| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats Ikeda, I., Y. Imasato, et al. (1992), Biochim Biophys Acta 1127(2): 141-6. Abstract: A(-)-epicatechin (EC) and (-)-epigallocatechin (EGC) mixture and a mixture of their gallates (ECG and EGCG, respectively) markedly lowered lymphatic cholesterol absorption in rats with a cannulated thoracic duct. A mixture of ECG and EGCG was more effective in reducing cholesterol absorption than the EC and EGC mixture. These catechins also tended to decrease lymphatic absorption of triacylglycerols, although not so pronounced as in cholesterol absorption. An in vitro study on micellar solubility of cholesterol showed that these catechin mixtures precipitated cholesterol solubilized in mixed bile salt micelles in a dose-dependent manner. A mixture of ECG and EGCG more effectively precipitated micellar cholesterol than a mixture of EC and EGC. When purified EC, EGC, ECG and EGCG were used, EGCG was more effective in precipitating micellar cholesterol than ECG. The effect of EC and EGC was comparable and weaker than their gallate esters. The bile acid concentration in the micelles was not affected by these catechins. A positive correlation was observed between the amount of coprecipitated EGCG and cholesterol. These results clearly show that tea catechins, in particular their gallate esters, effectively reduce cholesterol absorption from the intestine by reducing solubility of cholesterol in mixed micelles. The observation accounts for the hypocholesterolemic effect of tea catechins. |
| Tea catechins inhibit cholesterol oxidation accompanying oxidation of low density lipoprotein in vitro Osada, K., M. Takahashi, et al. (2001), Comp Biochem Physiol C Toxicol Pharmacol 128(2): 153-64. Abstract: Endogenous oxidized cholesterols are potent atherogenic agents. Therefore, the antioxidative effects of green tea catechins (GTC) against cholesterol oxidation were examined in an in vitro lipoprotein oxidation system. The antioxidative potency of GTC against copper catalyzed LDL oxidation was in the decreasing order (-)-epigalocatechin gallate (EGCG)=(-)-epicatechin gallate (ECG)>(-)-epicatechin (EC)=(+)-catechin (C)>(-)-epigallocatechin (EGC). Reflecting these activities, both EGCG (74%) and ECG (70%) inhibited the formation of oxidized cholesterol, as well as the decrease of linoleic and arachidonic acids, in copper catalyzed LDL oxidation. The formation of oxidized cholesterol in 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH)-mediated oxidation of rat plasma was also inhibited when the rats were given diets containing 0.5% ECG or EGCG. In addition, EGCG and ECG highly inhibited oxygen consumption and formation of conjugated dienes in AAPH-mediated linoleic acid peroxidative reaction. These two species of catechin also markedly lowered the generation of hydroxyl radical and superoxide anion. Thus, GTC, especially ECG and EGCG, seem to inhibit cholesterol oxidation in LDL by combination of interference with PUFA oxidation, the reduction and scavenging of copper ion, hydroxyl radical generated from peroxidation of PUFA and superoxide anion. |
| Tea consumption. relationship to cholesterol, blood pressure, and coronary and total mortality Stensvold, I., A. Tverdal, et al. (1992), Prev Med 21(4): 546-53. Abstract: BACKGROUND AND METHODS. The relation of tea to cholesterol, systolic blood pressure, and mortality from coronary heart disease and all causes was studied in 9,856 men and 10,233 women without history of cardiovascular disease or diabetes. All men and women 35-49 years of age from the county of Oppland (Norway) were invited to participate; the attendance rate was 90%. RESULTS. Mean serum cholesterol decreased with increasing tea consumption, the linear trend coefficient corresponded to a difference of 0.24 mmol/liter (9.3 mg/dl) in men and 0.15 mmol/liter (5.8 mg/dl) in women between drinkers of less than one cup and those of five or more cups/day, when other risk factors were taken into account. Systolic blood pressure was inversely related to tea with a difference between the same two tea groups of 2.1 mm in men and 3.5 mm in women. Altogether 396 men and 237 women died from all causes, and of these 141 and 18, respectively, died from coronary heart disease during the 12-year follow-up period. The mortality rate was higher (not statistically significant) among persons drinking no tea or less than one cup compared with persons drinking one or more cups/day. This applies to men and women and to coronary heart disease and all-cause mortality. For men, the relative risk (one or more versus less than one cup) for coronary death from Cox regression was 0.64 (95% CI:0.38, 1.07). |
| Teaching pediatric residents to control cholesterol with diet. C.A.D.R.E. Study Group Jackson, S. M. and P. M. Darden (1991), Ann N Y Acad Sci 623: 424-6. |
| Tear cholesterol levels in blepharitis Saatci, A. O., M. Irkec, et al. (1990), Ophthalmic Res 22(5): 269-70. Abstract: The tear levels of cholesterol of 17 patients with chronic blepharitis and 17 healthy subjects were determined by the photometric method. The mean cholesterol level of the patients was determined to be 56.1 +/- 8.9 (SEM) mg/dl. No statistically significant difference between the tear cholesterol levels of the two groups could be detected. |
| Tellurium blocks cholesterol synthesis by inhibiting squalene metabolism: preferential vulnerability to this metabolic block leads to peripheral nervous system demyelination Wagner-Recio, M., A. D. Toews, et al. (1991), J Neurochem 57(6): 1891-901. Abstract: Inclusion of 1.1% elemental tellurium in the diet of postweanling rats produces a peripheral neuropathy due to a highly synchronous primary demyelination of sciatic nerve; this demyelination is followed closely by remyelination. Sciatic nerves from animals fed tellurium for various times were removed and incubated ex vivo for 1 h with 14Cacetate, and radioactivity incorporated into individual lipid classes was determined. In nerves from rats exposed to tellurium, there was a profound and selective block in the conversion of radioactive acetate to cholesterol. Another radioactive precursor, 3Hwater, gave similar results. We suggest that tellurium feeding inhibits squalene epoxidase activity and that the consequent lack of cholesterol destabilizes myelin, thereby causing destruction of the larger internodes. Ex vivo incubation experiments were also carried out with liver slices. As with nerve, tellurium feeding caused accumulation in squalene of label from radioactive acetate, whereas labeling of cholesterol was greatly inhibited. Unexpectedly, however, incorporation of label from 3Hwater into both squalene and cholesterol was increased. Relevant is the demonstration that liver was the primary site of bulk accumulation of squalene, which accounted for 10% of liver dry weight at 5 days. Thus, accumulation of squalene (and other mechanisms, possibly including up-regulation of cholesterol biosynthetic pathways) drives squalene epoxidase activity at normal levels in liver even in the presence of inhibitors of this enzyme. This is reflected by continuing incorporation of 3Hwater into cholesterol; incorporation of this precursor takes place at many of the postsqualene biosynthetic steps for sterol formation. 14CAcetate entering the sterol pathway before squalene in liver is greatly diluted in specific activity when it reaches the large squalene pool, and thus increased squalene epoxidase activity does not transfer significant 14C label to sterols. In contrast to the situation with liver, synthesis of sterols is markedly depressed in sciatic nerve, and squalene does not accumulate to high levels. |
| Tellurium-induced alterations in 3-hydroxy-3-methylglutaryl-CoA reductase gene expression and enzyme activity: differential effects in sciatic nerve and liver suggest tissue-specific regulation of cholesterol synthesis Toews, A. D., J. F. Goodrum, et al. (1991), J Neurochem 57(6): 1902-6. Abstract: The demyelination of peripheral nerves that results from exposure of developing rats to tellurium is due to inhibition of squalene epoxidase, a step in cholesterol biosynthesis. In sciatic nerve, cholesterol synthesis is greatly depressed, whereas in liver, some compensatory mechanism maintains normal levels of cholesterol synthesis. This tissue specificity was further explored by examining, in various tissues, gene expression and enzyme activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Exposure to tellurium resulted in pronounced increases in both message levels and enzyme activity in liver, the expected result consequent to up-regulation of this enzyme in response to decreasing levels of intracellular sterols. In contrast to liver, levels of mRNA and enzyme activity in sciatic nerve were both decreased during the tellurium-induced demyelinating period. The temporal pattern of changes in 3-hydroxy-3-methylglutaryl-CoA reductase message levels in sciatic nerve seen following exposure to tellurium was similar to the down-regulation seen for mRNA specific for PNS myelin proteins. Possible mechanisms for differential control of cholesterol biosynthesis in sciatic nerve and liver are discussed. |
| Telomerase immortalization upregulates Rab9 expression and restores LDL cholesterol egress from Niemann-Pick C1 late endosomes Walter, M., J. P. Davies, et al. (2003), J Lipid Res 44(2): 243-53. Abstract: Niemann-Pick C (NPC) disease is a rare recessive lipidosis marked by excessive accumulation of LDL-derived free cholesterol and glycosphingolipids in the late endosomal-lysosomal (E-L) system. Here we report that ectopic expression of human telomerase reverse transcriptase (hTeRT) in human cells leads to an upregulation of the small GTPase Rab9 and its effector p40. Expression of hTeRT in NPC1 cells results in a correction of their cellular phenotype, including clearance of accumulated cholesterol from their E-L system. Specifically, in NPC1-TeRT cells, the transport of cholesterol from the E-L system to the plasma membrane is restored with a concomitant increase in cholesterol esterification. This effect is Rab9-specific since expression of Rab9 in untransformed NPC1 cells also leads to a reversal of their disease phenotype. These effects are also seen in normal TeRT-immortalized cells and it appears that TeRT expression leads to an increase in the transport of molecules, including cholesterol, from the E-L system, and may play a role in increasing cellular proliferation. These results suggest the existence of alternative endogenous therapeutic targets that can be modulated to reverse the NPC1 disease phenotype. |
| Temperature and cholesterol composition-dependent behavior of 1-myristoyl-2-12-(5-dimethylamino-1-naphthalenesulfonyl)aminododecanoyl-sn-glycero-3-phosphocholine in 1,2-dimyristoyl-sn-glycero-3-phosphocholine membranes Troup, G. M. and S. P. Wrenn (2004), Chem Phys Lipids 131(2): 167-82. Abstract: We present a steady-state and time-resolved fluorescence emission spectra analysis of the membrane probe 1-myristoyl-2-12-(5-dimethylamino-1-naphthalenesulfonyl)aminododecanoyl-sn-glycero-3-phosphocholine (DANSYL) in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol multi-lamellar vesicles (MLV) prepared by modified rapid solvent exchange. We report that the dose-dependent cholesterol-induced blue shifts in the steady-state fluorescence emission spectra observed in DMPC MLV are due to complex solvent effects that include time-dependent dipolar relaxation and the formation of internal charge transfer (ICT) states. A key finding of this investigation is identification of two distinguishable DANSYL populations existing at both shallow and deep locations in the membrane; these two DANSYL populations are evidence of laterally phase-separated domains at cholesterol compositions between X(chol) = 0.30 and 0.60 at 30 degrees C in DMPC MLV. |
| Temperature change of the ripple structure in fully hydrated dimyristoylphosphatidylcholine/cholesterol multibilayers Matuoka, S., S. Kato, et al. (1994), Biophys J 67(2): 728-36. Abstract: The ripple structure was studied as a function of temperature in fully hydrated dimyristoylphosphatidylcholine (DMPC)/cholesterol multibilayers using synchrotron x-ray small-angle diffraction and freeze-fracture electron microscopy. In the presence of cholesterol, the ripple structure appears below the pretransition temperature of pure DMPC multibilayers. In this temperature range the ripple periodicity is relatively large (25-30 nm) and rapidly decreases with increasing temperature. In this region, defined as region I, we observed coexistence of the P beta' phase and the L beta' phase. The large ripple periodicity is caused by the formation of the P beta' phase region in which cholesterol is concentrated and the L beta' phase region from which cholesterol is excluded. An increase in ripple periodicity also takes place in the narrow temperature range just below the main transition temperature. We define this temperature region as region III, where the ripple periodicity increases dramatically toward the main transition temperature. In region II, between regions I and III, the ripple periodicity decreases gradually with temperature. This behavior is quite similar to that of pure DMPC. Temperature-versus-ripple periodicity curves are parallel among pure DMPC and DMPCs with various cholesterol contents. We explain this behavior in terms of a model proposed by other workers. |
| Temperature-dependent aggregation of pH-sensitive phosphatidyl ethanolamine-oleic acid-cholesterol liposomes as measured by fluorescent spectroscopy Torchilin, V. P., V. G. Omelyanenko, et al. (1992), Anal Biochem 207(1): 109-13. Abstract: pH-sensitive liposomes made of phosphatidyl ethanolamine-oleic acid-cholesterol (4:2:4 molar ratio) at neutral pH values aggregate at approximately 40 degrees C. The aggregation is accompanied by liposome destabilization and by the release of intraliposomal fluorescent marker (calcein). Both aggregation and calcein leakage start at the temperature corresponding to the lipid phase transition into hexagonal phase. In the system studied the phase transition temperature interval is within 45 to 55 degrees C as estimated with the use of the fluorescent probe 1,6-diphenylhexatriene. The presence of cell cultivation medium RPMI 1640 decreases liposome aggregation temperature. The addition of 10% serum to the system decreases the temperature at which the aggregation proceeds still further. The conclusion that serum-free media should be used for cell experiments involving pH-sensitive liposomes is made. |
| Temperature-dependent effects of cholesterol on sodium transport through lipid membranes by an ionizable mobile carrier Wehrli, S., C. Ramirez, et al. (1992), Biochim Biophys Acta 1107(2): 319-30. Abstract: Temperature-jump relaxation experiments on Na+ transport by (221)C10-cryptand were carried out in order to study the influence of cholesterol and its temperature-dependence on ion transport through thin lipid membranes. The experiments were performed on large, negatively charged unilamellar vesicles (LUV) prepared from mixtures of dioleoylphosphatidylcholine, phosphatidic acid and cholesterol (mole fractions 0-0.43), at various temperatures and carrier concentrations. The initial rates of Na+ transport and the apparent rate constants of its translocation by (221)C10 increased with the carrier concentration and the temperature. The incorporation of cholesterol into the membranes significantly reduced the carrier concentration- and temperature-dependence of these two parameters. The apparent energy required to activate the transport decreased significantly with increasing carrier concentrations at any given cholesterol molar fraction, and increased significantly with the cholesterol molar fraction at any given carrier concentration. Our interpretation of the action of cholesterol on this transport system is based on the assumption that the binding cavity of cryptands is likely to be located towards the aqueous side of the dipole layer. The results are discussed in terms of the structural, physico-chemical and electrical characteristics of carriers and complexes, and of the interactions occurring between an ionizable mobile carrier and the membrane. |
| Temporal and spatial changes of free cholesterol and neutral lipids in rat brain after transient middle cerebral artery occlusion Kamada, H., K. Sato, et al. (2003), Neurosci Res 45(1): 91-100. Abstract: In order to examine lipid metabolism in relation to neural process following brain ischemia, we investigated temporal and spatial changes of free cholesterol (FC) and neutral lipids (NLs) after 90 min of transient middle cerebral artery occlusion (MCAO). Filipin and Nile Red stainings were performed to detect mainly FC and NLs, respectively. Double stainings for Nile Red plus ED1, MAP2, or GFAP were performed in order to identify cell type of positive stainings. Filipin stanining decreased during 1-7 day and lost at 21 day after transient MCAO in the ischemic core, but did not change in the penumbra. Nile Red positive droplets reached the maximum at 7 day after transient MCAO and gradually decreased in the core, while the peak time delayed in the penumbra. MAP2 immunoreactivity lost at 7 day in the core, and increased in the penumbra during 7-56 day. Most Nile Red positive droplets were double positive for ED1 in the core, and were localized within GFAP positive cells in the penumbra. These results suggest that changes of FC and NLs are different temporally and spatially between the core and penumbra in relation to degenerative and regenerative neural processes following brain ischemia. |
| Temporal and spatial localization of proteoglycan decorin transcripts during the progression of cholesterol-induced atherosclerosis in Japanese quail Velleman, S. G., C. S. Coy, et al. (2003), Connect Tissue Res 44(2): 69-80. Abstract: The temporal and spatial distribution of decorin transcripts, endothelial cells, and smooth muscle actin-producing cells were determined during the progression of atherosclerosis in the dorsal aortas of Japanese quail selected for cholesterol-induced atherosclerosis. The quail were placed on either a control diet or a diet containing 0.5% added cholesterol at approximately 16 weeks of age. Dorsal aortas were collected at 2-week intervals for 18 weeks after initiating cholesterol feeding. In situ hybridization for decorin showed the presence of decorin transcripts in the dorsal aorta intima of cholesterol-fed birds beginning at 6 weeks and continuing through the duration of the study. However, in the control-fed birds, decorin transcripts were not found in the intima but were prominent in the adventitia. In cholesterol-fed birds, immunohistochemical localization for endothelial cells showed that intima areas positive for decorin transcripts colocalized with both the endothelial cells and smooth muscle cell layers. In contrast in the control-fed birds, decorin transcripts aligned with the smooth muscle cell layers and not the endothelial cells. These results are suggestive of a potential role for endothelial cells in intimal decorin expression during atherosclerotic plaque formation. |
| Temporal trends (1986-1997) in cholesterol level assessment and management practices in patients with acute myocardial infarction: a population-based perspective Yarzebski, J., F. Spencer, et al. (2001), Arch Intern Med 161(12): 1521-8. Abstract: BACKGROUND: Elevated serum cholesterol levels are associated with increased risk for acute myocardial infarction (AMI) and adverse patient outcomes. It is unclear what proportion of patients have their serum cholesterol levels measured during hospitalization for AMI and are given hypolipidemic therapy. OBJECTIVE: To examine decade-long trends in measurement of serum cholesterol levels during hospitalization for AMI and use of hypolipidemic therapy. METHODS: Observational study of 5204 residents of the Worcester, Mass, metropolitan area hospitalized with validated AMI in all greater Worcester hospitals in seven 1-year periods from 1986 through 1997. RESULTS: Increases in the measurement of serum cholesterol levels during hospitalization for AMI were observed between 1986 and 1991, followed by a progressive decrease; only 24% of patients with AMI in 1997 underwent cholesterol level testing. Younger age, male sex, and absence of a history of cardiovascular disease were associated with an increased likelihood measurement of serum cholesterol levels. Although the relative use of hypolipidemic therapy increased significantly over time (0.4% in 1986 vs 10.7% in 1997), the absolute rate of use remained low. In patients with elevated serum cholesterol levels (>/=6.2 mmol/L >/=240 mg/dL), 1.9% received hypolipidemic therapy in 1986 and 36.6% in 1997. CONCLUSIONS: These findings suggest recent declines in the assessment of total cholesterol levels in patients hospitalized with AMI. Although the use of hypolipidemic therapy during hospitalization for AMI has increased over time, considerable room for improvement remains. |
| Ten different dietary fibers have significantly different effects on serum and liver lipids of cholesterol-fed rats Anderson, J. W., A. E. Jones, et al. (1994), J Nutr 124(1): 78-83. Abstract: The comparative effects of 10 different dietary fibers on serum and liver lipids were investigated by feeding male Sprague-Dawley rats diets containing 10 g cholesterol + 2 g cholic acid/kg diet, with 60 g fiber/kg diet. Diets were fed for 3 wk; cellulose was the control fiber. Rats fed psyllium (rich in soluble fiber) had the lowest serum and liver cholesterol concentrations. Rats fed other soluble fiber-rich fibers (oat gum, guar gum and pectin) also had significantly lower serum and liver cholesterol concentrations than rats fed cellulose. Although feeding diets containing both soluble and insoluble fibers (soybean fiber and oat bran) did not significantly alter serum cholesterol, liver cholesterol values were significantly lower than those of cellulose-fed rats. Rats fed rice bran, predominantly an insoluble fiber source, had significantly higher liver cholesterol and significantly lower body weight gains and serum triglyceride concentrations than cellulose-fed rats. Values for serum and liver cholesterol were similar for rats were fed insoluble-rich fibers (corn bran, cellulose and wheat bran). These observations indicate that feeding dietary fibers rich in soluble fiber produces lower serum and liver cholesterol concentrations than does feeding commonly available sources of water-insoluble fiber. |
| Ten-year changes in the obesity, abdominal adiposity, and serum lipoprotein cholesterol measures of Western Samoan men Galanis, D. J., J. Sobal, et al. (1995), J Clin Epidemiol 48(12): 1485-93. Abstract: Previously reported associations between abdominal adiposity and coronary heart disease (CHD) may be mediated through serum lipids. In the present longitudinal study, 43 Western Samoan men who participated in a 1982 study were recontacted for a second determination of anthropometric and serum lipoprotein cholesterol levels. The men showed dramatic increases in weight (mean change +/- SD: 10.5 +/- 8.8 kg), abdominal circumference (10.0 +/- 7.6 cm), total cholesterol (49.5 +/- 26.4 mg/dl), and non-HDL cholesterol (53.1 +/- 26.6 mg/dl). A new indicator was used to estimate changes in abdominal adiposity: the residual from the regression of change in the abdominal circumference on change in body weight (the AR). The AR was significantly correlated with changes in total (r = 0.38) and non-HDL cholesterol (r = 0.39). Changes in HDL cholesterol were correlated with changes in weight only (r = -0.37). These bivariate relations remained significant in multiple linear regression analyses. These longitudinal results are the first to suggest changes in abdominal adiposity are related to changes in total and non-HDL cholesterol levels. |
| Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease Pekkanen, J., S. Linn, et al. (1990), N Engl J Med 322(24): 1700-7. Abstract: To determine the associations of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol with mortality from coronary heart disease and cardiovascular disease, we studied 2541 white men who were 40 to 69 years old at base line and followed them for an average of 10.1 years. Seventeen percent had some manifestation of cardiovascular disease at base line, whereas the others did not. Among the men who had cardiovascular disease at base line, we found, after multivariate adjustment, that those with "high" blood cholesterol levels (above 6.19 mmol per liter) had a risk of death from cardiovascular disease, including coronary heart disease, that was 3.45 times higher (95 percent confidence interval, 1.63 to 7.33) than that for men with "desirable" blood cholesterol levels (below 5.16 mmol per liter). The corresponding hazard ratios were 5.92 (95 percent confidence interval, 2.59 to 13.51) for LDL cholesterol levels above 4.13 mmol per liter as compared with those below 3.35 mmol per liter, and 6.02 (95 percent confidence interval, 2.73 to 13.28) for HDL cholesterol levels below 0.90 mmol per liter as compared with those above 1.16 mmol per liter. All three lipid levels were also significant predictors of death from coronary heart disease alone (P less than 0.005). Total cholesterol and LDL cholesterol levels were also significant predictors of death from cardiovascular and coronary heart disease in men without preexisting cardiovascular disease, although at a lower level of absolute risk of death. Thus, the 10-year risk of death from cardiovascular disease for a man with preexisting cardiovascular disease increased from 3.8 percent to almost 19.6 percent with increasing levels of total cholesterol from "desirable" to "high," whereas the corresponding risk for a man who was free of cardiovascular disease at base line increased from 1.7 percent to 4.9 percent. Our findings suggest that total, LDL, and HDL cholesterol levels predict subsequent mortality in men 40 to 69 years of age, especially those with preexisting cardiovascular disease. |
| Teratogenic effect of the cholesterol synthesis inhibitor AY 9944 on rat embryos in vitro Repetto, M., J. C. Maziere, et al. (1990), Teratology 42(6): 611-8. Abstract: AY 9944 trans-1,4-bis(2-chlorobenzylaminomethyl) cyclohexane dihydrochloride is an amphiphilic cationic molecule. This chemical is an established inhibitor of cholesterol synthesis and is teratogenic in rats. The mechanisms of this teratogenicity remain to be clarified. This study used cultured rat whole embryos to ascertain whether AY 9944 had a direct effect on embryos, or whether its action was indirect, via the maternal cholesterol metabolism. Four experimental conditions were investigated: (A) controls; (B) 10 day untreated embryos were cultured in serum of treated rats; (C) 10 day untreated embryos were cultured in serum containing added AY 9944 (0-1,000 micrograms/ml); and (D) 10 day embryos from females treated on day 4 of gestation were cultured in normal serum. In group B there was no growth retardation; some slight nonspecific abnormalities were not significant. In group C, direct addition of AY 9944 to culture medium retarded growth and differentiation in a dose-dependent manner. No malformation was observed, but histological examinations showed numerous areas of cell necrosis, especially in the CNS. In group D, not only was growth retardation observed, but also characteristic malformations of AY 9944 teratogenesis, including pituitary agenesis. These results show that AY 9944 teratogenicity is initiated prior to day 10. |
| Ternary phase diagram of dipalmitoyl-PC/dilauroyl-PC/cholesterol: nanoscopic domain formation driven by cholesterol Feigenson, G. W. and J. T. Buboltz (2001), Biophys J 80(6): 2775-88. Abstract: A ternary phase diagram is proposed for the hydrated lamellar lipid mixture dipalmitoylphosphatidylcholine/dilauroylphosphatidylcholine/cholesterol (DPPC/DLPC/cholesterol) at room temperature. The entire composition space has been thoroughly mapped by complementary experimental techniques, revealing interesting phase behavior that has not been previously described. Confocal fluorescence microscopy shows a regime of coexisting DPPC-rich ordered and DLPC-rich fluid lamellar phases, having an upper boundary at apparently constant cholesterol mole fraction chi(chol) approximately 0.16. Fluorescence resonance energy transfer experiments confirm the identification and extent of this two-phase regime and, furthermore, reveal a 1-phase regime between chi(chol) approximately 0.16 and 0.25, consisting of ordered and fluid nanoscopic domains. Dipyrene-PC excimer/monomer measurements confirm the new regime between chi(chol) approximately 0.16 and 0.25 and also show that rigidly ordered phases seem to disappear around chi(chol) approximately 0.25. This study should be considered as a step toward a more complete understanding of lateral heterogeneity within biomembranes. Cholesterol may play a role in domain separation on the nanometer scale. |