Role of the phagosomal redox-sensitive TRP channel TRPM2 in regulating bactericidal activity of macrophages.

Acidification of macrophage phagosomes serves an important bactericidal function. We show here that the redox-sensitive transient receptor potential (TRP) cation channel TRPM2 is expressed in the phagosomal membrane and regulates macrophage bactericidal activity through the activation of phagosomal acidification. Measurement of the TRPM2 current in phagosomes identified TRPM2 as a functional redox-sensitive cation channel localized in the phagosomal membrane. Simultaneous measurements of phagosomal Ca2+ changes and phagosome acidification in macrophages undergoing phagocytosis demonstrated that TRPM2 was required to mediate the efflux of cations and for phagosomal acidification during the process of phagosome maturation. Acidification in phagosomes was significantly reduced in macrophages isolated from Trpm2-/- mice as compared to wild type, and acidification was coupled to reduced bacterial clearance in Trpm2-/- mice. Trpm2+/+ macrophages treated with the vacuolar H+-ATPase inhibitor bafilomycin showed reduced bacterial clearance, similar to that in Trpm2-/- macrophages. Direct activation of TRPM2 using adenosine diphosphate ribose (ADPR) induced both phagosomal acidification and bacterial killing. These data collectively demonstrate that TRPM2 regulates phagosomal acidification, and is essential for the bacterial killing function of macrophages.

The usefulness of an earphone-type infrared tympanic thermometer for intraoperative core temperature monitoring.

BACKGROUND: In this study we sought to determine the usefulness of a novel earphone-type infrared tympanic thermometer (IRT) for core temperature monitoring during surgery. METHODS: Two groups of patients were studied under different surgical conditions. The first group consisted of 18 adult patients (ASA I or II) who had been scheduled for elective surgery under general anesthesia. Before induction of general anesthesia, an earphone-type IRT was inserted into either the left or right ear canal. Tympanic temperature was monitored and recorded along with both rectal and esophageal temperatures during anesthesia. The second group consisted of eight adult patients (ASA II or III) who had been scheduled for cardiac surgery with cardiopulmonary bypass. Similar to the first group, tympanic temperature was measured by the earphone-type IRT and recorded along with the rectal and esophageal temperatures during cooling and rewarming phases of cardiopulmonary bypass. RESULTS: Study 1-The average temperature (+/-2 sd) measured with the IRT was +0.08 degrees C (+/-0.34 degrees C) above the esophageal temperature, and that with the rectal temperature was +0.11 degrees C (+/-0.55 degrees C) above the esophageal temperature. Study 2-The average temperature (+/-2 sd) measured with the IRT was +0.72 degrees C (+/-2.2 degrees C) above the esophageal temperature during cooling and warming phases during cardiac surgery with cardiopulmonary bypass. CONCLUSIONS: The earphone-type IRT might be used in a clinical setting for reliable and continuous core temperature monitoring during an operation.

[Usefulness of an earphone-type infrared tympanic thermometer for intraoperative core temperature monitoring].

BACKGROUND: Thermometers widely used intraoperatively are invasive and non-hygienic. We developed an earphone-type infrared tympanic thermometer and evaluated its usefulness as a core temperature monitor. METHODS: Sixteen adult patients who required nonabdominal surgery under general anesthesia were enrolled in this study. After induction of general anesthesia, thermistor probes were inserted into the rectum and esophagus for measurements of rectal and esophageal temperatures, respectively. An earphone-type infrared tympanic thermometer was inserted into the ear canal on one side. These measured temperatures were monitored and recorded at 1-min intervals. Regression analysis and Bland-Altman analysis were used to compare the data (tympanic/rectal temperatures) with esophageal temperature as a core temperature. RESULTS: Tympanic temperature showed a good correlation with esophageal temperature (r = 0.976, n= 2490, P < 0.001). The mean difference between these temperature monitors was+0.06 degrees C, and 2x standard deviation (SD) was 0.32 degrees C. Rectal temperature also showed a good correlation with esophageal temperature (r = 0.946, P < 0.001). The mean difference between these monitors was+0.22 degrees C, and 2 SD was 0.28. CONCLUSIONS: The earphone-type tympanic thermometer can be used in a clinical setting as a reliable core temperature monitor.

Effects of systemic administration of lidocaine and QX-314 on hyperexcitability of spinal dorsal horn neurons after incision in the rat.

Although systemic lidocaine has been shown to suppress postoperative pain in a clinical setting, the mechanisms of action of lidocaine have not been elucidated. The present study was therefore designed to determine the relative contribution of central and peripheral sites to the action of lidocaine on incision-induced hyperexcitation of spinal dorsal horn (SDH) neurons in the rat. Receptive field (RF) areas, spontaneous activities, and responses of single wide-dynamic-range (WDR) neurons of the SDH to nonnoxious and noxious stimuli were recorded before and after longitudinal incisions of 1cm through the skin, fascia, and muscle had been made in the center of their RFs of the hindquarters. Significant increases in spontaneous activities, RF sizes, and responses of WDR neurons to both nonnoxious and noxious stimuli were observed at 30 min after the incision (P<0.001). Systemic administration of lidocaine (1 mg/kg bolus plus 0.5 mg/kg/h and 2 mg/kg bolus plus 1 mg/kg/h) and QX-314 (1mg/kg bolus plus 0.5 mg/kg/h and 2 mg/kg bolus plus 1 mg/kg/h) significantly but temporarily suppressed and reversed the increases in spontaneous activity, responses to nonnoxious, and noxious stimuli and RF sizes (P<0.01). Systemic administration of the same doses of lidocaine and QX-314 did not affect responses of WDR neurons to nonnoxious or noxious stimuli or their RF sizes in sham-operated animals in which an incision had not been made. The results suggest that systemic administration of lidocaine has suppressive effects on postoperative pain mainly through peripheral sites of action.

[Effect of continuous extradural infusion of bupivacaine on diaphragmatic function after upper abdominal surgery].

BACKGROUND: Diaphragmatic function is impaired after abdominal surgery. We investigated the effect of continuous extradural infusion of bupivacaine on diaphragmatic function after upper abdominal surgery using respiratory inductive plethysmography (RIP). METHODS: Ten healthy patients for upper abdominal surgery were divided into two groups; the first group of patients with continuous extradural infusion of morphine (group 1) and the second group of patients with continuous extradural infusion of morphine and bupivacaine (group 2). RESULTS: On the first day after surgery, there was no significant difference between the visual analogue scale scores in the two groups. Abdominal contribution to tidal volume (VAB/VT) in group 1 was significantly decreased compared to that of the pre-operative value. VAB/VT in group 2 was significantly higher than that in group 1. CONCLUSIONS: Continuous extradural infusion of bupivacaine improves diaphragmatic function after upper abdominal surgery.