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Acetaminophen, a para-aminohenol derivative, was first clinically used in 1893. In 1980 s, the relevance of aspirin for Reye's syndrome became a problem, then acetaminophen came into use for various kinds of cases such as children, pregnant women and the elderly for pain management or alleviation of fever. However, because acetaminophen has a very weak COX-1 and COX-2 inhibitory effect it has weak or no anti-inflam- matory effect Therefore physicians do not wish to use acetaminophen for management of pain in which in- flammation is thought to be the main mechanism. But recently acetaminophen has become reevaluated as an indication for patients with chronic pain. In 2011, the maximum daily dose of acetaminophen in Japan was increased from 1,500 ng - day-- to 4,000 mg - day-1 (international dosage). As acetaminophen has few side effects of gastrointestinal and renal systems, its use is recommended for the control of long term pain man- agement The side effects of acetaminophen and their management are discussed.

Lactobacilli and bifidobacteria are probiotic bacteria that modify host defense systems and have the ability to extend the lifespan of the nematode Caenorhabditis elegans. Here, we attempted to elucidate the mechanism by which bifidobacteria prolong the lifespan of C. elegans. When the nematode was fed Bifidobacterium infantis (BI) mixed at various ratios with the standard food bacterium Escherichia coli strain OP50 (OP), the mean lifespan of worms was extended in a dose-dependent manner. Worms fed BI displayed higher locomotion and produced more offspring than control worms. The growth curves of nematodes were similar regardless of the amount of BI mixed with OP, suggesting that BI did not induce prolongevity effects through caloric restriction. Notably, feeding worms the cell wall fraction of BI alone was sufficient to promote prolongevity. The accumulation of protein carbonyls and lipofuscin, a biochemical marker of aging, was also lower in worms fed BI; however, the worms displayed similar susceptibility to heat, hydrogen peroxide, and paraquat, an inducer of free radicals, as the control worms. As a result of BI feeding, loss-of-function mutants of daf-16, jnk-1, aak-2, tol-1, and tir-1 exhibited a longer lifespan than OP-fed control worms, but BI failed to extend the lifespan of pmk-1, skn-1, and vhp-1 mutants. As skn-1 induces phase 2 detoxification enzymes, our findings suggest that cell wall components of bifidobacteria increase the average lifespan of C. elegans via activation of skn-1, regulated by the p38 MAPK pathway, but not by general activation of the host defense system via DAF-16.

Wnt signaling pathways play fundamental roles in the differentiation, proliferation and functions of many cells as well as developmental, growth, and homeostatic processes in animals. Low-density lipoprotein receptor (LDLR)-related protein (LRP) 5 and LRP6 serve as coreceptors of Wnt proteins together with Frizzled receptors, triggering activation of canonical Wnt/beta-catenin signaling. Here, we found that LRP10, a new member of the LDLR gene family, inhibits the canonical Wnt/beta-catenin signaling pathway. The beta-catenin/T cell factor (TCF) transcriptional activity in HEK293 cells was activated by transfection with Wnt3a or LRP6, which was then inhibited by co-transfection with LRP10. Deletion of the extracellular domain of LRP10 negated its inhibitory effect. The inhibitory effect of LRP10 was consistently conserved in HEK293 cells even when GSK3beta phosphorylation was inhibited by incubation with lithium chloride and co-transfection with constitutively active S33Y-mutated beta-catenin. Nuclear beta-catenin accumulation was unaffected by LRP10. The present studies suggest that LRP10 may interfere with the formation of the beta-catenin/TCF complex and/or its binding to target DNA in the nucleus, and that the extracellular domain of LRP10 is critical for inhibition of the canonical Wnt/beta-catenin signaling pathway.

The aim of this study was to investigate whether monitoring neuromuscular block at the masseter muscle (MM) would allow faster tracheal intubation when compared with that at the adductor pollicis muscle (APM).Twenty female patients undergoing gynecological surgery were enrolled into this study. Immediately after inducing anesthesia with fentanyl and propofol, both the left masseter and ulnar nerves were stimulated in a 2 Hz train-of-four (TOF) mode using peripheral nerve stimulators. Contractions of the MM were felt with the anesthesiologist's left hand lifting the patient's jaw and holding an anesthesia facemask, while those of the APM were visually observed. Immediately after the contracting responses of the muscles were confirmed, all of the patients received an iv bolus of vecuronium 0.1 mg kg(-1). Onset times after vecuronium were defined as the duration until the contractions became impalpable at the MM or invisible at the APM. When the contraction of the MM could no longer be felt, the conditions for laryngoscopy and tracheal intubation were assessed.Onset time evaluated tactually at the MM (mean +/- SD, 108.4 +/- 27.7 s) was significantly shorter than that evaluated visually at the APM (181.2 +/- 32.1 s, P0.0001). The intubating conditions for all patients were graded as either excellent or good.Tactual evaluation of muscle paralysis of the MM during induction of anesthesia is clinically useful since it leads to faster tracheal intubation.

We report the characterization of a new member of the low-density lipoprotein receptor (LDLR) gene family designated LRP10. Human LRP10 cDNA encodes a 1905 amino acid type I membrane protein consisting of five functional domains characteristic of the LDLR gene family. CHO-ldlA7 cells transfected with human LRP10 cDNA bound LDLR-associated protein, but not β-VLDL and HDL. Human LRP10 transcripts were primarily found in the brain, muscle and heart. In situ hybridization of the rat brain showed that the transcripts were intensely present in the cerebral cortex, hippocampus, choroid plexus, ependyma and granular layer. In the developing rat brain, transcript levels gradually increased from postnatal day 1 to 20. Immunofluorescence analysis indicated that LRP10 was observed in the ventricular zone of the embryonic day 14.5 mouse cerebral cortex. The present studies suggest that LRP10 may play a significant role in the brain physiology other than lipoprotein metabolism.

Background: The aim of this study is to compare the infusion rates required to maintain a constant neuromuscular block and the reversibility of rocuronium at the corrugator supercilii muscle (CSM) and the adductor pollicis muscle (APM). Methods: We randomly allocated 30 female patients into two groups of 15 patients each to monitor neuromuscular block at either the CSM or the APM. After induction of anaesthesia and laryngeal mask insertion, contraction of the CSM to the facial nerve stimulation or that of the APM to the ulnar nerve stimulation was quantified using an acceleromyograph during 1.0–1.5% end-tidal sevoflurane anaesthesia. All the patients received a bolus of 1 mg/kg rocuronium. When the first twitch (T1) of train-of-four (TOF) recovered to 10% of the control, rocuronium infusion was commenced and maintained at T1 of 10% of the control at the CSM or APM for 120 min. Immediately after rocuronium infusion was discontinued, the time required for 0.04 mg/kg neostigmine-facilitated recovery to a TOF ratio of 0.9 was recorded. Results: Rocuronium infusion dose after a lapse of 120 min was significantly larger in the CSM than in the APM [7.1 (2.3) vs. 4.7 (2.6) μg/kg/min; P=0.001]. The time for facilitated recovery was shorter in the CSM than in the APM [11.4 (3.8) vs. 16.2 (6.0) min; P=0.016]. Conclusion: A larger rocuronium infusion dose was required to maintain a constant neuromuscular block at the CSM. Neostigmine-mediated reversal was faster at the CSM.

Because of the chronic shortage of liver donors, hepatologists are required to prolong the liver transplant waiting period by preserving the hepatic reserve of scheduled recipients. This study examined the effectiveness of oral branched-chain amino acids (BCAAs), using outcome markers indicating pretransplant hepatic reserve. Fifty-six consecutive eligible patients with Child class A cirrhosis without major complications were randomly assigned to receive oral BCAA granules (12.45 g/day) for least 1 year or no BCAAs. Differences between groups in the Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, asialoscintigraphic clearance index (CI), and complications were examined. Of 50 remaining patients, 27 received BCAAs, and 23 received no BCAAs (mean duration, 3.2 years). The mean annual changes in the MELD score, CTP score, and asialoscintigraphic CI were smaller in the BCAA group than in the control group (-0.06 +/- 0.23 versus 0.10 +/- 0.40, P = 0.024, 0.06 +/- 0.30 versus 0.30 +/- 0.48, P = 0.037, and 0.00 +/- 0.02 versus 0.02 +/- 0.04, P = 0.040, respectively). The mean annual changes in the serum total bilirubin and the serum albumin in the BCAA group were better preserved than those in the control group (-0.07 +/- 0.20 versus 0.12 +/- 0.18 mg/dL, P < 0.001, and 0.07 +/- 0.13 versus -0.02 +/- 0.19 g/dL, P = 0.005, respectively); other laboratory variables were not significant. The incidence of overall major cirrhotic complications was lower in the BCAA group than in the control group [14.8% (4 of 27 patients) versus 30.4% (7 of 23 patients) at 3 years, P = 0.043]; only ascites was significant individually. In conclusion, early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in cirrhosis.

The mammalian cellular retinoic acid-binding proteins, CRABP-I and CRABP-II, bind retinoic acid which acts as an inducer of differentiation in several biological systems. To investigate a possible role for CRABP-II in bovine adipogenesis, we have cloned bovine CRABP-II cDNA and the coding region for CRABP-I. The predicted amino acid sequences of CRABP-II were highly conserved among several animal species (human, mouse, and rat at 97%, 93%, and 93%, respectively). The expression pattern of bovine CRABP-II was examined in greater details by applying RT-PCR to various bovine tissues. CRABP-II mRNA was expressed in most adipose-containing tissues. Moreover, the expression of CRABP-I and -II mRNA dramatically increased during the differentiation of adipocytes from bovine intramuscular fibroblast-like cells. The effects of retinoic acid on adipocyte differentiation of bovine intramuscular fibroblast-like cells were concentration-dependent. Retinoic acid activated the formation of lipid droplets at a level of 1 nM, whereas inhibition was observed at a level of 1 μM. CRABP-I gene was up-regulated and CRABP-II gene down-regulated by retinoic acid during adipocyte differentiation. These results suggest that CRABPs may play an important role in the regulation of intracellular retinoic acid concentrations during adipogenesis.

The aim of this study was to examine the efficacy of epidurally administered mepivacaine on recovery from vecuronium-induced neuromuscular block.Eighty patients were randomly assigned to one of two study groups. They were either given epidurally a bolus of 0.15 ml kg(-1) of mepivacaine 2%, followed by repetitive injections of 0.1 ml kg(-1) h(-1) throughout the study, or were not given epidurally. General anaesthesia was induced and maintained with fentanyl, propofol and nitrous oxide. Neuromuscular block was induced with vecuronium 0.1 mg kg(-1) and monitored using acceleromyographic train-of-four (TOF) at the adductor pollicis. Patients in each treatment group were randomized to receive neostigmine 0.04 mg kg(-1) at 25% recovery of the first twitch of TOF or to recover spontaneously to a TOF ratio of 0.9. The effect of epidural mepivacaine on speed of spontaneous and facilitated recovery of neuromuscular function was evaluated.The time from administration of vecuronium to spontaneous recovery to a TOF ratio of 0.9 was significantly longer in the epidural mepivacaine group [105.4 (14.2) min] as compared with the control group [78.5 (9.1) min, P0.01]. Neostigmine administered at 25% of control in T1 shortened recovery from neuromuscular block, however the time required for facilitated recovery to a TOF ratio of 0.9 in the epidural group was significantly longer than that in the control group [7.6 (1.6) min vs 5.8 (2.1) min, P0.01].In clinical anaesthesia, it should be recognized that epidurally administered mepivacaine delays considerably the TOF recovery from neuromuscular block.

Background This study was designed to recognize the importance of normalizing postoperative acceleromyographic train-of-four (TOF) ratio by the baseline TOF value obtained before neuromuscular block for ensuring adequate recovery of neuromuscular function. Methods In 120 patients, TOF responses of the adductor pollicis to the ulnar nerve stimulation were monitored by acceleromyography (AMG) during anaesthesia using propofol, fentanyl and nitrous oxide. Control TOF stimuli were administered for 30 min. A TOF ratio measured at the end of control stimulation was regarded as a baseline value. Neuromuscular block was induced with vecuronium 0.1 mg kg−1 and was allowed to recover spontaneously. Duration to a TOF ratio of 0.9 as calculated by AMG (DUR-raw 0.9) was compared with that of 0.9 as corrected by the baseline TOF ratio (i.e. 0.9×baseline TOF ratio; DUR-real 0.9). Results Baseline TOF ratios ranged from 0.95 to 1.47. The average TOF ratios observed every 5 min were constant throughout control stimulation from at time zero mean (SD) [range]; 1.11 (0.09) [0.94–1.42] to at 30 min 1.13 (0.11) [0.95–1.47]. The DUR-real 0.9 was 91.0 (18.0) [51.3–131.0] min and was significantly longer than the DUR-raw 0.9 (81.2 (16.3) [41.3–123.0] min). Conclusions Baseline TOF ratios measured by AMG are usually more than 1.0 and vary widely among patients. Therefore a TOF ratio of 0.9 displayed postoperatively on AMG does not always represent adequate recovery of neuromuscular function and should be normalized by baseline value to reliably detect residual paralysis.

A S b ORONARY ARTERY FISTULA (CAF) is an infrequent vascular anomaly that establishes a direct link between a arge subepicardial coronary artery and a cardiac chamber, ajor vessels, or other vascular structures. Although coronary rteriography remains the gold standard for the diagnosis of AF, it is not always possible to reveal the complete delineaion of CAF including its origin, course, and drainage. A case f left main CAF originating directly from the aorta is reported n which preoperative coronary arteriography failed to identify he site of drainage and intraoperative transesophageal echoardiography (TEE) was used to identify the precise location of rainage. Scheduled surgical repairs included closure of the rigin of the CAF (the left main coronary orifice from the aorta) nd closure of the drainage of the CAF combined with coronary rtery bypass graft (CABG) surgery to the left anterior decending artery and the circumflex artery. In this particular ase, the left anterior descending artery and the circumflex rtery were not scheduled for closure at their origins from the eft main CAF to keep the circulation available for the other eeding arteries to the left ventricle (LV) that might originate rom the CAF. Therefore, intraoperative TEE was also essential or confirmation of absence of fistulous flow and regional wall otion abnormalities of the LV.

川崎病治療中に巨大咽後膿瘍を発症し, 全身麻酔下に緊急排膿術を施行した1歳5ヵ月の小児症例を経験した. 川崎病における頸部リンパ節腫脹と咽後膿瘍は鑑別が難しく, 切開・排膿により初めて診断がつくこともまれではない. 本症例では, 膿瘍の大きさから挿管困難を予想し, 術前より意識下挿管を行った. また, 抜管後に膿を誤嚥しないよう, トレンデレンブルグ体位かつ側臥位で抜管した. 小児の挿管困難に対し, 緊急手術というかぎられた情報のなかで適切な麻酔管理, 術後管理の重要性を示した症例であった.

Cytoglobin/stellate cell activation-associated protein (Cygb/STAP) consists of a new class of hexacoordinate globin superfamily, which was recently discovered by a proteome analysis on the rat hepatic stellate cells. Unlike haemoglobin, myoglobin, and neuroglobin, Cygb/STAP is ubiquitously expressed in several organs, although its detailed localization has not been clarified. Immunohistochemistry and immunoelectron microscopy revealed that Cygb/STAP is uniquely localized in fibroblast-like cells in splanchnic organs, namely the vitamin A-storing cell lineage, but neither in epithelial cells, endothelial cells, muscle cells, blood cells, macrophages, nor dermal fibroblasts. The expression of Cygb/STAP was upregulated in fibrotic lesions of the pancreas and kidney in which activated fibroblast-like cells or myofibroblasts are known to increase in number. In cultured hepatic stellate cells, Cygb/STAP expression was augmented by the stimulation with sera, platelet-derived growth factor-BB, and transforming growth factor-beta 1. Overexpression of Cygb/STAP in NIH 3T3 cells induced the cells to lessen migratory activities and increase the expression of collagen alpha1(I) mRNA. These results indicate that Cygb/STAP is a tissue globin uniquely localized in splanchnic fibroblastic cell lineage and may play a role in fibrotic organ disorder.

Calcium-bound phosphoryl oligosaccharides (POs-Ca) were prepared from potato starch. Their solubility and in situ absorbability as a calcium source were investigated by comparing with the soluble calcium compounds, calcium chloride and calcium lactate, or insoluble calcium compounds, calcium carbonate and dibasic calcium phosphate. The solubility of POs-Ca was as high as that of calcium chloride and about 3-fold higher than that of calcium lactate. An in situ experiment showed that the intestinal calcium absorption rate of POs-Ca was almost comparable with that of the soluble calcium compounds, and was significantly higher (p

ベクロニウムによる筋弛緩からの自然回復時,顔面神経刺激により誘発される眼輪筋収縮反応と,尺骨神経刺激による母指内転筋収縮反応において,視覚的に四連反応時の減衰が識別不能になる際の四連反応比の差について検討した.減衰が確認できなくなった時点における四連反応比計測値は眼輪筋で有意に小さく(眼輪筋:0.47,母指内転筋:0.51, ),眼輪筋では母指内転筋に比し判別感度が劣る可能性が示唆された.つまり視覚的には筋弛緩効果の残存を母指内転筋同様,眼輪筋でも十分に評価できない.

The aim of the present study was to clarify the neurophysiological changes associated with analgesic and behavioral effects of low-dose ketamine HCl in patients suffering from chronic neuropathic pain. Ten in-patients with neuropathic pain participated in this single-blind, placebo-controlled study after giving written informed consent. Following intravenous injections of a saline solution (placebo), three bolus injections of 5 mg ketamine HCl were administered at 5 min intervals. Changes in pain perception were assessed using a numerical rating scale for pain. Behavioral changes, including psychotomimetic effects, were assessed using the Brief Psychiatric Rating Scale (BPRS). Electroencephalograms (EEG) and electrooculograms (EOG) were recorded continuously throughout the testing period. One minute EEG and closed-eye eye movements were quantified. The effects of ketamine were evaluated by comparing the neurophysiological and behavioral parameters obtained from the placebo and ketamine trials. Pain reduction was significantly correlated with ketamine-induced changes in hallucinatory behavior and excitement as measured by the BPRS. Ketamine injections caused a significant decrease in the EEGα amplitude without an accompanying reduction in EEG frequency. The EEGα amplitude reduction at the right central electrode was significantly related to subjective pain relief. Subanesthetic doses of ketamine significantly decreased rapid eye movements, but did not initiate slow eye movements. In conclusion, the present EEG-EOG/behavioral results indicate that ketamine-induced failure of neural integration between cortical–subcortical regions induces psychotic symptoms and alters pain perception on neuropathic pain.

The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid pool with cholestyramine enhanced CYP7A1 and CYP8B1 expression. We conclude that input from three negative regulatory pathways controls bile acid synthesis. One is mediated by SHP, and two are SHP independent and invoked by liver damage and changes in bile acid pool size.

The present study was undertaken to evaluate the Bioavailability of calcium-bound phosphoryl oligosaccharides (POs-Ca). POs-Ca was not hydrolyzed by artificial gastric acid. The gradual decrease of POs-Ca injected into the rat ligated jejunum loop was observed, suggesting that POs-Ca was hydrolyzed and absorbed in the small intestine. The overall rate of plasma glucose response after oral administration of POs-Ca to rats was similar to the case of administration of control saccharides, glucose and high-maltotetoraose syrup (TETRUP(R)-H). However, the glucose concentration of POs-Ca group at 0.25 h after administration was significantly lower than those of other groups. In the case of POs-Ca administration, plasma Ca concentration showed slight but significant increase during 0.25-0.5 h concurrent with the increase of plasma glucose . On the other hand, plasma P concentration decreased and then increased gradually from 2 h after the administration. Body weight gain, food intake and food efficiency of rats fed the diet containing 10% POs-Ca for 15 days were not different from those of rats fed control diet, and no diarrhea was observed in the POs-Ca group. The serum TG concentration of POs-Ca group was significantly lower than that of the control group. Other serum biochemical indices and organ (liver and cecum) weight were not significantly different among groups. From these results, it was assumed that the POs-Ca orally administered would be hydrolyzed into glucose, Ca, and P and then absorbed completely in the small intestine, therefore not causing acute diarrhea.

Apolipoprotein E (apoE) polymorphism is associated with onset of Alzheimer's disease (AD). We found seven polymorphisms in apoE receptor 2 (ApoER2), an apoE-binding receptor, in Japanese sporadic AD patients, but no association of ApoER2 polymorphisms with AD. We consider that the functions of ApoER2 in the brain may be compensated for by those of other apoE-binding receptors such as VLDL receptor.

We compared the effects of various types of beverages (teas, coffee, and cocoa) on D-galactosamine-induced liver injury by measuring plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in 7-wk-old male Wistar rats. The effects of five fractions extracted with different organic solvents from green tea, different types of dietary fibers, and some short chain fatty acids were also investigated. All of the beverages tested significantly suppressed D-galactosamine-induced enhancement of plasma enzyme activities when powdered beverages were added to the diet (30 g/kg) and fed to rats for 2 wk. Plasma ALT activities were 1155 +/- 82 [micromol/(min.L), control], 289 +/- 61 (green tea), 626 +/- 60 (roasted green tea), 471 +/- 84 (puerh tea), 676 +/- 69 (oolon tea), 423 +/- 76 (black tea), 829 +/- 53 (coffee), and 885 +/- 89 (cocoa). The profile of AST activities was similar. The caffeine-containing fraction from green tea had no significant effect, whereas the other four fractions, including the soluble fiber fraction, significantly suppressed liver injury. In addition to tea fibers, many other types of dietary fiber (hemicellulose, chitin, chitosan, alginate, pectin, guar gum, glucomannan, and inulin, but not cellulose) had liver injury-preventive effects when added to the diet (30 g/kg), suggesting that liver injury-prevention may be one of the general effects of dietary fibers. Of three short-chain fatty acids tested (acetate, propionate, and butyrate), only acetate prevented liver injury when added to the diet (15 g/kg), supporting the possibility that the liver injury-preventive effect of dietary fibers may be mediated at least in part by certain organic acids. These results suggest that several beverages possess preventive effects on certain types of liver injury, such as that induced by D-galactosamine, and that different constituents of high and low molecular weights contribute to the liver injury-preventive effects of green tea.

This study describes the in vitro digestibility and fermentability of high molecular weight (ca. 2,000,000) levan and its effect on the metabolism of lipids in growing rats fed cholesterol-free diets. Levan was synthesized from sucrose using bacterial levansucrase immobilized on a honeycomb-shaped ceramic support. Although body weight gain, weight of visceral organs, morphologic changes in the digestive tract, and the serum triacylglycerol and glucose concentrations were not affected by feeding levan diets for 4 weeks, a significant hypocholesterolemic effect was observed. Serum cholesterol level was decreased to 83% or 59% by feeding a 1% or 5% levan diet, respectively. The hypocholesterolemic effect was accompanied by a significant increase in fecal excretion of sterols and lipids. High molecular weight levan, though not hydrolyzed by the salivary amylases, was hydrolyzed by artificial gastric juice and was changed to a low molecular weight (ca. 4,000) levan with a small amount of fructose, but did not produce any fructooligosaccharides. Low molecular weight (ca. 6,000) levan was not hydrolyzed by either pancreatic juice or small intestinal enzymes. This suggests that, in vivo, low molecular weight levan derived from the high molecular weight material is not further digested and reaches the colon intact. The fermentation of low molecular weight levan (ca. 6,000) by several strains of bifidobacteria was not observed. These results showed that the hypocholesterolemic effect of levan may result from the prevention of intestinal sterol absorption, and not from the action of the fermentation products of levan.

The apolipoprotein E receptor 2 (apoER2) gene consists of a mosaic of exons, which may have been assembled by "exon shuffling." Analysis of apoER2 transcripts in several species reveals a lost repeat in the ligand-binding domain of primate apoER2. A pseudo-exon found in the primate apoER2 genes corresponds to the lost repeat but contains a crucial deletion that leads to a translational frameshift. The pseudo-exon sequence in primary transcripts of the human apoER2 gene is shown to be abolished by exon skipping due to two nucleotide substitutions at the 5'-splice donor adjacent to the pseudo-exon. These data suggest the occurrence of exon loss in the evolution of the primate apoER2 gene.

本研究により以下のことが明らかになった。1) DOFの同時投与により, Fe欠乏食の摂取によるHb濃度の低下が抑えられた。2) DOFの長期投与により十二指腸のFe吸収能力が高まることはなかった。3) in situ で十二指腸ループを用いたFe吸収試験においてはDOFがループ内でFeと共存するときにのみFe吸収が促進されることがわかった。

The dose-dependent effects of dietary eritadenine on the metabolism of linoleic acid and on the plasma cholesterol concentration were investigated to clarify the mechanism of the hypocholesterolemic action of eritadenine in rats. Rats were fed control or eritadenine-supplemented (2 to 20 mg/kg) diets for 14 d. Eritadenine supplementation significantly decreased both the plasma cholesterol concentration and the 20:4n-6/18:2n-6 ratio of liver microsomal and plasma phosphatidylcholine (PC) in a dose-dependent manner. Eritadenine was also found to decrease the activity of delta 6 desaturase in liver microsomes; there was significant correlation between the delta 6-desaturase activity and the 20:4n-6/18:2n-6 ratio in the PC of liver microsomes (r = 0.989, P < 0.001) or plasma (r = 0.986, P < 0.001). Certain plasma PC molecular species, as represented by 16:0-18.2, were increased by eritadenine in a dose-dependent manner, and certain plasma PC molecular species, as represented by 18:0-20:4, were conversely decreased by eritadenine. There was a significant correlation between the plasma total cholesterol concentration and the proportion of the sum of plasma PC molecular species which contain 18:1 or 18:2 in the sn-2 position. These results support the idea that the suppression of linoleic acid metabolism by eritadenine might be associated with the hypocholesterolemic action of eritadenine.

The effects of dietary protein types and methionine supplementation on phospholipid metabolism were investigated to clarify the mechanism of the hypocholesterolemic action of soybean protein in rats fed a cholesterol-free diet. The effect of switching from a casein diet to a soybean protein diet was also investigated. Rats were fed casein, soybean protein or soybean protein + methionine diet for 14 d. Compared with casein diet, feeding of soybean protein diet led to significantly higher proportions of linoleic acid and linoleic acid-containing molecular species, especially 16:0-18:2, in plasma and liver microsomal phosphatidylcholine (PC). In addition, significantly lower plasma cholesterol concentration, hepatic S-adenosylmethionine concentration and liver microsomal PC:phosphatidylethanolamine ratio resulted. These alterations caused by the soybean protein diet were significantly suppressed by supplementing methionine to the level of the casein diet (3.4 g/kg diet). The proportion of the sum of certain plasma PC molecular species, which contain 18:1 or 18:2 in the sn-2 position, increased in response to the switch from the casein diet to the soybean protein diet at a rate similar to the decrease in plasma cholesterol concentration; there was a significant correlation between the two variables (r = -0.992, P < 0.001). These results indicate that about 40% of the hypocholesterolemic action of soybean protein is due to the low methionine content of the protein and might be associated with alterations of the plasma phospholipid molecular species profile.

The effect of dietary eritadenine on plasma phosphatidylcholine (PC) molecular species composition was investigated in relation to its hypocholesterolemic action in rats fed different types of fats (olive oil, corn oil and linseed oil; 100 g/kg diet). Eritadenine supplementation (50 mg/kg diet) significantly decreased the plasma total cholesterol concentration, irrespective of dietary fat sources, and without change in the order of plasma cholesterol concentration among the fat groups (corn oil > olive oil > linseed oil). Eritadenine significantly decreased the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver microsomes of all the fat groups, while the PC:PE ratio was unaffected by dietary fat type. The fatty acid and molecular species composition of plasma PC was affected either directly or indirectly by the fatty acid composition of dietary fats. The proportion of linoleic acid and linoleic acid-containing molecular species (16:0-18:2 and 18:0-18:2) in plasma PC was the highest in rats fed linseed oil, despite the fact that linoleic acid concentration of linseed oil was only 1/3 that of corn oil. Eritadenine supplementation significantly increased the proportion of linoleic acid and linoleic acid-containing molecular species, especially 16:0-18:2, in plasma PC, irrespective of dietary fat source. Altered plasma PC molecular species composition, as represented by an increase in 16:0-18:2 PC, might contribute to the hypocholesterolemic action of eritadenine.

本研究により以下のことが明らかになった。1) DWB, DOFおよびPSFは二価鉄の利用性を促進した。PSFはその発泡度が高いほど大きく二価鉄の利用性を促進した。2) DWB, DOFおよびPSFは三価鉄の利用性には大きな影響を与えなかった。3) DOFおよびPSFの二価鉄利用性促進はFe吸収の促進によるものと推測された。

Isolation and characterization of a human cDNA demonstrated a novel lipoprotein receptor designated apolipoprotein E receptor 2 (apoER2). The new receptor consists of five functional domains resembling the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) receptors. LDL receptor deficient Chinese hamster ovary cells expressing human apoER2 bound apoE rich beta-migrating VLDL with high affinity and internalized. LDL was bound with much lower affinity to these cells. The 4.5- and 8.5-kb mRNAs for the receptor were most highly expressed in human brain and placenta. In rabbit tissues, multiple species of the mRNA with 4, 4.5, 5.5, 8.5, and 11 kb were detected most intensely in brain and testis and, to a much lesser extent, in ovary, but were undetectable in other tissues. In rat adrenal pheochromocytoma PC12 cells, the receptor mRNA was induced by treatment of the cells with nerve growth factor. The receptor transcripts were detectable most intensely in the cerebellar cortex, choroid plexus, ependyma, hippocampus, olfactory bulb and, to a much lesser extent, in the cerebral cortex as revealed by in situ hybridization histochemistry. In the cerebellar cortex, the receptor transcripts were densely deposited in Purkinje cell somata.

By screening a cDNA library constructed from aortic total RNA derived from Watanabe heritable hyperlipidemic (WHHL) rabbits by differential hybridization, we have obtained a cDNA encoding the kappa light chain of immunoglobulin. Northern blot analysis of total RNA prepared from aortas of WHHL and normal rabbits of various ages revealed that this light-chain mRNA accumulates gradually with age in aortas in WHHL rabbits. Northern blotting and in situ hybridization with an antisense oligonucleotide specific to rabbit immunoglobulin gamma heavy-chain mRNA also detected accumulation of this heavy-chain mRNA in advanced lesions of WHHL rabbit aortas. Moreover, immunohistochemical and electron microscopic analyses demonstrated the presence of plasma cells in the atherosclerotic lesions.

The type, characteristics and effect of low reactive laser equipment used for pain treatment in Japan are described in this section. Currently, low reactive laser therapy equipments marketed and used in Japan include diode laser therapeutic device with semiconductor as a medium consisting of aluminum, gallium and arsenic. Low reactive laser equipment comes in three models, the first type has a capacity of generating 1,000 mW output, and the second type has a capacity of generating 10 W output. The third type has four channels of output, 60, 100, 140 and 180 mW and we can select one channel out of the four channels. This model is also used as a portable device because of its light weight, and we can carry it to wards and to the outside of the hospital. Semiconductor laser has the capacity of deepest penetration and the effect tends to increase proportionally to the increasing output. Low reactive laser therapy is less invasive and lower incidence of complications. Although low reactive laser therapy might be effective for various pain disorders, the effect is different depending on the type of pain. We should keep in mind that this therapy will not give good pain relief equally in all patients with pain.

The main aim of this study was to compare the onset times of rocuronium evaluated subjectively and by acceleromyography at the masseter muscle (MM). Forty female patients were sequentially enrolled in this study. In the first 20 patients, neuromuscular block was evaluated subjectively. After induction of anesthesia with fentanyl and propofol, both the left masseter and ulnar nerves were stimulated in 2-Hz train-of-four (TOF) mode using peripheral nerve stimulators. Contractions of the MM were felt with an anesthesiologist’s left hand holding an anesthesia facemask; those of the adductor pollicis (APM) were visually observed. All the patients received a bolus of rocuronium, 0.6 mg/kg. Onset times after rocuronium were defined as the duration until the contractions became impalpable at the MM or invisible at the APM. At the time contraction of the MM had not been felt, intubating conditions were assessed. In the next 20 patients, contractions of the MM and the APM were concurrently quantified using acceleromyography after induction of anesthesia and laryngeal mask insertion. Following 0.6 mg/kg rocuronium, onset of the action was recorded. Onset of the action of rocuronium at the MM evaluated subjectively [mean (SD), 70.3 (17.7) s] was similar to that monitored acceleromyographically [73.3 (27.6) s, P > 0.05], and significantly shorter than that at the APM acceleromyographically [111.0 (34.8) s, P = 0.016]. Intubating conditions of 20 patients were graded either excellent or good. Subjective evaluation of contractions of the MM by an anesthesiologist’s hand may be reliable to determine faster timing for safe tracheal intubation.

The aim of this study was to examine optimum intubating dose of rocuronium in adult patients who had been scheduled for short duration surgery.Thirty patients were randomly assigned to receive rocuronium 0.4 mg x kg(-1), 0.5 mg x kg(-1) or 0.6 mg x kg(-1) during induction with propofol and fentanyl. Immediately after the adduction of thumb to the ulnar nerve stimulation could not be visually observed, the patients were intubated tracheally and the intubating conditions were evaluated. Thereafter, time to recover to train-of-four (TOF) counts of 4 was recorded during sevoflurane and nitrous oxide anesthesia.Intubating conditions after rocuronium 0.5 and 0.6 mg x kg(-1) were all graded either excellent or good. In contrast, inadequate conditions for safe and easy tracheal intubation were observed in 60% of the patients receiving 0.4 mg x kg(-1). Time to spontaneous recover to the TOF counts of 4 correlated with the intubating doses of rocuronium.For short duration surgeries, rocuronium 0.5 mg x kg(-1) was appropriate to perform safe tracheal intubation and minimize duration of action of rocuronium.

The purpose of this study was to quantify the relationship between the dose-response curve of vecuronium and duration of exposure to an end-tidal concentration of 1.7% sevoflurane in 67% nitrous oxide and oxygen. Forty adult patients, in groups of 10, were allocated randomly to receive vecuronium by a cumulative dose method at intervals of 15 min (group 15), 30 min (group 30), 60 min (group 60) or 90 min (group 90) after starting inhalation of sevoflurane. Neuromuscular function was monitored by acceleromyographic train-of-four (TOF) responses of the adductor pollicis muscle to ulnar nerve stimulation. Dose-response curves were constructed by least-squares regression analysis and the effective doses of vecuronium (ED50, ED90 and ED95) were estimated and compared between groups. Mean (SEM) ED50, ED90 and ED95 were 16.8 (0.5), 32.6 (1.7) and 40.9 (2.4) micrograms kg-1, respectively, in group 15; 10.6 (1.0), 20.8 (1.7) and 26.2 (2.2) micrograms kg-1, respectively, in group 30; 11.2 (1.1), 21.7 (1.6) and 27.3 (1.8) micrograms kg-1, respectively, in group 60; and 11.0 (1.1), 21.7 (1.6) and 27.5 (1.9) micrograms kg-1, respectively, in group 90. The values obtained in group 15 were significantly higher than those in the other three groups (P < 0.05). The results indicate that the duration of sevoflurane anaesthesia influences the dose-response of vecuronium and 30 min inhalation of 1.7% end-tidal concentration is sufficient to achieve a stable potentiating effect.

The main purpose of this study was to examine the effectiveness of the timing principle with 1 mg kg(-1) rocuronium for rapid sequence intubation. As secondary outcomes, propofol and lidocaine with or without remifentanil were examined to note their effects on the cardiovascular responses to laryngoscopy and intubation.Thirty patients were randomly allocated to one of two groups of 15 patients each: a lidocaine-treated group (L) and a lidocaine/remifentanil-treated group (LR). Thirty seconds after lidocaine 1 mg kg(-1) with or without infusion of remifentanil 1 microg kg(-1) min(-1), all patients received a bolus of rocuronium 1 mg kg(-1). Shortly afterwards, patients were given propofol 2-2.5 mg kg(-1). Intubating conditions and cardiovascular responses were observed 60 s after rocuronium. The time to spontaneous recovery of visible train-of-four (TOF) counts of 4 was observed at the thumb during 1.0-1.5% end-tidal sevoflurane and remifentanil anesthesia.All patients had excellent or good intubating conditions. Hypertension and tachycardia during laryngoscopy were well prevented in group LR, whereas they were significantly observed in group L. The times to reappearance of TOF counts of 4 were comparable in all groups [mean (SD); 63.6 (8.6) min in group L and 63.5 (11.6) min in group LR].Application of the timing principle with 1 mg kg(-1) rocuronium is beneficial for rapid tracheal intubation. Co-administered lidocaine, remifentanil and propofol can definitely suppress cardiovascular responses during laryngoscopy and intubation.

Because of the chronic shortage of liver donors, hepatologists are required to prolong the liver transplant waiting period by preserving the hepatic reserve of scheduled recipients. This study examined the effectiveness of oral branched-chain amino acids (BCAAs), using outcome markers indicating pretransplant hepatic reserve. Fifty-six consecutive eligible patients with Child class A cirrhosis without major complications were randomly assigned to receive oral BCAA granules (12.45 g/day) for least 1 year or no BCAAs. Differences between groups in the Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, asialoscintigraphic clearance index (CI), and complications were examined. Of 50 remaining patients, 27 received BCAAs, and 23 received no BCAAs (mean duration, 3.2 years). The mean annual changes in the MELD score, CTP score, and asialoscintigraphic CI were smaller in the BCAA group than in the control group (-0.06 +/- 0.23 versus 0.10 +/- 0.40, P = 0.024, 0.06 +/- 0.30 versus 0.30 +/- 0.48, P = 0.037, and 0.00 +/- 0.02 versus 0.02 +/- 0.04, P = 0.040, respectively). The mean annual changes in the serum total bilirubin and the serum albumin in the BCAA group were better preserved than those in the control group (-0.07 +/- 0.20 versus 0.12 +/- 0.18 mg/dL, P0.001, and 0.07 +/- 0.13 versus -0.02 +/- 0.19 g/dL, P = 0.005, respectively); other laboratory variables were not significant. The incidence of overall major cirrhotic complications was lower in the BCAA group than in the control group [14.8% (4 of 27 patients) versus 30.4% (7 of 23 patients) at 3 years, P = 0.043]; only ascites was significant individually. In conclusion, early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in cirrhosis.

Crisis management during regional anesthesia including peripheral nerve block, epidural anesthesia and spinal anesthesia was reviewed. Common crisis which is encountered during regional anesthesia includes toxic reaction to local anesthetic drugs, allergic reaction induced by local anesthetic drugs, reaction induced by epinephrine, nerve injury, hematoma etc. Concerning peripheral nerve block, crisis encountered during brachial plexus block, interscalene block and supraclavicular block used for surgical operation of upper extremity was discussed. On the other hands, there are various common crises encountered during epidural anesthesia and spinal anesthesia. These crises include hypotension, bradycardia, total spinal anesthesia, postspinal headache and infection, and hematoma in the spinal canal. Especially, epidural hematoma and epidural abcess have possibility to cause nerve defect symptoms such as motor paralysis and sensory disturbance if appropriate treatment was not started in early stage. Moreover crisis such as cauda equina syndrome and anterior spinal cord syndrome have possibility to remain permanent and hard to cure. We anesthesiologists should make efforts to prevent crisis, to detect crisis in early stage, and to treat it in early stage.

Fade of the muscle contraction evoked by indirect tetanic nerve stimulation shows residual neuromuscular block. Anticholinesterases can reverse the partial block; however, they may also inhibit normal neuromuscular transmission and can cause fading responses by misuse of these drugs. The aim of this study is to investigate how neostigmine acts on normal neuromuscular function.In cats, we observed a series of 8 consecutive muscular compound action potentials (mCAPs; M1-8) of the gastrocnemius muscle evoked by repetitive sciatic nerve stimulation at 100 Hz and calculated the M8/M1 amplitude ratio as an index of fading phenomenon. Neostigmine 0.05 mg x kg(-1) repetitively every 5 minutes before neuromuscular blocking agent had been administered, or after the complete recovery from vecuronium-induced block had been obtained.Neostigmine caused dose-dependent fade in the mCAPs. The mean doses (SD) of neostigmine for depressing M8/M1 ratio to 50% of baseline were 0.087 (0.029) mg x kg(-1) before use of neuromuscular blocking agent and 0.161 (0.070) mg x kg(-1) after the recovery from neuromuscular block. The fading responses induced by neostigmine were paradoxically reversed by small doses of vecuronium.Therapeutic doses of neostigmine administered during normal neuromuscular function cause fade of the repetitive muscle contractions. Neuromuscular monitoring should be used before the reversal with neostigmine.

This study was conducted to identify genes expressed during adipocyte differentiation of bovine intramuscular fibroblast-like cells using differential display reverse-transcriptase polymerase chain reaction. The presenilin enhancer-2 (PSENEN) gene was found to be down-regulated during adipocyte differentiation of bovine intramuscular fibroblast-like cells. The ectopic expression of bovine PSENEN in 3T3-L1 reduced adipogenesis and the inhibition of endogenous PSENEN by siRNA induced adipogenesis on d 4 of adipocyte differentiation of 3T3-L1 cells. Interestingly, the expression of gamma-secretase complex gene-related Notch signaling was decreased at d 2 and d 4 during adipocyte differentiation. In addition, expression of the Notch-signaling genes (Notch-1, Hes-1, Pref-1, adipsin) was regulated during adipocyte differentiation by regulation of PSENEN expression. These results suggest that PSENEN plays an important role in adipocyte differentiation and that Notch signaling is involved in adipogenesis.

The aim of this study was to examine the effect of landiolol hydrochloride, an ultrashort-acting beta(1)-blocker, on suxamethonium-induced neuromuscular block.Thirty patients were randomly allocated to receive a loading dose of landiolol, 0.125 mg x kg(-1) x min(-1) for 1 min, followed by an infusion at 0.04 mg x kg(-1) x min(-1), or placebo. Twenty minutes after the infusion of landiolol or placebo, suxamethonium 1 mg x kg(-1) was administered during propofolfentanyl-nitrous oxide anesthesia. Neuromuscular block was monitored by train-of-four (TOF) responses of the adductor pollicis muscle, applying acceleromyographic stimuli to the ulnar nerve.The onset of neuromuscular block did not differ between the groups. The time from administration of suxamethonium to spontaneous recovery to the first twitch of TOF (T1) of control was significantly longer in the landiolol group (mean [SD]; 12.2 [2.5] min), when compared with the control group (9.8 [2.6] min). However, the TOF ratios measured when the T1 had spontaneously recovered to 10%, 25%, 50%, 75%, 90%, and 100% of control was comparable between the groups.Landiolol delayed recovery from suxamethonium-induced paralysis. However, the interaction between the drugs seemed to be small in the clinical setting.

BACKGROUND: Although intrathecal midazolam has been reported to produce antinociceptive effects mediated by -aminobutyric acid type A-benzodiazepine receptor complexes in the spinal cord, the effects of systemic midazolam on nociception remain unclear. We performed this study to examine the effects of IV-administered midazolam on somatosympathetic A and C reflex discharges in brain-intact cats and decerebrate cats (with transection at midbrain level). METHODS: Somatosympathetic A and C reflexes were elicited in the inferior cardiac sympathetic nerve by electrical stimulation of myelinated (A) and unmyelinated (C) afferent fibers of the superficial peroneal nerve in 28 mature cats. After control somatosympathetic reflex responses were obtained, midazolam was administered IV to four groups of randomly allocated cats as follows: brain-intact cats at a dose of 0.03 mg/kg, brain-intact cats at a dose of 0.1 mg/kg, brain-intact cats at a dose of 0.5 mg/kg, and decerebrate cats at a dose of 0.1 mg/kg. RESULTS: C reflex discharges were significantly augmented at the dose of 0.03 mg/kg and significantly depressed at the dose of 0.1 and 0.5 mg/kg in brain-intact cats. C reflex discharges were also significantly depressed at the dose of 0.1 mg/kg in decerebrate cats. CONCLUSIONS: We have demonstrated that IV midazolam produces dose-related effects on somatosympathetic reflex discharges. The clinical implication of these findings is that the effect of midazolam on nociception depends on its dosage. It also appears that the infra-midbrain region plays a major role in mediating the depressive effects of midazolam on somatosympathetic C reflex discharges. (Anesth Analg 2007;105:832‐7)

Equipments used for light therapy include machinery used for irradiation by low reactive level laser, xenon light and linear polarized infra-red ray. Low reactive level laser is divided into two types of laser according to the medium by which laser is obtained ; semiconductor laser and helium-neon laser. Low reactive level laser has only one wave length and produces analgesia by action of light itself. On the other hands, Xenon light and linear polarized infra-red ray produce analgesia by warming effect induced by light in addition to the action of light itself. There are four methods of irradiation by these light sources; irradiation of acupuncture points, of trigger points, along nerves causing pain and of stellate ganglion area. Indication for light therapy includes various kinds of diseases such as herpes zoster, post herpetic neuralgia, cervical pain, lumbago due to muscle contracture, complex regional pain syndrome, arthralgia etc. However, we have to know that light therapy does not exert analgesic effects equally to all patients. But light therapy does not accompany pain and rarely shows any side effects. Therefore it is thought to be an alternative for patients who reject injection or patients who are not indicated for nerve block because of patients' conditions such as bleeding tendency.

The purpose of this randomized, multi-center phase III trial was to investigate the influence of sevoflurane and propofol on the neuromuscular blocking effects and pharmacokinetic parameters of Org 9426 (rocuronium bromide) in Japanese population.Thirty-nine adult Japanese patients participated in this randomized, multi-center study. Neuromuscular function was monitored continuously with TOF-Watch SX (Organon NV, Netherlands) after anesthetic induction with propofol. These subjects randomly received either 0.6 mg x kg(-1) or 0.9 mg x kg(-1) of rocuronium for endotracheal intubation. These two groups were further divided to two anesthetic regiments : sevoflurane group and propofol group. The difference in onset and recovery of rocuronium-induced neuromuscular block was statistically analyzed with two-way ANOVA.Mean duration for maximal block was 76 seconds and 66 seconds, respectively. The duration between Org 9426 administration and 25% recovery of first twitch response was significantly prolonged in patients given 0.9 mg x kg(-1) of Org 9426. Sevoflurane also significantly increased this duration. However, the serum concentration of Org 9426 was not statistically different between the four study groups.The duration of Org 9426-induced neuromuscular blockade was significantly increased under sevoflurane anesthesia compared to propofol anesthesia. This difference may be attributed to pharmacodynamic change.

The purpose of this study was to examine pharmacodynamics, pharmacokinetics and safety of Org 9426 (rocuronium bromide) in Japanese patients.Seventy-eight patients anesthetized with thiopental, droperidol, fentanyl and nitrous oxide, were randomized to receive either a single dose of Org 9426 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1). Contraction of the adductor pollicis to the ulnar nerve stimulation (0.1 Hz) was measured by acceleromyography. Blood was sampled over 6 hr and pharmacokinetic variables were calculated by plasma concentrations of Org 9426.Onset times for patients receiving 0.3 mg x kg(-1), 0.6 mg x kg(-1) or 0.9 mg x kg(-1) were 271.5 s, 140.0s and 125.4s, respectively. There was a dose-dependent increase in clinical durations until 25% recovery of twitch height (17.4 min in 0.3 mg x kg(-1) group, 37.2 min in 0.6 mg x kg(-1) and 60.4 min in 0.9 mg x kg(-1) group). Pharmacokinetic study revealed that elimination half life, steady state volume of distribution and plasma clearance of Org 9426 were 48-76 min, 146-181 ml x kg(-1), and 3.8-4.5 ml x min(-1) x kg(-1), respectively. No adverse effects were found except a case of local erythema on a forearm.The efficacy of neuromuscular block, stable pharmacokinetic behavior and excellent safety of Org 9426 were also confirmed in Japanese surgical patients.

A surgical patient with ventricular septal rupture after acute myocardial infarction is presented. The primary concern of general anesthesia was in the maintenance of systemic arterial pressure and reduction of afterload. General anesthesia was induced with a combination of fentanyl, ketamine, and propofol, which successfully suppressed fluctuations of hemodynamic variables associated with induction of anesthesia and tracheal intubation. Intravenous milrinone was used for inotropic support and reduction of systemic vascular resistance. The ventricular septal rupture was successfully repaired.