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Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans.Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects.Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev-1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf-2, daf-16, pmk-1, and skn-1.Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn-1 (encoding a component of the p38 MAPK pathway) and daf-16 (encoding a component of the IGF-1 pathway).

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.

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.

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.

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 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.

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.

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)

IT is well known that phantom limb pain can reappear or be exacerbated transiently during spinal anesthesia in amputees. 1 However, to the best of our knowledge, the reappearance of phantom limb pain immediately after nonamputation surgery in an amputee has not been reported. We herein present a patient with chief complaint of reactivation of phantom limb pain the day immediately after cervical myelopathy surgery.

This study describes the effects of mixtures of xanthan gum and galactomannan, guar gum, or locust bean gum, on the lipids in plasma and liver in non-diabetic and diabetic rats. Non-diabetic rats were fed cholesterol-free diets with 3% guar gum, locust bean gum, or xanthan gum (3G, 3L, and 3X), or a mixture of xanthan gum and guar gum or locust bean gum (1:2, w/w) (2G1X, 2L1X) for 2 weeks. Rats fed diets not containing these polysaccharides were used as controls. The total cholesterol in plasma and the triacylglycerol in liver were significantly lowered in rats fed the 2G1X diet. The 3G, 3X, 3L, and 2L1X diets showed no significant effect on the total cholesterol and triacylglycerol in plasma and liver. In the streptozotocin-induced (STZ) diabetic rats, the total cholesterol in plasma was lowered in rats fed the 3G, 3X or 2G1X diet for 4 weeks, and the 2G1X diet was more effective than the 3G and 3X diets. The triacylglycerol in plasma in STZ diabetic rats was also significantly lowered by the 2G1X diet. These results showed that a mixture of xanthan gum and guar gum has an improved hypolipidemic effect on non-diabetic and STZ diabetic rats. The effects of the 2G1X diet on the diabetic symptoms in STZ diabetic rats, suppression of food and water intakes, decrease in glucose in urine, and lowering of plasma glucose, were also observed.

We have quantified the potentiating effects of 1.7% sevoflurane (n = 12) on vecuronium-induced neuromuscular block and compared the results with those obtained during balanced anaesthesia with propofol (n = 12) or midazolam (n = 12) in 36 patients. Neuromuscular function was monitored using an accelerograph and the train-of-four responses of the adductor pollicis muscle to ulnar nerve stimulation. Vecuronium 0.1 mg kg-1 was administered as an intubating dose, and maintenance doses of 0.02 mg kg-1 were administered on three occasions when T1/T0 had recovered to 25%. Thereafter, spontaneous recovery was monitored until complete. Times to 25% recovery of T1/T0 (DUR25) after an intubating dose of vecuronium did not differ between groups (mean 44.2 (SD 18.7) min for sevoflurane, 38.3 (7.5) min for propofol and 35.5 (9.5) min for midazolam). DUR25 values after each maintenance dose were 29.8 (9.5) min, 30.3 (10.4) min and 31.6 (10.7) min during sevoflurane anaesthesia, and were significantly longer than values for propofol (21.7 (6.0) min, 21.5 (5.8) min and 21.9 (5.8) min) and midazolam (20.0 (5.9) min, 19.3 (7.7) min and 19.8 (8.0) min) (P0.05) in each case). Recovery index25-75% and interval from T1/T0 = 25% to T4/T1 = 0.7 after the final dose of vecuronium were significantly prolonged by sevoflurane (28.3 (13.2) min and 42.7 (16.4) min) compared with propofol (17.6 (6.1) min and 26.6 (9.8) min) or midazolam (16.3 (9.4) min and 26.0 (10.2) min) (P0.05 in each case).

We report herein the cDNA cloning of a novel member of the low-density lipoprotein receptor (LDLR) family termed LDLR-related protein 3 (LRP3). Human and rat LRP3 cDNAs encode a 770-amino-acid type 1 membrane protein with the following regions: a putative signal sequence, two isoleucine/leucine/valine-rich regions with an RGD sequence, two ligand-binding repeat regions, a putative transmembrane region, and a proline-rich cytoplasmic region with a tyrosine-based internalization signal. Fluorescencein situhybridization of human chromosomes revealed that the human LRP3 gene mapped to chromosome bands 19q12–q13.2. LRP3 transcript was detected in a wide range of human tissues, with the highest expression in skeletal muscle and ovary. Despite the presence of the ligand-binding repeats, CHO cells transfected with LRP3 did not bind β-migrating very-low-density lipoprotein or receptor-associated protein.

Dietary supplementation with powder of a green tea extract suppressed the enhancement of plasma alanine aminotransferase and aspartate aminotransferase activities induced by D-galactosamine, but not by carbon tetrachloride, in a dose-dependent manner in rats. The minimum dose to cause a significant effect was 1 to 2%. Drinking green tea also suppressed plasma enzyme activities. These results indicate that green tea had a liver injury-preventive effect.

Apolipoprotein E receptor 2 is a recently identified receptor that resembles low and very low density lipoprotein receptors. Isolation and characterization of genomic clones encoding human apolipoprotein E receptor 2 revealed that the gene spans approximately 60 kilobases and contains 19 exons. The positions of the exon/intron boundaries of the gene are almost identical to those of low and very low density lipoprotein receptors. Fluorescent in situ hybridization of human chromosomes revealed that the gene is located on chromosome 1p34. Isolation of a cDNA encoding a variant receptor and reverse transcription-polymerase chain reaction indicate the presence of multiple variants with different numbers of cysteine-rich repeats in the binding domain of the receptor. We also found a variant receptor lacking a 59-amino acid insertion in the cytoplasmic domain. The transcription start site was mapped to the position 236 base pairs upstream of the AUG translation initiator codon by primer extension analysis. Sequence inspection of the 5'-flanking region revealed potential DNA elements: AP-2, GC factor, PEA3, and Sp1. The minimal promoter region and a region required for nerve growth factor inducibility in PC12 cells were also determined.

To determine the influence of stimulation intensity on dose-response curves of three analgesics in halothane-anesthetized rats, continued immersion of the tail in 52.5 degrees C or 60 degrees C water for 15 s results first in a nociceptive reflex tail movement (tail flick = 2.8 +/- 0.4 s and 1.4 +/- 0.2 s, respectively), and a progressive increase in arterial blood pressure (delta BP = 21 +/- 1 and 24 +/- 1 mm Hg) and heart rate (delta HR = 27 +/- 2 and 32 +/- 2 beats/min). Intrathecally administered mu opioids, morphine (MOR), sufentanil (SUF), and [D-Ala2-N-Phe4,Gly-ol]-enkephalin (DAG), produced a dose-dependent inhibition of the tail flick and BP response with the relative activity being SUF = DAG > MOR. Although the magnitude of the response evoked by increasing stimulus intensity from 52.5 degrees C to 60 degrees C was increased only mildly (suggesting that both represented essentially supramaximal stimuli), this increase in stimulus intensity resulted in a significant rightward shift in the dose-response curves (decrease in apparent potency) of the three agonists, with the magnitude of the shift being MOR > SUF = DAG. Thus, the dose ratio (ED50 at 60 degrees C/ED50 at 52.5 degrees C) for these three analgesics given intrathecally on the tail flick and BP response was, respectively, 3.7 +/- 0.9 and 6500 +/- 465 for MOR; 0.5 +/- 0.9 and 2.4 +/- 0.9 for SUF; and 0.5 +/- 1.2 and 7.0 +/- 0.9 for DAG. Unlike SUF and DAG, with the 60 degrees C stimulus, the highest dose of MOR failed to abolish the BP and heart rate response. Previous work with an irreversible antagonist to define receptor occupancy requirements showed that the relative efficacy was SUF = DAG >> MOR. The present studies thus confirm the pharmacodynamically based prediction that for a given change in stimulus intensity, anesthetics with a high efficacy (DAG and SUF) show less shift in their dose response curves with a given increase in stimulus intensity than an agonist with low efficacy (MOR).

We evaluated vecuronium-induced neuromuscular block in both arms of a patient with cerebral palsy and hemiplegia. A remarkable resistance to vecuronium was observed in the hemiplegia side compared with cerebral palsy side. Complete recovery from neuromuscular block should be assessed in the cerebral palsy side that shows a delayed recovery.

The present paper shows a series of experiments carried out to elucidate the possible mechanism by which soybean protein isolate (SPI) produces a lower level of plasma cholesterol than casein in rats fed a cholesterol-free diet. When the plasma cholesterol level was in a steady state characteristic of casein and SPI, SPI in the diet was substituted for casein and vice versa. Within 3 days after substitution of dietary protein, the plasma cholesterol level in each group reached a steady state level similar to that in its previous counterpart. The inherent responses of plasma cholesterol to casein and SPI were not changed by the resection of the jejunum or the ileum and the administration of cholestyramine or beta-sitosterol. The rates of the sterol synthesis in vivo of the liver and the small intestine were significantly higher in SPI-fed rats than in casein-fed rats. The hypocholesterolemic effect of SPI disappeared when Met was supplemented at a level equivalent to casein. The effects of casein and SPI were reproduced by their equivalent amino acid mixtures. The ratio of the postprandial increment of Met concentration to that of Gly concentration in the portal plasma was significantly higher when casein and its amino acid mixture were fed than when SPI and its amino acid mixture were fed. The casein-induced increase in the level of plasma cholesterol was attributed to an increase in high density lipoprotein (HDL)-cholesterol. HDL-cholesterol concentration showed the positive correlation with the lecithin:cholesterol acyltransferase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

The contribution of enterohepatic circulation of cholesterol and bile acids in the hypocholesterolemic activity of soybean protein isolate (SPI) was compared with the activity of casein. Intact, sham-operated, jejunectomized or ileectomized adult rats were fed a cholesterol-free, purified diet containing either 20% casein or 20% SPI for 7 or 10 d. For the subsequent 7 d the diets were reversed. In intact rats the plasma cholesterol concentration (p-chol) was significantly higher when the casein diet was fed than when the SPI diet was fed. Within 3 d after the diet crossover, p-chol in each group of intact rats reached rapidly the same level as that in its previous counterpart. These rapid inherent responses of p-chol to the casein and SPI diets remained unchanged even when the jejunum or the ileum was resected, and p-chol in jejunectomized or ileectomized rats was similar to that found in sham-operated rats. The extent of the change in p-chol induced by exchanging dietary proteins was almost the same among intact, sham-operated, jejunectomized and ileectomized rats. These findings indicate that the interruption of enterohepatic circulation of cholesterol and bile acids is not the major factor involved in the differential effects of dietary proteins on p-chol.

Os Autores descrevem um caso de paracoccidioidomicose em Tóquio, o segundo observado no Japão. A paciente residiu cerca de cinco anos na zona urbana de São Paulo, onde provavelmente adquiriu a primo-infecção. Não tomou corticóides, nem teve história de outras afecções que justificassem a paracoccidioidomicose. Após três anos do retorno ao Japão apresentou linfadenopatia, comprometimento hepatesplênico e ausência de lesões pulmonares. O presente caso, com exame histopatoló-gico e cultivo positivos para Paracoccidioides brasiliensis também apresentou quadro soroló-gico compatível. O aspecto blástico das lesões ósseas, raro em arcos costáis nesta micose, bem como a linfadenopatia generalizada são discutidos. Tratamento à base de anfotericina B e ketoconazol ofereceu resultados favoráveis. Neste trabalho os Autores discutem o problema de "patologia de importação", com suas implicações. The Authors report a non-autochthonous case of paracoccidioidomycosis in Tokyo, the second related in Japan. The patient lived for nearly five years in the urban area of São Paulo, where probably she acquired the primary infection. There was no history of corticoid therapy or other diseases that could explain paracoccidioidomycosis. Three years after her return to Japan, she presented lymphadenopathy, hepatosplenic involvement and absence of pulmonary lesions. The present case, with histopathological examination and culture positive to Paracoccidioides brasiliensis also showed compatible serological results. The blastic feature of bone lesions, rare in ribs in this mycosis, as well as the generalized lymphadenopathy are discussed. Treatment with amphotericin B and ketoconazole offered good results. In this paper the Authors discuss the problem of the "pathology of importation" with its implications.