-
[show abstract]
[hide abstract]
ABSTRACT: Cholesterol and plant sterols are lipids which are abundantly present in a western type diet of animal and plant origin, respectively. The daily intake averages 300 mg/day each. Over the past decades, a steadily increasing consumption of plant sterol enriched dairy products (2-3g/day) took place to lower circulating LDL cholesterol concentrations. Like all unsaturated components, plant sterols can be attacked by reactive oxygen species resulting in plant sterol oxidation products (POPs). The most widespread methods for POP determination are high-performance liquid chromatography and gas-liquid chromatography. Yet, based on the low plasma POP concentrations in normophytosterolemic subjects (POPs: ∼0.3-4.5 ng/ml), a reliable quantification yielding an appropriate limit of detection remains a challenge. While the more abundantly present cholesterol oxidation products (COPs) have elaborately been studied, research on the metabolism and biological effects of POPs is only emerging. In relation to atherogenity, biological effects including modulation of cholesterol homeostasis, membrane functioning, and inflammation are attributed to POPs. Although mostly supra-physiological concentrations are applied in in vitro assays, anti-tumor activity, cytotoxicity and estrogen-competition have been attributed to specific POPs. However, it is not obvious, if and how POPs may exert in vivo adverse or beneficial health effects similar to those attributed to COPs. In the field of nutritional science, standardized methods for the determination POPs are required to perform relevant biological studies and to assess their presence in complex foods or biological tissues and fluids. The aim of this review is to provide an overview and evaluation of the published methods and an update on the biological effects attributed to POPs.
Biochimie 09/2012; · 3.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cholesterol and plant sterols are lipids which are abundantly present in a western type diet of animal and plant origin, respectively. The daily intake averages 300 mg/day each. Over the past decades, a steadily increasing consumption of plant sterol enriched dairy products (2-3 g/day) took place to lower circulating LDL cholesterol concentrations. Like all unsaturated components, plant sterols can be attacked by reactive oxygen species resulting in plant sterol oxidation products (POPs). The most widespread methods for POP determination are high-performance liquid chromatography and gas-liquid chromatography. Yet, based on the low plasma POP concentrations in normophytosterolemic subjects (POPs: ∼0.3-4.5 ng/mL), a reliable quantification yielding an appropriate limit of detection remains a challenge. While the more abundantly present cholesterol oxidation products (COPs) have elaborately been studied, research on the metabolism and biological effects of POPs is only emerging. In relation to atherogenity, biological effects including modulation of cholesterol homeostasis, membrane functioning, and inflammation are attributed to POPs. Although mostly supra-physiological concentrations are applied in in vitro assays, anti-tumor activity, cytotoxicity and estrogen-competition have been attributed to specific POPs. However, it is not obvious, if and how POPs may exert in vivo adverse or beneficial health effects similar to those attributed to COPs. In the field of nutritional science, standardized methods for the determination of POPs are required to perform relevant biological studies and to assess their presence in complex foods or biological tissues and fluids. The aim of this review is to provide an overview and evaluation of the published methods and an update on the biological effects attributed to POPs.
Biochimie 09/2012; · 3.02 Impact Factor
-
T Vanmierlo,
J Popp,
H Kölsch,
S Friedrichs,
F Jessen,
B Stoffel-Wagner,
T Bertsch,
T Hartmann,
W Maier,
K von Bergmann,
H Steinbusch,
M Mulder, D Lütjohann
[show abstract]
[hide abstract]
ABSTRACT: Plant sterols (sitosterol, campesterol, stigmasterol and brassicasterol) are solely dietary-derivable sterols that are structurally very similar to cholesterol. In contrast to peripheral cholesterol, plant sterols can cross the blood-brain barrier and accumulate within mammalian brain. As an impaired function of the cerebrospinal fluid (CSF)-blood barrier is linked to neurodegenerative disorders, i.e. Alzheimer's disease (AD), we investigated whether this results in altered plant sterol concentrations in CSF.
Applying gas chromatography/mass spectrometry analysis, plant sterol concentrations were measured in plasma and CSF of patients with AD (n = 67) and controls (n = 29). Age, gender, plasma-to-CSF albumin ratio, CSF Aβ(42) , CSF pTau, APOE4 genotype, and serum creatinine were applied as covariates in the statistical analysis for individual plant sterols in order to compare plasma and CSF plant sterol concentrations between patients with AD and controls.
Albumin quotient was a consistent predictor in CSF for cholesterol and methyl plant sterols campesterol and brassicasterol. Comparison of lipid parameters per diagnosis based on relevant predictors revealed significantly lower concentrations of brassicasterol (P < 0.001) in CSF of patients with AD. Binary logistic regression analysis revealed that brassicasterol improved the predictive value when added to pTau and Aβ42 in a biomarker model.
Brassicasterol might be a relevant additional biomarker in AD.
Acta Psychiatrica Scandinavica 05/2011; 124(3):184-92. · 4.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Itraconazole, a triazole antifungal agent, has been demonstrated to act as an inhibitor of the ligand induced pregnane X receptor-mediated transcriptional regulation of the CYP3A4 gene. Here, we study the potential endogenous serum marker of CYP3A4 activity, 4beta-hydroxycholesterol, during therapy with itraconazole.
8 male patients with onychomycosis received two 1-week cycles of treatment with 400 mg itraconazole once daily in an open, prospective exploratory trial. Fasting serum samples were taken at the beginning and at the end of each cycle. The levels of cholesterol were measured using gas chromatography-flame ionization detection, while cholesterol and bile acid precursors were quantified by gas chromatography-mass spectrometry.
Total cholesterol decreased by 10% (p < 0.0005) during the itraconazole treatment. Concentrations of the cholesterol precursor lanosterol and 24, 25-dihydrolanosterol increased 10- and 240-fold, respectively (p < 0.001 for both). Interestingly, the ratio of serum lathosterol to cholesterol, an indicator of endogenous cholesterol synthesis downstream from lanosterol, remained unchanged. Absolute and cholesterol-corrected concentrations of 4beta-hydroxycholesterol, formed by CYP3A4-mediated oxidation, decreased significantly during both cycles, on average by 29.1% (p = 0.0006) and 20.8% (p = 0.0062), respectively. The brain-specific cholesterol metabolite 24S-hydroxycholesterol as well as its ratio to cholesterol increased by 19.7% (p = 0.0422) and 34.9% (p = 0.0013), respectively, while the concentrations of the other bile acid precursors, 7alpha-hydroxycholesterol and 27-hydroxycholesterol, remained unchanged.
In conclusion, 4beta-hydroxycholesterol appears to be a sensitive endogenous surrogate marker in human serum for inhibition of CYP3A4 by itraconazole.
International journal of clinical pharmacology and therapeutics 12/2009; 47(12):709-15. · 1.18 Impact Factor
-
Hamostaseologie 10/2009; 29 Suppl 1:S116. · 1.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the long-term efficacy and safety profile of ezetimibe 10 mg/day in patients with homozygous sitosterolemia.
This was an extension of a multi-centre, randomised, double-blind, placebo-controlled base study in which patients with homozygous sitosterolemia and plasma sitosterol concentrations > 5 mg/dl were randomised 4 : 1 to ezetimibe 10 mg/day (n = 30) or placebo (n = 7) for 8 weeks. Patients who successfully completed the base study with > 80% compliance to study medication were eligible to enter two, successive, 1-year extension studies in which ezetimibe 10 mg/day was administered in an open-label manner. Patients remained on their current treatment regimen (e.g. bile salt-binding resins, statins and low-sterol diet) during the base and extension studies. Patients had to be off ezetimibe therapy for > or = 4 weeks prior to entering the first extension. Efficacy and safety/tolerability parameters were evaluated every 12 and 26 weeks in the first and second years respectively. The primary efficacy end-point was mean percentage change in plasma sitosterol from baseline to study end for the cohort of patients (n = 21) who successfully completed the second extension study.
Treatment with ezetimibe 10 mg/day led to significant mean percentage reductions from baseline in plasma concentrations of sitosterol (-43.9%; p < 0.001), campesterol (-50.8%; p < 0.001), low-density lipoprotein (LDL) sterols (-13.1%; p < 0.050), total sterols (-10.3%; p < 0.050) and apolipoprotein (apo) B (-10.1%; p < 0.050). No significant changes from baseline were observed for lathosterol, high-density lipoprotein sterol, triglycerides or apo A-1. Maximal reductions in sitosterol and campesterol occurred within the first 52 weeks of treatment and were sustained for the duration of the study. For LDL sterol, total sterols and apo B, maximal reductions were achieved early (by weeks 4 or 16) and waned slightly through the remainder of the study. Overall ezetimibe 10 mg was well tolerated.
In patients with homozygous sitoserolemia, long-term treatment with ezetimibe 10 mg/day for 2 years was effective in reducing plasma plant sterol concentrations with an overall favourable safety and tolerability profile.
International Journal of Clinical Practice 11/2008; 62(10):1499-510. · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the effect of ezetimibe (EZE) 40 mg/day on non-cholesterol sterol plasma concentrations in patients with homozygous sitosterolaemia (HoS).
This was a multi-centre, randomised, double-blind, placebo-controlled parallel group study. Twenty-seven patients (> or = 18 years) with HoS and plasma sitosterol levels > 5 mg/dl who had been taking EZE 10 mg/day for > or = 6 months prior to enrolment received open-label EZE 10 mg/day for the duration of the study and were randomised 1 : 1 to blinded EZE 30 mg/day (4 x EZE 10 mg tablets; n = 13) or placebo (1 x EZE 10 mg tablet and 3 x matching placebo tablets; n = 14) for 26 weeks. Patients were permitted to remain on other ongoing treatments (e.g. bile salt-binding resin, statin and/or low sterol diet). End-points included median per cent between-group changes from baseline in plasma sitosterol, campesterol, lathosterol, low-density lipoprotein (LDL) sterols, LDL cholesterol (LDL-C) measured by gas-liquid chromatography, and Achilles tendon thickness size measured radiographically.
Ezetimibe 40 mg/day resulted in median per cent changes from baseline in plasma sitosterol levels of 3.3% vs. -10% in the EZE 10 mg/day group, in plasma campesterol of -0.5% vs. -9.7% in the EZE 10 mg/day group, and in plasma lathosterol of 0.8% vs. 1.1% in the EZE 10 mg/day group (p = ns for all between-group differences). Median per cent changes in the EZE 40 mg/day and EZE 10 mg/day groups, respectively, were 1.3% and 0% for LDL sterols and 2.5% and 4.4% for LDL-C (p = ns for both between-group differences). At study end-point, Achilles tendon thickness remained unchanged in the EZE 40 mg/day group and increased slightly in the EZE 10 mg/day group (2.2%), yielding a non-significant between-group difference of -2.2%. EZE 40 mg/day was generally well tolerated.
In patients with HoS, treatment with EZE 40 mg/day for 26 weeks was no more effective at reducing plasma plant sterol concentrations vs. EZE 10 mg/day. EZE 40 mg/day had a safety and tolerability profile similar to EZE 10 mg/day.
International Journal of Clinical Practice 07/2008; 62(7):995-1000. · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The conversion of cholesterol into bile acids occurs via a long cascade of enzymatically regulated oxidative processes. Our aim was to examine if an up-regulation of hepatic cholesterol 7alpha-hydroxylase (CYP7A1) in humans by cholestyramine, a bile acid-binding resin, has an effect on the degradation of brain-specific 24S-hydroxycholesterol.
Six normocholesterolemic male volunteers received 4 g cholestyramine b.i.d. for 2 weeks in an open, prospective exploratory trial. Serum concentrations of lipoproteins and triglycerides were measured by routine enzymatic assays. Sterols and oxysterols were measured by gas chromatography/mass spectrometry.
Total and LDL-cholesterol decreased on the average by 9.3% (p = 0.002) and 19.8% (p = 0.001) after 2 weeks of treatment, respectively. Absolute serum concentrations of 7alpha-hydroxycholesterol, a marker for bile acid production, increased 4-fold after 2 weeks, while 24S- and 27-hydroxycholesterol remained unchanged. Treatment with cholestyramine elevated serum levels of lathosterol, an indicator for the endogenous synthesis of cholesterol, by 146% (p = 0.009).
In addition to lowering serum concentrations of total cholesterol and LDL-cholesterol, cholestyramine at a dose rate of 4 g b.i.d. causes a significant increase in the CYP7A1 catalyzed 7alpha-hydroxylation of cholesterol and an up-regulation of endogenous cholesterol synthesis, as proven indirectly by an increase in serum lathosterol levels. Total serum levels of 24S- and 27-hydroxycholesterol remained unchanged indicating that an up-regulation in CYP7A1 activity is not responsible for the subsequent oxidative degradation of these hydroxylated sterols.
International journal of clinical pharmacology and therapeutics 12/2007; 45(11):577-82. · 1.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Epidemiological studies have convincingly demonstrated a positive association between LDL-cholesterol (LDL-C) and coronary artery disease but, in the case of HDL-C, there is an inverse association. Administration of high doses of the antifungal agent ketoconazole (800 mg/d) reduces serum concentrations of total cholesterol and LDL-C and there is a tendency for an increase in HDL-C. Our goal was to examine whether high-dose itraconazole raises HDL-C in subjects with normal levels of cholesterol.
8 male patients with onychomycosis received 2 one-week cycles of treatment with itraconazole at a dose of 400 mg once daily in an open, prospective exploratory trial. Serum levels of itraconazole and its active metabolite hydroxyitraconazole were determined using high-performance liquid chromatography at the end of each treatment cycle. Fasting levels of serum lipoproteins and triglycerides were measured twice using routine enzymatic assays at the beginning and end of each cycle. The effects of itraconazole and hydroxyitraconazole on HDL-C metabolism were assessed in vitro using a human Caco-2 cell line and analyzing apoA-I levels with an enzyme-linked immunosorbent assay.
During itraconazole treatment total cholesterol and LDL-C decreased on average by 12% (p < 0.001) and 17% (p < 0.001), respectively, whereas HDL-C increased by 21% (p < 0.001). The ratio LDL: HDL-C, an index of atherogenic risk, decreased by 30% (p < 0.001). Incubation of Caco-2 cells in the presence of itraconazole and hydroxyitraconazole for 3 hours resulted in a significant increase in apoA-I concentration in the medium (913 and 412%, respectively) compared with control.
In addition to its inhibitory effect on cholesterol synthesis, high-dose itraconazole (400 mg/d) causes a significant decrease in serum LDL-C and, in contrast to ketoconazole, a significant increase in HDL-C. In vitro studies with Caco-2 cells indicate that the latter observation might be caused by an increase in apoA-I levels.
International journal of clinical pharmacology and therapeutics 07/2007; 45(7):377-84. · 1.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Levels of the brain-specific cholesterol metabolite 24S-hydroxycholesterol are proposed as possible biomarkers for multiple sclerosis (MS). It is not yet clear for which aspect of the MS disease manifestations 24S-hydroxycholesterol is a reflection. We studied the relation of serum levels of 24S-hydroxycholesterol and other sterols to the disease characteristics of acute experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Serum was analyzed for cholesterol precursors, oxysterols, and plant sterols during the course of disease development. Significantly increased levels of the cholesterol metabolites 24S-hydroxycholesterol and 27-hydroxycholesterol were observed on day 9, before the onset of clinical signs. The serum levels of these oxysterols gradually increased up to 193% and 415%, respectively, at day 17, when clinical symptoms had recovered. Total cholesterol levels were slightly but significantly decreased on day 9 and day 17 in treated animals. Serum levels of cholesterol precursors and plant sterols decreased gradually from day 11 and day 14, respectively. Immunostaining of the 24S-hydroxycholesterol-forming enzyme Cyp46 was shown in macrophage infiltrates. In vitro experiments confirmed the presence of Cyp46 in macrophages and showed a decreased expression after LPS treatment. The data indicate that changes in serum oxysterols occur early in EAE and can be formed by macrophages. These early changes indicate an important role for oxysterols in the development of EAE.
Journal of Neuroscience Research 06/2007; 85(7):1499-505. · 2.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Linkage analyses have identified a possible hot spot for a late-onset Alzheimer's disease (LOAD) risk gene on chromosome 10q21-22 and 10q25. It was also shown that cholesterol metabolism is involved in the pathogenic mechanisms of AD. The gene of lysosomal acid lipase (LIPA) is located next to the putative hot spot on chromosome 10. Its protein is involved in cholesterol metabolism and responsible for catalysing the hydrolysis of cholesteryl esters and triglycerides inside the lysosome. Previous publications reported controversial results on the role of LIPA polymorphisms on the risk of LOAD. We investigated two LIPA polymorphisms (rs1051338 and rs2297472) for their putative effect on the risk of LOAD in a homogenous sample of German origin. Genotypes of the investigated polymorphisms in AD patients and controls were compared. Also the effect of the LIPA gene polymorphisms on plasma cholesterol levels and 24S-hydroxycholesterol/cholesterol ratios on AD patients were investigated. None of the observed polymorphisms showed a significant influence on the risk of AD. We found that LIPA exon 2 polymorphism (rs1051338) influenced plasma 24S-hydroxycholesterol/cholesterol ratios in AD patients where carriers of the C/C allele presented with higher ratios than heterozygote carriers of the LIPA allele. Even though the biological function and gene location of LIPA on chromosome 10 suggest that LIPA might be a candidate for an AD risk gene, our results revealed that polymorphisms in LIPA did not influence the risk of AD in our study.
Neuroscience Letters 08/2006; 402(3):262-6. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: During the last three to four decades, interest in the interaction of circulating and brain cholesterol has increased. As the CNS matures and cholesterol pools in the brain become constant, the rate of de novo synthesis of cholesterol in the brain is expected to decline. We measured cholesterol, its precursors and its brain specific metabolite 24S-hydroxycholesterol in hippocampus from 7 female and 13 male corpses by highly sensitive and specific gas chromatography-mass spectrometry. Two age groups (young, n=10; elderly, n=10) were formed with a cut-off at the median age of 38 years. The amount of cholesterol was comparable in young and elderly subjects. The concentrations of the cholesterol precursors lanosterol and lathosterol were significantly higher in young (P=0.036 and 0.005, respectively) than in elderly subjects. In accordance, there was a significantly negative correlation between age and lathosterol concentrations (r=-0.505; P=0.023). Absolute levels of 24S-hydroxycholesterol in the brain were slightly, but not significantly, lower in the hippocampal specimens from the elderly subjects. We conclude that during aging, cholesterol synthesis is decreased in the hippocampus, while absolute cholesterol content remains at a stable level.
Neuroscience Letters 08/2006; 403(1-2):15-9. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Neuropeptide Y (NPY) is a neurotransmitter expressed in the central nervous system and involved in learning and memory. The NPY L7P polymorphism has been associated with altered cholesterol levels in obese patients. Since altered cholesterol metabolism is also involved in Alzheimer's disease (AD), the effects of two NPY polymorphisms (L7P and IVS1-100 T/G) on CSF and plasma cholesterol and 24S-hydroxycholesterol were investigated in AD patients and non-demented controls. Furtheremore, the effect of both NPY polymorphisms on the risk of AD was studied. The NPY IVS1-100 T/G polymorphism influenced CSF levels of cholesterol, whereas CSF and plasma levels of 24S-hydroxycholesterol and plasma cholesterol were not altered by genotype. NPY L7P polymorphism did not influence CSF or plasma cholesterol or 24S-hydroxycholesterol. Both NPY polymorphisms did not influence the risk of AD. Our data support the observation, that NPY polymorphisms might influence cholesterol metabolism, but might not act as major risk factor in AD.
Acta Neurovegetativa 03/2006; 113(2):231-8. · 2.73 Impact Factor
-
D Lütjohann
[show abstract]
[hide abstract]
ABSTRACT: During the last three to four decades there has been an increasing interest in the interaction of circulating and brain cholesterol. Recent in vivo and in vitro studies have furthered our knowledge of cholesterol metabolism in the central nervous system (CNS). As the CNS matures and cholesterol pools in the brain become constant, the rate of de novo synthesis of cholesterol in the brain markedly declines. Besides some excretion of apoE-bound cholesterol via the CSF, another quantitatively more important mechanism has been described - the conversion of cholesterol into 24S-hydroxycholesterol, that is, in contrast to cholesterol, able to traverse the blood-brain barrier (BBB). The enzyme (CYP46a1) mediating this conversion has been characterized at the molecular level and is mainly located in neurons. Like other oxysterols, 24S-hydroxycholesterol is efficiently converted into normal bile acids or excreted in bile in its sulfated and glucuronidated form. Within the last 10 years the interest in studying the mechanisms of this and other cholesterol transport systems has increased and the results from these in vivo and in vitro investigations are reviewed.
Acta neurologica Scandinavica. Supplementum 02/2006; 185:33-42.
-
[show abstract]
[hide abstract]
ABSTRACT: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor, that is involved in lipid and glucose metabolism, which both seem to influence the risk of Alzheimer's disease (AD). 24S-Hydroxycholesterol is the major cholesterol elimination product of the brain and plasma and CSF 24S-hydroxycholesterol levels are altered in patients with neurodegenerative diseases. We investigated the effect of the common Pro12Ala variant of the PPARgamma gene on plasma cholesterol levels and 24S-hydroxycholesterol/ cholesterol ratios in 124 AD patients and 77 healthy controls. Furthermore, the influence of PPARgamma polymorphism on the risk of AD in 247 AD patients and 324 healthy controls was investigated. We found that PPARgamma Pro12Ala polymorphism influenced plasma 24S-hydroxycholesterol/ cholesterol ratios in AD patients in that carriers of the Ala allele presented with higher ratios than homozygote carriers of the Pro-allele. PPARgamma polymorphism did not influence the risk of AD. These results might point to an influence of PPARgamma Pro12Ala polymorphism on the elimination of 24S-hydroxycholesterol.
Acta Neurovegetativa 11/2005; 112(10):1381-9. · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear hormone receptor, that is involved in lipid and glucose
metabolism, which both seem to influence the risk of Alzheimer’s disease (AD). 24S-Hydroxycholesterol is the major cholesterol
elimination product of the brain and plasma and CSF 24S-hydroxycholesterol levels are altered in patients with neurodegenerative
diseases. We investigated the effect of the common Pro12Ala variant of the PPARγ gene on plasma cholesterol levels and 24S-hydroxycholesterol/
cholesterol ratios in 124 AD patients and 77 healthy controls. Furthermore, the influence of PPARγ polymorphism on the risk
of AD in 247 AD patients and 324 healthy controls was investigated. We found that PPARγ Pro12Ala polymorphism influenced plasma
24S-hydroxycholesterol/ cholesterol ratios in AD patients in that carriers of the Ala allele presented with higher ratios
than homozygote carriers of the Pro-allele. PPARγ polymorphism did not influence the risk of AD. These results might point
to an influence of PPARγ Pro12Ala polymorphism on the elimination of 24S-hydroxycholesterol.
Acta Neurovegetativa 09/2005; 112(10):1381-1389. · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Plant sterol/stanol margarines are recommended as a lipid-lowering dietary supplement in the treatment of hypercholesterolemia. Parameters predicting the individual cholesterol-lowering effect have not been elucidated so far. Therefore, we investigated the responsiveness to sitostanol-supplemented margarine in a specially selected population.
From a total number of 137 male subjects with hypercholesterolemia, eight subjects with the lowest and eight subjects with the highest ratios of lathosterol to campesterol in serum were included in the study. They received 1 g sitostanol-supplemented margarine b.i.d. for four weeks. Serum lipoproteins, the cholesterol precursor lathosterol, the plant sterols campesterol and sitosterol were measured. Subjects with a low ratio of lathosterol to campesterol had a significant decrease of serum total cholesterol (-14.2%; p < 0.01) and LDL cholesterol (-13.8%; p < 0.01; responder). In subjects with a high ratio there was no significant change in total cholesterol and LDL cholesterol (2.2 and 4.3%; non-responder).
The ratio of serum lathosterol to campesterol predicts the reduction of total cholesterol and LDL cholesterol during administration of sitostanol-supplemented margarine in patients with mild hypercholesterolemia.
International journal of clinical pharmacology and therapeutics 07/2005; 43(7):305-10. · 1.18 Impact Factor
-
Neurology 05/2005; 64(8):1476. · 8.31 Impact Factor
-
H Kölsch,
M Linnebank, D Lütjohann,
F Jessen,
U Wüllner,
U Harbrecht,
K M Thelen,
M Kreis,
F Hentschel,
A Schulz,
K von Bergmann,
W Maier,
R Heun
[show abstract]
[hide abstract]
ABSTRACT: Glutathione S-transferase omega-1 (GSTO1) protects from oxidative stress, a risk factor for Alzheimer disease (AD), vascular dementia (VaD), and stroke. Polymorphisms in GSTO1 might influence the function of the protein and thus the risk of AD, VaD, and stroke.
The GSTO1 gene was screened for variations. The effect of the detected polymorphisms on the risk of AD, VaD, and stroke was evaluated. CSF levels of cholesterol and plasma homocysteine levels were compared according to the GSTO1 genotype.
Two missense polymorphisms in exon 4 of GSTO1 (Ala140Asp and Glu155DeltaGlu) were detected and tested for their association with AD, VaD, and stroke. The Asp/Asp and Ala/Asp genotypes increased the risk of stroke (p = 0.003, OR = 2.1), and the Asp/Asp genotype increased the risk of VaD (p = 0.02, OR = 2.2). GSTO1 polymorphisms did not influence the risk of AD, but the Asp allele influenced the age at onset (p = 0.05). In nondemented probands CSF levels of cholesterol were increased in carriers of the Asp/Asp genotype (p = 0.004); however, in patients with manifest dementia the authors found decreased CSF levels of cholesterol in carriers of the Asp/Asp genotype (p = 0.028). Serum homocysteine levels in stroke patients were higher in carriers of at least one Asp allele (p = 0.011).
The GSTO1 Asp allele may be a genetic risk factor for cerebrovascular diseases, and might influence the course of Alzheimer disease, even though effects vary in different studies.
Neurology 01/2005; 63(12):2255-60. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The concentrations of serum cholesterol, cholestanol and non-cholesterol sterols were measured in a patient with cerebrotendinous xanthomatosis under different therapeutic regimens. During treatment with chenodeoxycholic acid (CDCA) (750 mg/day) plus simvastatin (20 mg/day) for two years cholesterol and cholestanol concentrations averaged 188+/-10 mg/dl and 0.54+/-0.03 mg/dl. Thereafter treatment with simvastatin was discontinued. During treatment with low-density lipoprotein (LDL)-apheresis plus CDCA for 33 weeks, cholestanol concentrations reached almost normal levels (0.48+/-0.03 mg/dl immediately before and 0.32+/-0.02 mg/dl directly after LDL-apheresis, n=6). A further reduction of cholesterol and cholestanol was achieved by addition of simvastatin (20 mg/day). Cholesterol and cholestanol concentrations before and after LDL-apheresis during this treatment period averaged 122+/-4 mg/dl and 55+/-10 mg/dl, and 0.42+/-0.02 mg/dl and 0.18+/-0.06 mg/dl, respectively. Despite the consistent reduction of cholestanol to normal or even subnormal levels, a definite improvement of clinical symptoms was not noted. Our results suggest caution in the recourse to an aggressive cholestanol lowering therapy.
Neurological Sciences 11/2004; 25(4):185-91. · 1.32 Impact Factor
