| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Cholesterol crystal embolization demonstrated on GI biopsy Paraf, F., C. Jacquot, et al. (2001), Am J Gastroenterol 96(12): 3301-4. Abstract: OBJECTIVES: Cholesterol crystal embolism is a severe complication of atherosclerosis responsible for nonspecific cutaneous, renal, and, less often, digestive manifestations that may mimic other systemic diseases. METHODS: We reviewed retrospectively 10 patients with histologically proven cholesterol crystal emboli diagnosed by endoscopic GI biopsy. RESULTS: All patients had prior clinical manifestations of severe atherosclerosis and predisposing factors for cholesterol migration. They all had cutaneous manifestations of cholesterol crystal embolism, acute renal failure, and biological inflammatory syndrome. Digestive symptoms were found in the 10 patients: abdominal pain in eight, diarrhea in four, and GI bleeding in three. GI endoscopy ruled out specific digestive diseases, showing only a congestive or erosive mucosa. Histological diagnosis of cholesterol crystal emboli was based on gastric biopsy in nine patients, duodenal biopsy in four, colonic biopsy in three, and rectal biopsy in one, with six having positive biopsies on multiple sites. Outcome after the diagnosis of cholesterol crystal embolism was poor, with all patients requiring permanent hemodialysis. Death by atherosclerosis complications occurred in five patients. CONCLUSIONS: This cohort suggests that upper GI endoscopy may be helpful in demonstrating the presence of cholesterol crystal embolism, and that diagnosis of cholesterol crystal emboli on digestive tract biopsy indicates advanced systemic atherosclerosis disease of poor prognosis. |
| Cholesterol crystal embolization simulating focal myositis Germain, P., C. Dumoulin, et al. (2001), Joint Bone Spine 68(3): 267-9. Abstract: Cholesterol crystal embolization usually produces characteristic skin lesions. We report a case responsible for myositis of the calf without suggestive skin lesions. The outcome in this 58-year-old patient was spontaneously favorable. Cholesterol crystal embolization can produce a range of clinical symptoms, with the skin, kidneys, and eyes being the most common targets. Generalized forms can result in systemic disease. The diagnosis rests on histological findings, and the treatment is symptomatic. Anticoagulants have been shown to worsen the manifestations, whereas antiplatelet therapy may be useful. |
| Cholesterol crystal embolization, a rare cause of postoperative ischemic colitis Pfeifer, M., H. Kogel, et al. (1990), Vasa 19(1): 54-8. Abstract: An ischemic colitis of the descending Colon and Sigma in 3 patients following aorto-iliacal reconstruction was caused by embolism of cholesterol crystals. In all cases the stump pressure of the inferior mesenteric artery measured more than 40 Torr as an empiric value. Therefore a good collateral blood flow could be expected. Nevertheless a malperfusion of the left Colon occurred. These cases of postoperative ischemic colitis were caused by multiple cholesterol crystal emboli in the arterioles of the colon descendens and Sigma. The mobilisation and embolism of arteriosclerotic material during aorto-iliac reconstruction must be responsible for the unfortunate event. Awareness of a bowel ischemia following abdominal aortic surgery and immediate endoscopic control should lead to an early diagnosis and a higher survival rate. A decision to redo operation with left hemicolectomy is required at an early stage. |
| Cholesterol crystal embolization: more common than we thought? Lawson, J. M. (2001), Am J Gastroenterol 96(12): 3230-2. |
| Cholesterol crystal embolization-associated renal failure after therapy with recombinant tissue-type plasminogen activator Gupta, B. K., B. S. Spinowitz, et al. (1993), Am J Kidney Dis 21(6): 659-62. Abstract: We report the occurrence of renal failure due to cholesterol crystal embolization following thrombolytic therapy with intravenous recombinant tissue-type plasminogen activator (t-PA). No invasive vascular procedure had been performed. Although there is one case report of cholesterol crystal embolization following t-PA therapy with only extrarenal manifestations (N Engl J Med 321:1270, 1989), this is the first reported case of atheroembolic acute renal failure following t-PA therapy. |
| Cholesterol crystal morphology in acalculous gallbladder disease Landi, K., J. Sinard, et al. (2003), J Clin Gastroenterol 36(4): 364-6. Abstract: BACKGROUND: Biliary crystal morphology is best described in patients with gallbladder stones, but most patients undergoing bile collection for microscopy have a clinical diagnosis of acalculous gallbladder disease. We investigated the morphology of biliary crystals in such patients. STUDY: Bile was obtained for polarizing microscopy from fresh cholecystectomy specimens of patients with a clinical diagnosis of acalculous or calculous gallbladder disease. Slides for microscopy were prepared by touch contact with bile in freshly opened gallbladder specimens, and following aspiration of gallbladder bile through a 5-French cannula. RESULTS: Bile was examined from five patients with a clinical diagnosis of acalculous gallbladder disease and five patients with known gallstones. Needle-like cholesterol crystals predominated in most patients without gallstones, whereas plate-like and dot-like crystals were more common in patients with gallstones. All three crystal types were seen in most patients. Crystal morphology was not affected by aspiration of bile through a 5-French cannula. CONCLUSIONS: Birefringent needles and dots should be recognized as cholesterol crystals during bile microscopy. These crystal morphologies may predominate in some patients with a clinical diagnosis of acalculous gallbladder disease. |
| Cholesterol crystal nucleation from enzymatically modified low-density lipoproteins: combined effect of sphingomyelinase and cholesterol esterase Guarino, A. J., T. N. Tulenko, et al. (2004), Biochemistry 43(6): 1685-93. Abstract: An assay detecting and quantifying cholesterol nucleation from low-density lipoproteins has been established. Forster resonance energy transfer between dehydroergosterol and dansylated lecithin becomes significantly alleviated as a consequence of conucleation of dehydroergosterol and cholesterol. The assay, in combination with dynamic light scattering, absorbance spectroscopy, and fluorescence microscopy, can be used to study aggregation and nucleation in model blood systems. Human plasma LDL was labeled with dehydroergosterol and dansylated lecithin by incubation with donor multilamellar liposomes and isolated by centrifugation. Exposure of labeled LDL (0.5 mg/mL of total lipids) to sphingomyelinase (0.0-0.2 unit/mL) led to modest particle aggregation but produced no changes in energy transfer and no crystallization. However, addition of sphingomyelinase produced significant particle aggregation, nucleation, and crystallization, in a dose-dependent fashion, in samples that were previously treated with the enzyme, cholesterol esterase (0.2 unit/mL). The combination of cholesterol esterase and sphingomyelinase led to a significant alleviation of energy transfer, which preceded by 24 h the appearance of fluorescent, microscopic sterol crystals. These results point to a synergistic effect between cholesterol esterase and sphingomyelinase, suggesting that mere aggregation of LDL is insufficient to promote nucleation, and crystal formation likely proceeds in the intracellular space after LDL uptake by macrophages. |
| Cholesterol crystal nucleation: a decade-long search for the missing link in gallstone pathogenesis Afdhal, N. H. and B. F. Smith (1990), Hepatology 11(4): 699-702. |
| Cholesterol crystalline polymorphism and the solubility of cholesterol in phosphatidylserine Epand, R. M., D. Bach, et al. (2000), Biophys J 78(2): 866-73. Abstract: There is a marked hysteresis between the heating and cooling polymorphic phase transition of anhydrous cholesterol. At a scan rate of 0.05 degrees C/min the difference in transition temperatures between heating and cooling scans is approximately 10 degrees C. This phenomenon also occurs with mixtures of cholesterol with phosphatidylserine and can result in an underestimation of the amount of crystalline cholesterol in a sample that has not been cooled sufficiently. With 1-palmitoyl-2-oleoyl phosphatidylserine and 1-stearoyl-2-oleoyl phosphatidylserine the cholesterol crystallites form while the lipid remains in the L(alpha) phase. Sonication of dimyristoyl phosphatidylserine with a 0.4 mol fraction cholesterol results in the loss of cholesterol crystallite diffraction, but only a partial loss of the polymorphic transition detected by calorimetry. We therefore conclude that the thermal history of the sample can have profound effects on the appearance of the polymorphic phase transition of cholesterol by differential scanning calorimetry. Depending on the morphology of the vesicles, diffraction methods may underevaluate the amount of cholesterol crystallites present. |
| Cholesterol crystallisation in bile Portincasa, P., K. J. van Erpecum, et al. (1997), Gut 41(2): 138-41. |
| Cholesterol crystallite nucleation in supersaturated model biles from a thermodynamic standpoint Liu, C. L. and W. I. Higuchi (2002), Biochim Biophys Acta 1588(1): 15-25. Abstract: A rapid, silicone polymer film uptake method was used to determine the cholesterol (Ch) thermodynamic activity (A(T)) in taurocholate (TC)-lecithin (L) and taurochenodeoxycholate (TCDC)-L model biles supersaturated with Ch. Also, time-dependent quasielastic light scattering (QLS) measurements and microscopic observations were made to determine the nature of particle species and the Ch nucleation times. In all cases in which Ch-L vesicles were present, a linear relationship between the logarithm of Ch nucleation times and Ch A(T) was found. These findings support that Ch A(T) is the appropriate parameter that represents the Ch nucleation tendency and that vesicles are catalytic sites in the Ch nucleation process. When Ca2+, a nucleation promoter ion, was present in the supersaturated model biles, the increased values of Ch A(T) quantitatively correlated with shorter Ch nucleation times. These latter findings further demonstrate that Ch A(T) is the dominant factor in explaining the Ch nucleation tendencies in supersaturated model biles. |
| Cholesterol crystallization and macrophage apoptosis: implication for atherosclerotic plaque instability and rupture Geng, Y. J., J. E. Phillips, et al. (2003), Biochem Pharmacol 66(8): 1485-92. Abstract: The presence of abundant cholesterol crystals symbolizes the disorder of cholesterol metabolism during the development of atherosclerosis. Examination of cultured human THP-1 macrophages treated with the cholesterol oxide, 7-ketocholesterol, revealed a concentration- and time-dependent increase in formation of cholesterol crystals in the cells. Radioisotope labeling and X-ray diffraction confirmed the presence of 7-ketocholesterol crystalline domains (d space 35.8A). Under the normal cell culture condition (5% CO(2), 37 degrees), incubation with 7-ketocholesterol induced moderate levels of apoptosis. Elevating temperature from 37 to 40 degrees markedly reduces formation of the crystals in the macrophages. Meanwhile, at high temperatures, significantly increased numbers of apoptotic cells were detected in the cells treated with 7-ketocholesterol but not in those with native free cholesterol. These results suggest that hyperthermia inhibits cholesterol crystallization and promotes apoptotic effects of oxysterols on macrophages. |
| Cholesterol crystallization in gall-bladder bile of pigs given cholesterol-beta-cyclodextrin-enriched diets with either casein or soyabean concentrate as protein sources Catala, I., C. Juste, et al. (2000), Br J Nutr 83(4): 411-20. Abstract: Cholesterol precipitation from supersaturated bile is the earliest and determinant step in the formation of cholesterol gallstones, which is thought to be diet-dependent. Bile composition, appearance and growth of cholesterol crystals were studied in fresh gall-bladder biles from pigs adapted to four different protein-containing diets over 3 weeks: 160 g dietary protein/kg as casein (C16; n 6), or as soyabean-protein concentrate (S16; n 6), or a mixture of both protein sources (casein-soyabean protein, 70:30, w/w) (CS16; n 6), or 320 g of the mixed protein/kg (CS32; n 6). Moreover, all four diets contained 3 g cholesterol/kg and 50 g beta-cyclodextrin/kg as modifiers of bile composition towards cholesterol pro-crystallization. Cholesterol precipitation was most active after the high-protein diet, CS32, and the casein diet, C16, and lowest after the soyabean-protein diet, S16. It was intermediate after the mixed diet, CS16, but still much lower than in the former two groups. These diet-induced variations were suggested to be mediated through modifications in the biliary profile of bile acids, whereas all other biliary constituents studied were essentially unchanged. The fasting level of plasma cholesterol was lowest in both 160 g protein/kg diets containing soyabean protein (S16 and CS16), highest for the high-protein diet CS32, and intermediate for the C16 diet. These results should encourage clinical studies on the effect of soyabean protein, or other vegetable proteins, for primary or recurrence prevention of cholelithiasis at its earliest stage. |
| Cholesterol crystallization in human gallbladder bile: relation to gallstone number, bile composition, and apolipoprotein E4 isoform Van Erpecum, K. J., G. P. Van Berge-henegouwen, et al. (1998), Hepatology 27(6): 1508-16. Abstract: Patients with multiple cholesterol gallstones are at increased risk of recurrence after nonsurgical therapy, possibly because of fast biliary cholesterol crystallization. Serum apolipoprotein E4 (apo E4) is a risk factor for primary cholesterol gallstone formation as well as recurrence. We examined potential effects of stone number and apolipoprotein E genotype on crystallization and on various crystallization-influencing factors in gallbladder biles of 36 cholesterol stone patients (25 multiple stones: 10 carrying the epsilon4 allele). Biliary cholesterol saturation, bile salt composition or concentrations of total protein, immunoglobulin (Ig)A, IgG, alpha1-acid glycoprotein, haptoglobin, or mucin--all crystallization promoters--did not differ between multiple and solitary stone patients, apparently not explaining different speed of crystallization (crystal observation time 3.5 +/- 0.6 days vs. 12.7 +/- 2.4 days, respectively; P =.0003). In contrast, biliary aminopeptidase-N activities (2,607 +/- 592 mU/mL vs. 947 +/- 185 mU/mL; P =.04) were higher and IgM levels (179 +/- 39 vs. 65 +/- 8 mg/L; P =.09) tended to be higher in the case of multiple stones. Although patients carrying the epsilon4 allele had similar stone numbers and crystallization as patients without the epsilon4 allele, their cholesterol saturation index (CSI) was lower (1.08 +/- 0.09 vs. 1.54 +/- 0.13; P =.01), whereas total protein and bile salt concentrations tended to be higher with preferential taurine-conjugation. In conclusion, fast cholesterol crystallization is associated with multiple stones but not with apolipoprotein E4. Whereas fast crystallization may contribute to high recurrence rates after nonsurgical therapy in case of multiple gallstones, the mechanism for increased risk of gallstone formation in patients carrying the epsilon4 allele remains unknown. |
| Cholesterol crystallization in model biles: effects of bile salt and phospholipid species composition Moschetta, A., G. P. vanBerge-Henegouwen, et al. (2001), J Lipid Res 42(8): 1273-81. Abstract: Cholesterol in human bile is solubilized in micelles by (relatively hydrophobic) bile salts and phosphatidylcholine (unsaturated acyl chains at sn-2 position). Hydrophilic tauroursodeoxycholate, dipalmitoyl phosphatidylcholine, and sphingomyelin all decrease cholesterol crystal-containing zones in the equilibrium ternary phase diagram (van Erpecum, K. J., and M. C. Carey. 1997. Biochim. Biophys. Acta. 1345: 269-282) and thus could be valuable in gallstone prevention. We have now compared crystallization in cholesterol-supersaturated model systems (3.6 g/dl, 37 degrees C) composed of various bile salts as well as egg yolk phosphatidylcholine (unsaturated acyl chains at sn-2 position), dipalmitoyl phosphatidylcholine, or sphingomyelin throughout the phase diagram. At low phospholipid contents left two-phase (micelle plus crystal-containing) zone, tauroursodeoxycholate, dipalmitoyl phosphatidylcholine, and sphingomyelin all enhanced crystallization. At pathophysiologically relevant intermediate phospholipid contents central three-phase (micelle plus vesicle plus crystal-containing) zone, tauroursodeoxycholate inhibited, but dipalmitoyl phosphatidylcholine and sphingomyelin enhanced, crystallization. Also, during 10 days of incubation, there was a strong decrease in vesicular cholesterol contents and vesicular cholesterol-to-phospholipid ratios (approximately 1 on day 10), coinciding with a strong increase in crystal mass. At high phospholipid contents right two-phase (micelle plus vesicle-containing) zone, vesicles were always unsaturated and crystallization did not occur. Strategies aiming to increase amounts of hydrophilic bile salts may be preferable to increasing saturated phospholipids in bile, because the latter may enhance crystallization. |
| Cholesterol crystallization-promoters in human bile: comparative potencies of immunoglobulins, alpha 1-acid glycoprotein, phospholipase C, and aminopeptidase N1 Abei, M., J. Schwarzendrube, et al. (1993), J Lipid Res 34(7): 1141-8. Abstract: Concanavalin A (Con A)-binding glycoproteins accelerate the rate of cholesterol crystal formation as a prelude to gallstone formation. Immunoglobulins (IgM, IgA, and IgG), aminopeptidase N (APN), phospholipase C (pcPLC), and alpha 1-acid glycoprotein from this Con A fraction have all been proposed as candidate promoters. We immunopurified each of the six putative promoters and examined their comparative effects by adding equal amounts to a cholesterol crystal growth assay. The effects of immunoabsorptive removal of each of the specific candidate promoters from native bile were also compared. In additional studies, the potency of these proteins was in the following order: IgM > IgA = AAG > IgG. APN and pcPLC showed no effect on cholesterol crystal growth at their apparent physiological concentrations. In subtractive experiments, only a minor loss (< 10%) of net promoting activity from that of the whole Con A-bound fraction was observed after immunoabsorptive removal of pcPLC, APN, or immunoglobulins. Total removal of AAG, however, showed a far greater loss (/33%) of the net promoting activity. These data indicate that AAG accounts for the greatest portion of net biliary Con A-bound promoting activity derived from currently defined and well-identified glycoproteins. However, more than 60% of total Con A-binding promoting activity remains unaccounted for, indicating the presence of other important and still unidentified promoters in human bile. |
| Cholesterol crystallization-promoting activity of aminopeptidase-N isolated from the vesicular carrier of biliary lipids Nunez, L., L. Amigo, et al. (1993), FEBS Lett 329(1-2): 84-8. Abstract: Different hydrophobic glycoproteins are associated to native biliary vesicles, which are the major carrier of biliary cholesterol. Some of these proteins promote cholesterol crystallization, a key step in cholesterol gallstone formation. This study was specifically conducted to identify the 130 kDa biliary vesicle-associated glycoprotein and to determine its in vitro effect on the cholesterol crystal formation time. The 130 kDa vesicular glycoprotein was identified as aminopeptidase-N by amino acid sequencing and specific enzymatic assay. Polyclonal antibodies raised against aminopeptidase-N allowed us to determine its concentration in human hepatic bile, which varied from 17.3 to 57.6 micrograms/ml. Aminopeptidase-N showed a concentration-dependent cholesterol crystallization activity when it was added to supersaturated model bile at a concentration range usually found in native bile. Because of this promoting effect on in vitro cholesterol crystal formation, we suggest that biliary aminopeptidase-N may play a critical role in the pathogenesis of cholesterol gallstone disease. |
| Cholesterol crystals and IgE-containing immune complexes in rheumatoid pericarditis Van Offel, J. F., L. S. De Clerck, et al. (1991), Clin Rheumatol 10(1): 78-80. Abstract: A 72-year-old rheumatoid arthritis patient is described presenting with acute dyspnoea and peripheral oedema. A pericardial effusion with signs of tamponade was diagnosed. Examination of the pericardial fluid revealed the presence of cholesterol crystals and IgE-containing immune complexes. The significance of these findings in the differential diagnosis of pericardial disease is discussed. |
| Cholesterol crystals as an etiological factor in non-resolving chronic inflammation: an experimental study in guinea pigs Nair, P. N., U. Sjogren, et al. (1998), Eur J Oral Sci 106(2 Pt 1): 644-50. Abstract: The presence of cholesterol crystals has been suggested to be a factor interfering with periapical healing after conventional endodontic treatment. This investigation addresses the role of cholesterol crystals in impairing healing by studying the tissue response to the crystals, which were implanted in animals. Pure cholesterol crystals, prepared to a mushy form, were placed in Teflon cages that were implanted subcutaneously in guinea pigs. The cage-contents were retrieved after 2, 4 and 32 wk of implantation and processed for light and electron microscopy. The cages revealed delicate connective tissue that grew in through perforations on the cage-wall. The crystals were densely surrounded by numerous macrophages and multinucleated giant cells, forming a well-circumscribed area of tissue reaction. The cells, however, were unable to eliminate the crystals during an observation period of 8 months. The congregation of macrophages and giant cells, known to be major sources of apical inflammatory and bone resorptive mediators, suggest that accumulation of cholesterol crystals can be a factor in the failure of certain apical periodontitis lesions to resolve after conventional root-filling therapy. |
| Cholesterol crystals in BAL fluid from patients with idiopathic pulmonary fibrosis Fireman, E., S. Spitzer, et al. (1996), Respir Med 90(6): 361-3. |