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A line of studies strongly suggest that the intravenous anesthetic, propofol, suppresses mitochondrial oxygen metabolism. It is also indicated that propofol induces the cell death in a reactive oxygen species (ROS)-dependent manner. Because hypoxia-inducible factor 1 (HIF-1) is a transcription factor which is involved in cellular metabolic reprogramming by modulating gene expressions of enzymes including glycolysis pathway and oxygen utilization of mitochondria, we examined the functional role of HIF-1 activity in propofol-induced cell death. The role of HIF-1 activity on oxygen and energy metabolisms and propofol-induced cell death and caspase activity was examined in renal cell-derived RCC4 cells: RCC4-EV cells which lack von Hippel-Lindau protein (VHL) protein expression and RCC4-VHL cells, which express exogenous VHL, and in neuronal SH-SY5Y cells. It was demonstrated that HIF-1 is involved in suppressing oxygen consumption and facilitating glycolysis in cells and that the resistance to propofol-induced cell death was established in a HIF-1 activation-dependent manner. It was also demonstrated that HIF-1 activation by treatment with HIFα-hydroxylase inhibitors such as n-propyl gallate and dimethyloxaloylglycine, alleviated the toxic effects of propofol. Thus, the resistance to propofol toxicity was conferred by HIF-1 activation by not only genetic deletion of VHL but also exposure to HIFα-hydroxylase inhibitors.

Background and Objectives The benefit of adding sciatic nerve block (SNB) to femoral nerve block to improve analgesia after total knee arthroplasty (TKA) is uncertain. We hypothesized that the effective duration of single-injection SNB is too short to improve postoperative analgesia and that this contributes to conflicting results on the efficacy of SNB after TKA. We evaluated this hypothesis in a prospective double-blind randomized controlled trial. Methods Sixty patients undergoing TKA were randomly allocated to a continuous SNB group or a single-injection SNB group. All patients received femoral nerve block (0.5% ropivacaine 20 mL) and SNB (0.2% ropivacaine 20 mL) and catheters were inserted into both peripheral nerve block sites before surgery. Both groups received continuous femoral nerve block and patient-controlled intravenous analgesia with morphine. Continuous SNB (0.2% ropivacaine 5 mL/h; continuous SNB group) or sham continuous SNB (0.9% normal saline 5 mL/h; single-injection SNB group) was provided after surgery. The primary outcome was total morphine consumption for 48 hours after surgery. Results Total morphine consumption in the 48-hour period after surgery was significantly lower in the continuous SNB group compared with the single-injection SNB group [4.9 (5.9) vs 9.7 (9.5) mg, P = 0.002]. Visual analog scale pain scores at rest were also significantly lower in the continuous SNB group (P = 0.035). Conclusions The combination of continuous femoral and SNB provides a superior opioid sparing effect and improves analgesia after TKA.

デクスメデトミジン（DEX）は意思疎通可能な鎮静状態，鎮痛作用および交感神経抑制作用を有するが，呼吸抑制作用はほとんど有さない．この優れた特性を生かして，Monitored Anesthesia Care（MAC）の使用薬剤としての手術時におけるDEXの使用が近年進められている．本稿では，気管支ファイバーによる覚醒下気管挿管時，気管狭窄患者の局所麻酔手術や覚醒下開頭術の閉頭時のMAC等におけるDEXの使用法に関して，文献，当院の経験および米国の臨床試験データを紹介する．

The intravenous anesthetic propofol (2,6-diisopropylphenol) has been used for the induction and maintenance of anesthesia and sedation in critical patient care. However, the rare but severe complication propofol infusion syndrome (PRIS) can occur, especially in patients receiving high doses of propofol for prolonged periods. In vivo and in vitro evidence suggests that the propofol toxicity is related to the impaired mitochondrial function. However, underlying molecular mechanisms remain unknown. Therefore, we investigated effects of propofol on cell metabolism and death using a series of established cell lines of various origins, including neurons, myocytes, and trans-mitochondrial cybrids, with defined mitochondrial DNA deficits. We demonstrated that supraclinical concentrations of propofol in not less than 50 μM disturbed the mitochondrial function and induced a metabolic switch, from oxidative phosphorylation to glycolysis, by targeting mitochondrial complexes I, II and III. This disturbance in mitochondrial electron transport caused the generation of reactive oxygen species, resulting in apoptosis. We also found that a predisposition to mitochondrial dysfunction, caused by a genetic mutation or pharmacological suppression of the electron transport chain by biguanides such as metformin and phenformin, promoted propofol-induced caspase activation and cell death induced by clinical relevant concentrations of propofol in not more than 25 μM. With further experiments with appropriate in vivo model, it is possible that the processes to constitute the molecular basis of PRIS are identified.

結核後遺症で，声門直下から気管分岐部に瘢痕性気管狭窄をきたした症例のバルーン拡張，ステント留置術の麻酔を経験した．高度かつ広範囲に狭窄があり，バルーン拡張時に長時間の無換気が予想されたため，ガス交換手段として体外循環を選択した．デクスメデトミジンで鎮静し，自発呼吸下に右大腿動静脈送脱血の経皮的心肺補助（PCPS）を開始し，全身麻酔を導入した．体外循環下でバルーン拡張術を施行後，狭窄部位に気管挿管し，PCPSを離脱した．後日，気管の浮腫が軽減したのちに，ステント留置術をデクスメデトミジン鎮静下，局所麻酔併用で施行した．著明な狭窄で換気困難が予測された症例に対し，体外循環を用いて安全な麻酔管理を行うことができた．

Calcium ion is one of the most important second messengers of cellular signal transduction including hypoxia-elicited signals. In this study, we investigated the effects of the L-type calcium channel blockers such as nifedipine, efonidipine cilnidipine, diltiazem, and verapamil, on the activity of hypoxia-inducible factor-1 (HIF-1), a key transcription factor in control of hypoxia-induced gene expression. Using the lung carcinoma cell line A549 cells, human aortic smooth muscle cells, and human umbilical vein endothelial cells, we demonstrated that cilnidipine exclusively suppressed HIF-1 activity and the expressions of downstream genes in a cell-type specific manner. We also demonstrated that cilnidipine blocked the synthesis of the HIF-1alpha protein not by affecting activity of the intracellular hypoxia-sensing element prolyl hydroxylases but inhibiting activity of Akt and mitogen-activated protein kinase and that the inhibition is not dependent on the effect on calcium homeostasis.

目的:腹腔鏡下胆嚢摘出術（LC）後に診断された胆嚢癌症例の病態を明らかにする．対象と方法:1992年から2004年の術前診断良性のLC 1665例のうち術後判明した胆嚢癌症例12例（0.72％）を2463例の開腹胆嚢摘出（OC）後判明の15例（0.61％）と比較検討した．結果:LC後12例の癌深達度はm 6例，mp 1例，ss 5例と早期癌が58.3％であった．OC後判明例に比較して癌の組織学的所見に差はなかった．LC後の症例ではm癌の全例は経過観察し，胆嚢管断端が癌陽性であった1例のmp癌と，ss癌5例中4例に胆嚢床切除にD2郭清を基本とし追加手術を行った．LC後のss癌1例が他病死，OC後のss癌2例が原病死したが，残る24例は無再発生存中である．結論:m癌ではLC後に追加切除なしで再発はみられずLCが適応となる可能性が示唆された．LC後のss癌判明例では追加切除により良好な成績が得られた．

A prominent feature of various inflamed and diseased tissue is the presence of low oxygen tension (hypoxia). Effector cells of the innate immune system must maintain their viability and physiologic functions in a hypoxic microenvironment. Monocytes circulating in the bloodstream differentiate into macrophages. During this process, cells acquire the ability to exert effects at hypoxic sites of inflammation. The transcription factor hypoxia-inducible factor 1 (HIF-1) mediates adaptive responses to reduced oxygen availability. In this study, we demonstrated that lipopolysaccharide (LPS) induces HIF-1 activation by enhancing both HIF-1alpha protein expression through a translation-dependent pathway and HIF-1alpha transcriptional activity in THP-1 human myeloid cells that have undergone macrophage differentiation but not in undifferentiated monocytic THP-1 cells. LPS-induced HIF-1 activation was blocked by treatment with antioxidant (N-acetylcysteine or thioredoxin-1), NADPH oxidase inhibitor (diphenyleneiodonium), indicating that reactive oxygen species generated in response to LPS are essential in this process. LPS-mediated activation of HIF-1 was independent of NF-kappaB activity. LPS-induced ROS generation and HIF-1 activation required the expression of Toll-like receptor 4 or myeloid differentiation factor (MyD) 88, thus providing a molecular basis for the selective activation of HIF-1 in differentiated THP-1 cells.

腹腔鏡下胃切除術は多くのディスポーザブル製品を使用するため，請求可能な材料費を上回る分の使用する材料費が開腹胃切除に比べて大きいといわれている。そこで腹腔鏡下胃切除におけるコスト面での問題を調査するために開腹胃切除と腹腔鏡下胃切除において使用した材料費の合計，手術料および入院費を比較した。 2007年8月から11月に当院で施行した幽門側胃切除 (開腹: ODG5例，腹腔鏡下: LADG5例)，胃全摘 (開腹: OTG5例，腹腔鏡下: LATG5例) において手術材料費，手術料，入院費用 (診療収入＋入院料) を調査した。胃切除術による利益＝胃切除の手術料－(使用したディスポーザブル製品の材料費－請求可能なディスポーザブル製品の材料費) とした。材料費は定価を用いた。 手術利益はODGが278,756.2円，LADGが190,292.8円，OTGが395,922.6円，LATGが330,653.6円となった。平均入院費用 (診療収入＋入院料) はODGが1,390,464円，平均入院期間は21.4日であり，1日あたりの平均入院費用は65,140.0円であった。それぞれLADGでは1,484,254.0円，18.8日，80,805.4円，OTGでは1,956,664.0円，24.4日，82,397.1円，LATGでは1,686,936.0円，18.4日，91,894.8円であった。 腹腔鏡下胃切除は開腹胃切除に比較して手術費は高いが手術による利益は少ない。現状では十分なコスト削減対策が必須である。全入院中の入院費は必ずしも高くならないが在院日数が短いため1日あたりの入院費は高い。

Proper glycemic control is one of the most important goals in perioperative patient management. Insulin secretion from pancreaticβ-cells in response to an increased blood glucose concentration plays the most critical role in glycemic control. Several animal and human studies have indicated that volatile anesthetics impair glucose-stimulated insulin secretion (GSIS). A convincing GSIS model has been established, in which the activity of ATP-dependent potassium channels (KATP) under the control of intracellular ATP plays a critical role. We previously reported that pimonidazole adduct formation and stabilization of hypoxia-inducible factor-1α(HIF-1α) were detected in response to glucose stimulation and that MIN6 cells overexpressing HIF-1αwere resistant to glucose-induced hypoxia. Genetic ablation of HIF-1αor HIF-1βsignificantly inhibited GSIS in mice. Moreover, we previously reported that volatile anesthetics suppressed hypoxia-induced HIF activationin vitroandin vivo.To examine the direct effect of volatile anesthetics on GSIS, we used the MIN6 cell line, derived from mouse pancreaticβ-cells. We performed a series of experiments to examine the effects of volatile anesthetics (sevoflurane and isoflurane) on GSIS and demonstrated that these compounds inhibited the glucose-induced ATP increase, which is dependent on intracellular hypoxia-induced HIF-1 activity, and suppressed GSIS at a clinically relevant dose in these cells.

Monocytes/macrophages of the myeloid lineage are the main cellular effectors of innate immunity. Hypoxia-inducible factor 1 (HIF-1) is essential for myeloid cell activation in response to inflammatory stimuli. However, it has not been established whether HIF-1 activity is induced during differentiation from monocyte to macrophage. We demonstrate that macrophage differentiation of THP-1 cells or monocytes from peripheral blood induces increased expression of both HIF-1alpha and HIF-1beta as well as increased HIF-1 transcriptional activity leading to increased expression of HIF-1 target genes. The increased HIF-1 activity in differentiated THP-1 cells resulted from the combined effect of increased HIF-1alpha mRNA levels and increased HIF-1alpha protein synthesis. Differentiation-induced HIF-1alpha protein and mRNA and HIF-1-dependent gene expression was blocked by treating cells with an inhibitor of the protein kinase C or MAP kinase signaling pathway. THP-1 cell differentiation was also associated with increased phosphorylation of the translational regulatory proteins p70 S6 kinase, S6 ribosomal protein, eukaryotic initiation factor 4E, and 4E binding protein 1, thus providing a possible mechanism for the modulation of HIF-1alpha protein synthesis. RNA interference studies demonstrated that HIF-1alpha is dispensable for macrophage differentiation but is required for functional maturation.

We have proposed a new piezoelectric oscillator circuit suitable for use in frequency range between 100 MHz and 1.24GHz. The proposed oscillator is composed of a colpitts oscillator and a two-stage common-emitter amplifier. The amplifier picks up the signal from the emitter of the oscillator transistor and feeds back the amplified signal to the base of the oscillator transistor with adequate phase shift. Simulation has shown that sufficiently large negative resistance can be obtained compared to the usual colpitts oscillator at 311MHz, 622MHz, 933MHz and 1.24GHz.

Adaptation to hypoxia and maintenance of O(2) homeostasis involve a wide range of responses that occur at different organizational levels in the body. One of the most important transcription factors that activate the expression of O(2)-regulated genes is hypoxia-inducible factor 1 (HIF-1). Nitric oxide (NO) mediates a variety of biological effects including relaxation of blood vessels and cytotoxicity of activated macrophages. We investigated the effect of the clinically used nitrates nitroglycerin (NTG), isosorbide dinitrate (ISDN), and sodium nitroprusside (SNP) on HIF-1-mediated transcriptional responses to hypoxia. We demonstrate that among the three nitrates, only SNP inhibits HIF-1 activation in response to hypoxia. In contrast, NTG or ISDN does not affect HIF-1 activity. SNP inhibits the accumulation of HIF-1alpha, the regulatory subunit of HIF-1, and the transcriptional activation of HIF-1alpha via a mechanism that is not dependent on either NO or soluble guanylate cyclase.

Hypoxia elicits a wide range of responses that occur at different organizational levels in the body. Hypoxia is not only a signal for energy conservation and metabolic change, but triggers expression of a select set of genes. The transcription factor hypoxia-inducible factor 1 (HIF-1) is now appreciated to be a master factor of the gene induction. Although knowledge on molecular mechanisms of HIF-1 activation in response to hypoxia is accumulating, the molecular mechanism of maintenance of HIF-1 activity under normoxic conditions remains to be elucidated. We demonstrate that the intravenous anesthetic propofol reversibly inhibits HIF-1 activity and the gene expression mediated by HIF-1 by blocking the synthesis of the HIF-1α subunit under 20% or 5% O2 conditions, but not under 1% O2 conditions.

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular adaptive responses to hypoxia. Levels of the HIF-1alpha subunit increase under hypoxic conditions. Exposure of cells to growth factors, prostaglandin, and certain nitric oxide donors also induces HIF-1alpha expression under non-hypoxic conditions. We demonstrate that muscarinic acetylcholine signals induce HIF-1alpha expression and transcriptional activity in a receptor subtype-specific manner using HEK293 cells transiently overexpressing each of M1-M4 muscarinic acetylcholine receptors. The muscarinic signaling pathways inhibited HIF-1alpha hydroxylation and degradation and induced HIF-1alpha protein synthesis that was confirmed by pulse labeling studies. Muscarinic signal-induced HIF-1alpha protein and HIF-1-dependent gene expression were blocked by treating cells with inhibitors of phosphatidylinositol 3-kinase, MAP kinase kinase, or tyrosine kinase signaling pathways. Dominant-negative forms of Ras and/or Rac-1 significantly suppressed HIF-1 activation by muscarinic signaling. Signaling via M1- and M3- but not M2- or M4-AchRs promote accumulation and transcriptional activation of HIF-1alpha. We conclude that muscarinic acetylcholine signals activate HIF-1 by both stabilization and synthesis of HIF-1alpha and by inducing the transcriptional activity of HIF-1alpha.

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular adaptive responses to hypoxia. Levels of the HIF-1alpha subunit increase under hypoxic conditions. Exposure of cells to certain nitric oxide (NO) donors also induces HIF-1alpha expression under nonhypoxic conditions. We demonstrate that exposure of cells to the NO donor NOC18 or S-nitrosoglutathione induces HIF-1alpha expression and transcriptional activity. In contrast to hypoxia, NOC18 did not inhibit HIF-1alpha hydroxylation, ubiquitination, and degradation, indicating an effect on HIF-1alpha protein synthesis that was confirmed by pulse labeling studies. NOC18 stimulation of HIF-1alpha protein and HIF-1-dependent gene expression was blocked by treating cells with an inhibitor of the phosphatidylinositol 3-kinase or MAPK-signaling pathway. These inhibitors also blocked NOC18-induced phosphorylation of the translational regulatory proteins 4E-BP1, p70 S6 kinase, and eIF-4E, thus providing a mechanism for the modulation of HIF-1alpha protein synthesis. In addition, expression of a dominant-negative form of Ras significantly suppressed HIF-1 activation by NOC18. We conclude that the NO donor NOC18 induces HIF-1alpha synthesis under conditions of NO formation during normoxia and that hydroxylation of HIF-1alpha is not regulated by NOC18.

An approximate method of analysis is proposed for calculating the start-up characteristics of a cascode crystal oscillator in terms of the exponential function and logarithmic and algebraic operations. The oscillator circuit is divided into the crystal resonator and the active circuit. The collector bias current dependence and the resonator current dependence of the negative resistance in the active circuit are treated by separation of variables. A new approximation equation is used for the resonator current dependence of the negative resistance. Then, an approximate equation for analysis of the transient response of the collector bias current is derived. By means of these, an approximate equation for analysis of the start-up characteristics of the resonator current is derived as well as an approximate equation for the resonator current at the start of the oscillation. With the obtained approximate analysis equation, two circuit examples with substantially different design conditions are analyzed. The results are compared with an oscillation simulation by SPICE. Sufficient agreement for practical purposes is found and the effectiveness of the proposed analysis method is confirmed. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(12): 32–43, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10166

マンモグラフィ併用乳癌検診の普及に伴い非触知微細石灰化病変が多く見受けられるようになってきた.当科では1998年4月より2002年3月までの間に視触診,超音波にて腫瘤性病変を認めないカテゴリー3以上の腫瘤非形成微細石灰化病変45例に対して,早期診断を目的にステレオガイド下生検を行った. 17/45例(37.8%)が乳癌と診断され,カテゴリー分類別乳癌頻度は,カテゴリー3: 2/10例(20.0%),カテゴリー4: 9/29例(31.0%),カテゴリー5: 6/6例(100%)であった.非浸潤癌は5例(29.4%),残りの12例は微小浸潤癌であった.郭清を施行した14例にリンパ節転移を認めなかったが,微小浸潤癌の1例は術後1年11カ月で遠隔転移をきたした.腫瘤非形成微細石灰化を呈する乳癌では非浸潤癌の頻度が高いが,マンモグラフィ併用乳癌検診の対象年齢が下がれば非浸潤癌発見率のさらなる増加が期待される.

AT-cut quartz crystal resonators are widely used in communication equipment, measurement instruments, computers and etc. The resonance frequency of AT-cut crystal resonator changes proportional to the square of its driving current. The frequency drive level dependency can be modeled by introducing nonlinearity in the equivalent series capacitance of a crystal resonator. We have determined the nonlinear parameter of a 26MHz crystal resonator from the measured data and simulated its frequency drive level dependency. The simulated results agreed well with the measured frequency drive level dependency. And we simulated the phase noise of a CMOS inverter crystal oscillator using the nonlinear model. We found the increase of phase noise of oscillator in the f -2 region.

In Japan, living-donor liver transplantation has long been the only solution for end-stage liver disease. During the past 10 years, 526 cases of living-donor liver transplantation have been performed at Kyoto University Hospital. This report reviews the authors experience of anaesthesia. The most important issue is the safety of the donor. As the percentage of adult recipients has increased, so has the age of donors and because risk for the donor increases with age, careful preoperative evaluation of the donor by the anaesthetist is needed. The principal differences between living-donor liver transplantation and cadaveric donor liver transplantation are surgical technique (the former is always a partial liver transplantation) and viability of the graft (should always be better with a living donor). The major problems concerning the intraoperative management of recipients in living-donor liver transplantation are how to deal with massive blood loss and postreperfusion syndrome.

UNLABELLED Xenon (Xe) suppresses wide dynamic range neurons in cat spinal cord to a similar extent as nitrous oxide (N2O). The antinociceptive action of N2O involves the descending inhibitory system. To clarify whether the descending inhibitory system is also involved in the antinociceptive action of Xe, we compared the effects of Xe on the spinal cord dorsal horn neurons with those of N2O in spinal cord-transected cats anesthetized with alpha-chloralose and urethane. We investigated the change of wide dynamic range neuron responses to touch and pinch by both anesthetics. Seventy percent Xe significantly suppressed both touch- and pinch-evoked responses in all 12 neurons. In contrast, 70% N2O did not show significant suppression in touch- and pinch-evoked responses. These results suggest that the antinociceptive action of Xe might not be mediated by the descending inhibitory system, but instead may be produced by the direct effect on spinal dorsal horn neurons. IMPLICATIONS Xenon (Xe) is an inert gas with anesthetic properties. We examined the antinociceptive effects of Xe and nitrous oxide (N2O) in spinal cord-transected cats. Our studies indicate that Xe has a direct antinociceptive action on the spinal cord that is greater than that of N2O.

The superoxide (O2.-) scavenging activity and neuroprotective effects of oxypurinol, a xanthine oxidase inhibitor, were compared with those of alpha-phenyl-N-tert-butyl nitrone (PBN). The rate constant for the reaction of oxypurinol with O2.- at pH 7.4 was 1.71 x 10(3) M(-1) s(-1) which was more than 100-fold that of PBN (1.65 x 10 M(-1) s(-1)). Oxypurinol inhibited the release of O2.- from stimulated neutrophils better than did PBN. However, oxypurinol did not attenuate the ischemic neuronal damage in gerbils, while PBN did. These results indicate that neither xanthine oxidase inhibiting activity nor O2.- scavenging activity correlates to the therapeutic efficacy of neuroprotective agents in ischemic-reperfusion injury.

We have compared the effects of xenon and nitrous oxide on central nervous system (CNS) electrical activity during sevoflurane anaesthesia in cats by recording the electroencephalogram (EEG), multi-unit activity of the midbrain reticular formation (R-MUA) and somatosensory evoked potentials (SEP). Basal anaesthesia with 2% and 5% sevoflurane was used. With 2% sevoflurane, 70% xenon initially produced rhythmic slow waves which were followed by bursts of high-amplitude sharp waves interrupted by low amplitude slow waves on the EEG. Xenon induced an initial increase, followed by a decrease in R-MUA. Nitrous oxide 70% decreased the amplitude of the EEG activity which was associated with an increase in R-MUA. Xenon suppressed the amplitude of both the initial positive and negative deflections of the SEP to a greater extent than nitrous oxide. With 5% sevoflurane anaesthesia, both anaesthetics increased the frequency of spikes on the EEG and facilitated R-MUA. These findings indicate that xenon has a stimulatory action on CNS background activity and a suppressive action on CNS reactive capability which is more potent than that of nitrous oxide.

BACKGROUND Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.

We compared the effects of xenon (Xe) on the spinal cord dorsal horn neurons with those of nitrous oxide (N 2 O) in cats anesthetized with chrolarose and urethane. We assessed the potency of both anesthetics by the inhibition of wide dynamic range neuron responses evoked by cutaneous noxious (pinch) stimulation to a hindpaw. During 70% Xe inhalation, the responses of 7 of 11 neurons to pinch stimulation were suppressed. N 2 O, 70%, suppressed it in 8 of 11 neurons. The potency of Xe and N 2 O was compared in six neurons that were suppressed by both anesthetics. After 20 min of Xe inhalation, the response to pinch was suppressed to 49.5% ± 8.2% (mean ± SE), while N 2 O, 70% in oxygen, suppressed it to 45.9% ± 7.9%. The difference between N 2 O and Xe was not significant. We conclude that Xe and N 2 O suppress the spinal cord dorsal horn neurons to a similar degree.

Background: Glial cells, including microglia and astrocytes, are considered the primary source of proinflammatory cytokines in the brain. Immune insults stimulate glial cells to secrete proinflammatory cytokines that modulate the acute systemic response, which includes fever, behavioral changes, and hypothalamic-pituitary-adrenal (HPA) axis activation. We investigated the effect of general anesthetics on proinflammatory cytokine expression in the primary cultured glial cells, the microglial cell line BV-2, the astrocytic cell line A-1 and mouse brain. Methodology/Principal Findings: Primary cultured glial cells were exposed to lipopolysaccharide (LPS) in combination with general anesthetics including isoflurane, pentobarbital, midazolam, ketamine, and propofol. Following this treatment, we examined glial cell expression of the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α). LPS-induced expression of IL-1β mRNA and protein were significantly reduced by all the anesthetics tested, whereas IL-6 and TNF-α mRNA expression was unaffected. The anesthetics suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation, but did not affect nuclear factor-kappaB and activator protein-1 activation. The same effect was observed with BV-2, but not with A-1 cells. In the mouse experiments, LPS was injected intraperitoneally, and isoflurane suppressed IL-1β in the brain and adrenocorticotropic hormone in plasma, but not IL-1β in plasma. Conclusions/Significance: Taken together, our results indicate that general anesthetics inhibit LPS-induced IL-1β upregulation in glial cells, particularly microglia, and affects HPA axis participation in the stress response.

Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil, has vasodilatory properties and is used widely in various clinical settings. In addition to acute vasodilatory properties, PGE1 may exert beneficial effects by altering protein expression of vascular cells. PGE1 is reported to be a potent stimulator of angiogenesis via upregulation of VEGF expression, which is under the control of the transcription factor hypoxia-inducible factor 1 (HIF-1). However, the molecular mechanisms behind the phenomenon are largely unknown. In the present study, we investigated the mechanism by which PGE1 induces HIF-1 activation and VEGF gene expression in human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs), both vascular-derived cells. HUVECs and HASMCs were treated with PGE1 at clinically relevant concentrations under 20% O2 conditions and HIF-1 protein expression was investigated. Expression of HIF- 1α protein and the HIF-1-downstream genes were low under 20% O2 conditions and increased in response to PGE1 treatment in both HUVECs and HASMCs in a dose- and time-dependent manner under 20% O2 conditions as comparable to exposure to 1% O2 conditions. Studies using EP-receptor-specific agonists and antagonists revealed that EP1 and EP3 are critical to PGE1-induced HIF-1 activation. In vitro vascular permeability assays using HUVECs indicated that PGE1 increased vascular permeability in HUVECs. Thus, we demonstrate that PGE1 induces HIF- 1α protein expression and HIF-1 activation under non-hypoxic conditions and also provide evidence that the activity of multiple signal transduction pathways downstream of EP1 and EP3 receptors is required for HIF-1 activation.

In this paper, we have made a 433 MHz dual-T SAW oscillator. The oscillator is made of an amplifier, variable gain amplifiers, phase shifters and dual-T SAW resonator circuit. Oscillation frequency can be changed by controlling the gains of variable gain amplifiers. The effective quality factor of the oscillator is enhanced by adjusting phase shifts of phase shifters. Frequency tunable range is about 1,200 ppm, exceeding the limit restricted by used SAW resonators. The effective quality factor of the oscillator is about 30,000, about three times of the unloaded Q of SAW resonators. Phase noise of the oscillator is estimated from the measured spectrum. Above 6 dB improvement of phase noise is obtained at 1kHz offset frequency compared to that of a colpitts oscillator.

Patients undergoing microvascular decompression surgery often experience postoperative nausea and vomiting (PONV). However, there is little information about the incidence of PONV after microvascular decompression. We hypothesized that microvascular decompression is an especially high-risk procedure for PONV in patients undergoing neurosurgery, and investigated risk factors related to PONV after neurosurgery. All patients who underwent craniotomy in our institution during a period of 2 years were investigated retrospectively. Medical charts were reviewed to identify PONV during the 24-h postoperative period and related risk factors. Multivariate logistic regression analysis was conducted to elucidate the impact of microvascular decompression on PONV after craniotomy. Among 556 craniotomy cases, 350 patients met the inclusion criteria. Multivariate logistic regression analysis showed that microvascular decompression was an independent risk factor for PONV after craniotomy (odds ratio 5.38, 3.02–9.60), in addition to female gender, non-smoker status, amount of intraoperative fentanyl administered, and cerebrovascular surgery. In this retrospective study, microvascular decompression surgery was an especially high-risk factor for PONV in patients undergoing craniotomy. It may be necessary to adopt a combination of prophylactic methods to reduce the incidence of PONV after microvascular decompression.

Background Ketamine, a noncompetitive N-methyl-D-aspartate antagonist, has psychotomimetic side effects. Recent studies have shown that noncompetitive N-methyl-D-aspartate antagonists cause morphologic damage to the cingulate and retrosplenial cortices and induce c-fos protein (c-Fos) in the same regions. Although benzodiazepines are effective in preventing these side effects, the neural basis of the drug interactions has not been established. Methods The effects of diazepam and halothane on c-Fos expression induced by ketamine were studied. Diazepam (1 and 5 mg/kg) or vehicle were administered subcutaneously, followed 7 min later by 100 mg/kg ketamine given intraperitoneally. Halothane (1.0 and 1.8%), was administered continuously from 10 min before ketamine administration until brain fixation. Two hours after ketamine injection, rats were perfused and their brains fixed and extracted. Brain sections were prepared in a cryostat and c-Fos expression was detected using immunohistochemical methods. Results Ketamine induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices, thalamus, and neocortex. Diazepam suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices in a dose-dependent manner, leaving the thalamus and neocortex less affected. Halothane suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices and the neocortex in a dose-dependent manner, leaving the thalamus relatively unaffected. Conclusion Halothane and diazepam inhibited ketamine-induced c-Fos expression in the cingulate and retrosplenial cortices, leaving the thalamus relatively unaffected.

Effect of nitrous oxide (N2O) on the somatosympathetic A- and C-reflexes was investigated using artificially ventilated rats anesthetized with alpha-chloralose and urethane. Somatocardiac sympathetic A- and C-reflexes were elicited in the inferior cardiac nerve by electrical stimulation of A and C afferent fibers of the tibial nerve, respectively. Both reflexes were depressed by inhalation of N2O for 20 min. The depression was greater in the C-reflex than in the A-reflex. The depressive effects of N2O on both reflexes were unchanged after pretreatment with intravenous naloxone (0.2 or 2.0 mg/kg) or by prolongation of the inhalation of N2O for 2 h. These results suggest that the opioid receptor is not involved and that acute tolerance is not developed in the depressive action of N2O on the somatosympathetic A- and C-reflexes.

We previously found that acute administration of a nitric oxide synthase (NOS) inhibitor (N omega-nitro-L-arginine methyl ester [L-NAME]) does not reduce the minimum alveolar anesthetic concentration (MAC) of halothane in rats. However, a recent study has suggested that brain NOS activity could not be inhibited by more than approximately 50% by acute administration of L-NAME. To investigate the effect of marked inhibition of NOS activity on the MAC of halothane, we measured cerebellar NOS activity, cerebellar cyclic guanosine monophosphate (cGMP) levels, and halothane MAC in rats chronically treated with L-NAME and compared the results to those of the saline-treated control group. Although the cerebellar NOS activity and cGMP levels were significantly decreased (14% and 2.7% of control, respectively) by L-NAME, the value of the halothane MAC was not significantly affected. These results suggest that the anesthetic action of halothane, as measured by its MAC in rats, is not related to NOS activity or cGMP levels in the brain.

In this paper, we have shown the method to obtain the ultra-high quality factor of a dual-T crystal resonator circuit. In this circuit, the phase shifters are inserted in each T circuit of the dual-T crystal resonator circuit. We have made the simulation and measurement of the proposed dual-T crystal circuit. The attained effective Q is about three times bigger than the unloaded Q of a crystal resonator (about 140,000). And we have made the oscillator using this dual-T circuit and made the simulation of phase noise. 30 through 60 dB improvement of phase noise is suggested in 1/f offset frequency region. The measurement shows the comparable phase noise improvement.