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.

[Combined use of the airway scope and fiberoptic bronchoscopy for tracheal intubation in a patient with a large epiglottic cyst].

A 26-year-old man was scheduled for surgical extraction of a large epiglottic cyst. Mask ventilation was possible under propofol anesthesia without muscle relaxant. It was difficult to see the glottis using either a Macintosh laryngoscope or by fiberoptic bronchoscopy. When the AWS laryngoscope (Hoya, Tokyo Japan) with a part of the blade removed, was inserted orally, it became possible to see the glottis with a part of the epiglottic cyst. A reinforced tube was inserted nasally, and a fiberoptic bronchoscope was passed through the tube into the trachea. The tube was then passed over the fiberscope into the trachea. We believe that the Pentax AWS laryngoscope may lift the epiglottis and its cyst atraumatically, and may facilitate nasal fiberoptic intubation in a patient with a large epiglottic cyst.

Propofol inhibits cyclo-oxygenase activity in human monocytic THP-1 cells.

PURPOSE: Monocytes/macrophages are key players in innate and adaptive immunity. Upon stimulation, they secrete prostanoids, which are produced by cyclooxygenase from arachidonic acid. Prostanoids influence inflammation and immune responses. We investigated the effect of propofol on prostaglandin E(2) and thromboxane B(2) production by the human monocytic cell line THP-1. METHODS: The THP-1 cells were cultured with lipopolysaccharide (1 microg ml(-1)) in the presence of clinically relevant sedative/anesthetic concentrations of propofol (0-30 microM) for 18 h, and the concentration of prostaglandin E(2) and thromboxane B(2) in culture supernatants was measured using an enzyme immunoassay. Intracellular cyclooxygenase protein expression was measured by flow cytometry. Cyclooxygenase activity was assessed by measuring production of prostaglandin E(2) and thromboxane B(2) by THP-1 cells after arachidonic acid (10 microM) substrate provision. RESULTS: Propofol decreased the production of prostaglandin E(2) (75.4 +/- 6.4 pg ml(-1) at 0 microM vs. 28.5 +/- 11.2 pg ml(-1) at 30 microM; P < 0.001) and thromboxane B(2) (282.4 +/- 79.2 pg ml(-1) at 0 microM vs. 40.4 +/- 21.7 pg ml(-1) at 30 microM; P < 0.001). The inhibition was not due to the decreased cyclooxygenase protein expression because intracellular staining of this enzyme was not affected by propofol. After arachidonic acid provision, prostaglandin E(2) and thromboxane B(2) production from activated THP-1 cells was significantly (P < 0.001) decreased with propofol, indicating direct suppression of cyclooxygenase activity with propofol. CONCLUSIONS: Propofol may modulate inflammation via the suppression of cyclooxygenase activity. Through the inhibition of prostanoid production, propofol may enhance immune responses.

[Use of the laryngeal mask airway prevents gas leak around a tracheal tube].

A 59-year-old man with cervical spondylosis was scheduled for a posterior spine surgery. After induction of anaesthesia with propofol and fentanyl, and neuromuscular blockade with vecuronium, the trachea was intubated using an 8.0-mm ID refinforced tube, without difficulty. After inflation of the cuff with 6 ml of air, there was no gas leak around the tube. The patient was placed in the prone position, and the head fixed to the operating table, using head pins. Several minutes later, there was a marked gas leak around the tracheal tube cuff. Addition of air to the cuff did not solve the problem, indicating rupture of the cuff. A size 5 laryngeal mask airway was inserted while the tracheal tube was left in place with the patient in the prone position. Inflation of the cuff of the laryngeal mask with 15 ml of air and occluding the connector part of the laryngeal mask prevented the gas leak, and adequate ventilation volume could be maintained afterwards. We believe that insertion of the laryngeal mask airway may be useful in minimizing gas leakage around a tracheal tube.

Effect of subhypnotic doses of dexmedetomidine on antitumor immunity in mice.

Dexmedetomidine, a selective alpha2 adrenergic receptor agonist, is a drug often used for sedation. Despite the high prevalence of sedating patients with tumors in intensive care settings, little is known about the effect of sedative drugs on tumor growth. We studied the effect of dexmedetomidine on antitumor immunity in mice. Subhypnotic doses of dexmedetomidine decreased interleukin (IL)-12 production from thioglycollate-induced macrophages. The treatment also decreased the ratio of the helper T lymphocytes subsets, Th1 to Th2 (Th1/Th2), in the spleen. Following subcutaneous inoculation of EL4 T-cell lymphoma cells, dexmedetomidine further decreased the splenic Th1/Th2 ratio and activity of EL4-specific cytotoxic T lymphocytes (CTLs). Finally, treatment with dexmedetomidine accelerated EL4 growth in mice. These data show that treatment of mice with subhypnotic doses of dexmedetomidine down-regulates antitumor immunity, possibly through the decreased production of IL-12 from antigen presenting cells, resulting in a Th2 shift and decreased CTL activity against EL4 in mice.

Ketamine-induced c-Fos expression in the mouse posterior cingulate and retrosplenial cortices is mediated not only via NMDA receptors but also via sigma receptors.

Ketamine induces marked c-fos expression in the posterior cingulate and retrosplenial cortices (PC/RS). We investigated whether NMDA and/or sigma receptors were involved in the c-Fos expression. The number of Fos-LI positive boutons in NMDA receptor knockout mice was significantly lower than that in wild-type mice. Rimcazole but not haloperidol significantly suppressed the c-Fos expression. The results indicate that the ketamine-induced c-Fos expression is mediated not only via NMDA receptors but also via sigma receptors.