In vivo quantification of gentamicin released from an implant coating.

Drug-releasing implants are gaining increasing interest. The present study reports a detailed physicochemical analysis of a polymeric coating based on poly(D,L-lactide) and the incorporated gentamicin combined with an in vitro and in vivo study of the gentamicin release. Differential scanning calorimeter, Fourier transform infrared spectroscopy, gel permeation chromatography and high-performance liquid chromatography showed no effect of the gamma sterilisation on the coating components or an interaction of the polymer and the gentamicin. Microbiological analysis revealed an inhibition of bacterial growth on the implant surface. For the in vivo study, gentamicin-coated wires were implanted into the tibiae of rats and harvested at different time points up to day 42. To monitor the release in vivo, gentamicin was quantified in serum, bone, endosteum, kidney, and on the explanted wires. Gentamicin was detectable over a time period of 42 days in the endosteum, up to seven days in the kidney, up to 4 h in the bone and at the end of the experiment on one of eight wires. The locally released gentamicin caused no histological changes of the kidney. Microbiologically active concentrations of released gentamicin were found in the endosteum up to 4 h after implantation. The combination of different methods supports the individual results, where quantification is complemented by visualisation or antimicrobial activity. This work demonstrates that the coating procedure results in no substantial alteration of the incorporated drug and that the in vitro burst release occurs also in vivo.

Progressing innovation in biomaterials. From the bench to the bed of patients.

A Translational Research Symposium was organized at the 2014 annual meeting of the European society for biomaterials. This brought together leading Tier one companies in clinical biomaterials and medical device markets, small and medium enterprises and entrepreneurial academics who shared their experiences on taking biomaterials technologies to commercial endpoints, in the clinics. The symposium focused on "Progressing Innovation in Biomaterials. From the Bench to the Bed of Patients". The aim of the present document is to illustrate the content of the symposium and to highlight the key lessons from selected lectures.

Serum adiponectin is decreased in patients with familial combined hyperlipidemia and normolipaemic relatives and is influenced by lipid-lowering treatment.

BACKGROUND AND AIMS: Hypoadiponectinemia has been reported in patients with familial combined hyperlipidemia (FCHL) presenting increased waist circumference and insulin resistance. However, no studies have evaluated this association in non-obese FCHL patients. Moreover, it is unclear whether correction of lipoprotein abnormalities may influence adiponectin levels in FCHL. METHODS AND RESULTS: We have compared serum levels of adiponectin in 199 non-obese FCHL patients (BMI 25.96+/-3.7), 116 normolipaemic (NL) non-affected relatives (BMI 24.4+/-4.0) and 192 controls (BMI 28.0+/-7.4). In a subgroup of FCHL patients, changes in adiponectin levels after treatment with atorvastatin (n=22) or fenofibrate (n=26) were also evaluated. FCHL patients as well as their NL relatives showed lower serum adiponectin levels compared to controls (9.7+/-5.4 microg/mL, 10.7+/-5.3 microg/mL and 17.3+/-13.7microg/mL, respectively; p<0.0001 for all comparisons). After controlling for confounders, the strongest association with hypoadiponectinemia was observed with family history of FCHL, followed by HDL-C (negatively) and age (positively). These variables jointly explained 15% of the total variance of serum adiponectin levels. After 24-week of treatment, adiponectin was increased by 12.5% (p<0.05) by atorvastatin and was reduced by 10% by fenofibrate, resulting in a treatment difference of 22.5% in favor of atorvastatin (p<0.017). CONCLUSIONS: FCHL patients showed lower serum adiponectin levels compared to controls. Also normolipaemic relatives of FCHL patients presented decreased levels of adiponectin, suggesting a possible common background in the determination of this abnormality. Overall, these observations indicate that hypoadiponectinemia may be an inherent characteristic of the FCHL phenotype. In FCHL patients hypoadiponectinemia may be partially corrected by atorvastatin but not by fenofibrate treatment.

Tumor necrosis factor alpha (TNFalpha) and its soluble receptor p75 (sTNF-R p75) in familial combined hyperlipidemia (FCHL).

BACKGROUND AND AIM: Familial combined hyperlipidemia (FCHL) is a genetic disorder of lipid metabolism associated with insulin resistance and abnormalities in fatty acid metabolism whose underlying mechanisms are largely unknown. Perturbations in the TNFalpha/TNF-R pathway may play a role in these abnormalities. METHODS AND RESULTS: We determined plasma levels of TNFalpha and sTNF-R p75 in 85 FCHL patients (TC 245+/-45 mg/dl; TG 260+/-148 mg/dl; apoB 148+/-37 mg/dl) and in 29 age- and sex-matched normolipemic relatives (NL) (TC 187+/-22.8 mg/dl; TG 115+/-37 mg/dl; apoB 106+/-16 mg/dl). Thirty-four normolipemic subjects (TC 180+/-34 mg/dl; TG 107+/-42 mg/dl; apoB 95+/-22 mg/dl) were also included as unrelated controls (NC). Plasma free fatty acids (NEFA) were also measured and insulin sensitivity was evaluated by HOMA. Levels of sTNF-R p75 were significantly reduced in FCHL compared to NL (2.30+/-0.55 ng/ml vs. 2.64+/-0.88 ng/ml, p<0.05) but not compared to NC (2.35+/-0.68 ng/ml). HOMA values were comparable in all groups and did not show any relation with plasma levels of sTNF-R p75. Logistic analysis demonstrated that a low concentration of sTNF-R p75 was an independent predictor of the affected status within FCHL families, but this role was no longer evident when FCHL patients were compared to NC. In FCHL, age (p<0.001) was positively, and TG (p=0.029) and HDL-C (p=0.025) were negatively correlated with plasma concentrations of sTNF-R p75. In the other groups, age (in NL) and non-HDL-C (in NC) were significantly correlated with sTNF-R p75. CONCLUSIONS: Although our data do not support a causative role of TNFalpha/TNF-R alterations in FCHL, they confirm that variation in TNF-R shedding may influence lipid phenotypic expression in FCHL families.

Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects.

BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed. METHODS AND RESULTS: A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. CONCLUSIONS: The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy.

Clinical and biochemical characterisation of patients with autosomal recessive hypercholesterolemia (ARH).

BACKGROUND AND AIM: Inherited hypercholesterolemias are common disorders characterised by elevated LDL-C levels and premature coronary heart disease. We have recently described a recessive form of hypercholesterolemia (autosomal recessive hypercholesterolemia, ARH) in which LDL catabolism is reduced because of a mutation in the gene coding for an adaptor protein that impairs LDL-receptor (LDL-R) activity in the liver. The aim of this study was to characterise in detail the phenotypes of subjects with homozygous and heterozygous ARH. METHODS AND RESULTS: We have so far identified six Italian families with ARH and studied the clinical and biochemical characteristics of 11 homozygotes (age 13-47 years) and 12 obligate heterozygotes (age 42-83 years). The study protocol included an evaluation of the lipoprotein profile, LDL-R activity in fibroblasts, LDL binding activity, and apo E genotype; a structured questionnaire (CHD risk factors, medical history, current medications); a physical examination, resting and stress ECG, ultrasound examinations (heart, carotid arteries, Achilles tendons) and coronary angiography. The pedigrees were characterised by the absence of vertical transmission; consanguinity was documented in two families. Only the two previously described Sardinian mutations, ARH1 (c.432insA) and ARH2 (c.65G > A), were identified in the probands. All of the ARH homozygotes had large tendinous xanthomas, two had exertional angina, and four a positive stress ECG. None had experienced myocardial infarction or stroke. More than half had instrumental signs of atherosclerosis such as a positive stress ECG or positive carotid echo-doppler examination. The ARH heterozygotes were consistently normal and had a normal lipid profile. CONCLUSIONS: The ARH phenotype resembles that of familial hypercholesterolemia (FH) homozygotes, but ARH may be a less serious illness. The absence of vertical transmission, and the presence of mild coronary heart disease and consanguinity, can suggest a possible diagnosis of ARH. ARH might be considered a phenocopy of FH but heterozygous subjects seem to have a consistently normal phenotype.

PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population.

BACKGROUND: The present study evaluated the role of the PON1 L55M polymorphism independently and in conjunction with the Q192R polymorphism on the risk of coronary atherosclerosis in an Italian population. MATERIALS AND METHODS: Three hundred and ninety-one subjects with significant coronary stenosis (> 50%) (coronary artery disease-positive; CAD+), 196 subjects with normal coronary arteries (< 10% stenosis) (CAD-) and 178 healthy controls were screened using a combination of polymerase chain reaction and restriction enzyme digestion. RESULTS: In the pooled population, the frequencies of L and M alleles were 0.63 and 0.37, respectively; the most common haplotypes were QQ/LM (24.2%) and QR/LL (21.8%) and a strong linkage disequilibrium between L/55 and R/192 alleles was observed (D' = -0.91; P < 0.0001). CAD+ subjects did not show any significant differences in the distribution of PON1-55 genotypes as compared to CAD- subjects and population controls (chi2 = 1.5, P = 0.8). After controlling for other risk factors, the low-concentration M allele was not associated with a significant change of CAD risk (OR 1.02; 95% CI 0.80-1.29; P = 0.87). Moreover, the L55M polymorphism did not show any interaction with other risk factors such as smoking, diabetes, hypertension, low levels of high-density lipoprotein (HDL) or high ratios of low-density to high-density lipoproteins. The combination of L55M with the Q192R polymorphism did not show any effect on CAD risk. However, a marginal decrease in myocardial infarction risk was detected when QQ/MM carriers (OR 0.51; 95% CI 0.26-0.99; P = 0.048), but not LL/RR carriers, were compared with subjects not homozygous for an L or R allele. CONCLUSIONS: These findings did not indicate a major effect of the PON1 L55M polymorphism, either alone or in combination with the Q192R polymorphism, on CAD risk. Additional studies are needed for a better evaluation of the role of the 55/192 PON1 genotypes in combination on myocardial infarction risk.

Lack of association of the common TaqIB polymorphism in the cholesteryl ester transfer protein gene with angiographically assessed coronary atherosclerosis.

The anti-atherogenic effect of cholesteryl ester transfer protein (CETP) genetic variants associated with lowered enzyme activity is controversial. Moreover, in a few studies, this effect has been evaluated in the presence of a certain risk factor constellation. We addressed this issue in a case-control study, where 415 subjects with angiographically documented coronary artery disease (CAD +), 397 subjects without CAD (in 215, CAD was excluded by coronarography (CAD-)), and 188 healthy population controls, were screened for the CETP TaqIB polymorphism. The prevalence of the low-activity TaqIB2 allele was 0.396 in CAD+, and 0.428 and 0.416 in CAD- and population controls, respectively (p = 0.40). Its presence was significantly associated with increased high-density lipoprotein cholesterol (HDL-C) in population controls (1.40 +/- 0.40 mmol/l in B1B1, 1.52 +/- 0.39 mmol/l in B1B2 and 1.58 + 0.46 mmol/l in B2B2; p < 0.03 for trend), but not in the other groups. The CETP TaqIB polymorphism accounted for < 1% of the HDL-C variance in the whole cohort (p = 0.048). After adjustment for other risk factors, the CETP TaqIB2 allele was found not to be associated with significant changes in CAD risk independently of an assumed either dominant (odds ratio (OR) 0.97; 95% confidence interval (CI) 0.66-1.44; p = 0.89) or recessive effect (OR 0.68; 95% CI 0.42-1.12; p = 0.13). The CETP TaqIB polymorphism did not show a significant interaction with other risk factors in influencing CAD risk. Our findings do not support the hypothesis that a genetic variant resulting in lowered CETP activity is associated with reduced risk of coronary atherosclerosis.

17beta-estradiol enhances the flux of cholesterol through the cholesteryl ester cycle in human macrophages.

Estrogens have been shown to have many positive effects on the function of arterial wall, and recent evidence suggest that 17beta-estradiol has a direct action in reducing the accumulation of cholesteryl ester in macrophages. The mechanisms underlying the effects of 17beta-estradiol on foam cell formation, however are poorly understood. The aim of this study is to investigate the role of 17beta-estradiol in the regulation of the cholesteryl ester cycle and cholesterol efflux in human macrophages. In addition, the influence of 17beta-estradiol on apolipoprotein E (apoE) and lipoprotein lipase (LDL) secretion by the cells was also tested. Human Monocyte Derived Macrophages (HMDM), matured in the presence or the absence of 17beta-estradiol, were loaded with [3H]-cholesteryl ester-labeled-acetyl LDL (low density lipoprotein) and the efflux of radioactivity into the medium was measured. The effect of 17beta-estradiol on cellular activities of acyl coenzyme A: cholesterol acyl transferase (ACAT), and both neutral and acid cholesteryl ester hydrolase (CEH) and the secretion of apoE and LDL into the medium, were also studied. The results indicate that 17beta-estradiol induces an increase in the amount of labeled cholesterol released from the cells and, the data obtained from the measurements of ACAT and CEH activities showed that, in estrogen-treated HMDM, the cholesteryl ester cycle favors the hydrolysis of lipoprotein cholesterol by CEH in comparison with its acylation by ACAT. In particular, for the first time a strong enhancement of neutral and acid CEH in human macrophages by 17beta-estradiol, was demonstrated. ApoE and LDL secretion increased during the maturation of monocytes to macrophages, and was not modified by 17beta-estradiol. In contrast, loading the cells with cholesterol by incubation in the presence of acetylated or oxidized LDL produced an increase in the levels of apoE secreted by both estrogen-treated and control macrophages. The activity of LPL found in the cell medium, on the other hand, in lipid loaded cells tended to be increased only in estrogen treated macrophages, suggesting that the effects of estrogen on unloaded macrophages are different from those produced on lipid-loaded macrophages. On the whole, the present findings suggest that one of the mechanisms by which 17beta-estradiol acts to reduce cholesterol accumulation in macrophages is by increasing reverse cholesterol transport through the enhancement of the cholesteryl ester cycle, so that the generation of intracellular unesterified cholesterol for excretion from the cells is favored.

The common mutations in the lipoprotein lipase gene in Italy: effects on plasma lipids and angiographically assessed coronary atherosclerosis.

The present study evaluated the role of the common lipoprotein lipase (LPL) mutations on the risk of dyslipidemia and coronary atherosclerosis in an Italian population. Cohorts of 632 patients undergoing coronary angiography, as well as 191 healthy controls, were screened by a combination of PCR and restriction enzyme digestion. In the pooled population, the frequencies of LPL D9N and N291S were 4.1%, with no homozygous carriers, whereas that of LPL S447X was 21% with 19.6% heterozygous and 1.4% homozygous carriers. Compared to non-carriers, LPL N291S carriers showed higher plasma triglycerides (TG) (p < 0.03) and increased risk of high TG phenotype (odds ratio [OR] 2.49, 95% Cl 1.06-5.81; p < 0.03). When this LPL mutation was associated with high body mass index (BMI) ( > 25 Kg/m2) or fasting, plasma insulin (> 10.6 mU ml(-1)) significantly reduced HDL-C levels were also observed. Carriers of the S447X mutation presented with higher HDL-C concentrations (p < 0.05) as compared to non-carriers; they also showed a significantly reduced risk of high TG/low HDL-C dyslipidemia (OR 0.34, 95%, Cl 0.12-0.99; p < 0.05). The favourable effect of the LPL S447X variant was even more pronounced in lean subjects and in those with low insulin levels. No significant influence on plasma lipids by the LPL D9N was observed. None of LPL variants was a significant predictor of angiographically assessed coronary atherosclerosis. At most, the risk was borderline, increased in N291S carriers and possibly decreased in S447X carriers.

A common mutation of the insulin receptor substrate-1 gene is a risk factor for coronary artery disease.

Insulin resistance is associated with increased risk of atherosclerosis. Insulin receptor substrate-1 (IRS-1) plays a key role in tissue insulin sensitivity. A common mutation (G972R) of the IRS-1 gene has been shown to impair IRS-1 function, and it has been associated with reduced insulin sensitivity and lipid abnormalities. This led us to investigate the role of the G972R mutation in predisposing individuals to coronary artery disease (CAD). The DNA of 318 subjects with angiographically documented coronary atherosclerosis (>50% stenosis) and 208 population control subjects was analyzed for the presence of the G972R mutation. This mutation was detected by nested polymerase chain reaction and BstNI restriction enzyme digestion. The frequency of the G972R mutation was significantly higher among patients with CAD than controls (18. 9% versus 6.8%, respectively; P<0.001). After controlling for other coronary risk factors, the relative risk of CAD associated with the G972R mutation was 2.93 (95% CI 1.30 to 6.60; P<0.02) in the entire cohort. This risk was found to be even higher in the subgroups of obese subjects (odds ratio [OR] 6.97, 95% CI 2.24 to 21.4; P<0.001) and subjects with clinical features of insulin resistance syndrome (OR 27.3, 95% CI 7.19 to 104.0; P<0.001). The IRS-1 gene variant was associated with a higher frequency of diabetes mellitus (14.9% among carriers versus 6.5% among noncarriers; P<0.01) and with a 60% increase of plasma total triglycerides (P<0.001). Also, plasma concentrations of total cholesterol and the ratio of total cholesterol to HDL cholesterol were significantly (P<0.001) higher among carriers than noncarriers, although to lesser a extent. These effects were independent of CAD status. The G972R mutation in the IRS-1 gene was found to be a significant independent predictor of CAD. Moreover, this mutation greatly increased the risk of CAD in obese subjects and in patients with the cluster of abnormalities of insulin resistance syndrome. Besides the increased frequency of diabetes, carriers showed a more atherogenic lipid profile, suggesting a potential role of the IRS-1 gene in the pathogenesis of lipid abnormalities associated with CAD.

Characterization of a new form of inherited hypercholesterolemia: familial recessive hypercholesterolemia.

We previously described a Sardinian family in which the probands had a severe form of hypercholesterolemia, suggestive of familial hypercholesterolemia (FH). However, low density lipoprotein (LDL) receptor activity in fibroblasts from these subjects and LDL binding ability were normal. The characteristics of the pedigree were consistent with an autosomal recessive trait. Sitosterolemia and pseudohomozygous hyperlipidemia were ruled out. A second Sardinian kindred with similar characteristics was identified. Probands showed severe hypercholesterolemia, whereas their parents and grandparents were normolipidemic. FH, familial defective apoprotein (apo) B, sitosterolemia, and cholesteryl ester storage disease were excluded by in vitro studies. We addressed the metabolic basis of this inherited disorder by studying the in vivo metabolism of LDL in 3 probands from these 2 families. 125I-LDL turnover studies disclosed a marked reduction in the fractional catabolic rate (0.19+/-0.01 versus 0.36+/-0.03 pools per day, respectively; P<0.001) and a significant increase in the production rate [20.7+/-4.4 versus 14. 0+/-2.4 mg. kg-1. d-1, respectively; P<0.01] of LDL apoB in the probands compared with normolipidemic controls. We then studied the in vivo biodistribution and tissue uptake of 99mtechnetium-labeled LDL in the probands and compared them with those in normal controls and 1 FH homozygote. The probands showed a significant reduction in hepatic LDL uptake, similar to that observed in the FH homozygote. A reduced uptake of LDL by the kidney and spleen was also observed in all patients. Our findings suggest that this recessive form of hypercholesterolemia is due to a marked reduction of in vivo LDL catabolism. This appears to be caused by a selective reduction in hepatic LDL uptake. We propose that in this new lipid disorder, a recessive defect causes a selective impairment of LDL receptor function in the liver.

The gln-Arg192 polymorphism of human paraoxonase gene is not associated with coronary artery disease in italian patients.

Serum paraoxonase (PON) is an HDL-bound enzyme protecting LDL from oxidation. A common polymorphism of the paraoxonase gene (PON1) involving a Gln-to-Arg interchange at position 192 has been demonstrated to modulate PON activity toward paraoxon, a nonphysiological substrate; Arg192 (allele B) is associated with higher activity than Gln192 (allele A). This polymorphism has been proposed as a genetic marker of risk for coronary artery disease (CAD). However, the relationships between codon 192 PON1 genotypes, coronary atherosclerosis, and the occurrence of myocardial infarction (MI) are still controversial. PON1 genotypes were determined in 472 consecutive subjects (>40 years old) who underwent coronary angiography. CAD (>50% stenosis) was detected in 310 subjects (CAD+); 162 subjects with <10% stenosis served as controls (CAD-). We also evaluated 204 randomly selected individuals as population controls. PON1 genotypes were determined by PCR and AlwI restriction enzyme digestion. Frequencies of alleles A and B were 0. 70 and 0.30 in angiographically assessed subjects and 0.73 and 0.27 in population controls, respectively (chi2=2.0; P<0.3). Distribution of PON1 genotypes in CAD+ were not significantly different from those in CAD- (chi2=2.10; P<0.3). Similarly, no differences were observed in the subgroup of CAD+ with MI nor in that at higher oxidative risk (smokers and/or diabetics). After controlling for other coronary risk factors, no association was found between PON1 alleles and the presence of CAD. PON1 AA genotype was associated with reduced concentration of apolipoprotein B-containing triglyceride-rich lipoproteins. This study did not provide evidence of a significant association between codon 192 PON1 genotypes and coronary atherosclerosis in Italian patients. However, it did confirm that the PON1 low-activity allele is associated with a less atherogenic lipid profile.

Angiotensin-converting enzyme gene polymorphism is not associated with coronary atherosclerosis and myocardial infarction in a sample of Italian patients.

BACKGROUND: The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been proposed as a genetic marker of the risk of ischaemic heart disease. However, the relationships between ACE genotypes, the development of coronary atherosclerosis and the occurrence of major coronary events are still controversial. METHODS: To investigate whether the ACE I/D (insertion/deletion) polymorphism predicts the risk of coronary stenosis and myocardial infarction (MI), ACE genotypes were determined in 394 consecutive patients who underwent coronary angiography. The presence determined in 394 consecutive patients who underwent coronary angiography. The presence of coronary artery disease (CAD) (defined by > 50% stenosis) was detected in 236 patients (CAD+); 85 of these individuals had a history of MI. Patients with coronary stenosis < 10% (n = 158) served as controls (CAD-). ACE genotypes were determined by agarose gel sizing after polymerase chain reaction (PCR) amplification. RESULTS: The distribution of ACE genotypes in CAD+ patients was not significantly different from that in CAD-patients (chi 2 = 2.63, P < 0.27). After controlling for other coronary risk factors, no significant increase in risk of CAD or MI was found to be associated with the D allele, regardless of whether the D allele was assumed to have a dominant, a codominant or a recessive effect. Similar results were observed in CAD+ patients at lower risk because of low body mass index and apolipoprotein B concentrations. Smoking, apolipoprotein B and history of hypertension were found to be independent predictors of CAD and MI. CONCLUSION: Our study did not provide evidence of a significant association between ACE genotypes and the development of coronary atherosclerosis. It also failed to support a role of ACE I/D polymorphism in favouring the conversion of coronary stenosis to MI.

Incorporation of photoluminescent polarizers into liquid crystal displays

Liquid crystal displays, the dominant flat panel display technology, are limited in brightness and energy efficiency because of the use of absorbing polarizers and color filters. Liquid crystal-based photoluminescent display devices have been fabricated that use thin, polarized photoluminescent layers that have highly anisotropic absorption or emission. These layers both polarize light and generate bright color. This approach can simplify device design and substantially increase device brightness, contrast, efficiency, and (in specific configurations) viewing angle.

Concentrations of apolipoprotein A-I-containing particles in patients with hypoalphalipoproteinemia.

This study was performed to determine relations among concentrations of high-density lipoprotein (HDL) apolipoprotein (apo) A-I and apoA-II and lipoproteins with apoA-I only (LpA-I) and with both apoA-I and apoA-II (LpA-I:A-II) in patients with low plasma levels of HDL cholesterol. Seventy-seven middle-aged men with low HDL cholesterol levels (< 40 mg/dL) were compared with 37 middle-aged men with normal HDL cholesterol levels (> 40 mg/dL). Low-HDL patients were divided into those with normotriglyceridemia (triglycerides < 250 mg/dL; n = 49) and hypertriglyceridemia (triglycerides > or = 250 mg/dL; n = 28). Total apoA-I and apoA-II concentrations and apoA-I levels in LpA-I were significantly lower in the two low-HDL groups compared with control subjects. Although low-HDL patients' apoA-I levels were numerically lower in LpA-I:A-II compared with control subjects' levels, the differences were not statistically significant. Thus, there is a preferential reduction in apoA-I levels of LpA-I compared with LpA-I:A-II in patients with low HDL cholesterol. This preferential reduction in LpA-I levels was observed in both normotriglyceridemic and hypertriglyceridemic patients. However, among low-HDL patients levels of apoA-I in LpA-I did not distinguish between those with and without coronary heart disease.

Erythrocyte fatty acid composition and gallstone disease: results of an epidemiological survey.

Within a cross-sectional study on the epidemiology of gallstone disease (GD) and its related factors, relation of GD to habitual dietary fat types has been investigated. Gallbladder status was assessed by ultrasound; fatty acid composition of the habitual diet was estimated by GLC of erythrocyte fatty acids. No differences in erythrocyte fatty acid composition were observed between women without gallstones, women with gallstones (aware and unaware of their condition), and women who had cholecystectomies. Multivariate analysis, including other diet-dependent and gallstone-related variables, showed no significant association between erythrocyte fatty acids and risk for gallstones. However, raised erythrocyte linoleic:saturated ratio was associated with increased risk for gallstones only in women with very low serum triglycerides. This latter finding needs further confirmation and is presently unexplainable. Our results suggest that dietary fatty acids do not play a major role in GD.

Lack of association between arterial blood pressure and erythrocyte fatty acid composition in an Italian population sample.

The relation between arterial blood pressure and erythrocyte fatty acid composition was investigated in a large urban female population aged 20-69 years. No significant differences in the relative amounts of saturated, monounsaturated and polyunsaturated (n-6 and n-3 series) fatty acids and in the mean polyunsaturated/saturated and linoleic/oleic ratios were observed in the different quartiles of both systolic and diastolic blood pressure. Moreover, there was no significant correlation between individual erythrocyte fatty acids and their ratios and either blood pressure or other risk factors for atherosclerosis (age, body mass index, total serum cholesterol and triglycerides). In the multivariate analysis no independent correlations between systolic and diastolic blood pressure and the individual erythrocyte fatty acids were observed; age and body mass index were strongly related to blood pressure. Our results do not confirm for erythrocyte fatty acids the reported associations between plasma fatty acids and blood pressure.

An improved gas-liquid chromatographic method for the determination of fecal neutral sterols.

The analysis of fecal neutral sterols has been improved by use of a highly selective gas-liquid chromatography column packed with SP-2401. This chromatographic column allows separation of cholesterol and cholestanol and delta 5-5 alpha plant sterol homologs without employing silver nitrate thin-layer chromatography. Furthermore, there is no need to derivatize neutral sterols before injection. The main fecal neutral sterols are well resolved; retention times are reproducible; detector response is reproducible, linear, and sensitive to 0.2 micrograms. This method, successfully used for fecal samples, may be suggested as a routine method for the clinical study of cholesterol metabolism.

Plasma and erythrocyte fatty acids: a methodology for evaluation of hypocholesterolemic dietary interventions.

A major source of concern in the management of hypercholesterolemia is the careful evaluation of adherence to dietary prescriptions. Routine analysis of plasma fatty acids to monitor adherence of hyperlipidemic outpatients to diets varied in lipid composition is a major task of our research group. Plasma fatty acid patterns are determined by gas-liquid chromatography 60 days after starting an experimental normocaloric diet with 37% fat calories and a polyunsaturated/saturated (P/S) ratio of 3.4. Where poor adherence is observed, the dietary message is administered more incisively or changed accordingly. It is also possible to identify with certainty diet-resistant hypercholesterolemic individuals, i.e., the true nonresponders, who represent only a minority. The determination of erythrocyte fatty acid patterns represents a useful index of adherence in long-term feeding studies and has been extensively carried out in subsamples of persons examined at the fourth rescreening of a controlled trial of primary prevention of coronary heart disease. Increases in mean erythrocyte linoleic/oleic (L/O) and P/S ratios were observed in persons undergoing collective or individual hypocholesterolemic treatment, mean changes being proportional to the different type of nutritional approach. In our opinion, this methodology is the most reliable technique not only for the identification of the different responses to hypocholesterolemic dietary recommendations but also to monitor fat consumption in population samples.