Cholesterol Journal Articles

Record 13361 to 13380

Usefulness of examination of the cholesterol versus triglyceride ratio for lipoprotein fractions in a patient with marked hyper-triglyceridemia
Sato, I., M. Hyakuta, et al. (2002), Rinsho Byori 50(10): 987-91.
Abstract: A patient consulted the emergency room with acute pancreatitis, hypertriglyceridemia, and diabetes mellitus, and was later admitted to the hospital. Serum levels of total cholesterol(TC) and total triglyceride (TTG), and the cholesterol(Chol) versus triglyceride(TG) ratio(Chol/TG) for lipoprotein fractions were examined periodically during the course of treatment using Chol/Trig Combo, which identifies Chol and TG by differential staining. On admission, the patient's TTG, pancreatic amylase and glucose levels were 4020 mg/dl, 2012 IU/l, and 242 mg/dl, respectively. Clinofibrate administration resulted in a decrease in Chol and TG values for all fractions. However, the Chol/TG ratios were unchanged(HDL of 0.2 to 0.4, VLDL of approximately 0.13, and LDL of 0.1 to 0.2: Reference values from 103 healthy students were as follows: HDL 5.8 +/- 2.0, VLDL 0.39 +/- 0.1, and LDL 4.9 +/- 1.3Mean +/- SD.). During clinofibrate treatment, TC and TG values gradually increased. Clinofibrate was discontinued and fenofibrate administration was initiated. This was followed by a dramatic improvement in TC, TTG and Chol/TG values for both HDL and LDL. The monitoring of lipoprotein fraction values proved useful for determining the treatment regimen for this patient with hypertriglyceridemia.

Usefulness of lowering low-density lipoprotein cholesterol to <70 mg/dl and usefulness of C-reactive protein in patient selection
Kent, S. M. and A. J. Taylor (2003), Am J Cardiol 92(10): 1224-7.
Abstract: C-reactive protein levels may identify patients likely to benefit from lowering low-density lipoprotein (LDL) cholesterol to ultra-low levels. We find that above-average C-reactive protein with statin therapy predicts failure of carotid intima-media thickness regression in those with currently defined optimal LDL cholesterol (<100 mg/dl) but not if LDL cholesterol is <70 mg/dl.

Usefulness of non-high-density lipoprotein cholesterol determinations in the diagnosis and treatment of dyslipidemia
Hirsch, G. A. and R. S. Blumenthal (2003), Am J Cardiol 91(7): 827-30.

Usefulness of parental serum total cholesterol levels in identifying children with hypercholesterolemia
Benuck, I., S. S. Gidding, et al. (1992), Am J Cardiol 69(8): 713-7.
Abstract: It was hypothesized that healthy children with high cholesterol levels may have parents who exceed acceptable cholesterol levels established by the National Cholesterol Education Program. One hundred sixty families (320 parents, 263 children aged 3 to 10 years) were evaluated for total cholesterol and other risk factors. Before the study, almost half of the parents had not had serum total cholesterol measured. The odds ratio for a child having a total cholesterol greater than or equal to 5.17 mmol/liter (200 mg/dl) was 13.6:1 (confidence interval 5.7 to 32.5) for a child with at least 1 parent having cholesterol greater than or equal to 6.20 mmol/liter (240 mg/dl) versus a child whose parents had low total cholesterol. Testing only children who had at least 1 parent with a total cholesterol greater than or equal to 5.17 mmol/liter (200 mg/dl) had a sensitivity of 98% for detecting children's total cholesterol greater than or equal to 5.17 mmol/liter. It is concluded that parental total cholesterol is useful in identifying children with high total cholesterol levels. Pediatricians may identify a large number of parents with hypercholesterolemia not previously recognized.

Usefulness of serum total cholesterol/triglyceride ratio for predicting the presence of small, dense LDL
Yoshida, A., M. Kouwaki, et al. (2004), J Atheroscler Thromb 11(4): 215-9.
Abstract: OBJECTIVE: We examined the usefulness of the serum total cholesterol (TC)/triglyceride (TG) and LDL-cholesterol (LDL-C)/TG ratios for predicting the presence of small, dense LDL, by comparing them with the established indicators of small, dense LDL, such as the LDL-migration index (LDL-MI) and LDL-C/Apolipoprotein B (ApoB) ratio. MATERIALS AND METHODS: Fasting serum lipid was analyzed in 99 Japanese hyperlipidemic and normolipidemic subjects (34 males and 65 females, 59.4 +/- 11.9 years old). RESULTS: A good negative correlation was observed between LDL-MI and log (TC/TG) (R(2) = 0.473, p < 0.0001). There was a strong positive correlation between LDL-C/ApoB and log (TC/TG) (R(2) = 0.665, p < 0.0001). Similar results were obtained using LDL-C instead of TC. Using LDL-MI > 0.4 as an indicator of small, dense LDL, the upper limit of TG was estimated to be 140-142 mg/dl. CONCLUSION: TC/TG and LDL-C/TG may offer a convenient and simple clinical tool for predicting the presence of small, dense LDL. Particularly, TC/TG could be an easy-to-use indicator of small, dense LDL for general practitioners.

Usefulness of the total cholesterol to high-density lipoprotein cholesterol ratio in predicting angiographic coronary artery disease in women
Hong, M. K., P. A. Romm, et al. (1991), Am J Cardiol 68(17): 1646-50.
Abstract: To investigate the relation between lipids and angiographic coronary artery disease (CAD) in women, fasting lipid profiles were obtained on 108 women undergoing coronary angiography (group I). CAD, defined as greater than or equal to 25% luminal diameter narrowing in a major coronary artery, was present in 57 (53%). Neither serum total cholesterol nor triglyceride levels correlated with the presence of CAD. Mean total/high-density lipoprotein (HDL) cholesterol ratio was higher among women with than without CAD (5.5 +/- 0.3 vs 4.2 +/- 0.2, p less than 0.0001). Multiple regression analyses identified a higher total/HDL cholesterol ratio as the variable most predictive of the presence (p less than 0.001), extent (number of narrowed arteries) (p less than 0.0001), and severity (% maximum stenosis) (p less than 0.001) of CAD. Age and lack of estrogen use were also independently associated with the presence of CAD, age and low-density lipoprotein cholesterol level were additional indicators of extent, and age was the only other discriminator of severity of CAD. In 56 women with total cholesterol less than 200 mg/dl (group II), mean total/HDL cholesterol ratio was higher in women with (n = 24) than without CAD (4.3 +/- 0.2 vs 3.5 +/- 0.2, p = 0.01). Higher total/HDL cholesterol ratio was the variable most predictive of the presence of CAD (p = 0.01), and the lone variable associated with severity (p less than 0.001) after adjustment for other risk factors. Age was independently associated with presence and extent, and hypertension was also independently related to extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of total cholesterol/HDL-cholesterol ratio in the management of diabetic dyslipidaemia
Gimeno-Orna, J. A., E. Faure-Nogueras, et al. (2005), Diabet Med 22(1): 26-31.
Abstract: AIMS: Our aim was to evaluate the usefulness of the total cholesterol/HDL-cholesterol ratio (TC/HDL) in predicting the cardiovascular risk of Type 2 diabetic patients. METHODS: Prospective cohort study with inclusion of 418 Type 2 diabetic individuals with follow-up until the appearance of a cardiovascular event. The predictive power of updated mean lipid values during follow-up was analysed by means of Cox proportional hazard models. An estimate was made of the relative risk (RR) conferred by high levels of TC/HDL stratified by LDL-cholesterol levels. RESULTS: Sixty-six cardiovascular events occurred during an average follow-up of 4.7 years (sd 1.5). The main lipid predictor of vascular events was mean TC/HDL ratio hazard ratio (HR) = 1.46; 95% confidence interval (CI) 1.25, 1.7; P < 0.0001. In the multivariate model with simultaneous inclusion of mean TC/HDL and mean LDL-cholesterol, both were significant predictors of cardiovascular disease HR (1 unit) = 1.37; 95% CI 1.16, 1.62; P = 0.0003 and HR (1 mmol/l) = 1.5; 95% CI 1.04, 2.18; P = 0.03, respectively. The LDL adjusted RR for cardiovascular events due to high TC/HDL ratio, with 4.5 cut-off point, was 2.5 (95% CI 1.4, 4.3; P = 0.0007). For the stratum of subjects with average LDL cholesterol < 3.5 mmol/l, RR was 1.2 (95% CI 0.5, 2.8; P = NS) and for the stratum of average LDL cholesterol > 3.5 mmol/l, RR was 4 (95% CI 1.8, 9; P = 0.00013), with heterogeneity among strata (P = 0.044). CONCLUSIONS: It could be useful to include the TC/HDL ratio in treatment guides for diabetic dyslipidaemia, given their high predictive value and strong interaction with LDL cholesterol.

User-defined serum aspartate and alanine aminotransferase, cholesterol, triglycerides, urea, and uric acid for the Beckman synchron CX 4/5 using Ames Sera-Pak reagents
Lolekha, P. H. and P. Nitipaichit (1992), J Clin Lab Anal 6(5): 245-56.
Abstract: Beckman aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, triglycerides, urea, and uric acid Liquid Reagents for Synchron CX 4/5 (48, 48, 25, 60, 26, and 30 cents US/test, respectively) are expensive. We have established our own methods for serum AST, ALT, cholesterol, triglycerides, urea, and uric acid (6, 6, 5, 12, 13, and 6 cents US/test, respectively) using Ames Sera-Pak reagents. Linearity of our AST, ALT, cholesterol, triglycerides, urea, and uric acid methods were either similar to or higher than the Beckman methods. The within run and day-to-day run precisions were acceptable. Recovery of our AST, ALT, cholesterol, triglycerides, urea, and uric acid were excellent. Our results for AST, ALT, cholesterol, triglycerides, urea, and uric acid correlated well with the Beckman results. Bilirubin (340.8 mumol/L) did not significantly interfere on our AST, ALT, cholesterol, triglycerides, and urea, while its concentrations of 165.8 mumol/L started giving negative interference on uric acid. Turbidity (2+) did not interfere significantly on our AST and ALT but started giving positive interference on cholesterol, triglycerides, urea, and uric acid. Hemolysis (2+) gave positive interference on our cholesterol, triglycerides, urea, and uric acid. Stability of Ames Sera-Pak working reagents was at least 30 days for AST, ALT, urea, and uric acid and 40 days for cholesterol and triglycerides.

U-shape relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness and evidence for extreme interindividual variation in dietary cholesterol absorption in humans
Sehayek, E., C. Nath, et al. (1998), J Lipid Res 39(12): 2415-22.
Abstract: A possible relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness was examined in 18 normal subjects fed low fat low cholesterol, high fat low cholesterol, and high fat high cholesterol diets. For the group, neither dietary cholesterol nor dietary fat affected the percentage dietary cholesterol absorption, whereas dietary cholesterol intake raised total and LDL-C and dietary fat raised total, LDL, and HDL-C. On a fixed diet there was approximately a 2-fold variation among subjects in percentage dietary cholesterol absorption. Subjects also varied in response to dietary cholesterol and fat with regard to dietary cholesterol absorption and plasma lipoprotein responsiveness. There was a U-shaped parabolic relationship between dietary cholesterol-induced percent change in LDL-C and the change in percentage dietary cholesterol absorption (R2 = 0.62, P = 0.005). A similar but weaker relationship characterized the responsiveness of HDL-C (R2 = 0.38, P = 0.05). For the group, increased cholesterol intake raised dietary cholesterol mass absorption from 1.6 to 4.6 mg/kg per day, but the range of increase was from 1 to 4.7 mg/kg per day. Increased fat intake also affected dietary cholesterol mass absorption with most subjects displaying a strong inverse relationship between fat intake and mass absorption (r = -0.77, P < 0.003). In summary: i) the percentage change in dietary cholesterol absorption in response to dietary cholesterol does appear to regulate diet responsiveness of LDL and HDL-C, and ii) the large variability in percent absorption and changes in percentage and mass absorption in response to dietary cholesterol suggest the presence of genetically determined differences among individuals in the regulation of dietary cholesterol absorption.

Using advanced intercross lines for high-resolution mapping of HDL cholesterol quantitative trait loci
Wang, X., I. Le Roy, et al. (2003), Genome Res 13(7): 1654-64.
Abstract: Mapping quantitative trait loci (QTLs) with high resolution facilitates identification and positional cloning of the underlying genes. The novel approach of advanced intercross lines (AILs) generates many more recombination events and thus can potentially narrow QTLs significantly more than do conventional backcrosses and F2 intercrosses. In this study, we carried out QTL analyses in (C57BL/6J x NZB/BlNJ) x C57BL/6J backcross progeny fed either chow or an atherogenic diet to detect QTLs that regulate high-density lipoprotein cholesterol (HDL)concentrations, and in (C57BL/6J x NZB/BlNJ) F11 AIL progeny to confirm and narrow those QTLs. QTLs for HDL concentrations were found on chromosomes 1, 5, and 16. AIL not only narrowed the QTLs significantly more than did a conventional backcross but also resolved a chromosome 5 QTL identified in the backcross into two QTLs, the peaks of both being outside the backcross QTL region. We tested 27 candidate genes and found significant mRNA expression differences for 12 (Nr1i3, Apoa2, Sap, Tgfb2, Fgfbp1, Prom, Ppargc1, Tcf1, Ncor2, Srb1, App, and Ifnar). Some of these underlay the same QTL, indicating that expression differences are common and not sufficient to identify QTL genes. All the major HDL QTLs in our study had homologous counterparts in humans, implying that their underlying genes regulate HDL in humans.

Using rough sets, neural networks, and logistic regression to predict compliance with cholesterol guidelines goals in patients with coronary artery disease
Dubey, A. K. (2003), AMIA Annu Symp Proc: 834.
Abstract: Coronary artery disease is a leading cause of death and disability in the United States and throughout the developed world. Results from large randomized, blinded, placebo-controlled trials have demonstrated clearly the benefit of lowering LDL cholesterol in lowering the risk for coronary artery disease. Unfortunately, despite the quantity of evidence, and the availability of medications that can efficiently lower LDL cholesterol with few side effects, not everyone who could benefit from cholesterol lowering interventions actually receives them. Despite the dissemination of national care guidelines for the evaluation and treatment of cholesterol levels (NCEP - National Cholesterol Education Program), compliance with such guidelines is suboptimal. There clearly is room for improvement in narrowing the gap between evidence based guidelines and actual clinical practice. The ability to classify those patients who are or will likely to be noncompliant on the basis of patient data routinely collected during patient care could be potentially useful by enabling the focusing of limited health care resources to those who are or will be at high risk of being under treated. In order to explore this possibility further, we attempted to create such classifiers of cholesterol guideline compliance. To do this, we obtained data from an ambulatory electronic medical record system at use at the MGH adult primary care practices for over 20 years. We obtained the data from this hierarchically-structured EMR using its own native query language, called MQL (Medical Query Language). Next, we applied to the collected data the machine learning techniques of rough set theory, neural networks (feed forward backpropagation nets), and logistic regression. We did this by using commonly available software that for the most part is freely available via the internet. We then compared the accuracy of the classifier models using the receiver operating characteristic (ROC) area and C-index summary metrics.

Using serum cholesterol as a screening test for preventing coronary heart disease: the five fundamental flaws of the American College of Physicians Guidelines
Forrester, J. S. and P. K. Shah (1997), Am J Cardiol 79(6): 790-2.
Abstract: The guidelines ignore the common catastrophic first presentation of coronary disease, the powerful predictive value of serum cholesterol in young persons, the effectiveness of cholesterol-lowering interventions, the low cost of effective dietary modification, and the effectiveness of lipid lowering in women and in the elderly.

Using the new cholesterol guidelines in everyday practice
Sprecher, D. L. and J. P. Frolkis (2001), Cleve Clin J Med 68(7): 617-22.
Abstract: The third Adult Treatment Panel guidelines from the National Cholesterol Education Program, released in May 2001, depart from previous guidelines in several ways. As in previous guidelines, treatment and treatment goals are based not only on lipid levels but also on the patient's risk status. The method for calculating risk, however, has been refined considerably. Patients are classified in the highest-risk group if they have any of these disorders: known coronary artery disease, diabetes mellitus, peripheral vascular disease, abdominal aortic aneurysm, carotid artery disease, or a 10-year risk of a coronary event of more than 20% (as determined by use of a scoring method).

Utility of direct measurement of low-density lipoprotein cholesterol in dyslipidemic pediatric patients
Ticho, B. S., E. J. Neufeld, et al. (1998), Arch Pediatr Adolesc Med 152(8): 787-91.
Abstract: BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) levels are the primary basis for treatment guidelines established for hyperlipidemic children and adolescents. Levels of LDL-C are commonly monitored by means of the Friedewald formula, an indirect calculation that requires an overnight fast. A new method has been developed for the direct measurement of LDL-C (DLDL-C) that does not require fasting. We evaluated the clinical utility of this method. DESIGN: We determined LDL-C concentrations simultaneously by the DLDL-C method, Friedewald equation, and beta-quantification (reference procedure). SETTING: Pediatric dyslipidemia clinic at Children's Hospital, Boston, Mass. PATIENTS: Ninety-two fasting hyperlipidemic pediatric patients. RESULTS: At the LDL-C concentration cutoffs commonly used for making therapeutic decisions, the DLDL-C method had a significant negative bias (P< or =.05) and misclassified patients into incorrect treatment groups more often than the Friedewald method. The negative predictive value for the DLDL-C method was lower than that for the Friedewald method (P< or =.05), and the cost of determining LDL-C level with the new method was 3 times greater. CONCLUSIONS: The misclassification potential for LDL-C, and the assay costs, were greater for the DLDL-C method than for the Friedewald calculation. Despite the apparent advantages of the DLDL-C method, we conclude that for hyperlipidemic children the utility of this new method is not advantageous over the conventional Friedewald method. In some conditions, such as in diabetes or marked hypertriglyceridemia, the DLDL-C method may be useful.

Utility of non-high-density lipoprotein cholesterol in hemodialyzed patients
Schreier, L., A. I. Gonzalez, et al. (2004), Metabolism 53(8): 1013-5.
Abstract: Non-high-density lipoprotein-cholesterol (HDL-C) is proposed as a strong predictor of cardiovascular disease (CVD). Measuring non-HDL-C, as total cholesterol minus HDL-C, is convenient for routine practice because, among other advantages, fasting is not required. There are limited data of non-HDL-C in end-stage renal disease patients. We applied non-HDL-C calculation to 50 chronic renal patients receiving maintenance hemodialysis (HD) and 20 healthy subjects, apart from measurement of low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) HDL, intermediate-density lipoprotein-cholesterol (IDL-C), apoprotein (apo) B, and triglycerides. HD patients presented higher plasma triglycerides and IDL-C and lower HDL-C than the control group, even after adjustment for age (P <.05). VLDL-C increased in HD patients (P <.001) while differences in non-HDL-C did not reach significance (P =.08). To detect which parameter constitutes a better marker of CVD risk among HD patients, a receiver-operating characteristic (ROC) analysis was performed considering HD patients in the highest risk group for CVD. In the ROC graphic, the plots of VLDL and IDL-C exhibited the greater observed accuracy and the best performance, while non-HDL-C showed a curve close to the 45 degrees line indicating that this parameter is a poor discriminator for evaluating CVD risk among HD patients. Non-HDL-C calculation, expressing all apo B-containing lipoproteins, may miss the significant contribution of each atherogenic lipoprotein, such as increase in IDL. This observation would not be in agreement with the currently proposed application of non-HDL-C a useful tool for risk assessment among HD patients.

Utilization of carbon from dietary polyunsaturates for brain cholesterol synthesis during early postnatal development in the rat: a 13C NMR study
Likhodii, S. S. and S. C. Cunnane (1995), Magn Reson Med 34(6): 803-13.
Abstract: Incorporation of 13C from a dietary precursor into cholesterol was studied in neonatal rats. Rats were given uniformly 13C-enriched polyunsaturated fatty acids intragastrically and total lipid extracts of liver and brain were analyzed by 13C-NMR 1, 4, 8, and 15 days later. 13C-enrichment was detected in brain but not in liver cholesterol. Maximal 13C-labeling was observed 4 days after injection of the label. Spectra revealed that 70% of newly incorporated 13C had 13C as an adjacent neighbor, the other 30% had 12C as the neighbor. Double quantum NMR revealed the arrangement in the cholesterol skeleton of the 13C-13C pairs transferred from precursors to cholesterol. Desmosterol, an intermediate of cholesterol synthesis, was identified in the spectra of brain lipids. Comparison of 13C-13C unit arrangements in both cholesterol and desmosterol allowed carbons 26 and 27 of desmosterol to be unambiguously assigned.

Utilization of lipid-lowering drugs in elderly persons with increased serum low-density lipoprotein cholesterol associated with coronary artery disease, symptomatic peripheral arterial disease, prior stroke, or diabetes mellitus before and after an educational program on dyslipidemia treatment
Ghosh, S. and W. S. Aronow (2003), J Gerontol A Biol Sci Med Sci 58(5): M432-5.
Abstract: BACKGROUND: We report the prevalence of use of lipid-lowering drugs in elderly persons with increased serum low-density lipoprotein (LDL) cholesterol associated with coronary artery disease (CAD), symptomatic peripheral arterial disease (PAD), prior stroke, and diabetes mellitus before and after an educational program on the treatment of dyslipidemia. METHODS: In an academic nursing home, we investigated the prevalence of use of lipid-lowering drugs in persons, mean age 77 +/- 9 years (40% men and 60% women), with a serum LDL cholesterol > or = 100 mg/dl associated with the aforementioned ailments before and after a 5-month educational program on the treatment of dyslipidemia was given to physicians and nurse practitioners. RESULTS: After the educational program, the prevalence of use of lipid-lowering drugs to treat the targeted elderly population increased (p <.001) in persons with CAD from 29% (18 of 63 persons) to 70% (44 of 63 persons), in persons with symptomatic PAD from 28% (5 of 18 persons) to 79% (15 of 19 persons), in persons with prior stroke from 24% (11 of 45 persons) to 64% (28 of 44 persons), and in diabetics from 26% (14 of 53 persons) to 67% (35 of 52 persons). CONCLUSION: A 5-month educational program on dyslipidemia treatment given to physicians and nurse practitioners in an academic nursing home improved the prevalence of use of lipid-lowering drugs in persons with increased serum LDL cholesterol associated with CAD, symptomatic PAD, prior stroke, and diabetes mellitus.

Utilization of monensin for detection of microdomains in cholesterol containing membrane
Bransburg-Zabary, S., E. Nachliel, et al. (1996), Biochim Biophys Acta 1285(2): 146-54.
Abstract: The effect of cholesterol on the monensin mediated proton-cation exchange reaction was measured in the time-resolved domain. The experimental system consisted of a black lipid membrane equilibrated with monensin (Nachliel, E., Finkelstein, Y. and Gutman, M. (1996) Biochim. Biophys. Acta 1285, 131-145). The membrane separated two compartments containing electrolyte solutions and pyranine (8-hydroxypyrene 1,3,6-trisulfonate) was added on to one side of the membrane. A short laser pulse was used to cause a brief transient acidification of the pyranine-containing solution and the resulting electric signal, derived from proton-cation exchange, was measured in the microsecond time domain. Incorporation of cholesterol had a clear effect on the electric transients as measured with Na+ or K+ as transportable cations. The measured transients were subjected to rigorous analysis based on numeric integration of coupled, non-linear, differential rate equations which correspond with the perturbed multi-equilibria state between all reactants present in the system. The various kinetic parameters of the reaction and their dependence on the cholesterol content had been determined. On the basis of these observations we can draw the following conclusions: (1) Cholesterol perturbed the homogeneity of the membrane and microdomains were formed, having a composition that differed from the average value. The ionophore was found in domains which were practically depleted of phosphatidylserine. (2) The diffusivity of the protonated monensin (MoH) was not affected by the presence of cholesterol, indicating that the viscosity of the central layer of the membrane was unaltered. (3) The diffusivity of the monensin metal complexes (MoNa and MoK) was significantly increased upon addition of cholesterol. As the viscosity along the cross membranal diffusion route is unchanged, the enhanced motion of the MoNa and MoK is attributed to variations of the electrostatic potential within the domains.

Utilization of uniformly labeled 13C-polyunsaturated fatty acids in the synthesis of long-chain fatty acids and cholesterol accumulating in the neonatal rat brain
Cunnane, S. C., S. C. Williams, et al. (1994), J Neurochem 62(6): 2429-36.
Abstract: Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18-carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20- and 22-carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13C-enriched 16- and 18-carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U-13C-polyunsaturated fatty acid mixture, 13C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13C enrichment remained high in the phospholipids and cholesterol for 15 days. 13C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16- and 18-carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long-chain saturated and monounsaturated fatty acids and cholesterol.

Vaccinia virus penetration requires cholesterol and results in specific viral envelope proteins associated with lipid rafts
Chung, C. S., C. Y. Huang, et al. (2005), J Virol 79(3): 1623-34.
Abstract: Vaccinia virus infects a wide variety of mammalian cells from different hosts, but the mechanism of virus entry is not clearly defined. The mature intracellular vaccinia virus contains several envelope proteins mediating virion adsorption to cell surface glycosaminoglycans; however, it is not known how the bound virions initiate virion penetration into cells. For this study, we investigated the importance of plasma membrane lipid rafts in the mature intracellular vaccinia virus infection process by using biochemical and fluorescence imaging techniques. A raft-disrupting drug, methyl-beta-cyclodextrin, inhibited vaccinia virus uncoating without affecting virion attachment, indicating that cholesterol-containing lipid rafts are essential for virion penetration into mammalian cells. To provide direct evidence of a virus and lipid raft association, we isolated detergent-insoluble glycolipid-enriched membranes from cells immediately after virus infection and demonstrated that several viral envelope proteins, A14, A17L, and D8L, were present in the cell membrane lipid raft fractions, whereas the envelope H3L protein was not. Such an association did not occur after virions attached to cells at 4 degrees C and was only observed when virion penetration occurred at 37 degrees C. Immunofluorescence microscopy also revealed that cell surface staining of viral envelope proteins was colocalized with GM1, a lipid raft marker on the plasma membrane, consistent with biochemical analyses. Finally, mutant viruses lacking the H3L, D8L, or A27L protein remained associated with lipid rafts, indicating that the initial attachment of vaccinia virions through glycosaminoglycans is not required for lipid raft formation.

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