Phomactin E, F, and G: new phomactin-group PAF antagonists from a marine fungus Phoma sp.
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Epoxy Compounds↗
Biomedical subjects
M Sugano
Publications and source records attributed to M Sugano.
alpha-Tocopherol enhances the hypocholesterolemic action of sesamin in rats.
The effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was examined in rats given a cholesterol-enriched diet. When different levels (0.05 and 0.2%) of sesamin were fed, the supplementation of 1% alpha-tocopherol significantly accentuated the hypocholesterolemic action of sesamin, particularly with the higher sesamin level, although alpha-tocopherol alone did not affect the concentration of serum cholesterol. The dose-dependent promoting effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was confirmed by supplementing different levels (0.2 and 1%) of alpha-tocopherol to a fixed level of sesamin (0.2%). alpha-Tocopherol was still effective at the 0.2% level. The metabolism of sesamin in the liver S9 fraction appeared to be interfered with alpha-tocopherol in vitro, suggesting a possible role of alpha-tocopherol in maintenance of the availability of sesamin.
Animals↗
Lymphatic absorption of oxidized cholesterol in rats.
The absorption of cholesterol and of cholesterol oxidation products (oxidized cholesterols) was compared in lymph-cannulated rats. We found that the lymphatic absorption of an intragastrically administered, emulsified lipid meal containing 25 mg of cholesterol or 25 mg of oxidized cholesterols, within 24 h, was approximately 67 and 30%, respectively. The absorption rate of individual oxidized cholesterols differed considerably and was approximately 30% for 7 alpha-hydroxycholesterol, 42% for 7 beta-hydroxycholesterol, 32% for 5 beta-epoxycholesterol, 28% for 5 alpha-epoxycholesterol, 15% for cholestanetriol and 12% for 7-ketocholesterol. Moreover, cholesterol oxidation products delayed the absorption of oleic acid as triolein. Approximately 35 and 48% of cholesterol was recovered in chylomicrons (CM) and very low density lipoprotein (VLDL), respectively. In contrast, 54 and 40% of the oxidized cholesterols was recovered in CM and VLDL, respectively, although there was a significant difference in the distribution of individual oxidized cholesterols. The results of the present study indicate that oxidized cholesterols are absorbed to a lesser extent than is cholesterol, that they disturb fat absorption and that they distribute differently between lymphatic lipoproteins.
Absorption↗
Effects of bile acids and lectins on immunoglobulin production in rat mesenteric lymph node lymphocytes.
We investigated the effect of bile acids either alone or in combination with lectins on immunoglobulin (Ig) production in vitro of rat mesenteric lymph node (MLN) lymphocytes to examine their immunoregulatory activities. Among free bile acids examined, chenodeoxycholic acid stimulated IgE production by MLN lymphocytes and inhibited IgA production at the concentration of 0.3 mM, whereas cholic and deoxycholic acids exerted the comparable effect at 3 mM. Among conjugated bile acids, deoxycholic acid derivatives stimulated IgE production more strongly than cholic acid derivatives. On the other hand, free and conjugated bile acids did not affect IgG production. The IgE production by MLN lymphocytes was stimulated by concanavalin A and inhibited by pokeweed mitogen, and the effect of phytohemmagglutinin and lipopolysaccharide was marginal. These lectins did not affect IgA and IgG production by the lymphocytes. In the presence of lectins, free bile acids affected IgE production at 0.03 mM. These results suggest the possibility that bile acid is a stimulant for food allergy.
Animals↗
Identification of an active principle in essential oils and hexane-soluble fractions of Curcuma xanthorrhiza Roxb. showing triglyceride-lowering action in rats.
Curcuma xanthorrhiza Roxb. (C. xanthorrhiza), known as temu lawak or Javanese turmeric, has been traditionally used in Indonesia for food and medicinal purposes. As little attention has been focused on the role of C. xanthorrhiza in lipid metabolism, the hypotriglyceridaemic activity and the active principles of the essential oil and hexane-soluble fractions prepared from C. xanthorrhiza were investigated in rats. The major component (approx. 65%) of the essential oil was identified as alpha-curcumene by capillary gas chromatography/mass spectrometry. Addition of essential oils (0.02%), prepared by steam distillation, to a purified diet resulted in a lower hepatic triglyceride concentration without influencing the serum triglyceride, whereas addition of the hexane-soluble fraction (0.5%) resulted in a lower concentration of serum as well as liver triglycerides. Rats fed the essential oil and hexane-soluble fraction had lower hepatic fatty acid synthase activity. The fraction containing alpha-curcumene, prepared from the hexane-soluble fraction by silica gel column chromatography, suppressed the synthesis of fatty acids from [14C]acetate in primary cultured rat hepatocytes. Thus, alpha-curcumene is one of the active principles exerting triglyceride-lowering activity in C. xanthorrhiza.
Animals↗
Living related liver transplantation in children.
We reviewed 37 living related liver transplantations (LRLT) performed by our department during the last 27 months on children with end-stage liver disease. The patients were 15 boys and 22 girls aged 7 months to 15 years with biliary atresia (27), cryptogenic cirrhosis (3), Budd-Chiari syndrome (2), progressive intrahepatic cholestasis (2), protoporphyria (1), Wilson's disease (1), and fulminant hepatitis (1). The donors were 14 fathers and 23 mothers. Grafts were made from the left lateral segment (19), left lateral segment with partial S4 (11), left lobe (6), and right lobe (1). After graft harvesting all donors resumed normal liver function and normal life. The recipient underwent total hepatectomy with preservation of the inferior vena cava. FK506 and low-dose steroids were used for immunosuppression. The survival rate was 90% (27/30) in elective cases and 57% (4/7) in emergency cases. Six recipients had functioning grafts but died of extrahepatic complications. Hepatic vein stenosis occurred in 3 cases at 3 months after LRLT and was successfully treated by balloon dilatation. Portal vein stenosis occurred in 1 case at 8 months after LRLT and was also safely dilated. We incurred no hepatic artery thrombosis after introducing microsurgery techniques. Among 12 viral, 5 bacterial, and 3 fungal postoperative infections, 1 Candida pneumonia and 1 EBV-associated lymphoma were lethal. Three patients with ABO-blood group compatible grafts and one with an incompatible graft developed acute rejection, which was controlled in evey case by steroid bolus and/or increasing the dose of FK506. There were no definite episodes of rejection in ABO-identical cases. Children with moderate growth retardation (> or = -1.5 SD of normal growth) caught up in growth soon after LRLT, but those with severe retardation (<-1.5 SD) were slow to attain age-normal height. Appropriate timing, meticulous surgical procedures, and comprehensive management of complications are crucial for successful outcome with LRLT. LRLT is a promising option for alleviating the shortage of livers for pediatric transplantation and may be regarded as an independent modality to supplement cadaver donation.
Acute Disease↗
Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA.
A series of Human Immunodeficiency Virus type-1 protease (HIV-1 PR) inhibitors that contain 3-amino-2-hydroxy-4-phenylbutanoic acid (AHPBA) at the scission site of the substrate were prepared and evaluated for their inhibitory activity. Preliminary studies on the chain length of inhibitors and the hydroxyl configuration of AHPBA indicated that small (2S,3S)-derivatives, composed of the regions between the P3 and P2' sites, showed enough inhibitory activity toward HIV-1 PR to become prototypes for further structural modification. Systematic replacement at the sites from P3 to P2' revealed that some bicyclic heteroarylcarbonyl derivatives possessed strong potency and good enzyme selectivity.
Amino Acid Sequence↗
Dietary modifications of the biliary bile acid glycine:taurine ratio and activity of hepatic bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1) in the rat.
Effects of dietary manipulations on the biliary bile acid glycine:taurine (G:T) ratio and the activity of hepatic bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1) in the post-mitochondrial fraction of liver homogenates were examined in the rat. The G:T ratio in rats fed on the diet containing 100 g pectin/kg (2.18) was markedly higher than that in the animals fed on the diet containing 100 g cellulose/kg (0.09). The diets containing either 10 g cholesterol/kg or 5 g sodium cholate/kg, especially the latter, also increased the G:T ratio (0.77 and 2.33 respectively) compared with a control diet free of these steroids (0.34). When the saturating concentrations of taurine (20 mM) and glycine (100 mM) were the substrates, dietary pectin relative to cellulose significantly increased the activity of both taurine- and glycine-dependent bile acid-CoA:amino acid N-acyltransferase, but neither dietary bile acid nor cholesterol influenced it. In spite of the marked difference in the G:T ratio among the rats given various types of experimental diet, the bile acid-CoA:amino acid N-acyltransferase reaction produced taurine-but little glycone-conjugated bile acid when both taurine and glycine coexisted at physiological concentration ranges in the assay media. Dietary manipulations modified the hepatic taurine concentrations and the changes were inversely correlated with those in the G:T ratio. However, hepatic concentration of taurine (1.67-4.82 mumol/g) in rats given various types of experimental diet was comparable with or even higher than the reported Michaelis constant (Km) value of N-acyltransferase for this compound (0.8-2.5 mM).(ABSTRACT TRUNCATED AT 250 WORDS)
Acyltransferases↗
Influence of Korean pine (Pinus koraiensis)-seed oil containing cis-5,cis-9,cis-12-octadecatrienoic acid on polyunsaturated fatty acid metabolism, eicosanoid production and blood pressure of rats.
The effects of dietary Korean pine (Pinus koraiensis)-seed oil containing a peculiar trienoic acid (cis-5,cis-9,cis-12-18:3, pinolenic acid, approximately 18%) on various lipid variables were compared in rats with those of flaxseed (Linum usitatissimum L.) oil, safflower (Carthamus tinctorius L.) oil and evening primrose (Oenothera biennis L.) oil under experimental conditions where the effects of different polyunsaturated fatty acids could be estimated. In Sprague-Dawley rats fed on diets containing 100 g fat and 5 g cholesterol/kg, the hypocholesterolaemic activity of pinolenic acid was intermediate between alpha-linolenic and linoleic acids. Analysis of the fatty acid composition of liver phosphatidylcholine indicated that, in contrast to alpha-linolenic acid, pinolenic acid does not interfere with the desaturation of linoleic acid to arachidonic acid. However, the effects on ADP-induced platelet aggregation and aortic prostacyclin production were comparable. When spontaneously hypertensive rats were fed on diets containing 100 g fat/kg but free of cholesterol, gamma-linolenic and pinolenic acids, as compared with linoleic acid, increased prostacyclin production and tended to reduce platelet aggregation. In addition, pinolenic acid attenuated the elevation of blood pressure after 5 weeks of feeding. Thus, the results of the present studies indicate the beneficial effects of pinolenic acid on various lipid variables.
Animals↗
Lack of influence of low blood cholesterol levels on pancreatic carcinogenesis after initiation with N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters.
The effects of a cholesterol-free diet, a cholesterol-free diet supplemented with sesamin, and a diet supplemented with sesamin on pancreatic carcinogenesis of N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in 140 female Syrian golden hamsters. BOP (70 and 20 mg/kg body wt) was injected s.c. twice at an interval of 2 weeks at the beginning of the experiment. Starting 3 weeks thereafter, the animals were maintained on basal diet, cholesterol-free diet, basal diet plus sesamin, or cholesterol-free diet plus sesamin for a further 15 weeks. All surviving hamsters were killed at week 18, and the pancreatic tissues examined histologically. The incidences of pancreatic neoplastic and preneoplastic lesions in each group did not show any statistically significant variation. The cholesterol-free diet significantly decreased the cholesterol contents of the serum, pancreas and liver, and sesamin supplement significantly decreased the cholesterol contents of the serum and liver. Both the cholesterol-free diet and sesamin decreased the serum lipoperoxide levels. The results thus indicated that low cholesterol per se and sesamin exert no significant influence on BOP-initiated pancreatic carcinogenesis in hamsters, at least within the 4 month period after carcinogen treatment.
Animals↗
alpha-Linolenic, eicosapentaenoic and docosahexaenoic acids affect lipid metabolism differently in rats.
Rats were fed purified diets containing 10% fat with constant (n-6):(n-3) polyunsaturated fatty acids [(n-6):(n-3); 2.3-2.6] and polyunsaturated:saturated fatty acids (1) ratios. This was obtained with alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid added at 1 g/100 g diet. Eicosapentaenoic acid and docosahexaenoic acid were added as the ethyl esters. The concentration of plasma cholesterol in rats fed docosahexaenoic acid was significantly lower than in those fed alpha-linolenic acid. The concentration of plasma triglyceride was significantly lower in rats fed eicosapentaenoic acid than in those fed docosahexaenoic acid. Docosahexaenoic acid significantly reduced hepatic cholesterol compared with alpha-linolenic acid and eicosapentaenoic acid. Both eicosapentaenoic acid and docosahexaenoic acid decreased hepatic triglyceride compared with alpha-linolenic acid, but this effect was more pronounced in the docosahexaenoic acid group. There was no significant difference in fecal excretion of neutral and acidic steroids and apparent fat absorption. In rats fed docosahexaenoic acid, the proportion of arachidonic acid in liver microsomal phosphatidylcholine was lower than in those fed eicosapentaenoic acid. The same tendency was observed in plasma, platelet and aortic phosphatidylcholine and liver microsomal phosphatidylethanolamine and phosphatidylinositol. Dietary docosahexaenoic acid, but not eicosapentaenoic acid, significantly decreased aortic production of prostacyclin compared to alpha-linolenic acid, whereas platelet aggregation by collagen was not affected by the difference in dietary (n-3) polyunsaturated fatty acids.
Animals↗
Hemodynamics and hepatic energy metabolism in canine model of acute hepatic venous occlusion with mesocaval shunt.
The relationship between portal hemodynamics and the energy metabolism of the liver with acute hepatic venous occlusion (HVO) was investigated by assessing the changes in the hepatic blood flow, arterial blood ketone body ratio (AKBR) and adenylate energy charge potential (ECP) of the liver tissue in canine model. Acute HVO was induced by the ligation of both the supra- and infrahepatic inferior vena cava (IVC) over the protruding ends of a heparin-coated polyethylene cannula inserted into the IVC. All dogs with only HVO (n = 5) died within 30 min. HVO dogs with additional mesocaval (MC) shunt (n = 10) survived longer than 7 days, during which time their AKBR were maintained in the normal range (over 1.0). ECP was also maintained above the normal level (over 0.850) during the 28-day period. Along with increasing portal pressure caused by the narrowing of the shunt anastomosis, the hepatic blood flow decrease gradually, resulting in a sudden decrease in AKBR and ECP when the portal pressure increased over 11 mm Hg. It is suggested that the normalization of portal pressure is one of the most important factors for maintaining the hepatic energy metabolism and that MC shunt is an effective therapy for maintaining the function of the liver with HVO, as long as portal pressure can be kept within normal range.
Animals↗
Trans fatty acids: effects on eicosanoid production.
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Animals↗
Studies of human immunodeficiency virus type 1 (HIV-1) protease inhibitors. III. Structure-activity relationship of HIV-1 protease inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere.
Systematic replacement of the P4-P2 subsites of substrate-based human immunodeficiency virus type 1 protease (HIV-1 PR) inhibitors containing cyclohexylalanylalanine hydroxyethylene dipeptide isostere (Cha-psi [H.E.]-Ala) at positions corresponding to the scissile sites of substrates was carried out. The structure-activity relationship revealed that compounds with the combination of hydrophilic P3 and beta-branched hydrophobic P2 amino acids generally showed strong inhibitory activity against HIV-1 PR. In particular, compounds 4 (Boc-Orn-Val-Cha-psi [H.E.]-Ala-NHBun; Bu(n) = n-butyl, Ki = 11 nM) and 6 (Z-Orn-Val-Cha-psi [H.E.]-Ala-NHBun, Ki = 8 nM) exhibited good enzyme selectivity, possessing no significant inhibitory activities toward closely related aspartic proteases, pepsin, cathepsin D, and renin. As a possible model system for (anti-Mo-MSV/MLV complex (Mo-MSV = Moloney murine sarcoma virus; MLV = murine leukemia virus)) activity was investigated. Both compounds were found to inhibit moderately the focus formation of Mo-MSV/MLV complex in NIH3T3 cells (compound 4, IC50 = 1.8 microM; compound 6, IC50 = 1.0 microM).
Amino Acid Sequence↗
Lymphatic transport of stearic acid and its effect on cholesterol transport in rats.
Lymphatic transport of stearic acid, given as completely hydrogenated rapeseed oil (R10), 9 to 1 (R9) and 5 to 5 (R5) mixtures of R10, and soybean oil and completely hydrogenated tallow (T) was examined in the rat cannulated thoracic duct. R10, R9, R5, and T contained 91.4, 81.5, 46.5, and 63.6% stearic acid, respectively. A large portion of the remaining fatty acids in T was palmitic acid (31%). These fats were emulsified with bile salt and albumin, and administered via a stomach tube. Lymphatic recovery of stearic acid at 24 h was lowest in R10 and highest in R5, and intermediate in R9 and T. Recovery of oleic and linoleic acids in rats given R5 was almost complete and significantly higher than that of stearic acid. When T was given, the 24 h recovery of stearic acid was significantly lower than that of palmitic acid. A highly inverse correlation between the recovery and the content of stearic acid in administered fats was observed in R10, R9, and R5. Lymphatic recovery of cholesterol was almost parallel with that of stearic acid. Although the content of stearic acid in T was lower than that in R9, the recovery of stearic acid and cholesterol was almost similar. The results indicate that the rate of lymphatic recovery of stearic acid is affected by the quantity and quality of coexisting fatty acids.
Absorption↗
Effects of dietary short-necked clam, Tapes japonica, on serum and liver cholesterol levels in mice.
Male mice were fed cholesterol-supplemented diets containing short-necked clams or defatted short-necked clams for 2 weeks under the dietary regimen of the same dietary level of protein (20%), fat (5%), and cholesterol (0.5%). Casein was used as a control protein. Similar results were obtained in two separate experiments with either boiled (Exp. 1) or steamed (Exp. 2) short-necked clams. The concentration of serum cholesterol in mice fed a clam diet was lower than in those fed control and defatted clam diets. Delipidation of clam raised the concentration of serum triglyceride. Both clams and defatted clams markedly reduced the concentration of hepatic cholesterol. Fecal excretion of neutral steroids was significantly increased by clam but not defatted clam, whereas the excretion of acidic steroids was stimulated by both specimens, in particular defatted clam. The results suggest that the hypocholesterolemic effect of short-necked clams is attributed to its lipid fraction, whereas non-lipid components contribute to the reduction of hepatic cholesterol and increased fecal excretion of bile acids.
Animals↗
Effect of dietary fats on cholesterol metabolism and eicosanoid production in hamsters fed undigested fraction of soybean protein.
The undigested fraction of soybean protein (UDF) exerts a markedly greater hypocholesterolemic effect than soybean protein itself in rats. The present study was undertaken to confirm the effect in hamsters, a more appropriate animal model for human cholesterol metabolism. Hamsters were given diets containing UDF at a nitrogen level equivalent to the 20% casein diet. Dietary fats, at the 10% level, were perilla oil and safflower oil. There was apparently no increase in the serum and liver cholesterol levels in both groups of animals cholesterol-enriched diets that had been fed for 38 days. Fecal excretion of neutral and acidic steroid tended to be higher in the perilla oil group than in the safflower oil group. The perilla oil group significantly increased 20:5n-3 in liver phosphatidylcholine and phosphatidylethanolamine accompanying a decrease in 20: 4n-6. Such changes were not so evident in liver phosphatidylinositol. The production of leukotriene B4 and the concentration of prostaglandin E2 in the spleen were higher in the safflower oil group than in the perilla oil group. Thus, the hypocholesterolemic effect of the undigested fraction of soybean protein was apparently reproduced even in hamsters. Dietary fat-induced changes in lipid parameters in hamsters resembled those observed in rats.
Animals↗
Ascidian entactin/nidogen. Implication of evolution by shuffling two kinds of cysteine-rich motifs.
Entactin/nidogen, a major component of the basement membrane, has a domain structure comprising three globular domains, and thread-like and rod-like domains connecting them. It contains six epidermal-growth-factor-(EGF)-like motifs and one thyroglobulin-like motif. In the present study, ascidian entactin/nidogen has been identified by a monoclonal antibody technique. We prepared anti-(ascidian entactin/nidogen)IgG, named anti-AsEnt1, then cloned the cDNA of ascidian entactin/nidogen using anti-AsEnt1 as a probe, and determined its entire sequence. Mainly because the deduced amino acid sequence exhibited high similarity to mouse entactin and human nidogen, and because the antigen localized in basement membrane of ascidian body-wall muscle, we have concluded that the antigen anti-AsEnt1 corresponds to the ascidian entactin/nidogen homologue. The deduced amino acid sequence of ascidian entactin/nidogen clearly showed that the ascidian homologue also has a domain structure. However, the ascidian homologue lacked the thread-like domain, and the rod-like domain differed from that of mouse entactin in composition, consisting of two kinds of cysteine-rich motifs, that is, the EGF-like motif and the thyroglobulin-like motif. These results suggest that entactin/nidogen have evolved by modifying the domains, especially by shuffling the two kinds of cysteine-rich motifs.
Amino Acid Sequence↗