Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 127 records · Page 7Linked to original sources

PubMed1996

Stimulation of the activities of hepatic fatty acid oxidation enzymes by dietary fat rich in alpha-linolenic acid in rats.

The activities of hepatic fatty acid oxidation enzymes in rats fed perilla oil rich in alpha-linolenic acid (alpha-18:3) were compared with those fed saturated fats or safflower oil (the mixture of safflower oil and olive oil, 94:8, w/w) containing the same amount of polyunsaturated fatty acids with perilla oil exclusively as linoleic acid (18:2). When the rats were fed the diets containing 15% coconut, safflower, and perilla oils for 1 week, the rate of mitochondrial and peroxisomal oxidation of palmitoyl-CoA (16:0-CoA) in the liver homogenates was the highest in rats fed perilla oil. Among the rats fed the diets containing 15% palm, safflower, and perilla oils for 2 weeks, the rates of mitochondrial and peroxisomal oxidations of 16:0-, 18:2-, and alpha-18:3-CoAs were the highest in rats fed perilla oil, and the rate of oxidation of alpha-18:3-CoA by both pathways was higher than those of other acyl-CoAs in all groups. Dietary perilla oil relative to palm and safflower oils significantly increased the activities of carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, and 2,4-dienoyl-CoA reductase. The substrate specificity of carnitine palmitoyltransferase appeared to be responsible for differential rates of the mitochondrial oxidation of acyl-CoAs. The substrate specificity of acyl-CoA oxidase did not account for the preferential peroxisomal oxidation of alpha-18:3 relative to 18:2. The preferential mitochondrial and peroxisomal beta-oxidation of alpha-18:3-CoA relative to 16:0- and 18:2-CoAs was also confirmed in rats fed laboratory chow irrespective of the substrate/albumin ratios in the assay mixture. It was suggested that both substrate specificities and alterations in the activities of the enzymes in beta-oxidation pathway play a significant role in the regulation of the serum lipid concentrations in rats fed a diet rich in alpha-18:3.

Acyl-CoA Dehydrogenases↗

PubMed1996

Rice bran oil and human health.

The available data in humans suggest that rice bran oil (RBO) is an edible oil of preference for improving plasma lipid and lipoprotein profiles similar to more commonly used vegetable oils. The observation that blending RBO with safflower oil at a specific proportion magnifies the hypocholesterolemic efficacy is of particular interest with regard to utilization of this oil. The occurrence of peculiar components such as gamma-oryzanol and tocotrienols in RBO might be responsible for its hypocholesterolemic effect.

Anticholesteremic Agents↗

PubMed1996

Lymphatic transport of alpha-, gamma- and delta-tocotrienols and alpha-tocopherol in rats.

Lymphatic transport of alpha-, gamma- and delta-tocotrienols and alpha-tocopherol was measured in thoracic duct-cannulated rats. Animals were administered 3 ml of a test emulsion containing 200 mg sodium taurocholate, 50 mg fatty acid free-albumin, 200 mg fat and 100 mg of a mixture of tocotrienols and alpha-tocopherol (Exp. 1) or 10 mg of purified alpha-, gamma- or delta-tocotrienol or alpha-tocopherol (Exp. 2) through a gastric tube. Quantitative lymphatic recovery of oleic acid given as triolein was obtained in these experimental conditions. The 24-hours recovery of tocotrienols and alpha-tocopherol were 10-20% of the administered dose in Exp. 1. The recovery of alpha-tocotrienol was about 2-times higher than that of alpha-tocopherol, while that of gamma- and delta-tocotrienols was intermediate between these two alpha-forms. In Exp. 2, where these compounds were administered individually, the 24 hours recovery ranged from 22 to 37% of the administered dose. Again, the recovery of alpha-tocotrienol was significantly higher than that of the other tocotrienols and alpha-tocopherol, while that of gamma- and delta-tocotrienols and alpha-tocopherol was comparable. Thus, the results show the preferential absorption of alpha-tocotrienol compared to gamma- and delta-tocotrienols and alpha-tocopherol.

Animals↗

PubMed1995

Inhibitory effect of plasma FKBP12 on immunosuppressive activity of FK506.

To evaluate the roles of extracellular FKBP12, we examined the effect of extracellular FKBP12 on the immunosuppressive activity of FK506 in vitro and clinically. The ability of FK506 to suppress phytohemagglutinin-induced proliferative response of human peripheral blood mononuclear cells was inhibited in the presence of recombinant FKBP12 dose-dependently. We measured plasma levels of FKBP12 using a newly developed enzyme-linked immunosorbent assay system in 34 patients receiving FK506 after liver transplantation. In 7 patients with acute cellular rejection, plasma FKBP12 increased significantly at the onset of rejection compared with 1 week before onset (P < 0.05) and further increased to or remained at more than 250 ng/ml 1 week after onset. In 22 of 27 patients without acute cellular rejection, plasma FKBP12 was less than 70 ng/ml during the 4 weeks after transplantation. In the other 5 of 27 patients without acute cellular rejection, plasma FKBP12 exceeded 250 ng/ml. Rapid increase of plasma FKBP12 was observed in only one of these 5 patients, at the onset of high fever due to a liver abscess. There was no significant difference in whole blood trough levels of FK506 between the patients with or without acute cellular rejection. These results suggest that the rapid increase in plasma levels of FKBP12 may contribute to the occurrence and progress of acute cellular rejection probably by inhibiting the immunosuppressive activity of FK506.

Adolescent↗

PubMed1995

Digestion and lymphatic transport of eicosapentaenoic and docosahexaenoic acids given in the form of triacylglycerol, free acid and ethyl ester in rats.

Lymphatic transport of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids given as trieicosapentaenoyl glycerol (TriEPA) and tridocosahexaenoyl glycerol (TriDHA) was compared with that of ethyl ester and free acid in rats cannulated with thoracic duct. Trioleoylglycerol (TO) served as a control. EPA and DHA, compared with oleic acid, were slowly transported in lymph irrespective of fat types administered. Total 24-h recovery of DHA in all fat types and ethyl EPA was significantly lower compared to that of oleic acid. Lymphatic recovery of EPA and DHA in rats given TriEPA and TriDHA was significantly higher at the first 3 h after the administration compared to those given as free acid or ethyl ester. The recovery in rats given free acid at a later stage (9-24 h) was higher than that of the other fat types. As a result, the 24-h recovery was comparable between triacylglycerol (TAG) and free acid, while it was significantly lower in ethyl ester. Although TriEPA and TriDHA were slowly hydrolyzed by pancreatic lipase in vitro compared with TO and TAGs rich in EPA or DHA at the second position, the hydrolysis rate at 60 min incubation was comparable among the TAGs examined. The hydrolysis rate of ethyl esters was extremely low even in 6 h incubation with lipase. These observations show that presence of EPA and DHA at the 1- and 3-positions of TAGs does not result in their lower recovery in lymph. Processes after lipolysis may be responsible for their low recovery in lymph. In a separate study, slower lymphatic recovery of DHA given as free acid than TriDHA was improved by the simultaneous administration of TO, but not by free oleic acid. The observations suggest that the slow recovery of free acid is caused by delayed TAG synthesis in mucosal cells and/or low micellar solubility of fatty acids in the intestinal lumen due to a limited supply of 2-monoacylglycerol (MAG). A large portion of EPA and DHA were recovered in lymph chylomicrons and very low density lipoproteins (VLDL, > 95%) and incorporated into TAG (84-92%) fraction in all fat types examined. Lymphatic recovery rate of simultaneously administered cholesterol was influenced by the fat types given.

Animals↗

PubMed1995

Changes in lymphocyte beta 2-adrenoceptors after hepatic resection.

Hepatic resection promotes such a high degree of surgical stress that it induces deterioration of various vital functions, which may involve the breakdown of signal transduction systems. To investigate the influence of surgical stress on signal transduction, we studied ligand-receptor specific binding activity after hepatic resection, focusing on lymphocyte beta 2-adrenoceptors. The maximum binding capacity (Bmax) and the dissociation constant (KD) were determined by radioligand binding assay using (-)3H-CGP12177 as a ligand. In the hepatectomy group, Bmax significantly decreased from 1380 +/- 109 to 799 +/- 49 receptors/cell on postoperative day (POD) 3 and to 802 +/- 93 receptors/cell on POD 7 (P < 0.05). In the control group, however, it did not significantly change after the operation. No significant changes in KD were found in either of these groups. The Bmax alteration was not due to the redistribution of lymphocyte subsets or receptor down regulation, but to the decrease in the Bmax of the individual subset. The hepatectomy group was divided into two groups according to the postoperative arterial ketone body ratio (AKBR): Group A, AKBR maintained at 0.7 or more; and Group B, AKBR decreased to below 0.7. The Bmax decrease, a percentage of the preoperative value, of Group B was significantly smaller than that of Group A (48.4 +/- 3.9 and 72.3 +/- 7.3%, respectively, P < 0.05). These results suggest that intense surgical stress, produced by hepatic resection, may influence even ligand-receptor binding parameters, and the decrease in AKBR can indicate the magnitude of surgical stress.

Adrenergic beta-Antagonists↗

PubMed1995

The ratio of reduced glutathione/oxidized glutathione is maintained in the liver during short-term hepatic hypoxia.

Controversy persists as to whether reperfusion-induced injuries actually occur in the hepatocyte. The liver is the major source of glutathione, a scavenger of hydrogen peroxide. The aim of this study was to evaluate the sensitivity of the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) [GSH:GSSG] as an index of hepatic metabolic stress. A total of 121 rats were studied. The superior mesenteric vein (SMV) was occluded for 30 min, and this was followed by 0, 10, or 120 min of reperfusion. Total glutathione and GSSG levels in the liver, bile, and plasma were quantified, using glutathione reductase-coupled enzymatic assays. Results indicated that the hepatic GSH/GSSG ratio was maintained after an occlusion of the SMV, despite a decrease in adenosine triphosphate (ATP) level and energy charge potential. However, plasma levels of total glutathione and GSSG in the inferior vena cava increased after SMV occlusion and continued to increase after reperfusion. Biliary GSSG efflux decreased during 30-min occlusion of the SMV, and remained low even after reperfusion. The liver maintains homeostasis despite a decrease in biliary GSSG efflux, probably by secreting excess GSSG into the hepatic vein when the SMV is occluded. We conclude that the total amount of glutathione and GSSG in the plasma is directly correlated with oxidative stress in the liver.

Animals↗

PubMed1995

Oxidized cholesterol modulates age-related change in lipid metabolism in rats.

For three weeks, male Sprague-Dawley rats at either four weeks (young) or eight months (adult) of age were pair-fed one of the purified diets free of or containing either 0.2% of oxidized cholesterol mixture (cholesterol oxidation products) or 0.2% of cholesterol. Although the food intake was similar, dietary oxidized cholesterol lowered body weight gain in young rats, but did not increase relative liver weight, in contrast to the enlargement seen with dietary cholesterol. Oxidized cholesterol, compared to cholesterol, tended to reduce the activity of hepatic 3-hydroxy-3-methylglutaryl CoA reductase and cholesterol 7 alpha-hydroxylase, particularly the latter in aged rats, and prevented the rise in the concentration of liver cholesterol at both ages. It also tended to increase the activity of hepatic delta 6 desaturase, particularly in young rats. Moreover, oxidized cholesterol in relation to cholesterol influenced liver and serum lipid concentrations in different ways, and increased lipid peroxidation at both ages. The ratio of splenic CD4+/CD8+ T-lymphocytes increased with age, but the influence of cholesterol and oxidized cholesterol was comparable. Thus, oxidized cholesterol may specifically disturb growth and age-related changes in the lipid metabolism in rats.

Aging↗

PubMed1995

Effects of randomization of partially hydrogenated corn oil on fatty acid and cholesterol absorption, and tissue lipid levels in rats.

Randomization of partially hydrogenated corn oil containing approximately 45% of trans octadecenoic acid only slightly, but not significantly, increased the lymphatic fatty acid absorption in rats. No effect of randomization was observed on cholesterol absorption. When rats were fed these fats at the 8.8% level (with 1.2% safflower oil) for three weeks, the concentrations of serum cholesterol, and serum and liver phospholipid were significantly higher in randomized fat than in control fat, which was composed of 9% high-oleic safflower oil and 1% palm oil. Liver cholesterol tended to be higher in randomized fat. In contrast, nonrandomized fat was not hyperlipidemic compared to control fat. Although the fatty acid composition of liver phospholipids suggested a possible interference of trans fatty acid with the metabolism of linoleic acid to arachidonic acid, there was no effect of randomization. In the two hydrogenated fat groups, trans octadecenoic acid was incorporated and distributed similarly in adipose tissue triacylglycerol. These observations indicated that randomization of partially hydrogenated fat is not beneficial to various lipid parameters in rats.

Absorption↗

PubMed1995

Octadecatrienoic acids as the substrates for the key enzymes in glycerolipid biosynthesis and fatty acid oxidation in rat liver.

The activities of key enzymes in glycerolipid biosynthesis and fatty acid oxidation were compared using CoA esters of naturally occurring positional isomers of octadecatrienoic acids (18:3) as the substrates. The trienoic acids employed were 9,12,15-18:3 (alpha-18:3), 6,9,12-18:3 (gamma-18:3), and 5,9,12-18:3 (pinolenic acid which is a fatty acid contained in pine seed oil, po-18:3). The activities of microsomal glycerol 3-phosphate acyltransferase obtained with various 18:3 were only slightly lower than or comparable with those obtained with palmitic (16:0), oleic (18:1), and linoleic (18:2) acids. Mitochondrial glycerol 3-phosphate acyltransferase was exclusively specific for saturated fatty acyl-CoA. The activities of microsomal diacylglycerol acyltransferase measured with various polyunsaturated fatty acyl-CoAs were significantly lower than those obtained with 16:0- and 18:1-CoAs. Among the polyunsaturated fatty acids, gamma-18:3 gave the distinctly low activity. The Vmax values of the mitochondrial carnitine palmitoyltransferase I were significantly higher with alpha-18:3 and po-18:3 but not gamma-18:3, than with 16:0 and 18:2, while the apparent Km values were the same irrespective of the types of acyl-CoA used except for the distinctly low value obtained with gamma-18:3. The response to an inhibitor of the acyltransferase reaction, malonyl-CoA, was appreciably exaggerated with 18:2, alpha-18:3, and po-18:3 more than with 16:0 and 18:1. However, the response with gamma-18:3 was the same as with 16:0. Thus, some of glycerolipid biosynthesis and fatty acid oxidation enzymes could discriminate not only the differences in the degree of unsaturation of fatty acids but also the positional distribution of double bond among the naturally occurring 18:3 acids.

Acyltransferases↗

PubMed1995

Quantitation of hepatitis C viral RNA in liver and serum samples using competitive polymerase chain reaction.

AIMS: To investigate whether the amount of hepatitis C viral RNA (HCV-RNA) in liver and serum can predict the effectiveness of interferon treatment in patients with chronic hepatitis C. METHODS: The amount of HCV-RNA in frozen liver tissues and sera of 22 patients with chronic hepatitis C was determined before and after interferon alfa treatment by the competitive reverse transcriptional polymerase chain reaction method. RESULTS: Patients with small amounts of HCV-RNA in serum before treatment showed a significantly more effective response to interferon treatment. After treatment, HCV-RNA disappeared from both the liver and serum of all patients who sustained complete response (n = 11); in contrast, HCV-RNA decreased but persisted in the liver of all those who relapsed after cessation of treatment (n = 11). CONCLUSIONS: The elimination of hepatitis C virus from the liver as well as from the serum seems to be essential for sustained remission. The quantitation of HCV-RNA in liver biopsy specimens obtained after treatment would be a highly accurate predictor of whether relapse is likely to occur.

Base Sequence↗

PubMed1995

Differential effects of geometrical isomers of octadecadienoic acids on ketogenesis and lipid secretion in the livers from rats fed a cholesterol-enriched diet.

The effect of cis,cis (cc)- and trans,trans (tt)-9,12-octadecadienoic (18:2) acids on ketogenesis and lipid secretion was compared in isolated perfused livers from cholesterol-fed rats. The hepatic uptake of 18:2 acids was comparable in both isomers. The livers perfused with cc-18:2 acid in comparison with those perfused without fatty acid substrate produced approximately 4-fold more ketone bodies accompanying the rise of the beta-hydroxybutyrate:acetoacetate ratio, while the tt-acid isomer further increased these parameters. The hepatic secretion rates of triglyceride and phospholipid as well as cholesterol were all elevated on perfusing the cc-18:2 acid as compared to without fatty acid. In contrast, the rates observed with the tt-18:2 acid isomer except for phospholipid were intermediate, indicating a reciprocal response in ketogenesis and lipid secretion by the trans isomer. The rate of incorporation of trans-fatty acid into perfusate triglyceride and cholesterol ester were lower than cis-acid, but vice versa into perfusate phospholipids. On the other hand, the effects of trans-fatty acid on the concentration and composition of hepatic lipids were less clear. These results emphasize the differential effect of geometrical isomers of the 18:2 acids on oxidation and esterification even in the livers containing a high level of cholesterol.

3-Hydroxybutyric Acid↗

PubMed1995

Effects of sesamin and alpha-tocopherol, individually or in combination, on the polyunsaturated fatty acid metabolism, chemical mediator production, and immunoglobulin levels in Sprague-Dawley rats.

Feeding sesamin and alpha-tocopherol in combination, both at the 0.5% dietary level, to Sprague-Dawley rats for 3 weeks resulted in a trend toward decreasing the proportion of 20:4n-6 and 22:5n-6 and increasing that of 18:2n-6 in phosphatidylcholine from various tissues, suggesting interference with the metabolism of linoleic acid. This dietary manipulation significantly reduced the production of leukotriene C4 in the lung, the splenic production of leukotriene B4, and reduction of the plasma histamine level. Simultaneous administration of sesamin and alpha-tocopherol significantly increased the production of IgA, IgG, and IgM by mesenteric lymph node lymphocytes, while the IgE level tended to be reduced. These effects were not necessarily apparent by feeding these compounds separately. Thus, sesamin and alpha-tocopherol in combination would be effective for regulating the eicosanoid production and modifying the immune function.

Animals↗

PubMed1995

Free bile acids inhibit IgE production by mouse spleen lymphocytes stimulated by lipopolysaccharide and interleukins.

The interaction of IL-4, IL-5, and free bile acids with the immunoglobulin production by mouse spleen lymphocytes was studied to examine their immunoregulatory activity. In the absence of lipopolysaccharide (LPS), IL-4 enhanced the IgE and IgG production significantly and the IgA production weakly, but not the IgM production. On the other hand, IL-5 had an inhibitory tendency on the IgE and IgA production, though not significantly. In the presence of LPS, both IL-4 and IL-5 significantly enhanced the IgE production by mouse splenic lymphocytes. When the lymphocytes were cultured with the physiological concentration of free bile acids (10 microM) and LPS for 3 days, chenodeoxycholic acid inhibited the IgE production, but cholic and deoxycholic acids did not. In the presence of IL-4 or IL-5, these bile acids cancelled the stimulatory effects of interleukins and rather significantly inhibited the IgE production. These results suggest that these free bile acids act as an anti-allergic agent.

Animals↗

PubMed1995

Systemic release of mucosal mast-cell protease in primed brown Norway rats after feeding with beta-lactoglobulin.

The plasma level of mucosal mast-cell protease was examined to find whether such measurements could be an indicator of allergic response to beta-lactoglobulin (beta-LG) challenged orally by rats. Brown Norway rats, which had been raised on a bovine milk-free diet, were systemically sensitized on day 0 with a low dose of beta-LG, and then by an oral administration of beta-LG for 3 h on day 14. The oral challenge with beta-LG in saline, when compared to saline alone, resulted in a systemic elevation of rat mast-cell protease II (RMCPII), one of the specific markers for gut mucosal mast-cell secretion. The challenge with beta-LG in a fat emulsion further increased the level of plasma RMCPII. This manipulation, however, was not successful for detecting any significant difference in mucosal leucotriene C4, another allergic mediator. An oral challenge with polymerized beta-LG did not induce any elevation of the protease, but resulted in a lower plasma level of beta-LG-specific IgG. This animal model is thus relevant to investigate the events regulating the mucosal hypersensitivity and humoral immunity to food proteins.

Administration, Oral↗

PubMed1995

Effects of human menopausal gonadotrophin (hMG) for superovulation in Japanese Black cattle.

Sixty-four Japanese Black parous cows were divided into 5 dosage groups (I, II, III, IV, V) and administered either human menopausal gonadotrophin (hMG) or FSH by intramuscular injection. No significant differences were observed between the hMG-treated groups. The average number of recovered ova/embryos in cows treated with 900 IU was significantly greater (P < 0.05) than in cows treated with FSH. The percentage of high-quality transferable embryos was highest in the 600 IU hMG-treated group. Also, FSH-treated cows produced a significantly larger number of unfertilized ova compared to hMG-treated cows. The results suggest that hMG treatment is sufficient for Japanese Black Cattle at a dose of 600 IU for 3 days, and that a 2-day treatment regime is also possible.

Animals↗

PubMed1995

Antihypercholesterolemic effect of undigested fraction of soybean protein in young female volunteers.

The significant antihypercholesterolemic effect of the undigested high molecular fraction (HMF) of soybean protein is known in rats, but such an effect has not been shown in humans. The present two experiments were designed to elucidate it in humans. Subjects were female university students who had relatively high serum cholesterol levels for their age. In Experiment 1, subjects took 8% of their total energy from casein, soybean protein isolate (SPI), or HMF daily for 14 days. Five basic menus and snacks were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. The HMF group showed decreased low-density lipoprotein cholesterol (LDL-C) as compared to other groups. In Experiment 2, subjects took 4% of total energy from casein or HMF daily for a menstruation period. Five basic menus and snacks which contained two egg yolks (about 500 mg cholesterol) were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. A decrease in LDL-C and an increase in high-density lipoprotein cholesterol (HDL-C) were observed in the HMF group as compared to the casein group. Fecal acidic steroid excretion was greater in the HMF group than in the casein group (p < 0.05). The results confirmed that HMF increases fecal steroid excretion and reduces serum cholesterol levels in humans.

Adult↗

PubMed1995

Repression of fat-dependent intestinal apo A-IV mRNA abundance by medium chain triacylglycerols and proteins, and elevation by carbohydrates of fat-dependent apo A-IV transport in suckling rat pups.

Nutrients regulating intestinal apo A-IV synthesis and secretion in developing rats have not been clearly defined. We examined the effect of ingestion of fats, carbohydrates and proteins on the abundance of intestinal apo A-IV mRNA and the serum concentration of apo A-IV in 14-day-old suckling rat pups fasted overnight. In pups ingesting long-chain fatty acid-fat (soybean oil, triolein: LCT), there was a prompt elevation of the mRNA at 1.5 h after ingestion, although a graded dose of soybean oil did not result in a comparable elevation of the apo A-IV mRNA. In pups on MCT, but not trilaurin, there was a repression of the LCT-dependent elevation of the message. In pups on Intralipid (composed of soybean oil, lecithin and glycerol), mRNA was elevated at 6 h after ingestion. Administration of Intralipid with lactose, glucose, fructose and sucrose induced a rapid elevation of mRNA together with elevation of serum apo A-IV, although administration of casein, whey proteins and soybean proteins resulted in repression of the Intralipid-dependent mRNA elevation. The message correlated weakly to the serum apo A-IV and triacylglycerols and with no correlation to intestinal fat accumulation. These results suggest that metabolic events following the ingestion of milk components modulate intestinal apo A-IV expression in developing rats, possibly through mucosal fatty acid utilization.

Animals↗