OBJECTIVE

Women with polycystic ovary syndrome (PCOS) are assumed to be at increased risk for cardiovascular diseases. This study examined the variations in oxidised low-density lipoprotein (OxLDL) concentration in relation to insulin levels in young women with PCOS.

METHODS

Cross-sectional clinical study in tertiary cares research hospitals. A total of 179 women with PCOS (79 overweight) and 56 age- and body mass index-matched controls were examined.

METHODS

Blood samples were collected in follicular phase of the cycle for the basal glucose, total-, high-density lipoprotein-cholesterol (HDL-C) and LDL-cholesterol, OxLDL, triglycerides, apolipoprotein-A1 (Apo-A1) and B (Apo-B), lipoprotein (a), insulin, testosterone and sex hormone-binding globulin (SHBG). Homeostatic model index (HOMA) and free androgen index (FAI) were determined.

RESULTS

Overweight and normal weight women with PCOS had higher concentrations of OxLDL than their control counterparts (P = 0.007 and 0.003 respectively). Both the basal insulin (P = 0.003) and HOMA values (P < 0.001) were significantly higher in overweight than normal weight patients. Testosterone and FAI were higher in patients than in the respective controls (P < 0.001). The only independent predictor of increased OxLDL concentration in normal weight patients was Apo-B-to-Apo-A1 ratio (P < 0.001, odds ratio (OR) 6.1; 95% confidence interval (CI) 2.3-16.4), while in obese PCOS, it was total cholesterol-to-high-density lipoprotein cholesterol ratio (P < 0.001, OR 2.8; 95% CI 1.6-4.9).

CONCLUSIONS

Young normal weight and overweight PCOS women have similarly increased OxLDL levels. Our results may indicate the presence of primary alteration in lipid metabolism in patients with PCOS. To answer the question whether the alteration in LDL particle size can by itself pose a higher cardiovascular risk, a careful follow-up of these women is needed.

Genetic studies have identified polymorphisms at the apolipoprotein (Apo) A1 gene associated with HDL cholesterol and apolipoprotein levels, and a relationship between the severity of coronary artery disease and polymorphisms at the 5'-end of Apo A1 has been also reported. This study was designed to examine the relationship between polymorphism at the Apo A1 gene and the risk of early coronary artery disease. Furthermore, the association of the polymorphism with the classical risk factors was analyzed. A total of 176 male patients (mean age 43 +/- 5 years) diagnosed as having unstable angina (53 cases) or myocardial infarction (123 cases) were prospectively evaluated. Data referring to hypertension, diabetes and tobacco consumption were recorded. The levels of total cholesterol, HDL cholesterol, Apo A1 and B and triglycerides were determined. DNA was obtained from the 176 patients and from 200 controls. In order to determine the Apo A1 genotypes at two polymorphic sites (G/A at -75 bp, and C/T at +83 bp), DNA was PCR amplified and digested with MspI. The frequency of carriers of the rare allele at the -75 bp site (M1-) was 0.34 in cases and 0.24 in controls (p < 0.05). The frequencies of the M1- allele among patients with angina and myocardial infarction were 0.43 (p = 0.009, angina vs. controls) and 0.30, respectively. No significant association between this polymorphism and other cardiovascular risk factors was found. No difference in the frequencies for carriers of the rare allele at the +83-bp polymorphism (M2) was observed among patients with angina (0.08 vs. 0.07) or myocardial infarction (0.04 vs. 0.07), and no association between this polymorphism and tobacco, hypertension and diabetes was noted. Patients carrying the rare M2- allele had a lower concentration of total cholesterol compared to those without this allele (183 +/- 29 vs. 223 +/- 54, p < 0.04) and HDL cholesterol was also lower among patients carrying the M2- (26 +/- 4 vs. 33 +/- 9, p < 0.02). In our community male patients with a diagnosis of coronary artery disease and age less than 50 years showed a higher frequency of the M1- allele at the -75-bp site of the Apo A1 gene. There was a significant increase in the frequency of the M1- allele in patients with unstable angina and no association with risk factors. In the +83-bp polymorphism there was no difference in the allelelic frequencies or the risk factors, except for the HDL cholesterol and total cholesterol where the patients with the allele M2- had lower levels than those homozygous for the M2+.

BACKGROUND

Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults.

METHODS

Subjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA(1c)]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit, for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in Canadian adults.

RESULTS

All biomarkers were significantly associated with BMI (P ≤ 0.001). ApoA1 (β = -0.31, P < 0.0001), HDL-C (β = -0.61, P < 0.0001), and 25(OH)D (β = -0.25, P < 0.0001) were inversely associated with BMI, while all other biomarkers showed positive linear associations. Distinct patterns of association were noted among normal weight, overweight, and obese groups, excluding CRP which showed a significant positive association with BMI in the overall population (β = 2.80, P < 0.0001) and in the normal weight (β = 3.20, P = 0.02), overweight (β = 3.53, P = 0.002), and obese (β = 2.22, P = 0.0002) groups.

CONCLUSIONS

There is an apparent profile of cardiometabolic and inflammatory biomarkers that emerges as BMI increases from normal weight to obesity. Understanding these profiles may permit developing an effective approach for early risk prediction for cardiometabolic disease.

Side-effects following long-term endocrine therapy might have clinical implications. The aim of this study was to study potential methods to detect effects on plasma induced by hormonal therapies. The composite methylene (chemical shift between 1.2-1.4 ppm) and methyl (0.8-0.9 ppm) aliphatic peaks of the 1H magnetic resonance spectrum (500 MHz) were analysed in consecutive plasma samples of 23 cancer patients drawn before and during treatment with hormonally acting drugs. The aliphatic peaks were analyzed for line width at half-height and then averaged. In addition, 13C magnetic resonance spectroscopy (125 MHz) analyses were done in selected patients. The blood samples were analyzed for triglyceride, cholesterol, apolipoprotein A1 (apo A1), and apolipoprotein B (apo B) levels. The methylene line width increased significantly after 9 weeks of tamoxifen (41.4 vs. 37.6 Hz). A trend of differences was observed in the saturated part of the 13C magnetic resonance spectrum. A significant decrease in total cholesterol (mean decrease, 13%), increases in apo A1 (9%) and in the ratio of apo A1 to apo B (28%), but unchanged total triglycerides were found, indicating a decrease in LDL and increase in HDL lipoproteins in these patients following tamoxifen therapy. During dose escalation with the aromatase inhibitor exemestane, the methylene line width seemed to decrease (31.9 vs 38.8 Hz, at 12 weeks and baseline, respectively). Significant decreases in total (13%) and HDL (32%) cholesterol, apo A1 (25%), and total triglyceride (16%) levels were found during the same interval. The apo A1/apo B ratio decreased by 25%. For patients on dexamethasone, the proton aliphatic line widths increased one day after the initiation of therapy. The changes in line shape observed during dexamethasone therapy indicated lower levels of triglyceride-rich relative to triglyceride-poor lipoproteins, consistent with results from the lipid analyses. In conclusion, nuclear magnetic resonance spectroscopy might have potential to detect effects on plasma induced by endocrine therapy. The lipid analyses in these patients were in support of the changes in lipid profile as evaluated by nuclear magnetic resonance spectroscopy.

Sphingomonas sp. A1 possesses a high molecular weight (HMW) alginate uptake system composed of a novel pit formed on the cell surface and a pit-dependent ATP-binding cassette (ABC) transporter in the inner membrane. The transportation of HMW alginate from the pit to the ABC transporter is mediated by the periplasmic HMW alginate-binding proteins AlgQ1 and AlgQ2. We determined the crystal structure of AlgQ2 complexed with an alginate tetrasaccharide using an alginate-free (apo) form as a search model and refined it at 1.6-A resolution. One tetrasaccharide was found between the N and C-terminal domains, which are connected by three extended hinge loops. The tetrasaccharide complex took on a closed domain form, in contrast to the open domain form of the apo form. The tetrasaccharide was bound in the cleft between the domains through van der Waals interactions and the formation of hydrogen bonds. Among the four sugar residues, the nonreducing end residue was located at the bottom of the cleft and exhibited the largest number of interactions with the surrounding amino acid residues, suggesting that AlgQ2 mainly recognizes and binds to the nonreducing part of a HMW alginate and delivers the polymer to the ABC transporter through conformational changes (open and closed forms) of the two domains.

BACKGROUND

Physical activity (PA) and sedentary behavior (SED) may have independent effects on health and disease. This might be due to PA and SED having distinct effects on lipoprotein metabolism. The aim of this study was to determine associations between lipoprotein subclass particle concentrations (-P) and accelerometer-measured SED and moderate-to-vigorous PA (MVPA) in a sample of healthy adult subjects.

METHODS

Lipoprotein subclass particle concentrations were determined by proton nuclear magnetic resonance spectroscopy, whereas SED and MVPA were measured using Agtigraph GT1M and GT3X+ accelerometers. We obtained valid data in 73 subjects (30 men and 43 women, age 40.5 ± 10.6 years; body mass index 24.0 ± 2.8). Multiple regression analysis was used to determine associations (partial correlations) with lipoproteins.

RESULTS

Positive associations were detected between SED and small VLDL-P, large LDL-P and TG (partial r = 0.24 to 0.25, p < .047). Corresponding associations were non-significant for MVPA (partial r = -0.12 to 0.04, p>> .355). On the contrary, MVPA was positively associated with large HDL-P, average HDL size, Apo A1 and HDL-cholesterol (partial r = 0.28 to 0.50, p < .027), whereas SED was not (partial r = -0.06 to 0.07, p>> .607).

CONCLUSIONS

There might be a specific effect of SED versus MVPA on lipoprotein metabolism. However, our results must be interpreted carefully due to possible effect-modification by gender and a low sample size. Thus, our findings should be viewed as preliminary.

Apolipoprotein A1 (Apo A-I), the most abundant component of high-density lipoprotein (HDL), is an anti-inflammatory molecule, yet its potential role in the pathogenesis of multiple sclerosis (MS) has not been fully investigated. In this study, Western blot analyses of human plasma showed differential Apo A-I expression in healthy controls compared to MS patients. Further, primary progressive MS patients had less plasma Apo A-I than other forms of MS. Using experimental allergic encephalomyelitis (EAE) as a model for MS, Apo A-I deficient mice exhibited worse clinical disease and more neurodegeneration concurrent with increased levels of pro-inflammatory cytokines compared to wild-type animals. These data suggest that Apo A-I plays a role in the pathogenesis of EAE, a model for MS, creating the possibility for agents that increase Apo A-I levels as potential therapies for MS.

To evaluate the effect of moderate intensity of aerobic exercise on elderly people with mild Alzheimer's disease, we recruited fifty volunteers aged 50 years to 80 years with cognitive impairment. They were randomized into two groups: aerobic group (n=25) or control group (n=25). The aerobic group was treated with cycling training at 70% of maximal intensity for 40 min/d, 3 d/wk for 3 months. The control group was only treated with heath education. Both groups were received cognitive evaluation, laboratory examination before and after 3 months. The results showed that the Minimum Mental State Examination score, Quality of Life Alzheimer's Disease score and the plasma Apo-a1 level was significantly increased (P<0.05), the Alzheimer's Disease Assessment Scale-cognition score, Neuropsychiatric Inventory Questionnaire score was significantly decreased.(P<0.05) in aerobic group before and after 3 months in aerobic group. For the control group, there was no significant difference in scores of Alzheimer's Disease Assessment Scale-cognition, Neuropsychiatric Inventory Questionnaire, Quality of Life Alzheimer's Disease, Apo-a1 (P>0.05), while Minimum Mental State Examination scores decreased significantly after 3 months (P<0.05). In conclusion, moderate intensity of aerobic exercise can improve cognitive function in patients with mild Alzheimer's disease.

BACKGROUND

TCF7L2 rs7903146 is an important genetic factor predicting type 2 diabetes (T2DM) which has also been linked to higher cardiovascular risk. To date, there is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism.

RESULTS

We studied whether rs7903146 influenced postprandial lipid metabolism in three different populations (healthy young men, metabolic syndrome (MetS) patients and elderly persons). Eighty-eight healthy males were submitted to a single saturated fatty acid-rich test meal. Additionally, 110 middle-aged MetS patients and 20 healthy elderly persons (≥ 65 years) were submitted to three different dietary models followed by test meals. Minor allele homozygotes for rs7903146 showed a worse postprandial lipemia profile in young males, as seen by a lower HDL-cholesterol and Apo A1 concentration during the postprandial lipemia and a trend towards higher triglycerides (TG), than the other genotypes. In healthy elderly persons, carriers of the minor allele showed higher total cholesterol, LDL-cholesterol, Apo B and TG in the fasting state, and a higher postprandial area under the curve for total cholesterol, Apo B, small-triglyceride rich lipoprotein (TRL) cholesterol and small-(TRL) triglycerides. These results were accompanied by differential changes in adipokines. We did not observe any influence of rs7903146 on the postprandium of MetS patients.

CONCLUSIONS

Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk observed in these persons.

BACKGROUND

ClinicalTrials.gov NCT00429195.

The transient receptor potential channel A1 (TRPA1) is unique among ion channels of higher vertebrates in that it harbors a large ankyrin repeat domain. The TRPA1 channel is expressed in the inner ear and in nociceptive neurons. It is involved in hearing as well as in the perception of pungent and irritant chemicals. The ankyrin repeat domain has special mechanical properties, which allows it to function as a soft spring that can be extended over a large range while maintaining structural integrity. A calcium-binding site has been experimentally identified within the ankyrin repeats. We built a model of the N-terminal 17 ankyrin repeat structure, including the calcium-binding EF-hand. In our simulations we find the calcium-bound state to be rigid as compared to the calcium-free state. While the end-to-end distance can change by almost 50% in the apo form, these fluctuations are strongly reduced by calcium binding. This increase in stiffness that constraints the end-to-end distance in the holo form is predicted to affect the force acting on the gate of the TRPA1 channel, thereby changing its open probability. Simulations of the transmembrane domain of TRPA1 show that residue N855, which has been associated with familial episodic pain syndrome, forms a strong link between the S4-S5 connecting helix and S1, thereby creating a direct force link between the N-terminus and the gate. The N855S mutation weakens this interaction, thereby reducing the communication between the N-terminus and the transmembrane part of TRPA1.

BACKGROUND

Lipoproteins are closely associated with the atherosclerotic vascular process. Elevated levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (apo AI) in plasma indicate a low probability of coronary heart disease (CHD) together with enhanced longevity, and elevated levels of low-density lipoprotein-cholesterol (LDL-C) and apo B indicate an increased risk of CHD and death. Studies linking gene activation and the induction of cytochrome P450 with elevated plasma levels of apo AI and HDL-C and lowered plasma levels of LDL-C presented a new potential approach to prevent and treat atherosclerotic disease.

OBJECTIVE

This is a review aimed at clarifying the effects of P450-enzymes and gene activation on cholesterol homeostasis, the atherosclerotic vascular process, prevention and regression of atherosclerosis and the manifestation of atherosclerotic disease, particularly CHD, the leading cause of death in the world.

RESULTS

P450-enzymes maintain cellular cholesterol homeostasis. They respond to cholesterol accumulation by enhancing the generation of hydroxycholesterols (oxysterols) and activating cholesterol-eliminating mechanisms. The CYP7A1, CYP27A1, CYP46A1 and CYP3A4 enzymes generate major oxysterols that enter the circulation. The oxysterols activate-via nuclear receptors-ATP-binding cassette (ABC) A1 and other genes, leading to the elimination of excess cholesterol and protecting arteries from atherosclerosis. Several drugs and nonpharmacologic compounds are ligands for the liver X receptor, pregnane X receptor and other receptors, activate P450 and other genes involved in cholesterol elimination, prevent or regress atherosclerosis and reduce cardiovascular events.

CONCLUSIONS

P450-enzymes are essential in the physiological maintenance of cholesterol balance. They activate mechanisms which eliminate excess cholesterol and counteract the atherosclerotic process. Several drugs and nonpharmacologic compounds induce P450 and other genes, prevent or regress atherosclerosis and reduce the occurrence of non-fatal and fatal CHD and other atherosclerotic diseases.

BACKGROUND

Recent research has focused on the use of inflammatory biomarkers in the prediction of cardiovascular risk. However, information is scant regarding the association between these inflammatory markers with other cardiovascular risk factors in Asian Indians, particularly in women.

OBJECTIVE

To explore the association between inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) and white blood cell (WBC) count and cardiovascular risk factors such as overall and central adiposity, blood pressure, lipid and lipoprotein variables and fasting glucose.

METHODS

We conducted a cross-sectional analysis on 100 women aged 35-80 years. Participants were selected following cluster sampling methodology from 12 different randomly selected urban wards of Kolkata Municipal Corporation.

RESULTS

Hs-CRP has a significant association with body mass index (BMI) ( p < 0.001) and waist circumference (WC) (p = 0.002). Significant inverse associations were observed between high-density lipoprotein cholesterol (HDL-C) and both inflammatory markers, hs-CRP (p = 0.031) and WBC count, (p = 0.014). Apolipoprotein A1 (Apo A1) was also negatively associated with hs-CRP. WBC count has significant correlation with fasting glucose and total cholesterol (TC) /HDL-C ratio. Using logistic regression, adjusting for age, BMI (odds ratio/OR, 1.186; confidence interval/CI, 1.046-1.345; p = 0.008) and WC (OR, 1.045; CI, 1.005-1.087; p = 0.027) were the covariates significantly associated with hs-CRP.

CONCLUSIONS

In the present study, risk factors like BMI, WC, and HDL-C and apo A1 show significant association with hs-CRP. WBC count was significantly correlated with HDL-C, fasting glucose, TC/HDL-C ratio in women.

OBJECTIVE

To determine the association between glycated hemoglobin (HbA1c) and angiographically proven coronary artery disease (CAD) and its severity in nondiabetic individuals.

METHODS

We enrolled 299 consecutive individuals undergoing coronary angiography for suspected ischemia. Patients were included if they had no history of prior revascularization or diabetes mellitus and had fasting blood glucose<126mg/dl (7.0mmol/l) and HbA1c<6.5% (47mmol/mol). The severity of the CAD was also evaluated using the Gensini score. Serum HbA1c (NGSP certified Method), highly sensitive C-reactive protein (hsCRP), lipid profile, insulin and APO lipoprotein A1 and B100 levels were measured.

RESULTS

Mean age was 58.8±10.4 year; 60.9% men. One hundred forty seven patients had significant CAD (≥50% stenosis in any major vessel). With increasing HbA1c levels, there was a significant increase in the prevalence of CAD and number of vessels involved. In multivariate analysis, HbA1c emerged as an independent predictor of significant CAD (OR: 2.8, 95% CI: 1.3-6.2, p=0.009). Adjusted ORs for the occurrence of CAD were highest in subjects with both hsCRP and HbA1c in the upper 2 quartiles (OR: 4.183; 95% CI: 1.883-9.290, p<0.0001). There was a significant association between Gensini score and increasing HbA1c tertiles (p=0.038). The ideal cut-off value of HbA1c for prediction of the occurrence of CAD was 5.6% 38mmol/mol) (sensitivity: 60.5%, specificity: 52%).

CONCLUSIONS

In non-diabetic subjects, HbA1c could be utilized for risk stratification of CAD and its severity, independent of traditional cardiovascular risk factors, insulin resistance and inflammatory markers.

Abnormal blood lipid profiles may be observed both in HIV-infected individuals who are untreated and in those receiving highly active antiretroviral therapy (HAART). Besides maintaining optimal control of HIV replication and the preservation of immunity, treatment regimens ideally should have minimal or no metabolic side-effects. Nevirapine (NVP)-based HAART has beneficial effects on the lipid profile, in both treatment-näive and treatment-experienced patients, unlike protease inhibitor (PI)-based HAART. In antiretroviral (ARV)-naive patients enrolled in the Fat Redistribution and Metabolic Substudy (FRAMS) of the Atlantic Study, the NVP-containing regimen increased total cholesterol, high density lipoprotein (HDL) cholesterol concentration and particle size and apolipoprotein A1 (apo A1) levels at 24 weeks. The changes in HDL cholesterol plasma levels were demonstrated to be sustained in a subset of 98 FRAMS patients at 96 weeks. Switching from a PI-containing regimen to a PI-sparing regimen containing NVP has likewise been shown to favorably alter lipid profiles in two open label studies. In one study, one or more lipid profile parameters (total cholesterol, low density lipoprotein [LDL] cholesterol, LDL particle size, very low density lipoprotein cholesterol [VLDL1] HDL cholesterol, HDL particle size) had reverted to normal after 24 weeks in significantly more NVP-treated patients than PI-treated patients (69% versus 23%, p < .05). The 12-month results from the Barcelona PI Switch Study indicated that NVP improved lipid profiles over 12 months after PI-treated patients were switched to NVP. In conclusion, first-line NVP treatment is associated with a favorable lipoprotein profile, i.e., an increase in HDL-cholesterol and apo A1 plasma levels The lipid profile observed in patients who are switched from a PI-based regimen to a NVP-based regimen improves in a very similar fashion. These favorable lipid profiles may be of clinical benefit in reducing the risk for coronary artery disease in HIV-1 infected patients who are receiving long-term antiretroviral therapy.

Dysregulated macrophage cholesterol homoeostasis lies at the heart of early and developing atheroma, and removal of excess cholesterol from macrophage foam cells, by efficient transport mechanisms, is central to stabilization and regression of atherosclerotic lesions. The present study demonstrates that transient overexpression of STARD3 {START [StAR (steroidogenic acute regulatory protein)-related lipid transfer] domain 3; also known as MLN64 (metastatic lymph node 64)}, an endosomal cholesterol transporter and member of the 'START' family of lipid trafficking proteins, induces significant increases in macrophage ABCA1 (ATP-binding cassette transporter A1) mRNA and protein, enhances [(3)H]cholesterol efflux to apo (apolipoprotein) AI, and reduces biosynthesis of cholesterol, cholesteryl ester, fatty acids, triacylglycerol and phospholipids from [(14)C]acetate, compared with controls. Notably, overexpression of STARD3 prevents increases in cholesterol esterification in response to acetylated LDL (low-density lipoprotein), blocking cholesteryl ester deposition. Thus enhanced endosomal trafficking via STARD3 induces an anti-atherogenic macrophage lipid phenotype, positing a potentially therapeutic strategy.

BACKGROUND

Several genetic variants in the ATP-binding cassette transporter A1 (ABCA1) gene have associated with modifications of serum high-density lipoprotein cholesterol (HDL-C) levels and the susceptibility for coronary heart disease, but the findings are still controversial in diverse racial/ethnic groups. Bai Ku Yao is an isolated subgroup of the Yao minority in southern China. The present study was undertaken to detect the possible association of V825I (rs2066715) polymorphism in the ABCA1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

METHODS

A total of 677 subjects of Bai Ku Yao and 646 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Polymerase chain reaction and restriction fragment length polymorphism assay combined with gel electrophoresis were performed for the genotyping of V825I variant, and then confirmed by direct sequencing.

RESULTS

The levels of serum total cholesterol (TC), HDL-C, apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G and A alleles was 57.4% and 42.6% in Bai Ku Yao, and 57.7% and 42.3% in Han (P>> 0.05); respectively. The frequency of GG, GA and AA genotypes was 33.7%, 47.4% and 18.9% in Bai Ku Yao, and 33.4%, 48.6% and 18.0% in Han (P>> 0.05); respectively. There was no difference in the genotypic and allelic frequencies between males and females in the both ethnic groups. The subjects with AA genotype in Bai Ku Yao had higher serum TC levels than the subjects with GG and GA genotypes (P < 0.05). The participants with AA genotype in Han had lower serum HDL-C and ApoAI levels than the participants with GG and GA genotypes (P < 0.05 for each), but these results were found in males but not in females. Multivariate linear regression analysis showed that the levels of TC in Bai Ku Yao and HDL-C and ApoAI in male Han were correlated with genotypes (P < 0.05 for all). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, and blood pressure in both ethnic groups (P < 0.05-0.001).

CONCLUSIONS

The present study suggests that the V825I polymorphism in the ABCA1 gene is associated with male serum HDL-C and ApoAI levels in the Han, and serum TC levels in the Bai Ku Yao populations. The difference in the association of V825I polymorphism and serum lipid levels between the two ethnic groups might partly result from different ABCA1 gene-environmental interactions.

Low-density lipoprotein (LDL) provides a highly versatile natural nanoplatform for delivery of optical and MRI contrast agents, photodynamic therapy agents and chemotherapeutic agents to normal and neoplastic cells that over express LDL receptors (LDLR). Extension to other lipoproteins ranging in diameter from approximately 5-10 nm (high density lipoprotein, HDL) to over a micron (chilomicrons) is feasible. Loading of contrast or therapeutic agents has been achieved by covalent attachment to protein side chains, intercalation into the phospholipid monolayer and extraction and reconstitution of the triglyceride/cholesterol ester core. Covalent attachment of folate to the lysine side chain amino groups was used to reroute the LDL from its natural receptor (LDLR) to folate receptors and could be utilized to target other receptors. A semi-synthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles (MIONs) with carboxylated cholesterol and overlaying a monolayer ofphospholipid to which Apo A1, Apo E or synthetic amphoteric alpha-helical polypeptides were adsorbed for targeting HDL, LDL or folate receptors, respectively. These particles can be utilized for in situ loading of magnetite into cells for MRI monitored cell tracking or gene therapy.

BACKGROUND

The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism.

OBJECTIVE

To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia.

METHODS

A randomized double-blind sequential cross-over study.

METHODS

Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated.

RESULTS

No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/-35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02).

CONCLUSIONS

A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.

BACKGROUND

For the most part, the benefits of monounsaturated-rich diets (MUFA-diet) have been related to their action on plasma lipid levels. However other non-lipidic effects could also be involved in their protective effects. One of these involves the decrease in plasma levels of plasminogen activator inhibitor type 1 (PAI-1), the main inhibitor of fibrinolysis. Given that the PAI-1 is of endothelial origin, one hypothesis is that the MUFA-diet could protect against CHD by modulating some endothelial components.

RESULTS

Healthy male subjects (n = 25) received three different consecutive diets, each lasting 28 days: a low fat NCEP-I-diet, with 28% calories as fat, 10% saturated fat (SAT), 12% monounsaturated (MUFA) and 6% polyunsaturated (PUFA); a MUFA-diet, with 38% calories as fat, 10% SAT, 22% MUFA and 6% PUFA; and a SAT rich-diet (SAT-diet), with 38% calories as fat, 20% SAT, 12% MUFA and 6% PUFA. After each dietary period, the plasma lipid profile was determined, including total cholesterol, HDL cholesterol, LDL cholesterol, total triglyceride, apo A1, apo B plasma levels and conjugated diene formation, after incubation of LDL particles with Cu 5 microM/l. Endothelial products measured in plasma were von Willebrand factor (vWF), E-selectin, Thrombomodulin and Tissue Factor Pathway Inhibitor (TFPI) levels. We observed a decrease in vWF, PAI-1 and TFPI plasma levels and an increase in lag time of conjugated diene formation after the MUFA-diet. There was a positive correlation between the decreases in TFPI and vWF and the changes in total cholesterol, LDL-C, apo B plasma levels. The decrease in TFPI was negatively correlated with the increase in lag time of conjugated diene formation. PAI-1 plasma levels were positively correlated with total cholesterol, LDL-C and triglycerides and negatively correlated with HDL-C.

CONCLUSIONS

Consumption of a Mediterranean-type MUFA-diet produces a decrease in plasma levels of vWF, TFPI and PAI-1 plasma levels in young healthy males. Given that these substances are of endothelial origin, one could suggest that the MUFA of the diet has a beneficial effect on endothelial function resulting in protective changes against thrombogenesis.

Some data of previous literature have emphasized a negative correlation between plasma apo A1, HDL cholesterol and coronary heart disease. The present paper stresses a high negative correlation existing both in females and males between values of index body weight (IBW) and plasma levels of HDL cholesterol and apo A1. No correlation has been found between age and, respectively, HDL cholesterol, apo A1 and apo B.

Psoriasis is characterized by defects in the normal cycle of epidermal development that lead to epidermal hyperproliferation, altered maturation of skin cells, vascular changes and inflammation. Also, psoriasis has been associated with an abnormal plasma lipid metabolism. Changes in plasma lipid and lipoprotein composition in patients with psoriasis may be the reason for the increased risk of atherosclerosis in these patients. We determined serum concentrations of lipids, lipoproteins and apolipoprotein Al and B (apo A1 and apo B) in 72 patients with psoriasis and 30 age matched controls. Serum lipoprotein (a) (Lp(a)), apo A1 and apo B were measured by immunoprecipitation assays, and the lipids and other biochemical parameters by enzymatic methods. Serum Lp(a) and triglyceride (TG) were significantly higher in patients with psoriasis than in healthy control subjects (p<0.01 for both). Apo B was also found to be higher in the patient group, but the difference was not significant. The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apo A1 did not differ significantly from those of the controls. These observations imply that serum Lp(a) and TG concentrations may play a role as risk factors for atherosclerotic disease in patients with psoriasis.

Recently we have demonstrated that cholesterol level in LDL-containing circulating immune complexes (CIC cholesterol) correlates with the presence of coronary atherosclerosis. In the present study we attempted to clarify whether CIC cholesterol level correlates with the severity of coronary atherosclerosis. The second task was to reveal the diagnostic value of CIC cholesterol in comparison with other lipid and lipoprotein parameters used as markers of dislipidaemia associated with atherosclerosis. The subjects were 107 patients with angiographically-documented coronary atherosclerosis and 66 patients with documented extracoronary atherosclerosis. Only CIC cholesterol and the apo B/apo A-1 ratio contributed strongly to the discrimination between patients with coronary atherosclerosis and those without stenoses. On the other hand, total cholesterol, triglycerides, HDL cholesterol, apo B, Lp[a] and apo A1 did not correlate with the presence and severity of coronary atherosclerosis. Subjects with stenosis of extracoronary arteries had significantly higher CIC levels than healthy donors. Sensitivity, specificity and accuracy of coronary atherosclerosis diagnosis were assessed for each parameter examined. It was revealed that CIC cholesterol is the most reliable marker of coronary atherosclerosis as compared to other chemical parameters. In addition, the CIC cholesterol level diagnoses extracoronary atherosclerosis with high accuracy.

OBJECTIVE

To investigate changes in lipid, lipoprotein and apolipoprotein profiles in persons with spinal cord injury (SCI) during the first 2 years post-injury, and to determine whether changes in risk profiles were associated with sport activity and/or changes in physical capacity parameters.

METHODS

Risk profiles and physical capacity were investigated in 19 subjects with recent SCI during rehabilitation (t1) and +/- 1 year after discharge from rehabilitation (t2).

METHODS

Changes in total plasma cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein-A1 (ApoA1), apolipoprotein-B (ApoB) concentrations, the ratios TC/HDL-C, LDL-C/HDL-C, ApoA1/ApoB and HDL-C/ApoA1, and physical capacity (maximal isometric strength, sprint power output, maximal power output, aerobic power).

RESULTS

Risk profile parameters changed towards more favorable values at t2, except for HDL-C (P=0.06), TG and HDL-C/ApoA1. Sport activity and changes of the physical capacity were the most important determinants of changes in lipid and (apo)lipoprotein profiles, showing more favorable values with larger increases of the physical capacity and in persons who were physically active.

CONCLUSIONS

Results show that the lipid and (apo)lipoprotein profiles improve in persons with SCI during the first 2 years post-injury, and that improving the physical capacity or being physically active can improve the lipid and (apo)lipoprotein profiles.

Lipoprotein(a) (Lp(a)) has close structural homology with plasminogen and, at least in vitro, may interfere with fibrinolysis. Any changes in the serum Lp(a) concentration during and following myocardial infarction (MI) and whether the serum Lp(a) level is affected by streptokinase (SK) are therefore of interest. Serum Lp(a) levels immediately before and 3 h after completion of an intravenous infusion of SK in 39 patients with acute MI were not significantly different (median 31.3 mg/dl before and 35.9 mg/dl after). Furthermore, SK added during the serum Lp(a) assay did not affect the result, except at very high concentrations of SK (1000 units/ml). Serum Lp(a) and fasting lipids were measured daily for 3 days following definite MI in 13 patients and then after 14 and 42 days. There was no significant change in serum Lp(a) following MI. In marked contrast, C-reactive protein levels in these patients increased steeply immediately following MI. Thus, there was no early 'acute-phase response' in serum Lp(a) levels after MI. However, greater variation in its concentration was observed at day 14 than at other times. Serum cholesterol, apolipoprotein B and apolipoprotein A1 concentrations decreased significantly following MI, whereas a significant transient increase in serum triglycerides occurred. Forty-two days after MI all lipid and lipoprotein values had regained their day 1 levels, except for apo A1, which remained depressed.