Cholesterol Articles and Abstracts

For medical practitioners and the general public - Cholesterol Journal Article Catalog.

Cholesterol Journal Articles



Record 11761 to 11780
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Soy protein may affect plasma cholesterol through copper
Klevay, L. M. (1994), Am J Clin Nutr 60(2): 300-1.

Soy protein peptic hydrolysate with bound phospholipids decreases micellar solubility and cholesterol absorption in rats and caco-2 cells
Nagaoka, S., K. Miwa, et al. (1999), J Nutr 129(9): 1725-30.
Abstract: This experiment was designed to evaluate the effects of casein, soy protein, soy protein with bound phospholipids (SP), soy protein peptic hydrolysate (SPH) or soy protein peptic hydrolysate with bound phospholipids (SPHP) on the micellar solubility of cholesterol and the taurocholate binding capacity in vitro. We also evaluated the effects of various proteins on cholesterol metabolism in rats and Caco-2 cells. SPHP had a significantly greater bile acid-binding capacity than that of SPH in vitro. Micellar cholesterol solubility in vitro was significantly lower in the presence of SPHP compared to casein tryptic hydrolysate (CTH). The cholesterol micelles containing SPHP and SPH significantly suppressed cholesterol uptake by Caco-2 cells compared to the cholesterol micelles containing CTH. Consistent with these findings in the in vivo cholesterol absorption study using radioisotopes, fecal excretion of total steroids was significantly greater in rats fed the SPHP diet compared with those fed the casein, soy protein, SP and SPH diets. Serum total cholesterol was significantly lower in rats fed SPHP than in those fed casein. The concentrations of total lipids and cholesterol in liver were significantly lower in the SPHP-fed group compared with all other groups. These results suggest that the suppression of cholesterol absorption by direct interaction between cholesterol-mixed micelles and SPHP in the jejunal epithelia is part of the mechanism underlying the hypocholesterolemic action of SPHP. SPHP may also inhibit the reabsorption of bile acids in the ileum, thus lowering the serum cholesterol level.

Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells
Lovati, M. R., C. Manzoni, et al. (2000), J Nutr 130(10): 2543-9.
Abstract: The activation of LDL receptors was described recently in a human hepatoma cell line (Hep G2) exposed both to alpha + alpha' subunits from 7S soy globulin and to Croksoy(R)70, a commercial isoflavone-poor soy concentrate. To assess the final identity of the peptide(s) putatively responsible for the biochemical effect, experiments were performed in Hep G2 cells, exposed either to synthetic peptides corresponding to specific sequences of 7S soy globulin or to peptides from the in vitro digestion of Croksoy(R)70. Moreover, the ability of the whole 7S globulin, its subunits and whole Croksoy(R)70 to interfere in the apolipoprotein B (apo B) secretion in the medium as well as in sterol biosynthesis was evaluated in the same model. Increased (125)I-LDL uptake and degradation vs. controls were shown after Hep G2 incubation with a synthetic peptide (10(-)(4) mol/L, MW 2271 Da) corresponding to positions 127-150 of the 7S globulin. Cells exposed to Croksoy(R)70 enzyme digestion products showed a more marked up-regulation of LDL receptors vs. controls, compared with vs. Hep G2 cells incubated with undigested Croksoy(R)70. Among soy-derived products, only the 7S globulin inhibited apo B secretion and (14)C-acetate incorporation when tested in Hep G2 cells at a concentration of 1.0 g/L. These findings support the hypothesis that if one or more peptides can reach the liver after intestinal digestion, they may elicit a cholesterol-lowering effect. Moreover, the protein moiety, devoid of isoflavone components, is likely to be responsible for this major biochemical effect of soy protein.

Soy protein reduces the arterial low-density lipoprotein (LDL) concentration and delivery of LDL cholesterol to the arteries of diabetic and nondiabetic male cynomolgus monkeys
Wagner, J. D., L. Zhang, et al. (2000), Metabolism 49(9): 1188-96.
Abstract: We have previously shown that soy protein consumption improves lipoprotein concentrations and reduces the progression of atherosclerosis in cynomolgus monkeys. The mechanism for these beneficial effects is unclear. The purpose of this study was to determine potential mechanisms for the atheroprotective effects of soy and to determine if these effects extend to diabetic monkeys. We designed an experiment with a 2 x 2 factorial design in which adult male monkeys (N = 23) were fed an atherogenic diet with a protein source of either soy isolate or casein and lactalbumin, and the monkeys were either control or streptozotocin-induced diabetic. Diabetics had significantly increased fasting glucose and glycated hemoglobin (GHb) levels; this relationship was not affected by the type of dietary protein. Diabetics also had increased total (TC) and low-density lipoprotein cholesterol (LDLC) concentrations. However, soy consumption significantly reduced TC and LDLC concentrations in both control and diabetic monkeys. Plasma and arterial LDL metabolism was determined by injecting 125I-LDL at 48 hours and 131I-tyramine cellobiose LDL at 1 hour prior to necropsy. This allowed a determination of the arterial LDL concentration, permeability, and arterial LDL delivery. An increase in the whole-body plasma LDL fractional catabolic rate (FCR) was found with soy. Soy significantly reduced the arterial LDL concentration across all arterial sites by an average of 50%. Soy also significantly reduced the delivery of LDLC to all arterial sites by an average of 40%. While this was primarily due to the lower plasma LDLC concentration, LDL permeability in the carotid bifurcation and internal carotid arteries was also reduced. There was no additional effect of diabetes. These beneficial effects on plasma and arterial LDL metabolism would be expected to reduce atherosclerosis and were found in both control and diabetic monkeys.

Soy protein with or without isoflavones, soy germ and soy germ extract, and daidzein lessen plasma cholesterol levels in golden Syrian hamsters
Song, T., S. O. Lee, et al. (2003), Exp Biol Med (Maywood) 228(9): 1063-8.
Abstract: Dietary isolated soy protein (ISP, containing approximately equal amounts of daidzein and genistein), ethanol-extracted ISP (ISP (-)), soygerm or soygerm extract (containing large amounts of daidzein and glycitein and little genistein) and the isoflavone, daidzein, were hypothesized to lessen plasma cholesterol in comparison with casein. Sixty male and 60 female golden Syrian hamsters (6-8 weeks of age) were randomly assigned to six treatments fed for 10 weeks. Four of the experimental diets (ISP, daidzein, soygerm, and soygerm extract) contained 1.3 mmol total isoflavones/kg. The ISP (-) diet contained 0.013 mmol isoflavone/kg, whereas the casein diet contained no isoflavones. Hamsters fed ISP, ISP (-), daidzein, soygerm, and soygerm extract had significantly less plasma total cholesterol (by 16%-28%), less non-HDL cholesterol (by 15%-50%) and less non-HDL/HDL cholesterol ratios compared with hamsters fed casein (P < 0.01). For male hamsters, there were no differences among treatments in plasma HDL concentrations. Female hamsters fed ISP (-) had significantly greater HDL levels (P < 0.01) than females fed casein or daidzein. Triglyceride concentration was significantly less in hamsters fed ISP (-) compared with the casein-fed females. Because soy protein with or without isoflavones, soygerm and soygerm extract, and daidzein lessened plasma cholesterol to an approximately equal extent, soy protein alone, varying mixtures of isoflavones, and other extractable components of soy are responsible for cholesterol-lessening effects of soy foods, mainly due to their effects to lessen LDL cholesterol.

Soy protein, thyroid regulation and cholesterol metabolism
Forsythe, W. A., 3rd (1995), J Nutr 125(3 Suppl): 619S-623S.
Abstract: The effects of dietary protein on plasma cholesterol concentrations are well documented: animal proteins (casein) are hypercholesterolemic compared with plant proteins (soy protein). Although this effect of protein source on plasma cholesterol has been shown in many species, the mechanism is not completely understood. This paper reviews the relationship between dietary protein source and plasma thyroxine concentration. The basic premise is that feeding soy protein lowers plasma cholesterol concentration by causing an increase in plasma thyroxine concentrations. The metabolic changes involving cholesterol that occur when soy protein is fed are discussed. These changes are consistent with changes induced by elevating thyroxine. Data are presented from animal studies showing that feeding soy protein to laboratory animals consistently elevates plasma thyroxine concentrations. Furthermore, this elevation in plasma thyroxine concentrations precedes the change in plasma cholesterol concentrations: a necessary requirement for hypothesizing a causative effect. Possible mechanisms as to how a dietary protein source affects plasma thyroxine are also presented.

Soy proteins reduce progression of a focal lesion and lipoprotein oxidiability in rabbits fed a cholesterol-rich diet
Castiglioni, S., C. Manzoni, et al. (2003), Atherosclerosis 171(2): 163-70.
Abstract: The effects of different dietary proteins on the progression of a focal atheromatous lesion and on lipoprotein oxidiability were studied in male New Zealand rabbits. Focal lesions were induced on common carotid arteries by applying an electric current, using a bipolar microcoagulator. After surgery, animals were fed for 90 days two different diets, both with 1% cholesterol, 15% saturated fatty acids and 20% protein: the protein source was constituted in one group (SOY) by 16% soy protein isolate plus 4% milk whey proteins, in the other (CASEIN) by 16% casein plus 4% milk whey proteins. Lower levels of plasma cholesterol and triglycerides (-47 and -65%, respectively) (P < 0.05) were detected in the SOY versus the CASEIN group at the end of treatment. Cryosection analyses of the carotids, indicated a highly significant reduction (-39%; P < 0.05) in the focal lesion progression in the SOY versus the CASEIN group. Copper-mediated oxidation of low-density lipoprotein (LDL) from rabbits fed the two different diets, performed in vitro by analysis of conjugated diene formation, showed a significantly longer lag phase in the SOY (150 +/- 5 min) versus the CASEIN animals (20 +/- 3 min) (P < 0.05). These data, while confirming the well-known lipid lowering properties of soy proteins, indicate, in this animal model, a remarkable activity on a focal atheromatous lesion, possibly also linked to a powerful antioxidant activity.

Soy sterol esters and beta-sitostanol ester as inhibitors of cholesterol absorption in human small bowel
Normen, L., P. Dutta, et al. (2000), Am J Clin Nutr 71(4): 908-13.
Abstract: BACKGROUND: Plant sterols are natural dietary components with serum cholesterol-lowering properties. The lowering of serum cholesterol by plant sterols is believed to be the result of an inhibition of cholesterol absorption in the small bowel, although increased bile acid excretion has also been suggested. The difference in effect of saturated and unsaturated plant sterols on cholesterol absorption needs to be elucidated further. OBJECTIVE: The primary aim of this study was to measure small-bowel cholesterol absorption and sterol excretion in addition to hepatic cholesterol synthesis after intake of soy sterol esters and beta-sitostanol ester corresponding to 1.5 g plant sterols/d. DESIGN: Seven ileostomy subjects were studied during a control period and 2 intervention periods when either soy sterol esters or beta-sitostanol ester was added to a basal diet. Ileostomy bags were collected every other hour and frozen immediately for analysis of nutrients and sterols. RESULTS: Cholesterol absorption was 56% (43-65%) in the control period and decreased to 38% (32-46%) in the soy sterol ester period (P = 0.00) and to 39% (30-48%) in the beta-sitostanol ester period (P = 0.00). CONCLUSION: Esterified soy sterols and beta-sitostanol inhibited cholesterol absorption equally, despite the different structures of the plant sterols.

Soyasaponins lowered plasma cholesterol and increased fecal bile acids in female golden Syrian hamsters
Lee, S. O., A. L. Simons, et al. (2005), Exp Biol Med (Maywood) 230(7): 472-8.
Abstract: A study was conducted in hamsters to determine if group B soyasaponins improve plasma cholesterol status by increasing the excretion of fecal bile acids and neutral sterols, to identify group B soyasaponin metabolites, and to investigate the relationship between a fecal group B soyasaponin metabolite and plasma lipids. Twenty female golden Syrian hamsters, 11-12 weeks old and 85-125 g, were randomly assigned to a control diet or a similar diet containing group B soyasaponins (containing no isoflavones), 2.2 mmol/kg, for 4 weeks. Hamsters fed group B soyasaponins had significantly lower plasma total cholesterol (by 20%), non-high-density lipoprotein (HDL) cholesterol (by 33%), and triglycerides (by 18%) compared with those fed casein (P < 0.05). The ratio of total cholesterol to HDL cholesterol was significantly lower (by 13%) in hamsters fed group B soyasaponins than in those fed casein (P < 0.05). The excretion of fecal bile acids and neutral sterols was significantly greater (by 105% and 85%, respectively) in soyasaponin-fed hamsters compared with those fed casein (P < 0.05). Compared with casein, group B soyasaponins lowered plasma total cholesterol levels and non-HDL cholesterol levels by a mechanism involving greater excretion of fecal bile acids and neutral sterols. Hamsters fed group B soyasaponins statistically clustered into two fecal soyasaponin metabolite-excretion phenotypes: high excreters (n = 3) and low excreters (n = 7). When high and low producers of this soyasaponin metabolite were compared for plasma cholesterol status, the high producers showed a significantly lower total-cholesterol-to-HDL-cholesterol ratio compared with the low producers (1.38 +/- 0.7 vs. 1.59 +/- 0.13; P < 0.03). Greater production of group B soyasaponin metabolite in hamsters was associated with better plasma cholesterol status, suggesting that gut microbial variation in soyasaponin metabolism may influence the health effects of group B soyasaponins.

Soybean protein diet and plasma cholesterol: from therapy to molecular mechanisms
Sirtori, C. R., R. Even, et al. (1993), Ann N Y Acad Sci 676: 188-201.

Soybean protein lowers serum cholesterol levels in hamsters: effect of debittered undigested fraction
Gatchalian-Yee, M., Y. Arimura, et al. (1997), Nutrition 13(7-8): 633-9.
Abstract: The undigested fraction (UDF) of soybean protein exerts a marked hypocholesterolemic effect in relation to soybean protein (SOY) in rats. The present study was conducted to confirm whether UDF was effective in hamsters as in rats in combination with different fat sources, either perilla oil (PER) or safflower oil (SAF). Because the hamster, unlike the rat, disliked the bitter taste of UDF, the effect of debittering UDF also was studied. Cholesterol-enriched (0.2%) diets containing 20% protein and 10% fat were fed to hamsters for 4 wk. UDF was more hypocholesterolemic than soybean protein in hamsters regardless of the dietary fat source. The ratio of high-density lipoprotein to total cholesterol essentially remained unchanged. The debittered UDF, without influencing food intake and thereby weight gain, exerted a significant hypocholesterolemic effect comparable with UDF in relation to SOY accompanying stimulation of fecal neutral and acidic steroid excretion. The fatty acid composition of liver phospholipids was influenced by the type of the dietary protein, and both UDF seemed to interfere characteristically more than SOY with the desaturation systems between linoleic acid and arachidonic acid. Thus, the debittered UDF, similar to UDF, exerted a distinct influence on the various parameters of lipid metabolism in relation to SOY.

Soymilk intake is associated with plasma and liver lipid profiles in rats fed a high-cholesterol diet
Chen, J. R., S. M. Liu, et al. (2004), Nutrition 20(10): 929-33.
Abstract: OBJECTIVE: This study investigated the effects of soymilk on lipid metabolism in Sprague-Dawley rats fed a cholesterol-enriched (0.3%) diet. METHODS: Thirty male Sprague-Dawley rats weighing 230.0 +/- 9.8 g were randomly assigned to one of three groups: control, S1 (containing 15% soymilk powder in the diet), and S2 (22.5%). After 8 wk, lipid profiles of the plasma, liver, and feces were determined. RESULTS: Body weight gain, daily food intake, and feeding efficiency showed no differences across groups (P > 0.05). The experimental groups had significantly lower plasma levels of cholesterol, triacylglycerol, and low-density lipoprotein cholesterol than the control group (P < 0.05) at weeks 4 and 8. However, total fecal excretion of neutral steroid did not significantly differ across groups (P > 0.05). CONCLUSION: Soymilk affects the metabolism of plasma cholesterol in Sprague-Dawley rats.

Spatial and temporal distribution of intracellular free cholesterol in brains of a Niemann-Pick type C mouse model showing hyperphosphorylated tau protein. Implications for Alzheimer's disease
Treiber-Held, S., R. Distl, et al. (2003), J Pathol 200(1): 95-103.
Abstract: Niemann-Pick type C (NPC) disease is a fatal hereditary neurovisceral disorder with diagnostically relevant intracellular accumulation of cholesterol in non-brain tissue, for example the spleen and fibroblasts. In the brain, many ballooned neurons are seen. Using filipin microfluorodensitometry, significant accumulations of free cholesterol in specified neurons have been described in NPC patients. The present study demonstrates spatial and temporal accumulation of free cholesterol in the brains of homozygous NPC (-(npc)/-(npc)) mice, a widely acknowledged mouse model, and in primarily cultured neurons therefrom. Intraneuronal storage of free cholesterol was already prominent at a pre-clinical stage in various grey matter areas of the murine cerebral cortex. Hippocampal areas showed differential development of the pathological distribution of free cholesterol. The pyramidal cells in the CA3 sector of Ammon's horn were affected much earlier than in CA1. Some of the deeper cerebral nuclei were affected only slightly, even at the final stage. Neurons (E15-E17) cultured in a cholesterol-free medium also showed massive accumulation of intracellular free cholesterol. In addition, brains from the murine NPC model for Alzheimer's disease (AD)-like changes in the microtubule-associated protein tau were tested using the Gallyas silver technique and AT8-immunolabelling, since both human diseases are accompanied by intraneuronal tangles made up of tau protein aggregations. Although the analysis failed to show classical silver-stainable tangles of the AD type in the NPC mice, tau protein phosphorylated at epitopes considered to represent early stages of AD was found. This further strengthens the concept that an alteration in cholesterol metabolism may play an important role in AD. The NPC mouse model may thus serve as a tool to analyse the role of cholesterol in initial changes of tau that eventually lead to the formation of tangles in both NPC and AD.

Spatiotemporal changes of free cholesterol and neutral lipids after transient middle cerebral artery occlusion in rats
Kamada, H., K. Sato, et al. (2002), Ann N Y Acad Sci 977: 115-22.

Specialized physical training programs: effects on serum lipoprotein cholesterol, apoproteins A-I and B and lipolytic enzyme activities
Giada, F., G. Baldo-Enzi, et al. (1991), J Sports Med Phys Fitness 31(2): 196-203.
Abstract: To determine the effects of different types of physical training on lipid metabolism, serum lipids, lipoprotein cholesterol, apoproteins A-I and B, hepatic (HTGL), extrahepatic (LPL) and total (PHLA) post-heparin lipoprotein lipase activities were studied in elite athletes engaged in aerobic ("B", no. 13), anaerobic ("C", no. 17) and mixed ("D", no. 9) training programs and in a group of sedentary controls ("A", no. 15). In the aerobic and mixed groups serum triglycerides were significantly lower compared to sedentary controls while total serum cholesterol and LDL cholesterol, as well as serum apoprotein B levels were only slightly lower. HDL cholesterol and HDL2 cholesterol were slightly higher while serum cholesterol/HDL cholesterol (2.89 +/- 0.37 vs 3.6 +/- 0.47, p less than 0.01) and LDL cholesterol/HDL cholesterol (1.69 +/- 0.38 vs 2.23 +/- 0.43, p less than 0.05) ratios were significantly lower only in aerobic athletes compared to the control group. PHLA and LPL activities were slightly higher in the aerobic group than in controls, while PHLA and HTGL were significantly lower in aerobic and mixed athletes. No significant correlations were found between HDL cholesterol and energy expenditure during training, indexes of adipose mass or lipolytic enzyme activities. The results of this cross-sectional study seem to indicate that specialized training programs have a different effect on lipoprotein pattern and lipolytic enzyme activities, and only aerobic exercise has a potentially antiatherogenic effect.

Species difference in cholesterol 7alpha-hydroxylase expression of rabbit and rat liver microsomes after bile duct ligation
Tanaka, S., M. Kinowaki, et al. (2004), J Surg Res 119(1): 36-40.
Abstract: BACKGROUND: Bile duct ligation (BDL) produces a good animal model for investigation of the metabolic changes in obstructive jaundice. The aim of this study was to investigate the species difference in expression of cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) in rabbits and rats after BDL. MATERIALS AND METHODS: Ten male New Zealand white rabbits weighing 2.5-3 kg and 12 male Wistar strain rats weighing 250-300 g were used. Half the animals underwent BDL, and half were sham operated (Sham). The animals were sacrificed on day 5 after operation. The livers were harvested, and levels of mRNA and 7alpha-hydroxylase activity were determined. Concentrations of serum bilirubin and bile acids were also measured. RESULTS: In BDL rats, the levels of mRNA were increased 30%, and 7alpha-hydroxylase activity was three times that of the Sham group. In BDL rabbits, however, these values were approximately 60 and 50% lower than the Sham group, respectively. Serum bile acid concentrations increased up to 13 times in BDL rabbits and 70 times in BDL rats over that of the Sham groups. Serum cholesterol and serum total bilirubin concentration also increased after BDL in both animals. CONCLUSION: These results suggest that there is a species difference in the expression of 7alpha-hydroxylase after BDL in rabbits and rats and the reason for this difference is most likely pretranslational regulation.

Species difference in cholesteryl ester cycle and HDL-induced cholesterol efflux from macrophage foam cells
Hakamata, H., A. Miyazaki, et al. (1994), Arterioscler Thromb 14(11): 1860-5.
Abstract: The species difference in the turnover rates of the cholesteryl ester (CE) cycle in macrophage foam cells (MFC) was examined in mice and rats. MFC were induced by acetyl-LDL and pulsed with 3Holeate, followed by a chase with 14Coleate. The replacement of the initial amount of cholesteryl 3Holeate by cholesteryl 14Coleate within 24 hours was 63% in mouse MFC, whereas it was 33% in rat MFC. The corresponding replacement in rabbit MFC was < 10%. In addition, HDL removed 41% of the CE mass from mouse MFC but only 22% from rat MFC. HDL-induced CE reduction from mouse MFC was enhanced by 40% by the inhibitor for acyl-coenzyme A:cholesterol acyltransferase (58-035), whereas the enhancing effect was not observed with rat MFC. These results indicate that the rate of CE turnover may serve as a critical factor to determine the capacity of MFC to respond to HDL-induced CE reduction, suggesting the possibility that the species difference in the turnover rates of the CE cycle in MFC might explain, in part, the species difference in susceptibility to experimental atherosclerosis.

Species differences in the inhibiting effect of fluvastatin, a new inhibitor of HMG-CoA reductase, on cholesterol biosynthesis
Yamamoto, A., S. Itoh, et al. (1994), Res Commun Mol Pathol Pharmacol 86(3): 325-34.
Abstract: Cholesterol synthesis both ex vivo and in vivo in liver and ileum of hamsters was significantly inhibited by fluvastatin. This ex vivo inhibition was considerably lower in fluvastatin-treated hamsters than in fluvastatin-treated rats. In hamsters and rats, fluvastatin was more potent than pravastatin on inhibitory activities of sterol synthesis in liver, but not in the hamster ex vivo. This may indicate that, in part, the hydrophobicity of the fluvastatin molecule confers the selectivity and metabolism in the liver of hamsters and rats to originate from the species differences.

Species specificity in the blood cholesterol-lowering effect of YM-16638
Goto, S., T. Shimokawa, et al. (1996), Br J Pharmacol 118(1): 174-8.
Abstract: 1. The compound YM-16638, 5-3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl thio-1,3,4-thiadiazol-2-ylthio acetic acid was developed in a series of in vitro and in vivo studies as a leukotriene D4 receptor antagonist. 2. In a clinical trial as a leukotriene antagonist drug, this compound was found to have a potent serum cholesterol lowering effect in normolipidaemic healthy male volunteers. 3. In the present study, we investigated the serum cholesterol lower effect of this compound in various species of experimental animals. 4. Administration of YM-16638 did not cause a significant decrease in serum total cholesterol (TC) in mice (up to 200 mg kg-1, body weight per day for 28 days), rats (200 mg kg-1 for 15 days) or rabbits (90 mg kg-1 for 18 days). In hamsters, administration of YM-16638 orally or by peritoneal injection at 50 mg kg-1 or more daily for 7 days caused a significant decrease in serum TC and the rate of body weight gain. In monkeys, serum TC did not change in YM-16638-administered squirrel monkeys (50 mg kg-1 daily for 3 weeks), but a significant decrease in serum TC was observed in cynomolgus monkeys (33% decrease at 30 mg kg-1 for 4 weeks) and rhesus monkeys (27% decrease at 30 mg kg-1 for 3 weeks) without any serious decrease in body weight. These results were consistent with those in a phase I study with human subjects. In contrast, serum alanine aminotransferase (ALT) level decreased in all animals after YM-16638 treatment. 5. From these results, we conclude that YM-16638 has a potent hypocholesterolaemic effect, but that this effect if species-specific and is only recognized clearly in human subjects and old-world monkeys.

Specific accumulation of cholesterol-rich liposomes in the inflammatory tissue of rats with adjuvant arthritis
Love, W. G., N. Amos, et al. (1990), Ann Rheum Dis 49(8): 611-4.
Abstract: High performance liquid chromatography has shown that after intravenous injection cholesterol-poor liposomes (100 nm) are unstable and their phospholipid is redistributed. Under identical conditions cholesterol-rich liposomes remain structurally intact within the circulation. When injected intravenously cholesterol-rich liposomes accumulate within the inflamed paws of rats with adjuvant induced arthritis to the same extent as cholesterol-poor liposomes. Uptake in inflamed tissue of three cholesterol-rich liposome preparations was always significantly greater than the uptake noted in normal tissue. The degree of accumulation in inflamed tissue was found to depend on the size of the liposome, with the greatest uptake, 7% of the injected dose, achieved by the smallest vesicle (100 nm). These results indicate that intact liposomes accumulate at inflamed joint tissue sites. Therefore the passive targeting of anti-inflammatory drugs encapsulated within these liposomes could be contemplated.


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