| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Paradoxical lowering of high-density lipoprotein cholesterol level in 2 patients receiving fenofibrate and a thiazolidinedione Ebcioglu, Z., J. Morgan, et al. (2003), Ann Intern Med 139(9): W80. |
| Paradoxical severe decrease in serum HDL-cholesterol after treatment with a fibrate Olukoga, A. O. (2002), J Clin Pathol 55(9): 718. |
| Paradoxical severe decrease in serum HDL-cholesterol after treatment with a fibrate: reply by the authors Crook, M., J. Lynas, et al. (2002), J Clin Pathol 55(12): 976. |
| Parallel regulation of sterol regulatory element binding protein-2 and the enzymes of cholesterol and fatty acid synthesis but not ceramide synthesis in cultured human keratinocytes and murine epidermis Harris, I. R., A. M. Farrell, et al. (1998), J Lipid Res 39(2): 412-22. Abstract: After permeability barrier perturbation there is an increase in the mRNA levels for key enzymes necessary for lipid synthesis in the epidermis. The mechanism(s) responsible for this regulation is unknown. Sterol regulatory element binding proteins-1a, 1c, and -2 (SREBPs) control the transcription of enzymes required for cholesterol and fatty acid t synthesis in response to modulations of sterol levels. We now demonstrate that SREBP-2 is the predominant SREBP in human keratinocytes and murine epidermis, while SREBP-1 is not detected. Sterols regulate SREBP-2 mRNA levels in keratinocytes and the epidermis and the proteolytic cleavage of SREBP-2 to the mature active form in keratinocytes. In parallel to the increase in mature active SREBP, there is a coordinate increase in mRNA levels for cholesterol (HMG-CoA reductase, HMG-CoA synthase, farnesyl diphosphate synthase, and squalene synthase) and fatty acid (acetyl-CoA carboxylase, fatty acid synthase) synthetic enzymes. However, mRNA levels for serine palmitoyl transferase (SPT), the first committed step for ceramide synthesis, do not increase in parallel. The increase of mRNA for enzymes required for epidermal cholesterol and fatty acid synthesis is consistent with both the previously described early increase of cholesterol and fatty acid synthesis after barrier disruption and a role for SREBP-2 in the regulation of cholesterol and fatty acid synthesis for epidermal barrier homeostasis. In contrast, SPT appears to be regulated by different mechanisms, consistent with the different time course of its stimulation after barrier disruption. |
| Parameters influencing cholesterol oxidation Kim, S. K. and W. W. Nawar (1993), Lipids 28(10): 917-22. Abstract: The purpose of this study was to investigate the effects of temperature, oxidation time, presence of water, pH, type of buffer and form of substrate used on cholesterol oxidation. Microcrystalline cholesterol films, both solid and melted, and aqueous suspensions of film fragments were used as substrates. Use of dispersing agents was avoided. Quantitative analysis of the unaltered substrate and the products of its autoxidation was carried out by gas chromatography over the course of oxidation. Solid cholesterol films were found to be resistant to autoxidation in the dry state. However, when heated at 125 degrees C, a sudden increase in oxidation rate occurred at a point coinciding with the visible melting followed by a plateau of the oxidation rate. All of the autoxidation products formed underwent further decomposition. Film fragments of cholesterol oxidized at a faster rate in aqueous suspensions than when oxidized in the dry state. In aqueous suspensions, the differences in the resistance of cholesterol to oxidation were not significant within the pH range 6.0-7.4, except for the early stages of oxidation. The 7-ketocholesterol/7-hydroxycholesterol ratio dropped significantly with increasing pH. However, at all pH levels tested, this ratio remained relatively constant during the 6 h of heating. While the 7 beta-hydroxycholesterol/7 alpha-hydroxycholesterol ratio was not affected by pH in the range of 6.0-7.4, at pH 7.4 a high preference was observed for the cholesterol beta-epoxide over its alpha-isomer.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Paraoxonase 1 (PON1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine Rosenblat, M., J. Vaya, et al. (2005), Atherosclerosis 179(1): 69-77. Abstract: We investigated the role of HDL-associated paraoxonase 1 (PON1) in HDL-mediated macrophage cholesterol efflux by using HDL derived from wild type mice (Control-HDL), from human PON1-transgenic mice (HDL-PON1Tg) or from PON1-knockout mice (HDL-PON1(0)). Cholesterol efflux from mouse peritoneal macrophages (MPM) or from J774 A.1 macrophage cell line by HDL-PON1Tg, was significantly increased (by 60%) compared to HDL-PON1(0). We demonstrated that this PON1 effect was associated with an increased HDL binding to the cells, as the binding of HDL-PON1Tg (or HDL-PON1(0) that was enriched with PON1) was increased by 50% compared to that of HDL-PON1(0). Using either a cAMP analogue, to increase ABCA1 receptor expression, or rabbit anti-mouse SR-BI specific antibody to block the SR-BI receptor, PON1 stimulation of HDL binding and of HDL-mediated macrophage cholesterol efflux, were both found to involve the ABCA1 transporter. Studies with PON1 specific inhibitors revealed that PON1 activity was required for its stimulation of HDL-mediated macrophage cholesterol efflux. Upon incubation of macrophages with Control-HDL or with HDL-PON1Tg, macrophage lysophosphatidylcholine (LPC) content was increased by 3.7- and 7.5-fold, respectively. Such an LPC enrichment of macrophages resulted in up to 60% increased HDL binding to the cells, and a 41% increased HDL-mediated cholesterol efflux. Similarly, macrophage loading with LPC (by either adding LPC, or PON1 or phospholipase A(2)) significantly increased apolipoprotein A-I (apoA-I) mediated cholesterol efflux by 104, 65 and 56%, respectively, in ABCA1 overexpressing macrophages. We conclude that HDL-associated PON1 may contribute to the attenuation of atherosclerosis development by its ability to act on macrophage phospholipids, to form LPC, in turn, stimulates HDL binding and HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter. |
| Paraoxonase 1 and platelet-activating factor acetylhydrolase activities in patients with low hdl-cholesterol levels with or without primary hypertriglyceridemia Brites, F. D., J. Verona, et al. (2004), Arch Med Res 35(3): 235-40. Abstract: BACKGROUND: Previous studies have shown that high density lipoprotein (HDL)-deficient states are associated with reduced paraoxonase 1 (PON1) activity. However, HDL reduction caused by primary hypertriglyceridemia has not been fully explored. The aim of the present study was to evaluate whether PON1 and platelet-activating factor acetylhydrolase (PAF-AH), two antioxidant enzymes, were altered in patients with low HDL-cholesterol levels with or without primary hypertriglyceridemia in comparison with control normolipemic subjects. METHODS: We studied 24 patients with low HDL-cholesterol levels with (n=12) or without (n=12) primary hypertriglyceridemia in comparison with 12 control subjects who presented normal HDL-cholesterol and triglyceride levels. Paraoxon and phenylacetate were used as substrate for measuring PON1 activities and 1-hexadecyl-2-3Hacetyl-glycero-3-phosphocholine for platelet-activating factor acetylhydrolase (PAF-AH) activity. Double substrate method was used to assign phenotypes. Lipid, lipoprotein, apolipoprotein, and lipoprotein particles were determined by standardized methods. RESULTS: Both PON1 activities were significantly reduced in patients with low HDL-cholesterol levels. This reduction could be selectively attributed to the hypertriglyceridemic subgroup. PAF-AH activity was not different between hypoalphalipoproteinemic patients and controls. PON1 activities correlated positively and significantly with HDL-cholesterol, HDL2-cholesterol, HDL3-cholesterol, HDL-phospholipids, apo A-I, apo A-II, and LpA-I:A-II. PAF-AH correlated positively and significantly with total and low density lipoprotein-cholesterol. CONCLUSIONS: Data from this study would suggest that in hypoalphalipoproteinemic syndrome, particularly when associated with hypertriglyceridemia, there is impairment in enzymatic antioxidant activity exclusively related with HDL. |
| Paraoxonase genotype modifies the effect of pravastatin on high-density lipoprotein cholesterol Malin, R., R. Laaksonen, et al. (2001), Pharmacogenetics 11(7): 625-33. Abstract: Paraoxonase (PON) is an enzyme carried by high-density lipoprotein cholesterol (HDL-C). Two gene polymorphisms leading to amino acid substitutions of methionine for leucine at position 55 (M/L55) and arginine for glutamine at position 192 (R/Q192) modulate the activity of the enzyme and possibly also lipid and apolipoprotein concentrations. Our purpose was to examine the effect of the PON genotype on HDL-C and apolipoprotein AI (apo AI) responses to pravastatin treatment. Fifty-one mildly hypercholesterolemic male subjects (mean age 35 +/- 4 years) were enrolled by this prospective, randomized, double-blind study. Lipid concentrations were measured at baseline and after 6 months of pravastatin (n = 25) or placebo (n = 26) therapy. Low active (MM, ML or QQ) and high active (LL or RQ, RR) PON genotype groups were related to lipid and apolipoprotein concentration changes. Pravastatin increased the apo AI concentration 12% (P = 0.017, RANOVA) and tended to increase the HDL-C concentration (P = 0.095, RANOVA) in R allele carriers but not in QQ homozygotes. Significant predictors of the change in apo AI concentration during pravastatin treatment were R/Q192 genotype (P = 0.002), apo AI concentration at baseline (P = 0.002) and M/L55 genotype (P = 0.042). Correspondingly, R/Q192 (P = 0.009) and M/L55 (P = 0.050) genotypes were the statistically significant determinants of HDL-C concentration change. The PON genotype thus modifies the effect of pravastatin on serum HDL-C and apo AI concentrations. This could partly explain the contradictory results obtained from previous studies on the effects of statins on the serum HDL-C concentration. |
| Parent and physician response to children's cholesterol values of 200 mg/dL or greater: the Child and Adolescent Trial for Cardiovascular Health Experiment Nader, P. R., M. Yang, et al. (1997), Pediatrics 99(5): E5. Abstract: OBJECTIVE: To determine parental actions and concerns and physician responses to parental notification that a child's cholesterol value was 200 mg/dL or greater, a value recommended by the National Cholesterol Education Program to warrant physician follow-up and evaluation. METHODOLOGY: A telephone survey of parents (n = 784) and physicians (n = 117) was carried out after parental notification of a total blood cholesterol value obtained as part of measurement done while participating in the Child and Adolescent Trial for Cardiovascular Health in 96 schools located in California, Louisiana, Minnesota, and Texas. RESULTS: Only 20% of parents contacted physicians. Factors associated with this action included whether the parent was notified once or twice, the level of the cholesterol, previous cholesterol testing in the parent, and medical insurance that covered the visit. Family history of cardiovascular disease, when other factors were considered, did not increase the likelihood that a physician contact would be made. After contact with the physician, 59% of physicians reported evaluating children for cholesterol; about half reported repeating the cholesterol determination. CONCLUSION: Parental knowledge of a child's cholesterol value of 200 mg/dL or greater did not result in substantially further seeking of health care. |
| Parents' behavior and attitudes toward screening children for high serum cholesterol levels Lannon, C. M. and J. Earp (1992), Pediatrics 89(6 Pt 2): 1159-63. Abstract: The American Academy of Pediatrics, concerned that pediatric cholesterol screening may lead to mislabeling and overly restrictive diets, stresses laboratory confirmation and nutritional follow-up for children with elevated cholesterol levels. Parents' behavior and attitudes toward screening children for high cholesterol were studied. During an 8-week period in summer of 1989 all children 2 through 15 years of age seen for well-child examinations at a community pediatric group practice were offered cholesterol screening by finger-stick method. Most parents were well-educated and white. Of 439 children screened, 134 (31%) had cholesterol levels above the recommended cutoff point of 175 mg/dL (75th percentile). Only 63 children returned for confirmatory lipid panels; parents of children who did not return were interviewed. Reasons for noncompliance included "not sure test machine was accurate" (67%); "child too traumatized by finger stick" (47%); and "will try low-cholesterol diet before recheck" (40%). A third of these parents believed that confirmation of an elevated cholesterol level "would make the child worry too much." Only 29% of these parents talked with a dietician. In this middle-class, well-educated population, a large proportion of children had elevated screening cholesterol values, but few complied with American Academy of Pediatrics guidelines. As a result, many children may be mislabeled as hypercholesterolemic and may not benefit from screening. |
| Parents' beliefs about cholesterol and its effects on their children Price, J. H., S. K. Telljohann, et al. (1994), Psychol Rep 74(2): 611-21. Abstract: A random sample of parents of primary grade children (N = 500) was obtained from two higher socioeconomic-status suburban elementary schools. The respondents (n = 277) were well educated (92% attended or graduated from college), white (92%), primarily higher in socioeconomic status (79% earned more than $50,000/year), and female (70%). Two-thirds of the parents believed that all elementary school children should have their cholesterol levels checked, 70% believed high cholesterol in children was serious, yet only 21% believed their child would develop a high cholesterol level. To control their children's cholesterol level, the majority of parents (73%) made lifestyle changes for their children since the majority believed high cholesterol levels would clog arteries (95%) and cause heart disease (90%). Parents most often received their information on cholesterol from magazines (73%), newspapers (62%), and physicians (52%). |
| Partial lecithin:cholesterol acyltransferase (LCAT) deficiency in Balkan endemic nephropathy Pavlovic, N. M., Z. Varghese, et al. (1991), Kidney Int Suppl 34: S102-4. Abstract: The role of lipid abnormalities has been also implicated in the progression of renal diseases. The search for lipid abnormalities in Balkan endemic nephropathy (BEN) has roused sporadic interest and has not been fully elucidated. This study was performed in 54 healthy subjects from the families affected with BEN (group A), 18 members from non-affected families living in the same location (group B), and 25 control subjects (group C). Lipid profiles and lecithin:cholesterol acyltransferase (LCAT) were determined in each subject. The most striking distinction between the groups was that of the LCAT activity, which was abnormally low in group A (39 +/- 2), significantly different (P less than 0.0001) from that of the other groups. Thirty individuals from group A were those accounting for the low LCAT activity (A1). This group had a significantly lower total cholesterol and free cholesterol than all of the other subjects. The entire group A subjects had a significantly lower percentage of free cholesterol than the other two groups. There was no significant difference in HDL cholesterol between any of the groups, but group A1 had significantly higher HDL than group C (P less than 0.04). What emerges from our study is that a certain proportion of subjects from BEN families have a peculiar form of lipid abnormalities associated with an abnormal LCAT activity. At present we have no explanation for these findings. We believe that these changes may have an important role in the pathogenesis of BEN. |
| Partial lecithin-cholesterol acyltransferase (LCAT) deficiency syndrome Brites, F. D., K. M. Fernandez, et al. (1999), Medicina (B Aires) 59(1): 89-92. Abstract: This syndrome is a pathological entity of low incidence which mainly affects high density lipoprotein (HDL) metabolism. We here show the first case reported in our country, observed in a 63-year-old woman who showed bilateral corneal opacity and eruptive xanthomas in both arms. The lipoprotein profile disclosed severe hypertriglyceridemia and normocholesterolemia, although the percentage of cholesteryl esters was low. Plasma levels of HDL-cholesterol and HDL major apolipoproteins, A-I and A-II, were markedly decreased. The patient also showed glucose intolerance and hematological alterations related to abnormal lipid composition of erythrocyte membranes. As evaluated by the exogen substrate method, LCAT activity proved to be 82% lower in the patient than in a control subject. It is noteworthy that the patient had experienced cardiac events and presented hypertension, neither of which has been commonly documented in partial LCAT deficiency syndromes. |
| Partial replacement of bile salts causes marked changes of cholesterol crystallization in supersaturated model bile systems Nishioka, T., S. Tazuma, et al. (1999), Biochem J 340 (Pt 2): 445-51. Abstract: Cholesterol crystallization is a key step in gallstone formation and is influenced by numerous factors. Human bile contains various bile salts having different hydrophobicity and micelle-forming capacities, but the importance of lipid composition to bile metastability remains unclear. This study investigated the effect of bile salts on cholesterol crystallization in model bile (MB) systems. Supersaturated MB systems were prepared with an identical composition on a molar basis (taurocholate/phosphatidylcholine/cholesterol, 152 mM:38 mM: 24 mM), except for partial replacement of taurocholate (10, 20, and 30%) with various taurine-conjugated bile salts. Cholesterol crystallization was quantitatively estimated by spectrophotometrically measuring crystal-related turbidity and morphologically scanned by video-enhanced microscopy. After partial replacement of taurocholate with hydrophobic bile salts, cholesterol crystallization increased dose-dependently without changing the size of vesicles or crystal morphology and the rank order of crystallization was deoxycholate>chenodeoxycholate>cholate (control MB). All of the hydrophilic bile salts (ursodeoxycholate, ursocholate and beta-muricholate) inhibited cholesterol precipitation by forming a stable liquid-crystal phase, and there were no significant differences among the hydrophilic bile-salt species. Cholesterol crystallization was markedly altered by partial replacement of bile salts with a different hydrophobicity. Thus minimal changes in bile-salt composition may dramatically alter bile lipid metastability. |
| Partial replacement of saturated fatty acids with almonds or walnuts lowers total plasma cholesterol and low-density-lipoprotein cholesterol Abbey, M., M. Noakes, et al. (1994), Am J Clin Nutr 59(5): 995-9. Abstract: Sixteen normolipidemic male volunteers aged 41 +/- 9 y (mean +/- SD) consumed a diet providing 36% of energy as fat (92 g fat/d) for 9 wk. A daily supplement of nuts (providing half of the total fat intake) was provided against a common background diet. In the first 3-wk period the background diet was supplemented with raw peanuts (50 g/d), coconut cubes (40 g/d), and a coconut confectionary bar (50 g/d), designed to provide 47 g fat with a ratio of polyunsaturated to monounsaturated to saturated fatty acids (P:M:S) to match the Australian diet (reference diet). During the following 3 wk the background diet was supplemented with monounsaturated fatty acid-rich raw almonds (84 g/d), equivalent to 46 g fat, and during the final 3-wk period the background diet was supplemented with polyunsaturated fatty acid-rich walnuts (68 g/d), equivalent to 46 g fat. Compared with the reference diet there were significant reductions in total and LDL cholesterol, 7% and 10%, respectively, after supplementation with almonds, and 5% and 9%, respectively, after supplementation with walnuts. |
| Partial transfection of liver with a synthetic cholesterol 7 alpha-hydroxylase transgene is sufficient to stimulate the reduction of cholesterol in the plasma of hypercholesterolemic mice Agellon, L. B. (1997), Biochem Cell Biol 75(3): 255-62. Abstract: The effect of administering a synthetic transgene encoding cholesterol 7 alpha-hydroxylase (cyp7) on plasma cholesterol metabolism of intact mice was investigated. The synthetic cyp7 transgene (Tg1) was constructed by placing the cDNA sequence encoding the full-length cyp7 polypeptide under the control of a heavy metal inducible metallothionein promoter. The transgene was complexed with asialoorosomucoid-polylysine conjugate and introduced into mice via the tail vein. Cell marking experiments using a beta-galactosidase (lacZ) transgene as a tag showed that 5-10% of the liver can be transfected by this procedure. Administration of the Tg1 transgene to older hypercholesterolemic chow-fed mice resulted in about a 50% reduction of plasma cholesterol, regardless of whether or not transgene expression was induced by zinc treatment. In diet-induced hypercholesterolemic mice, the reduction (20%) in total plasma cholesterol was seen only when transgene expression was induced, and this reduction was due primarily to a decrease in non-high-density lipoprotein cholesterol. The maximum reduction was evident at 6 days after the introduction of the transgene and was no longer evident after 9 days. Introduction of the Tg1 transgene into young chow-fed mice had no effect on the already low levels of plasma cholesterol. However, compared with the no-transgene and lacZ transgene controls, the gallbladder bile acid content of Tg1-treated mice was increased. The results show that non-viral-mediated delivery of a synthetic transgene encoding cyp7 to a subpopulation of hepatocytes in the liver of intact hypercholesterolemic mice is sufficient to facilitate the temporary reduction of plasma cholesterol content. |
| Participation in a worksite cholesterol education program in a university setting Greene, G. W. and I. Strychar (1992), J Am Diet Assoc 92(11): 1376-81. Abstract: Three hundred ninety-six employees of a large northeastern university participated in a blood cholesterol screening and provided follow-up data about their participation in a videotape cholesterol education program. Ten percent of these employees watched the videotape program; these individuals were significantly more likely to be at high risk for cardiovascular disease than were persons who chose not to watch the videotape. Persons participating in the cholesterol education program significantly increased their nutrition knowledge and significantly decreased their fat intake compared with nonparticipants. The most important reason given for watching the videotape was "concern about my cholesterol level." Reasons given for not watching the videotape were that it was "not well advertised" or that it was shown "at an inconvenient time." Although all 98 employees at high risk for cardiovascular disease were referred to their physicians for diagnostic evaluation, one third of these employees reported not seeing their physicians. These findings indicate that worksite cholesterol screening and education programs can improve nutrition knowledge and dietary behavior; however, these programs should develop strategies to increase participation and should follow up physician referrals. |
| Participation of cholesterol in hypochlorite-induced oxidation of cholesterol-phosphatidylcholine liposomes Momynaliev, K. T., V. M. Govorun, et al. (1996), Biull Eksp Biol Med 121(5): 516-9. |
| Participation of serum albumin and LDL-cholesterol in impaired blood cell-filterability affected by white blood cells in patients with cerebral thrombosis Yoshida, H., S. Takamatsu, et al. (1992), Scand J Clin Lab Invest 52(7): 641-6. Abstract: We examined the effect of white blood cells (WBCs) on the red blood cell (RBC)-filterability, and the influence of plasma components on their interaction of their microcirculatory behaviour in cerebral thrombosis patients. Subjects studied were 20 patients with a history of cerebral thrombosis (60 +/- 4.7 years old) (mean +/- SD) and 28 healthy controls (59 +/- 5.4 years old). Filterability indices of RBC suspension (RFI) and suspension with RBCs plus WBCs (RWFI) were measured by the method of Nuclepore filtration. The values of RFI in patients and controls were 0.44 +/- 0.12 and 0.56 +/- 0.16 ml min-1 (mean +/- SD), and RWFIs were 0.33 +/- 0.092 and 0.40 +/- 0.11 ml min-1, respectively. The differences in both of these values between patients and controls were significant (p < or = 0.01 for RFI and p < or = 0.05 for RWFI, based on Student's t test, respectively). Both RFI and RWFI in bed-ridden patients were lower than those in the more active counterparts (p < or = 0.05, based on Student's t test). In patients, RFI and RWFI correlated positively with serum albumin (r = +0.515, p < 0.05; r = +0.533, p < 0.05, based on Student's t test, respectively). The net lowering effect of WBCs on RFI (RFI-RWFI) correlated positively with serum LDL-cholesterol in patients (r = +0.574, p < 0.01, based on Student's t test). WBCs play a significant role in reducing RFI, and its effect is related to the pathemas of patients.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Participation of sterol carrier protein-2 in cholesterol metabolism Kesav, S., J. McLaughlin, et al. (1992), Biochem Soc Trans 20(4): 818-24. |