| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Uptake of 3H-7-cholesterol along the arterial wall at an area of stenosis Deng, X., Y. Marois, et al. (1994), Asaio J 40(2): 186-91. Abstract: Abnormal uptake of atherogenic substances and lipid infiltration have been believed to contribute to the localized genesis and development of atherosclerosis, as well as to late failures of synthetic arterial prostheses. To verify the theoretical prediction that accumulation of lipoproteins on the luminal surface of arterial walls occurs in the regions of disturbed flow, we have carried out an in vitro mass transfer experiment to test the effect of a pseudo steady recirculation flow on the uptake of 3H-7-cholesterol by the arterial wall at a surgically created stenosis. It was found that, as predicted by the theory, in the flow field of the stenosis the uptake of labeled cholesterol reached a maximum around the reattachment point of the vortex distal to the stenosis, where the wall shear stress was lowest (zero). This value of the highest uptake rate was almost twice the average, whereas the uptake level was at a minimum at the stenosis itself where the wall shear stress was highest. The lowest uptake was only 60% of the average. These results provide strong support to our hypothesis, based upon the theory that, in addition to the flow induced changes to the biologic function of endothelial cells, the disturbed flow with slow recirculation itself favors the accumulation of atherogenic lipoproteins at the blood-endothelium boundary, therefore playing an important role in the localized pathogenesis and development of atherosclerosis. |
| Uptake of a cholesterol-rich emulsion by breast cancer Graziani, S. R., F. A. Igreja, et al. (2002), Gynecol Oncol 85(3): 493-7. Abstract: OBJECTIVE: Overexpression of low-density lipoprotein (LDL) receptors occurs in several cancer cell lines and offers a unique strategy for drug targeting by using LDL as vehicle. However, the native lipoprotein is difficult to obtain and handle. Previously, we showed that a lipidic emulsion (LDE) similar to the lipid structure of native LDL may bind to LDL receptors and be taken up by acute myelocytic leukemia cells. We also showed that LDE can also concentrate in ovarian cancer tissue. In this study, we tested whether LDE is taken up by breast carcinoma. METHODS: LDE labeled with (99m)Tc was injected into 18 breast cancer patients, and nuclear medicine images of the tumor and metastatic sites were acquired. Subsequently, LDE labeled with 3Hcholesteryl oleate was intravenously injected into 14 breast cancer patients 24-30 h before total mastectomy procedure. Fragments of normal and of breast cancer tissue excised during surgery were lipid extracted with chloroform/methanol and their radioactivity was measured in a scintillation solution. RESULTS: (99m)Tc-LDE images of the primary tumor and of metastasis sites were obtained in all 18 breast cancer patients. As directly measured in the tumor and in the normal mammary tissue, the amount of the emulsion radioactive label in the tumor was 4.5 times greater than in the normal tissue (range 1.2- to 8.8-fold). CONCLUSION: LDE concentrates much more in malignant breast tumor tissue than in the normal tissue. Thus it has potential to carry drugs or radionuclides directed against mammary carcinoma cells for diagnostic or therapeutic purposes. |
| Uptake of a cholesterol-rich emulsion by neoplastic ovarian tissues Ades, A., J. P. Carvalho, et al. (2001), Gynecol Oncol 82(1): 84-7. Abstract: OBJECTIVE: Previously, it was shown that a lipidic emulsion (LDE) composed of phospholipids and cholesterol esters which binds to low-density lipoprotein (LDL) receptors may concentrate in acute myeloid leukemia cells. In this study, we aimed to verify whether LDE also has the ability to concentrate in malignant ovarian cancer after being injected into the blood circulation of the patients. METHODS: Three groups of women scheduled for surgery were included in the survey: 13 bearing malignant tumors, 9 with benign ovarian tumors, and 13 without ovarian tumor who were scheduled to undergo oophorectomy due to malignant disease of the uterine cervix or endometrium. On the day prior to surgery they were injected with LDE labeled with (14)Ccholesteryl oleate. Specimens of tumors and normal ovaries excised during surgery were lipid extracted and analyzed for radioactivity counting. Results were expressed in radioactive count (cpm) per gram of tissue. RESULTS: The mean of the uptakes of the emulsion radioactivity by the malignant tumors was roughly eightfold greater when compared with that of the contralateral normal ovaries (2261 +/- 1444 and 275 +/- 137 cpm/g, respectively, P < 0.012), benign tumors, and normal ovaries of the patients without ovarian tumors. CONCLUSION: LDE has the ability to concentrate in malignant ovarian tumor tissue. Therefore, it can be used as a vehicle to direct cytotoxic drugs against malignant ovarian tumors, thus diminishing the side effects of chemotherapy. |
| Uptake of cholesterol by small intestinal brush border membrane is protein-mediated Thurnhofer, H. and H. Hauser (1990), Biochemistry 29(8): 2142-8. Abstract: Absorption of cholesterol by small intestinal brush border membrane from either mixed micelles or small unilamellar vesicles is protein-mediated. It is a second-order reaction. The kinetic data are consistent with a mechanism involving collision-induced transfer of cholesterol. With micelles as the donor particle, there is net transfer of cholesterol while with small unilamellar vesicles as the donor, cholesterol is evenly distributed between the two lipid pools at equilibrium. The cholesterol absorption by brush border membrane from both mixed micelles and small unilamellar vesicles reveals saturation kinetics. Proteolytic treatment of brush border membrane with papain releases about 25% of the total membrane protein. As a result, the cholesterol uptake by brush border membrane changes from a second-order reaction to a first-order one. The reaction mechanism changes from collision-induced cholesterol uptake to a mechanism involving diffusion of monomeric cholesterol through the aqueous phase. The protein(s) released into the supernatant by papain treatment of brush border membrane exhibit(s) cholesterol exchange activity between two populations of small unilamellar vesicles. The supernate-protein(s) bind(s) the spin-labeled cholesterol analogue 3-doxyl-5 alpha-cholestane. |
| Uptake of exogenous free cholesterol induces upregulation of tissue factor expression in human monocyte-derived macrophages Lesnik, P., M. Rouis, et al. (1992), Proc Natl Acad Sci U S A 89(21): 10370-4. Abstract: Lipid-laden macrophages present as foam cells may contribute to the hyperthrombotic state of human atherosclerotic lesions by the production of tissue factor (TF). We investigated the effect of exogenous nonlipoprotein cholesterol on the expression of TF by human monocyte-derived macrophages in culture. Nonlipoprotein cholesterol at 50 micrograms/ml increased TF activity 4-fold; TF induction was dose- and time-dependent. Expression of TF activity was positively correlated with the free cholesterol content of monocyte-derived macrophages, was increased upon inhibition of cholesterol esterification, and reflected de novo synthesis of TF protein. TF expression in cholesterol-loaded macrophages remained sensitive to stimulation (approximately 12-fold) by bacterial lipopolysaccharide, indicating that intracellular free cholesterol and lipopolysaccharide act by distinct mechanisms in inducing TF procoagulant activity. Our results suggest that loading human monocyte-derived macrophages with free cholesterol induces upregulation of TF expression, thereby contributing to thrombus formation at sites of plaque rupture. |
| Uptake of glucose and cholesterol by the ovary of sheep and cattle and the influence of arterial LH concentrations Rabiee, A. R. and I. J. Lean (2000), Anim Reprod Sci 64(3-4): 199-209. Abstract: Time series analysis methods were used to evaluate the relationships between the uptake of glucose and cholesterol, and arterial luteinizing hormone (LH) concentrations. Classical arterio-venous difference methods were applied to study ovarian uptake of metabolites. Arterial and venous samples (n=20) were obtained from six cows and nine sheep every 10min. There were highly significant positive cross-correlations of 0.5 for cattle and 0.8 for sheep between the uptake of glucose and cholesterol at lag 0. All individual cross-correlations were significant for sheep. Uptake of these metabolites was not significantly associated with arterial LH concentrations in the cows.This study suggests that glucose may promote cholesterol uptake into the ovarian cells or vice versa. This study is the first to identify such a relationship. If these findings are repeated, the possibility exists that control of the oestrous cycle and fertility may be achieved by seeking a common regulator of uptake of these metabolites or by uncoupling the association between glucose and cholesterol. |
| Uptake of high density lipoprotein cholesterol ester by HepG2 cells involves apolipoprotein E localized on the cell surface Leblond, L. and Y. L. Marcel (1993), J Biol Chem 268(3): 1670-6. Abstract: High density lipoprotein (HDL) cholesterol ester (CE) is taken up by many cells without simultaneous uptake of HDL apoprotein. The studies described herein demonstrate that the selective uptake of cholesterol ester by HepG2 cells is reduced by antibody directed against the receptor-binding domain of apoE (monoclonal antibody (mAb) 1D7) but not by antibody directed against the NH2-terminal portion of the molecule. The reduction, by 1D7, of HDL cholesteryl ester uptake is not due to apoE acquisition by the labeled HDL preparation or by the transfer of 3HCE of HDL to apoE-containing lipoproteins and uptake by the apoB/E or apoE receptors. Rather, it appears that mAb 1D7 recognizes apoE localized at the cell surface of HepG2 cells. This conclusion is supported by the fact that: 1) reduction of HDL-CE uptake by HepG2 cells is observed within 15 min after the addition of the antibody-ligand mixture; 2) 1D7 is similarly effective in reducing the selective uptake of HDL-CE when added to the ligand or to the cells; 3) three different anti-apoE mAbs (1D7, 3B7, and 3H1) bind specifically to the surface of the cells. We have also demonstrated that heparin (5 mg/ml) does not reduce the amount of apoE-immunoreactive material bound at the cell surface when added before or after the binding period. 1D7, but not 3B7 or 3H1, binds less in the presence of heparin. The observations are consistent with a localization of apoE on the cell membrane rather than on lipoproteins bound to apoB/E or apoE receptors. |
| Uptake, distribution and binding of vertebrate and invertebrate steroid hormones and time-dependence of ponasterone A binding in Calliphora vicina. Comparisons among cholesterol, corticosterone, cortisol, dexamethasone, 5 alpha-dihydrotestosterone, 1,25-dihydroxyvitamin D3, ecdysone, estradiol-17 beta, ponasterone A, progesterone, and testosterone Bidmon, H. J. and W. E. Stumpf (1991), Histochemistry 96(5): 419-34. Abstract: The presence of specific binding sites for radiolabelled vertebrate-type and arthropod-type steroid hormones was investigated in several organs including salivary gland, and central nervous system of third instar Calliphora vicina larvae by thaw-mount autoradiography. Ponasterone A, a 20-hydroxyecdysone agonist and 20-hydroxyecdysone are the only steroids which bind to nuclear high affinity binding sites. These binding sites are DNA associated while nucleoli show no tracer binding. Ecdysone, an endogenous 20-hydroxyecdysone precursor, is taken up by target cells but no significant nuclear binding occurs. 1,25-Dihydroxyvitamin D3 concentrates in cytoplasm only and its uptake is highest compared to all other steroids. Progesterone and testosterone show weak accumulation in the cytoplasm, while for cholesterol, corticosterone, cortisol, dexamethasone, dihydrotestosterone and estradiol-17 beta, no noticeable uptake occurs. For ponasterone A, a clear time dependence of uptake and intracellular distribution is visible, suggesting the existence and involvement of specific ecdysteroid uptake and transport mechanisms. These results suggest the presence of binding sites for various mammalian steroids in insects. Whether vertebrate steroid hormones or metabolites of them play a role in insects or whether the uptake and binding is based on chemical similarities alone without biological significance remains to be further investigated. |
| Uptake, metabolism, and cytotoxicity of isomeric cholesterol-5,6-epoxides in rabbit aortic endothelial cells Sevanian, A., J. Berliner, et al. (1991), J Lipid Res 32(1): 147-55. Abstract: The isomeric cholesterol-5,6-epoxides represent two common cholesterol autoxidation products and along with their principal metabolic product, 3 beta,5 alpha,6 beta-cholestane triol, are purportedly angiotoxic. The uptake and cytotoxic action of these compounds was examined in cultured rabbit aortic endothelial cells emphasizing mechanisms of uptake and metabolic fate. The isomeric cholesterol epoxides are incorporated with equal facility and in a dose-dependent manner. The pattern of uptake, which is markedly influenced by media serum concentration and by temperature, suggests that these compounds are partly incorporated through association with serum lipoproteins. After incorporation, both epoxide isomers are rapidly converted to cholestane triol which readily exits the cells. Cholestane triol is further metabolized to an ester-type product representing up to 10% of the added cholesterol epoxides by 24 h of incubation. The order of cytotoxic potency of these cholesterol oxides is: cholestane triol greater than cholesterol-beta-epoxide greater than cholesterol-alpha-epoxide, with LD50 concentrations ranging from 23 to greater than 150 microM in confluent cells. Cholestane triol and cholesterol-beta-epoxide are twice as cytotoxic to subconfluent cells as compared to confluent cells, whereas cholesterol-alpha-epoxide is essentially equitoxic to confluent and subconfluent cells. Cholesterol epoxide cytotoxicity is significantly reduced by treatments in the absence of serum in accord with substantial reduction in uptake when incubations are performed in serum-free media. Our findings show that these cytotoxic cholesterol oxides are incorporated by endothelial cells through a combination of receptor-mediated and nonspecific or passive mechanisms; however, the efficacy of uptake and resulting toxicity is substantially influenced by serum lipoproteins. |
| Uptake, transfer, and esterification of cell-derived cholesterol in plasma of patients with familial HDL-deficiency von Eckardstein, A., Y. Huang, et al. (1996), Z Gastroenterol 34 Suppl 3: 143-4. |
| Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats Balasubramanian, T. (2003), ScientificWorldJournal 3: 930-6. Abstract: In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs), can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels. |
| Urinary excretion of mevalonic acid as an indicator of cholesterol synthesis Lindenthal, B., A. Simatupang, et al. (1996), J Lipid Res 37(10): 2193-201. Abstract: Urinary excretion of mevalonic acid was investigated as an indicator of cholesterol synthesis. In normolipemic volunteers, excretion of mevalonic acid averaged 3.51 +/- 0.59 (SD) micrograms/kg x day1; (n = 24) and was not different from patients with hypercholesterolemia (3.30 +/- 0.92 micrograms/kg x day1; n = 24). In patients with cerebrotendineous xanthomatosis, the excretion was significantly higher (8.55 +/- 1.92 micrograms/kg x day1; n = 6, P < 0.001) but comparable to volunteers treated with cholestyramine (6.69 +/- 2.6 micrograms/kg x day1; n = 5). A significant correlation was found between 24-h excretion of mevalonic acid and cholesterol synthesis (r = 0.835; n = 35; P < 0.001). The coefficient of variation of excretion of mevalonic acid during 3 consecutive days was small (9.8%; n = 7). However, urinary output of mevalonic acid was significantly higher during the night (164 +/- 14 micrograms/12-h) than during the day (129 +/- 9 micrograms/12-h; n = 11; P < 0.05). In patients treated with simvastatin (40 mg/day) for 6 weeks, the ratio of mevalonic acid to creatinine in a morning urine sample decreased significantly compared to pretreatment values (110 +/- 25 micrograms/g vs. 66 +/- 25 micrograms/g; P < 0.001). Furthermore, the ratio of mevalonic acid to creatinine in a morning urine sample correlated with the ratio from the 24-h collection period (r = 0.714; n = 34; P < 0.001). The results indicate that the analysis of urinary mevalonic acid, either in 24-h collection or in a single morning sample, is an attractive method for evaluation of long and very short term changes of the rates of cholesterol synthesis. |
| Urinary nitrate excretion in cholesterol-fed rabbits: effect of a chronic treatment by N-iminoethyl-L-lysine, a selective inhibitor of inducible nitric oxide synthase Behr-Roussel, D., A. Rupin, et al. (2000), Eur J Pharmacol 388(3): 275-9. Abstract: To evaluate the influence of atherosclerosis on the global production of NO, we studied the effect of a 0.3% cholesterol-enriched diet on urinary nitrate excretion in rabbits during 69 weeks. To examine whether the inducible nitric oxide synthase (iNOS) present in atherosclerotic lesions could participate in NO excretion, hypercholesterolemic rabbits were treated chronically with the selective iNOS inhibitor, N-iminoethyl-L-lysine (L-NIL; 5 mg/kg/day). Urinary nitrate excretion was higher in hypercholesterolemic than in control rabbits throughout the study period and decreased progressively with time in both groups; L-NIL had no significant effect on urinary nitrate excretion. These data illustrate that systemic NO production is enhanced in hypercholesterolemia and that iNOS, present within the plaque, might not participate in this enhanced NO production. |
| Ursodeoxycholate conjugates protect against disruption of cholesterol-rich membranes by bile salts Heuman, D. M. and R. Bajaj (1994), Gastroenterology 106(5): 1333-41. Abstract: BACKGROUND/AIMS: Ursodeoxycholic acid attenuates hepatocellular injury in cholestatic disorders, possibly by counteracting membrane disruptive effects of endogenous bile salts. The possible physicochemical basis of this protective effect was explored by using model membranes composed of egg phosphatidylcholine and cholesterol. METHODS: Large unilamellar vesicles containing trapped 3H inulin were prepared by extrusion and gel filtration. Vesicle disruption (release of trapped inulin) was quantified using rapid centrifugal ultrafiltration. RESULTS: Disruption of membranes increased with bile salt concentration, hydrophobicity, and increasing ionic strength. Disruption decreased with a decreasing bile salt/phospholipid ratio or an increasing cholesterol/phospholipid ratio. Vesicle disruption by taurodeoxycholate (3 alpha, 12 alpha-dihydroxy-5 beta-cholanoyl taurine) was reduced in a concentration-dependent manner by addition of tauroursodeoxycholate (3 alpha,7 beta-dihydroxy-5 beta-cholanoyl taurine) (TUDC) when the cholesterol/phospholipid ratio was > or = 0.5, but TUDC was not protective at a cholesterol/phospholipid ratio < or = 0.2. Glycoursodeoxycholate (3 alpha,7 beta-dihydroxy-5 beta-cholanoyl glycine) was somewhat less protective than TUDC, and unconjugated ursodeoxycholate (3 alpha,7 beta-dihydroxy-5 beta-cholanoate) (UDC) had little effect. Taurine conjugates of several other hydrophilic bile salts were also protective, but protection was not strictly proportional to hydrophilicity. CONCLUSIONS: Conjugates of UDC and other hydrophilic bile salts can reduce disruption of cholesterol-rich model membranes by more toxic bile salts via a purely physicochemical mechanism. UDC conjugates in vivo may protect the cholestatic liver by preventing bile salt disruption of the cholesterol-rich canalicular membrane. |
| Ursodeoxycholate stabilizes phospholipid-rich membranes and mimics the effect of cholesterol: investigations on large unilamellar vesicles Guldutuna, S., B. Deisinger, et al. (1997), Biochim Biophys Acta 1326(2): 265-74. Abstract: Ursodeoxycholate is used to treat primary biliary cirrhosis and is incorporated into hepatocyte plasma membranes. Its steroid nucleus binds to the apolar domain of the membrane, in a similar position to cholesterol. Therefore the question arises whether ursodeoxycholate has a similar effect on membrane structure and stability as cholesterol. Using differential scanning calorimetry the thermotropic behavior of egg phosphatidylcholine and dimyristoylphosphatidylcholine were studied after incubation with cholesterol or ursodeoxycholate. Large unilamellar vesicles were prepared with cholesterol contents of 0-50%. Following incubation of these vesicles with different amounts of ursodeoxycholate, vesicle stability in a gravitational field was investigated by measuring the phospholipid and cholesterol release. Vesicle size was studied by laser light scattering after incubation with cheno- and ursodeoxycholate, and the release of entrapped carboxyfluorescein was measured by means of fluorescence spectroscopy. Increasing cholesterol diminished the enthalpy of the phase transition in the membrane. Ursodeoxycholate decreased the enthalpy of the phase transition at even lower concentrations. Lipid release from vesicles in a high gravitational field diminished with increasing cholesterol content of the vesicles. Ursodeoxycholate had a comparable effect, which increased as the cholesterol content of the vesicles was decreased. Chenodeoxycholate damaged vesicles, whereas ursodeoxycholate did not. Cholesterol and ursodeoxycholate (below its critical micellar concentration) decreased the carboxyfluorescein release from vesicles induced by chenodeoxycholate. Thus like cholesterol, ursodeoxycholate is incorporated into phospholipid model membranes and reduces the change in enthalpy of the gel to liquid-crystalline phase transition. Like cholesterol ursodeoxycholate also maintains membrane stability and prevents membrane damage induced by mechanical and chemical stress. |
| Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group Petroni, M. L., R. P. Jazrawi, et al. (2001), Aliment Pharmacol Ther 15(1): 123-8. Abstract: BACKGROUND: Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization. AIM: To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy. PATIENTS AND METHODS: A total of 154 symptomatic patients with radiolucent stones (< or = 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6-monthly oral cholecystography and ultrasonography for up to 24 months. RESULTS: Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side-effects or dropout rate. Complete gallstone dissolution on an intention-to-treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively. CONCLUSION: There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain. |
| Ursodeoxycholic acid and cholesterol induce enterohepatic cycling of bilirubin in rodents Mendez-Sanchez, N., M. A. Brink, et al. (1998), Gastroenterology 115(3): 722-32. Abstract: BACKGROUND & AIMS: Oral administration of ursodeoxycholic acid (UDCA) and cholesterol causes bile salt malabsorption; the former by competition for and the latter by down-regulation of ileal bile acid transporters. Because ileectomy in rats induces enterohepatic cycling of bilirubin, the hypothesis that dietary steroids might have the same effect was tested. METHODS: Male inbred C57L/J mice and Sprague-Dawley rats were fed low doses of UDCA, chenodeoxycholic acid (CDCA), or cholesterol added to laboratory chow with simultaneous chow-fed controls. After 1 week (mice) or 2 weeks (rats), indices of bile salt malabsorption and enterohepatic cycling of bilirubin were measured, including bilirubin secretion rates into bile, serum and intestinal bilirubin and bile salt levels, and urobilinogen levels in cecum, large intestine, and feces. RESULTS: Dietary UDCA and cholesterol, but not CDCA, significantly increased bilirubin secretion rates into bile. In UDCA-fed mice, gallbladder biles contained increased levels of bilirubin conjugates and unconjugated bilirubin, and in 60%, granules of amorphous calcium bilirubinate precipitated. Dietary cholesterol and bile acids, particularly UDCA, increased cecal bile salt levels, unconjugated bilirubin and urobilinogen concentrations, and decreased fecal bilirubin outputs, consistent with colonic absorption. CONCLUSIONS: By causing bile salt malabsorption, dietary UDCA and cholesterol induce enterohepatic cycling of bilirubin. |
| Ursodeoxycholic acid decreases viscosity and sedimentable fractions of gallbladder bile in patients with cholesterol gallstones Fischer, S., I. Muller, et al. (2004), Eur J Gastroenterol Hepatol 16(3): 305-11. Abstract: OBJECTIVES: Ursodeoxycholic acid (UDCA) therapy is associated with reduced risk of biliary pain and acute cholecystitis or pancreatitis in patients with cholesterol gallstones. The underlying mechanisms are understood incompletely, which prompted us to study the influence of UDCA treatment on composition, viscosity and sedimentable fractions of gallbladder bile in 25 patients with symptomatic cholesterol gallstones. METHODS: In two randomised groups, either UDCA (750 mg daily) or placebo was given to each patient 10-12 days before cholecystectomy. Gallbladder bile was collected intraoperatively and analysed for protein, mucin, lipid composition, cholesterol crystal observation time, amount of cholesterol in vesicles, viscosity and sedimentable fractions (cholesterol, protein, mucin, bilirubin). RESULTS: UDCA-treated patients showed longer cholesterol crystal observation times and lower concentrations of total cholesterol and percentages of vesicular cholesterol in gallbladder bile. The concentrations of protein and mucin in gallbladder bile tended to be lower in the UDCA-treated group, but phospholipids, bile acids and bilirubin did not differ between the groups. Viscosity and the total sedimentable fractions of gallbladder bile decreased in the UDCA-treated patients. CONCLUSIONS: UDCA treatment reduces total and vesicular cholesterol, the formation of cholesterol crystals, viscosity, and the total amount of sedimentable fractions in gallbladder bile. These observations might explain, at least partially, why UDCA treatment attenuates the occurrence of biliary pain and complications in gallstone patients. |
| US consumer body calls for review of cholesterol guidelines Lenzer, J. (2004), Bmj 329(7469): 759. |
| Use and outcomes of a cholesterol-lowering intervention for rural elderly subjects Ives, D. G., L. H. Kuller, et al. (1993), Am J Prev Med 9(5): 274-81. Abstract: Few studies have evaluated the efficacy of cholesterol-lowering interventions in a community setting and have included a control or comparison group. As part of a preventive health demonstration project in rural Pennsylvania, Medicare beneficiaries underwent cholesterol screening to identify high-risk individuals with serum cholesterol levels > or = 240 mg/dL. These high-risk individuals were randomized to a cholesterol-lowering intervention through either local hospitals or physicians' offices or to a control group. Baseline and follow-up serum cholesterol levels collected two to three years later were compared according to service location (hospital versus physician's office), intervention attendance, degree of participation, baseline heart disease history, and cholesterol-lowering medication use at follow-up. Serum cholesterol levels decreased between 5.7% and 6.6% in the hospital-based and physician-based groups, as well as in a control group not offered the intervention. Participation rates did not differ between treatment groups, nor did participation affect serum cholesterol levels. Attendance level and heart disease history were not associated with a greater decrease in serum cholesterol levels. Individuals reporting cholesterol-lowering drug use at follow-up had significantly higher baseline serum cholesterol levels and a significantly greater decrease in total serum cholesterol (P <.0001) than those not on medication. Both nonpharmacological (diet) and pharmacological (drug) interventions will reduce serum cholesterol levels and heart attack risk. The study results suggest that, at least for older individuals, the impact of nonpharmacological interventions on the community is minimal. We conclude that only very aggressive treatment will significantly loser serum cholesterol levels in older individuals at risk for heart attack. |