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Biomedical subjects

T Hamazaki

Publications and source records attributed to T Hamazaki.

At least 19 recordsLinked to original sources

Changes in fatty acid composition in rat blood and organs after infusion of eicosapentaenoic acid ethyl ester.

An infusible emulsion of 10% eicosapentaenoic acid ethyl ester (EPA-EE, 99.2% pure) was prepared. Three ml of the emulsion was infused into tail veins of 20 Wistar rats weighing approx. 300 g. They were killed 1 h, 6 h, 24 h, 3 d and 7 d after the infusion, and fatty acid composition of various organs and plasma was analyzed along with that of control rats. There was no lipidosis in any organs of any rats. It was estimated that not less than 98% of infused EPA was cleared from plasma during the first hour after the infusion. EPA concentrations reached their peaks within 6 h after EPA infusion in plasma lipid fractions and in the phospholipid fraction of liver, heart, lung, kidney and spleen. The fatty acid composition of the phospholipid fraction of heart was very stable, and was not altered by EPA infusion except for a very slight increase in EPA at 1 h after the infusion (0.18% at 0 h to 0.56%). However, EPA concentrations increased markedly in the free fatty acid fraction of heart at 1 h after the infusion (0.15% at 0 h to 4.23%). Arachidonic acid concentrations decreased significantly within 24 h in the phospholipid fraction of organs except for heart. EPA emulsion might be useful for patients in whom a rapid increment in EPA in tissues is beneficial.

Animals

Reduction in the ADP release from shear-stressed red blood cells by fish oil administration.

Fish oil concentrate (5.4 g/day) was administered to 8 young male volunteers and to 7 middle-aged male volunteers for 1 week. ADP released into the supernatant of red blood cell (RBC) suspension by a shear stress of 375/sec for 3 min was measured before and after fish oil administration. Before the administration the ADP release from shear-stressed RBCs in the middle-aged group was significantly higher than in the young group. After the administration the ADP release was reduced significantly in the young group (by 46%, p less than 0.001) and nonsignificantly in the middle-aged group (by 54%, p = 0.09). If the two groups were combined, the reduction was also significant (by 50%, p less than 0.005). This reduction was significantly correlated with the improvement of RBC filterability after fish oil administration (n = 13, r = 0.62, p less than 0.05). We suggest that the reduction of the ADP release from shear-stressed RBCs is one of the mechanisms of action of eicosapentaenoic acid against thrombotic disease.

Adenosine Diphosphate

Comparison of the conversion rates of alpha-linolenic acid (18:3(n - 3)) and stearidonic acid (18:4(n - 3)) to longer polyunsaturated fatty acids in rats.

The delta 6-desaturase reaction is regarded to be the rate-limiting step in the conversion of linoleic acid (18:2(n - 6)) to arachidonic acid (20:4(n - 6)). The same is probably also the case with the conversion of alpha-linolenic acid (18:3(n - 3)) to eicosapentaenoic acid (20:5(n - 3)). However, there are very few in vivo studies that directly compared the conversion rate between 18:3(n - 3) and stearidonic acid (18:4(n - 3)), which is the delta 6-desaturated product of 18:3(n - 3). We compared this rate by feeding rats on a lipid-free diet supplemented with lard (9%, w/w) and 18:3(n - 3) ethyl ester (1%) diet or on a diet containing lard (9%) and 18:4(n - 3) ethyl ester (1%). A lard (10%)-supplemented diet was used as the control diet. The fatty acid compositions of total phospholipids, triglycerides and free fatty acids of both liver and plasma were measured after 1 or 3 weeks on different diets. The molar ratio of 20:5(n - 3) of most lipid fractions was about 2-fold higher in rats fed the 18:4(n - 3)-supplemented diet than in rats fed the 18:3(n - 3)-supplemented diet. 18:4(n - 3) was found in the liver lipid fraction in only a very small amount, even in the 18:4(n - 3)-supplemented groups. Thus, desaturation at C-6 is suggested to be the rate-limiting step in the conversion of 18:3(n - 3) to 20:5(n - 3).

Animals

Reduction of delayed-type hypersensitivity by the injection of n-3 polyunsaturated fatty acids in mice.

The effects of injection of n-3 polyunsaturated fatty acids (PUFAs) on the delayed-type hypersensitivity (DTH) response was investigated in mice. Mice were immunized with sheep red blood cells (SRBCs). Six days later 50 microliters of a 20% SRBC suspension was injected into the right hind footpad of each mouse. Just before the challenge of SRBCs, various amount of a trieicosapentaenoyl-glycerol emulsion (10%) was injected through tail veins (5 mice per each dose). Then 24 hr later the dorsoventral thickness of the right hind footpad was measured and compared with that of the left hind footpad. The difference in thickness between both footpads was regarded as the DTH response. The effect of the emulsion on DTH was dose-dependent; the DTH responses (in mm) in the control group (injected with 0.5 ml of a 2.5% glycerol solution through tail veins) and EPA-injected groups (with 5 mg, 10 mg, and 20 mg) were 1.53 +/- 0.16 (mean +/- SEM), 1.09 +/- 0.14, 0.43 +/- 0.07 (P less than 0.005), and 0.36 +/- 0.13 (P less than 0.005), respectively. The DTH response was also depressed by the injection of a tridocosahexaenoyl-glycerol emulsion. Consequently, n-3 PUFA emulsions have clinical implication in DTH-related diseases such as rejection of allografts.

Animals

Intravenous infusion of trieicosapentaenoyl-glycerol and LTB4 and LTB5 production by leukocytes of rabbits.

During myocardial infarction leukotriene B4 (LTB4) is probably a major determining factor of tissue damage because it can amplify the inflammatory reaction by recruiting leukocytes and degranulating them. Oral administration of eicosapentaenoic acid (EPA) is known to reduce LTB4 production by polymorphonuclear leukocytes (PMNL). However, it takes several weeks for EPA to take effect. In this study, we formulated a trieicosapentaenoyl-glycerol emulsion and infused it into rabbits (0.8 g EPA/kg). In the ex vivo study, the inhibition of LTB4 production by PMNL from EPA-infused rabbits was maximal (32-60% of preinfusion values, P less than 0.01) 6 h after the infusion. There was also a tendency toward reduced LTB4 production 1, 24, and 168 h after the infusion. A lower dose (0.2 g EPA/kg) also reduced LTB4 production (45% of preinfusion values, P less than 0.02) 6 h after the infusion. There was no significant change in LTB4 production in control groups in which soybean oil emulsion was infused instead of EPA. EPA infusion might be useful for reduction of tissue damage in the acute phase of LTB4-related diseases such as acute myocardial infarction.

Animals

Intravenous infusion of n-3 polyunsaturated fatty acids.

Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) is regarded as beneficial for the prevention and treatment of atherosclerosis and thrombosis and chronic inflammatory diseases like rheumatoid arthritis and psoriasis. It may be possible to treat some acute diseases like acute myocardial infarction or acute rejection of grafted organs if it is possible to make n-3 PUFA take effect quickly (in hours instead of days). Three sets of experiments were done. In Experiment 1, emulsion of trieicosapentaenoyl-glycerol (EPA-TG) and tridocosahexaenoyl-glycerol was infused through rabbit ear veins, and the leukotriene B4/B5 production from polymorphonuclear leukocytes was measured at different time points by high-performance liquid chromatography. In Experiment 2, delayed type hypersensitivity (DTH) of mice was measured with sheep red blood cells as an antigen. Pure n-3 PUFA emulsions or a control solution were infused through tail veins just before the second challenge of the antigen. DTH was measured 24 hr after the second challenge. In Experiment 3, human natural killer cell activity was measured using K562 target cells before and after the infusion of pure EPA-TG emulsion to an antecubital vein. Leukotriene B4 production by rabbit polymorphonuclear leukocytes was depressed by 40% by EPA-TG infusion. DTH was suppressed almost completely by n-3 PUFA infusion. Natural killer cell activity was suppressed almost completely by EPA-TG infusion in 8 hr. DTH, natural killer cell activity, and leukotriene B4 production are probably related to acute rejection of grafted organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Preschool children's prosocial judgments and their reasoning in the empathic situations].

The purpose of this study was to examine preschool children's prosocial judgments and their reasoning for prosocial episodes. One hundred children were individually asked to do prosocial judgments and their reasoning for three prosocial episodes: helping, sharing, and comforting. In the episode there was a crying or a normal facial expression of a person in distress under the condition of high and low empathic situations. The results indicated that the crying face and high empathic situation increased the rate of prosocial judgment more than the normal face and low empathic situation, respectively, and older children (5-year-olds) did prosocial judgment than younger ones (4-year-olds). Furthermore, the crying face induced the empathic reasoning, especially in the high empathic situation. These results supported that preschool children were able to use the empathic reasoning reflected in the negative facial expression and the cause of distress of the victim.

Child Behavior

[The effects of role playing on prosocial behavior in preschool children].

The purpose was to examine the effects of two types of role-playing experience on prosocial behavior in preschool children. Subjects were 72 6-year-olds. In the Empathy role-playing (E), each pair of children enacted alternately a victim and an eyewitness using a glove puppet, in which the emphasis was only on empathizing with the victim. In the Empathy and Helping role-playing (EH), they enacted alternately a victim and a helper, in which the emphasis was on empathizing and helping a victim. In the Control role-playing (C), they played roles alternately of a customer and a salesman in a grocery store. All children were assessed as for helping and sharing behaviors for a real victim before and after the role playing session. In the comparison between pre- and post-tests for helping behavior. All groups (C, E, EH) increased helping tendency, but only in EH group the proportion of subjects, whose attitude changed from helper to non-helper. As for sharing behavior, all three groups increased the number of sharing significantly in the post-test.

Child

Eicosapentaenoic acid inhibits antigen-presenting cell function of murine splenocytes.

Recently, many investigators have studied the effects of eicosapentaenoic acid (EPA)-rich fish oil on immune function and immune disease. However, effects of dietary supplementation of fish oil or EPA on the immune system are still unclear. In the present study, the effects of EPA on antigen presentation were investigated. We have used antigen-specific helper T-cell clones that proliferate in the presence of antigen [keyhole limpet haemocyanin (KLH)] and spleen cells as antigen-presenting cells (APC). Mice were divided into two groups and fed an experimental diet or a control diet for 4 weeks ad libitum. In mice fed the experimental diet, the arachidonic acid (AA) content of spleen cells was decreased and that of EPA and docosapentaenoic acid was increased markedly compared to those of the control diet. Dietary enrichment with EPA inhibited the ability of accessory cells to present antigen to murine helper T-cell clones. This effect was observed for two distinct helper T-cell clones, Th1 and Th2. We also examined the effects of EPA-TG emulsion on APC function. The direct addition of EPA-TG emulsion to a T-cell proliferation assay system suppressed APC function. The inhibition was proportional to the concentration of EPA-TG emulsion. Pretreatment of splenocytes with EPA-TG emulsion resulted in inhibition of APC function. Inhibition of antigen presentation by dietary supplementation with EPA might depress immune reactivity.

Animals

Effect of eicosapentaenoic and docosahexaenoic acid on natural killer cell activity in human peripheral blood lymphocytes.

The effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on natural killer (NK) cell activity in human peripheral blood lymphocytes were studied. The direct addition of trieicosapentaenoyl-glycerol (EPA-TG) or tridocosahexaenoylglycerol (DHA-TG) emulsion to a cytotoxicity assay system significantly suppressed NK cell activity. The addition of lipoxygenase inhibitor AA861 also inhibited NK cell activity. The inhibition was proportional to the concentration of EPA-TG emulsion. DHA-TG emulsion, or AA861. The presence of both EPA-TG emulsion or DHA-TG emulsion and AA861 at the same time led to a greater inhibitory effect on NK cell activity than when these emulsions were used separately. The inhibitory effect caused by these lipids or lipoxygenase blockade could not be reversed by adding back exogenous leukotrienes to the assay system. Preincubation of effector cells with EPA-TG or DHA-TG emulsion resulted in a significant inhibition of their NK cell activity. NK cell activity of human lymphocytes was markedly decreased after the infusion of EPA-TG emulsion into healthy volunteers. Thus, in vivo use of EPA-TG or DHA-TG emulsion may influence immune reactivity of the host, although the mechanism has not yet been elucidated.

Benzoquinones

Changes in fatty acid composition in rat blood and organs after infusion of docosahexaenoic acid ethyl ester.

An infusible emulsion of docosahexaenoic acid ethyl ester (DHA-EE) was prepared. One hundred milliliters of the emulsion contained 10 g DHA-EE (90% pure). Three milliliters of the emulsion was infused into tail veins of 22 Wistar rats weighing approximately 300 g. They were killed 1, 6, and 24 h and 3 and 7 d after the infusion, and fatty acid composition of various organs and plasma was analyzed along with that of control rats. DHA concentrations reached their peaks within 24 h after DHA infusion in plasma lipid fractions and in the phospholipid fraction of liver and lung. DHA did not increase at all in cardiac phospholipid fraction. However, DHA concentrations increased markedly (from 0.7% to 11%) in the free fatty acid fraction of heart 1 h after the infusion. DHA emulsion might be useful for patients in whom a rapid increment in DHA in tissues is beneficial.

Animals

Reduction in microalbuminuria in diabetics by eicosapentaenoic acid ethyl ester.

Eicosapentaenoic acid (EPA) ethyl ester (1.8 g/d) was administered to 16 diabetic patients (5 insulin-dependent and 11 noninsulin-dependent diabetics) for 6 mon. EPA in total plasma fatty acids increased from 4.0 +/- 2.4 mol% (mean +/- SD) to 7.5 +/- 3.1 mol% (p less than 0.001). Albumin excretion, measured with spot urine, was significantly reduced from 65 to 36 mg/g creatinine (geometric means, p less than 0.001). Fasting blood sugar levels, glycohemogloblin, body weight and blood pressure did not change significantly during the study. There were also no significant changes in serum levels of creatinine, urea nitrogen, total cholesterol and triglycerides. Although no overt hemorrhage was observed in the patients, hematocrit was reduced from 42.6 +/- 2.8% to 41.0 +/- 3.9% (p less than 0.02). Ten other similar diabetic patients (4 insulin-dependent and 6 noninsulin-dependent diabetics) were followed as a reference group, not concomitantly, for 6 mon with neither EPA ethyl ester nor placebo. The parameters mentioned above were not changed significantly in this group during 6 mon. EPA administration might retard the appearance of overt diabetic nephropathy.

Aged

Changing dietary patterns.

Previously traditional dietary patterns in Japan are no longer typical. The current changing conditions provide an opportunity to examine more closely some important health conditions associated with the changed lifestyle and concentrations of dietary total fat and saturated fatty acid, and the ratio of n-3 to n-6 polyunsaturated fatty acids in the diet.

Diet

[Trends in studies of prosocial behavior].

The present article provides an analysis of past trends and recent developments in studies of prosocial behavior which began in the latter half of the 1960s. Particular emphasis is placed on studies relating to the subsequent bystander effect, the development of decision-making models incorporating interactions of various factors, empathy, perspective-taking, and prosocial moral judgment as an important mediating factor in motivation, including the viewpoint of self-perception. The article concludes by considering the relevance of studies of prosocial behavior to psychology at large and the directions such studies might take in the future.

Decision Making

Effect of eicosapentaenoic acid ethyl ester on proteinuria of streptozotocin-induced diabetes mellitus in rats.

Streptozotocin (45 mg/kg) was intravenously administered to 7-week-old Wistar rats through their tail veins. After 11 days, the rats were divided into two groups. One group was fed a lipid-free diet (90%, w/w) plus lard (8%) and safflower oil (2%) for four weeks (Diet 1 group, n = 12). The other group was fed in the same way, except that safflower oil was replaced by 90% pure eicosapentaenoic acid (EPA) ethyl ester (Diet 2 group, n = 13). Twenty-four-hour urine was collected just before the diets started and during the experiment at 7-day intervals. In the second and third week, the levels of proteinuria were significantly lower in the Diet 2 group than they were in the Diet 1 group. There was no significant difference in the levels of creatinine, urea nitrogen, or lipids in plasma or in body weights between the two groups after four weeks on the diets. Because Diet 2 reduced proteinuria of diabetic rats compared to Diet 1, an EPA-rich diet may retard the development of diabetic nephropathy.

Animals

Urinary excretion of PGI2/3-M and recent N-6/3 fatty acid intake.

Epidemiological studies were performed in a Japanese fishing village when catches of fish were highest and in a Japanese farming village with usual fish consumption. Intake of eicosapentaenoic, docosahexaenoic and also arachidonic acid were significantly higher in the fishing village during the 3 days of the study than in the farming village. The correlation between eicosapentaenoic acid intake on the day when urine was collected and excretion of delta 17-2,3-dinor-6-keto-prostaglandin F1 alpha, the main urinary metabolite of prostaglandin I3, was highly significant, whereas there was no correlation between arachidonic or linoleic acid intake and excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha, the main urinary metabolite of prostaglandin I2. We suggest that the arachidonic acid pool for prostaglandin I2 production is not quickly influenced by dietary linoleic or arachidonic acid because of a large pool size of arachidonic acid and a slow conversion of linoleic acid to arachidonic acid, while prostaglandin I3 formation is directly related to the intake of eicosapentaenoic acid.

6-Ketoprostaglandin F1 alpha

Favorable effects of fish oil concentrate on risk factors for thrombosis in renal allograft recipients.

The incidence of thromboembolic complications in renal allograft recipients is very high. Since fish oil has antithrombotic properties, we administered 18 capsules of fish oil concentrate (1.5 g of eicosapentaenoic acid, EPA, and 0.7 g of docosahexaenoic acid) per day to 14 renal allograft recipients for 6 months. Another group of recipients served as controls. In the treated group the levels of EPA and docosahexaenoic acid in erythrocyte membrane lipids increased significantly after the fish oil treatment. Red blood cell filterability significantly increased in the treated group compared with the case of the control group. Epinephrine-induced platelet aggregation increased significantly in the control group, and this change was significantly different from that of the treated group (almost a null change). At the end of the study, the ratio of the main urinary metabolite of prostacyclin I2/3 to the metabolite of thromboxane A2/3 was significantly higher in the treated group than in the control group. In conclusion, we suggest that fish oil concentrate may favorably affect risk factors for thromboembolic complications in renal allograft recipients.

Adult

Comparison of the increment in plasma eicosapentaenoate concentrations by fish oil intake between young and middle-aged volunteers.

The effect of age on eicosapentaenoic acid (20:5 n-3; EPA) incorporation into plasma lipids was investigated in young volunteers (8 males, 19 +/- 1 yr) and middle-aged volunteers (6 males, 53 +/- 7 yr). They were asked to take 5.4 g fish oil per day for one week. The increment in EPA in the cholesteryl ester fraction after the supplementation was significantly greater in the middle-aged group (delta = 1.69%) than in the young group (delta = 0.44%) (p less than 0.05). The food intake analyzed for 3 consecutive days just before the supplementation revealed that the young group took more linoleate (17 vs. 10 g) than the middle-aged group. There was a significant inverse correlation between the increment in EPA in the cholesteryl ester fraction after the supplementation and daily linoleate intake among all the volunteers combined (r = -0.63, p less than 0.02). The higher increment in EPA in cholesteryl ester in the middle-aged group might be due to less intake of linoleate and not due to the difference in age itself.

Administration, Oral