LDL oxidative modification and carotid atherosclerosis: results of a multicenter study.

OBJECTIVE: Serum LDL conjugated diene concentration is a marker of oxidative modification of LDL. We investigated the relationship between LDL conjugated dienes and cross-sectional subclinical atherosclerosis assessed by carotid IMT in high-risk subjects of a multicenter study. METHODS: Serum LDL conjugated dienes and ultrasonographically assessed carotid intima-media thickness (IMT(mean), IMT(max) and IMT(mean-max)) were available for 553 subjects from Finland, France, Italy, the Netherlands, and Sweden. RESULTS: In multivariate regression analysis, gender (p < 0.001), age (p < 0.001), systolic blood pressure (IMT(mean), p = 0.01; IMT(mean-max), p = 0.05) and serum LDL conjugated dienes (p = 0.02 for both IMT(mean) and IMT(mean-max)) were the strongest determinants of IMT variation, adjusted for study center, ultrasound videotape reader and serum LDL cholesterol. Pack-years of smoking, added into the regression model, did not destroy the significant association between increased serum LDL conjugated dienes and IMT. Ratio of LDL conjugated dienes to LDL particle cholesterol was higher in subjects of Northern recruiting centers than of Southern centers (r = 0.39, p < 0.0001). CONCLUSIONS: There was a cross-sectional association between in vivo increased LDL oxidative modification and subclinical atherosclerosis after adjustment for traditional risk factors. The subjects in Northern countries of Europe had more oxidatively modified lipids per cholesterol in LDL particle than subjects in Southern countries.

Low ß-carotene concentrations increase the risk of cardiovascular disease mortality among Finnish men with risk factors.

BACKGROUND & AIMS: Healthy diet rich in fruits and vegetables is an important factor in prevention of cardiovascular diseases (CVD). Some previous epidemiological studies have suggested that dietary and serum carotenoids are associated with decreased CVD mortality, but the results have been inconsistent. We assessed relations between the concentrations of serum carotenoids and CVD mortality among Eastern Finnish men. METHODS & RESULTS: The study population consisted of 1031 Eastern Finnish men aged 46-65 years in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. Subjects were classified quartiles according to concentrations of carotenoids and subgroups according to risk factors. Hazard ratios of serum lycopene, α-carotene and ß-carotene were estimated by the Cox proportional hazard model after adjusting for potential confounding factors. During the median 15.9-year follow-up, 122 deaths from CVDs, were identified among the cohort subjects. Low serum concentrations of ß-carotene were strongly related to an increased CVD mortality risk after adjustment for confounders. For ß-carotene, the hazard ratio (95% confidence interval) for the lowest versus highest quartile was 2.23 (1.26-3.93; P=0.006). However, the strongest risk of CVD mortality was observed among smokers with lowest levels of ß-carotene (HR=3.15, 95%, CI: 1.19-8.33; P=0.020). Other carotenoids and the sum of carotenoids were not significantly related to increased risk of CVD mortality. CONCLUSIONS: Low concentrations of serum ß-carotene concentrations may increase the risk for CVD mortality among Eastern Finnish men; thus elevated serum concentrations of ß-carotene may have clinical and public health relevance.

Plasma carotenoids are related to intima--media thickness of the carotid artery wall in men from eastern Finland.

BACKGROUND: Several previous epidemiological studies have suggested that high plasma concentrations of carotenoids may slow the development of early atherosclerosis, but results have been inconclusive. METHODS: We examined the effect of carotenoids on early atherosclerosis in a population-based study. The association between plasma carotenoid concentrations and intima-media thickness of the common carotid artery (CCA-IMT) was investigated in 1212 elderly men (aged 61-80 years) in Eastern Finland. They were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis, and plasma concentrations of carotenoids were measured by high-performance liquid chromatography. RESULTS: Men in the lowest quartile of CCA-IMT had significantly higher concentrations of plasma ß-cryptoxanthin, lycopene and α-carotene than men in the highest quartile (P for the differences: 0.043, 0.045 and 0.046, respectively), after adjustment for age, examination year, body mass index, smoking, alcohol intake, years of education, symptomatic coronary heart disease (CHD) or CHD history, diabetes, low-density lipoprotein cholesterol, medications and season. The concentrations of plasma ß-cryptoxanthin, lycopene and α-carotene decreased linearly with increasing CCA-IMT. CONCLUSIONS: The results of this study suggest that high plasma concentrations of ß-cryptoxanthin, lycopene and α-carotene may be associated with decreased carotid atherosclerosis in elderly men from eastern Finland.

Suitability of Smopex-102 cation-exchange fiber for analytical purposes and drug monitoring.

The present study aimed to evaluate the suitability of Smopex-102 cation-exchange fiber for the separation of acidic and basic model drugs from biological fluids (e.g. serum) prior to chromatographic analysis. In addition, the interactions of the drugs with the fiber were studied. The study found that basic antidepressant model drugs bound to a considerably greater extent than acidic drugs to poly(acrylic acid) (PAA) grafted Smopex-102 cation-exchange fiber from 25 mM HEPES buffer (pH 7.0) and spiked serum. Drug binding from serum decreased except for acidic drugs due to drug distribution between serum proteins and cation-exchange fiber. Electrostatic interactions were possibly the most important factors affecting drug binding to the fiber. Basic drugs were released most effectively from the fiber by using acetic acid (mean released amount 123.7 +/- 36.3% and mean absolute recovery 95.4 +/- 23.8%). Results demonstrated that the cation-exchange fiber evaluated might be a potential material for separating basic drugs from protein-free and proteinaceous (e.g. serum) liquid solutions for subsequent monitoring and evaluation. However, the drug release solution and release time must be optimized more precisely in order to validate described sample preparation method for each basic drug.

Suitability of collection tubes with separator gels for collecting and storing blood samples for therapeutic drug monitoring (TDM).

In this study, we present significant changes occurring in serum drug concentrations while using blood collection tubes that contain a barrier gel. This report also contains results with antidepressant drugs, which have not been studied before with human samples. The drug concentrations were measured either with high performance liquid chromatography (HPLC) or fluorescence polarization immunoassay (FPIA). The results show that gel tubes are suitable for blood collection for antiepileptic, antibiotic, asthma and cardioactive drug measurements, since only slight adsorption was seen (0-5%). However, the studied tubes are not suitable for blood collection of antidepressants nor benzodiazepines, because the adsorption can be 5-30%. The adsorption was even higher (up to 40%) when samples were stored for 24 h after centrifugation in gel tubes. When the centrifugation step was performed after storage the effect of the barrier gel was lower (only 0-13%). Antidepressant drug measurements performed from patient specimens collected in the studied gel tubes and stored for 3 h showed <10% adsorption of the studied drugs. After 24 h storage time, concentrations of all analysed drugs decreased even more: adsorbed amount of drugs were about 5-20%. The studied gel tubes are proposed to be satisfactory for blood collection for antidepressant drug measurements if separation step is performed within 3 h after blood clotting. With the spiked samples the adsorption to barrier gel was higher, so it seems that adsorption is faster when drugs are not highly bound to serum proteins.

Adsorption of drugs onto a poly(acrylic acid) grafted cation-exchange membrane.

The influence of pH, ionic strength and the concentration of albumin in the adsorption medium as well as the charge and lipophilicity of a model drug on their adsorption onto poly(acrylic acid) grafted poly(vinylidene fluoride) (PAA-PVDF) membranes was evaluated. The PAA-PVDF membrane is a responsive porous polymer membrane that we have studied for controlled drug delivery. Sodium salicylate (anionic), flunitrazepam (neutral), primidone (neutral), desipramine (cationic) and thioridazine (cationic) were used as model drugs. The extent of drug adsorption was dependent on pH. Drug adsorption was enhanced by the dissociation of the grafted PAA chains and by a positive charge and a high lipophilicity of the drug. Increasing the ionic strength of the medium retarded the adsorption of the cationic drugs. Interestingly, the present results showing that drugs are adsorbed onto the membrane while albumin is not adsorbed onto the membrane suggest that the PAA-PVDF membrane may be suitable for separating drugs from proteinaceous substances for subsequent monitoring and evaluation.