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Biomedical subjects

T Hamazaki

Publications and source records attributed to T Hamazaki.

At least 55 records · Page 3Linked to original sources
PubMed1996

Docosahexaenoic acid-rich fish oil does not affect serum lipid concentrations of normolipidemic young adults.

Fish oils, purified eicosapentaenoic acid and docosahexaenoic acid (DHA) have been reported to improve blood lipid concentrations, especially those of triglycerides in humans. However, to our knowledge there have been no double-blind studies investigating the effects of DHA-rich fish oil on blood lipid concentrations. Therefore, we conducted a placebo-controlled double-blind study. Twenty-four healthy, normolipidemic young adults took either DHA-rich fish oil capsules containing 1.5-1.8 g of DHA or control oil capsules containing 97% soybean oil and 3% fish oil for 13 wk. Blood samples were taken at the start and end of the study, and serum lipids concentrations were compared. There were no significant changes over time in the DHA group in the following serum lipids: total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, lipoprotein(a), and apolipoproteins A1 and B. In contrast, apolipoprotein A1 concentrations slightly (10%) but significantly increased over time in the control group. Docosahexaenoic acid at a dose of less than 2 g/d did not change serum lipid concentrations of normolipidemic subjects. The effects of DHA in hyperlipidemic patients remain to be investigated in a double-blind study.

Adult↗
PubMed1996

Dietary (n-9) eicosatrienoic acid from a cultured fungus inhibits leukotriene B4 synthesis in rats and the effect is modified by dietary linoleic acid.

Eicosatrienoic acid (ETrA) is the (n-9) homologue of (n-6) arachidonic acid (AA) and (n-3) eicosapentaenoic acid (EPA). ETrA can be synthesized endogeneously, but tissue levels are normally undetectable except in essential fatty acid (EFA) deficiency. An ETrA-rich oil extracted from a cultured fungus was used to prepare diets which had varying levels of ETrA (0-8 g/kg diet) in combination with one of two levels of linoleic acid (LA, 2.2 or 9.5 g/kg diet). All diets were sufficient in essential fatty acids. Groups of rats were fed these diets for 4 wk after which leucocyte fatty acid content and leukotriene B4 (LTB4) synthesis were measured. The influence of dietary LA on ETrA accumulation in cells was studied and correlations with LTB4 synthesis determined. ETrA was efficiently incorporated into peritoneal exudate cell (PEC) phospholipids with no evident saturation being observed with levels up to 10 mol/100 mol total fatty acids in peritoneal exudate cells. Cellular ETrA levels were lower (P < 0.001) in rats fed the higher level of LA. ETrA accumulation in peritoneal exudate cells correlated (r(2) = 0.63, P < 0.05) with reduced LTB4 synthesis which was attributable to LTA hydrolase inhibition. Thus, dietary ETrA from a biological source can accumulate in leucocytes and suppress inflammatory eicosanoid synthesis. The findings justify further studies into the biochemical and anti-inflammatory effects of dietary ETrA, which could be incorporated into palatable food additives.

8,11,14-Eicosatrienoic Acid↗
PubMed1996

[Immunosuppressive effect of intravenously injected docosahexaenoic acid on single lung allotransplantation in the rat].

Docosahexaenoic acid (DHA) is an omega 3 polyunsaturated fatty acid. The purpose of this study was to evaluate the immunosuppressive effect of intravenously injected DHA in rat orthotopically transplanted allograft lung. Based on the results of the post-operative treatment, the recipients were divided into four groups; Group A (n = 3): normal. Group B (n = 3): isotransplantation with no immunosuppressive drugs. Group C (n = 6): allotransplantation with no immunosuppressive drugs. Group D-1 (n = 3): allotransplantation with DHA at a dose of 0.5 g/kg/day x 2 at 0 and 3 post-operative days (POD). Group D-2 (n = 3): allotransplantation with DHA at a dose of 0.5 g/kg/day x 4 at 0, 1, 3 and 5 POD. Group D-3 (n = 6): allotransplantation with DHA at a dose of 0.5 g/kg/day x 4 at 0, 1, 2 and 3 POD. In Groups A and B, F344 rats were used as donor and recipient. In Groups C and D, F344 rats were used as recipient and WKAH rats as donor. Studies on morphology, bronchoalveolar lavage (BAL) and peripheral blood cells were performed at 7 POD after sacrifice. Histological changes in Group D-3 were milder than those in Grop C and D-1, but were more progressive than those in Groups A and B which showed no rejection. Peripheral leukocytes and polymorphonuclear leukocytes counts in Groups D-1, D-2, and D-3 were higher than those in Groups, A, B and C. Total cells and lymphocytes of BAL in Groups D-2 and D-3 were less than those in Group C, but total cells and polymorphonuclear leukocytes of BAL in Groups D-2 and D-3 were more than those in Groups A and B. This study suggested that intravenously injected DHA had an immunosuppressive effect on the allotransplanted lung in the rats.

Animals↗
PubMed1995

Large deletions in the genome of Chlorella virus CVK1.

Large (30-45 kbp) deletions were induced in the Chlorella virus CVK1 genome by UV irradiation. Restriction endonuclease maps of the mutant genomes showed that these deletions occurred in a region located from 1.5 kbp to 47 kbp from the left DNA end. The nucleotide sequences determined around the deletion boundaries indicate that the deletion process took place by both homologous and nonhomologous recombinations. In one case, the recombination site was within a region of about 600 bp, consisting of 40 tandem repetitions of a 15-bp sequence element. The deleted region may contain several multigene families. Northern blot analyses with probes including the genes for translational elongation factor 3 and DNA polymerase showed no discernible aberrancy in the gene expression patterns in the mutants. However, at least two protein bands were missing from the mutant virions.

Base Sequence↗
PubMed1995

Changes in the fatty acid composition of immune cells and plasma by intravenous injection of dihomo-gamma-linolenic acid in mice.

An injectable emulsion of 10% tridihomo-gamma-linolenoyl glycerol (DGLA-TG, 96% pure) was prepared. 0.5 ml of the emulsion was injected into tail veins of 6-week-old C3H/HeSlc mice. They were killed 1, 3, 6, 12 and 24 h after the injection. The fatty acid composition of the phospholipid (PL) fraction of plasma, splenocytes and thymocytes was analysed along with that of control mice. DGLA concentrations increased markedly 1 h after the injection in the plasma (from 2.2% to 13.2%) and splenocyte (from 1.1% to 10.1%) PL fractions; they decreased rapidly thereafter. On the other hand, DGLA concentrations in the thymocyte PL fraction did not increase markedly. These data may be useful for planning animal experiments with DGLA emulsions, should these be developed as an experimental drug in the future.

8,11,14-Eicosatrienoic Acid↗
PubMed1995

Clinorotation inhibits chondrogenesis in micromass cultures of embryonic mouse limb cells.

Studies of the response of mammalian chondrocytes to gravitational changes in vivo, in organ culture, and in cell culture show that chondrogenesis is reduced in microgravity or by unloading, and increased by low levels of excess g. To investigate the cellular responses to microgravity using a ground based model, micromass cultures were exposed to simulated weightlessness on two clinostats. For rotation on the large clinostat, cultures were set up in Rose chambers, and cells were videotaped and photographed at several time periods after rotation began. For the smaller clinostat, cultures were set up in T-flasks, and two axes of rotation for clinostated cultures were used. Stationary controls [+1 g, -1 g (upside-down), and sideways] as well as rotation controls were employed. Rotation rate was 30 rpm for both clinostatted cultures and rotation controls. Chondrocyte differentiation was assessed by cartilage specific alcian blue staining. Significantly fewer alcian blue stained nodules were present in clinostatted cultures than in stationary controls or rotation controls. Nodules that did not stain with alcian blue, probably due to unsulfated matrix were present in all cultures. The number of nodules in sideways controls was greater than in any other culture (108% of +1 g controls), probably due to ongoing stimulus of the cell via cytoskeletal components. The results show that chondrocytes in culture respond to changes in the gravity vector in a predictable manner, and that carefully controlled clinostat studies can be useful adjuncts to and predictors for spaceflight experiments.

Animals↗
PubMed1994

The effect of oral administration of eicosapentaenoic and docosahexaenoic acids on acute inflammation and fatty acid composition in rats.

To investigate effects of eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) on acute inflammation, we fed rats either of the following four diets: an EPA-rich diet for 5 or 15 days, a DHA-rich diet for 5 or 15 days, a control diet for 5 or 15 days, and standard chow for 15 days. At the end of diets, the carrageenan-induced swelling of footpads was measured. Peritoneal cells were analyzed for their fatty acids in the phospholipid fraction. The swelling was similarly reduced in the EPA and DHA groups (p < 0.05, if fed for 15 days) compared with rats fed the control diet for 15 days. The mean proportion of arachidonic acid (AA) to the sum of highly unsaturated fatty acids was correlated (r = 0.87) to the mean degree of swelling among all dietary groups (n = 7). Effects of EPA and DHA might be explained by the reduced availability of AA for eicosanoid formation represented by the proportion of AA.

Animals↗
PubMed1994

Effect of eicosapentaenoic acid ethyl ester on albuminuria in streptozotocin-induced diabetic rats.

Wistar rats (4-week-old) were administered with streptozotocin (45 mg/kg) through tail veins. After 3 months, diabetic rats were divided into 2 groups. One group (EPA group, n = 16) was fed a lipid-free diet (90%, w/w) plus lard (8%) and 90% pure eicosapentaenoic acid ethyl ester (2%) for 6 months. The other group (control group, n = 16) was fed in the same way except that eicosapentaenoic acid ethyl ester was replaced by safflower oil. Twenty-four-hour urine was collected just before starting the experimental diets and during the 6-month experimental period at monthly intervals. There were no differences in food intake and body weight between the two groups throughout the experiment. The mean microalbuminuria of the EPA group became significantly lower than that of the control group after 4 months on the diets through the end of the study (6 months). The mean microalbuminuria levels at the end of the study were 1.38 mg/day in the EPA group (n = 9) and 5.19 mg/day in the control group (n = 6) (p < 0.01). Eicosapentaenoic acid administration might retard the progression of diabetic nephropathy by reducing microalbuminuria.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Suppressive effect of interleukin-4 (IL-4) on IL-6 production by adherent rheumatoid synovial cells.

Interleukin-6 (IL-6) has recently been characterized as a mediator of multiple inflammatory responses. Excessive production of this cytokine has been demonstrated in the joints of patients with rheumatoid arthritis (RA). On the other hand, anti-inflammatory effects of IL-4 have recently been demonstrated. We therefore investigated the suppressive effect of IL-4 on IL-6 production by synovial cells in patients with RA. Freshly prepared adherent rheumatoid synovial cells expressed IL-6 mRNA and spontaneously produced a large amount of IL-6 in culture. This spontaneous production of IL-6 was significantly suppressed by IL-4. The suppressive effect of IL-4 on IL-6 production was demonstrated in all patients with RA tested in this study. On the other hand, IL-6 mRNA levels already expressed in adherent synovial cells were not reduced by IL-4 in 24 hr of culture. The suppressive effect of IL-4 on IL-6 production suggests that IL-4 is an important physiological regulator of IL-6 production in synovial cells.

Adult↗
PubMed1993

Intravenous injection of tridihomo-gamma-linolenoyl-glycerol into mice and its effects on delayed-type hypersensitivity.

Highly purified tridihomo-gamma-linolenoyl-glycerol (DGLA-TG) was emulsified with egg yolk lecithin as a 10% (wt/vol) DGLA-TG emulsion. We injected 0.05 or 0.5 mL of the emulsion into mice through the tail vein and investigated its effects on the fatty acid composition of spleen cells and on delayed-type hypersensitivity (DTH) response. At 1 h after the injection, dihomo-gamma-linolenic acid (DGLA) concentrations were increased significantly in the total phospholipid fraction of spleen cells from 1.21 +/- 0.13 mol% to 2.09 +/- 0.74 mol% (P < 0.02) and 7.95 +/- 1.25 mol% (P < 0.001) in the 0.05-mL and 0.5-mL groups, respectively. Mice, which had already been immunized with sheep red blood cells (SRBC), were challenged by the injection of SRBC into the right-hind footpad. Intravenous injection into mice with 0.5 mL of the emulsion immediately before the challenge almost completely suppressed DTH response measured by the swelling of the right-hind footpads 24 h thereafter. This inhibitory effect on the DTH response was significant with as little as 0.05 mL of the emulsion, whereas a soybean oil emulsion was not effective at all. In conclusion, intravenous injection of a DGLA emulsion increased DGLA concentrations in immune cells within 1 h and suppressed the DTH reaction.

8,11,14-Eicosatrienoic Acid↗
PubMed1993

Intravenous infusion of tridihomo-gamma-linolenoyl-glycerol reduces leukotriene B4 production in the rat and rabbit.

1. We have formulated an infusible emulsion of 10% tridihomo-gamma-linolenoyl-glycerol (94% pure) and investigated the effects of its infusion on leukotriene B4 production. 2. We infused the emulsion into the ear veins of two rabbits in a dose of 0.8g of tridihomo-gamma-linolenoyl-glycerol/kg. Polymorphonuclear leucocytes were obtained from rabbits before the infusion, and 6, 24, 72 and 168 h after. The ionophore-stimulated leukotriene B4 production by polymorphonuclear leucocytes was reduced to about 50% of baseline as early as 6 h after the infusion and remained reduced until 24 h after the infusion. 3. To closely investigate the changes in leukotriene B4 production at 6 h after the infusion, we infused 1.0 g of tridihomo-gamma-linolenoyl-glycerol/kg into the tail veins of eight male Wistar rats. Six hours later, peritoneal macrophages were obtained from four rats for the analysis of ionophore-stimulated leukotriene B4 production. Peritoneal cells and blood samples were also obtained from the remaining rats for fatty acid analysis. Another eight rats were used without prior infusion for baseline determination. 4. The production of leukotriene B4 by macrophages was significantly reduced to 42% of baseline, and the plasma free dihomo-gamma-linolenic acid was markedly increased from 0.26 to 4.82 mol%, in 6 h. 5. We conclude that the infusion of a tridihomo-gamma-linolenoyl-glycerol emulsion is able to decrease leukotriene B4 production and to increase the dihomo-gamma-linolenic acid concentrations in the plasma and peritoneal cells of rats in 6 h.

8,11,14-Eicosatrienoic Acid↗
PubMed1993

Intravenous infusion of tridocosahexaenoyl-glycerol emulsion into rabbits. Effects on leukotriene B4/5 production and fatty acid composition of plasma and leukocytes.

Leukotriene (LT) B4 is a major chemical activator of PMN. Inhibitory effects of oral administration of docosahexaenoic acid (DHA) on LTB4 synthesis by PMN are known. We intravenously infused tridocosahexaenoyl-glycerol (DHA-TG) emulsion into rabbits in three different doses, namely 0.8, 0.4, or 0.2 g DHA/kg, and investigated the changes in LTB4/5 production by ionophore-activated PMN. The averaged LTB4 production by PMN was significantly reduced to 57 and 59% of baseline at 6 h after the infusion of 0.8 and 0.4 g DHA/kg, respectively (P < 0.05), but not after the infusion of 0.2 g DHA/kg or 0.8 g soybean oil/kg. The combined concentrations of both DHA and eicosapentaenoic acid in the PMN phospholipid fraction were significantly increased at 6 h after the infusion of 0.8 or 0.4 g DHA/kg but not after the infusion of 0.2 g DHA/kg or 0.8 g soybean oil/kg. Oral administration of 0.8 g DHA/kg did not increase DHA or eicosapentaenoic acid in the PMN phospholipid fraction and did not decrease LTB4 production by PMN at 6 h after administration. We suggest that the infusion of 0.4-0.8 g DHA/kg might be beneficial to patients who suffer from diseases that are related to the acute elevation of LTB4 production.

Animals↗
PubMed1993

Infusion of EPA and DHA lipid emulsions: effects on heart lipids and tolerance to ischaemia-reperfusion in the isolated rat heart.

The aim of the present study was to examine the effect of acute infusion of lipid emulsions enriched with either docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) on heart lipids, tolerance to infusion and to ischaemia-reperfusion. Isolated rat hearts were subjected to a 10 min lipid infusion period prior to 25 min of total global ischaemia and 30 min of reperfusion. Effects on physiology and metabolism were recorded during infusion and reperfusion. A more than doubled increase of DHA and a 12-fold increase of EPA in terms of relative concentration was demonstrated in the free fatty acid fraction after infusion with the respective triglyceride emulsions, without any profound change in physiology. High levels of DHA were associated with a reduced recovery of left ventricular developed pressure (LVDP) and increased release of lactate dehydrogenase (LDH) during reperfusion, while the hearts infused with the EPA-emulsion showed a recovery comparable to the control group. Heart lipid peroxidation, evaluated by release of thiobarbituric acid reactive substances (TBARS) in effluate, was about 4-fold higher in the DHA-group compared to the EPA-group during start of reperfusion and may in part explain the reduced recovery observed in these hearts. The present study demonstrates enrichment of DHA and EPA in the free fatty acid fraction after a short period of infusion. Protective effects of the emulsions were not found, instead the data indicate harmful effects of DHA during ischaemia-reperfusion. However, the presence of TBARS in this emulsion could have influenced the results.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗