fell down again and femoral bone was fractured during rehabilitation. Anesthesia was induced with propofol followed by rocuronium 0.9 mg x kg(-1) i.v. Anesthesia was maintained with propofol and remifentanil, and rocuronium was administered to maintain PTC of 10 or less. The surgery was completed in 150 minutes. At the end of surgery, a laryngeal mask was inserted and the tracheal tube was removed. TOF ratio recovered to 80% 8 minutes after sugammadex 2 mg kg(-1) i.v., and increased to 100% 3 minutes after additional 1 mg x kg(-1). Intraocular pressure stayed below 20 mmHg during the intervention. We could achieve full reversal of neuromuscular blockade and suppress increase in intraocular pressure with use of sugammadex.

Sevoflurane causes greater QTc interval prolongation in elderly patients than in younger patients.

BACKGROUND: Sevoflurane and droperidol prolong the QT interval, and advancing age is not only associated with a prolongation of the QT interval but is also a risk factor for drug-induced QT interval prolongation. In this study, we compared the effect of sevoflurane and droperidol on the corrected QT (QTc) interval and the dispersion of ventricular repolarization (time interval from the peak to the end of the T wave [Tp-e]) in elderly patients with those in younger patients. METHODS: Under sevoflurane anesthesia (1.5%-2.5%) with an antiemetic dose of droperidol (1.25 mg), the QT interval and the Tp-e interval, which indicates transmural dispersion of repolarization across the myocardial wall, were measured in 30 elderly patients (70 years and older) and in 30 younger patients (20-69 years) for 2 hours. The QT interval was normalized for heart rate (QTc) using 3 different formulas: Bazett, Matsunaga, and Van de Water. Data are presented as mean +/- sd. RESULTS: The elderly group was 24.4 years older (P < 0.05) than the younger group. The QTc intervals in the 2 groups before anesthesia were not significantly different. Using all 3 formulas, the QTc interval in the elderly patient group was significantly prolonged by sevoflurane (the QTc intervals at preanesthesia and 60, 75, 90, and 120 minutes after sevoflurane exposure were 0.434 +/- 0.028 seconds, 0.450 +/- 0.037 seconds, 0.463 +/- 0.037 seconds, 0.461 +/- 0.037 seconds, and 0.461 +/- 0.038 seconds, respectively, with the Bazett formula). The sevoflurane-induced QTc interval prolongation in the elderly patient group was significantly greater than that in the younger patient group (0.450 +/- 0.037 seconds vs 0.432 +/- 0.034 seconds, 60 minutes after sevoflurane exposure; 0.463 +/- 0.037 seconds vs 0.441 +/- 0.037 seconds, 75 minutes after sevoflurane exposure; and 0.461 +/- 0.038 seconds vs 0.436 +/- 0.030 seconds, 120 minutes after sevoflurane exposure with the Bazett formula), but the sevoflurane-induced QTc interval prolongation was neither further enhanced with time nor by droperidol. The Tp-e interval was not affected in either group. CONCLUSION: Sevoflurane causes greater QTc interval prolongation in elderly patients than in younger patients. Although sevoflurane does not affect the transmural dispersion of repolarization and sevoflurane-induced QTc prolongation does not advance with time and by droperidol administration, QT interval prolongation and its associated arrhythmias should be carefully monitored during sevoflurane anesthesia in elderly patients.

Airway management in an infant with double aortic arch.

A 2-month old male was admitted due to repeated cyanotic attacks. He had suffered from stridor and retractive breathing since birth. Double aortic arch was diagnosed and the vascular ring formed by the double aortic arch was compressing the trachea. Multirow detector computed tomography showed that he had a right-dominant double aortic arch with left ductus arteriosus and an aberrant left subclavian artery, and that the narrowest part of the trachea, where the diameter was 2.0 mm, was located 9.0 mm above the carina. Airway management in patients with extreme narrowing of the trachea is challenging for anesthesiologists. He was scheduled for ligation and division of the left aortic arch and ductus arteriosus. In the operating theater, anesthesia was slowly induced with sevoflurane (0-4%) in oxygen. After mask ventilation was confirmed to be adequate, a 4.0 mm internal diameter endotracheal tube (ETT) was inserted and advanced smoothly beyond the tracheal stenosis. The tip of the ETT was placed just above the carina using a fiber optic bronchoscope (fiberscope) that was passed through the ETT. Since mechanical ventilation was adequate, vecuronium was administered. Surgery was conducted in the right lateral position and using a left thoracotomy approach. Anesthesia was maintained with sevoflurane (2-3%). After positioning, right one-lung ventilation was performed unexpectedly. However, anesthetic management was achieved without difficult ventilation during surgery. The tip of the ETT was pulled past the stenotic part before transfer to the intensive care unit (ICU). A patent trachea during spontaneous breathing under CPAP (5 and 2 cmH(2)O) was confirmed with a bronchofiberscope in the ICU. After weaning from mechanical ventilation, he had the persistence of mild stridor despite improvement of respiratory symptoms.

[Spinal anesthesia in a patient with SMON disease].

We report a patient with subacute myelo-optico-neuropathy (SMON) in whom spinal anesthesia was employed to treat fracture of the femur neck. An 87-year-old woman was diagnosed as having SMON at the age of 45. The patient was admitted to our hospital with fracture of the femur neck. Aspiration pneumonia was also suspected with shadow in the right lung on the chest X-P The percutaneous oxygen saturation (Spo2) with room air was 77%. Spinal anesthesia with 5 mg of 0.5% hyperbaric bupivacaine and 20 mcg of fentanyl was performed at L3-4. The level of anesthesia was T4. During surgery, no severe pain in the lower limbs was observed. Three hours after the end of surgery, the level of anesthesia was T9. On the day after surgery, the extent of dysesthesia and reflex were similar to those before surgery. General anesthesia has been chosen in SMON patients, because there was a report of severe pain of the lower limbs after spinal anesthesia with dibucaine. In our patient, general anesthesia was considered inappropriate due to hypoxemia. We used a mixture of bupivacaine and fentanyl for spinal anesthesia, because the neurotoxicity of bupivacaine is weaker than that of dibucaine.

[Propofol triggers a marked body temperature increase in a patient with fulminant malignant hyperthermia (MH) without inducing other symptoms of MH].

A 53-year-old woman who had experienced symptoms of fulminant malignant hyperthermia (MH) by sevoflurane a week before and her MH muscle biopsy revealing positive later, underwent the right hemicolectomy under total intravenous anesthesia with propofol and fentanyl. The patient's body temperature increased at a rate of 0.6 degree C per 15 min from 37.5 to 39.4 degrees C, but other symptoms of MH, such as tachycardia, arrhythmia, acidemia, and hypoxemia, were obviously slight in comparison with those induced by sevoflurane. The body temperature decreased after discontinuation of propofol and administration of dantrorene injection. When the patient received continuous propofol infusion for the purpose of sedation in the intensive care unit again, the body temperature gradually increased to 40 degrees C. However, it decreased to 37.8 degrees C after discontinuation of propofol and dantrorene injection again. It is well recognized that propofol is not a MH trigger, but it shoud be noted that some MH patients could experience a hypermetabolic state, such as hyperthermia, even by propofol.

Involvement of TORC2, a CREB co-activator, in the in vivo-specific transcriptional control of HTLV-1.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) causes adult T -cell leukemia (ATL) but the expression of HTLV-1 is strongly suppressed in the peripheral blood of infected people. However, such suppression, which may explain the long latency in the development of ATL, is readily reversible, and viral expression resumes quickly with ex vivo culture of infected T -cells. To investigate the mechanism of in vivo -specific transcriptional suppression, we established a mouse model in which mice were intraperitoneally administered syngeneic EL4 T -lymphoma cells transduced with a recombinant retrovirus expressing a GFP-Tax fusion protein, Gax, under the control of the HTLV-1 enhancer (EL4-Gax). RESULTS: Gax gene transcription was silenced in vivo but quickly up-regulated in ex vivo culture. Analysis of integrated Gax reporter gene demonstrated that neither CpG methylation of the promoter DNA nor histone modification was associated with the reversible suppression. ChIP-analysis of LTR under suppression revealed reduced promoter binding of TFIIB and Pol-II, but no change in the binding of CREB or CBP/p300 to the viral enhancer sequence. However, the expression of TORC2, a co-activator of CREB, decreased substantially in the EL4-Gax cells in vivo, and this returned to normal levels in ex vivo culture. The reduced expression of TORC2 was associated with translocation from the nucleus to the cytoplasm. A knock-down experiment with siRNA confirmed that TORC2 was the major functional protein of the three TORC-family proteins (TORC1, 2, 3) in EL4-Gax cells. CONCLUSION: These results suggest that the TORC2 may play an important role in the in vivo -specific transcriptional control of HTLV-1. This study provides a new model for the reversible mechanism that suppresses HTLV-1 expression in vivo without the DNA methylation or hypoacetylated histones that is observed in the primary cells of most HTLV-1 -infected carriers and a substantial number of ATL cases.

Vaccines using dendritic cells, differentiated with propofol, enhance antitumor immunity in mice.

Dendritic cell-based vaccines are useful for enhancing antitumor immunity. It has been suggested that propofol, an intravenous anesthetic, can enhance antitumor immunity in mice. We tested vaccine efficacy for eliciting antitumor immunity, using dendritic cells differentiated from bone marrow cells in the presence of propofol. Propofol-differentiated (but not control vehicle-differentiated) dendritic cells significantly delayed the growth of B16 melanoma in vivo. In vitro cytotoxic T cell activity was not affected by propofol. However, natural killer cell activity in mice vaccinated with dendritic cells differentiated in propofol was significantly upregulated, compared to unvaccinated mice.

Propofol suppresses prostaglandin E(2) production in human peripheral monocytes.

Prostaglandin E(2) secreted from monocytes/macrophages plays important roles in immunity and in inflammation. Currently, propofol, an intravenous anesthetic, is the most widely used drug for the anesthesia and sedation of patients, including those who are vulnerable to infection and/or immunosuppression. Here we report that propofol suppressed prostaglandin E(2) production in lipopolysaccharide-activated human peripheral monocytes. The suppressive effects of propofol were ascribed to its inhibition of cyclooxygenase-2 activity rather than to effects on cyclooxygenase protein expression or substrate availability. Thus, propofol seems to have a prominent effect on immunity and inflammation.