南 浩一郎

Adrenomedullin (AM), a hypotensive peptide originally isolated from human pheochromocytoma, has been reported to regulate renal functions. In patients with glomerulonephritis, the serum levels of AM are elevated as well as hypertensive agents norepinephrine (NE) and angiotensin II (AII). The effects of AM on the NE- or AII-induced presser effects and renal blood flow responses, however, are not well clarified. We examined the effects of AM on blood pressure and renal blood flow induced by NE or AII in anesthetized rats. Arterial blood pressure and renal blood flow were measured using a calibrated pressure transducer and a laser Doppler flowmeter, respectively. Drugs were injected into the tail vein with a syringe. Intravenous administration of AM (1-3 nmol/kg) decreased the arterial blood pressure in anesthetized rats in a dose-dependent manner, whereas it did not affect the renal blood flow. NE or AII administration in anesthetized rats caused both increases in blood pressure and decreases in renal blood flow. Simultaneous administration of AM with NE or AII prevented the increasing effects of blood pressure and inhibited the decreases in renal blood flow caused by NE or AII. These findings suggest that AM may have a protective role against the presser effects and decrease in renal blood flow caused by NE or AII.

14歳男児.1歳時に先天性多発性関節拘縮症と診断され,今回,両股関節の屈曲拘縮に対し,両股関節周囲軟部組織解離術が予定された.術前検査では呼吸・循環系に問題はなく,血液生化学ではCPKの軽度高値を示した以外,正常であった.術3日前より,悪性高熱予防目的にダントロレンを経口投与した.麻酔は,プロポフォール 30mg静注後,ベクロニウムを計2mg投与した.挿管後,亜酸化窒素-酸素-プロポフォールで維持し,執刀前にペンタゾシン投与を行った.手術中の呼吸・循環系,体温は安定し,術後も良好であった

68歳女で,腹部巨大腫瘍の手術前日に腫瘍の栄養動静脈を確認する目的で血管造影を行ったところ突然肺塞栓症を発症した.この為周術期の再塞栓に備えてワーファリン,ウロキナーゼによる抗凝固線溶療法を開始すると共に,麻酔中に発生した場合の早期発見の為に呼気終末二酸化炭素濃度測定,カプノグラムの装着,肺動脈圧モニタとしてのSwan-Ganzカテーテル挿入などを行った.Swan-Ganzカテーテルは抗血栓療法のルートとしても使えるようにしておいた.また緊急percutaneous cardio-pulmonary support挿入に備えて右大腿動脈に9Fのシースを挿入した.術後の塞栓予防にはA-Vインパルスシステムを用いた.手術は術中再塞栓を起こすことなく終了し,術後も問題なく経過した

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Toshio Narahashi and Kinya Kuriyama. The presentations were (1) Modulation of neuroreceptors and ion channels by alcohol, by T. Narahashi; (2) Inhibition by ethanol of NMDA and AMPA receptor-channels, by P. Illes, K. Wirkner, W. Fischer, K. Muhlberg, P. Scheibler, and C. Allgaier; (3) Effects of ethanol on metabotropic glutamate receptors, by K. Minami; (4) Acute alcohol actions on the 5-HT3 ligand-gated ion channel, by D. Lovinger; (5) Inhibition of NMDA receptors by MK801 attenuates ethanol-induced taurine release from the hippocampus, by F. Lallemand, R.J. Ward, and P. DeWitte; and (6) Effect of ethanol on voltage-operated Ca2+ channels in hepatic stellate cells, by T. Itatsu, Y. Takei, II. Oide, M. Hirose, X. E. Wang, S. Watanabe, M. Tateyama, R. Ochi, and N. Sato.

We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K-ATP) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 muM to 1 mM inhibited [H-3]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 muM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of KATP mediators. Cromakalim, a KATP activator, and glibenclamide, a KATP inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway. Copyright (C) 2001 S. Karger AG, Basel.

Several reports have highlighted the risk of pulmonary embolisms during the preoperative period in patients with large abdominal tumors obstructing the inferior vena cava. We describe a patient who developed pulmonary embolism just before surgery. A 64-year-old female was scheduled to undergo elective resection of a large abdominal tumor under general anesthesia. She had no signs of deep venous thrombosis, but on the day of the operation, pulmonary embolism developed suddenly. Anticoagulant therapy was performed. Capnography and pulmonary artery pressure were monitored during the perioperative period to detect the recurrence of pulmonary embolism. The percutaneous cardio-pulmonary support (PCPS) was also prepared. The operation was performed successfully. In this patient, the pulmonary embolism occurred suddenly during the preoperative period, even though we had ruled out the existence of deep venous thrombosis. This case report emphasizes the risk of pulmonary embolism in any patient with a large abdominal tumor obstructing the inferior vena cava. This case of a large abdominal tumor suggests that capnography, monitoring of pulmonary artery pressure and preparation of a PCPS in case of pulmonary embolism during surgery are necessary even in patients without signs of deep venous thrombosis.

Arthrogryposis multiplex congenita (AMC) is a syndrome with multiple persistent limb contractures, often accompanied by associated anomalies. Pediatric patients with AMC frequently require operations, necessitating general endotracheal anesthesia. We report on the anesthesia used for a 14-year-old male with AMC, who required the surgical removal of soft tissue from both hip joints. We used propofol and vecuronium bromide to induce anesthesia, and maintained anesthesia with 40% nitrous oxide, oxygen, and propofol at 6 mg · kg-1 · 1 hr-1. Both induction and maintenance were smooth, and no hyperthermia occurred perioperatively. Propofol can be safely used for anesthesia in AMC patients.

Arnold-Chiari malformation is a congenital disorder with caudal displacement of the cerebellar tonsils through the foramen magnum into the cervical canal. We report difficulty with ventilation during the induction of anesthesia due to apnea and laryngospasm in a 5-year-old female with Arnold-Chiari malformation type II diagnosed at birth. She had had short periods of apnea during infancy, but was asymptomatic recently. Slow induction of anesthesia was performed using sevoflurane, but just after induction, the patient developed apnea and we could not ventilate her due to laryngospasm. We woke her up, and induced anesthesia with barbiturates. The operation was performed without complications, but she had another apnea attack with laryngospasm at extubation. This case suggests that it is important to be aware of the possibility of apnea due to disorder of the respiratory center in patients with Arnold-Chiari deformity.

Angelman症候群は重度精神遅滞,てんかん,容易に起こる笑い,失調性歩行,小頭と大きい下顎をもつ特異的な顔貌などを特徴とする遺伝性疾患で,下顎の突出と巨舌がみられる.症例は4歳,男児.身長104cm,体重14kg.1歳6ヵ月時に,睡眠時無呼吸を指摘され,両側口蓋扁桃摘出とアデノイド切除術が予定された.麻酔導入はセボフルランの自発呼吸下で行い,気管挿管は容易にできた.術中の呼吸,循環動態に問題はなく無事に手術を終了した.本症候群の麻酔管理には重度精神遅滞に対する導入時の鎮静,小頭と巨舌による上気道閉塞対策,筋弛緩薬の作用増強などに注意する必要がある.

硬膜外麻酔後に神経症状が出現したことを契機に発見された, 硬膜内クモ膜嚢腫の症例を経験した. 症例は66歳, 女性. 子宮脱, 膀胱脱のため膣式子宮全摘出術が予定された. L_3/4間から硬膜外カテーテルを挿入したが, 出血もなくカテーテル挿入も容易であった. プロポフォールで導入後, スキサメトニウムで筋弛緩を得た後に気管挿管を行った. 硬膜外麻酔と酸素, 亜酸化窒素, イソフルランで麻酔を維持した. 術中は異常なく麻酔を終了した. 術後3日目より両側のL₁からL₄までの知覚低下を訴えたため, magnetic resonance imaging (MRI) でL₁からL₃にかけて血腫が疑われた. 椎弓切除術が施行され, 硬膜内クモ膜嚢腫が発見された. 硬膜外麻酔後の神経脱落症状の原因の一つに脊柱管内クモ膜嚢腫があると思われる.

Background: Norepinephrine transporters (NETs) terminate the neuronal transmission of norepinephrine, which is released from noradrenergic neurons. To investigate the interaction with NET, the authors examined the effects of short- and long-term treatment with anesthetics on the activity and mRNA level of NET Methods: To assay [H-3]norepinephrine uptake, bovine adrenal medullary cells in culture were incubated with [H-3]norepinephrine in the presence of intravenous anesthetics, including propofol thiamylal, and diazepam, To study the direct interaction between the anesthetics and NET, the effect of propofol on the binding of [H-3]desipramine to the plasma membrane was examined. To study the long-term effect of anesthetics, [H-3]norepinephrine uptake by cells pretreated with propofol for 6-24 h and [H-3]desipramine binding after pretreatment for 12 h were measured. Simultaneously, we examined the effect of anesthetics on the expression of NET mRNA using the reverse transcriptase-polymerase chain reaction. Results: All of the intravenous anesthetics inhibited [H-3]norepinephrine uptake In a concentration-dependent manner. The active concentrations of propofol (1-3 muM) and thiamylal (less than or equal to 30 muM) were Similar to those encountered clinically. The kinetic analysis revealed that all the anesthetics noncompetitively inhibited [H-3]norepinephrine uptake. Propofol inhibited [H-3]desipramine binding with a potency similar to that observed in [H-3]norepinephrine uptake. Scatchard analysis showed that propofol competitively inhibited [H-3]desipramine binding. On the other hand, long-term treatment of cells with propofol (10 mum) enhanced the NET functional activity and [3H]desipramine binding, and also increased the level of NET mRNA, Conclusions: These results suggest that intravenous anesthetics have a dual effect on NET; short-term treatment causes inhibition, whereas long-term treatment leads to up-regulation. The interaction of intravenous anesthetics with NET may modulate the neuronal transmission of norepinephrine during anesthesia.

40歳女.全身麻酔下で腹式単純子宮全摘術中,サイズ3のラリンジアルマスク(LMA)の挿入15分後に両側の急性顎下部腫大を認めた.この原因がLMA挿入であることを確認するため,カフ内圧を上昇させてLMA体積を増大させると,顎下腺は有意に増大し大きく変形した.LMA抜去直後に腫大は消失した.耳鼻科診療で唾石症や唾液腺疾患は指摘されず,後遺症は無かった.LMAが顎下腺を圧排し変形し直接刺激したため,唾液分泌が亢進したことが顎下腺腫大を来したと考察した

Pancuronium stimulates the cardiovascular system, whereas vecuronium, a derivative of pancuronium, has far fewer effects. The inhibition of norepinephrine transporter (NET) in the sympathetic nervous system may partly account for the stimulatory actions of pancuronium. To investigate the mechanism of action of pancuronium on NET, we examined the effects of pancuronium on NET activity by using cultured bovine adrenal medullary, cells and compared pancuronium with other neuromuscular blocking drugs. Pancuronium (1-300 mu M) inhibited desipramine-sensitive [H-3]norepinephrine (NE) uptake in a concentration-dependent manner. Vecuronium (100-300 mu M) and d-tubocuarine (300 mu M) also decreased [H-3]NE uptake but were less potent than pancuronium at clinical concentrations. Succinylcholine had little effect on [H-3]NE uptake. Saturation analysis showed that pancuronium and vecuronium reduced an apparent maximum velocity (V-max) of [H-3]NE uptake without altering Michaelis-Menten constant, indicating noncompetitive inhibition. Pancuronium did not inhibit the specific binding of [H-3]desipramine to plasma membranes isolated from bovine adrenal medulla. A protein kinase C inhibitor, GF109203X, did not affect the inhibition of [H-3]NE uptake by pancuronium, Pancuronium enhanced the inhibition of NET induced by ketamine. These results suggest that pancuronium, with clinically relevant concentrations, inhibits NET activity by interacting with a site distinct from the recognition site for NE and the desipramine binding site on the transporter.

就業中の化学物質曝露中毒事例の情報提供のあり方を検討した.産業現場では多種多様の化学物質が使用されており,ヒトでの毒性がよくわかっていない物質による中毒事例も少なくなかった.中毒事例は経気道曝露が多かった.就業中の化学物質曝露中毒事例の情報提供には,起因物質の毒性情報の提供と共に,曝露時の作業環境,臨床経過等を産業医学的かつ臨床医学的に解析したデータを提供することが必要と考えられた

A 40-year-old woman was scheduled for abdominal hysterectomy. Moderate difficulty in tracheal intubation was expected on preoperative evaluation. A size 3 laryngeal mask airway (LMA) was inserted after the induction of general anesthesia. The LMA insertion was accomplished smoothly at the first attempt and there was no air leakage during manual ventilation. Soon after the insertion, acute swellings were noted in the bilateral submandibular triangle regions. Enlargement and deformity of the submandibular glands were diagnosed by ultrasonography. The enlargements increased with elevated pressure of the LMA cuff, but disappeared completely in five minutes after removal of the LMA. Such enlargement did not occur with subsequent tracheal intubation. The patient had an uneventful postoperative course without any residual sequelae. We should pay attention to possible submandibular gland swellings by LMA insertion.

A 73-year-old woman who suffered from progressive hoarseness for 6 years and dysphagia without pain for 1 year presented with a soft tissue deposition on the posterior region of the vocal cords and narrowing in the subglottic area. Biopsy of this soft tissue and histological examination revealed laryngeal amyloidosis. A tracheostomy and partial removal of the amyloid were performed with general anesthesia. The airway was secured with a smaller diameter endotracheal tube which was inserted atraumatically with Magill's forceps. The larynx is a rare site for amyloidosis. Laryngeal amyloidosis is fragile and hemorrhagic. Therefore, massive bleeding may occur during intubation. Anesthetists should take care in intubating the tracheas of these patients and be aware of other systemic diseases in laryngeal amyloidosis. (C) 1999 by Elsevier Science Inc.

4ヵ月児の声門直下の90%の気道狭窄を伴う頸部の血管腫に対して,ラリンジアルマスク(LMA)を用いて麻酔管理を行なった.麻酔はセボフルランとフェンタニルで導入し,LMAを挿入後,酸素-セボフルラン-フェンタニルを用い自発呼吸下に麻酔を維持した.術中はLMAを介し気管支ファイバースコープで持続的に気道観察を行ない,気道を閉塞させることなく無事麻酔を終了した.気道狭窄を伴う気管腫瘍に対しては,術中にLMAを介し気管支ファイバースコープで持続的に気道観察を行なうことは手術中の気道閉塞の予防に有効である.

Effects of the intravenous anaesthetic ketamine on the desipramine-sensitive noradrenaline transporter (NAT) were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NAT (bNAT). Incubation (1-3 h) of adrenal medullary cells with ketamine (10-300 mu M) caused an in crease in appearance of catecholamines in culture medium. Ketamine (10-1000 mu M) inhibited desipramine-sensitive uptake of [H-3] noradrenaline (NA) (IC50=97 mu M) Saturation analysis showed that ketamine reduced V-max of [H-3]NA uptake without changing K-m, indicating a non-competitive inhibition. Other inhibitors of NAT, namely cocaine and desipramine, showed a competitive inhibition of [H-3]NA uptake while a derivative of ketamine, phencyclidine, showed a mixed type of inhibition. Ketamine (10-1000 mu M) also inhibited the specific binding of [H-3]desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [H-3]desipramine binding revealed that ketamine increased K-d without altering B-max, indicating a competitive inhibition. In transfected Xenopus oocytes expressing the bNAT, ketamine attenuated [H-3]NA uptake with a kinetic characteristic similar to that of cultured adrenal medullary cells. These findings are compatible with the idea that ketamine non-competitively inhibits the transport of NA by interacting with a site which partly overlaps the desipramine binding site on the NAT.

両側性先天性眼瞼下垂と外斜視を伴ったmyotubular myopathy患者の左水平筋前後転術の周術期管理を経験した.患者は術前より全身性び漫性の筋萎縮と筋力低下及び呼吸機能の低下が認められたため,筋弛緩薬を使用せずチアミラール-セボフルラン-亜酸化窒素で麻酔を行った.手術後,患者は覚醒遅延をきたし,更に術後約20時間以上にわたる筋脱力状態をきたした.Myotubular myopathyを呈する患者の麻酔においては麻酔薬により筋脱力状態が遷延することに注意が必要である

The aim of this study was to investigate the effect of long-term treatment with interferon (IFN)-alpha on the noradrenaline transporter of bovine adrenal medullary cells. Treatment of cultured adrenal medullary cells with IFN-alpha caused a decrease in uptake of [H-3]noradrenaline by the cells in time (4-48 h)- and concentration (300-1,000 U/ml)-dependent manners. IFN-beta also inhibited [H-3]noradrenaline uptake to a lesser extent than did IFN-alpha, whereas IFN-gamma had little effect. An anti-IFN-alpha antibody reduced the effect of IFN-alpha on [H-3]noradrenaline uptake. Saturation analysis of [H-3]noradrenaline uptake showed that the inhibitory effect of IFN-alpha was due to a reduction in the maximal uptake velocity (V-max values without altering apparent Michaelis constant (K-m) values. Incubation of cells with IFN-alpha caused a translocation of protein kinase C from the soluble to the particulate fraction in the cells. The effect of IFN-alpha on [H-3]noradrenaline uptake was diminished in protein kinase C-down-regulated cells. Incubation of cells with IFN-alpha for 48 h significantly reduced the specific binding of [H-3]desipramine to crude plasma membranes isolated from cells. Scatchard analysis of [H-3]desipramine binding revealed that IFN-alpha decreased the maximal binding (B-max) values without any change in the dissociation constant (K-m) values. These findings suggest that IFN-alpha suppresses the function of noradrenaline transporter by reducing the density of the transporter in cell membranes through, at least in part, a protein kinase C pathway.

Molecular mechanisms of anesthetic action on neurotransmitter receptors are poorly understood. The major excitatory neurotransmitter in the central nervous system is glutamate, and recent studies found that volatile anesthetics inhibit the function of the alpha-amino-3-hydroxyisoxazolepropionic acid subtype of glutamate receptors (e.g. glutamate receptor 3 (GluR3)), but enhance kainate (GluR6) receptor function, We used this dissimilar pharmacology to identify sites of anesthetic action on the kainate GluR6 receptor by constructing chimeric GluR3/GluR6 receptors, Results with chimeric receptors implicated a transmembrane region (TM4) of GluR6 in the action of halothane. Site directed mutagenesis subsequently showed that a specific amino acid, glycine 819 in TM4, is important for enhancement of receptor function by halothane (0.2-2 mM). Mutations of Gly-819 also markedly decreased the response to isoflurane (0.2-2 mM), enflurane (0.2-2 mM), and 1-chloro-1,2,2-trifluorocyclobutane (0.2-2 mM). The nonanesthetics 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane had no effect on the functions of either wild-type GluR6 or receptors mutated at Gly-819. Ethanol and pentobarbital inhibited the function of both wild-type and mutant receptors. These results suggest that a specific amino acid, Gly-819, is critical for the action of volatile anesthetics, but not of ethanol or pentobarbital, on the GluR6 receptor.

We have recently reported inhibitory effects of carbamazepine (CBZ) on ion channel-mediated secretion of catecholamines in bovine adrenal medullary cells. Here, we report the effects of carbamazepine-10,li-epoxide (CBZ-E), an active metabolite of CBZ, and carbamazepine-10,11-diol (CBZ-D), a non-active metabolite, on Na-22(+) influx, Ca-45(2+) influx and catecholamine secretion in cultured adrenal medullary cells. CBZ-E, but not CBZ-D inhibited Na-22(+) influx. Ca-45(2+) influx and catecholamine secretion induced by carbachol or veratridine with a half-maximal inhibitory concentration (IC50) of 0.26 or 0.68 mu g/ml, respectively. CBZ-E also inhibited high K+-evoked Ca-45(2+) influx and catecholamine secretion (IC50 = 0.3 mu g/ml), but CBZ-D did not. These findings suggest that CBZ-E, but not CBZ-D, attenuates catecholamine secretion by inhibiting nicotinic acetylcholine receptor-associated ion channels: voltage-dependent Na+ channels and voltage-dependent Ca2+ channels in the cells. This inhibition of CBZ-E as well as CBZ may be related to the clinical effects in neuropsychiatric disorders.

The effects of lymphocytes and their conditioned medium on catecholamine efflux and uptake were examined in cultured bovine adrenal medullary cells. Go-culture of adrenal medullary cells with lymphocytes for 3 days caused an increase in appearance of catecholamines in the culture medium. Treatment of adrenal medullary cells with a conditioned medium prepared from lymphocytes also enhanced the appearance of catecholamines in culture medium in time- (8-48 h) and concentration-dependent manners. Heat treatment of the conditioned medium at 60 and 100 degrees C for 10 min reduced its stimulatory effect to 59 and 20% of control, respectively. After gel filtration on a Sephadex G-25 column or dialysis (<8 kDa molecular mass cutoff), the stimulatory activity of the conditioned medium was found in a high molecular fraction. The conditioned medium had little effect on the activity of lactate dehydrogenase in the medium of cultured adrenal medullary cells and on desipramine-sensitive [H-3]norepinephrine uptake by the cells. These findings suggest that lymphocytes release a heat-sensitive factor(s) (molecular mass of more than 8 kDa) which increases efflux of catecholamines from cultured adrenal medullary cells. (C) 1998 Elsevier Science Ireland Ltd.

We describe a case of an unco-operative patient with recessive dystrophic epidermolysis bullosa in whom difficult tracheal intubation was anticipated and fibreoptic bronchoscope guided tracheal intubation was successfully achieved after induction of general anaesthesia. Other problems in airway management associated with this disorder are discussed.

Previous studies have demonstrated that ethanol and volatile anesthetics inhibit the function of some metabotropic (G protein-coupled) receptors, including the 5-hydroxytryptamine(2), and muscarinic cholinergic receptors. The metabotropic glutamate receptors (mGluRs) show little sequence homology with most other metabotropic receptors and are important modulators of synaptic transmission in the mammalian central nervous system. It was of interest to determine drug actions on these receptors, and we investigated the effects of ethanol, halothane, the anesthetic compound F3 (I-chloro-l,2,2-trifluorocyclobutane), and the nonanesthetics F6 (1,2-dichlorohexafluorocyclobutane) and F8 (2,3-chlorooctafluorobutane) on the function of mGluR1 and mGluR5 expressed in Xenopus laevis oocytes. Halothane, F3, and ethanol inhibited mGluR5-induced Ca2+-dependent Cl- currents, yet pharmacologically relevant concentrations of these compounds had little effect on the glutamate-induced currents in the oocytes expressing mGluR1. F6 had inhibitory effects on both receptors, and F8 did not affect either mGluR1 or mGluR5 function. The protein kinase C (PKC) inhibitor GF109203X enhanced the glutamate-induced current, and the PKC activator phorbol-12-myristate-13-acetate inhibited this current in the oocytes expressing mGluR5, but these compounds had little effect on mGluR1 function. GF109203X abolished the inhibitory effects of halothane, F3, and ethanol on mGluR5s. Conversely, the phosphatase inhibitor calyculin A prolonged the action of halothane and ethanol. Furthermore, mutation of a PKC consensus site (Ser890) of mGluR5 abolished the inhibitory effects of halothane, F3, and ethanol. These results suggest that ethanol and volatile anesthetics inhibit mGluR5 because they promote PKC-mediated phosphorylation.

We studied the effects of C-type natriuretic peptide (CNP) on rat cultured mesangial cell proliferation. (1) Exposure to CNP (10 nM-1 mu M for 72 h) inhibited [H-3]thymidine incorporation into mesangial cells in a concentration-dependent manner. Atrial natriuretic peptide (1 nM-1 mu M), a peptide related to CNP, also decreased [3H]thymidine incorporation into these cells in a concentration-dependent manner. (2) Both CNP (10 nM-1 mu M) and atrial natriuretic peptide (10 nM-1 mu M) also decreased mesangial cell number. (3) The cyclic GMP analog, 8-bromo-cyclic GMP (100 mu M and 1 mM), mimicked the inhibitory effects of CNP and atrial natriuretic peptide on [H-3]thymidine incorporation into mesangial cells, whereas inhibitors of protein kinase C, protein kinase A, and protein kinase G reduced the effect of both natriuretic peptides. Moreover, the phoshpatase inhibitor, calyculin A, increased [H-3]thymidine incorporation into mesangial cells. (4) CNP and atrial natriuretic peptide decreased interleukin-1-, interleukin-6-, platelet derived growth factor-, angiotensin II-induced [H-3]thymidine incorporation into mesangial cells. These results suggest that CNP exerts inhibitory effects on mesangial cell proliferation and that this effects depend on protein phosphorylation pathways.

Anesthetics (and ethanol) are known to produce amnesia as well as immobilization. Recent identification of a nonimmobilizing (nonanesthetic) agent (F6 or 1,2-dichlorohexafluorocyclobutane) that impairs learning and memory suggests that distinct mechanisms may be responsible for these two actions of anesthetic agents. Muscarinic receptors are believed to play a role in memory and learning, and we asked if a specific subtype of these receptors is affected by anesthetics as well as the new nonanesthetic. We investigated the effects of halothane, a novel halogenated anesthetic compound F3 (1-chloro-1,2,2-trifluorocyclobutane) and ethanol on acetylcholine-induced current mediated by a muscarinic m(1) receptor expressed in Xenopus oocytes. We also studied the effects of halogenated nonanesthetic compounds, F6 and F8 (2,3-chlorooctafluorobutane) on muscarinic m(1) receptors. Halothane, F3, F6 and ethanol inhibited muscarinic m(1) receptor-induced Ca2+-dependent Cl- currents at pharmacologically relevant concentrations. F8 had no effect on acetylcholine-induced muscarinic m(1) receptor function. The protein kinase C inhibitor, bisindolylmaleimide I (GF109203X), enhanced the acetylcholine-induced current and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), inhibited this current. GF109203X abolished the inhibitory effects of halothane, F3 and ethanol on muscarinic m(1) receptors but had no effect on actions of F6. These results demonstrate that anesthetics and a nonanesthetic inhibit the function of muscarinic m(1) receptors and suggest activation of protein kinase C as the mechanism of action of anesthetics and ethanol on these receptors. (C) 1997 Elsevier Science B.V.

We studied the effects of ketamine and propofol on rat cultured mesangial cell (MC) proliferation. The 72-hexposure to ketamine (1-100 mu M) inhibited [H-3]thymidine incorporation into the MC in a concentration-dependent manner. Propofol, however, was not effective at inhibition of MC proliferation at doses from 1 to 100 mu M. Ketamine also decreased the cell number at clinically relevant concentrations and increased adenosine 3',5'-cyclic monophosphate (cAMP) levels in MC. We also studied the effects of ketamine on cytokine-induced [H-3]thymidine incorporation info the cells. Ketamine decreased the tumor necrosis factor-alpha (TNF-alpha)-, interleukin 1 (IL-1)-, and interleukin 6 (IL-6)- induced [H-3]thymidine incorporation into the cells. It also decreased angiotensin II (Ag II)-induced [H-3]thymidine incorporation. These results suggest that ketamine has inhibitory effects on MC proliferation, but that propofol does not. Because ketamine inhibits TNF-alpha-, IL-1-, and IL-6-induced MC proliferation, it may be useful in suppressing the cell growth clinically.

We investigated the effects of adrenomedullin on rat mesangial cell proliferation. Adrenomedullin (10(-10)-10(-7) M) inhibited both [H-3]thymidine incorporation into cultured rat mesangial cells and cell proliferation in a concentration-dependent manner. Adrenomedullin (10(-10)-10(-6) M) stimulated cyclic adenosine monophosphate accumulation in rat mesangial cells in a-concentration-dependent manner. These findings suggest that adrenomedullin inhibits proliferation of rat mesangial cells probably through a cyclic adenosine monophosphate-dependent mechanism.

To elucidate the mechanism of protamine-induced hypotension, we examined the effects of protamine on catecholamine secretion in bovine adrenal medullary cells and on the serum norepinephrine in the rat. 1) In bovine adrenal medullary cells in culture, protamine at concentrations of 10 to 100 mu g/ml inhibited catecholamine secretion stimulated by carbachol. The inhibitory effect of protamine was diminished by heparin at concentrations of 3.5 to 14 U/ml. Protamine suppressed carbachol-stimulated Na-22(+) influx and Ca-45(++) influx at a concentration similar to that which inhibited catecholamine secretion. Protamine (10-100 mu g/ml) also inhibited veratridine-induced Na-22(+) influx and Ca-45(++) influx and 56 mM K+-evoked Ca-45(++) influx. The inhibition of these ion influxes by protamine was closely correlated with that of catecholamine secretion. 2) In rats, i.v. administration of protamine (10 mg/kg) attenuated the arterial blood pressure and the serum norepinephrine. There was a high correlation (r = 0.96) between the serum norepinephrine and the arterial blood pressure in protamine-treated rats. Furthermore, pretreatment with heparin (1000 U/kg) abolished the protamine-induced decreases in arterial blood pressure and serum norepinephrine. Because protamine seems to inhibit catecholamine secretion by interfering with Na+ influx and Ca++ influx to adrenal medullary cells, the protamine-induced hypotension may be, at least in part, due to inhibition of norepinephrine release and ion channel activities of sympathetic nerve terminals in rats.

KN-62, an inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), inhibited significantly catecholamine secretion and tyrosine hydroxylase activity stimulated by acetylcholine in cultured bovine adrenal medullary cells. KN-62, however, showed an additional inhibitory effect on acetylcholine-induced Ca-45(2+) influx, which is essential for functional responses. Carbachol-stimulated Na-22(+) influx, veratridine-induced Na-22(+) influx, and 56 mM K+-evoked Ca-45(2+) influx were also attenuated by KN-62. Inhibitions by KN-62 of these ion influxes were correlated closely with those of catecholamine secretion, KN-04, which is a structural analogue of KN-62 but does not inhibit CaM kinase II activity, elicited inhibitory effects on the three kinds of stimulant-evoked ion influxes with an inhibitory potency similar to KN-62. These results suggest that KN-62 inhibits catecholamine secretion and tyrosine hydroxylase activation due to mainly its ion channel blockade on the plasma membrane rather than the inhibition of CaM kinase II activity in the cells.

In the central and peripheral noradrenergic neurons, the balance between noradrenaline release and reuptake determines the level of noradrenaline at the synaptic cleft or the nerve ending. In the present study, we examined the effects of propofol, an intravenous general anaesthetic, on catecholamine secretion and noradrenaline uptake in cultured bovine adrenal medullary cells and on the serum noradrenaline and blood pressure in rats. In cultured adrenal medullary cells, propofol (10-50 mu mol/l) concentration-dependently inhibited catecholamine secretion stimulated by carbachol. Propofol suppressed carbachol-evoked Na-22(+) influx as well as Ca-45(2+) influx at concentrations similar to those which suppressed the catecholamine secretion. Propofol (10-50 mu mol/l) also inhibited veratridine-evoked Na-22(+) influx, Ca-45(2+) influx and catecholamine secretion, whereas it had little effect on the Ca-45(2+) influx and catecholamine secretion induced by 56 mmol/l K+. Cultured adrenal medullary cells show [H-3] noradrenaline uptake which is sensitive to imipramine. Propofol (10-50 mu mol/l) significantly inhibited the imipramine-sensitive uptake of [H-3] noradrenaline. In rats, intravenous administration of propofol(2.5 mg/kg) lowered serum noradrenaline and arterial blood pressure. From these findings, in spite of inhibiting noradrenaline uptake, propofol at anaesthetic concentrations (10-30 mu mol/l) seems to reduce catecholamine secretion by interfering with Na+ influx through voltage-dependent Na+ channels as well as nicotinic acetylcholine receptor-associated ion channels in the adrenal medulla and, probably, in the sympathetic nervous system. This may explain the propofol-induced hypotension during anaesthesia.

We investigated the effects of adrenomedullin on rat mesangial cell proliferation. Adrenomedullin (10-10-10-7M) inhibited both [3H]thymidine incorporation into cultured rat mesangial cells and cell proliferation in a concentration-dependent manner. Adrenomedullin (10 -10 −10-6 M) stimulated cyclic adenosine monophosphate accumulation in rat mesangial cells in a concentration-dependent manner. These findings suggest that adrenomedullin inhibits proliferation of rat mesangial cells probably through a cyclic adenosine monophosphate-dependent mechanism. © 1996 S. Karger AG, Basel.

THE laryngeal mask airway (LMA) has been used widely for airway management during general anesthesia in the last decade.(1) There have been reports in which the LMA successfully secured the airway as an alternative and as an aid to anticipated difficult tracheal intubation in patients with ankylosing spondylosis of the cervical spine or atlantooccipital joint due to severe rheumatoid arthritis.(2-4) However, Pennant and White suggested that the use of the LMA is contraindicated in patients who are unable to extend the neck because of ankylosing spondylitis, severe rheumatoid arthritis, or cervical spine instability.(1) This controversy remains unresolved. In this report, we describe anesthesia for a patient with advanced rheumatoid arthritis in whom LMA insertion was impossible. The reason was thought to be the acute angle between the oral and the pharyngeal axes at the back of the tongue. The investigated the correlation between the angle and difficulty of LMA insertion in an attempt to resolve the controversy.

The effects of carbamazepine (CBZ) on Na-22(+) influx, Ca-45(2+) influx, catecholamine secretion and cyclic GMP production were examined in cultured bovine adrenal medullary cells. 1) CBZ (40-120 mu mol/l) inhibited Na-22(+) influx evoked by carbachol in a concentration-dependent manner. CBZ inhibited carbachol-evoked Ca-45(2+) influx and catecholamine secretion at concentrations similar to those which suppressed Na-22(+) influx. 2) CBZ (4-120 mu mol/l) inhibited veratridine-induced Na-22(+) influx, Ca-45(2+) influx and catecholamine secretion. 3) CBZ (12 or 40-120 mu mol/l) suppressed 56 mmol/l K+-evoked Ca-45(2+) influx and catecholamine secretion, respectively. 4) Combination of CBZ with nitrendipine or omega-agatoxin-IVA produced further inhibition of 56 mmol/l K+- evoked Ca-45(2+) influx and catecholamine secretion, compared to the effect of CBZ alone, whereas CBZ-plus omega-conotoxin-GVIA did not produce any further inhibition. 5) CBZ (40 mu mol/l) attenuated the production of cyclic CMP caused by muscarine. These results suggest that CBZ at therapeutic concentrations (16-48 mu mol/l: 4-12 mu g/ml) inhibits catecholamine secretion by interfering with nicotinic acetylcholine receptor-associated ion channels, voltage-dependent Na+ channels and N-type voltage-dependent Ca2+ channels, and may have an antimuscarinic effect in adrenal medullary cells.

ムコ多糖症IH型(Hurler症候群)はα-L-iduronidase欠損によりムコ多糖類の蓄積をきたし,顔面の変形,巨大化,口唇肥大,舌肥大,下顎の狭小化などを呈するまれな症候群である.この症候群は,奇形のために気道確保困難,気管内挿管困難の可能性,術後の呼吸抑制が麻酔管理上問題となる.今回,われわれはこの症候群と診断された2歳8ヵ月の女児の角膜生検に対して,自発呼吸下でフェイスマスクを使用しセボフルランによる緩徐な導入後に気管内挿管をする計画を立てて麻酔に臨んだ.気道確保や気管内挿管は問題なく,無事手術を終えた.術後の呼吸抑制もなかった.本症候群の患者の麻酔では,気道管理に特に注意する必要があると思われた.