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Biomedical subjects

H Shimasaki

Publications and source records attributed to H Shimasaki.

At least 19 recordsLinked to original sources

Regional distribution of ethanolamine plasmalogen in the hippocampal CA1 and CA3 regions and cerebral cortex of the gerbil.

Although ethanolamine plasmalogens (EtnPm) are the predominant phospholipids in neural tissue, their physiological role has not been clarified. The biophysical conformation of EtnPm in the proteoliposome enhances the activity of the sodium-calcium exchanger, which has been proposed to induce intracellular calcium ion accumulation during ischemia and early reperfusion. The levels of EtnPm in the areas of the gerbil brain selectively vulnerable to ischemia, namely the hippocampal CA1 and CA3 regions and the cerebral cortex, were measured by high-performance thin-layer chromatography and gas-liquid chromatography. The concentration of EtnPm in the CA1 region, which is the most vulnerable to ischemic and anoxic stress, was 2.6- and 2.7-fold higher than that in the CA3 region and cerebral cortex, respectively. The significantly higher concentration of EtnPm in the hippocampal CA1 region may enhance sodium-calcium exchanger activity and play an important role in the vulnerability of this region to ischemia.

Animals↗

Antioxidative activity of 3,4-dihydroxyphenylacetic acid and caffeic acid in rat plasma.

The purpose of the present paper is to study and compare in vitro the inhibitory effect of 3,4-dihydroxyphenylacetic acid (DOPAC) and caffeic acid (CA) on lipid peroxidation in rat plasma. Rat plasma was oxidized at 37 degrees C by the radical initiators 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) or 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN). The consumption of endogenous alpha-tocopherol (alpha-TOH) and the accumulation of conjugated diene hydroperoxides were measured by high-performance liquid chromatography and by ultraviolet spectroscopy, respectively. Alpha-TOH was consumed at the same rate in the presence of 20 mM AAPH or 2 mM MeO-AMVN. DOPAC and CA suppressed the alpha-TOH consumption in a dose-dependent manner. A concentration of 50 microM of both phenolic acids was sufficient to induce a lag phase and to delay the rate of alpha-TOH consumption. The effect was more pronounced in rat plasma oxidation by AAPH than by MeO-AMVN. CA spared vitamin E more effectively than DOPAC in both oxidations. DOPAC and CA suppressed the formation of conjugated diene hydroperoxides. DOPAC and CA at concentration 50 microM suppressed alpha-TOH consumption during oxidation of soybean phosphatidylcholine (2.8 mM) multilamellar vesicles containing 15 microM alpha-TOH, in which the lipophilic initiator 2,2'-azobis (2,4-dimethylvaleronitrile) (6 mM) was incorporated. In conclusion, we demonstrated that DOPAC and CA in micromolar concentrations have antioxidant activity in rat plasma, a medium very close to the conditions in vivo, suggesting that supplementation with the phenolic acids will provide significant antioxidant protection.

3,4-Dihydroxyphenylacetic Acid↗

Mössbauer study of the reaction of laser-evaporated iron atoms with nitrogen molecules in low-temperature argon matrices.

Reaction products of laser-evaporated iron atoms with nitrogen molecules were investigated using a low-temperature matrix isolation technique. The products observed in the Mössbauer spectra were FeNNN, Fe(NN), and Fe(NN)2, isolated in argon matrices. Yields of the species changed, depending on the concentration of nitrogen in the matrix. A product assigned to Fe(NN)6 was obtained in a pure nitrogen matrix. Infrared spectra and molecular orbital calculations of the products support these findings.

Journal Article↗

Fat-soluble vitamin status is not affected by diacylglycerol consumption.

OBJECTIVE: The objective of this study was to examine the effect of dietary diacylglycerol (DAG) on the bioavailability of fat-soluble vitamins in comparison with triacylglycerol (TAG). METHODS: We conducted a long-term administration test of DAG and TAG in 27 healthy men aged 27-47 years. After measuring baseline values, subjects were randomized into two groups, one group (n = 15) was given DAG and the other (n = 12) was given TAG. Subjects ingested 20 g of DAG or TAG either in mayonnaise or an emulsion drink of their own choice at meals once a day for 12 weeks. At 4, 8 and 12 weeks, fasting blood samples were drawn and serum levels of vitamin A, E, and D were measured. RESULTS: There were no significant changes in vitamin A levels throughout the study period. Compared to the initial values (using a Student's t test for paired values), significant differences of vitamin E and D were seen at some points during the experiment. According to a two-way repeated measures analysis of variance, however, DAG and TAG (lipid) and time had no effect on fat-soluble vitamin levels. CONCLUSIONS: Our results indicate that DAG does not affect the absorption of the fat-soluble vitamins in diets.

Adult↗

Lethal forebrain ischemia stimulates sphingomyelin hydrolysis and ceramide generation in the gerbil hippocampus.

Ceramide, a hydrolyzed product of sphingomyelin, is reported to play an important role in apoptosis. In this study, we measured the sphingomyelin and ceramide levels in the hippocampus of the gerbil after transient forebrain ischemia for 5 min (lethal) or 2 min (sublethal). The aim was to examine alterations in the sphingomyelin cycle during delayed neuronal death, which we considered could be due to apoptosis. Sphingolipids were separated on high-performance thin-layer chromatography plates and analyzed by gas-liquid chromatography. At 30 min and 24 h after lethal ischemia, sphingomyelin levels were decreased and ceramide levels were increased compared with control levels. No significant changes were observed after sublethal ischemia. These results suggest that the sphingomyelin cycle may have a role in neuronal death.

Animals↗

Mössbauer studies on laser evaporated iron atoms and their reactions with oxygen in argon matrices.

Laser-evaporated iron atoms were isolated in low-temperature Ar matrices and their chemical reactions with oxygen were investigated by means of Mössbauer spectroscopy. Reactions of iron atoms with oxygen produce FeO, Fe(O2), FeO3, (O2)FeO2 and OFeO isolated in the Ar matrices and their yields vary depending on the concentration of oxygen. Similarly, FeO and Fe(O2) were obtained by the reaction of iron atoms with N2O. Infrared spectroscopy and molecular orbital calculations were applied to support their assignments.

Calorimetry↗

Comparison of the fatty acid composition of total lipids and phospholipids in breast milk from Japanese women.

Fatty acid (FA) composition of total lipids (TL) and phospholipids (PL) in breast milk obtained from 20 normal delivery healthy women in Tokyo, Japan was analyzed. Total lipids were extracted from the samples and then PL, consisting of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (Sph) and phosphatidylinositol (PI), were separated by two-dimensional thin-layer chromatography. The FA composition of TL and PL was analyzed by gas liquid-chromatography. Compared with previous reports, the contents of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in TL from Japanese women were higher than those from Chinese and Canadian women, which may be caused by different dietary habits and food types consumed by those populations. The contents of arachidonic acid (AA; 20:4n-6), EPA and DHA in PE and PI were much higher than those in PC. In addition, no significant correlation of EPA or DHA content was found between TL and PL. The findings indicate that PL especially PE and PI in human milk may be a source of EPA and DHA for infants in the rapid developmental stage. These results should be considered in infant formula production.

Chromatography, Gas↗

Therapeutic time window in the penumbra during permanent focal ischemia in rats: changes of free fatty acids and glycerophospholipids.

To better define a therapeutic time window for reducing the extent of damage in ischemic penumbra, the time courses of changes in the glycerophospholipid and free fatty acid (FFA) levels were determined in the rat cerebral cortex following induction of the permanent focal ischemia. Focal ischemia induced a biphasic increase in FFA levels in the cerebral cortex, which had been recognized as the ischemic penumbra during the early stages after permanent occlusion of the middle cerebral artery (MCA). The first increase in FFA levels, in which the polyunsaturated fatty acid (PUFA) contained a large number of arachidonic acid (C20:4) molecules, began at 30 min and reached a peak at 1 h, followed by transient return to each sham level 2-6 h after the onset of MCA occlusion. Thereafter, the delayed increase in FFA levels, showing more increases of docosahexaenoic acid (C22:6) molecules than the C20:4 in PUFA compositions, occurred at 24 h. In contrast, the levels of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) decreased rapidly at 30 min of ischemia and returned transiently to each sham level at 1-6 h. The levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), including polyphosphoinositides (PIPs), began to decrease significantly during the late stages, i.e., 24 h after induction of ischemia. These results suggest that the time-dependent changes in FFA and PIPs levels during the early stages of ischemia (until 6 h after induction) might be an important determinant of the subsequent neuronal death in the ischemic penumbra and that the breakdown of glycerophospholipids in the later stages after the induction of focal ischemia was associated with the development of infarction in the cerebral cortex.

Animals↗

Dietary diacylglycerol suppresses accumulation of body fat compared to triacylglycerol in men in a double-blind controlled trial.

We examined the effects of the long-term ingestion of dietary diacylglycerols (DG) in a double-blind controlled study of human lipid metabolism. Healthy men (n = 38; aged from 27 to 49 y, body mass index (BMI) ranging from 21.8 to 27.4 kg/m(2)) completed the study. To accustom the subjects to the test diets prior to the experiment, they were supplied with test diets of triacylglycerol (TG) oil for 4 wk (control period). The test oils (10 g/d) were included in bread, mayonnaise or shortbread and served for the breakfast. The target for total lipid intake was 50 g/d (15 g for breakfast, 15 g for lunch and 20 g for dinner) throughout the study. The subjects were then divided into two groups so that mean BMI and the hepatic fat content, determined by computed tomography, for each group were not different. One group (DG group) consumed test meals containing DG-rich oil (10 g/d) while the other group (TG group) consumed the same meal as during the control period. Ten grams of the DG-rich oil contained 5.5 g 1,3-DG, 2.5 g 1,2-DG and 2 g TG. The actual lipid intake during the study was 43 g/d. Body weight, BMI and waist circumference decreased in both groups at the end of the test period of 16 wk. However, the magnitudes of decreases in these variables were significantly greater in the DG group than in the TG group. Decreases of total fat, visceral fat area and subcutaneous fat area of the abdominal traverse images of computed tomography in the DG group were also significantly greater than those in the TG group. Hepatic fat content decreased significantly in the DG group while no change was observed in the TG group. Serum lipid concentrations (TG, total cholesterol, free fatty acid) and related metabolites (glucose, insulin, total ketone body) did not change significantly in either group. Thus, in contrast to TG, DG apparently suppressed accumulation of fat and possibly reduces the risk of diseases associated with visceral fat obesity.

Abdomen↗

Mild hypothermia reduces the rate of metabolism of arachidonic acid following postischemic reperfusion.

Free fatty acid (FFA) accumulation during cerebral ischemia has been described as an indicator of ischemic damage. Furthermore arachidonic acid (AA) metabolites, liberated from glycerophospholipids, have been confirmed to induce disturbances of membrane functions. Are there differences in AA levels in the hippocampus of normo- and hypothermic gerbils following ischemia-reperfusion? In an attempt to answer this question, we first studied the time course of changes in the amount of AA liberated from glycerophospholipids using gerbils subjected to 5 min of ischemia-reperfusion under normo- and mild hypothermia. FFAs (including AA) were separated from total lipids by Bond Elut (NH2) column chromatography and analyzed by gas-liquid chromatography. Mild intra-ischemic hypothermia (MIH) did not affect the ischemia-induced AA accumulation following of 5 min of forebrain ischemia. The accumulated AA amounts under MIH tend to decrease more slowly to baseline levels from 15 to 30 min of reperfusion than do the levels under normothermia. These results suggested that MIH reduced the rate of metabolism of AA after reperfusion and might suppress the generation of free radical, eicosanoids and other bioactive metabolites.

Animals↗

Fatty acid compositions of colostrum, cord blood, maternal blood and major infant formulas in Japan.

Lipid profiles in colostrum, cord blood, maternal blood and major infant formulas in Japan were analyzed. In the first part of the study, colostrum obtained from 36 normal delivery women and six kinds of infant formulas provided by three major milk companies were analyzed for their fatty acid composition using capillary gas-lipid chromatography. Although enriched with docosahexaenoic acid (DHA), the percent composition of DHA in the six infant formulas (0.15-0.21%) was significantly lower than that in the colostrum (1.1 +/- 0.54). Arachidonic acid (AA) and eicosapentaenoic acid (EPA) were present in the colostrum but not detectable in the infant formulas. It is recommended that although the exact amount of specific fatty acids needed in the infant diet was not completely known, to be as close as possible to natural breast milk, the level of DHA, EPA and AA should be raised in the infant formulas. In the second part of the study, 19 pairs of maternal and cord blood were analyzed for their lipid profile. All samples were from normal vaginal delivery. The measurement of cholesterol, triglycerides, phospholipids and free fatty acids was performed with commercially available enzymatic methods on an automated discrete random access analyzer. Total fatty acid was determined as described in the first part of the study. The results were analyzed with Spearman's rank correlation coefficient. No correlation could be found between maternal and fetal concentrations of cholesterol, triglycerides, phospholipids or total fatty acids. Correlation could be found in non-esterified fatty acids, in palmitic acids, and oleic acid levels. It was concluded that the lipid transport and metabolism in the fetal-placenta unit is complex and further delicate investigation is required.

Adult↗

[Are we legally allowed to administer blood for lifesaving to a patient who refuses it?].

We surveyed the literatures and discussed the legal issues whether we should administer blood for lifesaving to a patient who refuses it. The valid refusal of the transfusion requires the distinct intention of a competent patient. Minors below fifteen years of age are incompetent and their parents make a substituted judgement. Anyone must not give priority to the parents' belief and blood ought to be transfused if necessary for the children's benefits. We could evade liability for withholding blood only when we manage an operation arranged to succeed without blood transfusion, undergoing the sufficient treatments to avoid the risks, as well as on the basis of the valid refusal of a patient. The release deed and the intervention of hospital directors, ethics committees and courts are invalid for the immunity from liability. Anesthesiologists have to take the responsibility on themselves of administering blood or not. A statute law should be established to define what is a patient's valid intention and who is responsible.

Anesthesiology↗

Sphingomyelin changes in rat cerebral cortex during focal ischemia.

To better define the sphingolipid metabolism during focal brain ischemia, levels of ceramide, sphingomyelin, cerebroside and gangliosides were determined in rat cerebral cortex during focal ischemia produced by occlusion of the middle cerebral artery. Sphingomyelin began to decrease at 2 hours of ischemia and continued to decrease for 96 hours. In contrast, ceramide increased at 6 hours and increased to 4.2-fold at 96 hours after ischemia, and the fatty acid composition of ceramide was solely nonhydroxylated fatty acid similar to sphingomyelin. Hydroxylated fatty acid-linked cerebroside decreased at 6 hours of ischemia, whereas any significant decrease of nonhydroxylated fatty acid-linked cerebroside didn't occur for 96 hours of ischemia. There were no measurable changes in the levels of gangliosides. These results suggested that ceramide was produced in the cerebral cortex by the breakdown of sphingomyelin during early ischemia.

Animals↗

Inhibition of oxidation of low density lipoprotein by vitamin E and related compounds.

The oxidation of low density lipoprotein (LDL) was carried out aiming specifically at elucidating the anti-oxidant action of alpha-tocopherol. Lipophilic and hydrophilic azo compounds and copper induced the oxidation of LDL similarly to give cholesterol ester and phosphatidylcholine hydroperoxides as major products. The antioxidant potency of alpha-tocopherol in LDL was much poorer than in homogeneous solution. Doxyl stearic acids were used as spin probe and incorporated in LDL. The rate of reduction of doxyl nitroxide in LDL by ascorbate decreased with increasing distance from the LDL surface. From the competition between the spin probe and alpha-tocopherol in scavenging radical, it was found that the efficacy of radical scavenging by alpha-tocopherol became smaller as the radical went deeper into the interior of LDL. On the other hand, 2,2,5,7,8-pentamethyl-6-chromal spared the spin label regardless of the position of nitroxide. The antioxidant activity of chromanols against LDL oxidation increased with decreasing length of isoprenoid side chain at the 2-position. All these results were interpreted by location and low mobility of alpha-tocopherol in LDL. The tocopherol mediated propagation was observed notably at low rate of radical flux, but this was suppressed by reductant such as ascorbic acid and ubiquinol.

Amidines↗

Oxidized low-density lipoprotein induces the production of superoxide by neutrophils.

Exposure of guinea pig peritoneal neutrophils to ox-LDL led to the production of superoxide, which was measured by the formation of superoxide-dependent chemiluminescence. The cells exposed to unoxidized LDL, e.g. native LDL, acetyl-LDL, and self-aggregates of LDL showed no production of superoxide. The superoxide production was correlated with the levels of oxidative modification of LDL and reached a maximum between 10 and 30 min during incubation, but preincubating the cells with cytochalasin B decreased the superoxide production. These findings indicate that neutrophils rapidly take up ox-LDL by phagocytosis and generate superoxide which may cause superoxide-mediated lipid peroxidation in vivo.

Animals↗