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Biomedical subjects

S Tazuma

Publications and source records attributed to S Tazuma.

At least 73 records · Page 4Linked to original sources

Nucleation time and fatty acid composition of lecithin in human gallbladder bile.

We investigated the relationship between bile nucleation time and the fatty acid composition of biliary lecithin in human gallbladder bile. Bile samples from patients with cholesterol gallstones nucleated more rapidly than those from patients with noncholesterol gallstones or no stones. The biliary cholesterol concentration was highest in the cholesterol gallstone group and was correlated with the molar percentage of linoleic acid and arachidonic acid, with these percentages also being higher in bile from the cholesterol gallstone patients than in bile from the other two groups. In addition, the mucous glycoprotein concentration in bile was also significantly higher in the cholesterol gallstone group. Thirty-three patients in the no-stone group showed bile nucleation times of less than 21 days. Higher concentrations of cholesterol and mucous glycoprotein and higher molar percentages of arachidonic and linoleic acid were noted in these patients. These findings suggest that in humans, hepatic cholesterol hypersecretion is associated with the increased unsaturated fatty acid proportion in biliary phospholipids and gallbladder mucin hypersecretion, thereby causing rapid cholesterol crystal nucleation.

Bile↗

Effects of 16,16-dimethyl prostaglandin E2 on biliary mucous glycoprotein and gallstone formation in guinea pigs.

This study was performed to determine the effect of 16,16-dimethyl prostaglandin E2 (dmPGE2) on mucous glycoprotein secretion by the guinea pig gallbladder. The prostaglandin was given intraperitoneally for 4 weeks at daily doses of 0 (controls), 10, 20, or 30 micrograms/kg body weight (n = 18 at each dose). These 72 animals were fed normal chow. A 5th group of 18 animals received chow containing 1% cholesterol and 0.5% cholic acid, and no dmPGE2. There were statistically significant increases in the concentrations in gallbladder bile of mucous glycoprotein in the animals fed cholesterol and those treated with dmPGE2, as compared with the controls. Moreover, the animals treated with dmPGE2 formed black-pigmented gallstones, the incidence being dose-dependent, whereas all animals fed a cholesterol-rich diet formed amorphous yellow-brown gallstones. Even though these two types of gallstones appeared different on macroscopic examination, both consisted primarily of calcium phosphate and calcium bilirubinate. These results suggest that exogenous prostaglandin E2 increases concentrations of mucous glycoprotein in the gallbladder bile, resulting in gallstone formation by a mechanism in part similar to the one whereby cholesterol loading promotes gallstone formation in this model.

16,16-Dimethylprostaglandin E2↗

Effects of organic anions on biliary lipid secretion in rats. Importance of association with biliary lipid structures.

This study was performed to determine the effects of various organic anions on biliary lipid secretion in rats. We infused bile-salt-pool-depleted rats with sodium taurocholate at a constant rate, with or without various organic anions: Indocyanine Green (ICG), bromosulphophthalein (BSP), BSP-glutathione and Phenol Red (PR). BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile salt secretion (uncoupling), and this change was fully reversible. In contrast, ICG, BSP-glutathione and PR did not cause such an uncoupling of biliary lipids. In addition, the distribution pattern of each organic anion to various lipid particles was determined by gel-permeation chromatography. BSP was predominantly associated with bile salt micelles, whereas vesicular association was dominant for ICG, and both BSP-glutathione and PR formed only self-aggregations. From these data, we concluded that the uncoupling of biliary lipids from bile salt secretion by BSP resulted from the interaction between BSP and bile salt micelles in the bile canaliculus, and that this interaction inhibited the capacity of bile salts to induce the secretion of phospholipids and cholesterol.

Animals↗

Inhibitory effects of pravastatin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, on cholesterol gallstone formation in prairie dogs.

The effects of pravastatin on cholesterol gallstone formation were determined in prairie dogs. We fed 10 prairie dogs 1% cholesterol with or without 0.05% (w/w) pravastatin (n = 5, each) for 4 weeks. In addition, another 5 prairie dogs were fed a standard rodent chow as a control. Only the animals fed 1% cholesterol without pravastatin treatment formed cholesterol gallstones. Gallbladder bile from cholesterol-fed animals contained cholesterol monohydrate crystals, whereas those treated with pravastatin contained no crystal. Furthermore, marked increases in tissue cholesterol levels (serum, liver and bile), and in biliary mucous glycoprotein levels were evident in cholesterol-fed animals, whereas pravastatin treatment normalized these levels. These findings raise the possibility that such inhibitors might have a future role to play in the prevention of cholesterol gallstone formation and/or recurrence.

Animals↗

Gallbladder and biliary interventional radiology.

The past ten years have seen the introduction of a number of new techniques for the treatment of biliary diseases. In this report, we discuss the roles of both extracorporeal shock-wave lithotripsy and percutaneous treatment of gallstones, and we emphasize the changing role of these techniques since the advent of laparoscopic cholecystectomy. The literature on chemical cholecystectomy is reviewed with particular reference to experience in humans. Biliary endoprosthesis using expandable metallic stents is discussed in patients with benign and malignant biliary obstruction. Finally, we review the role of interventional radiologic procedures on liver transplant patients.

Biliary Tract Diseases↗

Effects of pravastatin (CS-514) on biliary lipid metabolism in patients with hyperlipidemia.

Pravastatin was administered to 20 patients with hyperlipidemia type IIa and IIb, for a period of 8 to 16 weeks at a daily dose of 10 to 20 mg, to investigate the effects on serum and biliary lipids. At the end of the treatment with pravastatin, the serum cholesterol level was significantly reduced, by 20%, compared with the control level. On the other hand, no significant differences were observed in serum high-density lipoprotein (HDL) cholesterol and triglyceride levels. Additionally, the administration of pravastatin did not change mode % compositions of biliary lipids, such as cholesterol, phospholipids, and total bile acids, as well as individual biliary bile acids. Consequently, there was not any significant change of the cholesterol saturation index. Based on the above results, our findings suggest that, for the treatment of hyperlipidemia, pravastatin is a highly effective cholesterol-lowering drug that does not affect biliary lipid metabolism.

Adult↗

[A study on the mechanisms whereby apolipoprotein A-1 (apo A-1) inhibits cholesterol crystal nucleation in human gallbladder bile].

The aim of the present study was to determine the mechanisms whereby apo A-1 retards cholesterol crystal nucleation in human gallbladder bile. Ten human gallbladder bile samples were sterilely collected from patients with gallstones at surgery, subsequently applied on gel permeation chromatography to separate various lipid particles. A non-micellar fraction coeluted with apo A-1 was ultrastructurally characterized by transmission electron microscopy (TEM). As results, that fraction containing very little or no apo A-1, 400-600 A in diameter, showed rapid transformation, i.e. rouleau formation, multilamellar formation and consequently microcrystal formation, whereas those rich in apo A-1, 200-400 A in diameter, showed very little transformation for 7 days. Those data indicated that apo A-1 stabilizes non micellar fraction by forming an apo A-1 and lipid complexed particle, resulting in prolonged cholesterol crystal nucleation.

Apolipoprotein A-I↗

Effect of ursodeoxycholic acid administration on nucleation time in human gallbladder bile.

The object of this study was to determine the effects of ursodeoxycholic acid administration on metastability in human gallbladder bile, as reflected by nucleation time. Bile samples from 10 patients with cholesterol gallstones who underwent preoperative ursodeoxycholic acid treatment exhibited a significantly longer median nucleation time (16 days) than those from 11 patients with cholesterol gallstones who received no preoperative treatment (4 days) (p less than 0.01). On the other hand, the median nucleation times of bile samples from 15 patients with noncholesterol gallstones and 24 patients without gallstones were 15 and 14 days, respectively. In addition, 3 mo of treatment with ursodeoxycholic acid significantly elevated the serum concentration of the antinucleating factor apolipoprotein A-I, from 133.3 +/- 12.3 to 148.6 +/- 13.2 mg/dl (p less than 0.05). These findings suggest that ursodeoxycholic acid retards cholesterol crystal nucleation, thereby inhibiting cholesterol gallstone formation. It is also possible that serum apolipoprotein A-I plays a role in this process.

Adult↗

[The study on factors affecting cholesterol solubility in bile: relation to biliary proteins including apolipoprotein A-1].

We studied the preferential distribution patterns of cholesterol and proteins to biliary lipid particles isolated from human gallbladder bile by gel permeation chromatography. In addition nucleation times of those bile samples were determined to estimate the metastability of bile cholesterol. Cholesterol dominantly incorporated into a non-micellar fraction in bile from cholesterol gallstone patients with and without preoperative treatment with ursodeoxycholic acid, whereas nucleation time was significantly longer in cholesterol gallstone patients with a preoperative treatment with ursodeoxycholic acid than that of those without any preoperative treatment (p less than 0.01). Furthermore the induced incorporation of apolipoprotein A-1 into a non-micellar fraction was found in bile from cholesterol gallstone patients with ursodeoxycholic acid. These results suggest that stabilizing effects of apolipoprotein A-1 on a non-micellar fraction has been induced by ursodeoxycholic acid treatment resulting in the retardation of cholesterol nucleation in bile.

Apolipoprotein A-I↗

Biliary secretion of organic anions in the dog: association with defined lipid particles.

Organic anions have recently been found to partition in vitro into various biliary lipid particulate species according to their relative hydrophobicities. To establish the physiological relevance of these observations, we intravenously injected various radiolabeled organic anions and assessed the distributions of parent compounds and their metabolites to lipid particles in canine bile. Partitioning into various biliary lipid particles was determined by gel permeation chromatography. Relative hydrophobicities of the various organic anions and their radiolabeled conjugates were determined by reverse-phase high-pressure liquid chromatography. A strong positive correlation (P less than 0.001) was found between percent vesicular association and degree of hydrophobicity for a given organic anion and/or its more polar conjugate. We conclude that 1) the hydrophobic-hydrophilic balance of organic anions is a key factor governing their partitioning to lipid particles secreted in bile; 2) the present study agrees well with our previously published in vitro observations; and 3) other chemical constituents, e.g., proteins, mucin, etc., appear to have little or no effect on organic anion transport in bile.

Aminolevulinic Acid↗

Transport of conjugated bilirubin and other organic anions in bile: relation to biliary lipid structures.

Using gel-permeation chromatography, we studied associative relationships between conjugated bilirubin and various biliary lipid particle species, including lecithin/cholesterol vesicles, mixed-lipid micelles, and simple bile salt micelles. Five other organic anions were comparably studied: phenol red, Evans blue, sulfobromophthalein, rose bengal, and indocyanine green. For compounds of intermediate hydrophobicity, including conjugated bilirubin, the dominant association was with a bile salt/organic anion hybrid particle of dimensions larger than that of a simple pure bile salt micelle. Vesicular association was found to be dominant only for the most hydrophobic organic anions, indocyanine green and rose bengal; conversely, the most hydrophilic anion, phenol red, showed no vesicular association. Accordingly, a strong positive correlation (P less than 0.001) was found between percent vesicular association and degree of hydrophobicity of the organic anion. Alkaline conditions (eluant pH 9) decreased or prevented vesicular hydrophobic interaction with all anions. We conclude that two important particulate mechanisms for transport in bile of conjugated bilirubin and other water-soluble anions are bile salt/organic anion hybrid particles and vesicles. For most organic anions of intermediate hydrophobicity, including conjugated bilirubin, the bile salt/organic anion hybrid particle is the dominant transport vehicle.

Bile↗

Effects of cerivastatin sodium, a new HMG-CoA reductase inhibitor, on biliary lipid metabolism in patients with hypercholesterolemia.

The use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has become common in the treatment of hypercholesterolemia. The present uncontrolled study was undertaken to determine the effect of cerivastatin sodium (BAY w 6228), a new HMG-CoA reductase inhibitor, on biliary lipid levels in patients with hypercholesterolemia. Twenty-one hypercholesterolemic patients (World Health Organization type IIa = 16 patients; type IIb = 5 patients) received placebo during a 4- to 6-week observation period, after which they received cerivastatin sodium 0.2 mg/d for 12 weeks. Fasting blood samples were drawn for the measurement of serum lipid levels early in the morning before the start of treatment and once a month for each of the 12 weeks of cerivastatin sodium treatment. Gallbladder bile samples were aspirated with a duodenal tube by cerulein stimulation to assess bile lithogenicity. Serum total cholesterol levels decreased markedly after 12 weeks. However, no significant difference was found in the molar percentage composition of biliary lipids (e.g., cholesterol, phospholipids, and total bile acids) or in individual biliary bile acids. Consequently, no significant change in bile cholesterol saturation index was found. The index values before and after 12 weeks of treatment were 0.81 +/- 0.38 and 0.80 +/- 0.47, respectively, whereas when patients were grouped by type of hypercholesterolemia, there was a tendency toward decreased lithogenicity in patients with type IIb but not type IIa hypercholesterolemia. We concluded that cerivastatin sodium was an effective cholesterol-lowering drug that did not appear to worsen biliary lipid metabolism and that may decrease lithogenicity in patients with type IIb hypercholesterolemia.

Adult↗