| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Phospholipid transfer protein mediates transfer of not only phosphatidylcholine but also cholesterol from phosphatidylcholine-cholesterol vesicles to high density lipoproteins Nishida, H. I. and T. Nishida (1997), J Biol Chem 272(11): 6959-64. Abstract: Phospholipid transfer protein (PLTP) purified from human plasma was found to enhance the transfer of cholesterol from single bilayer vesicles containing phosphatidylcholine and cholesterol to high density lipoprotein-3. The rate of cholesterol transfer was greatly influenced by the cholesterol content of the donor vesicles. The maximal rate was observed with the vesicles containing 20-25 mol % cholesterol. This was in contrast to a progressive decline in the rate of phosphatidylcholine transfer with an increase in the cholesterol content. To determine the binding of cholesterol and phosphatidylcholine to PLTP, the mixtures of PLTP and the vesicles containing 3H-labeled phosphatidylcholine and 14C-labeled cholesterol were incubated and subjected to sucrose density gradient centrifugation. Determination of the label profiles showed that cholesterol as well as phosphatidylcholine were transferred from the vesicles to PLTP. The reversible nature of the binding was shown by the transfer of labeled cholesterol and phosphatidylcholine bound to PLTP to the acceptor vesicles or low density lipoprotein. Isothermal equilibrium binding of PLTP for cholesterol and phosphatidylcholine showed that PLTP possessed a considerably higher affinity and binding capacity for phosphatidylcholine than for cholesterol. The phosphatidylcholine binding affinity and capacity were greater when PLTP was incubated with phosphatidylcholine vesicles without cholesterol. A possible importance of PLTP-mediated cholesterol transfer in the circulation was described. |
| Phospholipid vesicles and other cholesterol carriers in bile Gilat, T. and G. J. Somjen (1996), Biochim Biophys Acta 1286(2): 95-115. |
| Phospholipid/cholesterol model membranes: formation of cholesterol crystallites Bach, D. and E. Wachtel (2003), Biochim Biophys Acta 1610(2): 187-97. Abstract: Experimental data that define conditions under which cholesterol crystallites form in cholesterol/phospholipid model membranes are reviewed. Structural features of the phospholipids that determine cholesterol crystallization include the length and degree of unsaturation of the acyl chains, the presence of charge on the headgroups and interheadgroup hydrogen bonds. |
| Phospholipid/cholesteryl ester microemulsions containing unesterified cholesterol: model systems for low density lipoproteins Reisinger, R. E. and D. Atkinson (1990), J Lipid Res 31(5): 849-58. Abstract: As models for the effects of unesterified cholesterol (UC) on the lipid organization of low density lipoprotein (LDL), microemulsions containing either egg yolk phosphatidylcholine (EYPC) or dimyristoyl phosphatidylcholine (DMPC) as the surface component, cholesteryl oleate (CO) as the core component, and varying amounts of unesterified cholesterol were prepared by sonication. Gel filtration chromatography showed coelution of each of the lipid components, demonstrating the formation of well-defined microemulsion populations. Unesterified cholesterol incorporation into the microemulsions was proportional to the composition of the original mixture at low unesterified cholesterol compositions, but reached saturation at compositions of approximately 15 and 10 mol% unesterified cholesterol for EYPC/CO and DMPC/CO microemulsions, respectively. The Stokes' radius of the microemulsions was constant and similar to native LDL for initial compositions less than 15 mol% unesterified cholesterol, but increased at compositions above 15 mol%. In both EYPC/CO/UC and DMPC/CO/UC microemulsions, no significant changes were observed for the calorimetric or Van't Hoff enthalpy for the thermal transition of the core cholesteryl ester; however, increases in the transition temperature as a function of increasing unesterified cholesterol composition suggests that unesterified cholesterol has a stabilizing effect on the core transition. In DMPC/CO/UC microemulsions, the effect of unesterified cholesterol on the surface-located DMPC could be clearly observed as a broadening of the thermal transition of the acyl chains. These results demonstrate that unesterified cholesterol is located primarily in the surface of these protein-free lipid model systems for LDL. |
| Phospholipid-cholesterol bilayers under osmotic stress Sparr, E., L. Hallin, et al. (2002), Biophys J 83(4): 2015-25. Abstract: Isothermal (27 degrees C) phase behavior of dimyristoyl phosphatidyl choline-cholesterol mixtures at various osmotic pressures and cholesterol contents was investigated by means of isothermal sorption microcalorimetry and (2)H-nuclear magnetic resonance. The calorimetric method allows for simultaneous measurement of the partial molar enthalpy and the chemical potential (the osmotic pressure) of water, thus providing an almost complete thermodynamic description of the sorption process. From the experimental results, the Pi(osm) - X(chol) and the ternary composition phase diagrams are constructed. We note that there are strong similarities between the Pi(osm) - X(chol) phase diagram and the previously reported T - X(chol) phase diagram at excess water. At high cholesterol contents a single liquid ordered (L(alpha)(o)) phase is present over the whole range of water contents, implying that this phase has a remarkable stability not only at decreasing temperature but also at increasing osmotic pressure. At low cholesterol contents, the microcalorimetric experiments confirm the extraordinary property of cholesterol not to cause any substantial melting point depression. One important conclusion in the present study is that the P(beta) phase can dissolve cholesterol more readily than the L(beta) phase and that the addition of cholesterol induces the P(beta) phase. Finally, the putative P(beta) - L(alpha)(o) periodic modulated structure is discussed. |
| Phospholipids containing nitrogen- and sulfur-linked chains: kinetics of cholesterol exchange between vesicles Kan, C. C., R. Bittman, et al. (1991), Biochim Biophys Acta 1066(1): 95-101. Abstract: We have examined the kinetics of 14Ccholesterol exchange between unilamellar vesicles formed from the following synthetic glycerophosphatidylcholines: (a) those having acyl (OC(O)R), acylamino (NHC(O)R), carbamoyl (NHC(O)OR), and acylthio (SC(O)R) chains at the sn-2 position, and (b) those having alkyl (OR) and thioalkyl (SR) chains at the sn-1 position. Replacement of the glycerol oxygen atom at the sn-2 position of PC with a NH group did not affect the rate of cholesterol exchange to a significant extent, suggesting that the amide group of sphingomyelin is not primarily responsible for the very slow rate of exchange of cholesterol observed from sphingomyelin vesicles. Replacement of the glycerol oxygen at the sn-2 position of phosphatidylcholine with a sulfur atom caused the rate of spontaneous cholesterol exchange to increase by a factor of 1.6. Substitution of an O-alkyl chain for the acyl chain at the sn-1 position of 2-acylthiophosphatidylcholine or substitution of a thioalkyl chain for the O-alkyl sn-1 chain of 1-alkyl-2-acylaminodeoxyphosphatidylcholine also did not result in a marked difference in cholesterol exchange rate. The data suggest that interactions other than intermolecular hydrogen bonding are involved in determining the rates of intermembrane cholesterol exchange. Significantly, these kinetic studies also lend support to the continued use in model membranes of synthetic sulfur- and nitrogen-substituted phosphatidylcholines, which have been employed to study properties of lipolytic enzymes, since synthetic acylamino- and acylthio-phospholipids form vesicles that give cholesterol exchange rates that closely resemble those found in vesicles prepared with diester-phosphatidylcholines. |
| Phosphorus-containing inhibitors of HMG-CoA reductase. 1. 4-(2-arylethyl)hydroxyphosphinyl-3-hydroxy-butanoic acids: a new class of cell-selective inhibitors of cholesterol biosynthesis Karanewsky, D. S., M. C. Badia, et al. (1990), J Med Chem 33(11): 2952-6. |
| Photobleaching of arterial fluorescent compounds: characterization of elastin, collagen and cholesterol time-resolved spectra during prolonged ultraviolet irradiation Marcu, L., W. S. Grundfest, et al. (1999), Photochem Photobiol 69(6): 713-21. Abstract: To study the photobleaching of the main fluorescent compounds of the arterial wall, we repeatedly measured the time-resolved fluorescence of elastin, collagen and cholesterol during 560 s of excitation with nitrogen laser pulses. Three fluence rate levels were used: 0.72, 7.25 and 21.75 microW/mm2. The irradiation-related changes of the fluorescence intensity and of the time-resolved fluorescence decay constants were characterized for the emission at 390, 430 and 470 nm. The fluorescence intensity at 390 nm decreased by 25-35% when the fluence delivered was 4 mJ/mm2, a common value in fluorescence studies of the arterial wall. Cholesterol fluorescence photobleached the most, and elastin fluorescence photobleached the least. Photobleaching was most intense at 390 nm and least intense at 470 nm such that the emission spectra of the three compounds were markedly distorted by photobleaching. The time-resolved decay constants and the fluorescence lifetime were not altered by irradiation when the fluence was below 4 mJ/mm2. The spectral distortions associated with photobleaching complicate the interpretation of arterial wall fluorescence in terms of tissue content in elastin, collagen and cholesterol. Use of the time-dependent features of the emission that are not altered by photobleaching should increase the accuracy of arterial wall analysis by fluorescence spectroscopy. |
| Photoinduced interaction of thionine with phospholipid and cholesterol in artificial membranes SenVarma, C. and B. B. Bhowmik (1991), J Photochem Photobiol B 8(3): 295-305. Abstract: The photoinduced interaction of thionine dye with phosphatidylcholine (PC) (and its components, e.g. lysoPC, phosphorylcholine and choline) and oxidized cholesterol was studied in artificial membranes using spectrophotometric and photoelectrochemical methods. The results show that the dye (electron acceptor) in its singlet excited state forms 1:1 electron donor-acceptor (EDA) complexes with the lipids (electron donor). The electrode kinetics of the photoinduced redox reactions in the cell were also studied to confirm the mechanism of photoinduced interaction between the dye and the lipid. |
| Photoperoxidation of cholesterol in homogeneous solution, isolated membranes, and cells: comparison of the 5 alpha- and 6 beta-hydroperoxides as indicators of singlet oxygen intermediacy Korytowski, W., G. J. Bachowski, et al. (1992), Photochem Photobiol 56(1): 1-8. Abstract: Singlet oxygen (1O2) can react with cholesterol (Ch) to give three possible ene-addition hydroperoxides: 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH), and 3 beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH). The rates of dye-sensitized photogeneration and also the fates of 5 alpha-OOH and 6 beta-OOH in membrane bilayers have been studied and compared. Irradiation of unilamellar 14CCh/phospholipid vesicles in the presence of aluminum phthalocyanine tetrasulfonate or merocyanine 540 resulted in formation of 5 alpha-OOH and 6 beta-OOH, as determined by high performance liquid chromatography with radiochemical or electrochemical detection. The initial rate of 6 beta-OOH formation was 30-35% that of 5 alpha-OOH in a variety of liposomal systems. However, after a lag, 5 alpha-OOH invariably decayed via allylic rearrangement to 7 alpha-OOH (also known to be a free radical product), whereas 6 beta-OOH accumulated in unabated fashion until Ch depletion became limiting. Photooxidation of Ch in an isolated natural membrane (erythrocyte ghost) or in L1210 leukemia cells gave similar results. When the reaction was carried out in pyridine or methanol, the rate of 6 beta-OOH formation relative to 5 alpha-OOH was reduced by approximately half, with essentially no isomerization of the latter to 7 alpha-OOH.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Photosensitive liposomes as 'cages' for laser-triggered solute delivery: the effect of bilayer cholesterol on kinetics of solute release Bisby, R. H., C. Mead, et al. (1999), FEBS Lett 463(1-2): 165-8. Abstract: Liposomes containing acyl chains incorporating azobenzene chromophores have been investigated as potential 'caging' agents for fast solute release. On photolysis, trapped marker dye can be released from gel-phase liposomes within milliseconds. Solute release is markedly sensitive to the presence of cholesterol in the bilayer. Phospholipids bearing one saturated acyl chain and an azobenzene-substituted chain are ineffective as sensitisers unless cholesterol is present, while doubly substituted phospholipids sensitise release in its absence. Cholesterol markedly affects the temperature profile of solute release depending on the host phospholipid chain length. Solute release is not seen for lipid hosts with unsaturated acyl chains. |
| Photosensitized oxidation of cholesterol in biological systems: reaction pathways, cytotoxic effects and defense mechanisms Girotti, A. W. (1992), J Photochem Photobiol B 13(2): 105-18. Abstract: Cholesterol resembles other unsaturated lipids in being susceptible to peroxidative degradation when exposed to a sensitizing agent, exciting light of suitable wavelength and molecular oxygen. Selected hydroperoxides of cholesterol can be used as relatively convenient and reliable indicators of primary photochemical mechanisms, allowing a distinction to be made between free radical-mediated and singlet oxygen-mediated reactions. When generated in cell membranes, hydroperoxides of cholesterol and other lipids can have deleterious effects on membrane structure and function. Such damage may be exacerbated if these photoproducts undergo one-electron reduction to oxyl radicals which in turn initiate chain peroxidation reactions. Cells can resist these effects by using a membrane-based glutathione peroxidase to catalyze the two-electron reduction and detoxification of lipid hydroperoxides. Recent advances in our understanding of cholesterol photo-oxidation from the standpoints of (a) mechanistic information, (b) cytotoxicity and (c) cytoprotection are discussed in this article. |
| Phthalocyanine-sensitized lipid peroxidation in cell membranes: use of cholesterol and azide as probes of primary photochemistry Bachowski, G. J., E. Ben-Hur, et al. (1991), J Photochem Photobiol B 9(3-4): 307-21. Abstract: Various phthalacyanine (Pc) derivatives of phototherapeutic interest have been shown to be efficient type II (singlet oxygen, 1O2) sensitizers in aqueous and non-aqueous solutions. However, primary Pc photochemistry in biological environments, e.g. cell membranes, has not been studied in a definitive manner. To address this question, we used endogenous cholesterol in the erythrocyte ghost as a mechanistic reporter lipid Membranes sensitized with chloroaluminum Pc tetrasulfonate (AlPcS) and exposed to white light at 10 degrees C underwent lipid peroxidation, as indicated by the accumulation of hydroperoxides and thiobarbituric acid reactivity. Specific analysis of cholesterol photo-products by thin layer chromatography and high performance liquid chromatography revealed the presence of 3 beta-hydroxy-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), with much smaller amounts of 3 beta-hydroxycholest-5-ene-7 alpha-hydroperoxide (7 alpha-OOH) and 5 alpha-cholest-6-en-3 beta, 5-diol and cholest-5-en-3 beta, 7 alpha-diol (5 alpha-OH and 7 alpha-OH). Identification of 5 alpha-OOH as a major photoproduct provides unambiguous evidence for large scale 1O2 intermediacy. Azide inhibited lipid peroxidation in a dose-dependent fashion, providing additional support for a type II mechanism. However, the 1O2 quenching constant from Stern-Volmer analysis was approximately 50 times lower than that determined for a non-membrane probe, lactate dehydrogenase. The latter value agreed with literature values. A probable explanation is that membrane-bound dye generates most of the 1O2 involved in lipid peroxidation. Although azide can intercept any 1O2 escaping into (or formed in) the medium, it has limited access to 1O2 generated on the membrane and reacting (or being quenched) near its site of origin. |
| Physical activity and high density lipoprotein cholesterol Hartung, G. H. (1995), J Sports Med Phys Fitness 35(1): 1-5. |
| Physical activity and high density lipoprotein cholesterol levels: what is the relationship? Kokkinos, P. F. and B. Fernhall (1999), Sports Med 28(5): 307-14. Abstract: High density lipoprotein cholesterol (HDL-C) levels are strongly, inversely and independently associated with coronary heart disease (CHD). Increased physical activity is associated with reduced CHD mortality. This protection against CHD may partially be explained by the increase in HDL-C levels observed following aerobic exercise training. Many also agree that an exercise threshold needs to be met before such favourable changes in HDL-C metabolism can occur. Most likely, the exercise-induced changes in HDL-C are the result of the interaction amongst exercise intensity, frequency, duration of each exercise session and length of the exercise training period. Although a relative contribution of each exercise component (intensity, duration and frequency) is also likely, it has not been established. There is also substantial support for a dose-response relationship. Favourable changes in HDL-C appear to occur incrementally and reach statistical significance at approximately 7-10 miles per week or 1200 to 1600kcal. Exercise-induced changes in HDL-C may also be gender dependent. The volume of exercise required to increase HDL-C levels appears to be substantially more for women than men. This perhaps is due to higher HDL-C levels in women at baseline compared with men. However, the many other health benefits derived from increased physical activity should encourage women to participate in regular exercise regardless of the exercise effects on HDL-C levels. A practical approach in prescribing exercise for patients is to use moderate intensity exercises (70 to 80% of predicted maximal heart rate), 3 to 5 times per week, for a total of 7 to 14 miles per week. This is equivalent to approximately 1200 to 1600kcal per week. Moderate to low intensity exercise should be preferred because such exercise carries a lower risk for cardiac complications. In addition, patients are more likely to participate and sustain a lower than higher intensity exercise programme. It is also important to recognise that other modes of physical activity can also be encouraged for patients. Such activities should be associated with similar increases in HDL-C levels as long as they meet or exceed the caloric expenditure of 1200 to 1600kcal (7 to 14 miles per week of jogging). |
| Physical activity modulates the combined effect of a common variant of the lipoprotein lipase gene and smoking on serum triglyceride levels and high-density lipoprotein cholesterol in men Senti, M., R. Elosua, et al. (2001), Hum Genet 109(4): 385-92. Abstract: Physical activity has been identified as a protective factor against the occurrence and progression of coronary heart disease. The lipoprotein lipase (LPL) HindIII polymorphism has been associated with changes in triglyceride and high density lipoprotein (HDL)-cholesterol levels. We have investigated whether the association between the LPL HindIII genetic polymorphism and lipid levels is modified by physical activity. We have also tested the hypothesis that physical activity may interact with smoking and the LPL HindIII polymorphism to determine an individual's plasma lipid concentrations. A total of 520 men were selected from a representative sample used in a population study conducted in Gerona, Spain. The median value (291 kcal/day) of energy expenditure in leisure-time physical activity of the studied sample was selected as a cut-off to define sedentary or active subjects. Serum HDL-cholesterol was positively and significantly associated with the amount of daily energy expenditure in physical activity, whereas inverse associations were seen between physical activity and triglyceride concentration and with the triglyceride to HDL-cholesterol ratio. These effects were consistent across LPL HindIII genotypes. There was a statistically significant interaction between LPL genotype and smoking on lipid concentrations. No statistically significant differences were observed in lipid levels of active or sedentary non-smokers between H- carriers and H+H+ homozygotes for the LPL HindIII polymorphism. In smokers, sedentary H+H+ homozygotes showed significantly higher triglyceride and lower HDL-cholesterol concentrations than sedentary H- carriers. These differences were smaller and not statistically significant when lipid values of active H+H+ homozygotes were compared with active H- carriers. Among all subgroups, sedentary smokers with the H+H+ genotype had the most adverse lipid profile, which was considerably less adverse in H+H+ smokers who were physically active. These findings suggest that the presence of the H+H+ genotype has a deleterious effect on lipid profile in an adverse environment such as smoking, and that the expenditure of more than 291 kcal/day in physical activity attenuates this effect. |
| Physical effects of biologically formed cholesterol oxidation products on lipid membranes investigated with fluorescence depolarization spectroscopy and electron spin resonance Verhagen, J. C., P. ter Braake, et al. (1996), J Lipid Res 37(7): 1488-502. Abstract: Planar oriented membranes of 1-palmitoyl, 2-oleoyl-phosphatidylcholine (POPC) containing cholesterol, 19-hydroxycholesterol, 22S-hydroxycholesterol, or 25-hydroxycholesterol in concentrations up to 5 mol % were investigated with angle-resolved fluorescence depolarization and electron spin resonance measurements. Analyses of the data with the Brownian diffusion model show that the oxysterols have structural effects similar to those of cholesterol: an increase in molecular order and no change in the rotational diffusion coefficients of the probe molecules. Time-resolved fluorescence anisotropy measurements on diphenylhexatriene (DPH) in small unilamellar vesicles of POPC and DOPC were performed using oxysterols commonly found in oxidized low density lipoproteins (LDL) in comparison to membranes containing cholesterol or no sterols. Analyses using the Brownian rotational diffusion model show that most LDL-oxysterols affect the vesicle physical structure in a manner similar to cholesterol, viz. an increase in molecular order and a decrease in the dynamics. Cholesterol-alpha-epoxide has a much smaller ordering effect than cholesterol in POPC-vesicles. A similar effect was found for 7 beta-hydroxycholesterol in DOPC-vesicles. The tendency of the oxysterols to influence the molecular order as compared to pure cholesterol may contribute to cell membrane permeability changes affecting crucial cell functions and events leading to vascular cell injury. Increased LDL oxysterol levels may account for some of the structural changes noted for oxidatively modified LDL as well as its toxicity to vascular cells. |
| Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis Tulenko, T. N., M. Chen, et al. (1998), J Lipid Res 39(5): 947-56. Abstract: Small angle X-ray diffraction was used to examine arterial smooth muscle cell (SMC) plasma membranes isolated from control and cholesterol-fed (2%) atherosclerotic rabbits. A microsomal membrane enriched with plasma membrane obtained from animals fed cholesterol for up to 13 weeks showed a progressive elevation in the membrane unesterified (free) cholesterol:phospholipid (C/PL) mole ratio. Beyond 9 weeks of cholesterol feeding, X-ray diffraction patterns demonstrated a lateral immiscible cholesterol domain at 37 degrees C with a unit cell periodicity of 34 A coexisting within the liquid crystalline lipid bilayer. On warming, the immiscible cholesterol domain disappeared, and on cooling it reappeared, indicating that the immiscible cholesterol domain was fully reversible. These effects were reproduced in a model C/PL binary lipid system. In rabbits fed cholesterol for less than 9 weeks, lesser increases in membrane C/PL mole ratio were observed. X-ray diffraction analysis demonstrated an increase in membrane bilayer width that correlated with the C/PL mole ratio. This effect was also reproduced in a C/PL binary lipid system. Taken together, these findings demonstrate that in vivo, feeding of cholesterol causes cholesterol-phospholipid interactions in the membrane bilayer that alter bilayer structure and organization. This interaction results in an increase in bilayer width peaking at a saturating membrane cholesterol concentration, beyond which lateral phase separation occurs resulting in the formation of separate cholesterol bilayer domains. These alterations in structure and organization in SMC plasma membranes may have significance in phenotypic modulation or aortic SMC during early atherogenesis. |
| Physical fitness and reverse cholesterol transport Olchawa, B., B. A. Kingwell, et al. (2004), Arterioscler Thromb Vasc Biol 24(6): 1087-91. Abstract: BACKGROUND: Physical exercise is associated with a decreased risk of cardiovascular disease, which may be partly caused by the effect of exercise on the lipoprotein profile. The most consistent effect of exercise on lipoprotein metabolism is an increase in high-density lipoprotein (HDL). METHODS AND RESULTS: Parameters of reverse cholesterol transport (RCT) in 25 endurance-trained male athletes were compared with 33 age-matched males enjoying an active lifestyle. VO2max was higher in athletes than in controls (53.4+/-1.2 versus 38.8+/-1.0 mL/min per kg; P<0.01). The following differences in parameters of RCT were found: (1) plasma HDL cholesterol and apoA-I levels were higher in athletes compared with controls (1.7+/-0.1 versus 1.4+/-0.1 mmol/L; P<0.001; and 145+/-2 versus 128+/-3 mg/dL; P<0.001, respectively). Both correlated with VO2max up to the value of 51 mL/min per kg; (2) prebeta1-HDL was higher in athletes than in controls (54+/-4 versus 37+/-3 microg/mL; P<0.001) and correlated positively with VO2max; (3) lecithin cholesterol: acyltransferase activity was higher in athletes (29.8+/-1.2 versus 24.2+/-1.4 nmol/microL per hour; P<0.005); and (4) the capacity of plasma to promote cholesterol efflux from macrophages was higher in athletes (18.8%+/-0.8% versus 16.2%+/-0.3%; P<0.03). CONCLUSIONS: The likely reason for higher HDL concentration in physically fit people is increased formation of HDL from apoA-I and cellular lipids. |
| Physical laws of cholesterol gallstone fragmentation Neubrand, M., I. Greinwald, et al. (1997), Eur J Clin Invest 27(3): 234-41. Abstract: Efficient fragmentation is the most important prerequisite for successful treatment of gallstones by extracorporeally induced shock waves. No data are available on the amount of energy necessary for stone disintegration and on the threshold energy below which no further fragmentation occurs. We therefore performed an in vitro investigation on human cholesterol gallstones to elucidate physical laws governing shock-wave lithotripsy. First, the focal pressure of the lithotripter was measured to calculate the energy traversing a stone. Second, 96 gallstones from 16 gall bladders were analysed with respect to physicochemical composition, radiological features and ultrasound before fragmentation was performed. Energy for stone disintegration was constant within each stone family but varied between 4.6 mL-1 and 36.8J mL-1 in different families. This energy correlated linearly with stone volume. None of the radiological and physicochemical factors revealed a clear-cut correlation of the different energies necessary for similar stone disintegration. The threshold energy differed between 0.26 mJ and 1.04 mJ per pulse. In conclusion, stone volume was the best parameter predicting stone fragmentation. However, in cholesterol stones with a similar composition the required energy per volume varies considerably together with the threshold energy. Radiological and ultrasound parameters appear to be of minor importance in explaining these differences. |